Novel 11-hydroxy-9-keto-5,6-cis-13,14-cis-prostadienoic acid derivatives

Abstract

This disclosure describes certain 11-hydroxy and 11-deoxy-9-keto(or hydroxy)-prostanoic acid derivatives useful as bronchodilators, hypotensive agents, anti-ulcer agents, or as intermediates.

Description

BRIEF SUMMARY OF THE INVENTION

This invention relates to novel hydroxy substituted prostenoic acids and derivatives as well as to intermediates and methods for their preparation. These methods embrace novel and useful procedures for the preparation of prostaglandin E.sub.1, 11-deoxyprostaglandin E.sub.1, 13-dihydroxyprostaglandin E.sub.1, and other known biologically important prostaglandin congeners. The novel compounds of this invention may be represented by the following general formula: ##STR1## wherein n is an integer having the value 1 or 2; R.sub.1 is hydrogen, lower alkoxy, triphenylmethyl, or triphenylmethyl in which one or two of the phenol rings is substituted with an alkyl or an alkoxy group having up to 3 carbon atoms; R.sub.2 is a straight chain alkyl group having from 2 to 10 carbon atoms, a straight chain alkyl group having from 2 to 10 carbon atoms and substituted with one or two alkyl groups each having from one to three carbon atoms, a straight chain alkenyl group having from 3 to 10 carbon atoms and substituted with one or two alkyl groups having between them from 2 to 5 carbon atoms, or a straight chain alkynyl group having from 3 to 10 carbon atoms; R.sub.3 is hydroxy or an alkoxy group having from 1 to 12 carbon atoms; Y is a divalent radical selected from the group consisting of those of the formulae: ##STR2## Z is a divalent radical selected from the group consisting of those of the formulae: ##STR3## WHEREIN M IS AN INTEGER FROM 3 TO 8, INCLUSIVE, P IS AN INTEGER FROM 2 TO 6 INCLUSIVE, R.sub.4 is an alkyl group having up to 3 carbon atoms, and R.sub.5 is an alkyl group having up to 3 carbon atoms, a fluorine atom, or a phenyl group; R.sub.6 is hydrogen or an alkyl group having up to three carbon atoms; R.sub.7 is hydrogen or an alkyl group having up to 3 carbon atoms; and the moiety --C.sub.13 -C.sub.14 -- is ethylene, trans-vinylene, or cis-vinylene; with the first proviso that when n is 1, R.sub.1 is hydrogen, R.sub.7 is hydrogen, Z is --(CH.sub.2).sub.m -- and --C.sub.13 -C.sub.14 -- is ethylene or trans-vinylene than R.sub.2 does not include a straight chain alkyl group having from 2 to 10 carbon atoms; and with the second proviso that when Z is ##STR4## R.sub.1 is hydrogen, R.sub.2 is a straight chain alkyl group having from 2 to 10 carbon atoms and R.sub.7 is hydrogen then --C.sub.13 -C.sub.14 -- is ethylene or cis-vinylene; and with the third proviso that when R.sub.6 is alkyl then R.sub.1 is hydrogen; and with the fourth proviso that only one unsaturated bond can be directly adjacent to C.sub.15 ; and with the fifth proviso that when R.sub.7 is an alkyl group then the groups attached to the C.sub.8 position may have the 8.alpha.-alkyl(8-iso) configuration of the formula: ##STR5##

Embraced within the scope of the present invention are all the possible optical isomers of the above general formula. Also embraced within the scope of the present invention are the non-toxic, pharmaceutically acceptable salts of the novel compounds of the present invention when R.sub.3 is hydroxy. The cations comprised in these salts include, for example, the non-toxic metal cations such as the sodium ion, potassium ion, calcium ion, and magnesium ion as well as the organic amine cations such as the tri(lower alkyl)amine cations (e.g., triethylamine, triethanolamine) procaine, and the like.

This invention is particularly concerned with a compound selected from the group consisting of an optically active compound of the formula: ##STR6## and a racemic compound of that formula and the mirror image thereof wherein m is an integer from 2 to 5, inclusive, and n is an integer from 3 to 6, inclusive; R is selected from the group consisting of hydrogen and C.sub.1 -C.sub.4 alkyl; and the pharmacologically acceptable cationic salts thereof.

Preferred compounds of this invention include the racemic compound dl-9-oxo-11.alpha.,15-dihydroxy-5-cis,13-cis-prostadienoic acid, and the optically compound active compound of this formula, l-9-oxo-11.alpha.,15-dihydroxy-5-cis,13-cis-prostadienoic acid. Also preferred is the racemic compound, dl-9-oxo-11.alpha.,15-dihydroxy-4,20-bisnor-5-cis,13-cis-prostadienoic acid and the optically active compound of this formula, l-9-oxo-112,15-dihydroxy-4,20-bisnor-5-cis,13-prostadienoic acid.

The novel compounds of the present invention are usually obtainable as oils having characteristic absorption spectra. They are relatively insoluble in water but are relatively soluble in common organic solvents such as ethanol, ethyl acetate, dimethylformamide, and the like. The cationic salts of the compounds when R.sub.3 is hydroxy are, in general, white to yellow crystalline solids having characteristic melting points and absorption spectra. They are relatively soluble in water, methanol, and ethanol but are relatively insoluble in benzene, diethyl ether, and petroleum ether.

DETAILED DESCRIPTION OF THE INVENTION

The prostaglandins are a family of closely related compounds which have been obtained from various animal tissues, and which stimulate smooth muscle, lower arterial blood pressure, antagonize epinephrine-induced mobilization of free fatty acids, and have other pharmacological and auto-pharmacological effects in mammals. See Bergstrom et al., J. Biol. Chem. 238, 3555 (1963) and Horton, Experientia 21, 113 (1965) and references cited therein. All of the so called natural prostaglandins are derivatives of prostanoic acid: ##STR7## The hydrogen atoms attached to C-8 and C-12 are in trans-configuration. When the two side-chains (or the C-8 and C-12 hydrogens) are cis to each other, the compounds are referred to as 8-iso prostaglandins. The natural prostaglandins represent only one of the possible optical isomers. The compounds of this invention include all possible optical isomers.

The novel compounds of the present invention may be readily prepared from certain cycloalkenone intermediates which may be represented by the following general formula: ##STR8## wherein R'.sub.3 is an alkoxy group having from 1 to 12 carbon atoms; and n and Z are as hereinabove defined.

The cycloalkenone intermediates may be readily prepared from 2-carbethoxycyclopentanone or 2-carbethoxycyclohexanone in accordance with the reaction schemes set forth in Flowsheets A, B, C, I and J. ##STR9## wherein m and n are as hereinabove defined and X is iodo or bromo. In accordance with this reaction scheme, the cycloalk-2-en-1-ones (VIII) are developed by first converting 2-carbethoxycyclopentanone or 2-carbethoxycyclohexanone (I) to the sodium enolates thereof by means of sodium hydride in dimethoxyethane and then treating the sodium enolate with an ethyl .omega.-haloalkanoate (II). There is thus obtained the corresponding 2-carbethoxy-2-(.omega.-carbethoxyalkyl)cycloalkanone (III) which is then hydrolyzed and decarboxylated to afford the 2-(.omega.-carboxyalkyl)cycloalkanone (IV). This acid is then esterified with ethanol whereby the 2-(.omega.-carbethoxyalkyl)cycloalkanone (V) is obtained. The reaction conditions for carrying out the above sequence of reactions are well known in the art. The conversion of the cycloalkanone (V) to the enol acetate (VI) is effected by heating with acetic anhydride in the presence of p-toluenesulfonic acid. Preparation of the enol acetate (VI) usually requires heating for a period of from about 8 to 36 hours. During this period, it is preferable to allow by-product acetic acid to distill out in order to force the reaction to completion. The bromination of the enol acetates (VI) to the 2-bromocycloalkanones (VII) is preferably carried out in a two phase system as follows. A solution of bromine in chloroform is added to a rapidly stirred mixture of a solution of the enol acetate (VI) in chloroform and an aqueous solution of an acid acceptor such as calcium carbonate or soda ash. This addition is carried out at 0.degree.-5.degree. C. over a period of about half an hour, stirring is continued for an additional period of about half an hour to a few hours, and the product (VII) is then isolated by standard procedures. The dehydrobromination of the 2-bromocycloalkanones (VII) is preferably carried out in dimethylformamide with a mixture of lithium bromide and lithium carbonate at the reflux temperature for a period of about 30 minutes to an hour or so. The so formed cycloalk-2-en-1-ones (VIII) are also isolated by standard procedures well known in the art. Substitution of X-(CH.sub.2).sub.m -C(R.sub.4).sub.2 -CH.sub.2 CO.sub.2 C.sub.2 H.sub.5 for (II) in Flowsheet A and carrying through the sequence of transformations illustrated therein is productive of the following cycloalk-2-en-1-one (VIIIa): ##STR10## wherein X, n, m and R.sub.4 are as hereinabove defined.

The required cycloalk-2-en-1-one intermediates of general structure (XVI), wherein the side-chain has a lower alkyl group, fluorine atom or phenyl group alpha to the carbethoxy function, may be prepared in accordance with the following reaction scheme: ##STR11## wherein n, m and R.sub.5 are as hereinabove defined and G is a lower alkyl or aryl group. In accordance with this reaction scheme, the 2-(.omega.-carbethoxyalkyl)cycloalk-2-en-1-ones (IX) are converted to the corresponding 1-methoximino-2-(.omega.-carbethoxyalkyl)-2-cycloalkenes (X) by treatment with methoxyamine. With the ring carbonyl function thus blocked it is possible to effect a preferential reduction of the ester group by treatment with diisobutylaluminum hydride. The resulting alcohol (XI) is converted to a tosylate derivative (XII), which undergoes displacement on treatment with the sodium salt of a diethyl R.sub.5 -substituted malonate (XIII) to provide the disubstituted malonate derivatives (XIV). Hydrolysis and decarboxylation as well as concomittant cleavage of the methoximino blocking group provides the desired 2-(.omega.-carboxy-.omega.-R.sub.5 -substituted-alkyl)cycloalk-2-en-1-ones (XV), which are readily converted to the corresponding ester (XVI) by the usual procedure via the acid chloride and subsequent treatment with the appropriate alcohol in the presence of a tertiary amine.

The requisite 2-(.omega.-carbethoxy-.omega.-1-oxa-alkyl)cycloalk-2-en-1-ones (XXII) and 2-(.omega.-carbethoxy-.omega.-1-thia-alkyl)-cycloalk-2-en-1-ones (XXVI) may be prepared in accordance with the reaction schemes of Flowsheet C, wherein n and m are as hereinbefore defined. ##STR12##

In accordance with the reaction scheme shown in Flowsheet C, for the preparation of the oxa derivative (XXII), an appropriate 2-(.omega.-carbethoxyalkyl)cycloalk-2-en-1-one (XVII) is converted to the corresponding methoxime (XVIII), the ester function of which is then preferentially reduced with diisobutylaluminum hydride to afford the methoxime alcohol (XIX). The alcohol (XIX) is converted on treatment with n-butyl lithium to the lithio alcoholate, which then is O-alkylated by reaction with ethyl bromoacetate to provide (XX). Hydrolysis with acetone-aqueous hydrochloric acid furnishes the deblocked keto-acid (XXI), which is then re-esterified with ethanol in the presence of p-toluenesulfonic acid to give the required 2-(.omega.-carbethoxy-.omega.-1-oxa-alkyl)cycloalk-2-en-1-one (XXII). O-Alkylation can also be accomplished by treatment of the lithio alcoholate of (XIX) with sodium or other metal salt of bromoacetic acid, in which case the free carboxylic acid corresponding to ester (XX) is obtained. Hydrolysis as for (XX) provides the keto acid (XXI).

The preparation of the thia derivative (XXVI), proceeds from the intermediate alcohol (XIX), which after conversion to the tosylate intermediate (XXIII) and reaction with the sodium salt of ethyl mercaptoacetate furnishes intermediate (XXIV). Deblocking of XXIV with acetone-aqueous hydrochloric acid provides the keto-acid (XXV), which on re-esterification with ethanol gives the required 2-(.omega.-carbethoxy-.omega.-1-thia-alkyl)cycloalk-2-en-1-ones (XXVI).

Certain of the 11-deoxy-9-keto(or hydroxy)-prostanoic acid derivatives of this invention, as defined in the general formula on page 1 above, may be prepared from cycloalkenone (XXXI) and the triphenylmethoxy substituted 1-alkyne (XXVII) as depicted in Flowsheet D. In Flowsheet D, n, R.sub.3, R'.sub.3 and Z are as hereinabove defined; R'.sub.2 is a straight chain alkyl group having from 2 to 10 carbon atoms, a straight chain alkyl group having from 2 to 10 carbon atoms and substituted with one or two alkyl groups each having from one to three carbon atoms, a straight chain alkenyl methyl group having from two to nine carbon atoms, or a straight chain alkenyl methyl group having from two to nine carbon atoms and substituted with one or two alkyl groups having between them 2 to 5 carbon atoms; and R is a lower alkyl group. ##STR13##

In accordance with the reaction scheme of Flowsheet D, the triphenylmethoxy substituted 1-alkyne (XXVII) is treated with diisobutylaluminum hydride (XXVIII). This reaction of the 1-alkyne (XXVII) with diisobutylaluminum hydride (XXVIII) provides the alane (XXIX) containing the trans-double bond and is carried out in an inert solution such as benzene, toluene, and the like at temperatures in the range of 40.degree.-60.degree. C. for several hours. It can also be carried out in a solvent such as tetrahydrofuran, usually in an approximate 2:1 mixture with benzene or hexane; in which case the reaction requires somewhat more vigorous conditions, usually treating at about 70.degree.-75.degree. C. for about 18 hours. The subsequent reaction with methyl or n-butyl lithium (R-Li) is preferably carried out in a mixture of the above solvents with an ether-type solvent such as diethyl ether, dibutyl ether, tetrahydrofuran and the like. This reaction is rapid and is preferably carried out at 0.degree.-10.degree. C. with cooling. The conjugate 1,4-addition of the resulting alanate salt (XXX) to the cycloalk-2-en-1-one (XXXI) is preferably carried out at ambient temperatures for a period of 12 to 24 hours. This reaction is also best carried out in an ether-type solvent such as diethyl ether, dibutyl ether, tetrahydrofuran, and the like. The intermediate alanate-enolate adduct is then carefully hydrolyzed in situ with dilute hydrochloric acid with cooling, and the products (XXXII) are isolated in the usual manner well known in the art. Removal of the triphenylmethyl blocking group can then be accomplished by treating with weak acid. A preferred procedure involves heating at 45.degree. C. for 3.5 hours in a solvent system consisting of acetic acid:tetrahydrofuran:water in the proportion of 4:2:1. Saponification in the usual manner of the resulting alkyl ester (XXVIII, R.sub.3 =alkoxy) provides the corresponding carboxylic acid (XXXIII, R.sub.3 =OH).

All available evidence leads us to the conclusion that in the product (XXXIII) the two side-chains attached to C.sub.8 and C.sub.12 are trans to each other. However, we are not certain of the configurational relationship in product (XXXII) as it is obtained directly from the alanate process. These products may have the side-chains in a trans or cis relationship or they may be a mixture containing both the trans- and cis-isomers. This is indicated in the nomenclature of the compounds involved by the designation of 85.xi.. In order to ensure a trans-relationship in both (XXXII) and (XXXIII) these products can be submitted to conditions known in the literature to equilibrate the cis-8-iso-PGE.sub.1 to a mixture containing about 90% of the trans product. These conditions involve treatment with potassium acetate in aqueous methanol for 96 hours at room temperature.

The triphenylmethyl blocking group for the hydroxy function in (XXVII) etc. is an important feature of this process and other oxygen blocking groups, e.g., tetrahydropyranyl and alkyl, are not compatible with a clean cis-addition of diisobutyl aluminum hydride (XXVIII) to the alkyne (XXVII) to provide the desired trans-vinyl function. Alternative procedures for the preparation of novel lithio alanate reagents useful for the introduction of the .DELTA..sup.13 -trans 15-oxy .beta.-chain by conjugate 1,4-addition are illustrated in Flowsheet K further below.

The intermediates for the introduction of the .DELTA..sup.13 -15-hydroxy side-chain are an integral part of this invention and they may be represented by the following general formulae (A), (B), (C), (D) and (E) wherein R'.sub.2 is as hereinabove defined, R is a lower alkyl group, not necessarily the same for each use, and R' is an alkyl group having from one to 10 carbon atoms not necessarily the same for each use, W.sub.1 is lower alkoxy, triphenylmethyl, or a triphenylmethyl group in which one or two of the phenyl rings is substituted with a lower alkoxy group; W.sub.2 is lower alkoxy, triphenylmethyl, a triphenylmethyl group in which one or two of the phenyl rings is substituted with a lower alkoxy group, tetrahydropyranyl, .alpha.-(lower alkoxy) substituted lower alkyl, t-butyl, or a tri(lower alkyl)silyl group; X.sub.1 is iodo or bromo; s is an integer having the value of one to three inclusive, and t is an integer having the value of one to three inclusive, with the proviso that the sum of s and t must be equal to four. ##STR14##

The alanate conjugate addition procedure is also useful for the synthesis of prostaglandin E.sub.1 (XL) as illustrated in Flowsheet E. This reaction sequence is carried out in the same manner as described for the sequence in Flowsheet D. It is to be noted that the introduction of the .DELTA..sup.13 -15-oxy chain proceeds trans to the 11-oxy function. For this synthesis, it is best to use the tetrahydropyranyl or trialkylsilyl esters, since these esters can be hydrolyzed under conditions compatible with the stability of the .beta.-ketol feature of prostaglandin E.sub.1. Alkyl esters would be hydrolyzed by fermentation with Baker's Yeast. The tetrahydropyranyl or trialkylsilyl, and triphenylmethoxy blocking groups are removed by mild acid treatment, for example with acetic acid:tetrahydrofuran:water (4:2:1) as described hereinabove. Application of the lithio alanate conjugate addition process to the synthesis of prostaglandins E.sub.2 and E.sub.3 is described below in connection with Flowsheet N. ##STR15##

The 13-dihydro derivatives (C.sub.13 -C.sub.14 is ethylene) of this invention can be prepared by reduction of the .DELTA..sup.13 function in the corresponding 13-prostenoic acids or esters. This reduction can be accomplished by hydrogenation. However this procedure is not cleanly applicable in the presence of other double bonds in the molecule. In the latter instance the 13-dihydro derivatives are preparable via conjugate addition of a Grignard derivative (XLII) to cycloalkenone (XLI) in the presence of a catalyst such as the tributylphosphine-cuprous iodide complex as set forth in Flowsheet F, wherein n, Z, R.sub.2 and R'.sub.3 are as hereinabove defined; Q is a blocking group; and X is chlorine, bromine or iodine, preferably bromine or iodine. The blocking group (Q) for the hydroxyl function in (XLII) can be any group stable to the Grignard reagent and which can later be removed by chemical treatment (e.g., mild hydrolysis or catalytic hydrogenolysis in the absence of carbon to carbon double bonds elsewhere in the molecule) to which the remainder of the molecule is stable. Suitable blocking groups, therefore, may be, for example, benzyl, diphenylmethyl, triphenylmethyl, tetrahydropyranyl, or a moiety of the formula: ##STR16## wherein R.sub.11 is hydrogen, methyl or ethyl. Among the above-described blocking groups, we have found tert-butyl to be particularly convenient and useful. ##STR17##

In accordance with the above reaction scheme, the conjugate 1,4-addition of a 3-(substituted hydroxy)alkyl or alkenyl magnesium halide (XLII) to a cycloalk-2-en-1-one (XLI) is carried out in the presence of a catalyst. In general, Grignard reactions with conjugated ketones provide 1,2-addition products; conjugate 1,4-addition is usually accomplished when the reaction is carried out in the presence of a cuprous chloride or cuprous acetate catalyst. It is therefore most unexpected that the reaction of the cycloalkenone (XLI) with a Grignard reagent (XLII) in the presence of either of the aforementioned catalysts does not give appreciable amounts of the desired 1,4-conjugate addition products. The novel feature of our process is provided by the use, as a catalyst, of a cuprous halide complex with a tri-substituted phosphine, a trialkyl phosphonate, a tertiary amine or a heterocycle containing a basic nitrogen (e.g., pyridine). We have found it preferable to use tributylphosphine-cuprous iodide complex; (C.sub.4 H.sub.9).sub.3 P.multidot.CuI. The reaction is best carried out in the usual way in an ether-type solvent such as diethyl ether, dibutyl ether, tetrahydrofuran, and the like, at room temperature for a period of time of from two to 18 hours. The intermediate magnesium halide-enolate adduct is then hydrolyzed in situ, preferably with ammonium chloride, at room temperature and the product (XLIII) is isolated in the usual manner well known in the art.

When the blocking group is a tertiary alkyl moiety such as tert-butyl, deblocking of (XLIII) to afford (XLIV) is conveniently effected by treatment with glacial trifluoroacetic acid at from -5.degree. C. to 10.degree. C. for a period of one to three hours. Since this procedure may lead to partial trifluoroacetylation of the free hydroxy function, it is preferably followed by treatment with aqueous ammonia (about 1.0N concentration) for about 15 minutes at ambient temperatures. When the blocking group is tetrahydropyranyl, its removal is readily effected with dilute acid. When the blocking group is a moiety such as benzyl, diphenylmethyl or triphenylmethyl, deblocking of (XLIII) is conveniently effected by catalytic hydrogenolysis, procedures for which are well known in the art. In the instance of triphenylmethyl, deblocking is preferably effected by treating with acetic acid:tetrahydrofuran:water (4:2:1) at about 45.degree. C. for about 3.5 hours.

Mild acid treatment results in hydrolysis of the tetrahydropyranyl esters; alkyl esters can be hydrolyzed by the usual saponification techniques.

When the cycloalkanone esters (XLIII) are formed by quenching of the reaction mixture with aqueous ammonium chloride solution, the relative stereochemical relationship of the two side-chains is not known with certainty. Therefore, the bond linking the Grignard-derived side-chain to the cycloalkyl ring is indicated by a bond in (XLIII). However, in any case, the subsequent deblocking and ester hydrolysis procedures ensure the development, at least in predominant proportion, of the thermodynamically favored trans-relationship between the two side-chains, as is depicted in structure (XLIV) of the reaction scheme.

An alternative method for the introduction of the .DELTA..sup.13 -15-hydroxy side-chain involves 1,4-conjugate addition to cycloalkenone (LV) of a vinyl Grignard reagent [(LIII) + (LIV)] in the presence of a catalyst such as the tributylphosphine cuprous iodide complex followed by deblocking. From this process, in addition to the product (LVIII) containing the C.sub.13 -C.sub.14 moiety as a trans-vinylene function there also is obtained the corresponding product (LIX) in which the C.sub.13 -C.sub.14 moiety is a cis-vinylene function. These novel cis-.DELTA..sup.13 derivatives are also embraced within the scope of this invention. The reaction sequence for the "vinyl" Grignard process is illustrated in flowsheet G, which follows, and in which W.sub.2, n, Z, R.sub.3 and R'.sub.3 are as hereinabove defined, and R".sub.2 is a straight chain alkyl group having from 2 to 10 carbon atoms, or a straight chain alkyl group having from 2 to 10 carbon atoms and substituted with one or two alkyl groups having from one to three carbon atoms. ##STR18##

In accord with the reaction sequence of Flowsheet G the vinyl Grignard reagent (LIII+LIV), is prepared under an inert atmosphere in a relatively limited amount of anhydrous tetrahydrofuran. More vigorous conditions (e.g., heating in an oil bath at 70.degree.-80.degree. C., one hour), for the formation of the Grignard reagent (LIII+LIV) favors the proportion of .DELTA..sup.13 -cis isomer (LIX) in the product of conjugate addition. Milder conditions (for example 35.degree.-47.degree. C., 1 hour) favors the proportion of .DELTA..sup.13 -trans isomer (LVIII) in the final product.

Conjugate addition of the vinyl Grignard reagent mixture [(LIII) + (LIV)] to cycloalkenone (LV) is then preferably carried out by addition of the Grignard to the cycloalkenone dissolved in an ether type solvent, e.g., diethylether, containing a catalyst such as the tributylphosphine-cuprous iodide complex at a temperature of about 0.degree. C. After a period of about thirty minutes to three hours the reaction mixture is poured onto aqueous concentrated ammonium chloride solution to give (LVI) + (LVII). As explained hereinabove, at this stage the relationship of the two side-chains to each other is not determined. In any event, deblocking the 15-hydroxy function with weak acid (which procedure also hydrolyzes trialkylsilyl or tetrahydropyranyl esters) provides the product (LVIII) and (LIX) in which the chains are trans to each other. In the instance of alkyl esters, saponification provides the corresponding carboxylic acids. The .DELTA..sup.13 -cis and .DELTA..sup.13 -trans-isomers can be separated from each other by the usual techniques of chromatography; particularly useful is liquid-liquid partition chromatography.

The precursor 3-hydroxy-1-trans-alkenyl bromides (LI) can be prepared, as illustrated in Flowsheet G, by condensation of acetylene (XLV) with an acid chloride (XLVI) in the presence of aluminum trichloride. The resulting 3-oxo-1-chloro-trans-1-alkylene (XLVII) is then converted to the corresponding 1-bromo derivative (XLVIII), by reaction with excess lithium bromide. This reaction is preferably carried out in ketone solvents, such as 2-pentanone or acetone. Reduction of the 3-keto function in (XLVIII), with for example, sodium borohydride provides the alcohol (LI). The alcohol function is then blocked to give (LII). Alternatively, the 3-oxo vinyl bromide (XLVIII) can be prepared directly from the acyl bromide (L) and acetylene (XLIX) in the presence of aluminum tribromide, preferably in ethylene dibromide.

The "vinyl Grignard" procedure outlined in Flowsheet G represents a novel, useful and convenient procedure for the synthesis of 13-prostenoic acids and the novel Grignard reagents represented by formulae (LIII) and (LIV) are to be considered as embraced within the scope of this invention.

The "vinyl Grignard" technique can also be applied to a useful synthesis of prostaglandin E.sub.1 and the novel .DELTA..sup.13 -cis-prostaglandin-E.sub.1 as illustrated in Flowsheet H, below. Thus, treatment of cyclopentenone (LX) with Grignard [(LXI + (LXII)] in accordance with the considerations discussed hereinabove, provides the conjugate addition products (LXIII) plus (LXIV), mild acid hydrolysis of which furnishes prostaglandin E.sub.1 (LXV) and .DELTA..sup.13 -cis prostaglandin E.sub.1 (LXVI), separable by chromatography. ##STR19##

The preparation of the cycloalkenone intermediates (LXXVI, LXXVII) bearing a cis double bond in the carboxylic acid side chain can be accomplished by the sequence illustrated in Flowsheet I, which follows and in which n and p are as hereinabove defined. ##STR20##

In the above Flowsheet I, the sequence wherein a 2-carbalkoxycycloalkanone (LXVII) is transformed to a 2(.beta.-hydroxyethyl)cycloalk-2-en-1-one (LXXIII) is carried out in the manner described in Flowsheet A. Methyl ether cleavage of the corresponding 2-(.beta.-methoxymethyl)cycloalkenone is achieved by treating with boron tribromide. Oxidation of the alcohol (LXXIII) with Collins reagent [chromium trioxide-pyridine complex in methylene chloride under anhydrous conditions; J. C. Collins, W. W. Hess, and F. J. Frank, Tetrahedron Letters, 3363 (1968)] provides the aldehyde (LXXIV), which is then treated in anhydrous dimethylsulfoxide with the ylid (LXXV) prepared from an (.omega.-carboxyalkyl)triphenyl phosphonium bromide and sodium hydride. The use of dimethylsulfoxide as a solvent for this reaction leads to the predominant formation of the desired cis double bond derivative (LXXVI). The acid function in (LXXVI) can be esterified in the usual fashion; with diazomethane, the methyl ester (LXXVII) is obtained.

Cyclopentenones such as (LXXVI wherein n=1) may also be prepared by the sequence illustrated in Flowsheet J, which follows and in which p is as hereinabove defined. ##STR21##

In Flowsheet J above the bicyclic hemiacetal (LXXVIII) [P. A. Grieco, Journ. Org. Chem., 37, 2363 (1972)] is treated with ylid (LXXIX) to give the 1-hydroxy-3-cyclopentene (LXXX). Oxidation with Jones reagent gives the corresponding ketone (LXXXI), which on base treatment furnishes the required cyclopentenone (LXXXII), which can then be esterified in the usual manner.

Certain of the intermediates illustrated in Flowsheets I and J, in particular the compounds of formulae (LXXI), (LXXII), (LXXIII), (LXXIV), (LXXVI) (LXXVII) (and releated esters), (LXXX) and (LXXXI) are noval and useful compounds and are embraced within the scope of this invention.

Alternative procedures for the preparation of the alanate intermediates to that discussed in connection with Flowsheet D above are illustrated below in Flowsheet K, wherein R', R'.sub.2, R".sub.2 and W.sub.2 are as hereinabove defined. ##STR22##

In accordance with the sequence of Flowsheet K above the 1-iodo-trans-1-alkenyl-3-oxo derivative (LXXXIV) is prepared by iodide interchange, preferably in acetone or similar ketone, from the corresponding chloride (LXXXIII), the preparation of which is described in connection with Flowsheet G above. Reduction of (LXXXIV) to the alcohol (LXXXVI) can be accomplished in the usual manner with sodium borohydride. The hydroxy function is then blocked to give (LXXXV, R'.sub.2 -R".sub.2). Treatment of the acetylene, ##STR23## with one equivalent of disiamylborane (prepared in situ from diborane and 2-methyl-2-butene) and then with excess anhydrous trimethylamine oxide followed by treatment with an aqueous solution of excess sodium hydroxide and a tetrahydrofuran solution of excess iodine is also productive of (LXXXV). Treatment of the trans-1-alkenyl iodide (LXXXV) at low temperatures, preferably at about -30.degree. C. to -78.degree. C., in an inert solvent, e.g., hexane or toluene, with an alkyl lithium, e.g., butyl lithium, provides the trans-1-alkenyl lithium reagent (LXXXVII). Treatment of this lithio derivative with a tri-alkyl aluminum furnishes the trans-1-alkenyl trialkyl alanate (LXXXVIII). Treatment of a dialkyl aluminum chloride with two molar equivalents of lithio reagent (LXXXVII) gives the bis(trans-1-alkenyl)dialkyl alanate (LXXXIX) and treatment of an alkylaluminum dichloride with three molar equivalents of lithio reagent (LXXXVII) affords the tris(trans-1-alkenyl)alkyl alanate (XC).

Each of the three types of alanates, (LXXXVIII), (LXXXIX) and (XC), can be utilized for 1,4-conjugate addition reactions as described hereinabove in connection with Flowsheets D and E above. Thus, substitution of (LXXXVIII), (LXXXIX) or (XC) for alanate (XXX) in Flowsheet D will provide the indicated products of the Flowsheet. Similarly, substitution of (LXXXVIII), (LXXXIX) or (XC) in which R'.sub.2 is n-pentyl for alanate (XXXVII) in Flowsheet E provides prostaglandins E.sub.1. In general the mono alkenyl alanate (LXXXVIII) is preferred because it is more economical in the use of vinyl halide.

With regard to the cycloakenones of Flowsheets D, E, F, G and H it should be noted that the blocking groups for the 4-hydroxy function as well as for the carboxylic acid may also be a tri-alkylsilyl group, e.g., trimethylsilyl, dimethyl-t-butylsilyl or dimethylisopropylsilyl. Cyclopentenones blocked in this manner are illustrated below in formula (XCI) and (XCII) wherein m, n, Z and R' (not necessarily the same for each use) are as hereinabove defined. ##STR24##

All the novel products of this invention exclusive of certain intermediates bear a hydroxy or oxy function substituted at or at what ultimately becomes the C.sub.15 atom of the product prostanoic acids and esters. Thus in at least most instances a 15-"normal" and a 15-"epi" racemate is obtained in at least near equal proportions. Each of the racemates contains equal amounts of the enantionmer wherein C.sub.15 is in the S configuration and the enantiomer wherein it is in the R configuration. The racemates are separable from each other by the usual techniques of chromatography. Also, resolution in the usual way of the .beta.-chain precursor [for example, the resolution of 3-hydroxy-1-octyne is described in the literature see R. Pappo, P. Collins and C. Jung. Ann. N.Y. Acad. of Science, 180 (Prostaglandins), 64(1971); J. Fried et al., ibid, p. 381.] Resolution prior to the conjugate addition operation will provide the diastereomers wherein the C.sub.15 atom is either in the 15(S) or 15(R) configuration, as desired. Separation of the diastereomers so obtained, for example, by chromatography, will give the fully resolved (d and l) products provided there are no asymmetric carbon atoms other than at C.sub.8 and C.sub.12. The presence of other asymmetric sites requires additional resolution steps in order to obtain a single atipode. The compounds of this invention embrace all possible optical isomers.

The Il-deoxy-9-keto derivatives (XCIV) of this invention can be converted to the corresponding 9-hydroxy derivatives. If this conversion is effected with sodium borohydride, the product is a mixture of 9.alpha.- and 9.beta.-hydroxy derivatives (XCIII) and (XCV) as set forth in the following reaction scheme: ##STR25## wherein R.sub.2, R.sub.3, R.sub.6, R.sub.7, Z, n and --C.sub.13 -C.sub.14 -- are as hereinabove defined. In general, when the reaction is carried out with lithium perhydro-9b-boraphenalyl hydride [H. C. Brown and W. C. Dickason, Journ. Amer. Chem. Soc., 92, 709 (1970)] the product is at least predominantly the 9.alpha.-hydroxy-derivative (XCIII), wherein the 9-hydroxy group is cis to the side-chain attached to C.sub.8.

In accordance with accepted convention, an .alpha.-substituent at the 8-, 9-, or 12-positions is behind the plane of the paper whereas a .beta.-substituent at these positions is in front of the plane of the paper. This is usually represented by a --- bond for an .alpha.-substituent, a -- bond for a .beta.-substituent, and a bond where both are indicated. Thus, the 9-hydroxy derivatives may be variously represented as follows: ##STR26##

A useful procedure for the introduction of the 15-lower alkyl group (R.sub.6) is illustrated by the sequences of Flowsheet M, which follows. ##STR27##

In Flowsheet M above n, Z, R.sub.2, R.sub.7 and R.sub.6 are as hereinabove defined. In the sequence depicted in Flowsheet M the 9,15-diol (XCVI) is treated with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) (XCVII), which preferentially oxidizes the allylic alcohol function at C.sub.15 to give the 15-ketone (XCVIII). Blocking of the remaining hydroxy function as a trimethylsilyl ether gives (IC) which is reacted with the alkyl Grignard, R.sub.6 MgI, to give the 15-alkyl-15-hydroxy derivative (CI). Hydrolysis of the silyl ether blocking group then gives the diol ester (C), saponification of which gives (CII). Oxidation of the secondary 9-hydroxy function in (C) provides the 15-alkyl-9-oxo ester (CIII), saponification of which furnishes (CIV). (A similar sequence can be effected with the .DELTA..sup.13 -cis-series.)

The processes of this invention are also useful for the preparation of prostaglandin E.sub.2 and prostaglandin E.sub.3 and thus also PGF.sub.2.alpha. and PGF.sub.3.alpha. by reduction, for example with lithium perhydro-9b-boraphenalyl hydride. The 4-hydroxycyclopentanone intermediate (CXI) required for these syntheses is prepared in accordance with the procedure illustrated in Flowsheet N which follows and in which is also shown the transformation of this compound to prostaglandins E.sub.2 and E.sub.3. In Flowsheet N, J is an appropriate blocking group for the hydroxy and ester function in (CXI) which is compatible with the conjugate addition reaction and also is ultimately removable by acid-catalyzed hydrolysis or other techniques which will not disrupt the sensitive 11-oxy-9-keto system in the products (CXIII), (CXV), (CXVIII) and (CXVII). Particularly useful for this purpose are the tetrahydropyranyl group and various trialkylsilyl groups (e.g., dimethylisopropylsilyl, trimethylsilyl, dimethyl-t-butylsilyl and the like. ##STR28##

In accordance with the above reaction scheme the 3,4-epoxylactol (CV) [E. J. Corey and R. Noyori, Tetrahedron Letters, 311 (1970)] is treated with the ylide (CVI) to give the 3,4-epoxycyclopentanol (CVII) bearing the .alpha.-chain of the prostaglandin 2 series. Oxidation (for example with H.sub.2 CrO.sub.4.-H.sub.2 SO.sub.4 -ether or Jones reagent) of (CVII) provides the epoxy ketone (CVIII), mild base treatment of which results in the initial formation of the 4-hydroxycyclopent-2-en-1-one (CXI) and the isomeric 3-hydroxycyclopent-4-en-1-one (CX) as a mixture. Further treatment of this mixture with dilute base under mild conditions (preferably pH 10.3-10.6 for 24 hours) results in the isomerization of the 3-hydroxy isomer (CX) to the desired (CXI). We believe that the transformation of the epoxy ketone (CVIII) to the hydroxycyclopentenones (CX) and (CXI) and the isomerization of (CX) to (CXI) may take place through the intermediacy of the 3,4-diol (CIX). It is also conceivable that isomerization of (CX) to (CXI) procedes via the epoxy derivative (CVIII) or the corresponding .alpha.-epoxide (CXIb); it is further conceivable that (CVIII) proceeds to (CX) and (CXI) directly without the intermediacy of (CIX). Another possible intermediate for the isomerization of (CX) to (CXI) is the corresponding diene (CXIa). The preparation of (CXI) is also possible via the .alpha.-epoxide series from (CXIc) via the .alpha.-epoxide corresponding to (CVII) and (CVIII) such as (CXIb) or via a mixture of the .alpha. and .beta. epoxides. In practice, it is most convenient to utilize a mixture of .alpha.- and .beta.-epoxides (CXIc and CV). The hydroxy and acid function in the 4-hydroxycyclopentenones (CXI) are then appropriately blocked to give (CXII). Appropriate blocking groups are tetrahydropyranyl, trimethylsilyl, dimethyl-isopropylsilyl, dimethyl-t-butylsilyl and the like. Treatment of (CXII) with the lithio alanate (CXIV) or its equivalent (see the discussion hereinabove for Flowsheets K and E) gives the conjugate addition product (CXIII) in which the configuration at C.sub.8 is undetermined. Mild acid treatment, for example with acetic acid:tetrahydrofuran:water, (4:2:1), of (CXIII) results in the removal of blocking groups, and if necessary equilibration to the all-trans configuration, to give prostaglandin E.sub.2 (CXV). Similarly treatment of (CXII) with the lithio alanate (CXVI) gives prostaglandin E.sub.3 (CXVII).

Substitution in Flowsheet N, of ylide (CXIX), wherein p is as hereinabove defined, for the ylide (CVI) provides, by transformations analogous to those described in Flowsheet N [(CV) to (CXI) and (CXII)], the 4-hydroxycyclopent-2-en-1-ones (CXX) and their blocked ether-esters (CXXI). These novel and useful intermediates are a part of the present invention. ##STR29##

The 8.beta.-lower alkyl group (R'.sub.7) is introduced as illustrated in Flowsheet O below via the bromomagnesium enolate (CXXV). This novel and useful intermediate is obtained by conjugate addition of the 1-alkenyl Grignard reagent [(CXXIII) + (CXXIV)], preferably prepared at about 35.degree. C., to the cycloalkenone (CXXII) in the presence of a catalyst such as the tri-n-butylphosphine cuprous iodide complex as described hereinabove in connection with Flowsheets G and H. It is also possible to utilize for these purposes in an analogous manner the magnesio enolate (CXXVIII) obtained by conjugate addition of Grignard (XLII) to cycloalkenone (XLI) as described hereinabove in connection with Flowsheet F, in which case the 13,14-dihydro derivative of this invention are obtained. In Flowsheet O below, n, Z, R.sub.3, R'.sub.3, R'.sub.2, W.sub.2, R.sub.2, Q and X are as hereinabove defined and R'.sub.7 is an alkyl group having up to 3 carbon atoms. When the magnesio enolate (CXXV) is treated with a lower alkyl halide, e.g., methyl iodide, it undergoes alkylation at the 8.beta.-site providing, after deblocking of the 15-oxy group in intermediate (CXXVI), the 8.beta.-alkyl derivative (CXXVII). In the instance of alkyl esters, saponification gives the corresponding carboxylic acids (CXXVII, R.sub.3 =OH). The compounds corresponding to (CXXVII) wherein C.sub.13 -C.sub.14 is a cis-vinylene double bond are preferably prepared by utilizing the vinyl Grignard reagent prepared at temperatures in the range of 70.degree.-75.degree. C., as discussed hereinabove (Flowsheets G and H).

Also obtained from the alkylation of (CXXV) is the 8.alpha.-alkyl-8-iso derivative corresponding to (CXXVI), which after deblocking provides the 8.alpha.-alkyl-8-iso-products (CXXIX). Usually the 8.alpha.-product is formed to a significantly lesser extent than the 8.beta.-product (CXXVI). The 8.alpha. and 8.beta. products are separable from each other by the usual techniques of chromatography. ##STR30##

Application of the 8-alkylation process to the 11-oxy series provides the novel compounds of formula (CXXX), wherein R.sub.1, R.sub.2, R.sub.6, Y and C.sub.13 -C.sub.14 are as hereinabove defined and wherein R'.sub.7 is an alkyl group having up to 3 carbon atoms, R.sub.8 is selected from the group consisting of hydrogen, lower alkanoyl, tetrahydropyranyl and tri-lower alkylsilyl groups, R.sub.9 is selected from the group consisting of hydroxy, alkoxy having from 1 to 12 carbon atoms, tetrahydropyranyloxy and tri-lower alkyl silyloxy groups, Z.sub.2 is a divalent radical selected from the group consisting of those of the formulae: ##STR31## wherein m, p, R.sub.4 and R.sub.5 are as hereinabove defined; and the moiety ##STR32## also be the divalent radical ##STR33## with the proviso that only one unsaturated bond can be directly adjacent to C.sub.15 ; and with the second proviso that when R.sub.6 is alkyl then R.sub.1 is hydrogen; and with the third proviso that the groups attached to C.sub.8 may be in the 8.beta.-alkyl (8-iso) configuration: ##STR34##

The novel compounds of formula (CXXX) are also embraced by this invention. The preparation of these compounds may be illustrated by the reaction sequence of Flowsheet P below, wherein R.sub.9, Z.sub.2, W.sub.2, R".sub.2, R'.sub.7 and R.sub.3 are as hereinabove defined and R'.sub.8 has all the possibilities defined above for R.sub.8 except that it is not hydrogen. ##STR35##

In accordance with the sequence of Flowsheet P above, treatment of the ether-ester 4-oxycyclopentenone (CXXXI) with the 1-alkylene Grignard reagents [(CXIII) + (CXXIV)] (see Flowsheet O) gives the bromomagnesio enolate (CXXXII). This operation also results in the introduction of the trans C.sub.13 -C.sub.14 double bond (as shown in CXXXII), as well as the corresponding compound with the cis-double bond. The trans bond is favored when the Grignard is prepared at lower temperatures, about 35.degree. C.; the cis-bond at higher temperatures, about 70.degree.-75.degree. C. This point is more fully discussed above in connection with Flowsheets G and H. The magnesio enolate (CXXXII) is a key intermediate and when it is treated with a lower alkyl halide, e.g. methyliodide, it undergoes alkylation to give the 8.beta.-lower alkyl derivative (CXXXIII). Deblocking of the 15-hydroxy blocking group (e.g., triphenylmethyl), and of the 11-hydroxy tetrahydropyranyl or trialkylsilyl ether blocking groups as well as of the tetrahydropyranyl or trialkyl silyl esters is accomplished under mild acid conditions, e.g. heating at 45.degree. C. for 3.5 hours in a solvent system consisting of acetic acid:tetrahydrofuran:water (4:2:1). This procedure provides (CXXXV). The compounds of structure (CXXXV) or (CXXXIII) can be converted to 8.beta.-alkyl prostaglandins of the A class (CXXXIV) by treatment with acid or base, a preferred procedure involves treatment in tetrahydrofuran:water (2:1) solvent 0.5N in hydrochloric acid for about 70 hours at ambient temperatures.

The novel compounds of this invention represented by formula (CXXXIV) and related compounds are particularly interesting sunce they represent "stabilized" prostaglandin A types, which cannot rearrange to the biologically relatively inactive prostaglandins of the B series.

Utilization of Grignard (XLII) (see Flowsheet F, hereinabove) in the sequence of Flowsheet P provides the compounds of (CXXX) wherein C.sub.13 -C.sub.14 is ethylene. Provided there are no other double bonds in the molecule these substances can also be obtained by catalytic hydrogenation of the compounds represented by formula (CXXXV).

The alkylation process described above for Flowsheets O and P also gives the corresponding 8.alpha.-alkyl derivatives which are separable from the 8.beta.-alkyl isomer by chromatography. Thus, for example, in Flowsheet O treatment of enolate (CXXV) with R'.sub.7 I gives not only the 8.beta.-alkyl product (CXXVI) as shown, but there also is obtained the 8.alpha.-alkyl derivative (CXXXVI) shown below. In Flowsheet P, alkylation of enolate (CXXXII) also provides, in addition to (CXXXIII) shown, the 8.alpha.-alkyl-8-iso product (CXXXVII), shown below. These 8.alpha.-alkyl-8-iso derivatives can be deblocked and carried through the same series of transformation shown for the 8.beta.-derivatives (CXXVI) and (CXXXIII) in Flowsheets O and P, respectively. These novel 8.alpha.-alkyl-8-iso derivatives and their transformation products are also a part of this invention, as are the key intermediate enolates represented by structures (CXXV) and (CXXXII). ##STR36##

The novel compounds of the present invention have potential utility as hypotensive agents, anti-ulcer agents, agents for the treatment of gastric hypersecretion and gastric erosion, bronchodilators, antimicrobial agents, anticonvulsants, abortifacients, agents for the induction of labor, agents for the induction of menses, fertility-controlling agents, central nervous system regulatory agents, analgesic agents, salt and water-retention regulatory agents, diuretics, fat metabolic regulatory agents, serum-cholesterol lowering agents, anti-inflammatory agents and as agents for the inhibition of platelet aggregation, and for the treatment of periodontal disease, glaucoma, uveitis, sickle cell anemia and psoriasis. Certain of the novel compounds of this invention possess utility as intermediates for the preparation of other of the novel compounds of this invention.

The compounds of this invention provide protection against the ulcerogenic properties of indomethacin. This assay was carried out in the following manner.

Rats were starved for 48 hours (water was given ad libitum). Indomethacin (20 mg./kg. of body weight) was administered by the subutaneous route and one-half the dose of the test compound was administered by gavage at the same time. After 3 hours, the second half of the test compound was administered also by Gavage. Five hours after the administration of indomethacin the animals were decapitated and the stomachs removed. The stomachs were washed with distilled water, blotted on gauze, cut along the larger curvature, and the contents rinsed with distilled water. The stomachs were spread out, pinned on a cork and visualized under magnifying glass for ulcers. The criteria for scoring of ulcers was as previously reported. [Abdel-Galil et al. Brit. J. Pharmac. Chemotherapy 33:1-14 (1968)].

______________________________________Score______________________________________0 Normal stomach1 Petechial hemmorhage or pin point ulcer2 1 or 2 small ulcers3 Many ulcers, a few large4 Many ulcers, mainly large______________________________________

Control animals treated with indomethacin but not test compound consistently give scores of about 3.0-3.5. Control animals treated with neither indomethacin nor test compound give scores of about 0.5-0.8. The results obtained in this assay with typical compounds of the present invention are set forth in Table 1 below. Compounds producing a score of 2.5 or lower are considered to be active.

TABLE I______________________________________ Total Oral dose; mg./kg. of body ScoreCompound weight Treated Control______________________________________9-oxo-15-hydroxy-16-ethyl-13-trans-prostenoic acid 25 1.7 3.29-oxo-15-hydroxy-13-cis-prostenoicacid 100 1.3 3.09-oxo-15-hydroxy-2-ethyl-13-trans-prostenoic acid 50 2.2 3.09-oxo-8.beta.-methyl-15-hydroxy-13-trans-prostenoicacid 12.5 2.0 3.09-oxo-3-thia-15-hydroxy-13-trans-prostenoic acid 25 1.8 3.29-oxo-3-thia-15-epi-hydroxy-13-trans-prostenoicacid 25 2.3 3.2______________________________________

The novel compounds of the present invention are also effective inhibitors of gastric acid secretion and of ulcer development in experimental animals, and thus are potentially valuable as agents for the control of gastric acid secretion and of gastric erosion and an anti-ulcer agents. Gastric acid secretion inhibitory action is usually measured by the "Shay rat" procedure.sup.(1,2) with some modifications as follows.

The rats (male, CFE strain) were starved for 48 hours (water was given ad libitum) to permit evacuation of stomach contents. On the morning of the experiment, under ether anesthesia, the abdominal region was shaved and a midline incision (1-1 1/2") was made with a scapel. With the help of a closed curved hemostate the duodenum was picked up. Upon getting the duodenum into view, fingers were used to pull the stomach through the opening, the stomach was then gently manipulated with fingers to rid the stomach of air and residual matter which were pushed through the pylorus. Two-5 inch sutures were drawn under the pyloric-duodenal puncture. A ligature, at the juncture was formed with one of the threads. The second ligature was also formed but not tightened.

The test compound or the vehicle, usually 1 ml./mg. body weight, were injected into the duodenum as close as possible to the first ligature. After injection the second ligature was tightened below the injection site to minimize leakage. The stomach was placed back through the opening into the abdominal cavity, the area of incision was washed with saline and the incision was closed with autoclips. (Occasionally, instead of an intraduodenal injection, animals were dosed by the oral or subcutaneous route. In the latter case, dosing was done thirty to sixty minutes before the operation.)

Three hours later, the rats were decapitated and exanguinated, taking care that blood did not drain into the estophagus. The abdominal cavity was exposed by cutting with scissors and the esophagus close to the stomach was clamped off with a hemostat, the stomach was removed by cutting above the hemostat (the esophagus was cut) and between the two sutures. Extraneous tissue was removed, the stomach washed with saline and blotted on gauze. A slit was carefully made in the stomach which was held over a funnel and the contents were collected in a centrifuge tube. The stomach was futher cut along the outside edge and turned inside out. Two ml. H.sub.2 O were used to wash the stomach contents into the respective centrifuged tube. The combined stomach contents and wash were then centrifuged out for 10 minutes in the International Size 2 Centrifuge (setting at 30). The supernatant was collected, volume measured and recorded, 2 drops of a phenolphthalein indicator (1% in 95% ethanol) were added and the solution was titrated with 0.02N NaOH (or with 0.04N NaOH when large volumes of stomach contents were encountered) to pH 8.4 (because of usual coloring of the stomach contents, phenolphthalein was only used to permit visual indication that the end point was near) and the amount of acid present was calculated.

Compounds inducing inhibition of gastric acid secretion of 20% or more were considered active. In a representative operation, and merely by way of illustration, the results obtained with this assay with a typical compound of the present invention are given in Table 2, below.

TABLE 2______________________________________ Intraduodenal dose, mg./kg. PercentCompound of body weight Inhibition______________________________________9-oxo-15-hydroxy-3,3-dimethyl-13-trans-prostenoicacid 100 51______________________________________

Bronchodilator activity was determined in guinea pigs against bronchospasms elicited by intravenous injections of 5-hydroxytryptamine, histamine or acetylcholine by the Konzett procedure. [See J. Lulling, P. Lievens, F. El Sayed and J. Prignot, Arzeimittel-Forschung, 18 995 (1968).]

In the Table which follows bronchodilator activity for representative compounds of this invention against one or more of the three spasmogenic agents is expressed as an ED.sub.50 determined from the results obtained with three logarithemic cumulative intravenous doses.

TABLE 2A______________________________________Bronchodilator Activity (Konzett Assays)ED.sub.50, mg./kg. Spasmogenic Agent 5-hydroxy-Compound tryptamine histamine choline______________________________________9-oxo-15-hy-droxy-16-ethyl-13-trans-pro- -- 81.3 .times. 10.sup.-6 --stenoic acid9-oxo-15-hy-droxy-13-cis- 106 .times. 10.sup.-6 81.3 .times. 10.sup.-6 320 .times. 10.sup.-6prostenoicacid9-oxo-15-hy-droxy-2-ethyl- 329 .times. 10.sup.-6 145 .times. 10.sup.-6 533 .times. 10.sup.-613-trans-pro-stenoic acid9-oxo-15-hy-droxy-16-pro-stynoic acid 50.8 .times. 10.sup.-6 92.6 .times. 10.sup.-6 320 .times. 10.sup.-6______________________________________

The novel compounds of the present invention are useful as hypotensive agents and their prostaglandin-like hypotensive activity was demonstrated in the following test procedure. This procedure is a modification of the technique described by Pike et al., Prostaglandins, Nobel Symposium 2, Stockholm, June, 1966; p. 165.

Male Wistar strain rates (Royal Hart Farms) averaging approximately 250 grams in weight were fastened to rat boards in a supine position by means of canvas vests and limb ties. The femoral area was infiltrated subcutaneously with lidocaine and the iliac artery and vein were exposed and cannulated. Arterial blood pressure (systolic/diastolic) was recorded using a Statham P.sub.23 Db pressure, the animals were anethetized before use with pentobarbital, 30 mg./kg. of body weight intravenously, and also were given hexamethoxium bitartrate, 2 mg./kg. of body weight intravenously. The test compounds were prepared by ultrasonic dispersion in a saline-Tween 80.RTM. vehicle. A constant intravenous dose volume of 0.5 ml. was administered and test doses ranged from 0.1 to 10.0 mg./kg. of body weight. Increasing or decreasing doses were selected depending on the dose response obtained. In Table 2B below are set forth the minimal doses required to produce a decrease of about 10 mm. in diastolic blood pressure for typical compounds of the present invention.

TABLE 2B______________________________________HYPOTENSIVE ACTIVITY Minimal effective hypotensive doseCompound (mg./kg. of body wt.)______________________________________2-ethyl-9-oxo-15-hydroxy-13-trans-pro-stenoic acid <22-ethyl-9-oxo-15-epi-hydroxy-13-trans-pro-stenoic acid 2-42-ethyl-9-oxo-15-hydroxy-prostanoicacid 0.22-methyl-9-oxo-15-epi-hydroxy-13-trans-pro-stenoic acid 22-methyl-9-oxo-15-hydroxy-13-trans-pro-stenoic acid 28.beta.-methyl-9-oxo-15-hydroxy-13-trans-prostenoic acid 29-oxo-15-hydroxy-16-ethyl-13-trans-pro-stenoic acid <83,3-dimethyl-9-oxo-15-hydroxy-13-trans-pro-stenoic acid 89-oxo-15-hydroxy-13-cis-prostenoic acid 2-49-oxo-15-hydroxy-13-trans,17-cis-prosta-dienoic acid <29-oxo-15-hydroxy-16-prostynoic acid 29-oxo-15-hydroxy-5-cis,13-trans,17-cis-prosta-trienoic acid <23-oxa-9-oxo-15-hydroxy-13-trans-prostenoicacid <23-oxa-9-oxo-15-epi-hydroxy-13-trans-pro-stenoic acid 1-23-thia-9-oxo-15-hydroxy-13-trans-prostenoicacid 23-thia-9-oxo-15-epi-hydroxy-13-trans-prostenoic acid 29-oxo-15-hydroxy-16-trans-prostenoic acid <22-phenyl-9-oxo-15-hydroxy-13-trans-prostenoic acid 82-phenyl-9-oxo-15-epi-hydroxy-13-trans-pro-stenoic acid 2-82-fluoro-9-oxo-15-hydroxy-13-trans-pro-stenoic acid 87a,7b-bishomo-9-oxo-15-hydroxy-13-trans-prostenoic acid <89-oxo-10a-homo-15-hydroxy-13-trans-pro-stenoic acid 29-oxo-10a-homo-15-epi-hydroxy-13-trans-prostenoic acid 29-oxo-15-hydroxy-15-methyl-5-cis,13-trans,17-cis-prostatrienoicacid <2Ethyl 3-oxa-9-oxo-15-hydroxy-13-trans-prostenoate 0.2Ethyl 3-oxa-9-oxo-15-epi-hydroxy-13-trans-prostenoate 0.2Ethyl 9-oxo-10a-homo-15-hydroxy-13-trans-prostenoate 29-oxo-15-hydroxy-16,16-dimethyl-13-trans-prostenoic acid <29-oxo-15-hydroxy-17,17-dimethyl-13-trans-prostenoic acid 23-thia-9-oxo-15-hydroxy-16,16-dimethyl-13-trans-prostenoic acid <23-oxa-9-oxo-15-hydroxy-16,16-dimethyl-13-trans-prostenoic acid <2______________________________________

This invention will be described in greater detail in conjunction with the following specific examples. In these examples it is to be noted that Example 724 follows directly after Example 699.

In the examples which follow reference to 15-hydroxy or 15-oxy derivatives, unless otherwise indicated is inclusive of both the 15-epi and 15-normal racemates. In addition, all possible antipodes resulting from asymetry at C.sub.8, C.sub.12 and elsewhere in the prostenoic acid molecule are included.

EXAMPLE 1

Preparation of 2-carbalkoxy(methyl/ethyl)-2-(4carbethoxybutyl)-cyclopentan-1-one

To a stirred solution of the sodium cyclopentanone carboxylate enolate in dimethoxyethane, prepared from 187 g. (1.248 moles) of 2-cyclopentanone carboxylate (mixed methyl and ethyl esters), 52.4 g. (1.248 moles) sodium hydride (57.2% in mineral oil) and 1.6 l. of dimethoxyethane, is added dropwise 309 g. (1.212 moles) of ethyl 5-iodovalerate. The reaction mixture is stirred and heated at reflux for 18 hours. The mixture is cooled and filtered. The solvent is removed from the filtrate by evaporation and the residue is poured into dilute hydrochloric acid and extracted with ether. The combined extracts are washed with water and saline, dried over magnesium sulfate and evaporated to give an oil. The oil is distilled under reduced pressure to give 274 g. of a light yellow oil, b.p. 140.degree.-143.degree. C. (0.17 mm).

EXAMPLE 2

Preparation of 2-(4-carboxybutyl)cyclopenta-1-one

A stirred mixture of 274 g. of 2-carbalkoxy(mixed methyl and ethyl esters)-2-(4-carbethoxybutyl)cyclopentan-1-one (Example 1), 600 ml. of 20% hydrochloric acid and 325 ml. of acetic acid is heated at reflux of 20 hours. Solution occurs in approximately 1/2 hour. The solution is cooled and diluted with water and extracted with ether. The combined extracts are washed with saline and dried over magnesium sulfate and evaporated. The residue is evaporated twice with toluene to give 144 g. of an oil.

EXAMPLE 3

Preparation of 2-(4-carbethoxybutyl)cyclopentan-1-one

A stirred solution of 124 g. (0.673 mole) of 2-(4-carboxybutyl)cyclopentan-1-one (Example 2), 800 ml. of ethanol and 1 g. of p-toluenesulfonic acid monohydrate is heated at reflux for 18 hours. The solvent is evaporated and the residue is dissolved in ether. The ether solution is washed with saline, dilute sodium bicarbonate solution and again with saline, dried over magnesium sulfate and evaporated. The oil is distilled under reduced pressure to give 149 g. of a colorless oil, b.p. 106.degree. - 109.degree. C. (0.23 mm).

EXAMPLE 4

Preparation of 2-carbalkoxy(methyl/ethyl)-2-(3-carbethoxypropyl)-cyclopentan-1-one

In the manner described in Example 1, treatment of 2-cyclopentanone carboxylate (mixed methyl and ethyl esters) with sodium hydride in dimethoxyethane followed by ethyl 4-iodobutylrate gives a yellow oil, b.p. 136.degree.-137.degree. C. (0.16 mm).

EXAMPLE 5

Preparation of 2-(3-carboxypropyl)cyclopentan-1-one

In the manner described in Example 2, treatment of 2-carbalkoxy(mixed methyl and ethyl esters)-2-(3-carbethoxypropyl)cyclopentan-1-one (Example 4) with a 20% hydrochloric acid and acetic acid mixture gives a yellow oil.

EXAMPLE 6

Preparation of 2-(3-carbethoxypropyl)cyclopentan-1-one

In the manner described in Example 3, treatment of 2-(3-carboxypropyl)cyclopentan-1-one (Example 5) with p-toluene-sulfonic acid monohydrate in ethanol gives a colorless oil, b.p. 93.degree. C. (0.10 mm).

EXAMPLE 7

Preparation of ethyl and methyl 2-(6-carbethoxyhexyl)-1-cyclopentanon-2-carboxylate

In the manner described in Example 1, ethyl and methyl 2-cyclopentanone carboxylate is reacted with ethyl 7-bromoheptanoate to furnish the subject product, b.p. 147.degree. C. (0.09 mm).

EXAMPLE 8

Preparation of 2-(6-carboxyhexyl)cyclopentan-1-one

In the manner described in Example 2, ethyl and methyl 2-(6-carbethoxyhexyl)-1-cyclopentanone-2-carboxylate (Example 7) is hydrolyzed to furnish the subject product, b.p. 143.degree. C. (0.05 mm).

EXAMPLE 29

Preparation of 2-(6-carbethoxyhexyl)cyclopentan-1-one

In the manner described in Example 3, 2-(6-carboxyhexyl)cyclopentan-1-one (Example 8) is esterified to furnish the subject product, b.p. 110.degree. C. (0.03 mm).

EXAMPLE 10

Preparation of 1-acetoxy-2-(6-carbethoxyhexyl)cyclopent-1-ene

A stirred solution of 100 g. of 2-(6-carbethoxyhexyl)cyclopentan-1-one (Example 9) in 250 ml. of acetic anhydride containing 0.940 g. of p-toluenesulfonic acid monohydrate is heated to boiling under partial reflux allowing distillate at 118.degree. C. or less (i.e., acetic acid) to escape through a Vigreaux column equipped with a condenser to collect the distillate. After 16 hours, during which period actic anhydride is added in portions in order to keep the solvent level at at least 100 ml., the solution is cooled and poured cautiously into a stirred cold mixture of saturated sodium bicarbonate solution (400 ml.) and hexane (250 ml.). The resulting mixture is stirred for an additional 30 minutes during which period solid sodium bicarbonate is added periodically to insure a basic solution. The hexane layer is separated and washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness. Distillation of the residual oil gives 102 g. (87%) of pale yellow oil, b.p. 118.degree. C. (0.07 mm).

EXAMPLE 11

Preparation of 1-acetoxy-2-(3-carbethoxypropyl)cyclopent-1-ene

In the manner described in Example 10, treatment of 2-(3-carbethoxypropyl)cyclopentan-1-one (Example 6) with acetic anhydride and p-toluenesulfonic acid monohydrate gives a yellow oil, b.p. 98.degree.-103.degree. C. (0.35 mm).

EXAMPLE 12

Preparation of 1-acetoxy-2-(4-carbethoxybutyl)cyclopent-1-ene

In the manner described in Example 10, treatment of 2-(4-carbethoxybutyl)cyclopentan-1-one (Example 3) with acetic anhydride and p-toluenesulfonic acid monohydrate gives a yellow oil, b.p. 109.degree.-110.degree. C. (0.37 mm).

EXAMPLE 13

Preparation of 2-(6-carbethoxyhexyl)cyclopent-2-en-1-one

To a rapidly stirred mixture of 50 g. of 1-acetoxy-2-(6-carbethoxyhexyl)cyclopent-1-ene (Example 10) in 150 ml. of chloroform, 200 ml. of water and 18.8 g. of calcium carbonate, cooled in an ice bath, is added dropwise over a period of about 30 minutes, a solution of 30 g. of bromine in 50 ml. of carbon tetrachloride. After stirring for an additional 45 minutes the chloroform layer is separated and washed successively with dilute sodium thiosulfate solution, saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness under reduced pressure.

The residual oil is dissolved in 50 ml. of N,N-dimethylformamide and added to a mixture of 33 g. of lithium bromide and 32 g. of lithium carbonate in 375 ml. of N,N-dimethylformamide, previously dried by refluxing with 375 ml. of benzene under a Dean-Stark apparatus followed by distillation of the benzene. The mixture is stirred at the reflux temperature for 30 minutes, then cooled and poured into 850 ml. of ice-cold water. The resulting mixture is acidified (cautiously) with 4N hydrochloric acid and extracted with ether three times. The combined ether extracts are washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness under reduced pressure to afford 41.5 g. of an amber oil. In order to convert any isomeric material to the desired product, 41.5 g. of the above material is treated with 0.500 g. of p-toluenesulfonic acid monohydrate in 450 ml. of absolute alcohol at the reflux temperature for 18 hours. The solution is taken to dryness under reduced pressure. The resulting gum is dissolved in ether and washed with saturated sodium bicarbonate solution, saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness under reduced pressure. The residual oil is distilled to give 30.2 g. of product; b.p. 118.degree. C. (0.05 mm); .lambda..sub.max.sup.MeOH 229 m.mu. (.epsilon.9950); .lambda..sub.max 5.75, 5.85, 6.15, 8.45 .mu.; vapor phase chromatography shows 99% product, containing 1% 2-(6-carbethoxyhexyl)cyclopentan-1-one.

This product can be purified by the following procedure. A mixture of 120 g. of 2-(6-carbethoxyhexyl)-2-cyclopentenone, containing approximately 5% of the saturated analogue, and 7.67 g. (10 mole percent) of p-carboxyphenylhydrazine in 400 ml. of absolute ethanol is stirred at ambient temperatures for 18 hours and is then refluxed for 1 hour. The mixture is cooled, the solvent is evaporated, and the residue is taken up into 150 ml. of chloroform and passed through a column of 450 g. of aluminum oxide (Merck). The filtrate is evaporated to yield a colorless oil containing <0.5% of the saturated impurity.

EXAMPLE 14

Preparation of 2-(3-carbethoxypropyl)cyclopent-2-en-1-one

In the manner described in Example 13, bromination of 1-acetoxy-2-(3-carbethoxypropyl)cyclopent-1-ene (Example 11) followed by dehydrobromination with lithium bromide and lithium carbonate is productive of the subject compound.

EXAMPLE 15

Preparation of 2-(4-carbethoxybutyl)cyclopent-2-en-1-one

In the manner described in Example 13, treatment of 1-acetoxy-2-(4-carbethoxybutyl)cyclopent-1-ene (Example 12) with bromine and subsequent treatment of the brominated product with a mixture of lithium bromide and lithium carbonate in N,N-dimethylformamide is productive of the subject compound. Treatment of this product with p-carboxyphenylhydrazine by the procedure of Example 13 furnishes a product with contains less than 0.5% of the corresponding saturated ketone.

EXAMPLE 16

Preparation of 1-methoximino-2-(6-carbethoxyhexyl)-2-cyclopentene

To a mixture of 35.97 g. (0.151 mole) of 2-(6-carbethoxyhexyl)-2-cyclopentenone (Example 13) and 15.0 g. (0.180 mole) of methoxyamine hydrochloride in 300 ml. of absolute ethanol is added 25 ml. of pyridine and the resulting solution is stirred for 20 hours at ambient temperatures. The solvent is evaporated and the residue is partitioned between water and diethyl ether. The organic phase is washed with water and saturated brine, dried (Na.sub.2 SO.sub.4), and the solvent is evaporated to yield an oil. Distillation yields 38.7 g. of a colorless oil, b.p. 115.degree.-118.degree. C. (0.075 mm). IR (film): 1740, 1627, 1053, 890 cm.sup.-1. .lambda..sub.max (MeOH) 243 (13,000). NMR.delta.(CDCl.sub.3): 3.89.

EXAMPLE 17

Preparation of 1-methoximino-2-(7-hydroxyheptyl)-2-cyclopentene

To an ice cooled solution of 34.10 g. (0.128 mole) of 1-methoximino-2-(6-carbethoxyhexyl)-2-cyclopentene (Example 16) in 200 ml. of benzene under nitrogen is added dropwise 225 ml. of a 25% solution of diisobutyl aluminum hydride in hexane. The resulting solution is stirred for 2 hours at 0.degree.-5.degree. C., poured onto ice and dilute hydrochloric acid, and the aqueous phase is saturated with sodium chloride. The organic phase is separated, washed with saturated brine, dried (Na.sub.2 SO.sub.4), and evaporated to yield an oil. The latter is dissolved in 100 ml. of hot hexane and cooled to yield 24.3 g. of crystals, m.p. 62.degree.-64.degree. C. IR (KBr) 3260, 1630, 1059, 893 cm.sup.-1. .lambda..sub.max 243 (14,200). NMR (CDCl.sub.3).delta.: 2.37.

EXAMPLE 18

Preparation of 1-methoximino-2-(7-p-toluenesulfonyloxyheptyl)-2-cyclopentene

To a solution of 5.00 g. (0.0222 mole) of 1-methoximino-2-(7-hydroxyheptyl)-2-cyclopentene (Example 17) in 50 ml. of dry pyridine at 0.degree. C. is added 8.45 g. (0.0444 mole) of p-toluenesulfonyl chloride and the resulting solution is chilled at 5.degree. C. overnight. The mixture is partitioned between 300 ml. of ice water and diethyl ether. The organic phase is washed with 1:1 ice cold hydrochloric acid, cold water, and cold saturated brine, dried (NaSO.sub.4 /K.sub.2 CO.sub.3), and evaporated under reduced pressure at room temperature to yield an oil. The latter is dissolved in 600 ml. of hexane, treated with 0.5 g. of Darco, filtered and evaporated to yield 7.7 g. of a colorless oil. IR (film) 1600, 1192, 1182, 1053, 890 cm.sup.-1. .lambda.max (MeOH) 228 and 243.

EXAMPLE 19

Preparation of 1-methoximino-2-(8,8-dicarbethoxyoctyl)-2-cyclopentene

To an alcoholic solution of sodiodiethyl malonate, prepared from 0.847 g. (0.0368 g. atoms) of sodium, 100 ml. of absolute ethanol, and 7.05 g. (0.0440 mole) of diethyl malonate is added 7.7 g. of the tosylate of Example 18 and the mixture is refluxed for 2 hours under a nitrogen atmosphere. The mixture is partitioned between cold dilute hydrochloric acid and diethyl ether, and the organic phase is washed with water and saturated brine, dried (Na.sub.2 SO.sub.4), and evaporated to yield an oil. The excess diethyl malonate is distilled off under reduced pressure to yield 6.45 g. of a yellowish oil. IR (film) 1755, 1728, 1625, 1054, 890 cm.sup.-1.

EXAMPLE 20

Preparation of 1-methoximino-2-(8,8-dicarboxyoctyl)-2-cyclopentene

A mixture of 6.45 g. of the diester of Example 19 and 6.72 g. of potassium hydroxide in 150 ml. of 1:1 aqueous methanol is refluxed for 1 hour, cooled, and is partitioned between water and diethyl ether. The aqueous phase is acidified with hydrochloric acid, extracted with ether, and the organic phase is washed with water and saturated brine, dried (Na.sub.2 SO.sub.4) and evaporated to yield a solid. The solid is crystallized from benzene to yield 4.15 g. of tan crystals, m.p. 135.degree.-137.degree. C. (--CO.sub.2).

EXAMPLE 21

Preparation of 1-methoximino-2-(8-carboxyoctyl)-2-cyclopentene

A solution of 3.926 g. (0.0126 mole) of the diacid of Example 20 in 20 ml. of xylene is refluxed for 1.5 hours, cooled, and evaporated to yield a tan solid. IR (KBr) 1720, 1618, 1179, 1050, 986 cm.sup.-1.

EXAMPLE 22

Preparation of 2-(8-carboxyoctyl)cycopent-2-en-1-one

The acid methoxime from Example 21 is refluxed for 5 hours with 55 ml. of acetone and 20 ml. of 2N hydrochloric acid. The mixture is cooled, the solvent is evaporated, and the residue is partitioned between water and diethyl either. The organic phase is washed with water and saturated brine, dried (Na.sub.2 SO.sub.4), and evaporated to yield a tan solid. IR (KBr) 1745, 1665 cm.sup.-1. .lambda..sub.max (MeOH) 228 (12,600).

EXAMPLE 23

Preparation of 2-(8-carbethoxyoctyl)cyclopent-2-en-1-one

The acid ketone from Example 22 is Fisher esterified with 100 ml. of absolute ethanol, 100 ml. of benzene, and 20 mg. of p-toluenesulfonic acid for 6 hours, cooled, and the solvent is evaporated. The resulting oil is dissolved in 3:1 benzene-ether and the solution is passed through a column of 100 g. of Florisil.RTM.. The filtrate is evaporated and the residue is distilled to yield 2.97 g. of a colorless oil, b.p. 137.degree.-139.degree. C. (0.05 Torr).

EXAMPLE 24

Preparation of 2-(4-carbethoxybutyl)-2-cyclopentenone methoxime

Treatment of 2-(4-carbethoxybutyl)-2-cyclopentene (Example 15) with methoxyamine hydrochloride in the manner described in Example 16 gives an oil, b.p. 107.degree.-109.degree. C. (0.05 mm). IR (film): 1740, 1628, 1050, 885 cm.sup.-1. .lambda..sub.max (MeOH) 243 (13,600).

EXAMPLE 25

Preparation of 2-(5-hydroxypentyl)-2-cyclopentenone methoxime

Treatment of 2-(4-carbethoxybutyl)-2-cyclopentenomethoxime (Example 24) with diisobutyl aluminum hydride in the manner described in Example 17 gives crystals, m.p. 33.degree.-35.degree. C. IR (KBr) 3420, 1630, 1050, 886 cm.sup.-1. .lambda..sub.max.sup.MeOH 243 (12,020).

EXAMPLE 26

Preparation of 2-(5-p-toluenesulfonyloxypentyl)-2-cyclopentenone methoxime

Treatment of 2-(5-hydroxypentyl)-2-cyclopentenone methoxime (Example 25) with p-toluenesulfonyl chloride in pyridine in the manner described in Example 18 gives a colorless oil. IR (film) 1600, 1190, 1180, 1050, 885 cm.sup.-1.

EXAMPLE 27

Preparation of 2-(6,6-dicarbethoxyoctyl)-2-cyclopentenone methoxime

To a solution of sodio diethyl ethylmalonate, prepared from 1.63 g. (0.387 mole) of sodium hydride in mineral oil (57.2%), 100 ml. of ethylene glycol dimethyl ether and 8.5 g. (0.0452 mole) of ethyl diethyl malonate, is added 7.5 g. of tosylate from Example 26 in 20 ml. of ethylene glycol dimethyl ether and the mixture is refluxed for 3 hours and then allowed to stand at room temperature for 18 hours under nitrogen atmosphere. The reaction mixture is filtered and most of the solvent is removed. The mixture is partitioned between cold dilute hydrochloric acid and diethyl ether, and the organic phase is washed with water and saturated brine, dried (MgSO.sub.4), and evaporated to yield an oil. The excess ethyl diethyl malonate is distilled off under reduced pressure to yield 6.7 g. of a yellow oil. IR (film) 1755, 1728, 1627, 1050, 885 cm.sup.-1.

EXAMPLE 28

Preparation of 2-(6,6-dicarboxyoctyl)-2-cyclopentenone methoxime

Treatment of 2-(6,6-dicarbethoxyoctyl)-2-cyclopentenone methoxime (Example 26) with potassium hydroxide, and 1:1 aqueous methanol in the manner described in Example 20 gives a light yellow oil.

EXAMPLE 29

Preparation of 2-(6-carboxyoctyl)-2-cyclopentenone methoxime

In the manner described in Example 21, treatment of 2-(6,6-dicarboxyoctyl)-2-cyclopentenone methoxime (Example 28) with xylene at reflux for 18 hours gives a yellow oil.

EXAMPLE 30

Preparation of 2-(6-carboxyoctyl)-2-cyclopentenone

Treatment of 2-(6-carboxyoctyl)-2-cyclopentenone methoxime (Example 29) with acetone and 2N hydrochloric acid in the manner described in Example 22 gives a light yellow oil.

EXAMPLE 31

Preparation of 2-(6-carbethoxyoctyl)-2-cyclopentenone

Treatment of 2-(6-carboxyoctyl)-2-cyclopentenone (Example 30) with thionyl chloride and then treatment of the acid chloride with ethanol in the usual manner gives an amber oil. The oil is placed on a magnesia-silica gel column and eluted with 3:1 benzene:ether. The solvent is removed and the residue is distilled, b.p. 122.degree. C. (0.06 mm).

EXAMPLE 32

Preparation of diethyl 1,1-dimethyl-5-tetrahydropyranylpentylmanlonate

To 486 mg. (0.02 g.-atoms) of magnesium in 5 ml. of toluene containing one molar equivalent of tetrahydrofuran per equivalent of magnesium and one percent iodine (calculated in weight of magnesium) is added dropwise 3.86 g. (0.02 mole) of 4-chloro-1-tetrahydropyranyloxybutane over a period of one hour with stirring, under nitrogen at 70.degree. C. The reaction mixture is stirred at 70.degree. C. for four hours. This reagent is then added dropwise to 3 g. (0.015 mole) of ethyl isopropylidenemalonate in 40 ml. of tetrahydrofuran containing 392 mg. of tetrakis [iodo(tri-n-butylphosphine)copper (I)] and stirred at room temperature for 2 hours. The reaction mixture is poured into cold dilute hydrochloride acid and extracted with ether. The ether extract is dried over magnesium sulfate and concentrated to give 5.92 g. of subject product as an oil.

EXAMPLE 33

Preparation of diethyl 1,1-dimethyl-5-hydroxypentylmalonate

A solution of 3.5 g. (0.01 mole) of diethyl 1,1-dimethyl-5-tetrahydrofuranyloxypentylmalonate in 70 ml. of ethanol containing 3 ml. of hydrochloric acid is allowed to stir at room temperature for 18 hours. The solution is concentrated, diluted with water and extracted with ether. The ether extract is washed with wateer, dried over magnesium sulfate and concentrated to give 3.262 g. of a light yellow oil. The oil is purified by distillation, b.p. 116.degree.-117.degree. C. (0.05 mm).

EXAMPLE 34

Preparation of 3,3-dimethyl-7-hydroxyheptanoic acid

A mixture of 32 g. (0.117 mole) of diethyl 1,1-dimethyl-5-hydroxypentylmalonate, 25 g. of potassium hydroxide and 600 ml. of methanol-water (1:1) is heated at reflux for 8 hours and then allowed to stand at room temperature for 18 hours. The methanol is removed, diluted with water and the reaction mixture is acidified with concentrated hydrochloric acid. The mixture is extracted with ether. The extract is washed with water and saline, dried over anhydrous magnesium sulfate and concentrated to give 27 g. of 1,1-dimethyl-5-hydroxypentylmalonic acid. This crude oil is dissolved in 200 ml. of bis-(2-methoxyethyl)ether and is heated at reflux for 4 hours and then allowed to stand at room temperature overnight. The solvent is removed and the reaction mixture is diluted with water and extracted with ether. The organic solution is washed with saline, dried over magnesium sulfate and concentrated to give 18 g. of product as an oil.

EXAMPLE 35

Preparation of ethyl 3,3-dimethyl-7-chloroheptanoate

To a solution of 3.484 g. (0.02 mole) of 3,3-dimethyl-7-hydroxyheptanoic acid in 25 ml. of chloroform containing 3 drops of dimethylformamide is added 5.8 ml. (0.08 mole) of thionyl chloride and the solution is then heated at reflux for 3-4 hours. The solution is concentrated to give the intermediate 3,3-dimethyl-7-chloro-1-heptanoyl chloride. The acid chloride is dissolved in a minimum amount of benzene and added slowly to 20 ml. benzene, 10 ml. of ethanol and 2.65 ml. of collidine. The solution is heated at reflux for 1 hour and then concentrated. The residue is dissolved in ether, washed with water, dilute sodium bicarbonate solution and saline. The organic solution is dried over magnesium sulfate and concentrated to give 3.57 g. of product as a yellow oil.

EXAMPLE 36

Preparation of ethyl 3,3-dimethyl-7-iodoheptanoate

To a solution of 3.57 g. (0.0162 mole) of ethyl 3,3-dimethyl-7-chloroheptanoate in 100 ml. of methyl ethyl ketone is added 4 g. of sodium iodide and the mixture heated at reflux for 18 hours. The reaction mixture is cooled, filtered and concentrated. The residue is partitioned between ether and water. The aqueous phase is extracted several times with ether. The extract is washed with sodium bisulfite solution, water and saline. The organic solution is dried over magnesium sulfate and concentrated to give 4.182 g. of a yellow oil. The material is purified by distillation, b.p. 86.degree.-87.degree. C. (0.18 Torr).

EXAMPLE 37

Preparation of 2-carbalkoxy(methyl/ethyl)-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentan-1-one

This compound is prepared by treatment of sodio cyclopentanone carboxylate enolate with ethyl 3,3-dimethyl-7-iodoheptanoate by the procedure described in Example 1.

EXAMPLE 38

Preparation of 2-(6-carboxy-5,5-dimethylhexyl)cyclopentan-1-one

This compound is prepared by decarbalkoxylation of 2-carbalkoxy (mixed methyl and ethyl ester)-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentan-1-one by the procedure described in Example 2.

EXAMPLE 39

Preparation of 2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentan-1-one

Esterification of 2-(6-carboxy-5,5-dimethylhexyl)cyclopentan-1-one with ethanol by the procedure described in Example 3 is productive of the subject compound.

EXAMPLE 40

Preparation of 1-acetoxy-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentan-1-ene

This compound is prepared from 2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentan-1-one and acetic anhydride by the process described in Example 10.

EXAMPLE 41

Preparation of 2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-2-en-1-one

This compound is prepared from 1-acetoxy-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-1-ene via bromination and dehydrobromination according to the procedure described in Example 13.

EXAMPLE 42

Preparation of 2-(3-carbethoxypropyl)-1-methoximino-2-cyclopentene In the manner described for the preparation of the compound of Example 17, 2-(4-hydroxybutyl)-1-methoximino-2-cyclopentene is prepared from 2-(3-carbethoxypropyl)-2-cyclopentenone (Example 14) and methoxyamine hydrochloride.

EXAMPLE 43

Preparation of 2-(4-hydroxybutyl)-1-methoximino-2-cyclopentene

In the manner described for the preparation of the compound of Example 17, 2-(4-hydroxybutyl)-1-methoximino-2-cyclopentene is prepared from 2-(3-carbethoxypropyl)-1-methoximino-2-cyclopentene and diisobutylaluminum hydride.

EXAMPLE 44

Preparation of 2-(6-carbethoxy-5-oxahexyl)-1-methoximino-2-cyclopentene

To an ice cold solution of 4.833 g. (0.0266 mole) of 2-(4-hydroxypentane)-1-methoximino-2-cyclopentene in 50 ml. of dry tetrahydrofuran under nitrogen is added 16.7 ml. of 1.6 molar n-butyl lithium in hexane, dropwise. The reaction mixture is stirred for 0.5 hour and then 4.85 g. (0.029 mole) of ethyl bromoacetate is added dropwise. The reaction mixture is stirred overnight at room temperature and then refluxed for 1.5 hours. The reaction is cooled and poured into water and extracted several times with ether. The ether extracts are washed with saline, dried over magnesium sulfate, and concentrated. The residue is placed on an alumina column, chloroform being used as a wash solvent. The combined washings are concentrated to dryness to give 4.903 g. of product an a yellow oil.

EXAMPLE 45

Preparation of 2-(6-carboxy-5-oxahexyl)-2-cyclopentenone

In the manner described in Example 22, treatment of 2-(6-carbethoxy-5-oxahexyl)-1-methoximino-2-cyclopentene with acetone and 2N hydrochloric acid at reflux gives the subject compound as a yellow oil.

EXAMPLE 46

Preparation of 2-(6-carbethoxy-5-oxahexyl)-2-cyclopentenone

In the manner described in Example 23, treatment of 2-(6-carboxy-5-oxahexyl)-2-cyclopentenone with p-toluenesulfonic acid in ethanol produces the subject product as a light yellow oil.

EXAMPLE 47

Preparation of 2-(6-carboxy-5-oxahexyl)-1-methoximino-2-cyclopentene

To an ice cold solution of 3.66 g. (0.02 mole) of 2-(4-hydroxybutyl)-1-methoximino-2-cyclopentene (Example 43) in 50 ml. of 1,2-dimethoxyethane under nitrogen is added dropwise 17 ml. of 1.6 M n-butyl lithium in hexane. The reaction mixture is stirred for half an hour and then the lithium salt of chloroacetic acid, prepared from 1.89 g. (0.02 mole) of chloroacetic acid and 16 ml. of 1.6M n-butyl lithium in 20 ml. of dimethoxyethane, is added and the reaction mixture is heated at reflux for 48 hours. The solvent is evaporated and the residue is partitioned between ether and water. The aqueous phase is acidified with hydrochloric acid and extracted with ether. The organic phase is washed with water and saturated saline solution, dried (MgSO.sub.4), and evaporated to give 3.35 g. of a yellow oil.

EXAMPLE 48

Preparation of 2-(6-carboxy-5-oxahexyl)-2-cyclopenten-1-one

In the manner described in Example 22, treatment of 2-(6-carboxy-5-oxahexyl)-1-methoximino-2-cyclopentene (Example 47) with acetone and 2N hydrochloric acid at reflux gives the subject compound as a yellow oil.

EXAMPLE 49

Preparation of 1-methoximino-2-(4-methanesulfonyloxybutyl)-2-cyclopentene

To a solution of 1.83 g. (0.01 mole) of 1-methoximino-2-(4-hydroxybutyl)-2-cyclopentene (Example 43) in 10 ml. of methylene chloride containing 1.52 g. (0.015 mole) of triethylamine is added 1.265 g. (0.011 mole) of methanesulfonyl chloride over a period of 5-10 minutes at -10.degree.-0.degree. C. Stirring is continued for 15 minutes and the solution is then washed with cold water, cold 10% hydrochloric acid, cold sodium bicarbonate solution, and cold saline solution. The organic phase is dried (MgSO.sub.4) and concentrated to give an oil which solidifies upon cooling. Crystallization from ether-petroleum ether (30.degree.-60.degree. C.) gives 1.797 g. of white crystals, m.p. 67.degree.-68.degree. C.

EXAMPLE 50

Preparation of 1-methoximino-2-(5-cyanopentyl)-2-cyclopentene

A mixture of 2.75 g. (0.01 mole) of 1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene (Example 60) and 1.47 g. (0.03 mole) of sodium cyanide in 20 ml. of dry N,N-dimethylformamide is heated at 65.degree.-70.degree. C. for 3 hours. The cooled reaction mixture is poured into water and extracted with diethyl ether. The organic phase is washed with water and saturated saline solution, dried (MgSO.sub.4), and evaporated to give 1.89 g. of a light yellow oil.

EXAMPLE 51

Preparation of 1-methoximino-2-(5-carboxypentyl)-2-cyclopentene

A mixture of 1.89 g. (0.0092 mole) of 1-methoximino-2-(5-cyanopentyl)-2-cyclopentene (Example 50) and 1 g. (0.025 mole) of sodium hydroxide in 50 ml. of 1:1 aqueous-ethanol is refluxed for 48 hours, cooled, and partitioned between water and diethyl ether. The aqueous phase is acidified with hydrochloric acid, extracted with diethyl ether, and the organic phase is washed with water and saturated saline solution, dried (MgSO.sub.4), and evaporated to give 1.86 g. of a yellow oil.

EXAMPLE 52

Preparation of 2-(5-carboxypentyl)-2-cyclopentenone

A solution of 1.86 g. (0.00825 mole) 1-methoximino-2-(5-carboxypentyl)-2-cyclopentene (Example 51) in 44 ml. of acetone and 13.1 ml. of 2N hydrochloric acid is refluxed for 5 hours. The solvent is partially evaporated and a solid precipitates and is collected. The residue is extracted with diethyl ether and the organic phase is washed with saturated saline solution, dried (MgSO.sub.4), and evaporated to yield additional solid. The combined solid material is crystallized from ether/pet ether (30.degree.-60.degree. C.degree.) to yield crystalline material, m.p. 70.degree.-72.degree. C.

EXAMPLE 53

Preparation of 2-(5-carbethoxypentyl)-2-cyclopentenone

A solution of 1.309 g. (0.00668 mole) of 2-(5-carboxypentyl)-2-cyclopentenone (Example 52) and 90 mg. of p-toluenesulfonic acid in 150 ml. of ethanol is refluxed for 18 hours. The solvent is evaporated and the residue is dissolved in ether. The organic phase is washed with water, sodium bicarbonate solution, and saturated saline solution, dried (MgSO.sub.4), and evaporated to give 1.371 g. of a light yellow oil.

EXAMPLE 54

Preparation of 2-(5-acetoxypentyl)-2-carbomethoxy/carbethoxy-cyclopentanone

A mixture of sodiocyclopentanone carboxylate, prepared from 1200 g. (8.0 moles) of cyclopentanone carboxylate (methyl and ethyl esters) and 200 g. (8.3 moles) of mineral oil free sodium hydride in 10 l. of 1,2-dimethoxyethane, 1320 g. (8.0 moles) of 5-chloro-1-amyl acetate [M.E. Synerholm, Journ. Amer. Chem. Soc., 69, 2681 (1947), and 1200 g. (8.0 moles) of sodium iodide is refluxed under nitrogen for 18 hours. The mixture is cooled, concentrated to 4 l. and partitioned between dilute hydrochloric acid and diethy ether. The organic phase is washed with water and saturated brine, dried (MgSO.sub.4), and evaporated to yield 1920 g. of an oil.

EXAMPLE 55

Preparation of 2-(5-hydroxypentyl)cyclopentanone/2-(5-acetoxypentyl)-cyclopentanone

A mixture of 4,500 g. (16.2 moles) of 2-(5-acetoxypentyl)-2-carbomethoxy/carboethoxy-cyclopentanone (Example 54), 2.2 l. of glacial acetic acid, 1 l. of concentrated hydrochloric acid, and 1 l. of water is refluxed for 18 hours, cooled, and partitioned between saturated brine and benzene. The organic phase is washed with saturated brine, dried (MgSO.sub.4), and evaporated in vacuo to yield 3155 g. of an oil.

EXAMPLE 56

Preparation of 1-acetoxy-2-(5-acetoxypentyl)-1-cyclopentene

A solution of 400 g. (2.04 moles) of a mixture of 2-(5-hydroxypentyl)cyclopentanone and 2-(5-acetoxypentyl)cyclopentanone (Example 55) and 4.0 g. of p-toluenesulfonic acid monohydrate in 1 l. of acetic anhydride is refluxed at a rate to maintain a steady distillation of acetic acid from the reaction through a helix-packed fractionation column. The reaction is continued with the addition of acetic anhydride to maintain a constant volume until complete conversion of starting materials to product is evident. The mixture is cooled and partitioned between 2 l. of hexane and 3 l. of cold water containing solid sodium bicarbonate to maintain a neutral pH. The organic phase is washed with saturated brine, dried (MgSO.sub.4), and evaporated to yield 452 g. of an oil.

EXAMPLE 57

Preparation of 2-(5-acetoxypentyl)-2-cyclopentenone

To a well stirred mixture of 405 g. (4.05 moles) of calcium carbonate, 3 l. of water, and 2.5 l. of chloroform cooled to 5.degree. C. is added simultaneously 1016 g. (4.0 moles) of 1-acetoxy-2-(5-acetoxy-pentyl)-1-cyclopentene (Example 56) and a solution of 648 g. (4.05 moles) of bromine in 500 ml. of carbon tetrachloride at a rate to maintain a temperature below 10.degree. C. The mixture is stirred for half an hour after addition of the reagents and the phases are then separated. The organic phase is washed with 2% sodium thiosulfate solution, water, and saturated brine, dried (MgSO.sub.4), and evaporated in vacuo to an oil. The oil is immediately added to a refluxing slurry of 500 g. (5.0 moles) of calcium carbonate in 2.5 l of N,N-dimethylacetamide under nitrogen and the mixture is then refluxed for thirty minutes. The mixture is cooled, filtered, and partitioned between water and diethyl ether. The organic phase is washed with water and saturated brine, dried (MgSO.sub.4), and evaporated to yield 757 g. of an oil, b.p. 116.degree.-118.degree. C. (0.25 mm.).

EXAMPLE 58

Preparation of 1-methoximino-2-(5-acetoxypentyl)-2-cyclopentene

In the manner described for Example 16, 2-(5-acetoxypentyl)-2-cyclopentenone (Example 57) is treated with methoxyamine hydrochloride in pyridine and ethanol to yield the subject compound, b.p. 101.degree.-103.degree. C. (0.20 mm).

EXAMPLE 59

Preparation of 1-methoximino-2-(5-hydroxypentyl)-2-cyclopentene

A mixture of 74 g. (0.22 mole) of 1-methoximino-2-(5-acetoxypentyl)-2-cyclopentene (Example 58) and 56 g. (1.0 mole) of potassium hydroxide in 300 ml. of 1:1 aqueous methanol is refluxed for 2 hours and then cooled. The solvent is partially removed in vacuo and the residue is partitioned between saturated brine and diethyl ether. The organic phase is washed with saturated brine, dried (MgSO.sub.4), and evaporated to yield an oil which crystallized, m.p. 35.degree.-36.degree. C.

EXAMPLE 60

Preparation of 1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene

To a cold solution of 9.85 g. (0.05 mole) of 1-methoximino:2-(5-hydroxypentyl)-2-cyclopentene (Example 59) and 7.6 g. (0.075 mole) of triethylamine in 100 ml. of methylene chloride at -10.degree. C. is added 6.3 g. (0.055 mole) of methanesulfonyl chloride at a rate to maintain a temperature of -10.degree. to 0.degree. C. The mixture is then stirred for 15 minutes and then poured into ice water. The organic phase is washed with cold 10% hydrochloric acid, cold saturated sodium bicarbonate solution, and cold saturated brine, dried (MgSO.sub.4), and evaporated to yield a solid, m.p. 78.degree.-80.degree. C.

EXAMPLE 61

Preparation of 1-methoximino-2-(6,6-dicarbethoxyhexyl)-2-cyclopentene

To a suspension of sodiodiethylmalonate in 1,2-dimethoxyethane, prepared from 248 g. (1.55 moles) of diethyl malonate and 17.2 g. (0.95 mole) of mineral oil free sodium hydride in 1 l. of 1,2-dimethoxyethane under nitrogen, is added 170 g. (0.62 mole) of 1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene (Example 60) in 1.5 l. of 1,2-dimethoxyethane and the mixture is refluxed for 5 hours. The mixture is cooled, filtered, and the solvent is evaporated. The residue is partitioned between cold dilute hydrochloric acid and water, and the organic phase is washed with saturated brine, dried (MgSO.sub.4), and evaporated to remove solvent and excess diethyl malonate to yield 209 g. of an oil.

EXAMPLE 62

Preparation of 1-methoximino-2-(6,6-dicarboxyhexyl)-2-cyclopentene

In the manner described in Example 20, 1-methoximino-2-(6,6-dicarbethoxyhexyl)-2-cyclopentene is treated with potassium hydroxide in 1:1 aqueous methanol and then hydrochloric acid to yield the desired compound as crystals from diethyl ether, m.p. 110.degree.-115.degree. C.

EXAMPLE 63

Preparation of 1-methoximino-2-(6-carboxyhexyl)-2-cyclopentene

A solution of 141 g. (0.50 mole) of 1-methoximino-2-(6,6-dicarboxyhexyl)-2-cyclopentene in 500 ml. of bis-(2-methoxyethyl) ether is refluxed for 2 hours, cooled, and evaporated to yield an oil. The latter is crystallized from hexane to yield 92 g. of solid, m.p. 70.degree.-72.degree. C. cl EXAMPLE 64

Preparation of 2-(6-carboxyhexyl)-2-cyclopentenone

In the manner described in Example 22, treatment of 1-methoximino-2-(6-carboxyhexyl)-2-cyclopentene (Example 63) with acetone and 2N hydrochloric acid at reflux provides the subject compound.

EXAMPLE 65

Preparation of 2-(6-carbethoxyhexyl)-2-cyclopentenone

Fischer estification of 2-(6-carboxyhexyl)-2-cyclopentenone (Example 64) in the manner of Example 23 provides the subject compound.

EXAMPLE 66

Preparation of 1-methoximino-2-(6-fluoro-6,6-dicarbethoxyhexyl)-2-cyclopentene

To a solution of sodiodiethyl fluoromalonate, prepared from 2.062 g. (0.0491 mole) of sodium hydride in mineral oil (57.25), 40 ml. of dry N,N-dimethylformanide and 8.174 g. (0.0458 mole) of diethyl fluoromalonate is added dropwise 11.32 g. (0.0413 mole) of 1-methoximino-2-(5-methylsulfonyloxypentyl)-2-cyclopentene (Example 60) in 60 ml. of N,N-dimethylformamide. The mixture is reluxed for 2 hours under a nitrogen atmosphere. The mixture is concentrated and partitioned between cold dilute hydrochloric acid and diethyl ether, and the organic phase is washed with saturated brine, dried (MgSO.sub.4), and evaporated to yield 13.631 g. (92%) of a yellow oil.

EXAMPLE 67

Preparation of 1-methoximino-2-(6-fluoro,6,6-dicarboxyhexyl)-2-cyclopentene

A mixture of 13.631 g. of the diester of Example 66 and 16 g. of potassium hydroxide in 364 ml. of 1:1 aqueous methanol is refluxed for 5 hours, cooled, concentrated, and is partitioned between water and diethyl ether. The aqueous phase is acidified with hydrochloric acid, extracted with ether, and the organic phase is washed with saturated brine, dried (MgSO.sub.4) and evaporated to yield a solid. The solid is crystallized from diethyl ether petroleum ether (30.degree.-60.degree. C.) to give 10 g. (90%) of white crystals, m.p. 143.degree.-145.degree. C. (-CO.sub.2).

EXAMPLE 68

Preparation of 1-methoximino-2-(6-fluoro-6-carboxyhexyl)-2-cyclopentene

A solution of 10 g. of the diacid of Examle 67 in 60 ml. of 2-methoxyethyl ether is refluxed for 7 hours, cooled, and evaporated to yield 8.5 g. (95%) of a tan solid. A sample is crystallized from diethyl ether-petroleum ether (30.degree.-60.degree. C.) to give white crystals, m.p. 98.degree.-100.degree. C.

EXAMPLE 69

Preparation of 2-(6-fluoro-6-carboxyhexyl)cyclopent-2-en-1-one

The acid methoxime (8.5 g.) from Example 68 is refluxed for 5 hours with 180 ml. of acetone and 64 ml. of 2N hydrochloric acid. The mixture is cooled, the solvent is evaporated, and the residue is partitioned between water and diethyl ether. The organic phase is washed with saturated brine, dried (MgSO.sub.4) and evaporated to yield 7.4 g. (98%) of a light yellow oil.

EXAMPLE 70

Preparation of 2-(6-fluoro-6-carbethoxyhexyl)cyclopent-2-en-1-one

The acid ketone (7.4 g.) from Example 69 is Fisher esterified with 300 ml. of absolute ethanol and 400 mg. of p-toluenesulfonic acid for 18 hours, cooled and the solvent is evaporated. The resulting oil is dissolved in ether, washed with dilute sodium bicarbonate solution, and saline, dried (MgSO.sub.4), and evaporated to give 7.306 g. (86%) of a light yellow oil.

EXAMPLE 71

Preparation of 2-(7-cyanoheptyl)-1-methoximino-2-cyclopentene

Treatment of 1-methoximino-2-(7-p-toluenesulfonyloxy)-2-cyclopentene (Example 18) with sodium cyanide in the manner of Example 50 is productive of the subject compound.

EXAMPLE 72

Preparation of 2-(7-carboxyheptyl)-1-methoximino-2-cyclopentene

Alkaline hydrolysis of 2-(7-cyanoheptyl)-1-methoximino-2-cyclopentene(Example 71) by the procedure of Example 51 is productive of the subject compound.

EXAMPLE 73

Preparation of 2-(7-carboxyheptyl)-2-cyclopenten-1-one

Hydrolysis of the methoxime of Example 72 with acetone-hydrochloric acid by the procedure of Example 52 is productive of the subject compound.

EXAMPLE 74

Preparation of 2-(7-carbethoxyheptyl)-2-cyclopenten-1-one

Fisher estification of the carboxylic acid of Example 73 by the procedure of Example 53 is productive of the subject compound.

EXAMPLE 75

Preparation of 2-(6,6-dicarbethoxy-6-phenylhexyl)-1-methoximino-2-cyclopentene

Treatment of 1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene (Example 60) with sodio diethyl phenylmalonate by the procedure of Example 61 is productive of the subject compound.

EXAMPLE 76

Preparation of 2-(6,6-dicarboxy-6-phenylhexyl)-1-methoximino-2-cyclopentene

Alkaline hydrolysis of 2-(6,6-dicarbethoxy-6-phenylhexyl)-1-methoximino-2-cyclopentene (Example 75) by the procedure of Example 20 is productive of the subject diacid.

EXAMPLE 77

Preparation of 2-(6-carboxy-6-phenylhexyl)-1-methoximino-2-cyclopentene

Decarboxylation of 2-(6,6-dicarboxy-6-phenylhexyl)-1-methoximino-2-cyclopentene (Example 76) by the procedure of Example 63 is productive of the subject compound.

EXAMPLE 78

Preparation of 2-(6-carboxy-6-phenylhexyl)-2-cyclopentene-1-one

Methoxime cleavage of 2-(6-carboxy-6-phenylhexyl)-1-methoximino-2-cyclopentene (Example 77) in the manner of Example 69 is productive of the subject ketone.

EXAMPLE 79

Preparation of 2-(6-carbethoxy-6-phenylhexyl)-2-cyclopenten-1-one

Fisher esterification of the carboxylic acid of Example 78 in the manner of Example 70 is productive of the subject keto-ester.

EXAMPLE 80

Preparation of 2-(6-fluoro-6,6-dicarbethocyhexyl)-1-methoximino-2-cyclopentene

An ethanolic solution of sodium ethoxide, prepared from 0.389 g. of sodium and 40 ml. of absolute ethanol, is treated at ambient temperatures with 5.05 g. of 2-(6,6-dicarbethoxyhexyl)-1-methoximino-2-cyclopentene (Example 61). The resulting solution is cooled to -20.degree. C. and then treated with a stream of perchloryl fluoride until the mixture becomes neutral. The excess perchloryl fluoride is removed with a stream of nitrogen and the mixture is retreated with 10 ml. of an ethanolic solution of sodium ethoxide (from 0.350 g. of sodium) and then with perchloryl fluoride until the mixture becomes neutral. The excess perchloryl fluoride is removed with a stream of nitrogen and the mixture is filtered and evaporated to an oil. The latter is partitioned between ether and water and the organic phase is washed with saturated saline, dried (Na.sub.2 SO.sub.4) and evaporated to afford the subject compound.

EXAMPLE 81

Preparation of 2-(6-carbo-n-butoxyhexyl)cyclopent-2-en-1-one

A solution of 50 g. of 2-(6-carboxyhexyl)cyclopent-2-en-1-one [Bagli et al., Tetrahedron Letters, No. 5, 465 (1966)] in 1400 ml. of n-butanol containing 2.7 g. of p-toluenesulfonic acid monohydrate is allowed to stand at room temperature in a stoppered flask for about 24 hours. The solution is taken to dryness. The residue is taken up in ether and the ethereal solution is washed several times with saline solution, dried with anhydrous magnesium sulfate, and taken to dryness to afford the subject butyl ester.

EXAMPLES 82-84

Treatment of 2-(6-carboxyhexyl)cyclopent-2-en-1-one by the procedure of Example 81 with the appropriate alcohol affords the esters of the following table.

TABLE IV______________________________________Example Alcohol Product Ester______________________________________82 isopropanol 2-(6-carboisopropoxyhexyl)cyclopent-2- en-1-one83 methanol 2-(6-carbomethoxyhexyl)cyclopent-2-en- 1-one84 1-hydroxy- 2-(6-carbo-n-decycloxyhexyl)cyclopent-2- n-decane en-1-one______________________________________

EXAMPLE 85

Preparation of diethyl (5-chloro-1,1-dimethylpentyl)malonate

To magnesium (71 g. 2.92 moles) under 1 l. of ether containing a few crystals of iodine is added dropwise 1-chloro-4-bromobutane (500 g., 2.92 moles) over a period of 30 minutes with stirring under nitrogen. The reaction is maintained at a temperature of 0.degree. C. to 5.degree. C. by immersing in an acetone-Dry Ice bath periodically. After stirring for 30 minutes at room temperature, the solution is chilled to below 0.degree. C. and is then transferred to a dropping funnel from which it is added dropwise to diethyl isopropylidene malonate (440 g., 2.19 moles) [A. C. Cope and E. M. Hancock, J.A.C.S. 60, 2644 (1938)] dissolved in 1000 ml. of ether containing the tri(n-butyl)phosphine complex of copper (I) iodide (57g.) [G. B. Kaufman and L. A. Teter, Inorganic Synthesis, 7, 9(1963)] at -10.degree. C. with stirring under nitrogen over a period of two hours. After stirring at room temperature for four hours, the reaction mixture is poured into cold dilute hydrochloric acid and is extracted with ether. The combined ether extracts are washed with saline solution, dried over magnesium sulfate, and concentrated in vacuo to give 700 g. of crude amber oil, which is distilled under vacuum to yield two fractions: 212.4 g. with b.p. at 110.degree. C-135.degree. C. at 0.3 mm. and 100.0 g. with b.p. at 135.degree. C.-145.degree. C. at 0.3 mm. The total yield is 312.4 g. (49%).

EXAMPLE 86

Preparation of 3,3-dimethyl-7-chloroheptanoic acid

A mixture containing diethyl 5-(5-chloro-1,1-dimethylpentyl)malonate (648 g., 2.22 moles) potassium hydroxide (460 g.) and 8 liters of 1:1 isopropanol: water is stirred at room temperature overnight. Most of the isopropanol is distilled and the residue is diluted with water, and then carefully acidified with conc. hydrochloric acid. The mixture is extracted with ether and the extracts are washed with water and saline, dried over magnesium sulfate and concentrated in vacuo to give 548 g. of crude oil. The oil is dissolved in 3 liters of diglyne which is heated under reflux for 16 hours. About 2.7 l. of solvent is distilled, and the remainder is diluted with water and extracted with ether. The extracts are washed with saline, dried over magnesium sulfate and concentrated in vacuo to give 428 g. of crude oil (99%).

EXAMPLE 87

Preparation of ethyl 3,3-dimethyl-7-chloroheptanoate

To a solution of 3,3-dimethyl-7-chloroheptanoic acid (428 g., 2.21 moles) in 3 l. of chloroform containing 3 ml. of N,N-dimethylformamide is added 500 ml. of thionyl chloride and the resulting solution is tested under reflux for 3 hours. The reaction solution then is concentrated in vacuo and the residual acid chloride is dissolved in a minimum amount of benzene and added slowly to a solution containing 1260 ml. of 95% ethanol and 2520 ml. of benzene and 390 ml. of collidine. After heating under reflux for one hour, the solution is concentrated and the residue is dissolved in ether washed with water, dilute sodium bicarbonate solution and saline solution, dried over magnesium sulfate and concentrated to give 415 g. of crude oil, which is distilled under vacuum to yield two fractions 46.6 g. boiling at 75.degree. C. (0.3 mm.) and 236.7 g. boiling at 75.degree. C. - 80.degree. C. (0.3 mm). The total yield is 283.3 g. (60%) and the product is indicated to be 95% pure by g.l.c.

EXAMPLE 88

Preparation of methyl/ethyl 2-(6-carbethoxy-5,5-dimethylhexyl) cyclopentanone-2-carboxylate

Sodium hydride (67 g., 1.55 moles) is placed in a 3 l. round-bottom flask and to this is added 1.1 liters of glyme from a dropping funnel under nitrogen flow and with stirring. To the resulting grayish mixture is added the 2-carbalkoxycyclopentanone (mixed methyl and ethyl esters) dropwise over a period of 45 minutes with nitrogen flow whilst the temperature is maintained in the range of 40.degree.-55.degree.. Ethyl 3,3-dimethyl-7-chloroheptanoate (283 g., 1.28 moles) and potassium iodide (195 g., 1.32 moles) are added and the mixture is heated at reflux overnight. After most of the solvent is distilled, the residue is made acidic with dilute hydrochloric acid and is then extracted with ether. The ether extracts are washed with water and saline solution, dried over magnesium sulfate, and concentrated in vacuo to 500 g. of crude yellow oil, which is distilled to give 405 g. (94% yield) of oil with b.p. 140.degree.-180.degree. (0.8 mm).

EXAMPLE 89

Preparation of 7-(2-Cyclopentanone)-3,3 dimethylheptanoic acid

Methyl/Ethyl 2-(6-carbethoxy-5,5-dimethylhexyl) cyclopentanone-2-carboxylate (200 g., 0.6 moles), glacial acetic acid (180 ml) and 240 ml. of diluted hydrochloric acid, prepared from 100 ml. of conc. hydrochloric acid and 300 ml. of water, are placed in a 2 l. flask, containing a reflux condenser and a magnetic stirrer. The mixture then is stirred at reflux for 24 hours. The reaction mixture is cooled, 1 l. of water is added and the mixture is extracted several times with benzene. The organic extracts are combined, washed with saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to an oil (173.5 g.). The oil is rendered basic with sodium hydroxide solution, extracted with benzene and made acidic with hydrochloric acid and reextracted with benzene several times. The benzene layers are combined and washed with water, saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to yield 109.8 g. (78%) of crude oil, which was used without further purification in the next step.

EXAMPLE 90

Preparation of Ethyl 7-(2-Cyclopentanone)-3,3-dimethylheptanoate

To a solution of 7-(2-cyclopentanone)-3,3-dimethylheptanoic acid (45 g., 0.22 mol.) in 285 ml. of chloroform containing three drops of N,N-dimethylformamide is added dropwise 25 ml. of thionyl chloride. The solution is stirred at room temperature for twenty minutes, the solvent is removed at reduced pressure and the residual acid chloride is dissolved in a minimum amount of benzene and added slowly to a solution containing 115 ml. of ethanol, 230 ml. benzene and 30 ml. of collodine. This solution is heated under reflux for fifteen minutes and then concentrated. The residue is dissolved in ether, washed with water, diluted sodium bicarbonate solution and saline solution, dried over magnesium sulfate and concentrated to give 51 g. of crude oil. Distillation gives 40 g. (67%) b.p. 135.degree.-145.degree. (0.1 mm.) of oil.

EXAMPLE 91

Preparation of 1-Acetoxy-2-(6-carbethoxy-5,5-dimethylhexyl)-cyclopent-1-ene

A solution of ethyl 7-(2-cyclopentanone)-3,3-dimethylheptanoate (90 g., 0.336 mol.) and p-toluenesulfonic acid (0.94 g.) in 250 ml. of acetic anhydride is heated to boiling under partial reflux, allowing distillate at 118.degree. or less (i.e. acetic acid) to escape thru a Vigreux column equipped with a condenser to collect the distillate. After ten hours 130 ml. of distillate is collected. Another 50 ml. of acetic anhydride is added and the reaction is heated for five more hours; an additional 125 ml. of acetic anhydride is added, the reaction is heated for seven more hours; finally another 50 ml. of acetic anhydride is added and heating is continued for four more hours. The solution is cooled and poured (cautiously) into a cold (0.degree.-5.degree.) mixture of saturated aqueous sodium bicarbonate (400 ml.) and hexane (250 ml.). The resulting cold mixture is stirred for thirty minutes during which time portions of solid sodium bicarbonate are added periodically until carbon dioxide evalution ceases. The hexane layer is separated and washed with saturated sodium chloride solution until the washings are neutral, dried over magnesium sulfate and treated with Darco decolorizing charcoal for clarification and then evaporated to dryness leaving an amber colored oil (87.5 g., 84%).

EXAMPLE 92

Preparation of 2-(6-Carboxy-5,5-dimethylhexyl)cyclopent-2-en-1-one

To a rapidly stirred mixture of 1-acetoxy-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-1-ene (35 g., 0.113 mole) chloroform (95 ml.), water (125 ml.) and calcium carbonate (11.8 g.) cooled in an ice-bath is added dropwise over a period of thirty minutes a solution of bromine (18.8 g.) in carbon tetrachloride (31 ml.). After stirring in the cold for an additional 45 minutes the orange colored chloroform layer is separated and washed with dilute sodium bisulfite and saturated saline solution, dried over magnesium sulfate and taken to dryness in vacuo (bath temperature: 35.degree.-40.degree.) leaving an amber colored oil. A slurry of 100 ml. of N,N-dimethylacetamide and 16.5 g. of CaCO.sub.3 is stirred and heated to reflux under nitrogen flow. The above dried oil is added from a dropping funnel rapidly, maintaining reflux and nitrogen flow for thirty minutes. The cooled reaction mixture is filtered, and the precipitate is washed with ether. The filtrate is poured into two liters ice-cold water and is extracted with ether. The combined extracts and washing is washed with water, saturated saline, treated with decolorizing charcoal, filtered. The solvent evaporated in vacuo to give 24 g. (77%) of subject product.

EXAMPLE 93

Preparation of 4-bromo-2(6-carboxyhexyl)cyclopent-2-en-1-one

A stirred mixture of 35.9 g. (0.171 moles) of 2-(6-carboxyhexyl) cyclopent-2-en-1-one [Bagli et al., Tetrahedron Letters, No. 5, 465 (1966)], 35.0 g. (0.197 moles) of N-bromosuccinimide, and 600 ml. of carbon tetrachloride is refluxed for 35 minutes. The mixture is cooled to 5.degree. C. and filtered. The filtrate is washed with cold water, dried over magnesium sulfate, and taken to dryness to give an oil, .lambda. .sub.max..sup.MeOH = 225 m.mu. (8850); .nu.max. = 1705 (carbonyl groups) and 1625. cm.sup.-1 (olefin group).

EXAMPLE 94

Preparation of 2-(6-carboxyhexyl)-4-hydroxy-cyclopent-2-en-1-one

To a stirred solution of 10.6 g. (ca. 34 mmoles) of crude 4-bromo-2-(6-carboxyhexyl)cyclopent-2-en-1-one (Example 93) in 100 ml. of acetone and 65 ml. of water is added 8.80 g. (45.2 mmoles) of silver fluoborate during 2 minutes. The temperature is maintained at 25.degree.-30.degree. C. by external cooling. The mixture is stirred for 90 minutes, filtered, saturated with sodium chloride, and extracted with ether. The extract is extracted with half saturated sodium bicarbonate solutions. The basic solutions is reacidified with dilute hydrochloric acid, saturated with sodium chloride, and extracted with ether. The extract is washed with water and saturated sodium chloride solution, dried over magnesium sulfate, and concentrated. The crude product is purified by partition chromatography on Celite to give an oil; .lambda..sub.max..sup.MeOH = 233 m.mu.. (7360); .nu.max. = 3380 (hydroxyl groups), 1710 (carbonyl groups), and 1632 cm.sup.-1 (olefin group).

EXAMPLE 95

Preparation of 4-tetrahydropyranyloxy-2-(6-tetrahydropyranylcarboxyhexyl)cyclopent-2-en-1-one

To a stirred solution of 5.59 g. (24.6 mmoles) of 4-hydroxy-2-(6-carboxyhexyl) cyclopent-2-en-1-one (Example 94) and 20.7 g. (246 mmoles) of dihydropyran in 100 ml. of methylene chloride at 20.degree. C. is added 47 mg. (0.246 mmoles) of p-toluenesulfonic acid monohydrate in one portion. The temperature is maintained at 20.degree.-25.degree. C. by cooling and is stirred for one hour at that temperature. The solution is diluted with 200 ml. of ether and poured into a mixture of 40 ml. of saturated sodium bicarbonate solution, 40 ml. of saturated sodium chloride solution, and 80 ml. of water. The phases are separated, and the aqueous phase is extracted with additional ether. The total extract is washed successively with water and saturated sodium chloride solution, dried over potassium carbonate, and freed of volatile matter by concentration at reduced pressure to give an oil, .lambda..sub.max..sup.MeOH = 223 m.mu. (9500); .nu.max. 1730 (ester carbonyl group), 1705 (ketone carbonyl group), and 1030 cm.sup.-1 (tetrahydropyranyloxy groups).

EXAMPLE 96

Preparation of 2-(6,6-dicarbethoxyheptyl)-2-cyclopentenone methoxime

The subject compound is prepared from sodio diethyl methylmalonate and 2-(5-methanesulfonyloxypentyl)-2-cyclopentenone methoxime (Example 60) by the procedure described in Example 61.

EXAMPLE 97

Preparation of 2-(6-carboxyheptyl)-2-cyclopentenone methoxime

Saponification of 2-(6,6-dicarbethoxyheptyl)-2-cyclopentenone methoxime (Example 96) with potassium hydroxide by the method of Example 20 is productive of 2-(6,6-dicarboxyheptyl)-2-cyclopentenone methoxime, decarboxylation of which in the manner of Example 63 provides the subject compound.

EXAMPLE 98

Preparation of 2-(6-carboxyheptyl)-2-cyclopentenone

Methoxime cleavage of 2-(6-carboxyheptyl)-2-cyclopentenone methoxime (Example 97) in the manner of Example 22 provides the subject ketone.

EXAMPLE 99

Preparation of 2-(6-carbethoxyheptyl)-2-cyclopentenone

Esterification with ethanol of the acid chloride derived from 2-(6-carboxyheptyl)-2-cyclopentenone in the manner of Example 31 is productive of the subject compound.

EXAMPLE 100

Preparation of ethyl (methyl) 7-(2-carbethoxycyclohexan-1-on-2-yl)heptanoate

To a stirred suspension of 51 g. of sodium hydride (57% in mineral oil) in 675 ml. of dimethylformamide is added 200 g. of 2-cyclohexanone carboxylate (60% ethyl - 40% methyl esters) over a 1-5 hr. period with external cooling to maintain the temperature at 20.degree.-25.degree. C. The reaction mixture is stirred at ambient temperature for 15 minutes and heated to 50.degree. C. over 15 minutes. To the stirred mixture is added 300 g. of ethyl 7-bromoheptanoate during a 10 minute period. The reaction mixture is stirred at 50.degree.-60.degree. C. for 4 hours, cooled, and poured into water. The product is obtained by ether extraction. The extract is washed successively with water and saturated sodium chloride, dried and evaporated to give a liquid which is purified by distillation, IR 1735 cm.sup.-1 (ester carbonyls) and 1710 cm.sup.-1 (ketone carbonyl).

EXAMPLE 101

Preparation of 7 -(cyclohexan-1-on-2-yl)heptanoic acid

A stirred mixture of 380 g. of mixed methyl and ethyl esters of 7-(2-carbethoxycyclohexan-1-on-2-yl)heptanoate (Example 10), 202 ml. of concentrated sulfuric acid, 970 ml. of glacial acetic acid, and 970 ml. of water is refluxed for 22.5 hours. The cooled reaction mixture is treated with 380 g. of sodium carbonate and 2 liters of water and is extracted with ether. Acidic material is partitioned from the ether extract with 1.0M sodium carbonate. The aqueous phase is acidified with concentrated hydrochloric acid and extracted with ether. The extract is washed successively with water and saturated sodium chloride, dried, and evaporated to give an oil.

EXAMPLE 102

Preparation of ethyl 7-(cyclohexan-1-on-2-yl)heptanoate

A solution of 232 g. of 7-(cyclohexan-1-on-2-yl)heptanoic acid in 2500 ml. of ethanol is refluxed for 4.5 hours with 3.8 g. of p-toluenesulfonic acid monohydrate. The solution is diluted with 200 ml. of benzene, and boiling is continued for 2 hours as 200 ml. of distillate is removed. The volume of the solution is concentrated to 500 ml. After dilution with 500 ml. of ether the solution is extracted with a solution prepared from 50 ml. of saturated sodium bicarbonate, 50 ml. of saturated sodium chloride, and 100 ml. of water. The extract is washed with saturated sodium chloride, dried, and evaporated. The product is purified by distillation to give a liquid, IR 1740 cm.sup.-1 (ester carbonyl) and 1715 cm.sup.-1 (ketone carbonyl).

EXAMPLE 103

Preparation of 2-carbalkoxy(methyl/ethyl)-2-(3-carbethoxypropyl)-cyclohexan-1-one

The subject compound is prepared in the manner described in Example 10 by treatment of 2-cyclohexanone carboxylate (mixed methyl and ethyl esters) with sodium hydride and ethyl 4-iodobutyrate.

EXAMPLE 104

Preparation of 2-(3-carbethoxypropyl)cyclohexan-1-one

This compound is prepared from 2-carbalkoxy(methyl/ethyl)-2-(3-carbethoxypropyl)cyclohexan-1-one (Example 13) by decarbalkoxylation according to the procedure described in Example 11 followed by esterification by the procedure of Example 12.

EXAMPLE 105

Preparation of 2-(5-carbethoxypentyl)cyclohexan-1-one

This compound is prepared by alkylation of 2-cyclohexanone carboxylate (mixed methyl and ethyl esters) with ethyl 6-bromohexanoate according to the procedure of Example 10, followed by decarbalkoxylation according to the procedure of Example 11 and finally esterification by the procedure of Example 12.

EXAMPLE 106

Preparation of 2-(7-carbethoxyheptyl)cyclohexan-1-one

Alkylation of 2-cyclohexanone carboxylate (mixed methyl and ethyl esters) with ethyl 8-bromoctanoate in accordance with the procedure of Example 10, followed by decarbalkoxylation by the procedure of Example 11 and then esterification by the procedure of Example 12 is productive of the subject compound.

EXAMPLE 107

Preparation of ethyl 7-(1-acetoxycyclohex-1-en-2-yl)heptanoate

A stirred solution of 28.0 g. of ethyl 7-(cyclohexan-1-on-2-yl)heptanoate (Example 12), 170 mg. of p-toluenesulfonic acid monohydrate, and 25.6 g. of acetic anhydride is heated for 5 hours while allowing 8.0 g. of distillate to distill. The cooled solution is poured into a stirred, ice-cold mixture of 500 ml. of saturated sodium bicarbonate and 250 ml. of hexane. After one hour the hexane phase is separated, dried, and evaporated. The crude product is distilled to give a liquid, IR 1760 cm.sup.-1 (vinyl ester carbonyl) and 1740 cm.sup.-1 (ethyl ester carbonyl).

EXAMPLE 108

Preparation of 1-acetoxy-2-(3-carbethoxypropyl)cyclohex-1-ene

Treatment of 2-(3-carbethoxypropyl)cyclohexan-1-one (Example 14) with acetic anhydride by the procedure of Example 24 is productive of the subject compound.

EXAMPLE 109

Preparation of 1-acetoxy-2-(5-carbethoxypentyl)cyclohex-1-ene

Treatment of 2-(5-carbethoxypentyl)cyclohexan-1-one (Example 15) with acetic anhydride by the procedure of Example 24 is productive of the subject compound.

EXAMPLE 110

Preparation of 1-acetoxy-2-(7-carbethoxyheptyl)cyclohex-1-ene

Treatment of 2-(7-carbethoxyheptyl)cyclohexan-1-one (Example 16) with acetic anhydride by the procedure of Example 24 is productive of the subject compound.

EXAMPLE 111

Preparation of ethyl 7-(cyclohex-2-one-2-yl)heptanoate

To a stirred solution of ethyl 7-(1-acetoxycyclohex-1-en-2-yl)heptanoate (Example 24) in 750 ml. of acetic acid and 125 ml. of pyridine at 10.degree. C. is added a solution of 13.8 g. of bromine in 200 ml. of acetic acid over 20 minutes. The resulting solution is allowed to stand at ambient temperature for 45 minutes and is then decolorized with sodium sulfite. The solution is poured into 800 ml. of half-saturated sodium chloride and extracted with 1:1 hexane-ether. The extract is washed successively with water and saturated sodium chloride, dried over sodium carbonate, and evaporated to give 32 g. of the crude bromoketone. To a stirred suspension of 14.2 g. of lithium bromide and 16.6 g. of lithium carbonate in 250 ml. of anhydrous dimethylformamide at 80.degree. C. is added the above bromoketone. The stirred mixture is heated to boiling over 20 minutes and refluxed for 15 minutes. The cooled mixture is poured into 1000 ml. of water, acidified with dilute hydrochloric acid, and extracted with ether. The extract is washed successively with water and saturated sodium chloride, dried, and evaporated. The product is purified by distillation to give a liquid, IR 1740 cm.sup.-1 (ester carbonyl), 1685 cm.sup.-1 (ketone carbonyl), and 1650 cm.sup.-1 (olefin); NMR (CCl.sub.4) 6.63 (multiplet, vinyl proton).

EXAMPLE 112

Preparation of 2-(3-carbethoxypropyl)cyclohex-2-en-1-one

In accordance with the procedure of Example 40, bromination of 1-acetoxy-2-(3-carbethoxypropyl)cyclohex-1-ene (Example 25) followed by treatment with lithium bromide and lithium carbonate is productive of the subject compound.

EXAMPLE 113

Preparation of 2-(5-carbethoxypentyl)cyclohex-2-en-1-one

By the procedure of Example 40, bromination of 1-acetoxy-2-(5-carbethoxypentyl)cyclohex-1-ene (Example 26) followed by treatment with lithium bromide and lithium carbonate is productive of the subject compound.

EXAMPLE 114

Preparation of 2-(7-carbethoxyheptyl)cyclohex-1-en-2-one

By the procedure of Example 40, bromination of 1-acetoxy-2-(7-carbethoxyheptyl)cyclohex-1-ene (Example 27) followed by treatment with lithium bromide and lithium carbonate is productive of the subject compound.

EXAMPLE 115

Preparation of 2-(4-p-toluenesulfonyloxybutyl)-1-methoximino-2-cyclopentene

In the manner described in Example 34, treatment of 2-(4-hydroxybutyl)-1-methoximino-2-cyclopentene with p-toluene sulfonyl chloride in pyridine gives the subject product as a light yellow oil; IR (film): 1600, 1190, 1050, 885 cm.sup.-1.

EXAMPLE 116

Preparation of 2-(6-carbethoxy-5-thiahexyl)-1-methoximino-2-cyclopentene

To a stirred mixture of 1.465 g. (0.0348 mole) of sodium hydride (57.2% in mineral oil) in 50 ml. of dimethoxyethane, under nitrogen, is added slowly 4.8 g. (0.0347 mole) of ethyl-2-mercaptoacetate. The reaction mixture is stirred at room temperature for one hour and then a solution of 7.8 g. (0.0231 mole) of 2-(4p-toluenesulfonyloxybutyl)-1-methoximino-2-cyclopentene in 30 ml. of dimethoxyethane is added dropwise and stirred at room temperature for 18 hours. The solution is heated at reflux for one hour, cooled and poured into cold dilute hydrochloric acid and then extracted with ether. The combined ether extracts are washed with saline, dried over magnesium sulfate and evaporated to give 7.6 g. of subject product as a yellow oil.

EXAMPLE 117

Preparation of 2-(6-carboxy-5-thiahexyl)-2-cyclopentenone

In the manner described in Example 38, treatment of 2-(6-carbethoxy-5-thiahexyl)-1-methoximino-2-cyclopentene with acetone and 2N hydrochloric acid at reflux gives the subject product as a yellow oil.

EXAMPLE 118

Preparation of 2-(6-carbethoxy-5-thiahexyl)-2-cyclopentenone

In the manner described in Example 39, treatment of 2-(6-carboxy-5-thiahexyl)-2-cyclopentenone with p-toluenesulfonic acid in ethanol gives the subject ester as a yellow oil.

EXAMPLE 119

Preparation of 3-triphenylmethoxy-1-octyne

A mixture of 1.26 g. (10.0 mmoles) of 1-octyn-3-ol, 4.85 g. (15.0 mmoles) of triphenylmethyl bromide, and 50 ml. of dry pyridine is heated at 95.degree. C. for 60 minutes with occasional swirling. The solution is cooled, treated with water, and extracted with ether. The extract is washed successively with water and saturated sodium chloride solution, dried over magnesium sulfate, and concentrated. The crude product is purified by chromatography on Florisil and recrystallization from petroleum ether to give white crystals, m.p. 65.degree.-66.5.degree.,.mu.max. (KBr) 3280 (acetylenic hydrogen), 1605, 1030, and 702 cm.sup.-1 (triphenylmethoxy group).

EXAMPLE 120

Preparation of ethyl 9-oxo-15-triphenylmethoxy-13-trans-8.xi.-prostenoate

A stirred solution of 7.37 g. (20.0 mmoles) of 3-triphenylmethoxy-1-octyne (Example 119) in 10 ml. of benzene is treated with 16.7 mg. of 1.2 M diisobutylaluminum hydride in hexane, and the resulting solution is heated at 50.degree. C. for 2 hours. The solution is cooled to 0.degree. C. and treated with 10.5 ml. of 1.7 M methyl lithium in ether. After stirring for a 20 minute period at ambient temperature, the alanate solution is cooled to 0.degree. C. and treated with a solution of 3.98 g. (16.7 mmoles) of 2-(6-carbethoxyhexyl)cyclopent-2-en-1-one (Example 13) in 5 ml. of ether. The resulting solution is stirred at ambient temperature for 22.5 hours, diluted with ether, and poured into a stirred mixture 2N acetic acid and ice. After stirring until methane evolution ceases, the organic phase is separated and washed successively with water and saturated sodium chloride solution. The extract is dried over magnesium sulfate and concentrated. The crude product in the residue is purified by chromatography on silica gel to give an oil, .nu.max. 1735 (carbonyl groups), 967 (trans vinyl group), and 705 cm.sup.-1 (triphenylmethoxy group).

EXAMPLE 121

Preparation of ethyl 15-hydroxy-9-oxo-13 -trans-prostenoate

A 0.05M solution of ethyl 9-oxo-15-triphenylmethoxy-13-trans-8.xi.-prostenoate (Example 120) in glacial acetic acid-tetrahydrofuran-water (4:2:1) is heated at 45.degree. C. for 3.5 hours. The solvents are evaporated at reduced pressure, and the residue is dissolved in ether. The solution is washed successively with water, 0.5N sodium bicarbonate solution, and saturated sodium chloride solution; dried over magnesium sulfate; and concentrated. Column chromatography of the crude product on silica gel gives two epimeric substances which are purified separately by thin layer chromatography to give oils differing only in chromatographic behavior, .nu.max. 3470 (hydroxyl group), 1735 (carbonyl groups), and 967 cm.sup.-1 (trans vinyl group).

EXAMPLE 122

Preparation of 15-hydroxy-9-oxo-13-trans-prostenoic acid

A solution of 2 g. of ethyl 15-hydroxy-9-oxo-13,14-trans-prostenoate (Example 121) (mixture of racemates) in 32 ml. of methanol-water (1:1), containing 850 mg. of potassium hydroxide is stirred at ambient temperature for 18 hours. After acidification with 10% hydrochloric acid, the solution is extracted with ether several times. The combined ether extracts are washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness to give 1.69 g. (92%) of an oil which partially crystallizes. Recrystallized from ether-hexane gives white crystals, m.p. 79.degree.-81.degree. C.; nmr .delta.6.36 (s, hydroxyl and carboxyl groups), 5.61 (t, olefinic protons), 4.12 (s, C.sub.15 -H) and 0.90 (s, terminal methyl).

EXAMPLE 123

Preparation of tetrahydropyran-2-yl 9-oxo-11-tetrahydropyranyloxy-15-triphenylmethoxy-13-trans-8.xi.-prostenoate

In the manner described in Example 120, 13.6 g. (37 mmoles) of 3-triphenylmethoxy-1-octyne (Example 119) contained in 18.5 ml. of benzene is converted to an alanate reagent by treatment with 31 ml. of 1-2M diisobutylaluminum hydride in hexane and 21 ml. of 1.7M methyl lithium in ether. To the stirred, ice-cold reagent is added a solution of 10.97 g. (24.6 mmoles) of 2-(6-tetrahydropyranylcarboxyhexyl)-4-tetrahydropyranyloxycyclopent-2-en-1-one (Example 95) in 10 ml. of ether during 10 minutes. The resulting solution is stirred at ambient temperature for 20 hours, diluted with ether, and poured into a stirred mixture of 2N hydrochloric acid and ice. The organic phase is separated and washed successively with water and saturated sodium chloride solution. The extract is dried over magnesium sulfate, and the solvents are evaporated at reduced pressure to give the crude product as an oil, .nu.max. 1735 (carbonyl groups), 1030 (tetrahydropyranyloxy groups), 970 (trans vinyl group), and 705 cm.sup.-1 (triphenylmethoxy group).

EXAMPLE 124

Preparation of 11,15-dihydroxy-9-oxo-13-trans-prostenoic acids

A 0.05M solution of crude tetrahydropyran-2-yl 9-oxo-11-tetrahydropyranyloxy-15-triphenylmethoxy-13-trans-prostenoate (Example 123) in glacial acetic acid-tetrahydrofuran-water (4:2:1) is heated at 45.degree. C. for 3.5 hours. The solution is diluted with water and extracted with ether. The extract is washed successively with water and saturated sodium chloride solution and dried over magnesium sulfate. The solvents are removed at reduced pressure. Column chromatography of the residue on acid-washed silica gel gives the title compounds as a pair of epimeric substances which are purified separately by partition chromatography.

The fast-running epimer (15-epi-d,l-prostaglandin E.sub.1) is obtained as an oil, .nu.max. 1735 (ketone carbonyl group), 1710 (acid carbonyl group), and 967 cm.sup.-1 (trans vinyl group); NMR (acetone-d.sub..beta.) 5.68 (multiplet, vinyl hydrogens) and 4.11.delta. (multiplet, carbinolic hydrogens).

The slow-running epimer (d,l-prostaglandin E.sub.1) is recrystallized from ethyl acetate-petroleum ether to give white crystals, m.p. 100.degree.-105.degree. C., .nu.max. (KBr) 1725 (ketone carbonyl group), 1700 (acid carbonyl group), and 970 cm.sup.-1 (trans vinyl group); NMR (acetone-d.sub..beta.) 5.67 (multiplet, vinyl hydrogens) and 4.12 (multiplet, carbinolic hydrogens).

EXAMPLES 125 TO 139

In accordance with the method described in Example 119, the various 3-hydroxy-1-alkynes listed in the table below are converted to the corresponding 3-triphenylmethoxy-1-alkynes by treatment with triphenylmethyl bromide.

TABLE______________________________________125 1-heptyn-3-ol 3-triphenylmethoxyheptyne-1126 1-hexyn-3-ol 3-triphenylmethoxy-hexyne-1127 1-pentyn-3-ol 3-triphenylmethoxy-pentyne-1128 1-nonyne-3-ol.sup.a 3-triphenylmethoxy-nonyne-1129 1-decyne-3-ol.sup.b 3-triphenylmethoxy-decyne-1130 4-ethyl-1-octyne-3-ol 3-triphenylmethoxy-4-ethyl- octyne-1131 4-ethyl-1-hexyne-3-ol 3-triphenylmethoxy-4-ethyl- hexyne-1132 4-methyl-1-heptyne-3-ol 3-triphenylmethoxy-4-methyl- heptyne-1133 4-methyl-1-pentyne-3-ol 3-triphenylmethoxy-4-methyl- pentyne-1134 7-methyl-6-en-1-octyne- 3-triphenylmethoxy-7-methyl- 3-ol.sup.c 6-en-octyne-1135 6,7-dimethyl-6-en-1- 3-triphenylmethoxy-6,7- octyne-3-ol.sup.c dimethyl-6-en-octyne-1136 7-isobutyl-6-en-1- 3-triphenylmethoxy-7-isobutyl- octyne-3-ol.sup.c 6-en-octyne-1137 5-en-1-hexyne-3-ol.sup.d 3-triphenylmethoxy-5-en- hexyne-1138 5,9-dimethyl-9-en-1- 3-triphenylmethoxy-5,9- decyne-3-ol.sup.e dimethyl-9-en-decyne-1139 cis-5-en-1-octyne-3- 3-triphenylmethoxy-cis-5-en- ol.sup.f octyne-1______________________________________

References:

a. M. Bertrand, Bull. Soc. Chim. France, 461 (1956). b. F. Bohlmann and D. Ratz, Chem. Ber., 90, 2265 (1957). c. U.S. Pat. No. 3,452,105 (June 24, 1969); Chem. Abs., 71, 60678 (1969). d. A. Viola and J. H. MacMillan, Jour. Amer. Chem. Soc., 92, 2404 (1970). e. Sequin, Bull. Soc. Chim. France, 12, 948 (1945). f. J. Fried et al., Jour. Amer. Chem. Soc., 94, 4342 (1972).

EXAMPLES 140-256

Treatment of the cycloalkenone designated in the table below with the alanate [lithium diisobutyl-methyl-(3-triphenylmethoxy-1-trans-alkenyl)-alanate] prepared by treatment of the listed 3-triphenylmethoxy-1-alkyne with diisobutyl aluminum hydride followed with methyl lithium, all by the procedure described in Example 120, is productive 9-oxo-15-triphenylmethoxy-13-trans-8-.xi.-prostenoates of the table.

Table 3__________________________________________________________________________ Starting 3-triphenyl- Product Starting Cycloalkenone methoxy-l-alkyne of Alkyl 9-oxo-15-triphenylmethoxy-13-trans-Example of Example Example 8.xi.-prostenoate__________________________________________________________________________140 14 119 ethyl 9-oxo-15-triphenylmethoxy-5,6,7-tri- 9 nor-13-trans-8.xi.-prostencate141 23 119 ethyl 9-oxo-15-triphenylmethoxy-7a,7b-bis- 2 homo-13-trans-8.xi.-prostenoate142 31 119 ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-13- . trans-8.xi.-prostenoate143 41 119 ethyl 9-oxo-15-triphenylmethoxy-3,3-dimethy l- 13-trans-8.xi.-prostenoate144 46 119 ethyl 9-oxo-15-triphenylmethoxy-3-oxa-13- trans-8.xi.-prostenoate145 53 119 ethyl 9-oxo-15-triphenylmethoxy-7-nor-13- trans-8.xi.-prostenoate146 70 119 ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-13 - trans-8.xi.-prostenoate147 74 119 ethyl 9-oxo-15-triphenylmethoxy-7a-homo-13- 13-trans-8.xi.-prostenoate148 79 119 ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-13 - trans-8.xi.-prostenoate149 99 119 ethyl 9-oxo-15-triphenylmethoxy-2-methyl-13 - trans-8.xi.-prostenoate150 111 119 ethyl 9-oxo-15-triphenylmethoxy-10a-homo-13 -- trans-8.xi.-prostenoate151 112 119 ethyl 9-oxo-15-triphenylmethoxy-10a-homo-5, - 6,7-trinor-13-trans-8.xi.-prostenoate152 113 119 ethyl 9-oxo-15-triphenylmethoxy-10a-homo-7- nor-13-trans-8.xi.-prostenoate153 114 119 ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bis- homo-13-trans-8.xi.-prostenoate154 118 119 ethyl 9-oxo-15-triphenylmethoxy-3-thia-13- 13-trans-8.xi.-prostenoate155 81 119 butyl 9-oxo-15-triphenylmethoxy-13-trans-8. xi.- prostenoate156 82 119 isopropyl 9-oxo-15-triphenylmethoxy-13-tran s- 8.xi.-prostenoate157 83 119 methyl 9-oxo-15-triphenylmethoxy-13-trans-8 .xi. prostenoate158 84 119 n-decyl 9-oxo-15-triphenylmethoxy-13-trans- 8.xi.-prostenoate159 900 119 methyl 9-oxo-15-triphenylmethoxy-5-cis,13- trans-8.xi.-prostadienoate160 13 125 ethyl 9-oxo-15-triphenylmethoxy-20-nor-13- trans-8.xi.-prostenoate161 13 128 ethyl 9-oxo-15-triphenylmethoxy-20-methyl- 13-trans-8.xi.-prostenoate162 13 130 ethyl 9-oxo-15-triphenylmethoxy-16-ethyl-13 - trans-8.xi.-prostenoate163 13 132 ethyl 9-oxo-15-triphenylmethoxy-16-methyl-2 0- nor-13-trans-8.xi.-prostenoate164 13 134 ethyl 9-oxo-15-triphenylmethoxy-19-methyl-1 3- trans,18-8.xi.-prostadienoate165 13 135 ethyl 9-oxo-15-triphenylmethoxy-18,19-di-- methyl-13-trans,18-8.xi.prostadienoate166 13 139 ethyl 9-oxo-15-triphenylmethoxy-8.xi.-13-tr ans, 17-cis-prostadienoate167 14 139 ethyl 9-oxo-15-triphenylmethoxy-5,6,7-trino r- 8.xi.-13-trans,17-cis-prostadienoate168 15 139 ethyl 9-oxo-15-triphenylmethoxy-6,7-dinor-8 .xi. 13-trans,17-cis-prostadienoate169 23 139 ethyl 9-oxo-15-triphenylmethoxy-7a,7b-bisho mo- 8.xi.-13-trans,17-cis-prostadienoate170 31 139 ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-8.x i.-13- trans,17-cis-prostadienoate171 41 139 ethyl 9-oxo-15-triphenylmethoxy-3,3-dimethy l- 8.xi.-13-trans,17-cis-prostadienoate172 46 139 ethyl 9-oxo-15-triphenylmethoxy-3-oxo-8.xi. -13- trans,17-cis-prostadienoate173 53 139 ethyl 9-oxo-15-triphenylmethoxy-7-nor-8.xi. -13- trans,17-cis-prostadienoate174 70 139 ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-8. xi.-13- trans,17-cis-prostadienoate175 74 139 ethyl 9-oxo-15-triphenylmethoxy-7a-homo-8.x i.-13- trans,17-cis-prostadienoate176 79 139 ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-8. xi.-13- trans,17-cis-prostadienoate177 99 139 ethyl 9-oxo-15-triphenylmethoxy-2-methyl-8. xi.-13- trans,17-cis-prostadienoate178 111 139 ethyl 9-oxo-15-triphenylmethoxy-10a-homo-8. xi.-13- trans,17-cis-prostadienoate179 112 139 ethyl 9-oxo-15-triphenylmethoxy-10a-homo-5, 6,7- trinor-13-trans, 17-cis-prostadienoate180 113 139 ethyl 9-oxo-15-triphenylmethoxy-10a-homo-7- nor- 8.xi.-13-trans,17-cis-prostadienoate181 114 139 ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bish omo- 8.xi.-13-trans,17-cis-prostadienoate182 118 139 ethyl 9-oxo-15-triphenylmethoxy-3-thia-8.xi .-13- trans,17-cis-prostadienoate183 81 139 butyl 9-oxo-15-triphenylmethoxy-8.xi.-13-tr ans,17- cis-prostadienoate184 82 139 isopropyl 9-oxo-15-triphenylmethoxy-8.xi.-1 3-trans, cis-prostadienoate185 83 139 methyl 9-oxo-15-triphenyl-8.xi.-13-trans, 17-cis-prostadienoate186 84 139 n-decyl 9-oxo-15-triphenylmethoxy-8.xi.-13- trans,17- cis-prostadienoate187 14 136 ethyl 9-oxo-15-triphenylmethoxy-5,6,7-trino r-19- isobutyl-8.xi.-13-trans,18-prostadienoate188 14 137 ethyl 9-oxo-15-triphenylmethoxy-5,6,7,19,20 -penta- nor-8.xi.-13-trans-17,prostadienoate189 13 137 ethyl 9-oxo-15-triphenylmethoxy-19,20-dinor -8.xi.-13- trans,18-prostadienoate190 13 138 ethyl 9-oxo-15-triphenylmethoxy-17-methyl-2 0-iso- propenyl-8.xi.-trans-prostenoate191 15 131 ethyl 9-oxo-15-triphenylmethoxy-16-ethyl-6, 7,19, 20-tetranor-8.xi.-13-trans-prostenoate192 15 135 ethyl 9-oxo-15-triphenylmethoxy-18,19-dimet hyl-6, 7-dinor-8.xi.-13-trans,18-prostadienate193 23 130 ethyl 9-oxo-15-triphenylmethoxy-16-ethyl-7a ,7b- bishomo-8.xi.-13-trans-prostenoate194 23 134 ethyl 9-oxo-15-triphenylmethoxy-19-methyl-7 a,7b- bishomo-8.xi.-13-trans,18-prostadienoate195 31 126 ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-19, 20- dinor-8.xi.-13-trans-prostenoate196 31 129 ethyl 9-oxo-15-triphenylmethoxy-2,20-diethy l- 8.xi.-13-trans-prostenoate197 31 132 ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-16- methyl-8.xi.-20-nor-13-trans-prostenoate198 31 135 ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-18, 19-dimethyl-8.xi.-13-trans,18-prostadienoat e199 41 127 ethyl 9-oxo-15-triphenylmethoxy-3,3-dimethy l- 18,19,20-trinor-8.xi.-13-trans-prostenoate200 41 128 ethyl 9-oxo-15-triphenylmethoxy-3,3,20-tri- methyl-8.xi.-13-trans-prostenoate201 41 132 ethyl 9-oxo-15-triphenylmethoxy-3,3,16-tri methyl-20-nor-8.xi.-13-trans-prostenoate202 41 136 ethyl 9-oxo-15-triphenylmethoxy-3,3-dimethy l- 19-isobutyl-8.xi.-13-trans,18-prostadienoat e203 41 137 ethyl 9-oxo-15-triphenylmethoxy-3,3-dimethy l- 19,20-dinor-8.xi.-13-trans,17-prostadienoat e204 46 125 ethyl 9-oxo-15-triphenylmethoxy-3-oxa-20-no r- 8.xi.-13-trans-prostenoate205 46 128 ethyl 9-oxo-15-triphenylmethoxy-3-oxa-20- methyl-8.xi.-13-trans-prostenoate206 46 130 ethyl 9-oxo-15-triphenylmethoxy-3-oxa-16- ethyl-8.xi.-13-trans-prostenoate207 46 132 ethyl 9-oxo-15-triphenylmethoxy-3-oxa-16- methyl-20-nor-8.xi.-13-trans-prostenoate208 46 137 ethyl 9-oxo-15-triphenylmethoxy-3-oxa-19,20 - dinor-8.xi.-13-trans,17-prostadienoate209 53 137 ethyl 9-oxo-15-triphenylmethoxy-7,19,20-tri nor-8.xi.-13-trans,17-prostadienoate210 53 135 ethyl 9-oxo-15-triphenylmethoxy-7-nor-18,19 - dimethyl-8.xi.-13-trans,18-prostadienoate211 53 133 ethyl 9-oxo-15-triphenylmethoxy-7,18,19,20- tetranor-16-methyl-8.xi.-13-trans-prostenoa te212 70 125 ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-20 - nor-8.xi.-13-trans-prostenoate213 70 129 ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-20 - ethyl-8.xi.-13-trans-prostenoate214 70 131 ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-16 - ethyl-19,20-dinor-8.xi.-13-trans-prostenoat e215 70 132 ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-16 - methyl-20-nor-8.xi.-13-trans-prostenoate216 70 134 ethyl 9-oxo-15-triphenylmmethoxy-2-fluoro-1 9- methyl-8.xi.-13-trans,18-prostadienoate217 74 135 ethyl 9-oxo-15-triphenylmethoxy-7a-homo-18, 19- dimethyl-8.xi.-13-trans,18-prostadienoate218 74 137 ethyl 9-oxo-15-triphenylmethoxy-7a-homo-19, 20- dinor-8.xi.-13-trans,17-prostadienoate219 79 125 ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-20 - nor-8.xi.-13-trans-prostenoate220 79 129 ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-20 - ethyl-8.xi.-13-trans-prostenoate221 79 130 ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-16 - ethyl-8.xi.-13-trans-prostenoate222 79 133 ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-16 - methyl-18,19,20-trinor-8.xi.-trans-prosteno ate223 79 135 ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-18 , 19,-dimethyl-8.xi.-13-trans,18-prostadienoa te224 99 125 ethyl 9-oxo-15-triphenylmethoxy-2-methyl-20 - nor-8.xi.-13-trans-prostenoate225 99 128 ethyl 9-oxo-15-triphenylmethoxy-2,20-dimeth yl- 8.xi.-13-trans-prostenoate226 99 131 ethyl 9-oxo-15-triphenylmethoxy-2-methyl-16 - ethyl-19,20-dinor-8.xi.-13-trans-prostenoat e227 99 134 ethyl 9-oxo-15-triphenylmethoxy-2,19-dimeth yl- 8.xi.-13-trans,18-prostadienoate228 99 137 ethyl 9-oxo-15-triphenylmethoxy-2-methyl-19 , 20-dinor-8.xi.-13-trans,17-prostadienoate229 111 125 ethyl 9-oxo-15-triphenylmethoxy-10a-homo-20 - nor-8.xi.-13-trans-prostenoate230 111 128 ethyl 9-oxo-15-triphenylmethoxy-10a-homo-20 - methyl-8.xi.-13-trans-prostenoate231 111 130 ethyl 9-oxo-15-triphenylmethoxy-10a-homo-16 - ethyl-8.xi.-13-trans-prostenoate232 111 35 ethyl 9-oxo-15-triphenylmethoxy-10a-homo-18 , 19-dimethyl-8.xi.-13-trans,18-prostadienoat e233 111 137 ethyl 9-oxo-15-triphenylmethoxy-10a-homo-19 , 20-dinor-8.xi.-13-trans,17-prostadienoate234 112 129 ethyl 9-oxo-15-triphenylmethoxy-10a-homo-5, 6, 7-trinor-20-ethyl-8.xi.-13-trans-prostenoat e235 112 132 ethyl 9-oxo-15-triphenylmethoxy-10a-homo-5, 6, 7,20-tetranor-16-methyl-8.xi.-13-trans-pros t- enoate236 112 136 ethyl 9-oxo-15-triphenylmethoxy-10a-homo-5, 6,7- trinor-19-isobutyl-8.xi.-13-trans,18-prosta dienoate237 113 128 ethyl 9-oxo-15-triphenylmethoxy-10a-homo-20 - methyl-8.xi.-13-trans-prostenoate238 113 134 ethyl 9-oxo-15-triphenylmethoxy-10a-homo-19 - methyl-8.xi.-13-trans,18-prostadienoate239 114 125 ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bis- homo-20-nor-8.xi.-13-trans-prostenoate240 114 129 ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bis- homo-20-ethyl-8.xi.-13-trans-prostenoate241 114 132 ethyl 9-oxo-15-triphenylmethoxy-7a,10a- is- homo-16-methyl-20-nor-8.xi.-13-trans-proste noate242 114 134 ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bis- homo-19-methyl-8.xi.-13-trans,18-prostadien oate243 118 125 ethyl 9-oxo-15-triphenylmethoxy-3-thia-20-n or- 8.xi.-13-trans-prostenoate244 118 128 ethyl 9-oxo-15-triphenylmethoxy-3-thia-20-m ethyl- 8.xi.-13-trans-prostenoate245 118 130 ethyl 9-oxo-15-triphenylmethoxy-3-thia-16-e thyl- 8.xi.-13-trans-prostenoate246 118 133 ethyl 9-oxo-15-triphenylmethoxy-3-thia-16- B methyl-18,19,20-trinor-8.xi.-13-trans-prost enoate247 118 134 ethyl 9-oxo-15-triphenylmethoxy-3-thia-19-m ethyl- 8.xi.-13-trans,18-prostadienoate248 118 137 ethyl 9-oxo-15-triphenylmethoxy-3-thia-19,2 0- dinor-8.xi.-13-trans,17-prostadienoate249 900 125 methyl 9-oxo-15-triphenylmethoxy-20-nor-8.x i.-5- cis,13-trans-prostadienoate250 900 128 methyl 9-oxo-15-triphenylmethoxy-20-methyl- 8.xi.-5- cis,13-trans-prostadienoate251 900 130 methyl 9-oxo-15-triphenylmethoxy-16-ethyl-8 .xi.-5- cis,13-trans-prostadienoate252 900 132 methyl 9-oxo-15-triphenylmethoxy-16-methyl- 20- nor-8.xi.-5-cis,13-trans-prostadienoate253 900 134 methyl 9-oxo-15-triphenylmethoxy-19-methyl- 8.xi.-5- cis,13-trans,18-prostatrienoate254 900 135 methyl 9-oxo-15-triphenylmethoxy-18,19-dime thyl- 8.xi.-5-cis,13-trans,18-prostatrienoate255 900 137 methyl 9-oxo-15-triphenylmethoxy-19,20-dino r-8.xi.- 5-cis,13-trans,17-prostatrienoate256 900 139 methyl 9-oxo-15-triphenylmethoxy-8.xi.-5-ci s,13- trans,17-cis-prostatrienoate__________________________________________________________________________

EXAMPLE 257

Preparation of ethyl 9.alpha./.beta.,15-dihydroxy-13-trans-prostenoate

A solution containing 3 g. of ethyl 9-oxo-15-hydroxy-13-trans-prostenoate (Example 121) in 120 ml. of absolute alcohol containing 115 mg. of sodium borohydride is stirred at ambient temperature for 18 hours. The solution is poured into 300 ml. of saturated sodium chloride solution and the oily precipitate is extracted with ether. The ether is washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness to give subject product as an oil; .lambda. max, 2195, 5178, 8.45 .mu.; the product is a mixture of 9.alpha.- and 9.beta.-hydroxy derivatives.

EXAMPLES 258-374

Treatment of the designated 9-oxo-15-triphenylmethoxy derivatives listed in the table below, with glacial acetic acid-tetrahydropyran-water (4:2:1) in the manner described in Example 121 is productive of the corresponding 15-hydroxy derivatives of the table. This acid treatment also ensures a trans-relationship between the two side-chains attached to C.sub.8 and C.sub.12.

TABLE 4______________________________________ Starting 15-tri- phenylmethoxy Product Alkyl 9-oxo-Ex- derivative of 15-hydroxy-13-trans-ample Example prostenoates______________________________________258 140 Ethyl 9-oxo-15-hydroxy- 5,6,7-trinor-13-trans- prostenoate259 141 Ethyl 9-oxo-15-hydroxy- 7a,7b-bishomo-13- trans-prostenoate260 142 Ethyl 9-oxo-15-hydroxy- 2-ethyl-13-trans- prostenoate261 143 Ethyl 9-oxo-15-hydroxy- 3,3-dimethyl-13-trans- prostenoate262 144 Ethyl 9-oxo-15-hydroxy- 3-oxa-13-trans- prostenoate263 145 Ethyl 9-oxo-15-hydroxy- 7-nor-13-trans- prostenoate264 146 Ethyl 9-oxo-15-hydroxy- 2-fluoro-13-trans- prostenoate265 147 Ethyl 9-oxo-15-hydroxy- 7a-homo-13-trans- prostenoate266 148 Ethyl 9-oxo-15-hydroxy- 2-phenyl-13-trans- prostenoate267 149 Ethyl 9-oxo-15-hydroxy- 2-methyl-13-trans- prostenoate268 150 Ethyl 9-oxo-15-hydroxy-10a-homo-13-trans- prostenoate269 151 EThyl 9-oxo-15-hydroxy- 10a-homo-5,6,7-trinor- 13-trans-prostenoate270 152 Ethyl 9-oxo-15-hydroxy- 10a-homo-7-nor-13- trans-prostenoate271 153 Ethyl 9-oxo-15-hydroxy- 7a,10a-bishomo-13- trans-prostenoate272 154 Ethyl 9-oxo-15-hydroxy- 3-thia-13-trans- prostenoate273 155 Butyl 9-oxo-15-hydroxy- 13-trans-prostenoate274 156 Isopropyl 9-oxo-15- hydroxy-13-trans- prostenoate275 157 Methyl 9-oxo-15-hydroxy- 13-trans-prostenoate276 158 n-decyl 9-oxo-15- hydroxy-13-trans- prostenoate277 159 Methyl 9-oxo-15- hydroxy-5-cis,-13- trans-prostadienoate278 160 Ethyl 9-oxo-15-hydroxy- 20-nor-13-trans- prostenoate279 161 Ethyl 9-oxo-15-hydroxy- 20-methyl-13-trans- prostenoate280 162 Ethyl 9-oxo-15-hydroxy- 16-ethyl-13-trans- prostenoate281 163 Ethyl 9-oxo-15-hydroxy- 16-methyl-20-nor-13- trans-prostenoate282 164 Ethyl 9-oxo-15-hydroxy- 19-methyl-13-trans,18- prostadienoate283 165 Ethyl 9-oxo-15-hydroxy- 18,19-dimethyl-13- trans,18-prostadienoate284 166 Ethyl 9-oxo-15-hydroxy- 13-trans,17-cis- prostadienoate285 167 Ethyl 9-oxo-15-hydroxy- 5,6,7-trinor-13-trans, 17-cis-prostadienoate286 168 Ethyl 9-oxo-15-hydroxy- 6,7-dinor-13-trans- 17-cis-prostadienoate287 169 Ethyl 9-oxo-15-hydroxy- 7a,7b-bishomo-13- trans,17-cis-prosta- dienoate288 170 Ethyl 9-oxo-15-hydroxy- 2-ethyl-13-trans,17- cis-prostadienoate289 171 Ethyl 9-oxo-15-hydroxy- 3,3-dimethyl-13-trans, 17-cis-prostadienoate290 172 Ethyl 9-oxo-15-hydroxy- 3-oxa-13-trans,17-cis prostadienoate291 173 Ethyl 9-oxo-15-hydroxy- 7-nor-13-trans,17-cis- prostadienoate292 174 Ethyl 9-oxo-15-hydroxy- 2-fluoro-13-trans,17- cis-prostadienoate293 175 Ethyl 9-oxo-15-hydroxy- 7a-homo-13-trans,17- cis-prostadienoate294 176 Ethyl 9-oxo-15-hydroxy- 2-phenyl-13-trans,17- cis-prostadienoate295 177 Ethyl 9-oxo-15-hydroxy- 2-methyl-13-trans,17- cis-prostadienoate296 178 Ethyl 9-oxo-15-hydroxy- 10a-homo-13-trans,17- cis-prostadienoate297 179 Ethyl 9-oxo-15-hydroxy- 10a-homo-5,6,7-trinor- 13-trans,17-cis-prosta- dienoate298 180 Ethyl 9-oxo-15-hydroxy- 10a-homo-7-nor-13- trans,17-cis-prosta- dienoate299 181 Ethyl 9-oxo-15-hydroxy- 7a,10a-bishomo-13- trans,17-cis-prosta- dienoate300 182 Ethyl 9-oxo-15-hydroxy- 3-thia-13-trans,17- cis-prostadienoate301 183 Butyl 9-oxo-15-hydroxy- 13-trans,17-cis- prostadienoate302 184 Isopropyl 9-oxo-15- hydroxy-13-trans, 17- cis-prostadienoate303 185 Methyl 9-oxo-15-hydroxy- 13-trans,-17-cis- prostadienoate304 186 n-decyl 9-oxo-15- hydroxy-13-trans,17- cis-prostadienoate305 187 Ethyl 9-oxo-15-hydroxy- 5,6,7-trinor-19-iso- butyl-13-trans,18- prostadienoate306 188 Ethyl 9-oxo-15-hydroxy- 5,6,7,19,20-pentanor- 13-trans,17-prosta- dienoate307 189 Ethyl 9-oxo-15-hydroxy- 19,20-dinor-13-trans, 18-prostadienoate308 190 Ethyl 9-oxo-15-hydroxy- 17-methyl-20-isopro- penyl-13-trans-prosta- dienoate309 191 Ethyl 9-oxo-15-hydroxy- 16-ethyl-6,7,19,20- tetranor-13-trans- prostenoate310 192 Ethyl 9-oxo-15-hydroxy- 18,19-dimethyl-6,7- dinor-13-trans,18- prostadienoate311 193 Ethyl 9-oxo-15-hydroxy- 16-ethyl-7a,7b-bishomo- 13-trans-prostenoate312 194 Ethyl 9-oxo-15-hydroxy- 19-methyl-7a,7b-bis- homo-13-trans,18- prostadienoate313 195 Ethyl 9-oxo-15-hydroxy- 2-ethyl-19,20-dinor- 13-trans-prostenoate314 196 Ethyl 9-oxo-15-hydroxy- 2,20-diethyl-13-trans- prostenoate315 197 Ethyl 9-oxo-15-hydroxy- 2-ethyl-16-methyl-20- nor-trans-prostenoate316 198 Ethyl 9-oxo-15-hydroxy- 2-ethyl-18,19-dimethyl- 13-trans,18-prosta- dienoate317 199 Ethyl 9-oxo-15-hydroxy- 3,3-dimethyl-18,19,20- trinor-13-trans- prostenoate318 200 Ethyl 9-oxo-15-hydroxy- 3,3,20-trimethyl-13- trans-prostenoate319 201 Ethyl 9-oxo-15-hydroxy- 3,3,16-trimethyl-20- nor-13-trans-prosta- noate320 202 Ethyl 9-oxo-15-hydroxy- 3,3-dimethyl-19-iso- butyl-13-trans,18- prostadienoate321 203 Ethyl 9-oxo-15-hydroxy- 3,3-dimethyl-19,20- dinor-13-trans,17- prostadienoate322 204 Ethyl 9-oxo-15-hydroxy- 3-oxa-20-nor-13-trans- prostenoate -323 205 Ethyl 9-oxo-15-hydroxy- 3-oxa-20-methyl-13- trans-prostenoate324 206 Ethyl 9-oxo-15-hydroxy- 3-oxa-16-ethyl-13- trans-prostenoate325 207 Ethyl 9-oxo-15-hydroxy- 3-oxa-16-methyl-20- nor-13-trans- prostenoate326 208 Ethyl 9-oxo-15-hydroxy- 3-oxa-19,20-dinor-13- trans,17-prostadienoate327 209 Ethyl 9-oxo-15-hydroxy- 7,19,20-trinor-13- trans,17-prostadienoate328 210 Ethyl 9-oxo-15-hydroxy- 7-nor-18,19-dimethyl- 13-trans,18-prosta- dienoate329 211 Ethyl 9-oxo-15-hydroxy- 7,18,19,20-tetranor- 16-methyl-13-trans- prostenoate330 212 Ethyl 9-oxo-15-hydroxy- 2-fluoro-20-nor-13- trans-prostenoate331 213 Ethyl 9-oxo-15-hydroxy- 2-fluoro-20-ethyl-13- trans-prostenoate332 214 Ethyl 9-oxo-15-hydroxy- 2-fluoro-16-ethyl-19, 20-dinor-13-trans- prostenoate333 215 Ethyl 9-oxo-15-hydroxy- 2-fluoro-16-methyl-20- nor-13-trans-prostenoate- prostenoate334 216 Ethyl 9-oxo-15-hydroxy- 2-fluoro-19-methyl-13- trans,18-prostadienoate335 217 Ethyl 9-oxo-15-hydroxy- 7a-homo-18,19-dimethyl- 13-trans,18-prosta- dienoate336 218 Ethyl 9-oxo-15-hydroxy- 7a-homo-19,20-dinor- 13-trans,17-prosta- dienoate337 219 Ethyl 9-oxo-15-hydroxy- 2-phenyl-20-nor-13- trans-prostenoate338 220 Ethyl 9-oxo-15-hydroxy- 2-phenyl-20-ethyl-13- trans-prostenoate339 221 Ethyl 9-oxo-15-hydroxy- 2-phenyl-16-ethyl-13- trans-prostenoate340 222 Ethyl 9-oxo-15-hydroxy- 2-phenyl-16-methyl-18, 19,20-trinor-13-trans- prostenoate341 223 Ethyl 9-oxo-15-hydroxy- 2-phenyl-18,19-di- methyl-13-trans,18-pro- stadienoate342 224 Ethyl 9-oxo-15-hydroxy- 2-methyl-20-nor-13- trans-prostenoate343 225 Ethyl 9-oxo-15-hydroxy- 2,20-dimethyl-13-trans- prostenoate344 226 Ethyl 9-oxo-15-hydroxy- 2-methyl-16-ethyl-19, 20-dinor-13-trans- prostenoate345 227 Ethyl 9-oxo-15-hydroxy- 2,19-dimethyl-13-trans, 18-prostadienoate346 228 Ethyl 9-oxo-15-hydroxy- 2-methyl-19,20-dinor- 13-trans,17-prosta- dienoate347 229 Ethyl 9-oxo-15-hydroxy- 10a-homo-20-nor-13- trans-prostenoate348 230 Ethyl 9-oxo-15-hydroxy- 10a-homo-20-methyl-13- trans-prostenoate349 231 Ethyl 9-oxo-15-hydroxy- 10a-homo-16-ethyl-13- trans-prostenoate350 232 Ethyl 9-oxo-15-hydroxy- 10a-homo-18,19-dimethyl- 13-trans,18-prosta- dienoate351 233 Ethyl 9-oxo-15-hydroxy- 10a-homo-19,20-dinor- 13-trans,17-prosta- dienoate352 234 Ethyl 9-oxo-15-hydroxy- 10a-homo-5,6,7-trinor- 20-ethyl-13-trans- prostenoate353 235 Ethyl 9-oxo-15-hydroxy- 10a-homo-5,6,7,20- tetranor-16-methyl-13- trans-prostenoate354 236 Ethyl 9-oxo-15-hydroxy- 10a-homo-5,6,7-trinor- 19-isobutyl-13-trans, 18-prostadienoate355 237 Ethyl 9-oxo-15-hydroxy- 10a-homo-20-methyl-13- trans-prostenoate356 238 Ethyl 9-oxo-15-hydroxy- 10a-homo-19-methyl-13- trans,18-prostadienoate257 239 Ethyl 9-oxo-15-hydroxy- 7a,10a-bishomo-20-nor- 13-trans-prostenoate358 240 Ethyl 9-oxo-15-hydroxy- 7a,10a-bishomo-20- ethyl-13-trans-pro- stenoate359 241 Ethyl 9-oxo-15-hydroxy- 7a,10a-bishomo-16- methyl-20-nor-13-trans- prostenoate360 242 Ethyl 9-oxo-15-hydroxy- 7a,10a-bishomo-19- methyl-13-trans,18- prostadienoate361 243 Ethyl 9-oxo-15-hydroxy- 3-thia-20-nor-13-trans- prostenoate362 244 Ethyl 9-oxo-15-hydroxy- 3-thia-20-methyl-13- trans-prostenoate363 245 Ethyl 9-oxo-15-hydroxy- 3-thia-16-ethyl-13- trans-prostenoate364 246 Ethyl 9-oxo-15-hydroxy- 3-thia-16-methyl-18,19, 20-trinor-13-trans- prostenoate365 247 Ethyl 9-oxo-15-hydroxy- 3-thia-19-methyl-13- trans,18-prostadienoate366 248 Ethyl 9-oxo-15-hydroxy- 3-thia-19,20-dinor-13- trans,17-prostadienoate367 249 Methyl 9-oxo-15-hydroxy- 20-nor-5-cis,13-trans- prostadienoate368 250 Methyl 9-oxo-15-hydroxy- 20-methyl-5-cis,13- trans-prostadienoate369 251 Methyl 9-oxo-15-hydroxy- 16-ethyl-5-cis,13- trans-prostadienoate370 252 Methyl 9-oxo-15-hydroxy- 16-methyl-20-nor-5-cis, 13-trans-prostadienoate371 253 Methyl 9-oxo-15-hydroxy- 19-methyl-5-cis,13- trans,18-prosta- trienoate372 254 Methyl 9-oxo-15-hydroxy- 18,19-dimethyl-5-cis, 13-trans,18-prosta- trienoate373 255 Methyl 9-oxo-15-hydroxy- 19,20-dinor-5-cis,13- trans,17-prosta- trienoate374 256 Methyl 9-oxo-15-hydroxy- 5-cis,13-trans,17-cis- prostatrienoate______________________________________

EXAMPLES 375-491

Saponification of the alkyl esters designated in the following table by the method described in Example 122 is productive of the prostenoic acids of the table.

Table 5______________________________________ Starting alkyl 9- ProductEx- oxo-prostenoate 9-Oxo-15-hydroxy-13-ample of example trans-prostenoic acid______________________________________375 258 9-oxo-15-hydroxy-5,6,7- trinor-13-trans-pros- tenoic acid376 259 9-oxo-15-hydroxy-7a,7b- bishomo-13-trans-pros- tenoic acid377 260 9-oxo-15-hydroxy-2- ethyl-13-trans-pros- tenoic acid378 261 9-oxo-15-hydroxy-3,3- dimethyl-13-trans- prostenoic acid379 262 9-oxo-15-hydroxy-3-oxa- 13-trans-prostenoic acid380 263 9-oxo-15-hydroxy-7-nor- 13-trans-prostenoic acid381 264 9-oxo-15-hydroxy-2- fluoro-13-trans-pros- tenoic acid382 265 9-oxo-15-hydroxy-7a- homo-13-trans-pros- tenoic acid383 266 9-oxo-15-hydroxy-2- phenyl-13-trans-pros- tenoic acid384 267 9-oxo-15-hydroxy-2- methyl-13-trans-pros- tenoic acid385 268 9-oxo-15-hydroxy-10a- homo-13-trans-pros- tenoic acid386 269 9-oxo-15-hydroxy-10a- homo-5,6,7-trinor-13- trans-prostenoic acid387 270 9-oxo-15-hydroxy-10a- homo-7-nor-13-trans- prostenoic acid388 271 9-oxo-15-hydroxy-7a,- 10a-bishomo-13-trans- prostenoic acid389 272 9-oxo-15-hydroxy-3- thia-13-trans-pros- tenoic acid390 273 9-oxo-15-hydroxy-13- trans-prostenoic acid391 274 9-oxo-15-hydroxy-13- trans-prostenoic acid392 275 9-oxo-15-hydroxy-13- trans-prostenoic acid393 276 9-oxo-15-hydroxy-13- trans-prostenoic acid394 277 9-oxo-15-hydroxy-5-cis, 13-trans-prostadienoic acid395 278 9-oxo-15-hydroxy-20-nor- 13-trans-prostenoic acid396 279 9-oxo-15-hydroxy-20- methyl-13-trans-pros- tenoic acid397 280 9-oxo-15-hydroxy-16- ethyl-13-trans-pros- tenoic acid398 281 9-oxo-15-hydroxy-16- methyl-20-nor-13-trans- prostenoic acid399 282 9-oxo-15-hydroxy-19- methyl-13-trans,18- prostadienoic acid400 283 9-oxo-15-hydroxy-18,19- dimethyl-13-trans,18- prostadienoic acid401 284 9-oxo-15-hydroxy-13- trans,-17-cis-prosta- dienoic acid402 285 9-oxo-15-hydroxy-5,6,7- trinor-13-trans,17-cis- prostadienoic acid403 286 9-oxo-15-hydroxy-6,7-di- nor-13-trans,17-cis- prostadienoic acid404 287 9-oxo-15-hydroxy-7a,7b- bishomo-13-trans,17- cis-prostadienoic acid405 288 9-oxo-15-hydroxy-2- ethyl-13-trans,17-cis- prostadienoic acid406 289 9-oxo-15-hydroxy-3,3- dimethyl-13-trans,17- cis-prostadienoic acid407 290 9-oxo-15-hydroxy-3-oxa- 13-trans,17-cis-pros- tadienoic acid408 291 9-oxo-15-hydroxy-7-nor- 13-trans,17-cis-pros- tadienoic acid409 292 9-oxo-15-hydroxy-2- fluoro-13-trans,17-cis- prostadienoic acid410 293 9-oxo-15-hydroxy-7a- homo-13-trans,17-cis- prostadienoic acid411 294 9-oxo-15-hydroxy-2- phenyl-13-trans,17-cis- prostadienoic acid412 295 9-oxo-15-hydroxy-2- methyl-13-trans,17- cis-prostadienoic acid413 296 9-oxo-15-hydroxy-10a- homo-13-trans,17-cis- prostadienoic acid414 297 9-oxo-15-hydroxy-10a- homo-5,6,7-trinor-13- trans,17-cis-prosta- dienoic acid415 298 9-oxo-15-hydroxy-10a- homo-7-nor-13-trans,- 17-cis-prostadienoic acid416 299 9-oxo-15-hydroxy-7a,- 10a-bishomo-13-trans,- 17-cis-prostadienoic acid417 300 9-oxo-15-hydroxy-3-thia- 13-trans,17-cis-prosta- dienoic acid418 301 9-oxo-15-hydroxy-13- trans,17-cis-prosta- dienoic acid419 302 9-oxo-15-hydroxy-13- trans,17-cis-prosta- dienoic acid420 303 9-oxo-15-hydroxy-13- trans,17-cis-prosta- dienoic acid421 304 9-oxo-15-hydroxy-13- trans,17-cis-prosta- dienoic acid422 305 9-oxo-15-hydroxy-5,6,7- trinor-19-isobutyl-13- trans,18-prostadienoic acid423 306 9-oxo-15-hydroxy-5,6,7- 19,20-pentanor-13-trans, 17-prostadienoic acid424 307 9-oxo-15-hydroxy-19,20- dinor-13-trans,18- prostadienoic acid425 308 9-oxo-15-hydroxy-17,- methyl-20-isopropenyl- 13-trans-prostenoic acid426 309 9-oxo-15-hydroxy-16- ethyl-6,7,19,20-tetra- nor-13-trans-prostenoic acid427 310 9-oxo-15-hydroxy-18,19- dimethyl-6,7,-dinor-13- trans,18-prostadienoic acid428 311 9-oxo-15-hydroxy-16- ethyl-7a,7b-bishomo- 13-trans-prostenoic acid429 312 9-oxo-15-hydroxy-19- methyl-7a,7b-bishomo- 13-trans-18-prosta- dienoic acid430 313 9-oxo-15-hydroxy-2- ethyl-19,20-dinor-13- trans-prostenoic acid431 314 9-oxo-15-hydroxy-2,20- diethyl-13-trans-pros- enoic acid432 315 9-oxo-15-hydroxy-2- ethyl-16-methyl-20-nor- 13-trans-prostenoic acid433 316 9-oxo-15-hydroxy-2- ethyl-18,19-dimethyl- 13-trans,18-prosta- dienoic acid434 317 9-oxo-15-hydroxy-3,3- dimethyl-18,19,20-tri- nor-13-trans-prostenoic acid435 318 9-oxo-15-hydroxy-3,3- 20-trimethyl-13-trans- prostenoic acid436 319 9-oxo-15-hydroxy-3,3- 16-trimethyl-20-nor-13- trans-prostenoic acid437 320 9-oxo-15-hydroxy-3,3- dimethyl-19-isobutyl- 13-trans,18-prosta- dienoic acid438 321 9-oxo-15-hydroxy-3,3- dimethyl-19,20-dinor- 13-trans,17-prosta- dienoic acid439 322 9-oxo-15-hydroxy-3-oxa- 20-nor-13-trans-prost- enoic acid440 323 9-oxo-15-hydroxy-3-oxa- 20-methyl-13-trans- prostenoic acid441 324 9-oxo-15-hydroxy-3-oxa- 16-ethyl-13-trans- prostenoic acid442 325 9-oxo-15-hydroxy-3-oxa- 16-methyl-20-nor-13- trans-prostenoic acid443 326 9-oxo-15-hydroxy-3-oxa- 19,20-dinor-13-trans,- 17-prostadienoic acid444 327 9-oxo-15-hydroxy-7,19,- 20-trinor-13-trans,17- prostadienoic acid445 328 9-oxo-15-hydroxy-7-nor- 18,19-dimethyl-13- trans,18-prostadienoic acid446 329 9-oxo-15-hydroxy-7,18,- 19,20-tetranor-16-meth- yl-13-trans-prostenoic acid447 330 9-oxo-15-hydroxy-2- fluoro-20-nor-13-trans- prostenoic acid448 331 9-oxo-15-hydroxy-2- fluoro-20-ethyl-13- trans-prostenoic acid449 332 9-oxo-15-hydroxy-2- fluoro-16-ethyl-19,20- dinor-13-trans-pros- tenoic acid450 333 9-oxo-15-hydroxy-2- fluoro-16-methyl-20- nor-13-trans-pros- tenoic acid451 334 9-oxo-15-hydroxy-2- fluoro-19-methyl-13- trans,18-prostadienoic acid452 335 9-oxo-15-hydroxy-7a- homo-18,19-dimethyl- 13-trans,18-prosta- dienoic acid453 336 9-oxo-15-hydroxy-7a- homo-19,20-dinor-13- trans,17-prostadienoic acid454 337 9-oxo-15-hydroxy-2- phenyl-20-nor-13-trans- prostenoic acid455 338 9-oxo-15-hydroxy-2- phenyl-20-ethyl-13- trans-prostenoic acid456 339 9-oxo-15-hydroxy-2- phenyl-16-ethyl-13- trans-prostenoic acid457 340 9-oxo-15-hydroxy-2-phen- yl-16-methyl-18,19,20- trinor-13-trans-pros- tenoic acid458 341 9-oxo-15-hydroxy-2- phenyl-18,19-dimethyl- 13-trans,18-prosta- dienoic acid459 342 9-oxo-15-hydroxy-2- methyl-20-nor-13-trans- prostenoic acid460 343 9-oxo-15-hydroxy-2,20- dimethyl-13-trans- prostenoic acid461 344 9-oxo-15-hydroxy-2- methyl-16-ethyl-19,20- dinor-13-trans-pros- tenoic acid462 345 9-oxo-15-hydroxy-2,19- dimethyl-13-trans,18- prostadienoic acid463 346 9-oxo-15-hydroxy-2- methyl-19,20-dinor- 13-trans,17-prosta- dienoic acid464 347 9-oxo-15-hydroxy-10a- homo-20-nor-13-trans- prostenoic acid465 348 9-oxo-15-hydroxy-10a- homo-20-methyl-13- trans-prostenoic acid466 349 9-oxo-15-hydroxy-10a- homo-16-ethyl-13-trans- prostenoic acid467 350 9-oxo-15-hydroxy-10a- homo-18,19-dimethyl- 13-trans,18-prosta- dienoic acid468 351 9-oxo-15-hydroxy-10a- homo-19,20-dinor-13- trans,17-prostadienoic acid469 352 9-oxo-15-hydroxy-10a- homo-5,6,7-trinor-20- ethyl-13-trans-pros- tenoic acid470 353 9-oxo-15-hydroxy-10a- homo-5,6,7,20-tetra- nor-16-methyl-13-trans- prostenoic acid471 354 9-oxo-15-hydroxy-10a- homo-5,6,7-trinor-19- isobutyl-13-trans,18- prostadienoic acid472 355 9-oxo-15-hydroxy-10a- homo-20-methyl-13- trans-prostenoic acid473 356 9-oxo-15-hydroxy-10a- homo-19-methyl-13- trans,18-prostadienoic acid474 357 9-oxo-15-hydroxy-7a,10a- bishomo-20-nor-13- trans-prostenoic acid475 358 9-oxo-15-hydroxy-7a,10a- bishomo-20-ethyl-13- trans-prostenoic acid476 359 9-oxo-15-hydroxy-7a,10a- bishomo-16-methyl-20- nor-13-trans-prostenoic acid477 360 9-oxo-15-hydroxy-7a,10a- bishomo-19-methyl-13- trans,18-prostadienoic acid478 361 9-oxo-15-hydroxy-3-thia- 20-nor-13-trans-pros- tenoic acid479 362 9-oxo-15-hydroxy-3-thia- 20-methyl-13-trans- prostenoic acid480 363 9-oxo-15-hydroxy-3-thia- 16-ethyl-13-trans- prostenoic acid481 364 9-oxo-15-hydroxy-3-thia- 16methyl-18,19,20- trinor-13-trans-pros- tenoic acid482 365 9-oxo-15-hydroxy-3-thia- 19-methyl-13-trans,18- prostadienoic acid483 366 9-oxo-15-hydroxy-3-thia- 19,20-dinor-13-trans,- 17-prostadienoic acid484 367 9-oxo-15-hydroxy-20-nor- 5-cis,13-trans-prosta- dienoic acid485 368 9-oxo-15-hydroxy-20- methyl-5-cis,13-trans- prostadienoic acid486 369 9-oxo-15-hydroxy-16- ethyl-5-cis,13-trans- prostadienoic acid487 370 9-oxo-15-hydroxy-16- methyl-20-nor-5-cis,13- trans-prostadienoic acid488 371 9-oxo-15-hydroxy-19- methyl-5-cis,13-trans,- 18-prostatrienoic acid489 372 9-oxo-15-hydroxy-18,19- dimethyl-5-cis,13- trans-18-prostatrienoic acid490 373 9-oxo-15-hydroxy-19,20- dinor-5-cis,13-trans,- 17-prostatrienoic acid491 374 9-oxo-15-hydroxy-5-cis,- 13-trans,17-cis-prosta- trienoic acid______________________________________

EXAMPLE 492

Preparation of 3-(tert-butoxy)-1-iodooctane

Into a solution of 16.7 g. of 1-iodo-3-octanol [Shriner et al., J. Org. Chem. 4, 103 (1939)] in 250 ml. of methylene chloride is bubbled isobutylene at a fast rate until the solution is saturated. The solution is cooled and 2 ml. of concentrated sulfuric acid is added. The solution is stoppered and allowed to stand at room temperature for 3 days. After the solution is poured into 300 ml. of 5% sodium carbonate, the organic phase is separated, washed with brine, dried with anhydrous magnesium sulfate and evaporated to dryness. Distillation gave 13.9 g. (68%) of product, b.p. 59.degree. C. (0.008 mm).

EXAMPLE 493

Preparation of 15-(tert-butoxy)-9-oxoprostanoic acid, ethyl ester

To a Grignard solution, prepared from 5.05 g. of magnesium and 65.8 g. of 3-(tert-butoxy)-1-iodooctane in 150 ml. of diethyl ether under nitrogen atmosphere, is added 4.0 g. of copper iodide-tri-n-butylphosphine complex followed by dropwise addition of 49 g. of 2-(6-carbethoxyhexyl)cyclopent-2-en-1-one [Hardegger et al., Helv. Chim. Acta 50, 2501 (1967)] and the resulting mixture is stirred for 18 hours. Saturated ammonium chloride (110 ml.) is added followed by 100 ml. of water and 100 ml. of diethyl ether. Unreacted magnesium is removed by filtration. The ethereal layer is washed successively with aqueous sodium thiosulfate solution, ammonium chloride solution, and water, dried over magnesium sulfate and taken to dryness to give an oil. Distillation at 0.05 mm. (bath 100.degree.-185.degree. C.) gives 45.4 g. of material containing unreacted starting material and 30 g. (85% yield based on non-recovered starting material; see below) of residue which contains the desired product. This material is chromatographed on silica gel. The product is eluted with diethyl ether to give 25.2 g. (71% based on recovered starting material) of a syrup; this material has no significant ultra-violet absorption; .lambda..sub.max.sup.KBr 5.74, 7.20, 7.35, 8.35 .mu.; nmr 2H quartet.delta. 4.09 (OCH.sub.2 of ester), 1H broad singlet 3.57 (carbinolic proton), 5H overlapping multiplets 2.0-2.4 (protons next to C.dbd.O), 3H triplet 1.22 (CH.sub.3 of ethyl), 9H singlet 1.17 (CH.sub.3 's to t-butyl) and 3H triplet 0.9 (terminal methyl); mass spectrum: m/e 424.

EXAMPLE 494

Preparation of 15-hydroxy-9-oxoprostanoic acid, ethyl ester

A solution of 25 g. of 15-(tert-butoxy)-9-oxoprostanoic acid, ethyl ester in 100 ml. of trifluoroacetic acid is stirred in an ice bath for 1 hour and is then poured into 500 ml. of ice water and extracted several times with chloroform. The combined chloroform extracts are washed with saturated sodium bicarbonate solution, saturated sodium chloride solution, dried with anhydrous magnesium temperature sulfate, and taken to dryness. The resulting oil is dissolved in 200 ml. of 1N ammonium hydroxide in ethanol, kept at ambient temperature for 15 minutes, then taken to dryness. The residual oil is dissolved in chloroform and washed with 1N hydrochloric acid, saturated sodium chloride solution, dried and taken to dryness to give 21.7 g. (100%) of product as a yellow syrup. There is essentially no uv absorption; .lambda..sub.max.sup.KBr 2.90, 5.75, 8.45 .mu.; nmr 2H quartet .delta.4.13 (OCH.sub.2 of ester), 1H broad singlet 3.63 (carbinolic proton), 3H triplet (CH.sub.3 of ster), and 3H distorted triplet 0.92 (terminal methyl); mass spectrum: m/e 368.

EXAMPLE 495

Preparation of 15-hydroxy-9-oxoprostanoic acid

A suspension of 15 g. of 15-hydroxy-9-oxoprostanoic acid, ethyl ester in 230 ml. of aqueous methanol (1:1) containing 6.45 g. of potassium hydroxide is stirred at 50.degree. C. for 1 hour and then at room temperature for 18 hours. The resulting solution is acidified with 1N hydrochloric acid, saturated with sodium chloride, and extracted several times with diethyl ether. The combined ether extracts are washed twice with saturated sodium chloride solution, dried with anhydrous magnesium sulfate, and taken to dryness to give 13.1 g. (94%) of product as an oil. There is essentially no uv absorption; [.alpha.].sub.D.sup.25 0.degree. (1.0% in CHCl.sub.3); .lambda..sub.max.sup.KBr 2.80-3.70 (broad), 5.75, 5.87 .mu.; nmr 2H singlet .delta. 6.65 (hydroxyl and carboxyl protons), 1H broad singlet 3.63 (carbinolic proton), and 3H distorted triplet 0.93 (terminal methyl); mass spectrum: m/e 340.

EXAMPLE 496

preparation of 1-chloro-3-hydroxy-4-octyne

To 68 ml. of 1.6M butyllithium in hexane at -50.degree. C. is added dropwise, with stirring, 7.4 g. of 1-pentyne. The resulting white sludge is diluted with 20 ml. of hexane, brought to 10.degree. C. and treated with 11 g. of freshly prepared .beta.-chloropropionaldehyde (Org. Syn., Coll. Vol. I, p. 166) at such a rate that the temperature is maintained at 10.degree.-15.degree. C. The solution is allowed to stir at ambient temperature for 18 hours then treated with saturated ammonium chloride solution. The organic phase is separated, washed with dilute hydrochloric solution, dried with anhydrous magnesium sulfate and taken to dryness. Distillation gives 5.1 g. of product b.p. 65.degree.-66.degree. C. at 0.3 nm.; .lambda.max. 2.95 (--OH) and 4.55 .mu. (--C.tbd.C--); vapor phase chromatography shows one peak.

EXAMPLE 497

Preparation of 1-chloro-3-hydroxy-4-cis-octene

A solution of 2 g. of 1-chloro-3-hydroxy-4-octyne (Example 496) is hydrogenated in 50 ml. absolute alcohol using 200 mg. of Lindlar catalyst (5% Pd on CaCO.sub.3). The catalyst is removed by filtration and the mother liquor is taken to dryness to give 2 g. of an oil; .lambda. max. 2.95 (--OH) and 7.25 .mu. ##STR37##

EXAMPLE 498

Preparation of 3-hydroxy-1-iodo-4-octyne

A mixture of 15 g. of sodium iodide in 100 ml. of 2-butanone is stirred at the reflux temperature for 30 minutes. To the cooled mixture is added 12 g. of 1-chloro-3-hydroxy-4-octyne in 150 ml. of 2-butanone. The resulting mixture is stirred at the reflux temperature for 18 hours and then cooled and filtered. The mother liquor is taken to dryness and the residue is triturated with benzene and filtered. The benzene is taken to dryness to give the subject product as an oil. The material is shown to be homogeneous by vapor phase chromatography and thin layer chromatography.

EXAMPLE 499

Preparation of 3-hydroxy-1-iodo-4-cis-octen

The subject compound is prepared from 3-hydroxy-1-chloro-4-cis-octene and sodium iodide by the method of Example 498.

EXAMPLE 500

Preparation of 3-t-butoxy-1-iodo-4-octyne

The subject compound is prepared from 3-hydroxy-1-iodo-4-octyne (Example 498) and isobutylene by the method of Example 492.

EXAMPLE 501

Preparation of 3-t-butoxy-1-iodo-4-cis-octene

The subject compound is prepared from 3-hydroxy-1-iodo-4-cis-octene (Example 499) and isobutylene by the method of Example 492.

EXAMPLE 502

Preparation of 3-(tert-butoxy)-1-iodohexane

A mixture of 23.4 g. of 1-chloro-3-hexanol [Fourneau, et. al., Bull. Soc. Chem. France, 25, 367 (1919)] in 300 ml. of 2-butanone containing 30 g. of sodium iodide is stirred at the reflux temperature for 18 hours. The cooled solution is filtered and the mother liquor is taken to dryness. Distillation of the residue affords 32.9 g. (84%) of 1-iodo-3-hexanol, b.p. 105.degree. C. (10 mm). Treatment of this material in 500 ml. of methylene chloride, contaning 4 ml. of concentrated sulfuric acid, with isobutylene according to the procedure described in Example 492 gives 27 g. of crude material. Chromatography on florisil affords 16 g. of product; .lambda.max. 7.22 and 7.37 .mu. (tert-butyl group).

EXAMPLES 503-558

Treatment of the cyclopentenones designated in the table below with the designated Grignard reagents by the procedure of Example 493 is productive of the alkyl 9-oxo-15-t-butoxy-8.xi. -prostanoates and prostenoates of the table. 3-t-Butoxyoctylmagnesium iodide was prepared from 3-t-butoxy-1-iodooctane (Example 492); 3-t-butoxyhexyl magnesium iodide was prepared from 3-t-butoxy-1-iodohexane (Example 502), 3-t-butoxy-4-octynyl magnesium iodide was prepared from 3-t-butoxy-1-iodo-4-octyne (Example 500); and 3-t-butoxy-4-cis-octenyl magnesium iodide was prepared from 3-t-butoxy-1-iodo-4-cis-octene (Example 501).

Table 6__________________________________________________________________________ Starting cyclopentenone Product Alkyl 9-Oxo-15-t-butoxy-8.xi.-prostan oates,Example of Example Grignard Reagent prostynoates and prostenoates__________________________________________________________________________503 31 3-t-butoxyoctyl ethyl 9-oxo-15-t-butoxy-2-ethyl-8.xi.-prostan oate magnesium iodide504 41 3-t-butoxyoctyl ethyl 9-oxo-15-t-butoxy-3,3-dimethyl-8.xi.- magnesium iodide prostanoate505 46 3-t-butoxyoctyl ethyl 9-oxo-15-t-butoxy-3-oxa-8.xi.-prostanoa te magnesium iodide506 70 3-t-butoxyoctyl ethyl 9-oxo-15-t-butoxy-2-fluoro-8.xi.-prosta noate magnesium iodide507 79 3-t-butoxyoctyl ethyl 9-oxo-15-t-butoxy-2-phenyl-8.xi.-prosta noate magnesium iodide508 99 3-t-butoxyoctyl ethyl 9-oxo-15-t-butoxy-2-methyl-8.xi.-prosta noate magnesium iodide509 118 3-t-butoxyoctyl ethyl 9-oxo-15-t-butoxy-3-thia-8.xi.-prostano ate magnesium iodide510 900 3-t-butoxyoctyl methyl 9-oxo-15-t-butoxy-8.xi.-5-cis-prosteno ate magnesium iodide511 31 3-t-butoxyhexyl ethyl 9-oxo-15-t-butoxy-2-ethyl-19,20-dinor-8 .xi.- magnesium iodide prostanoate512 41 3-t-butoxyhexyl ethyl 9-oxo-15-t-butoxy-3,3-dimethyl-19,20- magnesium iodide dinor-8.xi.-prostanoate513 46 3-t-butoxyhexyl ethyl 9-oxo-15-t-butoxy-3-oxa-19,20-dinor-8.x i.- magnesium iodide prostanoate514 70 3-t-butoxyhexyl ethyl 9-oxo-15-t-butoxy-2-fluoro-19,20-dinor- 8.xi.- magnesium iodide prostanoate515 79 3-t-butoxyhexyl ethyl 9-oxo-15-t-butoxy-2-phenyl-19,20-dinor- 8.xi.- magnesium iodide prostanoate516 99 3-t-butoxyhexyl ethyl 9-oxo-15-t-butoxy-2-methyl-19,20-dinor- 8.xi.- magnesium iodide prostanoate517 118 3-t-butoxyhexyl ethyl 9-oxo-15-t-butoxy-3-thia-19,20-dinor-8. xi.- magnesium iodide prostanoate518 900 3-t-butoxyhexyl methyl 9-oxo-15-t-butoxy-19,20-dinor-8.xi.-5- cis- magnesium iodide prostenoate519 13 3-t-butoxy-4-oct- ethyl 9-oxo-15-t-butoxy-8.xi.-16-prostynoate ynyl magnesium iodide520 15 3-t-butoxy-4-oct- ethyl 9-oxo-15-t-butoxy-6,7-dinor-8.xi.-16- ynyl magnesium prostynoate iodide521 23 3-t-butoxy-4-oct- ethyl 9-oxo-15-t-butoxy-7a,7b-bishomo-8.xi.-1 6- ynyl magnesium prostynoate iodide522 31 3-t-butoxy-4-oct- ethyl 9-oxo-15-t-butoxy-2-ethyl-8.xi.-16-pros tynoate ynyl magnesium iodide523 41 3-t-butoxy-4-oct- ethyl 9-oxo-15-t-butoxy-3,3-dimethyl-8.xi.-16 - ynyl magnesium prostynoate iodide524 46 3-t-butoxy-4-oct- ethyl 9-oxo-15-t-butoxy-3-oxa-8.xi.-16-prosty noate ynyl magnesium iodide525 53 3-t-butoxy-4-oct- ethyl 9-oxo-15-t-butoxy-7-nor-8.xi.-16-prosty noate ynyl magnesium iodide526 70 3-t-butoxy-4-oct- ethyl 9-oxo-15-t-butoxy-2-fluoro-8.xi.-16-pro sytynoate ynyl magnesium iodide527 74 3-t-butoxy-4-oct- ethyl 9-oxo-15-t-butoxy-7a-homo-8.xi.-16-pros tynoate ynyl magnesium iodide528 79 3-t-butoxy-4-oct- ethyl 9-oxo-15-t-butoxy-2-phenyl-8.xi.-16-pro stynoate ynyl magnesium iodide529 81 3-t-butoxy-4-oct- butyl 9-oxo-15-t-butoxy-8.xi.-16-prostynoate ynyl magnesium iodide530 82 3-t-butoxy-4-oct- isopropyl 9-oxo-15-t-butoxy-8.xi.-16-prostyno ate ynyl magnesium iodide531 83 3-t-butoxy-4-oct- methyl 9-oxo-15-t-butoxy-8.xi.-16-prostynoate N ynyl magnesium iodide532 84 3-t-butoxy-4-oct- decyl 9-oxo-15-t-butoxy-8.xi.-16-prostynoate O ynyl magnesium iodide533 99 3-t-butoxy-4-oct- ethyl 9-oxo-15-t-butoxy-2-methyl-8.xi.-16-pro stynoate ynyl magnesium iodide534 118 3-t-butoxy-4-oct- ethyl 9-oxo-15-t-butoxy-2-methyl-8.xi.-16-pro stynoate ynyl magnesium iodide535 111 3-t-butoxy-4-oct- ethyl 9-oxo-15-t-butoxy-10a-homo-8.xi.-16-pro stynoate ynyl magnesium iodide536 113 3-t-butoxy-4-oct- ethyl 9-oxo-15-t-butoxy-10a-homo-7-nor-8.xi.- 16- ynyl magnesium prostynoate iodide537 114 3-t-butoxy-4-oct- ethyl 9-oxo-15-t-butoxy-7a,10a-bishomo-8.xi.- 16- ynyl magnesium prostynoate iodide538 900 3-t-butoxy-4-oct- methyl 9-oxo-15-t-butoxy-8.xi.-16-yne-5-cis- ynyl magnesium prostenoate iodide539 13 3-t-butoxy-4-cis- ethyl 9-oxo-15-t-butoxy-8.xi.-16-cis-prosteno ate octenyl magnesium iodide540 15 3-t-butoxy-4-cis- ethyl 9-oxo-15-t-butoxy-6,7-dinor-8.xi.-16-ci s- octenyl magnesium prostenoate iodide541 23 3-t-butoxy-4-cis- ethyl 9-oxo-15-t-butoxy-7a,7b-bishomo-8.xi.-1 6- oxtenyl magnesium cis-prostenoate iodide542 31 3-t-butoxy-4-cis- ethyl 9-oxo-15-t-butoxy-2-ethyl-8.xi.-16-cis- octenyl magnesium prostenoate iodide543 41 3-t-butoxy-4-cis- ethyl 9-oxo-15-t-butoxy-3,3-dimethyl-8.xi.-16 -cis- octenyl magnesium prostenoate iodide544 46 3-t-butoxy-4-cis- ethyl 9-oxo-15-t-butoxy-3-oxa-8.xi.-16-cis- octenyl magnesium prostenoate iodide545 53 3-t-butoxy-4-cis- ethyl 9-oxo-15-t-butoxy-7-nor-8.xi.-16-cis- octenyl magnesium prostenoate iodide546 70 3-t-butoxy-4-cis- ethyl 9-oxo-15-t-butoxy-2-fluoro-8.xi.-16-cis - octenyl magnesium prostenoate iodide547 74 3-t-butoxy-4-cis- ethyl 9-oxo-15-t-butoxy-7a-homo-8.xi.-16-cis- octenyl magnesium prostenoate iodide548 79 3-t-butoxy-4-cis- ethyl 9-oxo-15-t-butoxy-2-phenyl-8.xi.-16-cis - oxtenyl magnesium prostenoate iodide549 81 3-t-butoxy-4-cis- butyl 9-oxo-15-t-butoxy-8.xi.-16-cis-prosteno ate octenyl magnesium iodide550 82 3-t-butoxy-4-cis- isopropyl 9-oxo-15-t-butoxy-8.xi.-16-cis- octenyl magnesium prostenoate iodide551 83 3-t-butoxy-4-cis- methyl 9-oxo-15-t-butoxy-8.xi.-16-cis- octenyl magnesium prostenoate iodide552 84 3-t-butoxy-4-cis- decyl 9-oxo-15-t-butoxy-8.xi.-16-cis-prosteno ate octenyl magnesium iodide553 99 3-t-butoxy-4-cis- ethyl 9-oxo-15-t-butoxy-2-methyl-8.xi.-16-cis - oxtenyl magnesium prostenoate iodide554 118 3-t-butoxy-4-cis- ethyl 9-oxo-15-t-butoxy-3-thia-8.xi.-16-cis- octenyl magnesium prostenoate iodide555 111 3-t-butoxy-4-cis- ethyl 9-oxo-15-t-butoxy-10a-homo-8.xi.-16-cis - oxtenyl magnesium prostenoate iodide556 113 3-t-butoxy-4-cis- ethyl 9-oxo-15-t-butoxy-10a-homo-7-nor-8.xi.- 16- octenyl magnesium cis-prostenoate iodide557 114 3-t-butoxy-4-cis- ethyl 9-oxo-15-t-butoxy-7a,10a-bishomo-8.xi.- 16- octenyl magnesium cis-prostenoate iodide558 900 3-t-butoxy-4-cis- methyl 9-oxo-15-t-butoxy-8.xi.-5-cis-16-cis- octenyl magnesium prostadienoate iodide__________________________________________________________________________

EXAMPLES 559-614

Treatment of the 9-oxo-15-t-butoxy derivatives designated in the table below with trifluoroacetic acid and then with aqueous ammonia by the method described in Example 494 is productive of the 9-oxo-15-hydroxy esters of the table.

TABLE 7______________________________________ Starting 15-t-Ex- butoxy derivative Product Alkyl 9-oxo-15-ample of Example hydroxy derivative______________________________________559 503 Ethyl 9-oxo-15-hydroxy- 2-ethyl-prostanoate560 504 Ethyl 9-oxo-15-hydroxy- 3,3-dimethyl-prostano- ate561 505 Ethyl 9-oxo-15-hydroxy- 3-oxa-prostanoate562 506 Ethyl 9-oxo-15-hydroxy- 2-fluoro-prostanoate563 507 Ethyl 9-oxo-15-hydroxy- 2-phenyl-prostanoate564 508 Ethyl 9-oxo-15-hydroxy- 2-methyl-prostanoate565 509 Ethyl 9-oxo-15-hydroxy- 3-thia-prostanoate566 510 Methyl 9-oxo-15-hydroxy- 5-cis-prostenoate567 511 Ethyl (9-oxo-15-hydroxy- 2-ethyl-19,20-dinor- prostanoate568 512 Ethyl 9-oxo-15-hydroxy- 3,3-dimethyl-19,20- dinor-prostanoate569 513 Ethyl 9-oxo-15-hydroxy- 3-oxa-19,20-dinor- prostanoate570 514 Ethyl 9-oxo-15-hydroxy- 2-fluoro-19,20-dinor- prostanoate571 515 Ethyl 9-oxo-15-hydroxy- 2-phenyl-19,20-dinor- prostanoate572 516 Ethyl 9-oxo-15-hydroxy- 2-methyl-19,20-dinor- prostanoate573 517 Ethyl 9-oxo-15-hydroxy- 3-thia-19,20-dinor- prostanoate574 518 Methyl 9-oxo-15-hydroxy- 19,20-dinor-5-cis- prostenoate575 519 Ethyl 9-oxo-15-hydroxy- 16-prostynoate576 520 Ethyl 9-oxo-15-hydroxy- 6,7-dinor-16-prostyno- ate577 521 Ethyl 9-oxo-15-hydroxy- 7a,7b-bishomo-16-prost- ynoate578 522 Ethyl 9-oxo-15-hydroxy- 2-ethyl-16-prostynoate579 523 Ethyl 9-oxo-15-hydroxy- 3,3-dimethyl-16-prost- ynoate580 524 Ethyl 9-oxo-15-hydroxy- 3-oxa-16-prostynoate581 525 Ethyl 9-oxo-15-hydroxy- 7-nor-16-prostynoate582 526 Ethyl 9-oxo-15-hydroxy- 2-fluoro-16-prostynoate583 527 Ethyl 9-oxo-15-hydroxy- 7a-homo-16-prostynoate584 528 Ethyl 9-oxo-15-hydroxy- 2-phenyl-16-prostynoate585 529 Butyl 9-oxo-15-hydroxy- 16-prostynoate586 530 Isopropyl 9-oxo-15-hy- droxy-16-prostynoate587 531 Methyl 9-oxo-15-hydroxy- 16-prostynoate588 532 Decyl 9-oxo-15-hydroxy- 16-prostynoate589 533 Ethyl 9-oxo-15-hydroxy- 2-methyl-16-prostynoate590 534 Ethyl 9-oxo-15-hydroxy- 3-thia-16-prostynoate591 535 Ethyl 9-oxo-15-hydroxy- 10a-homo-16-prostynoate592 536 Ethyl 9-oxo-15-hydroxy- 10a-homo-7-nor-16- prostynoate593 537 Ethyl 9-oxo-15-hydroxy- 7a,10a-bishomo-16- prostynoate594 538 Methyl 9-oxo-15-hydroxy- 16-yne-5-cis-prostenoate595 539 Ethyl 9-oxo-15-hydroxy- 16-cis-prostenoate596 540 Ethyl 9-oxo-15-hydroxy- 6,7-dinor-16-cis-pros- tenoate597 541 Ethyl 9-oxo-15-hydroxy- 7a,7b-bishomo-16-cis- prostenoate598 542 Ethyl 9-oxo-15-hydroxy- 2-ethyl-16-cis-prosteno- ate599 543 Ethyl 9-oxo-15-hydroxy- 3,3-dimethyl-16-cis- prostenoate600 544 Ethyl 9-oxo-15-hydroxy- 3-oxa-16-cis-prostenoate601 545 Ethyl 9-oxo-15-hydroxy- 7-nor-16-cis-prostenoate602 546 Ethyl 9-oxo-15-hydroxy- 2-fluoro-16-cis-prosten- oate603 547 Ethyl 9-oxo-15-hydroxy- 7a-homo-16-cis-prosten- oate604 548 Ethyl 9-oxo-15-hydroxy- 2-phenyl-16-cis-prosten- oate605 549 Butyl 9-oxo-15-hydroxy- 16-cis-prostenoate606 550 Isopropyl 9-oxo-15-hy- droxy-16-cis-prostenoate607 551 Methyl 9-oxo-15-hydroxy- 16-cis-prostenoate608 552 Decyl 9-oxo-15-hydroxy- 16-cis-prostenoate609 553 Ethyl 9-oxo-15-hydroxy- 2-methyl-16-cis-pros- tenoate610 554 Ethyl 9-oxo-15-hydroxy- 3-thia-16-cis-prosteno- ate611 555 Ethyl 9-oxo-15-hydroxy- 10a-homo-16-cis-pros- tenoate612 556 Ethyl 9-oxo-15-hydroxy- 10a-homo-7-nor-16-cis- prostenoate613 557 Ethyl 9-oxo-15-hydroxy- 7a,10a-bishomo-16-cis- prostenoate614 558 Methyl 9-oxo-15-hydroxy- 5-cis-16-cis-prostadi- enoate______________________________________

EXAMPLES 615-662

Saponification of the 9-oxo-15-hydroxy alkyl esters designated in the table below by the procedure desccribed in Example 495 is productive of the carboxylic acids of the table.

TABLE 8______________________________________ Starting alkylEx- ester of Product 9-oxo-15-hydroxy-ample Example prostanoic acid______________________________________615 559 9-oxo-15-hydroxy-2-ethyl- prostanoic acid616 560 9-oxo-15-hydroxy-3,3-di- methyl-prostanoic acid617 561 9-oxo-15-hydroxy-3-oxa- prostanoic acid618 562 9-oxo-15-hydroxy-2-fluoro- prostanoic acid619 563 9-oxo-15-hydroxy-2-phenyl- prostanoic acid620 564 9-oxo-15-hydroxy-2-methyl- prostanoic acid621 565 9-oxo-15-hydroxy-3-thia- prostanoic acid622 566 9-oxo-15-hydroxy-5-cis- prostenoic acid623 567 9-oxo-15-hydroxy-2-ethyl- 19,20-dinor-prostanoic acid624 568 9-oxo-15-3,3-dimethyl-19, 20-dinor-prostanoic acid625 569 9-oxo-15-hydroxy-3-oxa- 19,20-dinor-prostanoic acid626 570 9-oxo-15-hydroxy-2-fluoro- 19,20-dinor-prostanoic acid627 571 9-oxo-15-hydroxy-2-phenyl- 19,20-dinor-prostanoic acid628 572 9-oxo-15-hydroxy-2-methyl- 19,20-dinor-prostanoic acid629 573 9-oxo-15-hydroxy-3-thia- 19,20-dinor-prostanoic acid630 574 9-oxo-15-hydroxy-19,20- dinor-5-cis-prostenoic acid631 575 9-oxo-15-hydroxy-16-pros- tynoic acid632 576 9-oxo-15-hydroxy-6,7-dinor- 16-prostynoic acid633 577 9-oxo-15-hydroxy-7a,7b-bis- homo-16-prostynoic acid634 578 9-oxo-15-hydroxy-2-ethyl- 16-prostynoic acid635 579 9-oxo-15-hydroxy-3,3-di- - methyl-16-prostynoic acid636 580 9-oxo-15-hydroxy-3-oxa-16- prostynoic acid637 581 9-oxo-15-hydroxy-7-nor-16- prostynoic acid638 582 9-oxo-15-hydroxy-2-fluoro- 16-prostynoic acid639 583 9-oxo-15-hydroxy-7a-homo- 16-prostynoic acid640 584 9-oxo-15-hydroxy-2-phenyl- 16-prostynoic acid641 589 9-oxo-15-hydroxy-2-methyl- 16-prostynoic acid642 590 9-oxo-15-hydroxy-3-thia- 16-prostynoic acid643 591 9-oxo-15-hydroxy-10a-homo- 16-prostynoic acid644 592 9-oxo-15-hydroxy-10a-homo- 7-nor-16-prostynoic acid645 593 9-oxo-15-hydroxy-7a,10a- bishomo-16-prostynoic acid646 594 9-oxo-15-hydroxy-16-yne-5- cis-prostenoic acid647 595 9-oxo-15-hydxroxy-16-cis- prostenoic acid648 596 9-oxo-15-hydroxy-6,7-dinor- 16-cis-prostenoic acid649 597 9-oxo-15-hydroxy-7a,7b-bis- homo-16-cis-prostenoic acid650 598 9-oxo-15-hydroxy-2-ethyl- 16-cis-prostenoic acid651 599 9-oxo-15-hydroxy-3,3-di- methyl-16-cis-prostenoic acid652 600 9-oxo-15-hydroxy-3-oxa-16- cis-prostenoic acid653 601 9-oxo-15-hydroxy-7-nor-16- cis-prostenoic acid654 602 9-oxo-15-hydroxy-2-fluoro- 16-cis-prostenoic acid655 603 9-oxo-15-hydroxy-7a-homo- 16-cis-prostenoic acid656 604 9-oxo-15-hydroxy-2-phenyl- 16-cis-prostenoic acid657 609 9-oxo-15-hydroxy-2-methyl- 16-cis-prostenoic acid658 610 9-oxo-15-hydroxy-3-thia- 16-cis-prostenoic acid659 611 9-oxo-15-hydroxy-10a-homo- 16-cis-prostenoic acid660 612 9-oxo-15-hydroxy-10a-homo- 7-nor-16-cis-prostenoic acid661 613 9-oxo-15-hydroxy-7a,10a- bishomo-16-cis-prosten- oic acid662 614 9-oxo-15-hydroxy-5-cis- 16-cis-prostadienoic acid______________________________________

EXAMPLE 663

Ethyl 9-oxo-15-hydroxy-16-trans-prostenoate

To a mixture of 1 g. of ethyl 9-oxo-15-hydroxy-16-prostynoate (Example 575), 11 ml. of water and 27 ml. of dimethylformamide is added 27 ml. of 0.45 N chromous sulfate solution. The mixture is stirred for 48 hours under nitrogen atmosphere. The mixture then is extracted with ether several times and the combined extracts are taken to dryness. Silica gel chromatography gives the subject product as an oil.

EXAMPLES 664-682

Treatment of the 9-oxo-15-hydroxy-16-prostynoates listed in Table 8A below with chromous sulfate in the manner of Example 663 is productive of the product 9-oxo-15-hydroxy-16-trans-prostenoates of the table.

TABLE 8A______________________________________ Starting ProductEx- 16-prostenoate 9-ox-15-hydroxy-16-ample of Example trans-prostenoate______________________________________664 576 Ethyl 9-oxo-15-hydroxy- 6,7-dinor-16-trans- prostenoate665 577 Ethyl 9-oxo-15-hydroxy- 7a,7b-bishomo-16-trans- prostenoate666 578 Ethyl 9-oxo-15-hydroxy- 2-ethyl-16-trans-pros- tenoate667 579 Ethyl 9-oxo-15-hydroxy- 3,3-dimethyl-16-trans- prostenoate668 580 Ethyl 9-oxo-15-hydroxy- 3-oxa-16-trans-prosten- oate669 581 Ethyl 9-oxo-15-hydroxy- 7-nor-16-trans-pros- tenoate670 582 Ethyl 9-oxo-15-hydroxy- 2-fluoro-16-trans-pros- tenoate671 583 Ethyl 9-oxo-15-hydroxy- 7a-homo-16-trans-pros- tenoate672 584 Ethyl 9-oxo-15-hydroxy- 2-phenyl-16-trans-pros- tenoate673 585 Butyl 9-oxo-15-hydroxy- 16-trans-prostenoate674 586 Isopropyl 9-oxo-15- hydroxy-16-trans-pros- tenoate675 587 Methyl 9-oxo-15-hydroxy- 16-trans-prostenoate676 588 Decyl 9-oxo-15-hydroxy- 16-trans-prostenoate677 589 Ethyl 9-oxo-15-hydroxy- 2-methyl-16-trans-pros- tenoate678 590 Ethyl 9-oxo-15-hydroxy- 3-thia-16-trans-pros- tenoate679 591 Ethyl 9-oxo-15-hydroxy- 10a-homo-16-trans-pros- tenoate680 592 Ethyl 9-oxo-15-hydroxy- 10a-homo-7-nor-16-trans- prostenoate681 593 Ethyl 9-oxo-15-hydroxy- 7a,10a-bishomo-16-trans- prostenoate682 594 Methyl 9-oxo-15-hydroxy- 5-cis,16-trans-prosta- dienoate______________________________________

EXAMPLES 683-698

Saponification of the alkyl 9-oxo-15-hydroxy-16-trans-prostenoates listed in Table 8B below by the procedure described in Example 495 is productive of the corresponding prostenoic acids of the table.

TABLE 8B______________________________________ Starting Product 9-oxo-15-Ex- alkyl ester hydroxy-16-transample of Example prostenoic acids______________________________________683 663 9-oxo-15-hydroxy-16- trans-prostenoic acid684 664 9-oxo-15-hydroxy-6,7- dinor-16-trans-prosten- oic acid685 665 9-oxo-15-hydroxy-7a,7b- bishomo-16-trans-pros- tenoic acid686 666 9-oxo-15-hydroxy-2- ethyl-16-trans-prosten- oic acid687 667 9-oxo-15-hydroxy-3,3- dimethyl-16-trans-pros- tenoic acid688 668 9-oxo-15-hydroxy-3-oxa- 16-trans-prostenoic acid689 669 9-oxo-15-hydroxy-7-nor- 16-trans-prostenoic acid690 670 9-oxo-15-hydroxy-2- fuoro-16-trans-pros- tenoic acid691 671 9-oxo-15-hydroxy-7a- homo-16-trans-prostenoic acid692 672 9-oxo-15-hydroxy-2- phenyl-16-trans-pros- tenoic acid693 677 9-oxo-15-hydroxy-2-meth- yl-16-trans-prostenoic acid694 678 9-oxo-15-hydroxy-3-thia- 16-trans-prostenoic acid695 679 9-oxo-15-hydroxy-10a- homo-16-trans-prostenoic acid696 680 9-oxo-15-hydroxy-10a- homo-7-nor-16-trans- prostenoic acid697 681 9-oxo-15-hydroxy-7a,10a- bishomo-16-trans-pro- stenoic acid698 682 9-oxo-15-hydroxy-5-cis, 16-trans-prostadienoic acid______________________________________

EXAMPLE 699

Preparation of 9-oxo-15-hydroxy-3,3-dimethylprostanoic acid

A 2 g. sample of 9-oxo-15-hydroxy-3,3-dimethyl-13-trans-prostenoic acid is hydrogenated using 700 mg. of 10% palladium on carbon in 50 ml. of absolute alcohol. The catalyst is removed by filtration and the mother liquor is taken to dryness to give 2 g. of subject compound as an oil.

EXAMPLE 723

Preparation of 1-chloro-trans-1-octen-3-one

To a slurry of 233.5 g. (1.75 moles) of aluminum chloride in 390 ml. of carbon tetrachloride, saturated with acetylene and cooled in an ice bath. is added over 20 minutes 201.9 g. (1.50 moles) of hexanoyl chloride. After the addition is complete, acetylene is bubbled into the mixture as rapidly as it is absorbed and for 1 hour after absorption becomes slow. The mixture is poured onto 1700 g. of ice and 720 ml. of saturated brine. The organic phase is separated and the aqueous phase is washed with ether. The combined organic phase and washings are washed with saturated brine, dried (Na.sub.2 SO.sub.4). and evaporated. The residual oil is combined with 10 g. of hydroquinone and distilled to yield a colorless oil, b.p. 51.degree.-52.degree. C. (0.10 torr).

EXAMPLE 724

Preparation of 1-iodo-trans-1-octen-3-one

A mixture of 54.5 g. (0.364 mole) of sodium iodide and 40 . (0.249 mole) of 1-chloro-trans-1-octen 3-one (Example 723) in 360 ml. of acetone is stirred and refluxed for 24 hours. The reaction mixture is cooled, filtered and concentrated. The residue is partitioned between water and ether. The organic phase is washed with dilute sodium bicarbonate solution, brine, dried (MgSO.sub.4) and evaporated to an oil. This material is used directly without purification.

EXAMPLE 725

Preparation of 1-bromo-trans-1-octen-3 one

A mixture of 68.0 g. (0.424 mole) of 1-chloro-trans-1-octen-3 one (Example 723) and 444 g. (4.24 moles) of anhydrous lithium bromide in 900 ml. of 2-pentanone is refluxed for 30 minutes, cooled, and partitioned between ice water and ether. The organic phase is washed with water and saturated brine, dried (NaSO.sub.4), and evaporated to an oil. This material is used directly without purification.

EXAMPLE 726

Preparation of 1-bromo-trans-1-octen-3-ol

To an ice cooled mixture of 14.29 g. (0.378 mole) of sodium borohydride in 400 ml. of anhydrous ethanol is added the crude 1-bromo-trans-1-octen-3-one (Example 725), from 0.424 mole of 1-chloro-trans-1-octen-3-one) over 30 minutes. The mixture is stirred for 2 hours with ice cooling and is then partitioned between ice water and benzene. The organic phase is washed with water and saturated brine, dried (Na.sub.2 SO.sub.4), and evaporated to an oil. Fractional distillation yields the title compound as a colorless oil, b.p. 66.degree.-68.degree. C. (0.025 torr).

EXAMPLE 727

Preparation of 1-chloro-trans-1-octen-3-ol

Treatment of 1-chloro-trans-1-octen-3-one (Example 723) with sodium borohydride in the manner of Example 726 is productive of the subject compound.

EXAMPLE 728

Preparation of 1-bromo-3-triphenylmethoxy-trans-1-octene

A mixture of 6.212 g. (0.030 mole) of 1-bromo-trans-1-octen-3-ol (Example 726) and 10.67 g. (0.033 mole) of triphenylmethyl bromide in 40 ml. of pyridine is heated to 100.degree. C. for 1.5 hours under an inert atmosphere. The mixture is cooled and filtered. The filtrate is partitioned between ice water and ether. The organic phase is washed with cold dilute hydrochloric acid, saturated sodium bicarbonate solution, and saturated brine, dried (NaSO.sub.4), and evaporated to an oil. The latter is dissolved in hexane and passed through 250 g. of florisil.RTM. to yield after evaporation a colorless oil. Found for C.sub.27 H.sub.29 OBr: C, 72.13; H, 6.61; Br, 17.57.

EXAMPLE 729

Preparation of 1-iodo-trans-1-octen-3-ol

Treatment of 63 g. (0.25 mole) of 1-iodo-trans-1-octen-3-one (Example 724) with sodium borohydride in the manner described in Example 726 gave 58 g. of yellow oil. The oil is purified by adsorption chromatography on a magnesia silica gel column using benzene as eluent to give a light yellow oil.

EXAMPLE 730

Preparation of 1-iodo-3-triphenylmethoxy-trans-1-octene

Treatment of 7.62 g. (0.03 mole) of 1-iodo-trans-1-octen-3-ol with 10.67 g. (0.033 mole) of triphenylmethyl bromide in pyridine in the manner described in Example 728 gave 13.448 g. (90%) of a colorless oil.

EXAMPLE 731

Preparation of 1-chloro-3-triphenylmethoxy-trans-1-octene

Treatment of 1-chloro-trans-1-octen-3-ol (Example 727) with triphenylmethyl chloride by the method described in Example 728 except that the heating period is extended to six hours provides the subject compound.

EXAMPLE 732

Preparation of 11-deoxy-prostaglandin-E.sub.1 methyl ester and methyl 15-hydroxy-9-oxo-13-cis-prostenoate

To a slurry of 0.535 g. (0.022 g. atom) of magnesium in 6 ml. of tetrahydrofuran is added under an inert atmosphere 2 ml. of a solution of 6.548 g. (0.01455 mole) of 1-bromo-3-trityloxy-trans-1-octene (Example 728) in 8 ml. of tetrahydrofuran. Reaction is initiated by warming the mixture to 45.degree. C. and adding 1 drop of methyl iodide. The remainder of the halide is added at a rate to maintain a temperature of 43.degree.-46.degree. C. and the mixture is heated at 45.degree. C. for 1 hour after complete addition of the halide. The Grignard reagent is cooled and added to an ice cooled solution of 2.615 g. (0.0117 mole) of 2-(6-carbomethoxyhexyl) 2-cyclopentenone (Example 83) and 0.229 g. of Copper (I) iodide-tri-in-butylphosphine in 6 ml. of ether over 6 minutes. The mixture is stirred with ice cooling for 30 minutes and poured into 200 ml. of saturated ammonium chloride. The mixture is extracted into ether and the organic phase is washed with water and saturated brine, dried (NaSO.sub.4) and evaporated. The residual oil is heated to 80.degree. C. for 30 minutes with 80% aqueous acetic acid under an inert atmosphere. This mixture is cooled, evaporated to dryness, and the residue is separated by dry column chromatography on silica gel using benzene-ethyl acetate 4:1 as eluent. The title compounds are isolated as oils with .DELTA.13 trans/.DELTA.13 cis in ratio of 10:1. Complete resolution is effected with partition chromatography [for a description see M. J. Weiss et al., Tetrahedron, 20, 357 (1964)] on acid-washed Celite -545 using heptane: acetonitrile (Hold Back Volume=1000 ml.); 11-deoxy-prostaglandin-E.sub.1 methyl ester is obtained in Hold Back Volume 3-5 and methyl 15-hydroxy-9-oxo-13-cis-prostenoate is obtained in Hold Back Volume 6-8.

EXAMPLE 733

Preparation of 11-deoxy-prostaglandin-E.sub.1 methyl ester and methyl 15-hydroxy-9-oxo-13-cis-prostenoate

To a slurry of 0.243 g. (0.010 g. atom) of magnesium in 4 ml. of tetrahydrofuran is added under an inert atmosphere 2 ml. of a solution of 4.494 g. (0.010 mole) of 1-bromo-3-trityloxy-trans-1-octene in 4 ml. of tetrahydrofuran. Reaction is initiated by warming the mixture to 65.degree. C. and adding 1 drop of methyl iodide. The remainder of the halide is added at a rate to maintain a temperature of 65.degree.-70.degree. C. and the mixture is heated at 75.degree.-80.degree. C. for 30 minutes after complete addition of the halide. The Grignard reagent is cooled and added to 2.243 g. (0.010 mole) of 2-(6-carbomethoxyhexyl)-2-cyclopentenone and 0.200 g. of copper (I) iodide-tri-n-butylphosphine in 6 ml. of ether and worked up with saturated ammonium chloride solution and aqueous acetic acid in the manner of Example 121. The products are isolated as described in Example 732 to yield 11-deoxy-prostaglandin E.sub.1 methyl ester and methyl 15-hydroxy-9-oxo-13-cis-prostenoate in a ratio of 2:1.

EXAMPLE 734

Preparation of 15-hydroxy-9-oxo-13-cis-prostenoic acid

Methyl 15-hydroxy-9-oxo-13-cis-prostenoic acid is treated with potassium hydroxide in aqueous methanol and worked up as described in Example 495 to yield the title compound, m.p. 71.degree.-75.degree. C.

EXAMPLE 735

Preparation of Prostaglandin-E.sub.1 and 9-oxo-11.alpha.,15-dihydroxy-13-cis-prostenoic acid

A Grignard reagent is prepared as described in Example 732 from 0.535 g. (0.022 g. atom) of magnesium, 6.742 g. (0.015 mole) of 1-bromo-3-triphenylmethoxy-trans-1-octene (Example 728), and 11 ml. of tetrahydrofuran at a temperature of 40.degree.-42.degree. C. The Grignard reagent is added to 3.95 g. of 2-(6-carbotetrahydropyranyloxyhexyl)-4-tetrahydropyranyloxy-2-cyclopentenone (Example 95) and 0.589 g. of copper (I) iodide tri-n-butylphosphine in 10 ml. of tetrahydrofuran and is worked up with ammonium chloride as described in Example 732. The protecting groups are removed by treating the worked up material, as described in Example 121, with 320 mol of acetic acid-water-tetrahydrofuran 2:1:1 at 45.degree. C. and the products are isolated by chromatography on silica gel with a benzene-ethyl acetate gradient and resolved via partition chromatography on acid-washed Celite 545.

EXAMPLE 736

Preparation of Prostaglandin-E.sub.1, and 9-oxo-11.alpha.,15-dihydroxy-13-cis-prostenoic acid

Treatment of 2-(6-carbotetrahydropyranylhexyl)-4-tetrahydropyranyloxy-2-cyclopentenone (Example 95) with the Grignard reagent prepared from 1-bromo-3-triphenylmethoxy-trans-1-octene (Example 728) in the presence of Copper (I) iodide tri-n-butylphosphine complex by the procedure described in Example 733 is productive of the subject compounds.

EXAMPLE 737

Preparation of 9.alpha.,15-dihydroxy-13-trans-prostenoic acid

To a solution of 433 mg. of 9-oxo-15-hydroxy-13-trans-prostenoic acid in 4.5 ml. of tetrahydrofuran, stirred in an ice bath under nitrogen atmosphere, is added dropwise 3.7 ml. of 0.76M lithium perhydro-9 -boraphenalylhydride. After 40 minutes at 0.degree. C. there is added 1.62 ml. of 3N sodium hydroxide followed by 1.62 ml. of 30% hydrogen peroxide. Ether is added and the resulting solution is b-boraphenalylhydride. with 2N hydrochloric acid. The ether layer is washed several times with saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness to give the subject product as an oil.

EXAMPLES 738-893

Treatment of the 9-oxo derivatives designated in the table below with lithium perhydro-9 b-boraphenalyl hydride by the procedure described in Example 737 provides the 9.alpha.,15-dihydroxy derivatives of the table.

TABLE 9______________________________________ Starting 9-oxo-Ex- derivative of Product 9.alpha.,15-Dihydroxyample Example Derivative______________________________________738 375 9.alpha.,15-dihydroxy-5,6,7- trinor-13-trans-prosten- oic acid739 376 9.alpha.,15-dihydroxy-7a,7b- bishomo-13-trans-pros- tenoic acid740 377 9.alpha.,15-dihydroxy-2-ethyl- 13-trans-prostenoic acid741 378 9.alpha.,15-dihydroxy-3,3-di- methyl-13-trans-prosten- oic acid742 379 9.alpha.,15-dihydroxy-3-oxa- 13-trans-prostenoic acid743 380 9.alpha.,15-dihydroxy-7-nor- 13-trans-prostenoic acid744 381 9.alpha.,15-dihydroxy-2-fluoro- 13-trans-prostenoic acid745 382 9.alpha.,15-dihydroxy-7a-homo- 13-trans-prostenoic acid746 383 9.alpha.,15-dihydroxy-2-phenyl 13-trans-prostenoic acid747 384 9.alpha.,15-dihydroxy-2-methyl- 13-trans-prostenoic acid748 385 9.alpha.,15-dihydroxy-10a-homo- 13-trans-prostenoic acid749 386 9.alpha.,15-dihydroxy-10a-homo- 5,6,7-trinor-13-trans- prostenoic acid750 387 9.alpha.,15-dihydroxy-10a-homo- 7-nor-13-trans-prosten- oic acid751 388 9.alpha.,15-dihydroxy-7a,10a- bishomo-13-trans-pros- tenoic acid752 389 9.alpha.,15-dihydroxy-3-thia- 13-trans-prostenoic acid753 390 9.alpha.,15-dihydroxy-13-trans- prostenoic acid754 391 9.alpha.,15-dihydroxy-13-trans- prostenoic acid755 392 9.alpha.,15-dihydroxy-13-trans- prostenoic acid756 393 9.alpha.,15-dihydroxy-13-trans- prostenoic acid757 394 9.alpha.,15-dihydroxy-5-cis,13- trans-prostadienoic acid758 395 9.alpha.,15-dihydroxy-20-nor- 13-trans-prostenoic acid759 396 9.alpha.,15-dihydroxy-20-meth- yl-13-trans-prostenoic acid760 397 9.alpha.,15-dihydroxy-16-ethyl- 13-trans-prostenoic acid761 398 9.alpha.,15-dihydroxy-16-meth- yl-20-nor-13-trans-pros- tenoic acid762 399 9.alpha.,15-dihydroxy-19-meth- yl-13-trans, 18-prosta- dienoic acid763 400 9.alpha.,15-dihydroxy-18,19-di- methyl-13-trans, 18-pros- tadienoic acid764 401 9.alpha.,15-dihydroxy-13-trans, 17-cis-prostadienoic acid765 402 9.alpha.,15-dihydroxy-5,6,7- trinor-13-trans, 17-cis- prostadienoic acid766 403 9.alpha.,15-dihydroxy-6,7-di- nor-13-trans, 17-cis- prostadienoic acid767 404 9.alpha.,15-dihydroxy-7a,7b- bishomo-13-trans, 17- cis-prostadienoic acid768 405 9.alpha.,15-dihydroxy-2-ethyl- 13-trans, 17-cis-pros- tadienoic acid769 406 9.alpha.,15-dihydroxy-3,3-di- methyl-13-trans, 17-cis- prostadienoic acid770 407 9.alpha.,15-dihydroxy-3-oxa- 13-trans, 17-cis-pros- tadienoic acid771 408 9.alpha.,15-dihydroxy-7-nor- 13-trans, 17-cis-pros- tadienoic acid772 409 9.alpha.,15-dihydroxy-2-fluoro- 13-trans, 17-cis-pros- tadienoic acid773 410 9.alpha.,15-dihydroxy-7a-homo- 13-trans, 17-cis-pros- tadienoic acid774 411 9.alpha.,15-dihydroxy-2-phen- yl-13-trans, 17-cis- prostadienoic acid775 412 9.alpha.,15-dihydroxy-2-meth- yl-13-trans, 17-cis- prostadienoic acid776 413 9.alpha.,15-dihydroxy-10a-ho- mo-13-trans, 17-cis- prostadienoic acid777 414 9.alpha.,15-dihydroxy-10a-ho- mo-5,6,7-trinor-13- trans, 17-cis-prostadi- enoic acid778 415 9.alpha.,15-dihydroxy-10a-ho- mo-7-nor-13-trans, 17- cis-prostadienoic acid779 416 9.alpha.,15-dihydroxy-7a,10a- bishomo-13-trans, 17- cis-prostadienoic acid780 417 9.alpha.,15-dihydroxy-3-thia- 13-trans, 17-cis-pros- tadienoic acid781 418 9.alpha.,15-dihydroxy-13- trans, 17-cis-prostadi- enoic acid782 419 9.alpha.,15-dihydroxy-13- trans, 17-cis-prostadi- enoic acid783 420 9.alpha.,15-dihydroxy-13- trans, 17-cis-prostadi- enoic acid784 421 9.alpha.,15-dihydroxy-13-trans, 17-cis-prostadienoic acid785 422 9.alpha.,15-dihydroxy-5,6,7- trinor-19-isobutyl-13- trans, 18-prostadien- oic acid786 423 9.alpha.,15-dihydroxy-5,6,7- 19,20-pentanor-13-trans, 17-prostadienoic acid787 424 9.alpha.,15-dihydroxy-19,20-di- nor-13-trans, 18-prosta- dienoic acid788 425 9.alpha.,15-dihydroxy-17,20-di- methyl-20-isopropenyl-13- trans-prostenoic acid789 426 9.alpha.,15-dihydroxy-16-ethyl- 6,7,19,20-tetranor-13- trans-prostenoic acid790 427 9.alpha.,15-dihydroxy-18,19- dimethyl-6,7-dinor-13- trans, 18-prostadienoic acid791 428 9.alpha.,15-dihydroxy-16-ethyl- 7a,7b-bishomo-13-trans- prostenoic acid792 429 9.alpha.,15-dihydroxy-19-meth- yl-7a,7b-bishomo-13- trans, 18-prostadienoic acid793 430 9.alpha.,15-dihydroxy-2-ethyl- 19,20-dinor-13-trans- prostenoic acid794 431 9.alpha.,15-dihydroxy-2,20-di- ethyl-13-trans-prosten- oic acid795 432 9.alpha.,15-dihydroxy-2-ethyl- 16-methyl-20-nor-13- trans-prostenoic acid796 433 9.alpha.,15-dihydroxy-2-ethyl- 18,19-dimethyl-13- trans, 18-prostadienoic acid797 434 9.alpha.,15-dihydroxy-3,3-di- methyl-18,19,20-trinor- 13-trans-prostenoic acid798 435 9.alpha.,15-dihydroxy-3,3,20- trimethyl-13-trans- prostenoic acid799 436 9.alpha.,15-dihydroxy-3,3,16- trimethyl-20-nor-13- trans-prostenoic acid800 437 9.alpha.,15-dihydroxy-3,3-di- methyl-19-isobutyl-13- trans, 18-prostadienoic acid801 438 9.alpha.,15-dihydroxy-3,3-di- methyl-19,20-dinor-13- trans, 17-prostadienoic acid802 439 9.alpha.,15-dihydroxy-3-oxa-20- nor-13-trans-prostenoic acid803 440 9.alpha.,15-dihydroxy-3-oxa-20- methyl-13-trans-prosten- oic acid804 441 9.alpha.,15-dihydroxy-3-oxa-16- ethyl-13-trans-prosten- oic acid805 442 9.alpha.,15-dihydroxy-3-oxa-16- methyl-20-nor-13-trans- prostenoic acid806 443 9.alpha.,15-dihydroxy-3-oxa- 19,20-dinor-13-trans, 17- prostadienoic acid807 444 9.alpha.,15-dihydroxy-7,19,20- trinor-13-trans, 17- prostadienoic acid808 445 9.alpha.,15-dihydroxy-7-nor- 18,19-dimethyl-13-trans, 18,prostadienoic acid809 446 9.alpha.,15-dihydroxy-7,18,19- 20-tetranor-16-methyl-13- trans-prostenoic acid810 447 9.alpha.,15-dihydroxy-2-fluoro- 20-nor-13-trans-prosten- oic acid811 448 9.alpha.,15-dihydroxy-2-fluoro- 20-ethyl-13-trans-pros- tenoic acid812 449 9.alpha.,15-dihydroxy-2-fluoro- 16-ethyl-19,20-dinor-13- trans-prostenoic acid813 450 9.alpha.,15-dihydroxy-2-fluoro- 16-methyl-20-nor-13- trans-prostenoic acid814 451 9.alpha.,15-dihydroxy-2-fluoro- 19-methyl-13-trans, 18- prostadienoic acid815 452 9.alpha.,15-dihydroxy-7a-homo- 18,19-dimethyl-13-trans, 18-prostadienoic acid816 453 9.alpha.,15-dihydroxy-7a-homo- 19,20-dinor-13-trans, 17-prostadienoic acid817 454 9.alpha.,15-dihydroxy-2-phenyl- 20-nor-13-trans-prosten- oic acid818 455 9.alpha.,15-dihydroxy-2-phenyl- 20-ethyl-13-trans-pros- tenoic acid819 456 9.alpha.,15-dihydroxy-2-phenyl- 16-ethyl-13-trans-pros- tenoic acid820 484 9.alpha.,15-dihydroxy-20-nor-5- cis, 13-trans-prostadi- enoic acid821 485 9.alpha.,15-dihydroxy-20-meth- yl-5-cis, 13-trans-pros- tadienoic acid822 486 9.alpha.,15-dihydroxy-16-ethyl- 5-cis, 13-trans-prosta- dienoic acid823 487 9.alpha.,15-dihydroxy-16-meth- yl-20-nor-5-cis, 13- trans-prostadienoic acid824 488 9.alpha.,15-dihydroxy-19-meth- yl-5-cis, 13-trans, 18- prostatrienoic acid825 489 9.alpha.,15-dihydroxy-18,19- dimethyl-5-cis, 13- trans, 18-prostatrien- oic acid826 490 9.alpha.,15-dihydroxy-19,20-di- nor-5-cis, 13-trans, 17- prostatrienoic acid827 491 9.alpha.,15-dihydroxy-5-cis,- 13-trans, 17-cis-prosta- trienoic acid828 734 9.alpha.,15-dihydroxy-13-cis- prostenoic acid829 735 9.alpha.,11.alpha.,15-trihydroxy-13- cis-prostenoic acid830 615 9.alpha.,15-dihydroxy-2-ethyl- prostanoic acid831 616 9.alpha.,15-dihydroxy-3,3-di- methyl-prostanoic acid832 617 9.alpha.,15-dihydroxy-3-oxa- prostanoic acid833 618 9.alpha.,15-dihydroxy-2-fluoro- prostanoic acid834 619 9.alpha.,15-dihydroxy-2-phenyl- prostanoic acid835 620 9.alpha.,15-dihydroxy-2-meth- yl-prostanoic acid836 621 9.alpha.,15-dihydroxy-3-thia- prostanoic acid837 622 9.alpha.,15-dihydroxy-5-cis- prostenoic acid838 623 9.alpha.,15-dihydroxy-2-ethyl- 19,20-dinor-prostanoic acid839 624 9.alpha.,15-dihydroxy-3,3-di- methyl-19,20-dinor-pros- tanoic acid840 625 9.alpha.,15-dihydroxy-3-oxa- 19,20-dinor-prostanoic acid841 626 9.alpha.,15-dihydroxy-2-fluoro- 19,20-dinor-prostanoic acid842 627 9.alpha.,15-dihydroxy-2-phenyl- 19,20-dinor-prostanoic acid843 628 9.alpha.,15-dihydroxy-2-meth- yl-19,20-dinor-prostan- oic acid844 629 9.alpha.,15-dihydroxy-3-thia- 19,20-dinor-prostanoic acid845 630 9.alpha.,15-dihydroxy-19,20-di- nor-5-cis-prostenoic acid846 631 9.alpha.,15-dihydroxy-16-pros- tynoic acid847 632 9.alpha.,15-dihydroxy-6,7-di- nor-16-prostynoic acid848 633 9.alpha.,15-dihydroxy-7a,7b- bishomo-16-prostynoic acid849 634 9.alpha.,15-dihydroxy-2-ethyl- 16-prostynoic acid850 635 9.alpha.,15-dihydroxy-3,3-di- methyl-15-prostynoic acid851 636 9.alpha.,15-dihydroxy-3-oxa-16- prostynoic acid852 637 9.alpha.,15-dihydroxy-7-nor-16- prostynoic acid853 638 9.alpha.,15-dihydroxy-2-fluoro- 16-prostynoic acid854 639 9.alpha.,15-dihydroxy-7a-homo- 16-prostynoic acid855 640 9.alpha.,15-dihydroxy-2-phenyl- 16-prostynoic acid856 641 9.alpha.,15-dihydroxy-2-methyl- 16-prostynoic acid857 642 9.alpha.,15-dihydroxy-3-thia- 16-prostynoic acid858 643 9.alpha.,15-dihydroxy-10a-ho- mo-16-prostynoic acid859 644 9.alpha.,15-dihydroxy-10a-ho- mo-7-nor-16-prostynoic acid860 645 9.alpha.,15-dihydroxy-7a,10a- bishomo-16-prostynoic acid861 646 9.alpha.,15-dihydroxy-16-yne- 5-cis-prostenoic acid862 683 9.alpha.,15-dihydroxy-16-trans- prostenoic acid863 684 9.alpha.,15-dihydroxy-6,7-di- nor-16-trans-prostenoic acid864 685 9.alpha.,15-dihydroxy-7a,7b- bishomo-16-trans-pros- tenoic acid865 686 9.alpha.,15-dihydroxy-2-ethyl- 16-trans-prostenoic acid866 687 9.alpha.,15-dihydroxy-3,3-di- methyl-16-trans-prosten- oic acid867 688 9.alpha.,15-dihydroxy-3-oxa-16- trans-prostenoic acid868 689 9.alpha.,15-dihydroxy-7-nor-6- trans-prostenoic acid869 690 9.alpha.,15-dihydroxy-2-fluoro- 16-trans-prostenoic acid870 691 9.alpha.,15-dihydroxy-7a-homo- 16-trans-prostenoic acid871 692 9.alpha.,15-dihydroxy-2-phenyl- 16-trans-prostenoic acid872 693 9.alpha.,15-dihydroxy-2-methyl- 16-trans-prostenoic acid873 694 9.alpha.,15-dihydroxy-3-thia- 16-trans-prostenoic acid874 695 9.alpha.,15-dihydroxy-10a-homo- 16-trans-prostenoic acid875 696 9.alpha.,15-dihydroxy-10a-homo- 7-nor-16-trans-prosten- oic acid876 697 9.alpha.,15-dihydroxy-7a,10a- bishomo-16-trans-pros- tenoic acid877 698 9.alpha.,15-dihydroxy-5-cis,- 16-trans-prostadienoic acid878 647 9.alpha.,15-dihydroxy-16-cis- prostenoic acid879 648 9.alpha.,15-dihydroxy-6,7-di- nor-16-cis-prostenoic acid880 649 9.alpha.,15-dihydroxy-7a,7b- bishomo-16-cis-prosten- oic acid881 650 9.alpha.,15-dihydroxy-2-ethyl- 16-cis-prostenoic acid882 651 9.alpha.,15-dihydroxy-3,3-di- methyl-16-cis-prosten- oic acid883 652 9.alpha.,15-dihydroxy-3-oxa- 16-cis-prostenoic acid884 653 9.alpha.,15-dihydroxy-7-nor- 16-cis-prostenoic acid885 654 9.alpha.,15-dihydroxy-2-fluoro- 16-cis-prostenoic acid886 655 9.alpha.,15-dihydroxy-7a-homo- 16-cis-prostenoic acid887 656 9.alpha.,15-dihydroxy-2-phenyl- 16-cis-prostenoic acid888 657 9.alpha.,15-dihydroxy-2-methyl- 16-cis-prostenoic acid889 658 9.alpha.,15-dihydroxy-3-thia- 16-cis-prostenoic acid890 659 9.alpha.,15-dihydroxy-10a-ho- mo-16-cis-prostenoic acid891 660 9.alpha.,15-dihydroxy-10a-ho- mo-7-nor-16-cis-prosten- oic acid892 661 9.alpha.,15-dihydroxy-7a,10a- bishomo-16-cis-prosten- oic acid893 662 9.alpha.,15-dihydroxy-5-cis,- 16-cis-prostadienoic acid______________________________________

EXAMPLE 894

Preparation of 2-carbalkoxy (methyl/ethyl)-2-(2-methoxyethyl)-cyclopentan-1-one

Treatment of 2-cyclopentanone carboxylate (mixed methyl and ethyl esters) with 2-methoxyethyl bromide by the method of Example 1 furnishes the subject compound as an oil, b.p. 90.degree. C. (0.1 mm).

EXAMPLE 895

Preparation of 2-(2-methoxyethyl)cyclopentan-1-one

Heating 8 g. of 2-carboalkoxy (methyl/ethyl)-2-(2-methoxyethyl)-cyclopentan-1-one (Example 894) in 8 ml. of 20% aqueous hydrochloric acid at reflux for 3.5 hours and isolating the product by the method of Example 2 furnishes the subject compound as an oil, b.p. 45.degree.-50.degree. C. (0.02 mm).

EXAMPLE 896

Preparation of 1-acetoxy-2-(2-methoxyethyl)cyclopent-1-ene

The subject compound is prepared from 2-(2-methoxyethyl)cyclopentan-1-one (Example 895) and acetic anhydride by the procedure of Example 10. The product is an oil, b.p. 60.degree. C. (0.2 mm.).

EXAMPLE 897

Preparation of 2-(2-hydroxyethyl)-cyclopent-2-en-1-one

The enol acetate of Example 896 is brominated and dehydrobrominated by the method described in Example 13. The crude product is then dissolved in methylene chloride and is added at -78.degree. C. to a methylene chloride solution containing about seven molar equivalents of boron tribromide. After one hour at -78.degree. C. the solution is allowed to warm to room temperature and is then kept at ambient temperatures for a total of 18 hours. The mixture is poured into water and extracted with ether. The organic phase is washed with saturated saline solution, then water and is dried. Evaporation of solvents leaves subject product, which is purified by distillation. The combined organic phases are washed with ice cold 5% sodium hydroxide solution, ice cold 5% hydrochloric acid, and saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness. Distillation gives a pale yellow oil; .lambda. max 5.85 .mu. (carbonyl group).

EXAMPLE 898

Preparation of 2-formylmethylcyclopent-2-en-1-one

Chromium trioxide (0.6 mol) is added to a stirring solution of (1.2 mol) of anhydrous pyridine in 1500 ml. of anhydrous methylene chloride cooled in an ice bath. The deep red suspension is stirred for 15 minutes at 0.degree. C. and 45 minutes at ambient temperature. A solution of 01.5 mol of 2-(2-hydroxyethyl)-cyclopent-2-en-1-one (Example 897) in 50 ml. of methylene chloride is added, all at once, to the suspension. A black tarry deposit is formed immediately. After stirring the mixture for 25 minutes at ambient temperature, the methylene chloride is decanted from the tarry precipitate which is then triturated several times with ether.

EXAMPLE 899

Preparation of 2-(6-carboxy-2-cis-hexenyl)-cyclopent-2-en-1-one

A mixture of 0.194 g. (0.007952 mole) of sodium hydride (free of mineral oil) and 5.5 ml. of dimethylsulfoxide is heated to 70.degree. C. until gas evolution ceases under a nitrogen atmosphere. The resulting solution is cooled below room temperature and treated with a solution of 1.400 g. (0.00316 mole) of 4-carboxybutyltriphenyl phosphonium bromide [E. J. Corey et al., J. Am. Chem. Soc., 91, 5675 (1969)] in 6 ml. of dimethylsulfoxide. To the resulting red solution is added 0.00263 mole of 2-formylmethylcyclopent-2-en-1-one (Example 898) in 2 ml. of dimethylsulfoxide and the mixture is stirred at room temperature for 2.25 hours. The mixture is poured into ice water, sodium hydroxide solution is added to pH 12, and the neutral materials are extracted with diethyl ether. The basic phase is acidified with dilute hydrochloric acid and is extracted with diethyl ether. The organic phase is washed with water and saturated brine, dried (Na.sub.2 SO.sub.4), and evaporated to a semicrystalline mass. The latter is triturated with hot hexane, the solids are filtered off, and the filtrate is evaporated to yield the subject product as an oil.

EXAMPLE 900

Preparation of 2-(6-carbomethoxy-2-cis-hexenyl)-cyclopent-2-en-1-one

Treatment of 2-(6-carboxy-2-cis-hexenyl)-cyclopent-2-en-1-one (Example 899) with diazomethane in the usual manner is productive of the subject ester.

EXAMPLES 901-909

Hydrogenation of 13-trans-prostenoic acids designated in the table below by the procedure of Example 699 is productive of the prostanoic acids of the table.

TABLE 10______________________________________ Starting 13- trans-pro- ProductEx- stenoic acid Prostanoicample of Example Acid______________________________________901 397 9-oxo-15-hydroxy- 16-ethyl-pro- stanoic acid902 398 9-oxo-15-hydroxy- 16-methyl-20- nor-prostanoic acid903 400 9-oxo-15-hydroxy- 18,19-dimethyl- prostanoic acid904 426 9-oxo-15-hydroxy- 16-ethyl-6,7,19, 20-tetranor-pro- stanoic acid905 428 9-oxo-15-hydroxy- 16-ethyl-7a,7b- bishomo-prostan- oic acid906 429 9-oxo-15-hydroxy- 19-methyl-7a,7b- bishomo-prostan- oic acid907 433 9-oxo-15-hydroxy- 2-ethyl-18,19- dimethyl-pro- stanoic acid908 436 9-oxo-15-hydroxy- 3,3,16-trimethyl- 20-nor-prostanoic acid909 476 9-oxo-15-hydroxy- 7a,10a-bishomo-16- methyl-20-nor- prostanoic acid______________________________________

EXAMPLES 910-915

Treatment of the 9-oxo-alkyl esters designated in the table below with sodium borohydride by the procedure described in Example 257 is productive of the corresponding 9-hydroxy derivative of the table. These products are obtained as 9.alpha.- and 9.beta.-hydroxy epimeric mixtures.

TABLE 11______________________________________ Starting 9-oxoEx- derivative of Productample Example 9.alpha./9.beta.-hydroxy derivative______________________________________910 260 ethyl 9.alpha./9.beta.,15-dihydroxy- 2-ethyl-13-trans- prostenoate911 261 ethyl 9.alpha./9.beta.,15-dihydroxy- 3,3-dimethyl-13-trans- prostenoate912 262 ethyl 9.alpha./9.beta.,15-dihydroxy- 3-oxa-13-trans- prostenoate913 266 ethyl 9.alpha./9.beta.,15-dihydroxy- 2-phenyl-13-trans- prostenoate914 272 ethyl 9.alpha./9.beta.,15-dihydroxy- 3-thia-13-trans- prostenoate915 284 ethyl 9.alpha./9.beta.,15-dihydroxy- 13-trans,17-cis- prostadienoate______________________________________

EXAMPLES 916-921

Saponification of the ethyl esters designated in the table below by the procedure described in Example 122 furnishes the carboxylic acids of the table.

TABLE 12______________________________________ Product 9.alpha./9.beta.,15-di-Ex- Starting ethyl hydroxy-13-trans-pro-ample ester of Example stenoic acid______________________________________916 910 9.alpha./9.beta.,15-dihydroxy- 2-ethyl-13-trans- prostenoic acid917 911 9.alpha./9.beta.,15-dihydroxy- 3,3-dimethyl-13- trans-prostenoic acid918 912 9.alpha./9.beta.,15-dihydroxy- 3-oxa-13-trans- prostenoic acid919 913 9.alpha./9.beta.,15-dihydroxy- 2-phenyl-13-trans- prostenoic acid920 914 9.alpha./9.beta.,15-dihydroxy- 3-thia-13-trans- prostenoic acid921 915 9.alpha./9.beta.,15-dihydroxy- 13-trans,17-cis- prostadienoic acid______________________________________

EXAMPLES 922-932

Treatment of the cycloalkenones of Table 13, which follows, with the Grignard reagent, prepared from 1-bromo-3-triphenylmethoxy-trans-1-octene and magnesium according to the procedure of Example 733, hydrolizing the intermediate 15-O-triphenylmethyl derivatives with glacial acetic acid-tetrahydrofura-water (4:2:1) according to the procedure of Example 121, and isolating the products in the manner described in Example 732 is productive of the product 9-oxo-15-hydroxy-13-cis-prostenoates and 9-oxo-15-hydroxy-13-trans-prostenoates of the table.

TABLE 13__________________________________________________________________________ Starting cyclopentenone Product 15-hydroxy-13-cis- Product 15-hydroxy-13-trans-Ex. Ester of Example prostenoate ester prostenoate ester__________________________________________________________________________922 23 ethyl 9-oxo-15-hydroxy-7a,7b- ethyl 9-oxo-15-hydroxy-7a,7b- bishomo-13-cis-prostenoate bishomo-13-trans-prostenoate923 31 ethyl 9-oxo-15-hydroxy-2-ethyl- ethyl 9-oxo-15-hydroxy-2- 13-cis-prostenoate ethyl-13-trans-prostenoate924 41 ethyl 9-oxo-15-hydroxy-3,3-di- ethyl 9-oxo-15-hydroxy-3,3-di- methyl-13-cis-prostenoate methyl 13-trans-prostenoate925 46 ethyl 9-oxo-15-hydroxy-3-oxa- ethyl 9-oxo-15-hydroxy-3-oxa- 13-cis-prostenoate 13-trans-prostenoate926 53 ethyl 9-oxo-15-hydroxy-7-nor- ethyl 9-oxo-15-hydroxy-7-nor- 13-cis-prostenoate 13-trans-prostenoate927 70 ethyl 9-oxo-15-hydroxy-2-fluoro- ethyl 9-oxo-15-hydroxy-2- 13-cis-prostenoate fluoro-13-trans-prostenoate928 84 n-decyl 9-oxo-15-hydroxy- n-decyl 9-oxo-15-hydroxy- 13-cis-prostenoate 13-trans-prostenoate929 99 ethyl 9-oxo-15-hydroxy-2-methyl- ethyl 9-oxo-15-hydroxy-2- 13-cis-prostenoate methyl-13-trans-prostenoate930 111 ethyl 9-oxo-15-hydroxy-10a-homo- ethyl 9-oxo-15-hydroxy-10a- 13-cis-prostenoate homo-13-trans-prostenoate931 118 ethyl 9-oxo-15-hydroxy-3-thia- ethyl 9-oxo-15-hydroxy-3- 13-cis-prostenoate thia-13-trans-prostenoate932 900 methyl 9-oxo-15-hydroxy-5- methyl 9-oxo-15-hydroxy-5- cis, 13-cis-prostadienoate cis, 13-trans- prostadienoate__________________________________________________________________________

EXAMPLES 933-942

Saponification of the 13-cis-prostenoate alkyl esters designated in Table 14 below by the method described in Example 122 is productive of the 13-cis-prostenoic acids of the Table.

TABLE 14__________________________________________________________________________ Starting 13-cis-prostenoateExample Ester of Example Product 13-cis-prostenoic acids.__________________________________________________________________________933 922 9-oxo-15-hydroxy-7a,7b-bishomo-13- cis-prostenoic acid934 923 9-oxo-15-hydroxy-2-ethyl-13-cis- prostenoic acid935 924 9-oxo-15-hydroxy-3,3-dimethyl-13-cis- prostenoic acid936 925 9-oxo-15-hydroxy-3-oxa-13-cis-prostenoic acid937 926 9-oxo-15-hydroxy-7-nor-13-cis-prostenoic acid938 927 9-oxo-15-hydroxy-2-fluoro-13-cis-prostenoic acid939 929 9-oxo-15-hydroxy-2-methyl-13-cis-prostenoic acid940 930 9-oxo-15-hydroxy-10a-homo-13-cis-prostenoic acid941 931 9-oxo-15-hydroxy-3-thia-13-cis-prostenoic acid942 932 9-oxo-15-hydroxy-5-cis, 13-cis-prostadienoic__________________________________________________________________________ acid

EXAMPLES 943-954

Treatment of the 9-oxo-13-cis-prostenoic acids and esters of Table 15 below with lithium perhydro-9 b-boraphenalyl hydride by the procedure described in Example 737 furnishes the 9.alpha.,15-dihydroxy-13-cis-prostenoic acids and esters of the table.

TABLE 15__________________________________________________________________________ Starting 9-oxo-13-cis- prostenoic derivativeExample of Example Product 9.alpha.,15-hydroxy-13-cis-prostenoic acid and esters__________________________________________________________________________943 933 9,15-dihydroxy-7a,7b-bishomo-13-cis-prostenoic acid944 934 9,15-dihydroxy-2-ethyl-13-cis-prostenoic acid945 935 9,15-dihydroxy-3,3-dimethyl-13-cis-prostenoic acid946 936 9,15-dihydroxy-3-oxa-13-cis-prostenoic acid947 937 9,15-dihydroxy-7-nor-13-cis-prostenoic acid948 938 9,15-dihydroxy-2-fluoro-13-cis-prostenoic acid949 939 9,15-dihydroxy-2-methyl-13-cis-prostenoic acid950 940 9,15-dihydroxy-10a-homo-13-cis-prostenoic acid951 941 9,15-dihydroxy-3-thia-13-cis-prostenoic acid952 942 9,15-dihydroxy-5-cis,-13-cis-prostadienoic acid953 932 methyl 9,15-dihydroxy-5-cis, 13-cis-prostadienoate954 928 n-decyl 9,15-dihydroxy-13-cis-prostenoate__________________________________________________________________________

EXAMPLE 955

Preparation of 1-iodo-trans-1-octen-3-ol

A solution of 78.2 g. (0.310 moles) of 1-iodo-trans-1-octen-3-one (Example 724) in 150 ml. of absolute ethanol is added dropwise over 2 hours to a slurry of 6.49 g. (0.172 moles) of sodium borohydride in 50 ml. of absolute ethanol cooled in an ice bath. After the addition is complete, the mixture is stirred for 2 hours with ice cooling and is then poured into 1 l. of water. The mixture is extracted into benzene and the organic phase is washed with saturated brine, dried (Na.sub.2 SO.sub.4) and evaporated. The resulting oil is dissolved into 400 ml. of absolute ethanol and treated with 5 mole percent of p-carboxyphenylhydrazine at 70.degree. C. for 1.5 hours to remove residual ketone. The mixture is cooled and evaporated and the residue is dissolved into 400 ml. of ether and is filtered. The filtrate is washed with dilute sodium bicarbonate solution and saturated brine, dried (Na.sub.2 SO.sub.4), and evaporated to an oil. This oil is chromatographed upon 2 Kg. of Florisil.RTM. packed in hexane and the product is obtained upon elution with benzene. Distillation of the product yields a colorless oil, b.p. 74.degree.-76.degree. C. (0.005 tor.).

EXAMPLE 956

Preparation of 1-iodo-3-(p-anisyldiphenylmethoxy)-trans-1-octene

A mixture of 14.92 g. (0.0588 mole) of 1-iodo-trans-1-octen-3-ol (Example 955) and 18.2 g. (0.0588 mole) of p-anisyldiphenylmethyl chloride in 165 ml. of dry pyridine is heated at 60.degree. C. for 18 hours under an inert atmosphere. The mixture is cooled and the solvent is evaporated in vacuo. The residue is partitioned between ether and water, and the organic phase is washed with water and saturated brine, dried (MgSO.sub.4), and evaporated. The residue is chromatographed upon 300 g. of Florisil.RTM. packed in hexane and the product is eluted with hexane and 4:1 hexane-benzene the yield a colorless oil.

EXAMPLE 957

Preparation of methyl esters of dl-11-deoxyprostaglandin-E.sub.1 and dl-11-deoxy-15-epi-prostaglandin E.sub.1

To a solution of 6.030 g. (0.01215 mole) of 1-iodo-3-triphenylmethoxy-trans-1-octene (Example 730) in 8 ml. of toluene cooled to -78.degree. C. under an inert atmosphere is added 5.2 ml. of a 2.34 M solution of n-butyllithium in hexane. The resulting solution is allowed to warm to -40.degree. C. and is maintained at this temperature for 1 hour. To the solution containing 3-triphenylmethoxy-trans-1-octenyllithium is then added 5.0 ml. of a 2.44 M (0.0122 mole) solution of trimethylaluminum in heptane and the mixture is allowed to warm to -10.degree. C. The mixture containing lithium trimethyl(3-triphenylmethoxy-trans-1-octenyl)alanate is then cooled to -78.degree. C. and to it is added a solution of 2.725 g. (0.01215 mole) of 2-(6-carbomethoxyhexyl)-2-cyclopentenone (Example 83) dissolved in 10 ml. of diethyl ether. The mixture is allowed to warm to room temperature and is stirred at ambient temperature for 18 hours. The mixture is then poured onto ice and diluted hydrochloric acid and is extracted into ether. The organic phase is washed with water and saturated brine, dried (Na.sub.2 SO.sub.4), and evaporated to yield a colorless oil. This oil is heated with 100 ml. of 80% aqueous acetic acid at 80.degree. C. for 1 hour under an inert atmosphere. The resulting mixture is cooled and evaporated in vacuo to dryness with 100 ml. of xylene to yield an oil. This oil is dry-column-chromatographed upon 400 g. of silica gel using 4:1 benzene-ethyl acetate as eluent to yield a total of 2.59 g. of dl-11-deoxyprostaglandin E.sub.1 and dl-11-deoxy-15-epi-prostaglandin E.sub.1 methyl esters.

EXAMPLE 958

Preparation of 4-(trimethylsiloxy)-2-(6-carbotrimethylsiloxyhexyl)cyclopent-2-en-1-one

To a solution of 5 g. of 2-(6-carboxyhexyl)-4-hydroxy-cyclopent-2-en-1-one (Example 94) in 10 ml. of dry N,N-dimethylformamide is added 5.4 g. of trimethylsilyl chloride in a nitrogen atmosphere. To the resulting solution cooled in a tap water bath is added 5.05 g. of triethylamine in 10 ml. of N,N-dimethylformamide dropwise. The resulting mixture is stirred at 60.degree. C. in an oil-bath for 2 hours, then at ambient temperatures for 18 hours. Triethylamine hydrochloride is removed by filtration and the filtrate is taken to dryness. The residual oil is distilled to give 2.6 g. of product, b.p. 156.degree.-157.degree. C. (0.07 mm.).

EXAMPLE 958A

Preparation of 4-(dimethylisopropylsiloxy)-2-(6-carbodimethylisopropylsiloxyhexyl)cyclopent-2-en-1-one

Treatment of 1 g. of 2-(6-carboxyhexyl)-4-hydroxy-cylopent-2-en-1-one in 2ml. of dry N,N-dimethylformamide containing 1.81 g. of dimethylisopropylsilyl chloride [E. J. C rey, R. K. Varma, J. Amer. Chem. Soc., 93, 7320 (1971)] 1.57 g. of triethylamine in 2 ml. of N,N-dimethylformamide in the manner described in Example 958 gives 1.45 g. of product after two evaporations with toluene.

EXAMPLE 959

Preparation of 4-(dimethyl-t-butylsiloxy)-2-(6-carbodimethyl-t-butylsiloxyhexyl)cyclopent-2-en-1-one

To a 0.degree. C. solution of 2.0 gm. (8.55 mole) 4-hydroxy-2-(6-carboxyhexyl)cyclopent-2-en-1-one (Example 94) and 3.65 gm. (54 mole) of imidazole in 5 ml. of dimethylformamide is added a slurry consisting of 4.07 gm. (27 mole) of dimethyl-t-butyl chlorosilane in 5 ml. of dimethylformamide. The slurry is rinsed in with an additional 1 ml. of dimethylformamide. The ice-bath is removed and the solution is stirred at 37.degree. C. for four hours. The solution is then poured into 140 ml. of water and the aqueous solution is extracted twice with 70 ml. of isomeric hexanes. The organic layers are combined, dried with magnesium sulfate and concentrated in vacuo to an oil. Toluene (50 ml.) is added twice and evaporated in vacuo to remove unwanted low boiling impurities.

The residue is maintained under active vacuum overnight to give 3.38 gm. (7.45 mole) of an oil, that shows no hydroxyl or carboxyl absorption in the infrared. .tau. max: 1720 cm.sup.-1 (unsaturated ketone and silyl ester), 840, 815, 795, 780 cm.sup.-1 (silyl ether and silyl ester).

EXAMPLE 960

Preparation of dl-prostaglandin E.sub.1 and dl-epi-prostaglandin E.sub.1

To a solution of 4.790 g. (0.0091 mole) of 3-(p-anisyldiphenylmethoxy)-trans-1-iodo-1-octene (Example 956) in 5 ml. of toluene cooled to -78.degree. C. under an inert atmosphere is added 3.9 ml. of 2.34 M n-butyllithium in hexane. The resulting solution is warmed to -40.degree. C. and is maintained at this temperature for 1 hour. To the solution containing 3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium is then added 3.6 ml. of a 2.44 M solution of trimethylaluminum in heptane and the mixture is allowed to warm to 0.degree. C. The solution containing lithium trimethyl[3-(p-anisyldiphenylmethoxy)-trans-1-octenyl]alanate is then added to a solution of 3.30 g. (0.00726 mole) of 2-(6 -carbo-t-butyldimethylsiloxyhexyl)-4-(t-butyldimethylsiloxy)-2-cyclopentenone (Example 959) dissolved in 10 ml. of ether cooled to -45.degree. C. under an inert atmosphere. The resulting solution is allowed to warm to room temperature and is stirred at ambient temperatures for 17 hours. The solution is then poured onto a mixture of 5 ml. of concentrated hydrochloric acid and 150 g. of ice. This mixture is stirred until the ice melts and is extracted into ether. The organic phase is washed with ice cold water and cold saturated brine, dried (Na.sub.2 SO.sub.4), and is evaporated (<37.degree. C.) in vacuo. The resulting oil is then heated to 38.degree. C. for 23 hours under an inert atmosphere with 100 ml. of 3:1:1 (V:V:V) acetic acid-tetrahydrofuran-water. The mixture is then evaporated with 150 ml. of xylene in vacuo ( <38.degree. C.) to yield an oil. Chromatography of this oil upon 115 g. of Silic -octenyllithium CC-4 (Mallinckrodt) using a benzene-ethyl acetate gradient as eluent yields dl-prostaglandin E.sub.1, m.p. 108.degree.-112.degree. (from ethyl acetate) and dl-15-epi-prostaglandin E.sub.1.

EXAMPLE 961

Preparation of 3-triphenylmethoxy-trans-1:octenyllithium

To a solution of 4.96 g. of 1-iodo-3-triphenylmethoxy-trans-1-octene (Example 730) in 10 ml. of toluene cooled to -78.degree. C. is added under an inert atmosphere 1 molar equivalent of n-butyllithium dissolved in hexane. The reaction mixture is allowed to warm to -40.degree. C. and is then maintained at that temperature for 1 hour to yield a hydrocarbon solution of 3-triphenylmethoxy-trans-1-octenyllithium.

EXAMPLE 962

Preparation of 3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium

to a solution of 5.26 g. of 1-iodo-3-(p-anisyldiphenylmethoxy)-trans-1-octene (Example 956) in 10 ml. of toluene, cooled to -78.degree. C., is added under an inert atmosphere 1 molar equivalent of n-butyllithium dissolved in hexane. The reaction mixture is allowed to warm to -40.degree. C. and is maintained at that temperature for 1 hour to yield a hydrocarbon solution of 3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium.

EXAMPLE 963

Preparation of lithium [3-triphenylmethoxy-trans-1-octenyl]-trimethylalanate

To a hydrocarbon solution of 3-triphenylmethoxy-trans-1-octenyllithium (Example 961) cooled to -40.degree. C. is added under an inert atmosphere 1 molar equivalent of trimethylaluminum dissolved in heptane to yield a hydrocarbon solution of the title compound.

EXAMPLE 964

Preparation of lithium [3-p-anisyldiphenylmethoxy)-trans-1-octenyl]-trimethylalanate

To a hydrocarbon solution of 3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium (Example 962) cooled to -40.degree. C. is added under an inert atmosphere 1 molar equivalent of trimethylaluminum dissolved in hexane to yield a hydrocarbon solution of the title compound.

EXAMPLE 965

Preparation of lithium [3-triphenylmethoxy-trans-1-octenyl]-tri-n-propylalanate

To a hydrocarbon solution of 3-triphenylmethoxy-trans-1-octenyllithium (Example 961) cooled to -40.degree. C. is added under an inert atmosphere 1 molar equivalent of tri-n-propylaluminum dissolved in hexane to yield a hydrocarbon solution of the title compound.

EXAMPLE 966

Preparation of lithium [3-(p-anisyldiphenylmethoxy)-trans-1-octenyl]-tri-n-hexylalanate

To a hydrocarbon solution of 3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium (Example 962) cooled to -40.degree. C. is added under an inert atmosphere 1 molar equivalent to tri-n-hexylaluminum dissolved in heptane to yield a hydrocarbon solution of the title compound.

EXAMPLE 967

Preparation of lithium [3-triphenylmethoxy-trans-1-octenyl]-tri-n-decylalanate

To a hydrocarbon solution of 3-triphenylmethoxy-trans-1-octenyllithium (Example 961) cooled to -40.degree. C. is added under an inert atmosphere 1 molar equivalent of tri-n-decylaluminum dissolved in heptane to yield a hydrocarbon solution of the title compound.

EXAMPLE 968

Preparation of lithium di-(3-triphenylmethoxy-trans-1-octenyl)-dimethylalanate

To a hydrocarbon solution of dimethylaluminum chloride cooled to -78.degree. C. is added under an inert atmosphere 2 molar equivalents of 3 -triphenylmethoxy-trans-1-octenyllithium (Example 961) dissolved in toluene-hexane solvent. The mixture is allowed to warm to 0.degree. C. to yield a hydrocarbon solution of the title compound.

EXAMPLE 969

Preparation of lithium di-[3-(p-anisyldiphenylmethoxy)-trans-1-octenyl]-diethylalanate

To a hexane solution of diethylaluminum chloride cooled to -78.degree. C. is added under an inert atmosphere 2 molar equivalents of 3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium (Example 962) dissolved in toluene-hexane solvent. The mixture is allowed to warm to 0.degree. C. to yield a hydrocarbon solution of the title compound.

EXAMPLE 970

Preparation of lithium tri-(3-triphenylmethoxy-trans-1-octenyl)-ethylalanate

To a hydrocarbon solution of ethylaluminum dichloride cooled to -78.degree. C. is added under an inert atmosphere 3 molar equivalents of 3-triphenylmethoxy-trans-1-octenyllithium (Example 961) dissolved in toluene-hexane solvent. The mixture is allowed to warm to 0.degree. C. to yield a hydrocarbon solution of the title compound.

EXAMPLE 971

Preparation of lithium tetra-(3-triphenylmethoxy-trans-1-octenyl)alanate

To a well stirred mixture of anhydrous aluminum chloride and hexane cooled to -78.degree. C. is added under an inert atmosphere 4 molar equivalents of 3 -triphenylmethoxy-trans-1-octenyllithium (Example 961) dissolved in toluene-hexane. The mixture is allowed to warm to 0.degree. C. to yield the title compound.

EXAMPLE 972

Preparation of lithium tetra-(3-p-anisyldiphenylmethoxy-trans-1-octenyl)alanate

To a well stirred mixture of anhydrous aluminum chloride and hexane cooled to -78.degree. C. is added under an inert atmosphere 4 molar equivalents of 3-p-anisyldiphenylmethoxy-trans-1-octenyllithium (Example 962) dissolved in toluene-hexane. The mixture is allowed to warm to 0.degree. C. to yield the title compound.

EXAMPLES 973-981

Substitution of lithium trimethyl(3-triphenylmethoxy-trans-1-octenyl)alanate in Example 957 with the lithium alanates of Examples 964, 965, 966, 967, 968, 969, 970, 971 or 972 is productive of the methyl esters of d, -11-deoxy-prostaglandin E.sub.1 and d, 11-deoxy-15-epi-prostaglandin E.sub.1.

EXAMPLES 982-990

Substitution of lithium trimethyl [3-(p-anisyldiphenylmethoxy)-trans-1-octenyl]alanate of Example 960 with the lithium alanates of Examples 965, 966, 967, 968, 969, 970, 971 or 972 is productive of d,l-prostaglandin-E.sub.1 and d,l-15-epi-prostaglandin E.sub.1.

EXAMPLE 991

Preparation of hexanoyl bromide

A mixture of 300 g. of hexanoic acid and 260 g. of phosphorus tribromide is heated at 80.degree. C. for 1.5 hours with stirring and protection from moisture. The mixture is cooled and the upper phase is decanted into a distilling flask. Distillation of this material yields 400 g. of the colorless acid bromide, b.p. 51.degree.-53.degree. C. (10 torr.).

EXAMPLE 992

Preparation of 1-bromo-trans-1-octen-3-one

A mixture of 300 g. of aluminum bromide and 250 ml. of 1,2-dibromoethane, cooled in an ice bath and protected from moisture, is saturated with acetylene. To the mixture is added with ice cooling 150 g. of hexanoyl bromide (Example 991) over a period of 20 minutes and the resulting mixture is treated with acetylene until gas uptake ceases. The reaction mixture is poured onto 500 ml. of saturated brine and 500 g. of ice. The resulting mixture is extracted twice with 500 ml. of ether. The combined organic extracts are washed twice with 500 ml. of saturated brine and dried with anhydrous sodium sulfate. To the organic phase is added 5 g. of hydroquinone and the solvent is evaporated in vacuo to yield the crude 1-bromo-trans-1-octen-3-one.

EXAMPLE 993

Preparation of 1-bromo-trans-1-octen-3-ol

To an ice cooled mixture of 20 g. of sodium borohydride in 800 ml. of anhydrous ethanol is added 160 g. of crude 1-bromo-trans-1-octen-3-one (Example 992) over a period of 0.5 hour. The mixture is stirred for 2 hours with ice cooling and is then partitioned between ice water and benzene. The organic phase is washed with water and saturated brine, dried (Na.sub.2 SO.sub.4), and evaporated to an oil. Distillation gives the product as an oil, b.p. 66.degree.-68.degree. C. (0.025 torr.).

EXAMPLE 994

Preparation of 4,4-dimethyl-1-octyn-3-ol

To a solution of 20.2 g. (0.220 mole) of lithium acetylide-ethylenediamine complex in 100 ml. of dry dimethylsulfoxide is added 25.6 g. (0.200 mole) of 2,2-dimethyl-1-hexanal, prepared according to the procedure of G. Stork and S. R. Dowd, J. Amer. Chem. Soc., 85, 2178 (1963), in 25 ml. of dimethylsulfoxide at a rate to maintain a temperature of 25.degree. C. (cooling). The mixture is then maintained at 25.degree. C. for 2 hours and is poured onto ice and excess hydrochloric acid. The mixture is extracted with ether and the organic phase is washed with water and saturated brine, dried (Na.sub.2 SO.sub.4), and evaporated to an oil. Distillation in vacuo yields the product as a colorless oil.

EXAMPLE 995

Preparation of 4,4-dimethyl-3-tetrahydropyranyloxy-1-octyne

To a solution of 23.1 g. (0.150 mole) of 4,4-dimethyl-1-octyn-3-ol (Example 994) in 126 g. of freshly distilled dihydropyran is added 1 drop of phosphorus oxychloride and the solution is maintained at ambient temperature in a tightly stoppered flask for 20 hours. Five drops of triethylamine are then added and the mixture is evaporated in vacuo to an oil. The oil is chromatographed on 600 g. of silica gel and the product is eluted with 5% ethyl acetate in benzene yielding a colorless oil.

EXAMPLE 996

Preparation of 4,4-dimethyl-1-iodo-trans-1-octen-3-ol

To 233 ml. of a 0.43M solution of disiamylborane in diglyme cooled to 0.degree. C. under an inert atmosphere is added 23.8 g. (0.100 mole) 4,4-dimethyl-3-tetrahydropyranyloxy-1-octyne (Example 995). The mixture is allowed to come to room temperature and is stirred at ambient temperature for 3 hours. The solution is cooled to 0.degree. C. and 22.5 g. (0.30 mole) of triethylamine oxide is added portionwise such that the temperature is maintained at 0.degree.-5.degree. C. The mixture is stirred at 0.degree. C. for 1 hour and is then poured into 150 ml. of 1 N sodium hydroxide followed immediately by a solution of 25.4 g. (0.100 mole) of iodine in 60 ml. of tetrahydrofuran. The mixture is stirred at ambient temperatures for 0.5 hour and poured into 500 ml. of water. The mixture is decolorized by addition of sodium thiosulfate solution and is extracted into ether. The organic phase is washed with water and the solvent is removed in vacuo. The residue is stirred at room temperature for 20 hours with 900 ml. 3:1:1 tetrahydrofuran-acetic acid-water. The solution is evaporated in vacuo and the residue is chromatographed on silica gel in benzene using 10-20% ethylacetate in benzene.

EXAMPLE 997

Preparation of 4,4-dimethyl-1-iodo-3-triphenylmethoxy-trans-1-octene

Treatment of 11.2 g. (0.0396 mole) of 4,4-dimethyl-1-iodo-trans-1-octen-3-ol (Example 996) with 12.8 g. of triphenylmethyl bromide in 50 ml. of pyridine and purification on Florisil.RTM., all as described in Example 728 gives the title compound.

EXAMPLE 998

Preparation of 5,5-dimethyl-1-octyn-3-ol

Treatment of 20.2 g. (0.220 mole) of lithium acetylide-ethylenediame complex in 100 ml. of dimethylsulfoxide with 25.6 g. (0.200 mole) of 3,3-dimethylhexanal [prepared according to the procedure of A. W. Burgstahler, J. Amer. Chem. Soc., 82, 4681 (1960)] and distillation of the product, all as described in Example 994 yields the title compound.

EXAMPLE 999

Preparation of 5,5-dimethyl-3-tetrahydropyranyloxy-1-octyne

Treatment of 23.1 g. (0.150 mole) of 5,5-dimethyl-1-octyn-3-ol (Example 998) with 126 g. of dihydropyran and 1 drop of phosphorus oxychloride as described in Example 995 gives the title compound.

EXAMPLE 1000

Preparation of 5,5-dimethyl-1-iodo-trans-1-octen-3-ol

Treatment of 23.8 g. (0.100 mole) of 5,5-dimethyl-3-tetrahydropyranyloxy-1-octyne (Example 999) successively with 233 ml. of 0.43 M disiamylborane in diglyme, 22.5 g. of trimethylamine oxide, 150 ml. of 1 N sodium hydroxide, 25.4 g. of iodine, and 900 ml. of 3:1:1 tetrahydrofuran-acetic acid-water as described in Example 996 gives the title compound.

EXAMPLE 1001

Preparation of 5,5-dimethyl-1-iodo-3-triphenylmethoxy-trans-1-octene

Treatment of 6.0 g. of 5,5-dimethyl-1-iodo-trans-1-octen-3-ol (Example 1000) with 6.9 g. of triphenylmethyl bromide in 30 ml. of pyridine and purification on Florisil.RTM., all as described in Example 728 gives the title compound.

EXAMPLE 1002

Preparation of 4,4-dimethyl-3-triphenylmethoxy-trans-1-octenyllithium

Treatment of 4,4-dimethyl-1-iodo-3-triphenylmethoxy-trans-1-octene (Example 997) with n-butyllithium in the manner of Example 961 provides a toluene-hexane solution of the subject trans-vinyl lithium derivative.

EXAMPLE 1003

Preparation of 5,5-dimethyl-3-triphenylmethoxy-trans-1-octenyllithium

Treatment of 5,5-dimethyl-1-iodo-3-triphenylmethoxy-trans-1-octene (Example 1001) with n-butyllithium in the manner of Example 961 provides a toluene-hexane solution of the subject trans-vinyl lithium derivative.

EXAMPLE 1004

Preparation of lithium (4,4-dimethyl-3-triphenylmethoxy-trans-1-octenyl)-trimethylalanate

The subject alanate in hydrocarbon solution is prepared according to the method of Example 963 from a hydrocarbon solution of 4,4-dimethyl-3-triphenylmethoxy-trans-1-octenyllithium (Example 1002) and trimethylaluminum.

EXAMPLE 1005

Preparation of lithium (5,5-dimethyl-3-triphenylmethoxy-trans-1-octenyl)-trimethylalanate

A hydrocarbon solution of the subject alanate is prepared from a hydrocarbon solution of 5,5-dimethyl-3-triphenylmethoxy-trans-1-octenyl lithium (Example 1003) and trimethylaluminum according to the procedure of Example 963.

EXAMPLES 1006-1031

Treatment of the cycloalkenones of Table 16 which follows with the indicated alanates according to the procedure of Example 957 provides the product 16,16-dimethyl or 17,17-dimethyl 13-trans-prostenoates of the table. The intermediate corresponding 15-O-triphenylmethyl derivatives are obtained prior to treatment with aqueous acetic acid.

TABLE 16______________________________________ Product from reaction with lithium (4,4-Dimethyl-3- Starting cyclo- triphenylmethoxy-trans-1- alkenone of octenyl)trimethylalanateExample Example (Example 1004)______________________________________1006 13 ethyl 9-oxo-15-hydroxy-16,- 16-dimethyl-13-trans-pro- stenoate1007 23 ethyl 9-oxo-15-hydroxy-16,- 16-dimethyl-7a,7b-bishomo- 13-trans-prostenoate1008 31 ethyl 9-oxo-15-hydroxy-16,- 16-dimethyl-2-ethyl-13- trans-prostenoate1009 41 ethyl 9-oxo-15-hydroxy-16,- 16-dimethyl-3,3-dimethyl- 13-trans-prostenoate1010 46 ethyl 9-oxo-15-hydroxy-16,- 16-dimethyl-3-oxa-13-trans- prostenoate1011 53 ethyl 9-oxo-15-hydroxy-16,- 16-dimethyl-7-nor-13-trans- prostenoate1012 70 ethyl 9-oxo-15-hydroxy-16,- 16-dimethyl-2-fluoro-13- trans-prostenoate1013 84 n-decyl 9-oxo-15-hydroxy- 16,16-dimethyl-13-trans- prostenoate1014 99 ethyl 9-oxo-15-hydroxy-16,- 16-dimethyl-2-methyl-13- trans-prostenoate1015 111 ethyl 9-oxo-15-hydroxy-16,- 16-dimethyl-10a-homo-13- trans-prostenoate1016 118 ethyl 9-oxo-15-hydroxy-16,- 16-dimethyl-3-thia-13-trans- prostenoate1017 900 methyl 9-oxo-15-hydroxy-16,- 16-dimethyl-5-cis,13-trans- prostadienoate1018 79 ethyl 9-oxo-15-hydroxy-16,- 16-dimethyl-2-phenyl-13- trans-prostenoate- Product from reaction with lithium (5,5-Dimethyl-3- Starting cyclo- triphenylmethoxy-trans-1- alkenone of octenyl)trimethylalanateExample Example (Example 1005)______________________________________1019 13 ethyl 9-oxo-15-hydroxy-17,- 17-dimethyl-13-trans-pro- stenoate1020 23 ethyl 9-oxo-15-hydroxy-17,- 17-dimethyl-7a,7b-bishomo- 13-trans-prostenoate1021 31 ethyl 9-oxo-15-hydroxy-17,- 17-dimethyl-2-ethyl-13- trans-prostenoate1022 41 ethyl 9-oxo-15-hydroxy-17,- 17-dimethyl-3,3-dimethyl- 13-trans-prostenoate1023 46 ethyl 9-oxo-15-hydroxy-17,- 17-dimethyl-3-oxa-13-trans- prostenoate1024 53 ethyl 9-oxo-15-hydroxy-17,- 17-dimethyl-7-nor-13-trans- prostenoate1025 70 ethyl 9-oxo-15-hydroxy-17,- 17-dimethyl-2-fluoro-13- trans-prostenoate1026 84 n-decyl 9-oxo-15-hydroxy- 17,17-dimethyl-13-trans- prostenoate1027 99 ethyl 9-oxo-15-hydroxy-17,- 17-dimethyl-2-methyl-13- trans-prostenoate1028 111 ethyl 9-oxo-15-hydroxy-17,- 17-dimethyl-10a-homo-13- trans-prostenoate1029 118 ethyl 9-oxo-15-hydroxy-17,- 17-dimethyl-3-thia-13-trans- prostenoate1030 900 methyl 9-oxo-15-hydroxy- 17,17-dimethyl-5-cis,13- trans-prostadienoate1031 79 ethyl 9-oxo-15-hydroxy-17,- 17-dimethyl-2-phenyl-13- trans-prostenoate______________________________________

EXAMPLES 1032-1055

Saponification of the 16,16-dimethyl or 17,17-dimethyl 13-trans-prostenoate alkyl esters of Table 17 below by the method of Example 122 provides the corresponding prostenoic acids of the Table.

TABLE 17______________________________________ Product 16,16-dimethyl or Starting alkyl 17,17-dimethyl-9-oxo-15-Exam- ester of hydroxy-13-trans-proste-ple Example noic acid______________________________________1032 1006 9-oxo-15-hydroxy-16,16-di- methyl-13-trans-prostenoic acid1033 1007 9-oxo-15-hydroxy-16,16-di- methyl-7a,7b-bishomo-13- trans-prostenoic acid1034 1008 9-oxo-15-hydroxy-16,16-di- methyl-2-ethyl-13-trans- prostenoic acid1035 1009 9-oxo-15-hydroxy-16,16-di- methyl-3,3-dimethyl-13- trans-prostenoic acid1036 1010 9-oxo-15-hydroxy-16,16-di- methyl-3-oxa-13-trans-pro- stenoic acid1037 1011 9-oxo-15-hydroxy-16,16-di- methyl-7-nor-13-trans-pro- stenoic acid1038 1012 9-oxo-15-hydroxy-16,16-di- methyl-2-fluoro-13-trans- prostenoic acid1039 1014 9-oxo-15-hydroxy-16,16-di- methyl-2-methyl-13-trans- prostenoic acid1040 1015 9-oxo-15-hydroxy-16,16-di- methyl-10a-homo-13-trans- prostenoic acid1041 1016 9-oxo-15-hydroxy-16,16-di- methyl-3-thia-13-trans- prostenoic acid1042 1017 9-oxo-15-hydroxy-16,16-di- methyl-5-cis,13-trans-pro- stadienoic acid1043 1018 9-oxo-15-hydroxy-16,16-di- methyl-2-phenyl-13-trans- prostenoic acid1044 1019 9-oxo-15-hydroxy-17,17-di- methyl-13-trans-prostenoic acid1045 1020 9-oxo-15-hydroxy-17,17-di- methyl-7a,7b-bishomo-13- trans-prostenoic acid1046 1021 9-oxo-15-hydroxy-17,17-di- methyl-2-ethyl-13-trans- prostenoic acid1047 1022 9-oxo-15-hydroxy-17,17-di- methyl-3,3-dimethyl-13- trans-prostenoic acid1048 1023 9-oxo-15-hydroxy-17,17-di- methyl-3-oxa-13-trans-pro- stenoic acid1049 1024 9-oxo-15-hydroxy-17,17-di- methyl-7-nor-13-trans-pro- stenoic acid1050 1025 9-oxo-15-hydroxy-17,17-di- methyl-2-fluoro-13-trans- prostenoic acid1051 1027 9-oxo-15-hydroxy-17,17-di- methyl-2-methyl-13-trans- prostenoic acid1052 1028 9-oxo-15-hydroxy-17,17-di- methyl-10a-homo-13-trans- prostenoic acid1053 1029 9-oxo-15-hydroxy-17,17-di- methyl-3-thia-13-trans-pro- stenoic acid1054 1030 9-oxo-15-hydroxy-17,17-di- methyl-5-cis,13-trans-pro- stadienoic acid1055 1031 9-oxo-15-hydroxy-17,17-di- methyl-2-phenyl-13-trans- prostenoic acid______________________________________

EXAMPLES 1056-1081

Treatment of the 9-oxo- acids and esters of Table 18 below with lithium perhydro-9b-boraphenalyl hydride by the procedure of Example 737 provides the 9.alpha.,15-dihydroxy-16,16-dimethyl or 17,17-dimethyl-13-trans-prostenoic acid of the Table.

TABLE 18______________________________________ Product 9.alpha.-15-Dihydroxy-16,- Starting 9-oxo 16-dimethyl or 17,17-di-Exam- derivative of methyl-13-trans-prostenoicple Example acids or esters______________________________________1056 1032 9.alpha.,15-dihydroxy-16,16-di- methyl-13-trans-prostenoic acid1057 1033 9.alpha.,15-dihydroxy-16,16-di- methyl-7a,7b-bishomo-13- trans-prostenoic acid1058 1034 9.alpha.,15-dihydroxy-16,16-di- methyl-2-ethyl-13-trans- prostenoic acid1059 1035 9.alpha.,15-dihydroxy-16,16-di- methyl-3,3-dimethyl-13- trans-prostenoic acid1060 1036 9.alpha.,15-dihydroxy-16,16-di- methyl-3-oxa-13-trans-pro- stenoic acid1061 1037 9.alpha.,15-dihydroxy-16,16-di- methyl-7-nor-13-trans-pro- stenoic acid1062 1038 9.alpha.,15-dihydroxy-16,16-di- methyl-2-fluoro-13-trans- prostenoic acid1063 1013 n-decyl 9.alpha.,15-dihydroxy-16,- 16-dimethyl-13-trans-proste- noate1064 1039 9.alpha.,15-dihydroxy-16,16-di- methyl-2-methyl-13-trans- prostenoic acid1065 1040 9.alpha.,15-dihydroxy-16,16-di- methyl-10a-homo-13-trans- prostenoic acid1066 1041 9.alpha.,15-dihydroxy-16,16-di- methyl-3-thia-3-trans-pro- stenoic acid1067 1042 9.alpha.,15-dihydroxy-16,16-di- methyl-5-cis,13-trans- prostadienoic acid1068 1043 9.alpha.,15-dihydroxy-16,16-di- methyl-2-phenyl-13-trans- prostenoic acid1069 1044 9.alpha.,15-dihydroxy-17,17-di- methyl-13-trans-prostenoic acid1070 1045 9.alpha.,15-dihydroxy-17,17-di- methyl-7a,7b-bishomo-13- trans-prostenoic acid1071 1046 9.alpha.,15-dihydroxy-17,17-di- methyl-2-ethyl-13-trans- prostenoic acid1072 1047 9.alpha.,15-dihydroxy-17,17-di- methyl-3,3-dimethyl-13- trans-prostenoic acid1073 1048 9.alpha.,15-dihydroxy-17,17-di- methyl-3-oxa-13-trans-pro- stenoic acid1074 1049 9.alpha.,15-dihydroxy-17,17-di- methyl-7-nor-13-trans-pro- stenoic acid1075 1050 9.alpha.,15-dihydroxy-17,17-di- methyl-2-fluoro-13-trans- prostenoic acid1076 1026 n-decyl 9.alpha.,15-dihydroxy- 17,17-dimethyl-13-trans- prostenoate1077 1051 9.alpha.,15-dihydroxy-17,17-di- methyl-2-methyl-13-trans- prostenoic acid1078 1052 9.alpha.,15-dihydroxy-17,17-di- methyl-10a-homo-13-trans- prostenoic acid1079 1053 9.alpha.,15-dihydroxy-17,17-di- methyl-3-thia-13-trans- prostenoic acid1080 1054 9.alpha.,15-dihydroxy-17,17-di- methyl 5-cis,13-trans-pro- stadienoic acid1081 1055 9.alpha.,15-dihydroxy-17,17-di- methyl-2-phenyl-13-trans- prostenoic acid______________________________________

EXAMPLE 1082

A solution of methyl 9-oxo-15-hydroxy-5-cis,13-trans,17-cis-prostatrienoate (Example 374) in tetrahydrofuran is added to 1.1 equivalent of lithium perhydro-9b-boraphenyalyl hydride in tetrahydrofuran at -78.degree. C. After 30 minutes equal volumes of 5% aqueous sodium carbonate and 30% aqueous hydrogen peroxide is added, and the solution is stirred 15 minutes. The solution is diluted with water and extracted with ether. The organic phase is dried (magnesium sulfate) and concentrated in vacuo to give methyl 9.alpha.,15.alpha.-dihydroxy-5-cis,13-trans,17-cis-prostatrienoate, contaminated with methyl 9.beta.,15.alpha.-dihydroxy-5cis,13trans,17cis-prostatienoate. The crude mixture of esters is dissolved in methylene chloride and added to a refluxing solution of 1.2 equivalents of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in methylene chloride. After 5 hours, the solution is cooled and filtered. The filtrate is diluted with two volumes of ether, extracted with 5% aqueous sodium carbonate and dried with magnesium sulfate. The solution is concentrated in vacuo to give methyl 9.alpha.-hydroxy-15-oxo-5cis-13-trans, 17cis-prostatrienoate and 9.beta.-hydroxy-15-oxo-5cis, 13trans,17cis-prostatrienoate. The crude material is dissolved in benzene and 1.2 equivalents each of triethylamine and trimethylsilyl chloride is added. The triethylamine hydrochloride is removed by filtration and the solution is concentrated in vacuo to give methyl 9.alpha.-trimethylsiloxy-15-keto-5cis,13trans,17cis-prostatrienoate and the corresponding 9.beta.-trimethylsiloxy derivative.

The siloxy derivatives are dissolved in ether at 0.degree. C. and 1.05 equivalents of methyl magnesium bromide in ether is added. After the reaction is complete, the solution is poured into saturated aqueous ammonium chloride and extracted with ether. The ether is dried and concentrated in vacuo to give methyl 9.alpha.-trimethylsiloxy-15.alpha.-hydroxy-15.beta.-methyl-5cis,13trans,17cis-prostatrienoate, and methyl 9.alpha.-trimethylsiloxy- 15.beta.-hydroxy-15.alpha.-methyl-5cis,13trans,17cis-prostatrienoate, methyl 9.beta.-trimethylsiloxy-15.alpha.-hydroxy-15.beta.-methyl-5cis,13trans,17cis-prostatrienoate, and methyl 9.beta.-trimethylsiloxy-15.beta.-hydroxy-15.alpha.-methyl 5cis,13trans,17-'cis-prostatrienoate. Hydrolysis of the siloxy functions of each in a solution of methanol, water and acetic acid (approximately 10:1:1, 3 hours ambient temperatures) and gives methyl 9.alpha.,15.alpha.-dihydroxy-15.beta.-methyl-5cis-13trans,17cis-prostatrienoate, methyl 9.alpha.,15.beta.-dihydroxy-15.alpha.-methyl-5cis,13trans, 17cis-prostatrienoate, methyl 9.beta.,15.alpha.-dihydroxy-15.beta.-methyl-5cis,13trans,17cis-prostatrienoate and methyl 9.beta.,15.beta.-dihydroxy-15.alpha.-methyl-5-cis,13trans,17cis-prostatrienoate separated by dry column chromatograpy and further purified by partition chromatography saponification (method of Example 122) of each component in 50% aqueous methanol with potassium hydroxide gives the corresponding free acids.

Treatment of a solution of methyl 9.alpha.,15.alpha.-dihydroxy-15.beta.-methyl-5cis,13trans,17cis-prostatrienoate in methylene chloride with Collins reagent (CrO.sub.3 -pyridine in methylene chloride) gives methyl 9-oxo-15.alpha.-hydroxy-15.beta.-methyl-5cis, 13trans,17cis-prostatrienoate, saponification of which (method of Example 122) gives 9-oxo-15.alpha.-hydroxy-15.beta.-methyl-5cis,13trans,17cis-prostatrienoate acid.

Similar treatment of the 15.beta.-hydroxy esters gives methyl 9-oxo-15.beta.-hydroxy-15.alpha.-methyl-5cis,13trans,17cis-prostatrienoate which gives 9oxo-15.beta.-hydroxy-15.alpha.-methyl-5cis,13trans,17cis-prostatrienoic acid after saponfication.

EXAMPLES 1083-1101

Treatment of the 9-oxo-15-hydroxy prostenoic esters of Table 18A below by the sequence of reactions described in Example 1082 is productive of the 9.alpha.,15-dihydroxy-15-methyl and the 9-oxo-15-hydroxy-15-methyl products of the table. Also prepared in the course of these reaction sequences are the ethyl (methyl for Example 1101) esters corresponding to the products of the table, the 9.beta.-hydroxy derivatives corresponding to the listed 9.alpha.-hydroxy derivatives and their ethyl esters, the 15-keto derivatives of the 9.alpha.- and 9.beta.-hydroxy compounds corresponding to the 9-oxo starting compounds, and the 9.alpha.- or 9.beta.-trimethyl-silyloxy ethyl esters of the 15-keto and 15-hydroxy-15-methyl compounds. In all cases both the 15.alpha.-hydroxy-15.beta.-methyl and the 15.beta.-hydroxy-15.alpha.-methyl products and intermediates are obtained. These epimers are separable by chromatographic procedures.

TABLE 18A______________________________________ Starting 9-oxo-Ex- 15-hydroxy-ester Product 15-hydroxy-ample of Example 15-methyl derivative______________________________________1083 260 9-oxo-15-methyl-15- hydroxy-2-ethyl-13- trans-prostenoic acid and 9.alpha.,15-dihydroxy- 15-methyl-2-ethyl-13- trans-prostenoic acid1084 261 9-oxo-15-hydroxy-15- methyl-3,3-dimethyl- 13-trans-prostenoic acid and 9.alpha.,15-di- hydroxy-15-methyl- 3,3-dimethyl-13-trans- prostenoic acid1085 262 9-oxo-15-hydroxy-15- methyl-3-oxa-13-trans- prostenoic acid and 9.alpha.,15-dihydroxy-15- methyl-3-oxa-13-trans- prostenoic acid1086 264 9-oxo-15-hydroxy-15- methyl-2-fluoro-13- trans-prostenoic acid and 9.alpha.,15-dihydroxy- 15-methyl-2-fluoro- 13-trans-prostenoic acid1087 266 9-oxo-15-hydroxy-15- methyl-2-phenyl-13- trans-prostenoic acid and 9.alpha.,15-dihydroxy- 15-methyl-2-phenyl- 13-trans-prostenoic acid1088 267 9-oxo-15-hydroxy-15- methyl-2-methyl-13- trans-prostenoic acid and 9.alpha.,15-dihydroxy- 15-methyl-2-methyl- 13-trans-prostenoic acid1089 268 9-oxo-15-hydroxy-15- methyl-10a-homo-13- trans-prostenoic acid and 9.alpha.,15-dihydroxy- 15-methyl-10a-homo- 13-trans-prostenoic acid1090 272 9-oxo-15-hydroxy-15- methyl-3-thia-13- trans-prostenoic acid and 9.alpha.,15-dihydroxy- 15-methyl-3-thia-13- trans-prostenoic acid1091 362 9-oxo-15-hydroxy-15- methyl-3-thia-20- methyl-13-trans-pro- stenoic acid and 9.alpha.,15- dihydroxy-15-methyl-3- thia-20-methyl-13- trans-prostenoic acid1092 343 9-oxo-15-hydroxy-15- methyl-2,20-dimethyl- 13-trans-prostenoic acid and 9.alpha.,15-di- hydroxy-15-methyl- 2,20-dimethyl-13- trans, prostenoic acid1093 323 9-oxo-15-hydroxy-15- methyl-3-oxa-20-methyl- 13-trans-prostenoic acid and 9.alpha.,15-di- hydroxy-15-methyl-3- oxa-20-methyl-13- trans-prostenoic acid1094 284 9-oxo-15-hydroxy-15- methyl-13-trans,17- cis-prostadienoic acid and 9.alpha.,15-dihydroxy-15- methyl-13-trans,17- cis-prostadienoic acid1095 287 9-oxo-15-hydroxy-15- methyl-7a,7b-bishomo- 13-trans, 17-cis-pro- stadienoic acid and 9a, 15-dihydroxy-15-methyl- 7a,7b-bishomo-13- trans, 17-cis-prosta- dienoic acid1096 290 9-oxo-15-hydroxy-15- methyl-3-oxa-13-trans, 17-cis-prostadienoic acid and 9a,15-dihydro- xy-15-methyl-3-oxa-13- trans, 17-cis-prosta- dienoic acid1097 291 9-oxo-15-hydroxy-15- methyl-7-nor-13-trans, 17-cis-prostadienoic acid and 9.alpha.,15-di- hydroxy-15-methyl-7- nor-13-trans, 17-cis- prostadienoic acid1098 292 9-oxo-15-hydroxy-15- methyl-2-fluoro-13- trans, 17-cis-prosta- dienoic acid and 9.alpha., 15-dihydroxy-15-methyl- 2-fluoro-13-trans, 17-cis-prostadienoic acid1099 293 9-oxo-15-hydroxy-15- methyl-7a-homo-13- trans, 17-cis-prosta- dienoic acid and 9.alpha.,15- dihydroxy-15-methyl-7a- homo-13-trans, 17-cis- prostadienoic acid1100 300 9-oxo-15-hydroxy-15- methyl-3-thia-13-trans, 17-cis-prostadienoic acid and 9.alpha.,15-di- hydroxy-15-methyl-3- thia-13-trans, 17-cis- prostadienoic acid1101 733 9-oxo-15-hydroxy-15- methyl-13-cis, 17-cis- prostadienoic acid and 9.alpha.,15-dihydroxy-15- methyl-13-cis, 17-cis prostadienoic acid______________________________________ *methyl 15-hydroxy-9-oxo-13-cis-prostenoate only

EXAMPLES 1102-1104

Hydrogenation of the 13-trans-prostenoic acids listed in Table 19 below by the procedure described in Example 699 is productive of the product prostanoic acids of the table. The product epimers are separable by chromatographic procedures.

TABLE 19______________________________________ Starting 15-hy- droxy-15-methyl- Product 15-hydroxy-Ex- 13-trans-pros- 15-methyl-prostanoicample tenoic acid acid______________________________________1102 9-oxo-15-hydroxy- 9-oxo-15-hydroxy-15- 15-methyl-3-oxa- methyl-3-oxa-prostanoic 13-trans-pros- acid tenoic acid (Example 1085)1103 9.alpha.,15-dihydroxy- 9.alpha.,15-dihydroxy-15- 15-methyl-3-oxa- methyl-3-oxa-pros- 13-trans-pros- tanoic acid tenoic acid (Example 1085)1104 9-oxo-15-hydroxy- 9-oxo-15-hydroxy-15- 15-methyl-10a- methyl-10a-homo-pros- homo-13-trans- tanoic acid prostenoic acid (Example 1089)______________________________________

EXAMPLE 1105

Preparation of all cis-2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanol

A solution of 1.42 g. (10.0 moles) of all-cis-5-hyroxy-2,3-oxidocyclopentylacetaldehyde-lactol (E. J. Corey and R. Noyori, Tetrahedron Letters, 1970, 311) in 5 ml. of DMSO is added to a stirred solution with the Wittig reagent [E. J. Corey et al, JACS, 91 5675 (1969)] also Example 1108 prepared from 13.3 g. (30 moles) of 4-carboxybutyltrphenylphosphonium bromide 2.52 g. (60 moles) of 57% sodium hydride dispersion, and 70 ml. of DMSO at 16.degree. C. during 1 minute.

The solution is stirred at ambient temperature for 20 hours and poured into a stirred mixture of methylene chloride, ice, and hydrochloric acid. The organic phase is separated, and the aqueous phase is extracted with methylene chloride, saturated with sodium chloride, and extracted with ether. The combined organic extracts are partitioned with sodium bicarbonate. The aqueous basic extract is acidified with dilute HCl, saturated with sodium chloride, and extracted with ethyl acetate. The extract is washed with brine, dried over magnesium sulfate, and concentrated to give the crude title compound as an orange oil.

EXAMPLE 1106

Preparation of all-cis-2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanone

To a stirred solution of ca. 1.6 moles of crude all-cis-2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanol (Example 1105) in 1.6 ml. of ether is added 1.6 ml. of 4.0 N chromic acid in 4N sulfuric acid at 0.degree. C. during 9 minutes. After stirring for 5 minutes at 0.degree. C. the solution is diluted with brine, ether, and ethyl acetate. The organic phase is treated with isopropanol, washed with brine and dried over magnesium sulfate. Evaporation of the solvent gives the subject compound as an oil.

EXAMPLE 1107

Preparation of 2-(6-carboxy-2-cis-hexenyl)-4-hydroxycyclopent-2-en-1-one

A solution of 1.0mmole of all-cis-2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanone (Example 1106) and 3.0 mmoles of sodium carbonate in 15 ml. of water is allowed to stand at room temperature for 3 hours. The solution is acidified with HCl, saturated with sodium chloride, and extracted with ether. The extract is washed with brine, dried over magnesium sulfate, and concentrated to give a mixture of the title compound and the isomeric compound, 2-(6-carboxy-2-cis-hexenyl)-3-hydroxycyclopent-4-en-1-one. Further treatment of this mixture with N/10 sodium hydroxide at room temperature for 30 minutes causes the rearrangement of the latter isomer to the title compound, which is isolated from basic solution as above.

EXAMPLE 1107a

Preparation of 2-(6-carboxy-2-cis-hexenyl)-4-hydroxycyclopent-2-en-1-one

Treatment of cis-anti-cis-5-hydroxy-2,3-oxidocyclopentylacetaldehyde-.gamma.-lactol (E. J. Corey and R. Noyori Tetrahedron Letters, 1970, 311) with 4-carboxybutyltriphenylphosphonium bromide as described in Example 1105 is productive of 2.beta.-(6-carboxy-2-cis-hexenyl)-3.alpha.,4.alpha.-oxidocyclopentan-1.beta.-ol which on on oxidation by the method of Example 1106 provides 2.beta.-(6-carboxy-2-cis-hexenyl)-3.alpha.,4.alpha.-oxidocyclopentanone, which in time on treatment with aqueous base by the procedure of Example 1107 furnishes the subject compound.

EXAMPLE 1108

Preparation of 4-carboxybutyltriphenylphosphonium bromide

A mixture of 103 g. of 5-bromovalevic acid and 152 g. of triphenylphosphine in 400 ml. of acetonitrile is refluxed for 48 hours, cooled, diluted with 100 ml. of benzene and allowed to crystallize. The crystals are filtered, washed with benzene and ether, to yield colorless material, m.p. 207.degree.-209.degree. C.

EXAMPLES 1109-1111

Treatment of the indicated .omega.-bromoalkanoic acids of Table 20 below with tripenylphosphine by the method described in Example 1108 produces the phosphonium bromides of the table.

TABLE 20______________________________________Ex- Starting .omega.-bromo- Productample alkanone acid Phosphonium bromide______________________________________1109 4-bromo-n-butyric 3-carboxypropyltri- acid phenylphosphonium bromide1110 6-bromo-n-hexanoic 5-carboxypentyltri- acid phenylphosphonium bromide1111 7-bromo-n-hepta- 6-carboxyhexyltri- noic acid phenylphosphonium bromide______________________________________

EXAMPLES 1112-1114

Treatment of all cis-5-hydroxy-2,3-oxidocyclopentylacetaldehyde-.gamma.-lactol with the Wittig reagent prepared from the indicated phosphonium bromides of Table 21 below, all by the procedure of Example 1105 is productive of the product compounds of the table.

TABLE 21______________________________________ Reagent phos-Ex- phonium bromide Productample of Example 3,4-oxidocyclopentanol______________________________________1112 1109 all cis-2-(5-carboxy-2- cis-pentenyl)-3,4-oxi- docyclopentan-1-ol1113 1110 all cis-2-(7-carboxy-2- cis-heptenyl)-3,4-oxi- docyclopentan-1-ol1114 1111 all cis-2-(8-carboxy-2- cis-octenyl)-3,4-oxi- docyclopentan-1-ol______________________________________

EXAMPLES 1115-1117

Oxidation of the cyclopentanols indicated in Table 22 below by the method described in Example 1106 furnishes the corresponding product 3,4-oxidocyclopentanones of the table.

TABLE 22______________________________________ Starting cyclo- ProductEx- pentan-1-ol of 3,4-oxidocyclopent-ample Example an-1-one______________________________________1115 1112 all cis-2-(5-carboxy- 2-cis-pentenyl)-3,4- oxidocyclopentan-1- one1116 1113 all cis-2-(7-carboxy- 2-cis-heptenyl)-3,4- oxidocyclopentan-1- one1117 1114 all cis-2-(8-carboxy- 2-cis-octenyl)-3,4- oxidocyclopentan-1- one______________________________________

EXAMPLES 1118-1120

Alkaline treatment of the 3,4-oxidocyclopentanones of Table 23 below by the process described in Example 1107 is productive of the 4-hydroxycyclopentenones of the table.

TABLE 23______________________________________ Starting 3,4- oxidocyclo- ProductEx- pentanone of 4-hydroxycyclo-ample Example pent-2-en-1-one______________________________________1118 1115 2-(5-carboxy-2- cis-pentenyl)-4- hydroxycyclo- pent-2-en-1-one1119 1116 2-(7-carboxy-2- cis-heptenyl)- 4-hydroxycyclo- pent-2-en-1-one1120 1117 2-(8-carboxy-2- cis-octenyl)-4- hydroxycyclo- pent-2-en-1-one______________________________________

EXAMPLES 1121-1124

Treatment of the 4-hydroxycyclopent-2-en-1-ones listed in Table 24 below with dihydropyran (in the manner of Example 95) is productive of the corresponding bis-tetrahydropyranyl ether-ester of the table.

TABLE 24______________________________________ Starting 4-hy- droxycyclopent- ProductEx- 2-en-1-one of bis-tetrahydropyranylample Example ether-ester______________________________________1121 1107 4-tetrahydropyranyloxy- 2-(6-carbotetrahydro- pyranyloxy-2-cis-hexenyl) cyclopent-2-en-1-one1122 1118 4-tetrahydropyranyloxy- 2-(5-carbotetrahydro- pyranyloxy-2-cis-pent- enyl)cyclopent-2-en-1- one1123 1119 4-tetrahydropyranyloxy- 2-(7-carbotetrahydro- pyranyloxy-2-cis-heptenyl)- cyclopent-2-en-1-one1124 1120 4-tetrahydropyranyloxy- 2-(8-carbotetrahydro- pyranyloxy-2-cis-octenyl)- cyclopent-2-en-1-one______________________________________

EXAMPLES 1125-1130

Treatment of the 4-hydroxycyclopent-2-en-1-ones listed in Table 25 below with the indicated trialkylsilyl chloride by the method described in Example 958 is productive of the bis-trialkylsilyl ether-esters of the table.

TABLE 25__________________________________________________________________________ Starting 4-hydroxy- cyclopentenone of Trialkylsilyl- ProductExample Example chloride bis-trialkylsilyl ether-ester__________________________________________________________________________1125 1107 (CH.sub.3).sub.3 SiCl 4-trimethylsiloxy-2-(6-carbotrimethyl- siloxy-2-cis-hexenyl)cyclopent-2-en-1-one1126 1118 (CH.sub.3).sub.3 SiCl 4-trimethylsiloxy-2-(5-carbotrimethyl- siloxy-2-cis-pentenyl)cyclopent-2-en-1-one1127 1119 (CH.sub.3).sub.3 SiCl 4-trimethylsiloxy-2-(7-carbotrimethyl- siloxy-2-cis-heptenyl)cyclopent-2-en-1-one1128 1120 (CH.sub.3).sub.3 SiCl 4-trimethylsiloxy-2-(8-carbotrimethyl- siloxy-2-cis-octenyl)cyclopent-2-en-1-one1130 1107 dimethyliso- 4-dimethylisopropylsiloxy-2-(6-carbodi- propyl silyl methylisopropylsiloxy-2-cis-hexenyl)cyclo- chloride pent-2-en-1-one__________________________________________________________________________

EXAMPLE 1131

Preparation of 1-oxo-2-hydroxy-bicyclo[3.3.0]oct-4-ene

A solution of 6.2 g. (50 mole) of the lactone of cis-2-hydroxycyclopent-4-ene-1-acetic acid [P.A. Grieco, J. Org. Chem., 37, 2363 (1972)] in 350 ml. toluene (dried over molecular sieves) is cooled to -75.degree. C. and treated dropwise under nitrogen with 84 ml. 0.89 M diisobutyl aluminum hydride (10.55 g., 74 mole) over a period of about one hour maintaining the temperature at -74.degree. .+-. 2.degree. C. The resulting clear solution is stirred at -75.degree. C. for two hours and poured with stirring into a mixture of 15 ml. of concentrated hydrochloric acid and 300 ml. of ice water. The mixture is stirred while warming to room temperature. The layers are separated and the aqueous layer is treated with salt and extracted with three small portions of ether. The combined organic portions are dried over sodium sulfate and evaporated at reduced pressure (75.degree. C. water bath) to yield the product (homogeneous by thin layer chromatography) as a pale yellow mobile liquid.

EXAMPLE 1132

Preparation of 1-hydroxy-2-(6-carboxy-2-cis-hexenyl)cyclopent-3-ene

A solution of the sodium salt of dimethyl sulfoxide is prepared by stirring under nitrogen a mixture of 160 ml. dry dimethyl sulfoxide (dried over molecular sieves and a few pellets of calcium hydride) with 6.0 g. (0.25 mole) of sodium hydride (prepared by washing 10.5 g. of 57% sodium hydride dispersion in mineral oil with two 30 ml. portions of hexane.) The mixture is warmed with stirring at 75.degree. C. (oil bath) for 2.5 hours.

This solution is added over about five minutes to a solution under nitrogen of 44 grams (0.1 mole) of 4-carboxybutyltriphenylphosphonium bromide (Example 1108) in 180 ml. of dry dimethyl sulfoxide. The resulting dark reddish brown solution is stirred for ten minutes, cooled to room temperature and treated with a solution of crude 1-oxa-2-hydroxybicyclo[3.3.0]oct-4-ene (6.2 g., 50 mole) (Example 1131) in 20 ml. of anhydrous dimethyl sulfoxide. The resulting solution is stirred 16 hours and then treated with 250 ml. of ice water.

This brown solution is extracted with two portions of ether to remove neutral material then made strongly acidic with hydrochloric acid. The solution is extracted into four 100 ml. portions of methylene chloride. The combined methylene chloride extracts are washed with water, then extracted with four 100 ml. portions of 5% sodium bicarbonate. The combined aqueous extracts are washed with methylene chloride and made acidic to Congo Red with concentrated hydrochloric acid. The mixture is extracted with three 100 ml. portions of methylene chloride. The organic extracts are combined, dried over sodium sulfate and the solvent is evaporated at reduced pressure. The residue (an oily solid) is extracted several times with ether and the ethereal extracts are combined and evaporated at reduced pressure to yield the crude product as a dark oil. The product is purified by chromatography on silica gel, eluting with ether. The product is a colorless liquid.

EXAMPLE 1133

Preparation of 2-(6-carboxy-2-cis-hexenyl)cyclopent-3-en-1-one

A solution of 3.2 g. (0.5 mole) of 1-hydroxy-2-(6-carboxy-2-cis-hexenyl)cyclopent-3-ene (Example 1132) in 60 ml. of reagent acetone is treated dropwise with a total of 6 ml. of 8N chromic acid in sulfuric acid at 0.degree. C. The oxidation is rather slow. The resulting mixture is dissolved in 200 ml. of water and the solution is extracted with six 50 ml. portions of ether. The combined ethereal extracts are dried over sodium sulfate and the solvent is evaporated at reduced pressure to yield the product as a yellow oil.

EXAMPLE 1134

Preparation of 2-(6-carboxy-2-cis-hexenyl)cyclopent-2-en-1-one

A solution of 3 g. of crude 2-(6-carboxy-2-cis-hexenyl)cyclopent-3-ene-1-one (Example 1133) in 100 ml. of 2% sodium hydroxide is stirred at 80.degree. C. under nitrogen for 1.5 hours. The cooled solution is acidified to Congo Red and extracted into ether. The ethereal extracts are dried over sodium sulfate and evaporated at reduced pressure to afford the product.

EXAMPLE 1135-1137

Treatment of 1-oxa-2-hydroxy-bicyclo[3.3.0]oct-4-ene by the procedure described in Example 1132 with the ylids derived from the phosphonium bromides listed in Table 26 below furnishes the product 1-hydroxy-cyclopent-3-enes of the table.

TABLE 26______________________________________ Product Starting phos- 1-hydroxy-2-(.omega.-carboxy-Ex- phonium bromide 2-cis-alkenyl)cyclopent-ample of Example 3-enes______________________________________1135 1109 1-hydroxy-2-(5-carboxy- 2-cis-pentenyl)cyclo- pent-3-ene1136 1110 1-hydroxy-2-(7-carboxy- 2-cis-heptenyl)cyclo- pent-3-ene1137 1111 1-hydroxy-2-(8-carboxy- 2-cis-octenyl)cyclo- pent-3-ene______________________________________

EXAMPLES 1138-1140

Oxidation of the 1-hydroxycyclopent-3-enes listed in Table 27 below by the procedure described in Example 1133 is productive of the product cyclopent-3-en-1-ones of the table.

TABLE 27______________________________________ Starting 1- Product hydroxycyclo- 2-(.omega.-carboxy-2-cis-Ex- pent-3-ene of alkenyl)cyclopent-3-ample Example en-1-one______________________________________1138 1135 2-(5-carboxy-2-cis- pentenyl)cyclopent-3- en-1-one1139 1136 2-(7-carboxy-2-cis- heptenyl)cyclopent-3- en-1-one1140 1137 2-(8-carboxy-2-cis- octenyl)cyclopent-3- en-1-one______________________________________

EXAMPLES 1141-1143

Base treatment according to the procedure described in Example 1134 of the cyclopent-3-ene-1-ones listed in Table 28 below is productive of the product cyclopent-2-en-1-ones of the table.

TABLE 28______________________________________ Starting 2-(.omega.- carboxy-2-cis- Product alkenyl)cyclo- 2-(.omega.carboxy-2-cis-Ex- pent-3-ene-1- alkenyl)cyclopent-ample one of Example 2-en-1-one______________________________________1141 1138 2-(5-carboxy-2-cis- pentenyl)cyclopent- 2-en-1-one1142 1139 2-(7-carboxy-2-cis- heptenyl)cyclopent- 2-en-1-one1143 1140 2-(8-carboxy-2-cis- octenyl)cyclopent- en-en-1-one______________________________________

EXAMPLES 1144-1146

Treatment of the listed 2-(.omega.-carboxy-2-cis-alkenyl)cyclopent-2-en-1-one of Table 29 below with diazomethane in the usual manner is productive of the product methyl esters of the table.

TABLE 29______________________________________ Product Starting car- 2-(.omega.-carbomethoxy-2-cis-Ex- boxylic acid alkenyl)cyclopent-2-en-ample of Example 1-one______________________________________1144 1141 2-(5-carbomethoxy-2-cis- pentenyl)cyclopent-2-en- 1-one1145 1142 2-(7-carbomethoxy-2-cis- heptenyl)cyclopent-2-en- 1-one1146 1143 2-(8-carbomethoxy-2-cis- octenyl)cyclopent-2-en- 1-one______________________________________

EXAMPLES 1147-1149

Treatment by the procedure of Example 120 of the cyclopentenones listed in Table 30 below with lithium diisobutylmethyl-(3-triphenylmethoxy-1-trans-5-cis-octadienyl) alanate, also prepared by the procedure of Example 120 from 3-triphenylmethoxy-cis-5-en-octyne-1 (Example 139), diisobutylaluminum hydride and methyl lithium, followed by hydrolysis of the intermediate 15-triphenylmethoxy derivatives by treatment with acetic acid-tetrahydrofuran-water (4:2:1) in the manner of Example 121, and then by saponification of the intermediate methyl esters by the process described in Example 122 is productive of the product prostatrienoic acids of the table.

TABLE 30______________________________________ Starting 2-(.omega.- carbomethoxy-2- Product cis-alkenyl)- 9-oxo-15-hydroxy-5-Ex- cyclopent-2-en- cis,13-trans,17-cis-ample 1-one of Example prostatrienoic acids______________________________________1147 1144 9-oxo-4-nor-15-hydroxy- 5-cis-13-trans-17- cis-prostatrienoic acid1148 1145 9-oxo-4a-homo-15-hydro- xy-5-cis-13-trans-17- cis-prostatrienoic acid1149 1146 9-oxo-4a-bishomo-15-hy- droxy-5-cis-13-trans- 17-cis-prostatrienoic acid______________________________________

EXAMPLES 1150-1159

Treatment of the ether-ester blocked 4-oxycyclopent-2-en-1-ones listed in Table 31 below with lithium trimethyl[3-(p-anisyldiphenylmethoxy)-trans-1-octenyl] according to the procedure described in Example 960 is productive of the 9-oxo-11.alpha.,15-dihydroxy-5-cis, 13-transprostadienoic acids of the table as well as of the corresponding 15-epi derivatives, separable from the listed 15-normal derivatives by chromatography.

TABLE 31______________________________________ Starting blocked Product 4-oxycyclopent- 9-oxo-11.alpha.,15-dihydroxy-Ex-2-en-1-one of5-cis, 13-trans-pros-ample Example tadienoic acids______________________________________1150 1121 9-oxo-11.alpha., 15-dihydroxy- 5-cis, 13-trans-prosta- dienoic acid (prosta- glandin E.sub.2)1151 1125 9-oxo-11.alpha., 15-dihydroxy- 5-cis, 13-trans-prosta- dienoic acid (prosta- glandin E.sub.2)1152 1130 9-oxo-11.alpha., 15-dihydroxy- 5-cis, 13-trans-prosta- dienoic acid (prosta- glandin E.sub.2)1153 1122 9-oxo-11.alpha., 15-dihydroxy- 4-nor-5-cis, 13-trans- prostadienoic acid1154 1126 9-oxo-11.alpha., 15-dihydroxy- 4-nor-5-cis, 13-trans- prostadienoic acid1155 1123 9-oxo-11.alpha., 15-dihydroxy- 4a-homo-5-cis, 13-trans- prostadienoic acid1156 1127 9-oxo-11.alpha., 15-hydroxy- 4a-homo-5-cis, 13-trans- prostadienoic acid1158 1124 9-oxo-11.alpha., 15-dihydroxy- 4a, 4b-homo-5-cis, 13- trans-prostadienoic acid1159 1128 9-oxo-11.alpha., 15-dihydroxy- 4a, 4b-homo-5-cis, 13- trans-prostadienoic acid______________________________________

EXAMPLE 1160-1169

Treatment by the procedure described in Example 123 of the ether-ester blocked 4-oxycyclopent-2-en-1-ones listed in Table 32 below with lithium diisobutylmethyl(3-triphenylmethoxy-1-trans-5-cis-octadienyl)alanate, prepared from 3-triphenylmethoxy-cis-5-en-octyne-1- (Example 139) by the procedure of Example 120, followed by the cleavage of blocking groups and isolation of products by the method described in Example 124 is productive of the 9-oxo-11.alpha.,15-dihydroxy-5-cis,13-trans,17-cis-prostatrienoic acids of the table; also formed are the corresponding 15-epi derivatives which are separable by chromatography from the listed 15-normal derivatives.

TABLE 32______________________________________ Starting blocked Product 4-oxycyclopent- 9-oxo-11.alpha., 15-dihydroxy-Ex- 2-en-1-one of 5-cis, 13-trans, 17-cis-ample Example prostatrienoic acids______________________________________1160 1121 9-oxo-11.alpha., 15-dihydroxy- 5-cis, 13-trans, 17- cis-prostatrienoic acid (prostaglandin E.sub.3)1161 1125 9-oxo-11.alpha., 15-dihydroxy- 5-cis,13-trans, 17-cis- prostatrienoic acid (prostaglandin E.sub.3)1162 1130 9-oxo-11.alpha., 15-dihydroxy- 5-cis, 13-trans, 17-cis- prostatrienoic acid (prostaglandin E.sub.3)1163 1122 9-oxo-11.alpha., 15-dihydroxy- 4-nor-5-cis, 13-trans, 17-cis-prostatrienoic acid1164 1126 9-oxo-11.alpha., 15-dihydroxy- 4-nor-5-cis, 13-trans, 17-cis-prostatrienoic acid1165 1123 9-oxo-11.alpha., 15-dihydroxy- 4a-homo-5-cis, 13- trans, 17-cis-prosta- trienoic acid1166 1127 9-oxo-11.alpha., 15-dihydroxy- 4a-homo-5-cis, 13- trans, 17-cis-prosta- trienoic acid1168 1124 9-oxo-11.alpha., 15-dihydroxy- 4a, 4b-bishomo-5-cis, 13-trans, 17-cis-prosta- trienoic acid1169 1128 9-oxo-11.alpha., 15-dihydroxy- 4a, 4b-bishomo-5-cis- 13-trans, 17-cis-prosta- trienoic acid______________________________________

EXAMPLE 1170

Preparation of 9-oxo-11.alpha.,15-dihydroxy-5-cis,13-cis-prostadienoic acid

Treatment in the manner described in Example 733 of 4-tetrahydropyranyloxy-2-(6-carbotetrahydropyranyloxy-2-cis-hexenyl)cyclopent-2-en-1-one (Example 1121) with the Grignard reagent prepared from magnesium and 1-bromo-3-triphenylmethoxy-trans-1-octene (Example 728) also as described in Example 733 in the presence of cuprous iodide tri-n-butylphosphine complex is productive after chromatography of prostaglandin E.sub.2 and 9-oxo-11.alpha.,15-dihydroxy-5-cis,13-cis-prostadienoic acid.

EXAMPLE 1171 and 1172

Treatment of the two 9-oxo derivative listed in Table 33 below with lithium perhydro-9b-boraphenalylhydride in the manner described in Example 737 furnishes the indicated 9.alpha.,15-dihydroxy-13-cis-prostenoic acids.

TABLE 33______________________________________ Starting 9-oxo- ProductEx- derivative of 9.alpha., 15-dihydroxy-13-cis-ample Example prostenoic acids______________________________________1171 736 9.alpha., 15-dihydroxy-13-cis- prostenoic acid1172 1170 9.alpha., 15-dihydroxy-5-cis- prostadienoic acid______________________________________

EXAMPLE 1173

Preparation of 1-bromo-4,4-dimethyl-3-tetrahydropyranyloxy-trans-1-octene

To an ice cooled solution of 3.5 g. (50 moles) of 2-methyl-2-butene in 25 ml. of tetrahydrofuran under an inert atmosphere is added 25 ml. of 1 M diborane in tetrahydrofuran dropwise over 10 minutes. The mixture is stirred at 0.degree.-5.degree. C. for 2 hours and then the solvent is removed under vacuum. The residue is dissolved in 20 ml. of carbon tetrachloride and to the resulting solution cooled to 0.degree. C. is added a solution of 5.25 g. (22 mole) of 4,4-dimethyl-3-tetrahydropyranyloxy-1-octyne (Example 995) in 10 ml. of carbon tetrachloride over 10 minutes. The cooling bath is removed and the mixture is allowed to stir at ambient temperature for 1.5 hours. The mixture is cooled to 0.degree. C. and a solution of 3.52 g. (22 moles) of bromine in 15 ml. of carbon tetrachloride is added over 10 minutes. The cooling bath is removed and the mixture is refluxed for 6 hours under an inert atmosphere. The mixture is cooled and poured into dilute sodium hydroxide solution. The organic phase is washed with water and saturated brine, dried (Na.sub.2 SO.sub.4), and evaporated. The residue is chromatographed upon silica gel and the title compound is isolated with 5% ethyl acetate in bezene.

EXAMPLE 1174

Preparation of 1-bromo-4,4-dimethyl-trans-1-octen-3-ol

A mixture of 3.19 g. (10 moles of 1-bromo-4,4-dimethyl-3-tetrahydropyranyloxy-trans-1-octene (Example 1173) and 90 ml. of 3:1:1 tetrahydrofuran-acetic acid-water is stirred at ambient temperatures for 20 hours. The solvent is evaporated in vacuo and the residue is chromatographed on silica gel. The title compound is isolated using 10-20% ethyl acetate in benzene.

EXAMPLE 1175

Preparation of 1-bromo-4,4-dimethyl-3-triphenylmethoxy-trans-1-octene

Treatment of 1.88 g. (8 moles) of 1-bromo-4,4-dimethyl-trans-1-octen-3-ol (Example 1174) with 2.58 g. (8 moles) of triphenylmethyl bromide in 20 ml. of pyridine and purification of Florisil .RTM., all as described in Example 728 gives the title compound.

EXAMPLE 1176

Preparation of 1-bromo-5,5-dimethyl-3-tetrahydropyranyloxy-trans-1-octene

Treatment of 7.15 g. (30 moles) of 5,5-dimethyl-3-tetrahydropyranyloxy-1-octyne (Example 999) with 33 moles of disiamylborane in carbon tetrachloride followed by 30 moles of bromide in carbon tetrachloride, refluxing the resulting mixture, and isolation by chromatography on silica gel, all as described in Example 1173 gives the title compound.

EXAMPLE 1177

Preparation of 1-bromo-5,5-dimethyl-trans-1-octen-3-ol

Treatment of 7.35 g. (23 moles) of 1-bromo-5,5-dimethyl-3-tetrahydropyranyloxy-trans-1-octene (Example 1176) with 200 ml. of 3:1:1 tetrahydrofuran-acetic acid-water and purification on silica gel all as described in Example 1174 gives the title compound.

EXAMPLE 1178

Preparation of 1-bromo-5,5-dimethyl-3-triphenylmethoxy-trans-1-octene

Treatment of 3.53 g. (15 moles) of 1-bromo-5,5-dimethyl-trans-1-octen-3-ol (Example 1177) with 4.85 g. (15 moles) of triphenylmethyl bromide in 35 ml. of pyridine and purification on Florisil .RTM., all as described in Example 728 gives the title compound.

EXAMPLE 1179

Preparation of 1-iodo-3-triphenylmethoxy-trans-1-octene

To a mixture of 0.650 g. (1691 mole) of sodium borohydride and 3.17 g. (45.2 moles) of 2-methyl-2-butene in 40 ml. of diglyme cooled to -5.degree. C. under an inert atmosphere is added over 15 minutes 3.24 g. (22.6 moles) of boron trifluoride ethereate and the resulting mixture is stirred at 0.degree. C. for 2 hours. To this mixture is then added over 5 minutes 8.32 g. (22.6 moles) of 3-triphenylmethoxy-1-octyne (Example 119) in 10 ml. of diglyme, the cooling bath is removed, and the mixture is stirred at ambient temperatures for 1.5 hours. The mixture is cooled to 0.degree. C. and 6.0 g. of finely divided anhydrous trimethylamine oxide is added over 10 minutes. The cooling bath is removed and the mixture is stirred at ambient temperatures for 0.5 hour. The mixture is then poured into 200 ml. of 15% sodium hydroxide solution, a solution of 16 g. (63 moles) of iodine in 20 ml. of tetrahydrofuran is added immediately, and the resulting mixture is stirred for 0.5 hour. The organic phase is separated and the aqueous phase is washed with ether. The combined organic phase and washings are decolorized with 5% sodium thiosulfate solution, washed with saturated brine, dried (Na.sub.2 SO.sub.4), and evaporated. The residue is dry-columned chromatographed upon alumina using hexane as eluent and the title compound is isolated as an oil.

EXAMPLE 1180

Preparation of 3-triphenylmethoxy-cis-oct-5-en-1-yne

Treatment of 22 g. of cis-oct-5-en-1-yne-3-ol, prepared according to the procedure of J. Fried, C.H. Lin., J.C. Sih, P. Dalven, G.F. Cooper, J. Amer. Chem. Soc., 94, 4342 (1972), with 58 g. of triphenylmethyl bromide in 100 ml. of pyridine and purification on Florisil .RTM., all as described in Example 728 gives the title compound.

EXAMPLE 1181

Preparation of 1-iodo-3-triphenylmethoxy-trans-1,cis-5-octadiene

Treatment of 20 g. of 3-triphenylmethoxy-cis-oct-5-en-1-yne with 55 moles of disiamylborane in diglyme, followed by trimethylamine-oxide, aqueous sodium hydroxide, and iodine, and purification of alumina, all as described in Example 1179, gives the title compound.

EXAMPLE 1182

Preparation of 1-bromo-3-triphenylmethoxy-trans-1,cis-5-octadiene

Treatment of 15 g. of 3-triphenylmethoxy-cis-oct-5-en-1-yne (Example 1180) with 41 moles of disiamylborane in tetrahydrofuran, replacing the solvent with carbontetrachloride, addition of 41 moles of bromine, and refluxing the mixture, all as described in Example 1173, and purification of the material upon Florisil .RTM. as described in Example 728 gives the title compound.

EXAMPLE 1183

Preparation of 1-iodo-3-triphenylmethoxy-trans-1-decene

Treatment of 3-triphenylmethoxy-1-decyne (Example 129) with disamylborane, trimethylamine oxide and iodine by the procedure described in Example 1179 is productive of the subject compound.

EXAMPLE 1184

Preparation of 1-iodo-3-triphenylmethoxy-trans-1-nonene

Treatment of 3-triphenylmethoxy-1-nonyne (Example 128) with disiamylborane, trimethylamine oxide and iodine by the process described in Example 1179 is productive of the subject compound.

EXAMPLE 1185

Preparation of 1-bromo-3-triphenylmethoxy-trans-1-decene

Treatment of 3-triphenylmethoxy-1-decyne (Example 129) with disiamylborane and the bromide by the procedure described in Example 1173 is productive of the title compound.

EXAMPLE 1186

Preparation of 1-bromo-3-triphenylmethoxy-trans-1-nonene

Treatment of 3-triphenylmethoxy-1-nonyne (Example 128) with disiamylborane and the bromine by the procedure described in Example 1173 is productive of the title compound.

EXAMPLE 1187

Preparation of the Grignard reagent of 1-bromo-3-triphenylmethoxy-trans-1-octene at 33.degree. C.

To a slurry of 0.585 g. (0.0241 g. atom) of magnesium and 5 ml. of tetrahydrofuran under an argon atomsphere is added 2 ml. of a solution of 7.536 (0.0168 mole) of 1-bromo-3-triphenylmethoxy-trans-1-octene (Example 728) in 10 ml. of tetrahydrofuran. The mixture is warmed to 35.degree. C. and reaction is initiated with 1 drop of methyl iodide. The reaction is allowed to exotherm to 37.degree. C. and then to cool to 33.degree. C. whereupon the remainder of the halide is added at a rate to maintain 33.degree. C. Afteer complete addition of the halide, the mixture is stirred at 33.degree. C. for 1 hour and is separated from the excess magnesium to yield a tetrahydrofuran solution of the title Grignard reagent.

EXAMPLE 1188

Preparation of 11-deoxy-8.beta.-methyl-prostaglandin E.sub.1 methyl ester, 11-deoxy-8.alpha.-methyl-8-iso-prostaglandin E.sub.1 methyl ester, methyl 15-hydroxy-8.beta.-methyl- 9-oxo-13-cis-prostenoate, and methyl 15-hydroxy-8.alpha.-methyl-9-oxo-8-iso-13-cis-prostenoate

The Grignard reagent, prepared as described in Example 1187 from 0.585 g. of magnesium, 7.536 g. of 1-bromo-3-triphenylmethoxy-trans-1-octene (Example 728), and 10 ml. of tetrahydrofuran, is added to an ice cooled solution of 3.76 g. of 2-(6-carbomethoxyhexyl)-2-cyclopentenone (Example 83) and 0.305 g. of copper (I) iodide-tri-n-butylphosphine complex in 10 ml. of tetrahydrofuran over 10 minutes under an inert atmosphere. The mixture is stirred with cooling of 0.5 hour and to it is then added 46 g. of methyl iodide. The cooling bath is removed and the mixture is stirred at ambient temperatures for 48 hours. The mixture is poured into saturated ammonium chloride solution and is extracted into ether. The organic phase is washed with saturated brine and is evaporated. The residue is heated to 80.degree. C. with 100 ml. of 80% aqueous acetic acid for 0.5 hour and the mixture is then evaporated to dryness. The residue is dry-column chromatography upon silica gel using 4:1 benzene-ethyl acetate as eluent to afford a mixture of 11-deoxy-8.beta.-methyl-prostaglandin E.sub.1 methyl ester and 11 -deoxy-8.alpha.-methyl-8-iso-prostaglandin E.sub.1 methyl ester and a mixture of methyl 15-hydroxy-8.beta.-methyl-9-oxo-13-cis-prostenoate and methyl 15-hydroxy-8.alpha.-methyl-9-oxo-8-iso-13-cis-prostenoate. Further separation of the 8.beta. and 8.alpha. isomers is accomplished by a combination of partition chromatography and thin layer chromatography.

EXAMPLES 1190 - 1205

Treatment by the preocedure of Example 1188 of the cyclopentenones listed in Table 34 below with the Grignard reagent, prepared as described in Example 1187 from the listed 1-bromo-3-triphenylmethoxy-1-trans-alkenes, and then with methyl iodide furnishes the product 8.alpha. and 8.beta. methyl prostenoates of the table. The products are all obtained via the corresponding 15-O-triphenylmethyl derivatives, which are hydrolytically cleaved as described in Example 1188.

TABLE 34__________________________________________________________________________ Starting 1-bromo-3- triphenylmethoxy-1- Starting cycloalkenene trans-alkene ofExample of Example Example Product 8-alkyl prostenoates__________________________________________________________________________1190 13 1175 ethyl 8-.beta.-methyl-9-oxo-15-hydroxy-16,16- dimethyl-13-trans-prostenoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-16,16- dimethyl-8-iso-13-trans-prostenoate ethyl 8.beta.-methyl-9-oxo-15-hydroxy-16,16- dimethyl-13-cis-prostenoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-16,16- dimethyl-8-iso-13-cis-prostenoate1191 13 1178 ethyl 8.beta.-methyl-9-oxo-15-hydroxy-17,17- dimethyl-13-trans-prostenoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-17,17- dimethyl-8-iso-13-trans-prostenoate ethyl 8.beta.-methyl-9-oxo-15-hydroxy-17,17- dimethyl-13-cis-prostenoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-17,17- dimethyl-8-iso-13-cis-prostenoate1192 13 1182 ethyl 8.beta.-methyl-9-oxo-15-hydroxy-13-trans, N 17-cis-prostadienoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-8-iso-13 - trans,17-cis-prostadienoate ethyl 8.beta.-methyl-9-oxo-15-hydroxy-13-cis, 17-cis-prostadienoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-8-iso- 13-cis, 17-cis-prostadienoate1193 13 1185 ethyl 8.beta.-methyl-9-oxo-15-hydroxy-20-ethyl- 13-trans-prostenoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-20-ethyl - 8-iso-13-trans-prostenoate ethyl 8.beta.-methyl-9-oxo-15-hydroxy-20-ethyl- a 13-cis-prostenoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-8-iso-20 - ethyl-13-cis-prostenoate1194 84 1186 decyl 8.beta.-methyl-9-oxo-15-hydroxy-20- methyl-13-trans-prostenoate decyl 8.alpha.-methyl-9-oxo-15-hydroxy-20- methyl-8-iso-13-trans-prostenoate decyl 8.beta.-methyl-9-oxo-15-hydroxy-20- methyl-13-cis-prostenoate decyl 8.alpha.-methyl-9-oxo-15-hydroxy-20- methyl-8-iso-13-cis-prostenoate1195 23 728 ethyl 8.beta.-methyl-9-oxo-15-hydroxy-7a,7b- bishomo-13-trans-prostenoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-7a,7b- bishomo-8-iso-13-trans-prostenoate ethyl 8.beta.-methyl-9-oxo-15-hydroxy-7a,7b- bishomo-13-cis-prostenoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-7a,7b- bishomo-8-iso-13-cis-prostenoate1196 31 1185 ethyl 8.beta.-methyl-9-oxo-15-hydroxy-2,20- bisethyl-13-trans-prostenoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-2,20- bisethyl-8-iso-13-trans-prostenoate ethyl 8.beta.-methyl-9-oxo-15-hydroxy-2,20- bisethyl-13-cis-prostenoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-2,20- bisethyl-8-iso-13-cis-prostenoate1197 46 1175 ethyl 8.beta.-methyl-9-oxo-15-hydroxy-3-oxa-16, 0 16-dimethyl-13-trans-prostenoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-3-oxa-16 , 16-dimethyl-8-iso-13-trans-prostenoate ethyl 8.beta.-methyl-9-oxo-15-hydroxy-3-oxa-16, F 16-dimethyl-13-cis-prostenoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-3-oxa-16 , 16-dimethyl-8-iso-13-cis-prostenoate1198 46 1182 ethyl 8.beta.-methyl-9-oxo-15-hydroxy-3-oxa- 13-trans,17-cis-prostadienoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-3-oxa- 8-iso-13-trans,17-cis-prostadienoate ethyl 8.beta.-methyl-9-oxo-15-hydroxy-3-oxa- 13-cis,17-cis-prostadienoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-3-oxa- 8-iso-13-cis,17-cis-prostadienoate1199 53 1186 ethyl 8.beta.-methyl-9-oxo-15-hydroxy-7-nor- 20-methyl-13-trans-prostenoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-7-nor- 20-methyl-8-iso-13-trans-prostenoate ethyl 8.beta.-methyl-9-oxo-15-hydroxy-7-nor- 20-methyl-13-cis-prostenoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-7-nor- 20-methyl-8-iso-13-cis-prostenoate1200 70 1178 ethyl 8.beta.-methyl-9-oxo-15-hydroxy-2-fluoro- b 17,17-dimethyl-13-trans-prostenoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-2-fluoro - 17,17-dimethyl-8-iso-13-trans-prostenoate ethyl 8.beta.-methyl-9-oxo-15-hydroxy-2-fluoro- 2 17,17-dimethyl-13-cis-prostenoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-2-fluoro - 17,17-dimethyl-8-iso-13-cis-prostenoate1201 111 728 ethyl 8.beta.-methyl-9-oxo-15-hydroxy-10a-homo- a 13-trans-prostenoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-10a-homo - 8-iso-13-trans-prostenoate ethyl 8.beta.-methyl-9-oxo-15-hydroxy-10a-homo- 0 13-cis-prostenoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-10a-homo - 8-iso-13-cis-prostenoate1202 79 1186 ethyl 8.beta.-methyl-9-oxo-15-hydroxy-2-phenyl- O 20-methyl-13-trans-prostenoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-2-phenyl - 20-methyl-8-iso-13-trans-prostenoate ethyl 8.beta.-methyl-9-oxo-15-hydroxy-2-phenyl- A 20-methyl-13-cis-prostenoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-2-phenyl - 20-methyl-8-iso-13-cis-prostenoate1203 900 1182 methyl 8.beta.-methyl-9-oxo-15-hydroxy- 5-cis,13-trans,17-cis-prostatrienoate methyl 8.alpha.-methyl-9-oxo-15-hydroxy-8-iso- r 5-cis,13-trans,17-cis-prostatrienoate methyl 8.beta.-methyl-9-oxo-15-hydroxy-5-cis, 13-cis,17-cis-prostatrienoate methyl 8.alpha.-methyl-9-oxo-15-hydroxy-8-iso- 0 5-cis,13-cis,17-cis-prostatrienoate1204 900 728 ethyl 8.beta.-methyl-9-oxo-15-hydroxy-5-cis, 13-trans-prostadienoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-8-iso- 5-cis,13-trans-prostadienoate ethyl 8.beta.-methyl-9-oxo-15-hydroxy-5-cis, 13-cis-prostadienoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-8-iso- 5-cis,13-cis-prostadienoate1205 900 1185 ethyl 8.beta.-methyl-9-oxo-15-hydroxy-20-ethyl- 4 5-cis,13-trans-prostadienoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-20-ethyl - 8-iso-5-cis,13-trans-prostadienoate ethyl 8.beta.-methyl-9-oxo-15-hydroxy-20-ethyl- a 5-cis,13-cis-prostadienoate ethyl 8.alpha.-methyl-9-oxo-15-hydroxy-20-ethyl - 8-iso-5-cis,13-cis-prostadienoate__________________________________________________________________________

EXAMPLES 1206-1273

Treatment of the designated 9-oxo-prostenoic acid and ester derivatives listed in Table 35 below with sodium borohydride in ethanol as described in Example 257 gives the product 9.alpha. and 9.beta. hydroxy derivatives of the table, which are separable by standard chromatographic techniques.

TABLE 35______________________________________Ex- Starting 9-oxo- Product 9-hydroxyample derivative derivatives______________________________________1206 11-deoxy-8.beta.- 11-deoxy-8.beta.-methyl-pros- methyl-prosta- taglandin F.sub.1 .alpha. and F.sub.1 .beta. glandin E.sub.1 meth- methyl esters yl ester (Example 1188)1207 11-deoxy-8.alpha.- 11-deoxy-8.alpha.-methyl-8-iso- methyl-8-iso- prostaglandin F.sub.1 .alpha. and prostaglandin F.sub.1 .beta. methyl esters E.sub.1 methyl ester (Example 1188)1208 methyl 15-hy- methyl 9.alpha./.beta.,15-di- droxy-8.beta.-meth- hydroxy-8.beta.-methyl-13- yl-9-oxo-13- cis-prostenoates cis-prostenoate (Example 1188)1209 methyl 15-hy- methyl 9.alpha./.beta.,15-dihydroxy droxy-8.alpha.-meth- 8.alpha.-methyl-8-iso-13-cis- yl-9-oxo-13- prostenoates cis-prosteno- ate (Example 1188)1210 ethyl 8.beta.-meth- ethyl 8.beta.-methyl-9.alpha./.beta.,15- yl-9-oxo-15- dihydroxy-16,16-dimeth- hydroxy-16- yl-13-trans-prosteno- 16-dimethyl- ates 13-trans- prostenoate (Example 1190)1211 ethyl 8.alpha.-meth- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- yl-9-oxo-15- dihydroxy-16,16-dimeth- hydroxy-16,- yl-8-iso-13-trans-pros- 16-dimethyl- tenoates 8-iso-13- trans-prosten- oate (Example 1190)1212 ethyl 8.beta.-meth- ethyl 8.beta.-methyl-9.alpha./.beta.,15- yl-9-oxo-15-hy- dihydroxy-16,16-dimeth- droxy-16,16- yl-13-cis-prostenoates dimethyl-13- cis-prosteno- ate (Example 1190)1213 ethyl 8.alpha.-meth- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- yl-9-oxo-15- dihydroxy-16,16-dimeth- hydroxy-16,- yl-8-iso-13-cis-prosten- 16-dimethyl-8- oates iso-13-cis- prostenoate (Example 1190)1214 8.beta.-methyl-9- ethyl 8.beta.-methyl-9.alpha./.beta.,15- oxo-15-hydrox- dihydroxy-17,17-dimeth- y-17,17-dimeth- yl-13-trans-prostenoates yl-13-trans- prostenoate (Example 1191)1215 ethyl 8.alpha.-meth- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- yl-9-oxo-15- dihydroxy-17,17-dimeth- hydroxy-17,17- yl-8-iso-13-trans-pros- dimethyl-8- tenoates iso-13-trans- prostenoate (Example 1191)1216 ethyl 8.beta.-meth- ethyl 8.beta.-methyl-9.alpha./.beta.,15- yl-9-oxo-15- dihydroxy-17,17-dimeth- hydroxy-17,17- yl-13-cis-prostenoates dimethyl-13- cis-prosteno- ate (Example 1191)1217 ethyl 8.alpha.-meth- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- yl-9-oxo-15-hy- dihydroxy-17,17-dimeth- droxy-17,17-di- yl-8-iso-13-cis-prosten- methyl-8-iso- oates 13-cis-prosten- oate (Example 1191)1218 ethyl 8.beta.-meth- ethyl 8.beta.-methyl-9.alpha./.beta.,15- yl-9-oxo-15-hy- dihydroxy-13-trans,17- droxy-13-trans- cis-prostadienoates 17-cis-prosta- dienoate (Exam- ple 1192)1219 ethyl 8.alpha.-meth- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- yl-9-oxo-15-hy- dihydroxy-8-iso-13-trans, droxy-8-iso-13- 17-cis-prostadienoates trans,17-cis- prostadienoate (Example 1192)1220 ethyl 8.beta.-meth- ethyl 8.beta.-methyl-9.alpha./.beta.,15- yl-9-oxo-15-hy- dihydroxy-13-cis,17- droxy-13-cis,- cis-prostadienoates 17-cis-prostadi- enoate (Example (1192)1221 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-8-iso-13-cis- droxy-8-iso-13- 17-cis-prostadienoates cis,17-cis-pros- tadienoate (Exam- ple 1192)1222 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-20-ethyl-13- droxy-20-ethyl-13- trans-prostenoates trans-prosteno- ate (Example 1193)1223 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-20-ethyl-8- droxy-20-ethyl-8- iso-13-trans-prosteno- iso-13-trans- ates prostenoate (Example 1193)1224 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-20-ethyl-13- droxy-20-ethyl-13- cis-prostenoates cis-prostenoate (Example 1193)1225 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-20-ethyl-8- droxy-20-ethyl- iso-13-cis-prostenoates 8-iso-13-cis- prostenoate (Example 1193)1226 decyl 8.beta.-methyl- decyl 8.beta.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-20-methyl-13- droxy-20-methyl- trans-prostenoates 13-trans-pros- tenoate (Example 1194)1127 decyl 8.alpha.-methyl- decyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-20-methyl-8- droxy-20-methyl- iso-13-trans-prosteno- 8-iso-13-trans- ates prostenoate (Example 1194)1128 decyl 8.beta.-methyl- decyl 8.beta.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-20-methyl-13- droxy-20-methyl- cis-prostenoates 13-cis-prosten- oate (Example 1194)1229 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-20-methyl-8- droxy-20-methyl- iso-13-cis-prostenoates 8-iso-13-cis- prostenoate (Example 1194)1230 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-7a,7b-bis- droxy-7a,7b-bis- homo-13-trans-prosteno- homo-13-trans- ates prostenoate (Example 1195)1231 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-7a,7b-bis- droxy-7a,7b-bis- homo-8-iso-13-trans- homo-8-iso-13- prostenoates trans-prosteno- ate (Example 1195)1232 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-7a,7b-bis- droxy-7a,7b-bis- homo-13-cis-prosteno- homo-13-cis-pros- ates tenoate (Example 1195)1233 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-7a,7b-bis- droxy-7a,7b-bis- homo-8-iso-13-cis-pros- homo-8-iso-13- tenoates cis-prostenoate (Example 1195)1234 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-2,20-bis- droxy-2,20-bis- ethyl-13-trans-prosteno- ethyl-13-trans- ates prostenoate (Example 1196)1235 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-2,20-bis- droxy-2,20-bis- ethyl-8-iso-13-trans- ethyl-8-iso-13- prostenoates trans-prosteno- ate (Example 1196)1236 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9.alpha.1.beta.,15- 9-oxo-15-hy- dihydroxy-2,20-bis- droxy-2,20-bis- ethyl-13-cis-prosteno- ethyl-13-cis- ates prostenoate (Example 1196)1237 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-2,20-bis- droxy-2,20-bis- ethyl-8-iso-13-cis-pros- ethyl-8-iso-13- tenoates cis-prostenoate (Example 1196)1238 ethyl 8.beta. -methyl- ethyl 8.beta.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-3-oxa-16,16- droxy-3-oxa-16,- dimethyl-13-trans-pros- 16-dimethyl-13- tenoates trans-prosteno- ate (Example 1197)1239 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-3-oxa-16,16- droxy-3-oxa-16,- dimethyl-8-iso-13-trans- 16-dimethyl-8- prostenoates iso-13-trans- prostenoate (Example 1197)1240 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-3-oxa-16,16- droxy-3-oxa-16,- dimethyl-13-cis-pros- 16-dimethyl-13- tenoates cis-prostenoate (Example 1197)1241 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-3-oxa-16,16- droxy-3-oxa-16,- dimethyl-8-iso-13-cis- 16-dimethyl-8- prostenoates iso-13-cis- prostenoate (Example 1197)1242 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-3-oxa-13- droxy-3-oxa-13- trans,17-cis-prostadi- trans,17-cis- enoates prostadienoate (Example 1198)1243 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-3-oxa-8-iso- droxy-3-oxa-8- 13-trans,17-cis-prosta- iso-13-trans,- dienoates 17-cis-prostadi- enoate (Example 1198)1244 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-3-oxa-13-cis- droxy-3-oxa-13- 17-cis-prostadienoates cis,17-cis-pros- tadienoate (Exam- ple 1198)1245 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-3-oxa-8-iso- droxy-3-oxa-8-iso- 13-cis,17-cis-prosta- 13-cis,17-cis- dienoates prostadienoate (Example 1198)1246 ethyl 8.beta. -methyl- ethyl 8.beta.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-7-nor-20- droxy-7-nor-20- methyl-13-trans-pros- methyl-13-trans- tenoates prostenoate (Example 1199)1247 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-7-nor-20- droxy-7-nor-20- methyl-8-iso-13-trans- methyl-8-iso-13- prostenoates trans-prosteno- ate (Example 1199)1248 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-7-nor-20- droxy-7-nor-20- methyl-13-cis-prosteno- methyl-13-cis- ates prostenoate (Example 1199)1249 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-7-nor-20- droxy-7-nor-20- methyl-8-iso-13-cis- methyl-8-iso- prostenoates 13-cis-prosteno- ate (Example 1199)1250 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-2-fluoro-17,- droxy-2-fluoro- 17-dimethyl-13-trans- 17,17-dimethyl- prostenoates 13-trans-prosten- oate (Example 12001251 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-2-fluoro-17,- droxy-2-fluoro- 17-dimethyl-8-iso-13- 17,17-dimethyl- trans-prostenoates 8-iso-13-trans- prostenoate (Example 1200)1252 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-2-fluoro-17,- droxy-2-fluoro-17- 17-dimethyl-13-cis-pros- 17-dimethyl-13- tenoates cis-prostenoate (Example 1200)1253 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-2-fluoro-17,- droxy-2-fluoro- 17-dimethyl-8-iso-13- 17,17-dimethyl- cis-prostenoates 8-iso-13-cis- prostenoate (Example 1200)1254 ethyl 8.beta. -methyl- ethyl 8.beta.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-10a-homo-13- droxy-10a-homo-13- trans-prostenoates trans-prosteno- ate (Example 1201)1255 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-10a-homo-8- droxy-10a-homo-8- iso-13-trans-prosteno- iso-13-trans- ates prostenoate (Example 1201)1256 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-10a-homo-13- droxy-10a-homo- cis-prostenoates 13-cis-prosten- oate (Example 1201)1257 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-10a-homo-8- droxy-10a-homo-8- iso-13-cis-prostenoates iso-13-cis-pros- tenoate (Example 1201)1258 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-2-phenyl-20- droxy-2-phenyl- methyl-13-trans-prosten- 20-methyl-13- oates trans-prosteno- ate (Example 1202)1259 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-2-phenyl-20- droxy-2-phenyl- methyl-8-iso-13-trans- 20-methyl-8-iso- prostenoates 13-trans-pros- tenoate (Example 1202)1260 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-2-phenyl-20- droxy-2-phenyl- methyl-13-cis-prosteno- 20-methyl-13-cis- ates prostenoate (Example 1202)1261 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-2-phenyl-20- droxy-2-phenyl- methyl-8-iso-13-cis- 20-methyl-8-iso- prostenoates 13-cis-prosteno- ates (Example 1202)1262 methyl 8.beta.-methyl- methyl 8.beta.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-5-cis,13- droxy-5-cis,13- trans,17-cis-prostatri- trans,17-cis-pros- enoates tatrienoate (Example 1203)1263 methyl 8.alpha.-methyl- methyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-8-iso-5-cis,- droxy-8-iso-5- 13-trans,17-cis-prosta- cis,13-trans,17- trienoates cis-prostatri- enoate (Example 1203)1264 methyl 8.beta.-methyl- methyl 8.beta.-methyl-9.alpha./.beta., 9-oxo-15-hy- 15-dihydroxy-5-cis,13- droxy-5-cis,13- cis,17-cis-prostatri- cis,17-cis-pros- enoates tatrienoate (Example 1203)1265 methyl 8.alpha.-methyl- methyl 8.alpha.-methyl-9.alpha./.beta.,15- 9-oxo-15-hy- dihydroxy-8-iso-5-cis- droxy-8-iso-5- 13-cis,17-cis-prostatri- cis,13-cis,17- enoates cis-prostatrien- oate (Example 1203)1266 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9.alpha./.beta.,- 9-oxo-15-hy- 15-dihydroxy-5-cis,13- droxy-5-cis,13- trans-prostadienoates trans-prostadi- enoate (Example 1204)1267 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,- 9-oxo-15-hy- 15-dihydroxy-8-iso-5- droxy-8-iso-5- cis,13-trans-prosta- cis,13-trans- dienoates prostadienoate (Example 1204)1268 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9.alpha./.beta.,- 9-oxo-15-hy- 15-dihydroxy-5-cis,13- droxy-5-cis,13- cis-prostadienoates cis-prostadien- oate (Example 1204)1269 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,- 9-oxo-15-hy- 15-dihydroxy-8-iso-5- droxy-8-iso-5- cis,13-cis-prostadien- cis,13-cis- oates prostadienoate (Example 1204)1270 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9.alpha./.beta.,- 9-oxo-15-hy- 15-dihydroxy-20-ethyl- droxy-20-ethyl- 5-cis,13-trans-prosta- 5-cis,13-trans- dienoates prostadienoate (Example 1205)1271 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,- 9-oxo-15-hy- 15-dihydroxy-20-ethyl- droxy-20-ethyl-8- 8-iso-5-cis,13-trans- iso-5-cis,13- prostadienoates trans-prostadien- oate (Example 1205)1272 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9.alpha./.beta.,- 9-oxo-15-hy- 15-dihydroxy-20-ethyl- droxy-20-ethyl- 5-cis,13-cis-prostadi- 5-cis,13-cis- enoates prostadienoate (Example 1205)1273 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9.alpha./.beta.,- 9-oxo-15-hy- 15-dihydroxy-20-ethyl- droxy-20-ethyl- 8-iso-5-cis,13-cis- 8-iso-5-cis,13- prostadienoates cis-prostadien- oate (Example 1205)______________________________________

EXAMPLES 1274-1299

In the manner of Example 93, the various cyclopentenones of Table 36, which follows, are converted to the corresponding 4-bromo derivatives.

TABLE 36______________________________________ StartingEx- Cyclopentenone Product 4-Bromocyclo-ample of Example pentenones______________________________________1274 13 4-bromo-2-(6-carbeth- oxyhexyl)-cyclopent-2- en-1-one1275 83 4-bromo-2-(6-carbo- methoxyhexyl)cyclopent- 2-en-1-one1276 15 4-bromo-2-(4-carbeth- oxybutyl)cyclopent-2-en- 1-one1277 14 4-bromo-2-(3-carbethoxy- propyl)cyclopent-2-en-1- one1278 2 4-bromo-2-(4-carboxy- butyl)cyclopent-2-en- 1-one1279 5 4-bromo-2-(3-carboxy- propyl)cyclopent-2-en-1- one1280 22 4-bromo-2-(8-carboxy- octyl)cyclopent-2-en-1- one1281 23 4-bromo-2-(8-carbethoxy- octyl)cyclopent-2-en-1- one1282 30 4-bromo-2-(6-carboxy- octyl)cyclopent-2-en-1- one1283 31 4-bromo-2-(6-carbethoxy- octyl)cyclopent-2-en-1- one1284 92 4-bromo-2-(6-carboxy- 5,5-dimethylhexyl)cyclo- pent-2-en-1-one1285 41 4-bromo-2-(6-carbethoxy- 5,5-dimethylhexyl)cyclo- pent-2-en-1-one1286 45 4-bromo-2-(6-carboxy-5- oxahexyl)cyclopent-2- oxahexyl)cyclopent-2- en-1-one1287 46 4-bromo-2-(6-carbethoxy- 5-oxahexyl)cyclopent-2- en-1-one1288 69 4-bromo-2-(6-carboxy-6- fluorohexyl)cyclopent- 2-en-1-one1289 70 4-bromo-2-(6-carbethoxy- 6-fluorohexyl)cyclopent- 2-en-1-one1290 52 4-bromo-2-(5-carboxy- pentyl)cyclopent-2-en-1- one1291 53 4-bromo-2-(5-carbethoxy pentyl)cyclopent-2-en- 1-one1292 73 4-bromo-2-(7-carboxy- heptyl)cyclopent-2-en-1- one1293 74 4-bromo-2-(7-carbethoxy- heptyl)cyclopent-2-en-1- one1294 78 4-bromo-2-(6-carboxy-6- phenylhexyl)cyclopent-2- en-1-one1295 79 4-bromo-2-(6-carbethoxy- 6-phenylhexyl)cyclopent- 2-en-1-one1296 81 4-bromo-2-(6-carbo-n- butoxyhexyl)cyclopent- 2-en-1-one1297 82 4-bromo-2-(6-carbo-iso- propoxyhexyl)-cyclo- pent-2-en-1-one1298 84 4-bromo-2-(6-carbo-n- decycloxyhexyl)cyclopent- 2-en-1-one1299 98 4-bromo-2-(6-carboxy- heptyl)-cyclopent-2-en- 1-one______________________________________

EXAMPLE 1300

Preparation of 4-hydroxy-2-(8-carboxyoctyl)cyclopent-2-en1-one

To a stirred solution of 57.2 g. of crude 4-bromo-2-(8-carboxyoctyl)cyclopent-2-en-1-one (Example 1280) in 500 ml. of acetone and 325 ml. of water at 3.degree. C. is added 44.1 g. (0.226 moles) of silver fluoborate during a 15 minute period. The mixture is stirred at 0.degree.-3.degree. C. for 2 hours and filtered. The filtrate is diluted with water, saturated with solid sodium chloride, and extracted with ether. The extract is washed with saturated sodium chloride solution, dried over magnesium sulfate, and concentrated. Partition chromatography of the residue on Celite gives white crystals, m.p. 58.degree.-66.degree. C., .lambda..sub.max..sup.MeOH = 223 m.mu. (7800); .nu.max (KBr) = 3340 (hydroxyl groups), 1705 (carbonyl groups), and 1625 cm.sup.-1 (olefin group).

EXAMPLE 1301

Preparation of 4-acetoxy-2-(6-carbethoxyhexyl)cyclopent-2-en-1-one

A mixture of 51.6 g. (0.137 moles) of crude 4-bromo-2-(6-carbethoxyhexyl)cyclopent-2-en-1-one (Example 1274), 27 g. (0.162 moles) of silver acetate, and 200 ml. of glacial acetic acid is stirred at reflux for 4.5 hours. The mixture is cooled, and solids are removed by filtration. The filtrate is concentrated and extracted with hot hexane. The extract is washed with saturated sodium bicarbonate solution and saturated sodium chloride solution, dried over mangesium sulfate, and concentrated to give an oil. The crude product is distilled at reduced pressure to give a liquid, b.p. 152.degree.-163.degree. C. (0.01 mm); .lambda..sub.max..sup.MeOH = 223 m.mu. (10700); .nu.max. = 1745 (ester carbonyl groups), 1725 (ketone carbonyl groups), and 1235 cm.sup.-1 (acetoxy group).

Exampls 1302-1326

By the procedure of Example 94 the various 4-bromo-cyclopentenones of the following Table 37 are solvolyzed in acetone-water in the presence of silver fluoborate to provide the product 4-hydroxycyclopentenones of the Table.

Table 37______________________________________ Starting 4-bromo ProductEx cyclopentenones 4-Hydroxycyclopent-2-ample of Exampleen-1-ones______________________________________1302 1274 4-hydroxy-2-(6-carb- ethoxyhexyl)cyclopent-2-en-1-one1303 1275 4-hydroxy-2-(6-carbo- methoxyhexyl)cyclopent-2-en-1-one1304 1276 4-hydroxy-2-(4-carb- ethoxybutyl)cyclopent-2-en-1-one1305 1277 4-hydroxy-2-(3-carb- ethoxypropyl)cyclopent-2-en-1-one1306 1278 4-hydroxy-2-(4-carboxy- butyl)cyclopent-2-en- 1-one1307 1279 4-hydroxy-2-(3-carboxy- propyl)cyclopent-2-en- 1-one1308 1281 4-hydroxy-2-(8-carb- ethoxyoctyl)cyclopent- 2-en-1-one1309 1282 4-hydroxy-2-(6-carboxy- octyl)cyclopent-2-en- 1-one1310 1283 4-hydroxy-2-(6-carb- ethoxyoctyl)cyclopent- 2-en-1-one1311 1284 4-hydroxy-2-(6-carboxy- 5,5-dimethylhexyl)- cyclopent-2-en-1-one1312 1285 4-hydroxy-2-(6-carb- ethoxy-5,5-dimethyl- hexyl)cyclopent-2-en- 1-one1313 1286 4-hydroxy-2-(6-carboxy- 5-oxahexyl)cyclopent- 2-en-1-one1314 1287 4-hydroxy-2-(6-carb- ethoxy-5-oxahexyl)- cyclopent-2-en-1-one1315 1288 4-hydroxy-2-(6-carboxy-6- fluorohexyl)cyclopent-2-en-1-one1316 1289 4-hydroxy-2-(carbethoxy-6- fluorohexyl)cyclopent-2-en-1-one1317 1290 4-hydroxy-2-(5-carboxypentyl)cy- clopent-2-en-1-one1318 1291 4-hydroxy-2-(5-carbethoxypentyl)- cyclopent-2-en-1-one1319 1292 4-hydroxy-2-(7-carboxyheptyl)cy- clopent-2-en-1-one1320 1293 4-hydroxy-2-(7-carbethoxyheptyl)- cyclopent-2-en-1-one1321 1294 4-hydroxy-2-(6-carboxy-6-phenyl hexyl)cyclopent-2-en-1-one1322 1295 4-hydroxy-2-(6-carbethoxy-6- phenylhexyl)cyclopent-2-en-1-one1323 1296 4-hydroxy-2-(6-carbo-n-butoxyhex- yl)cyclopent-2-en-1-one1324 1297 4-hydroxy-2-(6-carboisopropox- yhexyl)cyclopent-2-en-1-one1325 1298 4-hydroxy-2-(6-carbo-n-decylox- yhexyl)cyclopent-2-en-1-one1326 1299 4-hydroxy-2-(6-carboxyheptyl)cy- clopent-2-en-1-one______________________________________

Examples 1327-1337

By the procedure of Example 95, the various 4-hydroxy-cyclopentenones of Table 38, which follows, are converted to the tetrahydropyranyl 4-tetrahydropyranyloxycyclopentenone esters of the table.

Table 38______________________________________ Product Tetrahydropyran- Starting 4-hy- 2'-yl 4-tetrahydropy- droxycyclopenten- ran-2'-yl-oxycyclopent-Example one of Example 2-en-1-ones______________________________________1327 1306 4-tetrahydropyran-2'- yloxy-2-(4-carbotetra- hydropyran-2'-yloxy- butyl)cyclopent-2-en-1- one1328 1307 4-tetrahydropyran-2'- yloxy-2-(3-carbotetra- hydropyran-2'-yloxy- propyl)cyclopent-2-en- 1-one1329 1300 4-tetrahydropyran-2'- yloxy-2-(8-carbotetra- hydropyran-2'-yloxy- oxtyl)cyclopent-2-en-1- one1330 1309 4-tetrahydropyran-2'- yloxy-2-(6-carbotetra- hydropyran-2'-yloxy- octyl)cyclopent-2-en-1- one1331 1311 4-tetrahydropyran-2'- yloxy-2-(6-carbotetra- hydropyran-2'-yloxy- 5,5-dimethylhexyl)- cyclopent-2-en-1-one1332 1313 4-tetrahydropyran-2'- yloxy-2-(6-carbotetra- hydropyran-2'-yloxy-5- oxahexyl)cyclopent-2- en-1-one1333 1315 4-tetrahydropyran-2'- yloxy-2-(6-carbotetra- hydropyran-2'-yloxy-6- fluorohexyl)cyclopent- 2-en-1-one1334 1317 4-tetrahydropyran-2'- yloxy-2-(5-carbotetra- hydropyran-2'-yloxy- pentyl)cyclopent-2-en-1- one1335 1319 4-tetrahydropyran-2'- yloxy-2-(7-carbotetra- hydropyran-2'-yloxyhep- tyl)cyclopent-2-en-1- one1336 1321 4-tetrahydropyran-2'- yloxy-2-(6-carbotetra- hydropyran-2'-yloxy-6- phenylhexyl)cyclopent- 2-en-1-one1337 1326 4-tetrahydropyran-2'- yloxy-2-(6-carbotetra- hydropyran-2'-yloxy- heptyl)cyclopent-2-en- 1-one______________________________________

EXAMPLE 1338

Preparation of 4-tetrahydropyranyloxy-2-(6-carbethoxyhexyl)-cyclopent-2-en-1-one

To a stirred solution of 674 mg. (2.64 mmoles) of 4-hydroxy-2-(6-carbethoxyhexyl)cyclopent-2-en-1-one (Example 1302) and 2.22 g. (26.4 mmoles) of dihydropyran in 2.6 ml. of methylene chloride is added 5.0 mg. (0..026 mmoles) of p-toluenesulfonic acid monohydrate. After stirring for 20 minutes at room temperature the solution is diluted with ether and poured into saturated sodium chloride solution containing a little sodium bicarbonate. The organic phase is separated and washed with saturated sodium chloride solution. The extract is dried over magnesium sulfate, and volatile matter is evaporated at reduced pressure to give an oil, .lambda..sub.max..sup.MeOH = 224 m.mu. (7950); max. = 1735 (ester carbonyl group), 1710 (ketone carbonyl group), and 1030 cm.sup.-1 (tetrahydropyranyloxy group).

EXAMPLE 1339-1352

In the manner of Example 1338 the alkyl 4-hydroxy-cyclopentenone esters of Table 39, which follows, are converted to the corresponding 4-tetrahydropyranyloxy alkyl esters of the table.

TABLE 39______________________________________ Starting 4- hydroxycyclo- 4-tetrahydropyran-Ex- pentenone Esters 2'yloxycyclopent-ample of Example 2-en-1-one esters______________________________________1339 1303 4-tetrahydropyran-2'- yloxy-2-(6-carbomethoxy- hexyl)cyclopent-2-en-1- one1340 1304 4-tetrahydropyran-2'- yloxy-2-(4-carbethoxy- butyl)cyclopent-2-en-1- one1341 1305 4-tetrahydropyran-2'- yloxy-2-(3-carbethoxy- propyl)cyclopent-2-en-1- one1342 1308 4-tetrahydropyran-2'- yloxy-2-(8-carbethoxy- octyl)cyclopent-2-en-1- one1343 1310 4-tetrahydropyran-2'- yloxy-2-(6-carbethoxy- octyl)cyclopent-2-en-1- one1344 1312 4-tetrahydropyran-2'- yloxy-2-(6-carbethoxy-5, 5-dimethylhexyl)cyclo- pent-2-en-1-one1345 1314 4-tetrahydropyran-2'- yloxy-2-(6-carbethoxy-5- oxahexyl)cyclopent-2-en- 1-one1346 1316 4-tetrahydropyran-2'- yloxy-2-(6-carbethoxy-6- fluorohexyl)cyclopent- 2-en-1-one1347 1318 4-tetrahydropyran-2'- yloxy-2-(5-carbethoxy- pentyl)cyclopent-2-en- 1-one1348 1320 4-tetrahydropyran-2'- yloxy-2-(7-carbethoxy- heptyl)cyclopent-2-en-1- one1349 1322 4-tetrahydropyran-2'- yloxy-2-(6-carbethoxy-6- phenylhexyl)cyclopent-2- en-1-one1350 1323 4-tetrahydropyran-2'- yloxy-2-(6-carbo-n- butoxyhexyl)cyclopent-2- en-1-one1351 1324 4-tetrahydropyran-2'- yloxy-2-(6-carbo-iso- propoxyhexyl)cyclopent- 2-en-1-one1352 1325 4-tetrahydropyran-2'- yloxy-2-(6-carbo-n-dec- yloxyhexyl)cyclopent-2- en-1-one______________________________________

EXAMPLE 1353

Preparation of 8.beta.-methyl-prostaglandin E.sub.1, 8.alpha.-methyl-8-iso-prostaglandin E.sub.1, 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-13-cis-prostenoic acid, and 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-8-iso13-cis-prostenoic acid

The Grignard reagent, prepared as described in Example 1187 from 1..54 g. of magnesium, 22.5 g. of 1-bromo-3-triphenylmethoxy-trans-1-octene (Example 728), and 30 ml. of tetrahydrofuran, is added to an ice cooled solution of 17.75 g. of 11-tetrahydropyranyloxy-2-(6-carbotetrahydropranyloxyhexyl)-2-cyclopentenone (Example 95) and 1.25 g. of copper (I) iodide-tri-n-butylphosphine complex in 30 ml. of tetrahydrofuran over 15 minutes under an inert atmosphere. The mixture is stirred with cooling for 0.5 hour. To the mixture is then added 100 g. of methyl iodide, the cooling bath is then removed and the mixture is stirred at ambient temperatures for 48 hours. The mixture is then poured into ice cold saturated ammonium chloride solution and the layers are separated. The aqueous phase is washed with ether and combined organic phase and washings are washed with saturated brine, and evaporated in vacuo. The residue is heated to 45.degree. C. for 5 hours with 840 ml. of 4:2:1 tetrahydrofuranacetic acid-water under an inert atmosphere and is then evaporated to dryness in vacuo. The residue is chromatographed upon Silic AR CC-4.sup..RTM. using a benzene-ethyl acetate gradient as eluent to yield the title compounds as a mixture of 8.beta.-methyl-prostaglandin E.sub.1 and 8.alpha.-methyl-8-iso-prostaglandin E.sub.1 and a mixture of 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-13-cis-prostenoic acid and 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy 8-iso-cis-8.alpha. isomers; resolution of the mixtures is then accomplished by a combination of partition chromatography and thin-layer chromatography.

EXAMPLES 1354-1386

Treatment of the blocked 4-oxycyclopent-2-en-1-ones listed in Table 40 below by the procedure described in Example 1353 with the Grignard reagents, prepared by the procedure described in Example 1187 from the listed 1-bromo-3-triphenylmethoxy-1-trans-alkenes, and then with methyl iodide furnishes the product 8.alpha.- and 8.beta.-methyl prostenoates of the table. The products of Examples 1354-1378 inclusive are initially obtained as the corresponding 15-O-triphenyl-methyl-11-O-tetrahydropyranyl tetrahydropyranyl esters. These blocking groups are then cleaved by the procedure described in Example 1353 by treatment at 45.degree. C. for 5 hours with 4:2:1 tetrahydrofuran:acetic acid:water. The alkyl esters products of Examples 1379-1385 inclusive are obtained initially as the corresponding 15-O-triphenyl-methyl-11-O-tetrahydropyranyl derivatives. These 11- and 15-hydroxy blocking groups are then cleaved by the deblocking procedure described in Example 1353. The products of Example 1386 are initially obtained as the corresponding 15-O-triphenylmethyl derivatives, which are cleaved hydrolyticaly to the listed free 15-ols by the process described in Example 1353.

TABLE 40__________________________________________________________________________ Starting blocked Starting 1-bromo- 4-oxycyclopent- 3-triphenylmethoxy-Ex- 2-en-1-one of 1-trans-alkene ofample Example Example Product 8-methylprostenoic__________________________________________________________________________ acid1354 95 1175 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-16, 16- dimethyl-13-trans-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-16 ,16- dimethyl-8-iso-13-trans-prostenoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-16, 16- dimethyl-13-cis-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-16 ,16- dimethyl-8-iso-13-cis-prostenoic acid1355 95 1178 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy,17, 17- dimethyl-13-trans-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-17 ,17- dimethyl-8-iso-13-trans-prostenoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-17, 17- dimethyl-13-cis-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-17 ,17- dimethyl-8-iso-13-cis-prostenoic acid1356 95 1182 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-13- trans, 17-cis-prostadienoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-8- iso-13- trans,17-cis-prostadienoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-13- cis, 17-cis-prostadienoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-8- iso-13- cis,17-cis-prostadienoic acid1357 95 1185 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-20- ethyl- 13-trans-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-20 -ethyl- 8-iso-13-trans-prostenoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-20- ethyl- 13-cis-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-20 -ethyl- 8-iso-13-cis-prostenoic acid1358 1327 728 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-6,7 -dinor- 13-trans-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-6, 7-dinor- 8-iso-13-trans-prostenoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-6,7 -dinor- 13-cis-prostenoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-6,7 -dinor- 8-iso-13-cis-prostenoic acid1359 1328 1186 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-5,6 ,7-tri- nor-20-methyl-13-trans-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-5, 6,7-tri- nor-20-methyl-8-iso-13-trans-prostenoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-5,6 ,7-tri- nor-20-methyl-13-cis-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-5, 6,7-tri- nor-20-methyl-8-iso-13-cis-prostenoic acid1358 1327 728 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-6,7 -dinor- 13-trans-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-6, 7-dinor- 8-iso-13-trans-prostenoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-6,7 -dinor- 13-cis-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-6, 7-dinor- 8-iso-13-cis-prostenoic acid1359 1328 1186 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-5,6 ,7-tri- nor-20-methyl-13-trans-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-5, 6,7-tri- nor-20-methyl-8-iso-13-trans-prostenoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-5,6 ,7-tri- nor-20-methyl-13-cis-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-5, 6,7-tri- nor-20-methyl-8-iso-13-cis-prostenoic acid1360 1329 728 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-7a, 7b-bis- home-13-trans-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-7a ,7b-bis- homo-8-iso-13-trans-prostenoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-7a, 7b-bis- homo-13-cis-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-7a ,7b-bis- homo-8-iso-13-cis-prostenoic acid1361 1330 728 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-2-e thyl-13- trans-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-2- ethyl-8- iso-13-trans-prostenoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-2-e thyl-13- cis-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-2- ethyl-8- iso-13-cis-prostenoic acid1362 1331 1186 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-3,3 ,20-tri- methyl-13-trans-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-3, 3,20-tri- methyl-8-iso-13-trans-prostenoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-3,3 ,20-tri- methyl-13-cis-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-3, 3,20-tri- methyl-8-iso-13-cis-prostenoic acid1363 1332 728 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-3-o xa-13- trans-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-3- oxa-8-iso- 13-trans-prostenoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-3-o xa-13- cis-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-3- oxa-8- iso-13-cis-prostenoic acid1364 1332 1175 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-3-o xa-16,16- dimethyl-13-trans-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-3- oxa-16,16- dimethyl-8-iso-13-trans-prostenoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-3-o xa-16,16- dimethyl-13-cis-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-3- oxa-16,16- dimethyl-8-iso-13-cis-prostenoic acid1365 1332 1182 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-3-o xa-13- trans,17-cis-prostadienoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-3- oxa-8-iso- 13-trans,17-cis-prostadienoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-3-o xa-13- cis,17-cis-prostadienoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-3- oxa-8-iso- 13-cis,17-cis-prostadienoic acid1366 1332 1185 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-3-o xa-20- ethyl-13-trans-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-3- oxa-20- ethyl-8-iso-13-trans-prostenoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-3-o xa-20- ethyl-13-cis-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-3- oxa-20- ethyl-8-iso-13-cis-prostenoic acid1367 1333 1178 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-2-f luoro- 17,17-dimethyl-13-trans-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-2- fluoro- 17,17-dimethyl-8-iso-13-trans-prostenoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-2-f luoro- 17,17-dimethyl-13-cis-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-2- fluoro- 17,17-dimethyl-8-iso-13-cis-prostenoic acid1368 1334 728 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-7-n or-13- trans-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-7- nor-8- iso-13-trans-prostenoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-7-n or-13- cis-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-7- nor-8- iso-13-cis-prostenoic acid1369 1335 1175 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-7a- homo- 16,16-dimethyl-13-trans-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-7a -homo-16,16- dimethyl-8-iso-13-trans-prostenoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-7a- homo- 16,16-dimethyl-13-cis-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-7a -homo- 16,16-dimethyl-8-iso-13-cis-prostenoic acid1370 1336 728 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-2-p henyl- 13-trans-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-2- phenyl- 8-iso-13-trans-prostenoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-2-p henyl- 13-cis-prostenoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-2- phenyl- 8-iso-13-cis-prostenoic acid1371 1337 1182 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-2-m ethyl- 13-trans,17-cis-prostadienoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-2- methyl- 8-iso-13-trans,17-cis-prostadienoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-2-m ethyl- 13-cis,17-cis-prostadienoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-2- methyl- 8-iso-13-cis,17-cis-prostadienoic acid1372 1121 728 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-5-c is,13- trans-prostadienoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-8- iso-5- cis,13-trans-prostadienoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-5- cis,13- cis-prostadienoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-8- iso-5- cis,13-cis-prostadienoic acid1373 1121 1182 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-5-c is,13- trans,17-cis-prostatrienoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-8- iso-5- cis,13-trans,17-cis-prostatrienoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-5-c is, 13-cis,17-cis-prostatrienoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-8- iso- 5-cis,13-cis,17-cis-prostatrienoic acid1374 1121 1175 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-16, 16-di- methyl-5-cis,13-trans-prostadienoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-16 ,16-di- methyl-8-iso-5-cis,13-trans-prostadienoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-16, 16-di- methyl-5-cis,13-cis-prostadienoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-16 ,16-di- methyl-8-iso-5-cis,13-cis-prostadienoic acid1375 1122 1186 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-4-n or-20- methyl-5-cis,13-trans-prostadienoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-4- nor-20- methyl-8-iso-5-cis,13-trans-prostadienoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-4-n or-20- methyl-5-cis,13-cis-prostadienoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-4-n or-20- methyl-8-iso-5-cis,13-cis-prostadienoic acid1376 1123 1178 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-4a- homo-17, 17-dimethyl-5-cis,13-trans-prostadienoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-4a -homo-17, 17-dimethyl-8-iso-5-cis,13-cis-prostadienoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-4a- homo-17, 17-dimethyl-5-cis,13-cis-prostadienoic acid 8.alpha.-methyl-9-oxo-11.alpha. ,15-dihydroxy-4a-homo-17, 17-dimethyl-8-iso-5-cis,13-cis-prostadienoic acid1377 1124 1185 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-4a, 4b-bis- homo-20-ethyl-5-cis,13-trans-prostadienoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-4a ,4b-bis- homo-20-ethyl-8-iso-5-cis,13-trans-prosta- dienoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-4a, 4b-bis- homo-20-ethyl-5-cis,13-cis-prostadienoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-4a ,4b-bis- homo-20-ethyl-8-iso-5-cis,13-cis-prosta- dienoic acid1378 1124 1182 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-4a, 4b-bis- homo-5-cis,13-trans,17-cis-prostatrienoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-4a ,4b-bis- homo-8-iso-5-cis,13-trans,17-cis-prosta- trienoic acid 8.beta.-methyl-9-oxo-11.alpha.,15-dihydroxy-4a, 4b-bis- homo-5-cis,13-cis,17-cis-prostatrienoic acid 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydroxy-4a ,4b-bis- homo-8-iso-5-cis,13-cis-17-cis-prostatrienoic acid1379 1339 1186 Methyl 8.beta.-methyl-9-oxo-11.alpha.,15-dihydr oxy-20- methyl-13-trans-prostenoate Methyl-8.alpha.-methyl-9-oxo-11.alpha.,15-dihyd roxy-20- methyl-8-iso-13-trans-prostenoate Methyl 8.alpha.-methyl-9-oxo-11.alpha.,15-dihyd roxy-20- methyl-13-cis-prostenoate Methyl 8.alpha.-methyl-9-oxo-11.alpha.,15-dihyd roxy-20- methyl-8-iso-13-cis-prostenoate1380 1342 1182 Ethyl 8.beta.-methyl-9-oxo-11.alpha.,15-dihydro xy-7a,7b- bishomo-13-trans,17-cis-prostadienoate Ethyl 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydr oxy-7a,7b- bishomo-8-iso-13-trans,17-cis-prostadienoate Ethyl 8.beta.-methyl-9-oxo-11.alpha.,15-dihydro xy-7a,7b- bishomo-13-cis,17-cis-prostadienoate Ethyl 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydr oxy-7a,7b- bishomo-8-iso-13-cis,17-cis-prostadienoate1381 1343 1175 Ethyl 8.beta.-methyl-9-oxo-11.alpha.,15-dihydro xy-2- ethyl-16,16-dimethyl-13-trans-prostenoate Ethyl 8.alpha.-methyl-9-oxo-11.alpha. ,15-dihydroxy-2- ethyl-16-16-dimethyl-8-iso-13-trans- prostenoate Ethyl 8.beta.-methyl-9-oxo-11.alpha.,15-dihydro xy-2- ethyl-16,16-dimethyl-13-cis-prostenoate Ethyl 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydr oxy-2- ethyl-16,16-dimethyl-8-iso-13-cis-prostenoate1382 1344 1178 Ethyl 8.beta.-methyl-9-oxo-11.alpha.,15-dihydro xy-3,3- 17,17-tetramethyl-13-trans-prostenoate Ethyl 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydr oxy-3,3- 17,17-tetramethyl-8-iso-13-trans-prostenoate Ethyl 8.beta.-methyl-9-oxo-11.alpha.,15-dihydro xy-3,3- 17,17-tetramethyl-13-cis-prostenoate Ethyl 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydr oxy-3,3- 17,17-tetramethyl-8-iso-13-cis-prostenoate1383 1345 1178 Ethyl 8.beta.-methyl-9-oxo-11.alpha.,15-dihydro xy-3-oxa- 17,17-dimethyl-13-trans-prostenoate Ethyl 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydr oxy-3-oxa- 17,17-dimethyl-8-iso-13-trans-prostenoate Ethyl 8.beta.-methyl-9-oxo-11.alpha.,15-dihydro xy-3-oxa- 17,17-dimethyl-13-cis-prostenoate Ethyl 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydr oxy-3-oxa- 17,17-dimethyl-8-iso-13-cis-prostenoate1384 1350 728 Butyl 8.beta.-methyl-9-oxo-11.alpha.,15-dihydro xy-13- trans-prostenoate Butyl 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydr oxy-8-iso- 13-trans-prostenoate Butyl 8.beta.-methyl-9-oxo-11.alpha.,15-dihydro xy-13- cis-prostenoate Butyl 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydr oxy-8-iso- 13-cis-prostenoate1385 1352 1182 Decyl 8.beta.-methyl-9-oxo-11.alpha.,15-dihydro xy- 13-trans,17-cis-prostadienoate Decyl 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydr oxy-8-iso- 13-trans,17-cis-prostadienoate Decyl 8.beta.-methyl-9-oxo-11.alpha.,15-dihydro xy-13- cis-17-cis-prostadienoate Decyl 8.alpha.-methyl-9-oxo-11.alpha.,15-dihydr oxy-8-iso- 13-cis,17-cis-prostadienoate1386 1301 728 Ethyl 8.beta.-methyl-9-oxo-11.alpha.-acetoxy-15 -hydroxy- 13-trans-prostenoate Ethyl 8.alpha.-methyl-9-oxo-11.alpha.-acetoxy-1 5-hydroxy- 8-iso-13-trans-prostenoate Ethyl 8.beta.-methyl-9-oxo-11.alpha.-acetoxy-15 -hydroxy- 13-cis-prostenoate Ethyl 8.alpha.-methyl-9-oxo-11.alpha.-acetoxy-1 5-hydroxy- 8-iso-13-cis-prostenoate__________________________________________________________________________

EXAMPLE 1387

Preparation of 8.beta.-methyl-prostaglandin E.sub.1 (Example 1353) and 10 ml. of 1:9 aqueous acetic acid is heated to 65.degree. C. for 18 hours under an inert atmosphere. The solvent is removed in vacuo and the residue is purified upon Silic AR-CC-4.sup..RTM. using a benzene-ethylacetate gradient to yield the title compound.

EXAMPLES 1388-1522

treatment of the designated 8-methyl-9-oxo-11-hydroxy-prostenoic acid derivatives of Table 41 below with 1:9 aqueous acid and purification all as described in Example 1387 gives the corresponding 8-methyl-9-oxo-10,13-prostadienoic acids and esters of the table.

TABLE 41______________________________________ Starting 9-oxo- Product 8-methyl-9-oxo-Exam- 11-hydroxy 10,13-prostadienoicple derivative acids or esters______________________________________1388 8.alpha.-methyl-8-iso- 8.alpha.-methyl-8-iso-prosta- prostaglandin glandin A.sub.1 E.sub.1 (Example 1353)1389 8.beta.-methy-9-oxo- 8.beta.-methyl-11.alpha.,15-dihy- 11.alpha.,15-dihy- droxy-10,13-cis-prosta- droxy-13-cis- dienoic acid prostenoic acid (Example 1353)1390 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-11.alpha.,15-dihy- 11.alpha.,15-dihy- droxy-8-iso-10,13-cis- droxy-8-iso-13- prostadienoic acid cis-prostenoic acid (Example 1353)1391 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihy- droxy-16,16-dimethyl droxy-16,16-di- 10,13-trans-prostadie- methyl-13-trans- noic acid prostenoic acid (Example 1354)1392 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihy- droxy-16,16-dimethyl- droxy-16,16-di- 8-iso-10,13-trans-pro- methyl-8-iso-13- stadienoic acid trans-proste- noic acid (Exam- ple 1354)1393 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-16,16-dimethyl xy-16,16-di- 10,13-cis-prostadienoic methyl-13-cis- acid prostenoic acid (Example 1354)1394 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-16,16-dimethyl- xy-16,16-di- 8-iso-10,13-cis-pro- methyl-8-iso-13- stadienoic acid cis-prostenoic acid (Example 1354)1395 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-17,17-dimethyl xy-17,17-di- 10,13-trans-prostadie- methyl 13-trans- noic acid prostenoic acid (Example 1355)1396 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-17,17-dimethyl- xy-17,17-di- 8-iso-10,13-trans-pro- methyl-8-iso-13- stadienoic acid trans-prostenoic acid (Example 1355)1397 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro droxy-17,17-dimethyl xy-17,17-di- 10,13-cis-prostadie- methyl 13-cis- noic acid prostenoic acid (Example 1355)1398 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-17,17-dimethyl- xy-17,17-di- 8-iso-10,13-cis-pro- methyl-8-iso-13- stadienoic acid cis-prostenoic acid (Example 1355)1399 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-10,13-trans,17- xy-13-trans,17- cis-prostatrienoic cis-prostadi- acid enoic acid (Example 1356)1400 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-8-iso-10,13-trans,- xy-8-iso-13- 17-cis-prostatrienoic trans,17-cis- acid prostadienoic acid (Example 1356)1401 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-10,13-cis,17-cis- xy-13-cis,17-cis- prostatrienoic acid prostadienoic acid (Example 13561402 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-8-iso-10,13-cis,- xy-8-iso-13-cis,- 17-cis-prostatrienoic 17-cis-prostadi- acid enoic acid (Example 1356)1403 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-20-ethyl-10,13- xy-20-ethyl-13- trans-prostadienoic trans-proste- acid noic acid (Exam- ple 1357)1404 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-20-ethyl-8-iso- xy-20-ethyl-8- 10,13-trans-prostadi- iso-13-trans- enoic acid prostenoic acid (Example 1357)1405 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-20-ethyl-10,13- xy-20-ethyl-13- cis-prostadienoic acid cis-prostenoic acid (Example 1357)1406 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-20-ethyl-8-iso- xy-20-ethyl-8- 10,13-cis-prostadie- iso-13-cis-pro- noic acid stenoic acid (Example 1357)1407 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-6,7-dinor-10,13- xy-6,7-dinor-13- trans-prostadienoic trans-proste- acid noic acid (Exam- ple 1358)1408 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-6,7-dinor-8-iso- xy-6,7-dinor-8- 10,13-trans-prostadie- iso-13-trans- noic acid prostenoic acid (Example 1358)1409 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-6,7-dinor-10,13- xy-6,7-dinor-13- cis-prostadienoic acid cis-prostenoic acid (Example 1358)1410 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-6,7-dinor-8-iso- xy-6,7-dinor-8- 10,13-cis-prostadie- iso-13-cis-pro- noic acid stenoic acid (Example 1358)1411 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-5,6,7-trinor-20- xy-5,6,7-trinor- methyl 10,13-trans- 20-methyl 13- prostadienoic acid trans-prostenoic acid (Example 1359)1412 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-5,6,7-trinor-20- xy-5,6,7-trinor- methyl-8-iso-10,13- 20-methyl-8-iso- trans-prostadienoic 13-trans-pro- acid stenoic acid (Example 1359)1413 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-5,6,7-trinor-20- xy-5,6,7-trinor- methyl 10,13-cis-pro- 20-methyl 13- stadienoic acid cis-prostenoic acid (Example 1359)1414 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-5,6,7-trinor-20- xy-5,6,7-trinor- methyl-8-iso-10,13- 20-methyl-8- cis-prostadienoic acid iso-13-cis-pro- stenoic acid (Example 1359)1415 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-7a,7b-bishomo- xy-7a,7b-bishomo- 10,13-trans-prostadie- 13-trans-pro- noic acid stenoic acid (Example 1360)1416 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-7a,7b-bishomo- xy-7a,7b-bishomo- 8-iso-10,13-trans- 8-iso-13-trans- prostadienoic acid prostenoic acid (Example 1360)1417 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-7a,7b-bishomo- xy-7a,7b-bishomo- 10,13-cis-prostadie- 13-cis-proste- noic acid noic acid (Exam- ple 1360)1418 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-7a,7b-bishomo- xy-7a,7b-bishomo- 8-iso-10,13-cis-pro- 8-iso-13-cis- stadienoic acid prostenoic acid (Example 1360)1419 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-2-ethyl-10,13- xy-2-ethyl-13- trans-prostadienoic trans-proste- acid noic acid (Exam- ple 1361)1420 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-2-ethyl-8-iso- xy-2-ethyl-8- 10,13-trans-prostadi- iso-13-trans- enoic acid prostenoic acid (Example 1361)1421 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-2-ethyl-10,13- xy-2-ethyl-13- cis-prostadienoic acid cis-prostenoic acid (Example 1361)1422 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-2-ethyl-8-iso- xy-2-ethyl-8- 10,13-cis-prostadie- iso-13-cis-pro- noic acid stenoic acid (Example 1361)1423 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-3,3,20-trimethyl- xy-3,3,20-tri- 10,13-trans-prostadi- methyl-13-trans- enoic acid prostenoic acid (Example 1362)1424 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-3,3,20-trimethyl- xy-3,3,20-tri- 8-iso-10,13-trans-pro- methyl-8-iso-13- stadienoic acid trans-proste- noic acid (Example 1362)1425 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-3,3,20-trimethyl- xy-3,3,20-tri- 10,13-cis-prostadie- methyl-13-cis- noic acid prostenoic acid (Example 1362)1426 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-3,3,20-trimethyl- xy-3,3,20-tri- 8-iso-10,13-cis-pro- methyl-8-iso-13- stadienoic acid cis-prostenoic acid (Example 1362)1427 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-3-oxa-10,13-trans- xy-3-oxa-13- prostadienoic acid trans-proste- noic acid (Exam- ple 1363)1428 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-3-oxa-8-iso-10,- xy-3-oxa-8-iso- 13,trans-prostadienoic 13-trans-proste- acid noic acid (Exam- ple 1363)1429 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-3-oxa-10,13-cis- xy-3-oxa-13-cis- prostadienoic acid prostenoic acid (Example 1363)1430 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-3-oxa-8-iso-10,- xy-3-oxa-8-iso- 13-cis-prostadienoic 13-cis-proste- acid noic acid (Exam- ple 1363)1431 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-3-oxa-16,16-di- xy-3-oxa-16,16- methyl-10,13-trans-pro- dimethyl-13- stadienoic acid trans-proste- noic acid (Exam- ple 1364)1432 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-3-oxa-16,16-di- xy-3-oxa,16,16- methyl-8-iso-10,13- dimethyl-8-iso- trans-prostadienoic 13-trans-proste- acid noic acid (Exam- ple 1364)1433 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-3-oxa-16,16-di- xy-3-oxa-16,16- methyl-10,13-cis-pro- dimethyl-13-cis- stadienoic acid prostenoic acid (Example 1364)1434 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-3-oxa-16,16-di- xy-3-oxa-16,16- methyl-8-iso-10,13-cis- dimethyl-8-iso- prostadienoic acid 13-cis-proste- noic acid (Exam- ple 1364)1435 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-3-oxa-10,13- xy-3-oxa-13- trans,17-cis-prosta- trans,17-cis- trienoic acid prostadienoic acid (Example 1365)1436 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-3-oxa-8-iso-10,- xy-3-oxa-8-iso- 13-trans,17-cis-pro- 13-trans,17-cis- statrienoic acid prostadienoic acid (Example 1365)1437 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-3-oxa-10,13-cis,- xy-3-oxa-13-cis,- 17-cis-prostatrienoic 17-cis-prosta- acid dienoic acid (Example 1365)1438 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-3-oxa-8-iso-10,- xy-3-oxa-8-iso- 13-cis,17-cis-prosta- 13-cis,17-cis- trienoic acid prostadienoic acid (Example 1365)1439 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-3-oxa-20-ethyl- xy-3-oxa-20- 10,13-trans-prostadie- ethyl-13-trans- noic acid prostenoic acid (Example 1366)1440 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-3-oxa-20-ethyl- xy-3-oxa-20- 8-iso-10,13-trans- ethyl-8-iso-13- prostadienoic acid trans-proste- noic acid (Exam- ple 1366)1441 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-3-oxa-20-ethyl- xy-3-oxa-20- 10,13-cis-prostadie- ethyl-13-cis- noic acid prostenoic acid (Example 1366)1442 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-3-oxa-20-ethyl- xy-3-oxa-20- 8-iso-10,13-cis-pro- ethyl-8-iso-13- stadienoic acid cis-prostenoic acid (Example 1366)1443 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-2-fluoro-17,17- xy-2-fluoro-17,- dimethyl-10,13-trans- 17-dimethyl-13- prostadienoic acid trans-proste- noic acid (Exam- ple 1367)1444 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-2-fluoro-17,17- xy-2-fluoro-17,- dimethyl-8-iso-10,13- 17-dimethyl-8- trans-prostadienoic iso-13-trans- acid prostenoic acid (Example 1367)1445 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-2-fluoro-17,17- xy-2-fluoro-17,- dimethyl-10,13-cis- 17-dimethyl-13- prostadienoic acid cis-prostenoic acid (Example 1367)1446 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-2-fluoro-17,17- xy-2-fluoro-17,- dimethyl-8-iso-10,13- 17-dimethyl-8- cis-prostadienoic acid iso-13-cis-pro- stenoic acid (Example 1367)1447 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-7-nor-10,13-trans- xy-7-nor-13- prostadienoic acid trans-proste- noic acid (Exam- ple 1368)1448 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-7-nor-8-iso-10,- xy-7-nor-8-iso- 13-trans-prostadienoic 13-trans-pro- acid stenoic acid (Example 1368)1449 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-7-nor-10,13-cis- xy-7-nor-13-cis- prostadienoic acid prostenoic acid (Example 1368)1450 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha. ,15-dihydro- droxy-7-nor-8-iso-10,- xy-7-nor-8-iso- 13-cis-prostadienoic 13-cis-proste- acid noic acid (Exam- ple 1368)1451 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-7a-homo-16,16- xy-7a-homo-16,- dimethyl-10,13-trans- 16-dimethyl-13- prostadienoic acid trans-proste- noic acid (Exam- ple 1369)1452 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-7a-homo-16,16- xy-7a-homo-16,- dimethyl-8-iso-10,13- 16-dimethyl-8- trans-prostadienoic iso-13-trans- acid prostenoic acid (Example 1369)1453 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-7a-homo-16,16- xy-7a-homo-16,- dimethyl-10,13-cis- 16-dimethyl-13- prostadienoic acid cis-prostenoic acid (Example 1369)1454 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-7a-homo-16,16- xy-7a-homo-16,- dimethyl-8-iso-10,13- 16-dimethyl-8- cis-prostadienoic acid iso-13-cis-pro- stenoic acid (Example 1369)1455 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-2-phenyl-10,13- xy-2-phenyl-13- trans-prostadienoic trans-prostenoic acid acid (Example 1370)1456 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-2-phenyl-8-iso- xy-2-phenyl-8- 10,13-trans-prostadi- iso-13-trans- enoic acid prostenoic acid (Example 1370)1457 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-2-phenyl-10,13- xy-2-phenyl-13- cis-prostadienoic acid cis-prostenoic acid (Example 1370)1458 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-2-phenyl-8-iso- xy-2-phenyl-8- 10,13-cis-prostadie- iso-13-cis-pro- noic acid stenoic acid (Example 1370)1459 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-2-methyl-10,13- xy-2-methyl-13- trans,17-cis-prosta- trans,17-cis- trienoic acid prostadienoic acid (Example 1371)1460 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-2-methyl-8-iso- xy-2-methyl-8- 10,13-trans,17-cis- iso-13-trans,- prostatrienoic acid 17-cis-prostadi- enoic acid (Example 1371)1461 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-2-methyl-10,13- xy-2-methyl-13- cis,17-cis-prostatri- cis,17-cis-pro- enoic acid stadienoic acid (Example 1371)1462 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-2-methyl-8-iso- xy-2-methyl-8- 10,13-cis,17-cis-pro- iso-13-cis,17- statrienoic acid cis-prostadie- noic acid (Exam- ple 1371)1463 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-5,cis,10,13-trans- xy-5-cis,13- prostatrienoic acid trans-prosta- dienoic acid (Example 1372)1464 8.alpha.-methyl-9-oxo- 8.alpha. -methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-8-iso-5,cis,10- xy-8-iso-5,cis,- 13-trans-prostatrienoic 13-trans-prosta- acid dienoic acid (Example 1372)1465 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-5,cis,10,13-cis- xy-5,cis,13-cis- prostatrienoic acid prostadienoic acid (Example 1372)1466 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-8-iso-5,cis,10,13- xy-8-iso-5,cis,- cis-prostatrienoic acid 13-cis-prostadi- enoic acid (Example 1372)1467 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-5-cis,10,13- xy-5-cis,13- trans,17-cis-prosta- trans,17-cis- tetraeneoic acid prostatrienoic acid (Example 1373)1468 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-8-iso-5-cis,10,- xy-8-iso-5-cis,- 13-trans,17-cis-prosta- 13-trans,17-cis- tetraeneoic acid prostatrienoic acid (Example 1373)1469 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-5-cis,10,13-cis,- xy-5-cis,13-cis,- 17-cis-prostatetrae- 17-cis-prosta- neoic acid trienoic acid (Example 1373)1470 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-8-iso-5-cis,10,- xy-8-iso-5-cis,- 13-cis,17-cis-prostate- 13-cis,17-cis- traeneoic acid prostatrienoic acid (Example 1373)1471 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-16,16-dimethyl- xy-16,16-di- 5-cis,10,13-trans-pro- methyl-5-cis,13- statrienoic acid trans-prostadi- enoic acid (Exam- ple 1374)1472 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-16,16-dimethyl- xy-16,16-di- 8-iso-5-cis,10,13- methyl-8-iso-5- trans-prostatrienoic cis,13-trans- acid prostadienoic acid (Example 1374)1473 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-16,16-dimethyl- xy-16,16-di- 5-cis,10,13-cis-pro- methyl-5-cis,13- statrienoic acid cis-prostadie- noic acid (Exam- ple 1374)1474 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-16,16-dimethyl- xy-16,16-di- 8-iso-5-cis,10,13-cis- methyl-8-iso-5- prostatrienoic acid cis,13-cis-pro- stadienoic acid (Example 1374)1475 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-4-nor-20-methyl- xy-4-nor-20- 5-cis,10,13-trans-pro- methyl-5-cis,- statrienoic acid 13-trans-prosta- dienoic acid (Example 1375)1476 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-4-nor-20-methyl- xy-4-nor-20- 8-iso-5-cis,10,13- methyl-8-iso- trans-prostatrienoic 5-cis,13-trans- acid prostadienoic acid (Example 1375)1477 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-4-nor-20-methyl- xy-4-nor-20- 5-cis,10,13-cis-pro- methyl-5-cis,- statrienoic acid 13-cis-prostadi- enoic acid (Example 1375)1478 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-4-nor-20-methyl- xy-4-nor-20- 8-iso-5-cis,10,13- methyl-8-iso- cis-prostatrienoic 5-cis,13-cis- acid prostadienoic acid (Example 1375)1479 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-4a-homo-17,17-di- xy-4a-homo-17,- methyl-5-cis,10,13- 17-dimethyl-5- trans-prostatrienoic cis,13-trans- acid prostadienoic acid (Example 1376)1480 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-4a-homo-17,17-di- xy-4a-homo-17,- methyl-8-iso-5-cis,10- 17-dimethyl-8- 13-trans-prostatrienoic iso-5-cis,13- acid trans-prostadi- enoic acid (Exam- ple 1376)1481 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-4a-homo-17,17-di- xy-4a-homo-17,- methyl-5-cis,10,13-cis- 17-dimethyl-5- prostatrienoic acid cis,13-cis-pro- stadienoic acid (Example 1376)1482 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-4a-homo-17,17-di- xy-4a-homo-17,- methyl-8-iso-5-cis,10- 17-dimethyl-8- 13-cis-prostatrienoic iso-5-cis,13- acid cis-prostadie- noic acid (Exam- ple 1376)1483 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-4a,4b-bishomo- xy-4a,4b-bis- 20-ethyl-5-cis,10,13- homo-20-ethyl- trans-prostatrienoic 5-cis,13-trans- acid prostadienoic acid (Example 1377)1484 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-4a,4b-bishomo- xy-4a,4b-bis- 20-ethyl-8-iso-5-cis,- homo-20-ethyl-8- 10,13-trans-prostatrie- iso-5-cis,13- noic acid trans-prostadi- enoic acid (Example 1377)1485 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-4a,4b-bishomo- xy-4a,4b-bis- 20-ethyl-5-cis,10,13- homo-20-ethyl-5- cis-prostatrienoic cis,13-cis-pro- acid stadienoic acid (Example 1377)1486 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-4a,4b-bishomo- xy-4a,4b-bishomo- 20-ethyl-8-iso-5-cis,- 20-ethyl-8-iso- 10,13-cis-prostatrie- 5-cis,13-cis- noic acid prostadienoic acid (Example 1377)1487 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-4a,4b-bishomo- xy-4a,4b-bishomo- 5-cis,10,13-trans,17- 5-cis,13-trans,- cis-prostatetraenoic 17-cis-prostatri- acid enoic acid (Example 1378)1488 8.alpha. -methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-4a,4b-bishomo- xy-4a,4b-bishomo- 8-iso-5-cis,10,13- 8-iso-5-cis,13- trans,17-cis-prostate- trans,17-cis- traenoic acid prostatrienoic acid (Example 1378)1489 8.beta.-methyl-9-oxo- 8.beta.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-4a,4b-bishomo-5- xy-4a,4b-bishomo- cis,10,13-cis-17-cis- 5-cis,13-cis- prostatetraenoic acid 17-cis-prosta- acid trienoic acid (Example 1378)1490 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9-oxo-15-hy- 11.alpha.,15-dihydro- droxy-4a,4b-bishomo-8- xy-4a,4b-bishomo- iso-5-cis,10,13-cis- 8-iso-5-cis,13- 17-cis-prostatetrae- cis-17-cis-pro- noic acid statrienoic acid (Example 1378)1491 methyl 8.beta.-methyl- methyl 8.beta.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-20-methyl- hydroxy-20-methyl- 10,13-trans-prostadi- 13-trans-proste- enoate noate (Example 1379)1492 methyl 8.alpha.-methyl- methyl 8.alpha.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-20-methyl- hydroxy-20- 8-iso-10,13-trans-pro- methyl-8-iso- stadienoate 13-trans-pro- stenoate (Exam- ple 1379)1493 methyl 8.beta.-methyl- methyl 8.beta.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-20-methyl- hydroxy-20- 10,13-cis-prostadie- methyl-13-cis- noate prostenoate (Example 1379)1494 methyl 8.alpha.-methyl- methyl 8.alpha.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-20-methyl- hydroxy-20- 8-iso-10,13-cis-pro- methyl-8-iso- stadienoate 13-cis-proste- noate (Example 1379)1495 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-7a,7b-bis- hydroxy-7a,7b- homo-10,13-trans,17- bishomo-13- cis-prostatrienoate trans,17-cis- prostadienoate (Example 1380)1496 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-7a,7b-bis- hydroxy-7a,7b- homo-8-iso-10,13-trans,- bishomo-8-iso- 17-cis-prostatrienoate 13-trans,17- cis-prostadie- noate (Example 1380)1497 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9-oxo- 9-oxo-11.alpha.,15- 15-hydroxy-7a,7b,-bis- dihydroxy-7a,- homo-10,13-cis,17-cis- 7b-bishomo-13- prostatrienoate cis,17-cis-pro- stadienoate (Example 1380)1498 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-7a,7b-bis- hydroxy-7a,7b- homo-8-iso-10,13-cis,- bishomo-8-iso- 17-cis-prostatrienoate 13-cis,17-cis- prostadienoate (Example 1380)1499 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-2-ethyl- hydroxy-2-ethyl- 16,16-dimethyl-10,13- 16,16-dimethyl- trans-prostadienoate 13-trans-proste noate (Example 1381)1500 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-2-ethyl- hydroxy-2-ethyl- 16,16-dimethyl-8-iso- 16,16-dimethyl- 10,13-trans-prostadi- 8-iso-13-trans- enoate prostenoate (Example 1381)1501 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-2-ethyl- hydroxy-2-ethyl- 16,16-dimethyl-10,13- 16,16-dimethyl- cis-prostadienoate 13-cis-proste- noate (Example 1381)1502 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-2-ethyl- hydroxy-2-ethyl- 16,16-dimethyl-8-iso- 16,16-dimethyl- 10,13-cis-prostadie- 8-iso-13-cis- noate prostenoate (Example 1381)1503 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-3,3,17,17- hydroxy-3,3,17,- tetramethyl-10,13- 17-tetramethyl- trans-prostadienoate 13-trans-proste- noate (Example 1382)1504 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-3,3,17,17- hydroxy-3,3,17,- tetramethyl-8-iso-10,- 17-tetramethyl-8- 13-trans-prostadienoate iso-13-trans-pro- stenoate (Example 1382)1505 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-3,3,17,17- hydroxy-3,3,17,- tetramethyl-10,13-cis- 17-tetramethyl- prostadienoate 13-cis-proste- noate (Example 1382)1506 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-3,3,17,17- hydroxy-3,3,17,- tetramethyl-8-iso-10,- 17-tetramethyl- 13-cis-prostadienoate 8-iso-13-cis- prostenoate (Example 1382)1507 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-3-oxa-17,- hydroxy-3-oxa- 17-dimethyl-10,13-trans- 17,17-dimethyl- prostadienoate 13-trans-proste- noate (Example 1383)1508 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-3-oxa-17,17- hydroxy-3-oxa- dimethyl-8-iso-10,13- 17,17,-dimethyl- trans-prostadienoate 8-iso-13-trans- prostenoate (Example 1383)1509 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-3-oxa-17,17- hydroxy-3-oxa- dimethyl-10,13-cis- 17,17-dimethyl- prostadienoate 13-cis-proste- noate (Example 1383)1510 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-3-oxa-17,- hydroxy-3-oxa- 17-dimethyl-8-iso-10,- 17,17-dimethyl- 13-cis-prostadienoate 8-iso-13-cis- prostenoate (Example 1383)1511 butyl 8.beta.-methyl- butyl 8.beta.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-10,13-trans- hydroxy-13-trans- prostadienoate prostenoate (Example 1384)1512 buty 8.alpha.-methyl- butyl 8.alpha.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-8-iso-10,- hydroxy-8-iso-13- 13-trans-prostadienoate trans-prosteno- ate (Example 1384)1513 butyl 8.beta.-methyl- butyl 8.beta.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-13-cis-pro- hydroxy-13-cis- stadienoate prostenoate (Example 1384)1514 butyl 8.alpha.-methyl- butyl 8.alpha.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-8-iso-10,13- hydroxy-8-iso-13- cis-prostadienoate cis-prostenoate (Example 1384)1515 decyl 8.beta.-methyl- decyl 8.beta.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-10,13-trans,- hydroxy-13-trans,- 17-cis-prostatrienoate 17-cis-prostadi- enoate (Example 1385)1516 decyl 8.alpha.-methyl- decyl 8.alpha.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-8-iso-10,- hydroxy-8-iso- 13-trans,17-cis-prosta- 13-trans,17-cis- trienoate prostadienoate (Example 1385)1517 decyl 8.beta.-methyl- decyl 8.beta.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-10,13-cis- hydroxy-13-cis- 17-cis-prostatrienoate 17-cis-prostadi- enoate (Example 1385)1518 decyl 8.alpha.-methyl- decyl 8.alpha.-methyl-9-oxo- 9-oxo-11.alpha.,15-di- 15-hydroxy-8-iso-10,13- hydroxy-8-iso-13- cis-17-cis-prostatrie- cis-17-cis-pro- noate stadienoate (Example 1385)1519 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9-oxo- 9-oxo-11.alpha.-ace- 15-hydroxy-10,13-trans- toxy-15-hydroxy- prostadienoate 13-trans-proste- noate (Example 1386)1520 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9-oxo- 9-oxo-11.alpha.-ace- 15-hydroxy-8-iso-10,13- toxy-15-hydroxy- trans-prostadienoate 8-iso-13-trans- prostenoate (Example 1386)1521 ethyl 8.beta.-methyl- ethyl 8.beta.-methyl-9-oxo- 9-oxo-11.alpha.-ace- 15-hydroxy-10,13-cis- toxy-15-hydroxy- prostadienoate 13-cis-proste- noate (Example 1386)1522 ethyl 8.alpha.-methyl- ethyl 8.alpha.-methyl-9-oxo- 9-oxo-11.alpha.-ace- 15-hydroxy-8-iso-10,13- toxy-15-hydroxy- cis-prostadienoate 8-iso-13-cis- prostenoate (Example 1386)______________________________________

EXAMPLES 1523-1654

Treatment of the designated 9-oxo-prostenoic acid and ester derivatives listed in Table 42 below with sodium borohydride in ethanol as described in Example 257 gives the product 9.alpha. and 9.beta. hydroxy derivatives of the table, which are separable by standard chromatographic techniques.

TABLE 42______________________________________ Starting 8- Product methyl-9-oxo- 8-methyl-p.alpha./.beta.,- 11.alpha.,15-di- 11.alpha.,15-trihydroxy-Ex- hydroxy-13-prosten- 13-prostenoicample oic acid or ester acid or ester______________________________________1523 8.beta.-methyl-prosta- 8.beta.-methyl-prosta- glandin E.sub.1 glandin F.sub.1 .alpha./F.sub.1 .beta. (Example 1353)1524 8.alpha.-methyl-8-iso- 8.alpha.-methyl-8-iso-pros- prostaglandin E.sub.1 taglandin F.sub.1 .alpha./F.sub.1 .beta. (Example 1353)1525 8.beta.-methyl-9-oxo-11.alpha.- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-13-cis 15-trihydroxy-13- prostenoic acid cis-prostenoic acid (Example 1353)1526 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9.alpha./.beta., 11.alpha., 11.alpha.,15-dihydroxy- 15-trihydroxy-8-iso- 8-iso-13-cis-pros 13-cis-prostenoic tenoic acid acid (Example 1353)1527 8.beta.-methyl-9-oxo- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 11.alpha.,15-dihydroxy- 15-trihydroxy-16,16- 16,16-dimethyl-13- dimethyl-13-trans- trans-prostenoic prostenoic acid acid (Example 1354)1528 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.- 11.alpha.,15-dihydroxy- 15-trihydroxy-16,16- 16,16-dimethyl-8- dimethyl-8-iso-13- iso-13-trans-pros- trans-prostenoic acid tenoic acid (Example 1354)1529 8.beta.-methyl-9-oxo- 8.beta.-methyl-9.alpha./.beta.,11.alpha.- 11.alpha.,15-dihydroxy- 15-trihydroxy-16,16- 16,16-dimethyl-13-, dimethyl-13-cis- cis-prostenoic acid prostenoic acid (Example 1354)1530 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9.alpha./.beta.,11.alpha., 11.alpha.,15-dihydroxy- 15-trihydroxy-16,16- iso-13-cis-pros- dimethyl-8-iso-13- tenoic acid (Example 1354)1531 8.beta.-methyl-9-oxo-11.alpha.- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-17,17- 15-trihydroxy-17,17- dimethyl-13-trans- dimethyl-13-trans- prostenoic acid prostenoic acid (Example 1355)1532 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 11.alpha.,15-dihydroxy-8- 15-trihydroxy-17,17- iso-17,17-di- dimethyl-8-iso-13- methyl-13-trans- trans-prostenoic prostenoic acid acid (Example 1355)1533 8.beta.-methyl-9-oxo- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 11.alpha.,15-dihydroxy-17, 15-trihydroxy-17,17- 17-dimethyl-13-cis- dimethyl-13-cis- prostenoic acid prostenoic acid (Example 1355)1534 8.alpha.-methyl-9-oxo- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 11.alpha.,15-dihydroxy- 15-trihydroxy-8-iso- 17,17-dimethyl-8- 17,17-dimethyl-13- iso-13-cis-pros- cis-prostenoic tenoic acid acid (Example 1355)1535 8.beta.-methyl-9-oxo-11.alpha.- 8.beta.-methyl-9.alpha./.beta.,11.alpha.- 15-dihydroxy-13- 15-trihydroxy-13- trans-17-cis-pro- trans,17-cis-pros- stadienoic acid tadienoic acid (Example 1356)1536 8.alpha.-methyl-9-oxo-11.alpha.- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-8-iso- 15-trihydroxy-8-iso- 13-trans,17-cis- 13-trans-17-cis- prostadienoic acid prostadienoic acid (Example 1356)1537 8.beta.-methyl-9-oxo-11.alpha.- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-13-cis, 15-trihydroxy-13-cis, 17-cis-prostadienoic 17-cis-prostadienoic acid acid (Example 1356)1538 8.alpha.-methyl-9-oxo-11.alpha.- 8.alpha.-methyl-9-.alpha./.beta.,11.alpha.,- 15-dihydroxy-8-iso- 15-trihydroxy-8-iso- 13-trans-17-cis- 13-cis,17-cis-pros- prostadienoic acid tadienoic acid (Example 1356)1539 8.beta.-methyl-9-oxo-11.alpha.- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-20- 15-trihydroxy-20- ethyl-13-trans-pros- ethyl-13-trans-pros- tenoic acid tenoic acid (Example 1357)1540 8.alpha.-methyl-9-oxo-11.alpha.- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-20- 15-trihydroxy-20- ethyl-8-iso-13-trans- ethyl-8-iso-13- prostenoic acid trans-prostenoic (Example 1357)1541 8.beta.-methyl-9-oxo-11.alpha.- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-20-eth- 15-trihydroxy-20- yl-13-cis-prostenoic ethyl-13-cis-pro- acid stenoic acid (Example 1357)1542 8.alpha.-methyl-9-oxo-11.alpha.- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-20- 15-trihydroxy-20- ethyl-8-iso-13-cis- ethyl-8-iso-13-cis- prostenoic acid prostenoic acid (Example 1357)1543 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-6,7- 15-trihydroxy-6,7- dinor-13-trans-pros- dinor-13-trans-pros- tenoic acid tenoic acid (Example 1358)1544 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-6,7- 15-trihydroxy-6,7- dinor-8-iso-13-trans- dinor-8-iso-13- prostenoic acid trans-prostenoic (Example 1358) acid1545 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-6,7- 15-trihydroxy-6,7- dinor-13-cis- dinor-13-cis- prostenoic acid prostenoic acid (Example 1358)1546 8.alpha.-metehyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-6,7- 15-trihydroxy-6,7- dinor-8-iso-13-cis- dinor-8-iso-13-cis- prostenoic acid prostenoic acid (Example 1358)1547 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-diohydroxy-5,6,7- 15-trihydroxy-5,6,7- trinor-20-methyl-13- trinor-20-methyl-13- trans-prostenoic acid trans-prostenoic acid (Example 1359)1548 8.alpha.-methyl-9-oxo-11.alpha. ,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-5,6,7- 15-trihydroxy-5,6,7- trinor-20-:methyl-8- trinor-20-methyl-8- iso-13-trans-pros- iso-13-trans-prosten- tenoic acid oic acid (Example 1359)1549 8.beta.-methyl-9-oxo-11.alpha.- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-5,6,7,- 15-trihydroxy-5,6,7- trinor-20-methyl- trinor-20-methyl-13- 13-cis-prostenoic cis-prostenoic acid acid (Example 1359)1550 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-5,6,7- 15-trihydroxy-5,6,7- trinor-20-methyl-8- trinor-20-methyl-8- iso-13-cis-prosten- iso-13-cis-prosten- oic acid oic acid (Example 1359)1551 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-7a,7b- 15-trihydroxy-7a,7b- bishomo-13-trans- bishomo-13-trans- prostenoic acid prostenoic acid (Example 1360)1552 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-7a,7b- 15-trihydroxy-7a,7b- bishomo-8-iso-13- bishomo-8-iso-13- trans-prostenoic trans-prostenoic acid acid (Example 1360)1553 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.- 15-dihydroxy-7a,7b- 15-trihyroxy-7a,7b- bishomo-13-cis- bishomo-13-cis-pro- prostenoic acid stenoic acid (Example 1360)1554 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11 ,- 15-dihydroxy-7a,7b- 15-trihydroxy-7a,7b- bishomo-8-iso-13- bishomo-8-iso-13-cis- cis-prostenoic acid prostenoic acid (Example 1360)1555 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-2-eth- 15-trihydroxy-2- yl-13-trans-prosten- ethyl-13-trans- oic acid prostenoic acid (Example 1361)1556 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-2-eth- 15-trihydroxy-2- yl-8-iso-13-trans- ethyl-8-iso-13-trans- prostenoic acid prostenoic acid (Example 1361)1557 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-2-ethyl- 15-trihydroxy-2- 13-cis-prostenoic ethyl-13-cis-pro- acid stenoic acid (Example 1361)1558 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.- 15-dihydroxy-2- 15,trihydroxy-2- ethyl-8-iso-13-cis ethyl-8-iso-13-cis- prostenoic acid prostenoic acid (Example 1361)1559 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-3,3,20- 15-trihydroxy-3,3,20- trimethyl-8-iso-13- trimethyl-13-trans- trans-prostenoic prostenoic acid acid (Example 1362)1560 8.alpha.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9-.alpha./.beta.,11.alpha. ,- 15-dihydroxy-3,3,20-15-trihydroxy-3,3 trimethyl-8-iso-13- 20-trimethyl-8-iso- trans-prostenoic ac 13-trans-prostenoic acid (Example 1362) acid1561 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-3,3,20- 15-trihydroxy-3,3, trimethyl-13-cis- 20-trimethyl-13-cis- prostenoic acid prostenoic acid (Example 1362)1562 8.alpha.-methyl-9-oxo-11.alpha.- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-3,3,20- 15-trihydroxy-3,3,20- trimethyl-8-iso-13- trimethyl-8-iso-13- cis-prostenoic acid cis-prostenoic acid (Example 1362)1563 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-3-oxa- 15-trihydroxy-3-oxa-13-trans-prostenoic 13-trans-prostenoic acid acid (Example 1363)1564 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-3-oxa- 15-trihydroxy-3-oxa- 8-iso-13-trans- 8-iso-13-trans- prostenoic acid prostenoic acid (Example 1363)1565 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta. ,11.alpha.,- 15-dihydroxy-3-oxa-8 15-trihydroxy-3-oxa- 8-iso-13-cis-pro 8-iso-13-cis-pro- stenoic acid stenoic acid (Example 1363)1566 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-3-oxa- 15-trihydroxy-3-oxa- 8-iso-13-cis-pro- 8-iso-13-cis-pro- stenoic acid stenoic acid (Example 1363)1567 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.-11.alpha.,- 15-dihydroxy-3-oxa- 15-trihydroxy-3-oxa- 16,16-dimethyl-13- 16,16-dimethyl-13- trans-prostenoic trans-prostenoic acid acid (Example 1364)1568 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.-11.alpha.,- 15-dihydroxy-3-oxa-5-trihydroxy-3-oxa- 16,16-dimethyl-8- 16,16-dimethyl-8- iso-13-trans-pro- iso-13-trans-pro- stenoic acid stenoic acid (Example 1364)1569 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.-11.alpha.,- 15-dihydroxy-3-oxa- 15-trihydroxy-3-oxa- 16,16-dimethyl-13- 16,16-dimethyl-13- cis-prostenoic acid cis-prostenoic acid (Example 1364)1570 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.-11.alpha.,- 15-dihydroxy-3-oxa- 15-trihydroxy-3-oxa- 16,16-dimethyl-8- 16,16-dimethyl-8- iso-13-cis-pro- iso-13-cis-pro- stenoic acid stenoic acid (Example 1364)1571 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-3-oxa- 15-trihydroxy-3-oxa- 13-trana,17-cis- 13-trans,17-cis- prostadienoic acid prostadienoic acid (Example 1365)1572 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-3-oxa- 15-trihydroxy-3-oxa- 8-iso-13-trans,17- 8-iso-13-trans,17-cis-prostadienoiccis-prostadienoic acid acid (Example 1365)1573 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-3-oxa- 15-trihydroxy-3-oxa-13-cis,17-cis-pro-13-cis,17-cis- stadienoic acidprostadienoic acid (Example 1365)1574 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-3-oxa- 15-trihydroxy-3-oxa- 8-iso-13-cis,17-cis- 8-iso-13-cis,17-cis- prostadienoic acid prostadienoic acid (Example 1365)1575 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-3-oxa- 15-trihydroxy-3-oxa- 20-ethyl-13-trans- 20-ethyl-13-trans- prostenoic acid prostenoic acid (Example 1366)1576 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-3-oxa- 15-trihydroxy-3-oxa- 20-ethyl-8-iso-13- 20-ethyl-8-iso-13- trans-prostenoic trans-prostenoic acid acid (Example 1366)1577 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-3-oxa- 15-trihydroxy-3-oxa- 20-ethyl-13-cis- 20-ethyl-13-cis- prostenoic acid prostenoic acid (Example 1366)1578 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-3-oxa- 15-trihydroxy-3-oxa- 20-ethyl-8-iso-13- 20-ethyl-8-iso-13- cis-prostenoic acid cis-prostenoic acid (Example 1366)1579 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-2-flu- 15-trihydroxy-2- oro-17,17-dimethyl- fluoro-17,17-dimeth- 13-trans-prostenoic yl-13-trans-prosten- acid oic acid (Example 1367)1580 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihyhdroxy-2-flu- 15-trihydroxy-2- oro-17,17-dimethyl- fluoro-17,17-dimeth- 8-iso-13-trans- yl-8-iso-13-trans- prostenoic acid prostenoic acid (Example 1367)1581 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl 9.alpha./.beta.,11.alpha.,- 15-dihydroxy-2- 15-trihydroxy-2- fluoro-17,17-di- fluoro-17,17-dimeth- methyl-13-cis-pros- yl-13-cis-prostenoic tenoic acid acid (Example 1367)1582 8.alpha.-methyl-9-oxo-11.alpha. ,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-2-flu- 15-trihydroxy-2- oro-17,17-dimethyl- fluoro-17,17-dimeth- 8-iso-13-cis-pros- yl-8-iso-13-cis- tenoic acid prostenoic acid (Example 1367)1583 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-7-nor- 15-trihydroxy-7-nor- 13-trans-prostenoic 13-trans-prostenoic acid acid (Example 1368)1584 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-7-nor- 15-trihydroxy-7-nor- 8-iso-13-trans-pros- 8-iso-13-trans-pros- tenoic acid tenoic acid (Example 1368)1585 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-7-nor- 15-trihydroxy-7-nor- 13-cis-prostenoic 13-cis-prostenoic acid acid (Example 1368)1586 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-7-nor- 15-trihydroxy-7-nor- 8-iso-13-cis-prosten- 8-iso-13-cis-pro- oic acid stenoic acid (Example 1368)1587 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-7a-nomo- 15-trihydroxy-7a- 16,16-dimethyl-13- homo-16,16-dimethyl- trans-prostenoic 13-trans-prostenoic acid acid (Example 1369)1588 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihyhdroxy-7a- 15-trihydroxy-7a- homo-16,16-dimethyl- homo-16,16-dimethyl- 8-iso-13-trans-pros- 8-iso-13-trans-pro- tenoic acid stenoic acid (Example 1369)1589 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-7a- 15-trihydroxy-7a- homo-16,16-dimethyl- homo-16,16-dimethyl- 13-cis-prostenoic 13-cis-prostenoic acid acid (Example 1369)1590 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.crclbar.,11.alpha.,- 15-dihydroxy-7a- 15-trihydroxy-7a- homo-16,16-dimethyl- homo-16,16-dimethyl- 8-iso-13-cis-prosten- 8-iso-13-cis-pros- oic acid tenoic acid (Example 1369)1591 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-2-phen- 15-trihydroxy-2- yl-13-trans-prosten- phenyl-13-trans-pros- oic acid tenoic acid (Example 1370)1592 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-2-phen- 15-trihydroxy-2-phen- yl-8-iso-13-trans- yl-8-iso-13-trans- prostenoic acid prostenoic acid (Example 1370)1593 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-2-phen- 15-trihydroxy-2-phen- yl-13-cis-prostenoic yl-13-cis-prostenoic acid acid (Example 1370)1594 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-2-phen- 15-trihydroxy-2- yl-8-iso-13-cis- phenyl-8-iso-13-cis- prostenoic acid prostenoic acid (Example 1370)1595 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-2-meth- 15-trihydroxy-2-meth- yl-13-trans-17-cis- yl-13-trans,17-cis- prostadienoic acid prostadienoic acid (Example 1371)1596 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl;-9.alpha./.beta.,11.alpha.,- 15-diohydroxy-2- 15-trihydroxy-2-meth- methyl-8-iso-13- yl-8-iso-13 trans,17-cis-prosta- cis- dienoic acid acid (Example 1371)1597 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,121.alpha.,- 15-dihydroxy-2-meth- 15-trihydroxy-2- yl-13-cis,17-cis- methyl-13-cis,17-cis- prostadienoic acid prostadienoic acid (Example 1371)1598 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-2- 15-trihydroxy-2-meth- methyl-8-iso-13-cis, yl-8-iso-13-cis,17- 17-cis-prostadienoic cis-prostadienoic acid (Example 1371) acid1599 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta. ,11.alpha.,- 15-dihydroxy-5,cis,- 15-trihydroxy-5 cis- 13-trans-prosta- 13-trans-prostadien- dienoic acid oic acid (Example 1372)1600 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-8-iso- 15-trihydroxy-8-iso- 5-cis-13-trans-pros- 5 cis,13-trans-pros- tadienoic acid tadienoic acid (Example 1372)1601 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-5-cis, 15-trihydroxy-5-cis- 13-cis-prostadien- 13-cis-prostadienoic oic acid acid (Example 1372)1602 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-8-iso- 15-trihydroxy-8-iso- 5-cis-13-cis-prosta- 5 cis 13-cis-prosta- dienoic acid dienoic acid (Example 1372)1603 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-5-cis,- 15-trihydroxy-5-cis,- 13-trans,17-cis- 13-trans,17-cis- prostatrienoic acid (Example 1373)1604 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-8-iso- 15-dihydroxy-8-iso- 5-cis,13-trans,17- 5-cis,13-trans,17- cis-prostatrienoic cis-prostatrienoic acid acid (Example 1373)1605 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-5-cis,- 15-trihydroxy-5-cis,- 13-cis,17-cis-prosta- 13-cis,17-cis- trienoic acid prostatrienoic acid (Example 1373)1606 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-8-iso- 15-trihydroxy-8-iso- 5-cis,13-cis,17- 5-cis,13-cis,17-cis- cis-prostatrienoic prostatrienoic acid acid (Example 1373)1607 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-16,16- 15-trihydroxy-16,16- dimethyl-5-cis,13- dimethyl-5-cis,13- trans-prostadienoic trans-prostadienoic (Example 1374) acid1608 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-16,16- 15-trihydroxy-16,16- dimethyl-8-iso-5- dimethyl-8-iso-5-cis- cis,13-trans-prosta- 13-trans-prostadien- dienoic acid oic acid (Example 1374)1609 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-16,16- 15-trihydroxy-16,16- dimethyl-5-cis dimethyl-5-cis,13- 13-cis-prostadienoic cis-prostadienoic acid acid (Example 1374)1610 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihnydroxy-16,16- 15-trihydroxy-16,16- dimethyl-8-iso-5-cis- dimethyl-8-iso-5-cis- 13-cis-prostadienoic 13-cis-prostadienoic acid (Exampler 1374) acid1611 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-4-nor- 15-trihydroxy-4-nor- 20-methyl-5-cis,13- 20-methyl-5-cis,13- trans-prostadienoic trans-prostadienoic acid acid (Example 1375)1612 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-4-nor- 15-trihydroxy-4-nor- 20-methyl-8-iso-5- 20-methyl-8-iso- cis,13-trans-pros- 5-cis,13-trans- tadienoic acid prostadienoic acid (Example 1375)1613 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-4-nor- 15-trihydroxy-4-nor- 20-methyl-5-cis,13- 20-methyl-5-cis,13- cis-prostadienoic cis-prostadienoic acid acid (Example 1375)1614 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-4-nor- 15-trihydroxy-4-nor- 20-methyl-8-iso-5- 20-methyl-8-iso-5- cis,13-cis-prosta- cis,13-cis-prosta- dienoic acid dienoic acid (Example 1375)1615 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-4a-homo- 15-trihydroxy-4a- 17,17-dimethyl-5-cis- homo-17,17-dimethyl- 13-trans-prostadien- 5-cis,13-trans-pros- oic acid tadienoic acid (Example 1376)1616 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-4a-homo- 15-trihydroxy-4a- 17,17-dimethyl-8- homo-17,17-dimethyl- iso-5-cis,13-trans- 8-iso-5-cis,13-cis- prostadienoic acid prostadienoic acid (Example 1376)1617 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-4a-homo- 15-trihydroxy-4a- 17,17-dimethyl-5-cis- homo-17,17-dimethyl- 13-cis-prostadienoic 5-cis,13-cis-prosta- acid dienoic acid (Example 1376)1618 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-4a-homo- 15-trihydroxy-4a- 17,17-dimethyl-8-iso- homo-17,17-dimethyl- 5-cis,13-cis-prosta- 8-iso-5-cis,13-cis- dienoic acid prostadienoic acid (Example 1376)1619 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-4a,4b- 15-trihydroxy-4a,4b- bishomo-20-ethyl-5- bishomo-20-ethyl- cis,13-trans-prosta- 5-cis,13-trans-pros- dienoic acid tadienoic acid (Example 1377)1620 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-4a,4b- 15-trihydroxy-4a,4b- bishomo-20-ethyl-8- bishomo-20-ethyl-8- iso-5-cis,13-trans- iso-5-cis,13-trans- prostadienoic acid prostadienoic acid (Example 1377)1621 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-4a,4b- 15-trihydroxy-4a,4b- bishomo-20-ethyl-5- bishomo-20-ethyl-5- cis,13-cis-prosta- cis,13-cis-prosta- dienoic acid dienoic acid (Example 1377)1622 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-4a,4b- 15-trihydroxy-4a,4b- bishomo-20-ethyl-8- bishomo-20-ethyl-8- iso-5-cis,13-cis- iso-5-cis,13-cis- prostadienoic acid prostadienoic (Example 1377)1623 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-4a,4b- 15-trihydroxy-4a,4b- bis-homo-5-cis,13- bishomo-5-cis,13- trans,17-cis-prosta- trans,17-cis-prosta- trienoic acid trienoic acid (Example 1378)1624 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-4a,4b- 15-trihydroxy-4a,4b- bis-homo-8-iso-5-cis- bis-homo-8-iso-5-cis,- 13-trans,17-cis-pros- 13-trans,17-cis- tatrienoic acid prostatrienoic acid (Example 1378)1625 8.beta.-methyl-9-oxo-11.alpha.,- 8.beta.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-4a,4b- 15-tyrihydroxy-4a,4b- bis-homo-5-cis,13- bis-homo-5-cis,13- cis,17-cis-pros- cis-17-cis-prosta- tatrienoic acid trienoic acid (Example 1378)1626 8.alpha.-methyl-9-oxo-11.alpha.,- 8.alpha.-methyl-9.alpha./.beta.,11.alpha.,- 15-dihydroxy-4a,4b- 15-trihydroxy-4a,4b- bis-homo-8-iso-5-cis, bis-homo-8-iso-5- 13-cis-17-cis-pros- cis,13-cis,17-cis- tatrienoic acid prostatrienoic acid (Example 1378)1627 methyl 8.beta.-methyl-9- methyl 8.beta.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 20-methyl-13-trans- hydroxy-20-methyl- prostenoate 13-trans-prostenoate (Example 1379)1628 methyl 8.alpha.-methyl-9- methyl 8.alpha.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 20-methyl-8-iso-13- hydroxy-20-methyl- trans-prostenoate 8-iso-13-trans-pros- (Example 1379) tenoate1629 methyl 8.beta.-methyl-9- methyl 8.beta.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 20-methyl-13-cis- hydroxy-20-methyl- prostenoate 13-cis-prostenoate (Example 1379)1630 methyl 8.alpha.-methyl-9- methyl 8.alpha.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 20-methyl-8-iso-13- hydroxy-20-methyl- cis-prostenoate 8-iso-13-cis-pros- (Example 1379) tenoate1631 ethyl 8.beta.-methyl-9- ethyl 8.beta.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 7a,7b-bis-homo-13- hydroxy-7a,7b-bis- trans,17-cis-prosta- homo-13-trans,17- dienoate cis-prostadienoate (Example 1380)1632 ethyl 8.alpha.-methyl-9- ethyl 8.alpha.-methyl-9.alpha./- oxo-11.alpha.,15-dihydroxy- .beta.,11.alpha.,15-trihydroxy- 7a,7b-bis-homo-8-iso- 7a,7b-bis-homo-8- 13-trans,17-cis- iso-13-trans,17-cis- prostadienoate prostadienoate (Example 1380)1633 ethyl 8.beta.-methyl-9- ethyl 8.beta.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 7a,7b-bis-homo-13- hydroxy-7a,7b-bis- cis-17-cis-prosta- homo-13-cis,17-cis- dienoate prostadienoate (Example 1380)1634 ethyl 8.alpha.-methyl-9- ethyl 8.alpha.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 7a,7b-bis-homo-8- hydroxy-7a,7b-bis- iso-13-cis,17-cis- homo-8-iso-13-cis- prostadienoate 17-cis-prosta- (Example 1380) dienoate1635 ethyl 8.beta.-methyl-9- ethyl 8.beta.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 2-ethyl-16,16-dimeth- hydroxy-2-ethyl-16, yl-13-trans-prosten- 16-dimethyl-13- oate trans-prostenoate (Example 1381)1636 ethyl 8.alpha.-methyl-9- ethyl 8.alpha.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 2-ethyl-16,16-di- hydroxy-2-ethyl- methyl-8-iso-13- 16,16-dimethyl-8- trans-prostenoate iso-13-trans-pros- (Example 1381) tenoate1637 ethyl 8.beta.-methyl-9- ethyl 8.beta.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 2-ethyl-16,16-di- hydroxy-2-ethyl- methyl-13-cis-pros- 16,16-dimethyl-13- tenoate cis-prostenoate (Example 1381)1638 ethyl 8.alpha.-methyl-9- ethyl 8.alpha.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 2-ethyl-16,16-di- hydroxy-2-ethyl-16,- methyl-8-iso-13-cis- 16-dimethyl-8-iso- prostenoate 13-cis-prostenoate (Example 1381)1639 ethyl 8.beta.-methyl-9- ethyl 8.beta.-methyl- oxo-11.alpha. ,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 3,3,17,17-tetra- hydroxy-3,3,17,17- methyl-13-trans- tetramethyl-13- prostenoate trans-prostenoate (Example 1382)methyl-9-yl 8 ethyl 8.alpha.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 3,3,17,17-tetra- hydroxy-3,3,17,17- methyl-8-iso-13- tetramethyl-8-iso- trans-prostenoate 13-trans-prosten- (Example 1382) oate1641 ethyl 8.beta.-methyl-9- ethyl 8.beta.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 3,3,17,17-tetramethyl- hydroxy-3,3,17,17- 13-cis-prostenoate tetramethyl-13-cis- (Example 1382) prostenoate1642 ethyl 8.alpha.-methyl-9- ethyl 8.alpha.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 3,3,17,17-tetramethyl- hydroxy-3,3,17,17- 8-iso-13-cis-prosten- tetramethyl-8-iso- oate 13-cis-prostenoate (Example 1382)1643 ethyl 8.beta.-methyl-9- ethyl 8.beta.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 3-oxa-17,17-dimethyl- hydroxy-3-oxa-17,17- 13-trans-prostenoate dimethyl-13-trans- (Example 1383) prostenoate1644 ethyl 8.alpha.-methyl-9- ethyl 8.alpha.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 3-oxa-17,17-dimethyl- hydroxy-3-oxa-17,17- 8-iso-13-trans-pros- dimethyl-8-iso-13- tenoate trans-prostenoate (Example 1383)1645 ethyl 8.beta.-methyl-9- ethyl 8.beta.-methyl oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 3-oxa-17,17-dimethyl- hydroxy-3-oxa-17,17- 13-cis-prostenoate dimethyl-13-cis- (Example 1385) prostenoate1646 ethyl 8.alpha.-methyl-9- ethyl 8.alpha.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 3-oxa-17,17-dimethyl- hydroxy-3-oxa-17,17- 8-iso-13-cis-pros- dimethyl-8-iso-13- tenoate cis-prostenoate (Example 1383)1647 butytl 8.beta.-methyl-9- butyl 8.beta.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 13-trans-prostenoate hydroxy-13-trans- (Example 1384) prostenoate1648 butyl 8.alpha.-methyl-9- butyl 8.alpha.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 8-iso-13-trans- hydroxy-8-iso-13- prostenoate trans-prostenoate (Example 1384)1649 butyl 8.beta.-methyl-9- butyl 8.beta.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 13-cis-prostenoate hydroxy-13-cis- (Example 1384) prostenoate1650 butyl 8.alpha.-methyl-9- butyl 8.alpha.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 8-iso-13-cis-pros- hydroxy-8-iso-13- tenoate cis-prostenoate (Example 1384)1651 decyl 8.beta.-methyl-9- decyl 8.beta.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 13-trans,17-cis- hydroxy-13-trans,- prostadientoate 17-cis-prosta- (Example 1385) dienoate1652 decyl 8.alpha.-methyl-9- decyl 8.alpha.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 8-iso-13-trans,17- hydroxy-8-iso-13- cis-prostadienoatetrans,17-cis-pro- (Example 1385)1653 decyl 8.beta.-methyl-9- decyl 8.beta.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 13-cis,17-cis-pros- hydroxy-13-cis,17- tadienoate cis-prostadienoate1654 decyl 8.alpha.-methyl-9- decyl 8.alpha.-methyl- oxo-11.alpha.,15-dihydroxy- 9.alpha./.beta.,11.alpha.,15-tri- 8-iso-13-cis,17-cis- hydroxy-8-iso-13- prostadienoate cis,17-cis-prosta- (Example 1385) dienoate______________________________________

EXAMPLES 1655-1781

Saponification of the alkyl esters designated in Table 43 below by the procedure described in Example 495 is productive of the carboxylic acids of the table. The epimeric 9.alpha. and 9.alpha. hydroxy products are separable by the usual chromatographic procedures.

TABLE 43______________________________________Ex- Starting alkylample prostenoate Product prostenoic acid______________________________________1655 11-deoxy-8.beta.-meth- 11-deoxy-8.beta.-methyl-pros- yl-prostaglandin taglandin E.sub.1 E.sub.1 methyl ester (Example 1188)1656 11-deoxy-8.alpha.-meth- 11-deoxy-8.alpha.-methyl-8- yl-8-iso-prosta- iso-prostaglandin E.sub.1 glandin E.sub.1 meth- yl ester (Exam- ple 1188)1657 methyl 15-hy- 15-hydroxy-8.beta.-methyl-9- droxy-8.beta.-methyl oxo-13-cis-prostenoic 9-oxo-13-cis- acid prostenoate (Example 1188)1658 methyl-15-hy- 15-hydroxy-8.alpha.-methyl-8- droxy-8.alpha.-methyl- iso-9-oxo-13-cis- 8-iso-9-oxo-13- prostenoic acid cis-prostenoate (Example 1188)1659 11-deoxy-8.beta.-meth- 11-deoxy-8.beta.-methyl- yl-prostaglandin prostaglandin F.sub.1 .alpha./.beta. F.sub.1 .alpha./.beta. methyl esters (Ex. 1206)1660 11-deoxy-8.alpha.-meth- 11-deoxy-8.alpha.-methyl-8- yl-8-iso-prosta- iso-prostaglandin glandin F.sub.1 .alpha./.beta. F.sub.1 .alpha./.beta. methyl esters (Example 1207)1661 methyl 9.alpha.,15-di- 9.alpha.,15-dihydroxy-8.beta.-meth- hydroxy-8.beta.-meth- yl-13-cis-prostenoic yl-13-cis-pros- acid tenoate (Example 1208)1662 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-16,16-dimethyl-13- droxy-16,16-di- trans-prostenoic acid methyl-13-trans- prostenoate (Example 1190)1663 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-16,16-dimethyl-8- droxy-16,16-di- iso-13-trans-prosten- methyl-8-iso-13- oic acid trans-prosteno- ate (Example 1190)1664 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-16,16-dimethyl- droxy-16,16-di- 13-cis-prostenoic acid methyl-13-cis- prostenoate (Example 1190)1665 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-16,16-dimethyl- droxy-16,16-di- 8-iso-13-cis-prosten- methyl-8-iso-13- oic acid cis-prostenoate (Example 1190)1666 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-17,17-dimethyl- droxy-17,17-di- 13-trans-prostenoic methyl-13-trans- acid prostenoate (Example 1191)1667 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-17,17-dimethyl- droxy-17,17-di- 8-iso-13-trans-pros- methyl-8-iso-13- tenoic acid trans-prosteno- ate (Example 1191)1668 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-17,17-dimethyl- droxy-17,17-di- 13-cis-prostenoic acid methyl-13-cis- prostenoate (Example 1191)1669 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-17,17-dimethyl-8- droxy-17,17-di- iso-13-cis-prostenoic methyl-8-iso-13- acidcis-prostenoate (Example 1191)1670 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-13-trans,17-cis- droxy-13-trans,- prostadienoic acid 17-cis-prostadi- enoate (Example 1192)1671 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-8-iso-13-trans,17- droxy-8-iso-13- cis-prostadienoic acid trans-17-cis- prostendienoate (Example 1192)1672 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-13-cis,17-cis- droxy-13-cis-17- prostadienoic acid cis-prostadien- oate (Example 1192)1673 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-8-iso-13-cis,17- droxy-8-iso-13- cis-prostadienoic acid cis-17-cis-pros- tadienoate (Ex- ample 1192)1674 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-20-ethyl-13-trans- droxy-20-ethyl- prostenoic acid 13-trans-pros- tenoate (Example 1193)1675 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-20-ethyl-8-iso-13- droxy-20-ethyl- trans-prostenoic acid 8-iso-13-trans- prostenoate (Example 1193)1676 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-20-ethyl-13-cis- droxy-20-ethyl- prostenoic acid 13-cis-prosten- oate (Example 1193)1677 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-20-ethyl-8-iso-13- droxy-20-ethyl- cis-prostenoic acid 8-iso-13-cis- prostenoate (Example 1193)1678 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-7a,7b-bishomo-13- droxy-7a,7b-bis- trans-prostenoic acid homo-13-trans- prostenoate (Example 1195)1679 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-7a,7b-bishomo-8- droxy-7a,7b-bis- iso-13-trans-prostenoic homo-8-iso-13- acid trans-prosteno- ate (Example 1195)1680 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-7a,7b-bishomo-13- droxy-7a,7b-bis- cis-prostenoic acid homo-13-cis- prostenoate (Example 1195)1681 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-7a,7b-bishomo-8- droxy-7a,7b-bis- iso-13-cis-prostenoic homo-8-iso-13- acid cis-prostenoate (Example 1195)1682 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-2,20-bisethyl-13- droxy-2,20-bis- trans-prostenoic acid ethyl-13-trans- prostenoate (Example 1196)1683 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-2,20-bisethyl-8- droxy-2,20-bis- iso-13-trans-prostenoic ethyl-8-iso-13- acid trans-prosten- oate (Example 1196)1684 ethyl 8.beta.methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-2,20-bisethyl-13- droxy-2,20-bis- cis-prostenoic acid ethyl-13-cis- prostenoate (Example 1196)1685 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-2,20-bisethyl-8- droxy-2,20-bis- iso-13-cis-prostenoic ethyl-8-iso-13- acid cis-prostenoate (Example 1196)1686 ethyl 8.beta.-methyl- 8.beta.-methy-9-oxo-15-hy- 9-oxo-15-hy- droxy-3-oxa-16,16-di- droxy-3-oxa-16,- methyl-13-trans-pros- 16-dimethyl-13- tenoic acid trans-prosteno- ate (Example 1197)1687 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-3-oxa-16,16-di- droxy-3-oxa-16,- methyl-8-iso-13-trans- 16-dimethyl-8- prostenoic acidiso-13-trans- prostenoate (Example 1197)1688 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-3-oxa-16,16-di- droxy-3-oxa-16,- methyl-13-cis-prostenoic 16-dimethyl-13- acid cis-prostenoate (Example 1197)1689 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-3-oxa-16,16-di- droxy-3-oxa-16,- methyl-8-iso-13-cis- 16-dimethyl-8-iso- prostenoic acid 13-cis-prosteno- ate (Example 1197)1690 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-3-oxa-13-trans,- droxy-3-oxa-13- 17-cis-prostadienoic trans,17-cis- acid prostadienoate (Example 1198)1691 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-3-oxa-8-iso-13- droxy-3-oxa-8- trans,17-cis-prostadi- iso-13-trans,17- enoic acidcis-prostadieno- ate (Example 1198)1692 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy-9-oxo-15-hy- droxy-3-oxa-13-cis,17- droxy-3-oxa-13- cis-prostadienoic acid cis,17-cis-pros- tadienoate (Exam- ple 1198)1693 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-3-oxa-8-iso-13- droxy-3-oxa-8- cis,17-cis-prostadi- iso-13-cis,17- enoic acid cis-prostadieno ate (Example 1198)1694 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-7-nor-20-methyl- droxy-7-nor-20- 13-trans-prostenoic methyl-13-trans- acid prostenoate (Example 1199)1695 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-7-nor-20-methyl- droxy-7-nor-20- 8-iso-13-trans-pros-methyl-8-iso- tenoic acid 13-trans-pros- tenoate (Example 1199)1696 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-7-nor-20-methyl- droxy-7-nor-20- 13-cis-prostenoic acid methyl-13-cis- prostenoate (Example 1199)1697 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy droxy-7-nor-20-methyl- droxy-7-nor-20- 8-iso-13-cis-prosteno- methyl-8-iso- ic acid 13-cis-prosten- oate (Example 1199)1698 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-2-fluoro-17,17-di- droxy-2-fluoro- methyl-13-trans-pros- 17,17-dimethyl- tenoic acid 13-trans-pros- tenoate (Example 1200)1699 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-2-fluoro-17,17- droxy-2-fluoro- dimethyl-8-iso-13- 17,17-dimethyl- trans-prostenoic acid 8-iso-13-trans- prostenoate (Example 1200)1700 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-2-fluoro-17,17- droxy-2-fluoro- dimethyl-13-cis- 17,17-dimethyl- prostenoic acid 13-cis-prosten- oate (Example 1200)1701 ethyl 8.beta.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-2-fluoro-17,17- droxy-2-fluoro- dimethyl-i-iso-13-cis- 17,17-dimethyl- prostenoic acid 8-iso-13-cis- prostenoate (Example 1200)1702 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-10a-homo-13- droxy-10a-homo- trans-prostenoic acid 13-trans-pros- tenoate (Example 1201)1703 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-10a-homo-8-iso- droxy-10a-homo-8- 13-trans-prostenoic iso-13-trans- acid prostenoate (Example 1201)1704 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-10a-homo-13-cis- droxy-10a-homo- prostenoic acid 13-cis-prosten- oate (Example 1201)1705 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-10a-homo-8-iso- droxy-10a-homo- 13-cis-prostenoic acid 8-iso-13-cis- prostenoate (Example 1201)1706 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-2-phenyl-20-meth- droxy-2-phenyl- yl-13-trans-prostenoic 20-methyl-13- acid trans-prosteno- ate (Example 1202)1707 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-2-phenyl-20-meth- droxy-2-phenyl- yl-8-iso-13-trans-pros- 20-methyl-8-iso- tenoic acid 13-trans-pros- tenoate (Example 1202)1708 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-2-phenyl-20-meth- droxy-2-phenyl- yl-13-cis-prostenoic 20-methyl-13- acid cis-prostenoate (Example 1202)1709 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-2-phenyl-20-meth- droxy-2-phenyl- yl-8-iso-13-cis-prosten- 20-methyl-8-iso- oic acid 13-cis-prosten- oate (Example 1202)1710 methyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-5-cis,13-trans,17- droxy-5-cis,13- cis-prostatrienoic acid trans,17-cis- prostatrienoate (Example 1203)1711 methyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-8-iso-5-cis,13- droxy-8-iso-5- trans,17-cis-prostatri- cis,13-trans,17- enoic acid cis-prostatrien- oate (Example 1203)1712 methyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-5-cis,13-cis,17- droxy-5-cis,13- cis-prostatrienoic acid cis,17-cis-pros- tatrienoate (Example 1203)1713 methyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-8-iso-5-cis,13- droxy-8-iso-5- cis,17-cis-prostatri- cis,13-cis,17- enoic acid cis-prostatrien- oate (Example 1203)1714 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-5-cis,13-trans- droxy-5-cis,13- prostadienoic acid trans-prostadi- enoate (Example 12041715 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-8-iso-5-cis,13- droxy-8-iso-5- trans-prostadienoic cis,13-trans- acidprostadienoate (Example 1204)1716 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-5-cis,13-cis- droxy-5-cis,13- prostadienoic acid cis-prostadieno- ate (Example 1204)1717 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-8-iso-5-cis,13- droxy-8-iso-5- cis-prostadienoic acid cis,13-cis-pros- tadienoate (Exam- ple 1204)1718 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-20-ethyl-5-cis,13- droxy-20-ethyl- trans-prostadienoic acid 5-cis,13-trans-prostadienoate (Example 1205)1719 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-20-ethyl-8-iso-5- droxy-20-ethyl- cis,13-trans-prostadi- 8-iso-5-cis,13- enoic acid trans-prostadi- enoate (Example 1205)1720 ethyl 8.beta.-methyl- 8.beta.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-20-ethyl-5-cis,13- droxy-20-ethyl- cis-prostadienoic acid 5-cis,13-cis- prostadienoate (Example 1205)1721 ethyl 8.alpha.-methyl- 8.alpha.-methyl-9-oxo-15-hy- 9-oxo-15-hy- droxy-20-ethyl-8-iso- droxy-20-ethyl- 5-cis,13-cis-prosta- 8-iso-5-cis,13- dienoic acid cis-prostadien- oate (Example 1205)1722 1210 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-16,16-dimethyl-13- trans-prostenoic acid1723 1211 8.alpha.-methyl-9.alpha./.beta.,15-di- hydroxy-16,16-dimethyl- 8-iso-13-trans-pros- tenoic acid1724 1212 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-16,16-dimethyl-13- cis-prostenoic acid1725 1213 8.alpha.-methyl-9.alpha./.beta.,15-dihy- hydroxy-16,16-dimethyl 8-iso-13-cis-prostenoic acid1726 1214 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-17,17-dimethyl- 13-trans-prostenoic - acid1727 1215 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-17,17-dimethyl-8- iso-13-trans-prosten- oic acid1728 1216 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-17,17-dimethyl-13- cis-prostenoic acid1729 1217 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-17,17-dimethyl-8 iso-13-cis-prostenoic - acid1730 1218 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-13-trans,17-cis- prostadienoic acid1731 1219 8.alpha.-methhyl-9.alpha./.beta.,15-dihy- droxy-8-iso-13-trans,17- cis-prostadienoic acid1732 1220 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-13-cis,17-cis- prostadienoic acid1733 1221 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-8-iso-13-cis,17- cis-prostadienoic acid1734 1222 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-20-ethyl-13-trans- prostenoic acid1735 1223 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-20-ethyl-8-iso- 13-trans-prostenoic acid1736 1224 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-20-ethyl-13-cis- prostenoic acid1737 1225 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-20-ethyl-8-iso- 13-cis-prostenoic acid1738 1230 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-7a,7b-bishomo-13- trans-prostenoic acid1739 1231 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-7a,7b-bishomo-8- iso-13-trans-prosten- oic aid1740 1232 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-7a,7b-bishomo-13- cis-prostenoic acid1741 1233 8.alpha.-methyl-9.alpha./.beta.,155-dihy- droxy-7a,7b-bishomo-8-iso-13-cis-prostenoic acid1742 1234 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-2,20-bisethyl-13-trans-prostenoic acid1743 1235 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-2,20-bisethyl-8- iso-13-trans-prosten- oic acid1744 1236 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-2,20-bisethyl-13- cis-prostenoic acid1745 1237 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-2,20-bisethyl-8- iso-13-ccis-prostenoic acid1746 1238 8.beta.-methyl-9.alpha.,.beta.15-dihy- droxy-3-oxa-16,16-di- methyl-13-trans-pros- tenoic acid1747 1239 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-3-oxa-16,16-di- methyl-8-iso-13-trans- prostenoic acid1748 1240 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-3-oxa-16,16-di- methyl-13-cis-prosten- oic acid1749 1241 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-3-oxa-16,16-di- methyl-8-iso-13-cis- prostenoic acid1750 1242 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-3-oxa-13-trans,17- cis-prostadienoic acid1751 1243 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-3-oxa-8-isoo-13- trans,17-cis-prostadi- enoic acid1752 1244 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-3-oxa-13-cis,17- cis-prostadienoic acid1753 1245 8.alpha.-methyl-8.alpha./.beta.,15-dihy- droxy-3-oxa-8-iso-13- cis,17-cis-prostadien- oic acid1754 1246 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-7-nor-20-methyl 13-trans-prostenoic acid1755 1247 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-7-nor-20-methyl- 8-iso-13-trans-pros- tenoic acid1756 1248 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-7-nor-20-methyl- 13-cis-prostenoic acid1757 1249 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-7-nor-20-methyl- 8-iso-13-cis-prostene- ic acid1758 1250 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-2-fluoro-17,17- dimethyl-13-trans- prostenoic acid1759 1251 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-2-fluoro-17,17- dimethyl-8-iso-13- trans-prostenoic acid1760 1252 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-2-fluoro-17,17- dimethyl-13-cis-pros- tenoic acid1761 1253 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-2-fluoro-17,17- dimethyl-8-iso-13-cis- prostenoic acid1762 1254 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-10a-homo-13-trans- prostenoic acid1763 1255 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-10a-homo-8-iso- 13-trans-prostenoic acid1764 1256 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-10a-homo-13-cis- prostenoic acid1765 1257 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-10a-homo-8-iso- 13-cis-prostenoic acid1766 1258 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-2-phenyl-20-methy- yl-13-trans-prostenoic - acid1767 1259 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-2-phenyl-20-meth- yl-8-iso-13-trans-pros- tenoic acid1768 1260 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-2-phenyl-20-meth- yl-13-cis-prostenoic acid1769 1261 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-2-phenyl-20-meth- yl-8-iso-13-cis-prosten- oic acid1770 1262 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-5-cis,13-trans,17- cis-prostatrienoic acid1771 1263 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-8-iso-5-cis-13- trans,17-cis-prostatri- enoic acid1772 1264 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-5-cis,13-cis,17-cis-prostatrienoic acid1773 1265 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-8-iso-5-cis,13- cis,17-cis-prostatri- enoic acid1774 1266 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-5-cis,13-trans-prostadienoic acid1775 1267 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-8-iso-5-cis,13-trans-prostadienoic acid1776 1268 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-5-cis,133-cis-prostadienoic acid1777 1269 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-8-iso-5-cis,13-cis-prostadienoic acid1778 1270 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-20-ethyl-5-cis,13-trans-prostadienoic - acid1779 1271 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-20-ethyl-8-iso-5-cis,13-trans-pros- tadienoic acid1780 1272 8.beta.-methyl-9.alpha./.beta.,15-dihy- droxy-20-ethyl-5-cis,- 13-cis-prostadienoic acid1781 1273 8.alpha.-methyl-9.alpha./.beta.,15-dihy- droxy-20-ethyl-8-iso-5-cis,13-cis-prosta- dienoic acid______________________________________

EXAMPLES 1782-1815

Catalytic hydrogenation of the 13-trans-prostenoic acids or esters listed below in Table 44 by the procedure described in Example 699 furnishes the product prostanoic acids of the table.

TABLE 44______________________________________ Starting 13- trans-prostenoic ProductsEx- acid or ester of 8-methylprostanoicample Example acids or esters______________________________________1782 1206 Methyl 8.beta.-methyl-9.alpha./.beta., 15-dihydroxy- prostanoate1783 1207 Methyl 8.alpha.-methyl-9.alpha./.beta., 15-dihydroxy-8-iso- prostanoate1784 1210 Ethyl 8.beta.-methyl-9.alpha./.beta., 15-dihydroxy-16,16- dimethyl-prostanoate1785 1226 Decyl 8.beta.-methyl-9.alpha./.beta.. 15-dihydroxy-20-methyl- prostanoate1786 1655 8.beta.-methyl-9-oxo-15-di- hydroxy-prostanoic acid1787 1656 8.alpha.-methyl-9-oxo-15-di- hydroxy-8-iso-prostan- oic acid1788 1659 8.beta.-methyl-9.alpha./.beta., 15-di- hydroxy-prostanoic acid1789 1660 8.alpha.-methyl-90.alpha./.beta., 15-di- hydroxy-8-iso-prostan- oic acid1790 1678 8.beta.-methyl-9-oxo-15-hy- droxy-7a,7b-bishomo- prostanoic acid1791 1683 8.alpha.-methyl-9-oxo-15- hydroxy-2,20-bisethyl- 8-iso-prostanoic acid1792 1686 8.beta.-methyl-9-oxo-15- hydroxy-3-oxa-16,16- dimethyl-prostanoic acid1793 1694 8.beta.-methyl-9-oxo-15- hydroxy-7-nor-20- methyl-prostanoic acid1794 1702 8.beta.-methyl-9-oxo-15- hydroxy-10a-homo- prostanoic acid1795 1523 8.beta.-methyl-9.alpha./.beta.,11.alpha.,15- trihydroxy-prostanoic acid1796 1524 8.alpha.-methyl-9.alpha./.beta., 11.alpha.,15- trihydroxy-8-iso- prostanoic acid1797 1527 8.beta.-methyl-9.alpha./.beta., 11.alpha.,15- trihydroxy-16,16-di- methyl-prostanoic acid1798 1531 8.beta.-methyl-9.alpha./.beta., 11.alpha.,15- trihydroxy-17,17-di- methyl-prostanoic acid1799 1539 8.beta.-methyl-9.alpha./.beta.-11.alpha.,15- trihydroxy-20-ethyl- prostanoic acid1800 1552 8.alpha.-methyl-9.alpha./.beta., 11.alpha., 15- trihydroxy-7a,7b-bis- homo-8-iso-prostanoic acid1801 1551 8.beta.-methyl-9.alpha./.beta.,11.alpha.,15- trihydroxy-7a,7b-bis- homo-prostanoic acid1802 1555 8.beta.-methyl-9.alpha./.beta.,11.alpha.,15- trihydroxy-2-ethyl- prostanoic acid1803 1559 8.beta.-methyl-9.alpha./.beta.,11.alpha.,15- trihydroxy-3,3,20-tri- methyl-prostanoic acid1804 1563 8.beta.-methyl-9.alpha./.beta.,11.alpha.,15- trihydroxy-3-oxa- prostanoic acid1805 1567 8.beta.-methyl-9.alpha./.beta.,11.alpha.,15- trihydroxy-3-oxa-16, 16-dimethyl-prostanoic acid1806 1587 8.beta.-methyl-9.alpha./.beta.,11.alpha.,15- trihydroxy-7a-homo- 16,16-dimethyl-pro- stanoic acid1807 1643 Ethyl 8.beta.-methyl-9.alpha./.beta., 11.alpha.,15 trihydroxy-3- oxa-17,17-dimethyl- prostanoic acid1808 1816 8.beta.,15-dimethyl-9.alpha./.beta.,15- dihydroxy-prostanoic acid1809 1817 8.beta.,15-dimethyl-9-oxo- 15-hydroxy-prostanoic acid1810 1819 8.alpha.,15-dimethyl-9-oxo- 15-hydroxy-8-iso- prostanoic acid1811 1834 8.beta.,15-dimethyl-9.alpha./.beta., 11.alpha.,15-trihydroxy- prostanoic acid1812 1835 8.beta.,15-dimethyl-9-oxo- 11.alpha.,15-dihydroxy- prostanoic acid1813 1837 8.alpha.,15-dimethyl-9-oxo- 11.alpha.,15-dihydroxy-8- iso-prostanoic acid1814 1843 8.beta.,15-dimethyl-9-oxo- 11.alpha.,15-dihydroxy-7a, 7b-bishomo-prostanoic acid1815 1849 8.beta.,15-dimethyl-9-oxo- 11.alpha.,15-dihydroxy-3- oxa-prostanoic acid______________________________________

EXAMPLES 1816-1859

Treatment by the procedure described in Example 1082 by the 8-methyl-9.alpha./.beta.,15-dihydroxy-prostenoic acids listed in Table 45 below successively with 2,3-dichloro-5,6-dicyanobenzoquinone to give the corresponding 15-keto derivatives; 2.4 equivalents each of triethylamine and trimethylsilyl chloride to give the corresponding 9.alpha./.beta.-O-trimethylsilyl ether trimethylsilyl prostenoate ester in the instance of the 11.alpha.-hydroxy derivatives an additional 1.1 equivalent each of triethylamine and trimethylsilyl chloride is used and the 11.alpha.-O-trimethylsilyl ether derivative is obtained); methyl magnesium bromide to give the 15 -methyl-15-hydroxy bis or tris trimethylsilyl blocked ether-ester; methanol-water-acetic acid for deblocking of the trimethylsilyl ether and ester blocking groups to give the listed 9.alpha./.beta.-hydroxy-15-methyl-15-hydroxy derivatives. In the 11-deoxy series treatment of these 9.alpha./.beta.-hydroxy-15-methyl-15-hydroxy products with Collins reagent in methylene chloride provides the corresponding 11-deoxy-9-oxo-15-hydroxy-15-methyl-prostenoic acids, also listed in the table. In the 11.alpha.-hyroxy series, treatment of the 9.alpha./.beta. ,11.alpha.-15-trihydroxy-15-methyl derivatives with 1.1 molar equivalents each of triethylamine and trimethylsilyl chloride provides the corresponding 11.alpha.-O-trimethylsilyloxy-9.alpha./.beta.,15-dihydroxy derivative, which on oxidation in the usual way with Collins reagent in methylene chloride followed by silyl ether cleavage (treatment with methanol-water-acetic acid by the procedure described in Example 1082) provides the corresponding 9-oxo 11.alpha.,15-dihydroxy-15-methyl-prostenoic acids of the Table.

TABLE 45______________________________________ Starting 9.alpha./.beta.,(or 9.alpha.),15-dihydroxy- or 9.alpha./.beta. (or 9.alpha.), Product 11.alpha.,15-trihydroxy 8,15-dimethyl-15-hy-Ex- derivative of droxy-prostanoicample Example acids______________________________________1816 1659 8.beta.,15-dimethyl-9.alpha.,.beta.,15- dihydroxy-13-trans- prostenoic acid1817 1659 8.beta.,15-dimethyl-9-oxo- 15-hydroxy-13-trans- prostenoic acid1818 1660 8.alpha.,15-dimethyl-9.alpha.,15- dihydroxy-8-iso-13- trans-prostenoic acid1819 1660 8.alpha.,15-dimethyl-9-oxo- 15-hydroxy-8-iso-13- trans-prostenoic acid1820 1730 8.beta.,15-dimethyl-9.alpha./.beta.,15- dihydroxy-13-trans,17- cis-prostadienoic acid1821 1730 8.beta.,15-dimethyl-9-oxo- - 15-hydroxy-13-trans- N 17-cis-prostadienoic acid1822 1731 8.alpha.,15-dimethyl-9.alpha./.beta.,15- dihydroxy-8-iso-13- trans,17-cis-prosta- dienoic acid1823 1731 8.alpha.,15-dimethyl-9-oxo- 15-hydroxy-8-iso-13- trans,17-cis-prosta- dienoic acid1824 1738 8.beta.,15-dimethyl-9.alpha./.beta., 15-dihydroxy-7a,7b- bishomo-13-trans- prostenoic acid1825 1738 8.beta.,15-dimethyl-9-oxo- 15-hydroxy-7a,7b-bis- homo-13-trans-prost- enoic acid1826 1746 8.beta.,15-dimethyl-9.alpha./.beta., 15-dihydroxy-3-oxa-16, 16-dimethyl-13-trans- prostenoic acid1827 1746 8.beta.,15-dimethyl-9-oxo- 15-hydroxy-3-oxa-16, 16-dimethyl-13-trans- prostenoic acid1828 1750 8.beta.,15-dimethyl-9.alpha./.beta., 15-dihydroxy-3-oxa- 13-trans,17-cis- prostadienoic acid1829 1750 8.beta.,15-dimethyl-9-oxo- 15-hydroxy-3-oxa-13- trans,17-cis-prosta- dienoic acid1830 1770 8.beta.,15-dimethyl-9.alpha./.beta., 15-dihydroxy-6-cis, 13-trans,17-cis-prosta- trienoic acid1831 1770 8.alpha.,15-dimethyl-9-oxo- 15-hydroxy-5-cis,13- trans,17-cis-prosta- trienoic acid1832 1778 8.beta.,15-dimethyl-9.alpha./.beta., 15-dihydroxy-20-ethyl- 5-cis,13-trans- prostadienoic acid1833 1778 8.beta.,15-dimethyl-9-oxo- 15-hydroxy-20-ethyl-5- cis,13-trans-prosta- dienoic acid1834 1523 8.beta.,15-dimethyl-9.alpha./.beta., 11.alpha.,15-trihydroxy-13- trans-prostenoic acid1835 1523 8.beta.,15-dimethyl-9-oxo- 11.alpha.,15-dihydroxy-13- trans-prostenoic acid1836 1524 8.alpha.,15-dimethyl-9.alpha./.beta., 11.alpha.,15-trihydroxy-8- iso-13-trans-pros- tenoic acid1837 1524 8.alpha.,15-dimethyl-9-oxo- 11.alpha.,15-dihydroxy- 8-iso-13-trans- prostenoic acid1838 1535 8.beta.,15-dimethyl-9.alpha./.beta.,- 11.alpha.,15-trihydroxy-13- trans,17-cis-prosta- dienoic acid1839 1535 8.beta.,15-dimethyl-9-oxo- 11.alpha.,15-dihydroxy-13- trans,17-cis-prosta- dienoic acid1840 1539 8.beta.,15-dimethyl-9.alpha./.beta., 11.alpha.,15-trihydroxy-20- ethyl-13-trans-pro- stenoic acid1841 1539 8.beta. ,15-dimethyl-9-oxo- 11.alpha.,15-dihydroxy-20- ethyl-13-trans-pro- stenoic acid1842 1551 8.beta.,15-dimethyl-9.alpha./.beta., 11.alpha.,15-trihydroxy-7a, 7b-bishomo-13-trans- prostenoic acid1843 1551 8.beta.,15-dimethyl-9-oxo- 11.alpha.,15-dihydroxy-7a, 7b-bishomo-13-trans- prostenoic acid1844 1555 8.beta.,15-dimethyl-9.alpha./.beta., 11.alpha.,15-trihydroxy-2- ethyl-13-trans- prostenoic acid1845 1555 8.beta.,15-dimethyl-9-oxo- 11.alpha.,15-dihydroxy-2- ethyl-13-trans- prostenoic acid1846 1559 8.beta.,15-dimethyl-9.alpha./.beta., 11.alpha.,15-trihydroxy-3,3, 20-trimethyl-13-trans- prostenoic acid1847 1559 8.beta.,15-dimethyl-9-oxo- 11.alpha.,15-dihydroxy-3,3 20-trimethyl-13-trans- prostenoic acid1848 1563 8.beta.,15-dimethyl-9.alpha./.beta., 11.alpha.,15-trihydroxy-3- oxa-13-trans-prostenoic acid1849 1563 8.beta.,15-dimethyl-9-oxo- 11.alpha.,15-dihydroxy-3- oxa-13-trans-prostenoic acid1850 1571 8.beta.,15-dimethyl-9.alpha./.beta., 11.alpha.,15-trihydroxy-3- oxa-13-trans,17-cis- prostadienoic acid1851 1571 8.beta.,15-dimethyl-9-oxo- 11.alpha.,15-dihydroxy-3-oxa- 13-trans,17-cis-prosta- dienoic acid1852 1599 8.beta.,15-dimethyl-9.alpha./.beta., 11.alpha.,15-trihydroxy-5- cis,13-trans-prosta- dienoic acid1853 1599 8.beta.,15-dimethyl-9-oxo- 11.alpha.,15-dihydroxy-5- cis,13-trans-prosta- dienoic acid1854 1603 8.beta.,15-dimethyl-9.alpha./.beta., 11.alpha.,15-trihydroxy-5-cis, 13-trans,17-cis-prosta- trienoic acid1855 1603 8.beta.,15-dimethyl-9-oxo- 11.alpha.,15-dihydroxy-5- cis,13-trans,17-cis- prostatrienoic acid1856 1611 8.beta.,15-dimethyl-9.alpha./.beta., 11.alpha.,15-trihydroxy-4-nor- 20-methyl-5-cis,13- trans-prostadienoic acid1857 1611 8.beta.,15-dimethyl-9-oxo- 11.alpha.,15-dihydroxy-4- nor-20-methyl-5-cis, 13-trans-prostadienoic acid1858 1623 8.beta.,15-dimethyl-9.alpha./.beta., 11.alpha.,15-trihydroxy-4a, 4b-bishomo-5-cis,13- trans,17-cis-prosta- trienoic acid1859 1623 8.beta.,15-dimethyl-9-oxo- 11.alpha.,15-dihydroxy-4a, 4b-bishomo-5-cis,13- trans,17-cis-prosta- trienoic acid______________________________________

EXAMPLES 1860-1876

Treatment of the 8,15-dimethyl-9-oxo-11.alpha.-hydroxy derivatives listed in Table 46 below the aqueous acetic acid by the procedure described in Example 1387 is productive of the corresponding 10-prostenoic acid products of the table.

TABLE 46______________________________________ Starting 8,15-di- methyl-9-oxo-11.alpha.- ProductEx- hydroxy deriva- 8,15-dimethyl-9-oxo-ample tives of Example 10-prostenoic acid______________________________________1860 1835 8.beta.,15-dimethyl-9-oxo- 15-hydroxy-10,13-trans- prostadienoic acid1861 1837 8.alpha.,15-dimethyl-9-oxo- 15-hydroxy-8-iso-10, 13-trans-prostadienoic acid1862 1839 8.beta.,15-dimethyl-9-oxo- 15-hydroxy-10,13-trans, 17-cis-prostatrienoic acid1863 1841 8.beta.,15-dimethyl-9-oxo- 15-hydroxy-20-ethyl- 10,13-trans-prosta- dienoic acid1864 1843 8.beta.,15-dimethyl-9-oxo- 15-hydroxy-7a,7b-bis- homo-10,13-trans- prostadienoic acid1865 1845 8.beta.,15-dimethyl-9-oxo-15- hydroxy-2-ethyl-10,13- trans-prostadienoic acid1866 1847 8.beta.,15-dimethyl-9-oxo- 15-hydroxy-3,3,20-tri- methyl-10,13-trans- prostadienoic acid1867 1849 8.beta.,15-dimethyl-9-oxo- 15-hydroxy-3-oxa-10,13- trans-prostadienoic acid1868 1851 8.beta.,15-dimethyl-9-oxo- 15-hydroxy-3-oxa-10, 13-trans,17-cis-prosta- trienoic acid1869 1853 8.beta.,15-dimethyl-9-oxo- 15-hydroxy-5-cis,10,13- trans-prostatrienoic acid1870 1855 8.beta.p,15-dimethyl-9-oxo- 15-hydroxy-5-cis,10, 13-trans,17-cis-prosta- tetraenoic acid1871 1857 8.beta.,15-dimethyl-9-oxo- 15-hydroxy-4-nor-20- methyl-5-cis,10,13- trans-prostatrienoic acid1872 1859 8.beta.,15-dimethyl-9-oxo- 15-hydroxy-4a,4b-bis- homo-5-cis,10,13-trans, 17-cis-prostatetraenoic acid1873 1812 8.beta.,15-dimethyl-9-oxo-15- hydroxy-10-prostenoic acid1874 1815 8.beta.,15-dimethyl-9-oxo-15- hydroxy-3-oxa-10- prostenoic acid1875 1814 8.beta.,15-dimethyl-9-oxo-15- hydroxy-7a,7b-bishomo- 10-prostenoic acid1876 1813 8.alpha.,15-dimethyl-9-oxo- 15-hydroxy-8-iso-10- prostenoic acid______________________________________

EXAMPLE 1877

Preparation of 3-methoxy-1-octyne

To an ice-cooled solution of 63 g. of 1-octyn-3-ol in 300 ml. of dimethoxyethane is added under an inert atmosphere 312 ml. of 1.6 M n-butyllithium in hexane dropwise over 1 hour. To the mixture is then added 145 g. of methyl iodide and the resulting mixture is stirred at ambient temperatures for 24 hours and then treated to 60.degree. C. for 1 hour. The mixture is cooled and poured into cold dilute hydrochloric acid. The organic phase is separated, washed with water and saturated brine, dried (Na.sub.2 SO.sub.4), and evaporated to an oil, dried (Na.sub.2 SO.sub.4), and evaporated to an oil. Fractional distillation of the oil in vacuo yields the product as a colorless oil.

EXAMPLE 1878

Preparation of 1-Iodo-3-methoxy-trans-1-octene

Treatment of 3-methoxy-1-octyne (Example 1877) with disiamylborane, trimethylamine oxide, sodium hydroxide and iodine by the procedure described in Example 996 furnishes the title product.

EXAMPLE 1879

Preparation of 3-Methoxy-trans-1-octenyl lithium

Treatment of 1-iodo-3-methoxy-trans-1-octene (Example 1878) with butyl lithium in the manner of Example 961 provides a toluene-hexane solution of the subject trans-vinyl lithium derivative.

EXAMPLE 1880

Preparation of Lithium (3-methoxy-trans-1-octenyl)trimethylalanate

The subject alanate in hydrocarbon solution is prepared according to the method of Example 963 from a hydrocarbon solution of 3 -methoxy-trans-1-octenyl lithium (Example 1879) and trimethylaluminum.

EXAMPLES 1881-1895

Treatment of the cycloalkenones listed in Table 47 with lithium(3-methoxy-trans-1-octenyl)trimethylalanate (Example 1880) by the procedure described in Example 957 with the omission of the 80% aqueous acetic acid treatment (80.degree. C, 1 hour) followed by saponification of the intermediate alkyl prostenoates by the procedure described in Example 122 furnishes the product 9-oxo-15-methoxy-13-trans-prostenoic acids of the table.

TABLE 47______________________________________ Starting cyclo- Product 9-oxo-15-Ex- alkenone of methoxy-13-trans-ample Example prostenoic acid______________________________________1881 23 9-oxo-7a,7b-bishomo- 15-methoxy-13-trans- prostenoic acid1882 31 9-oxo-2-ethyl-15- methoxy-13-trans-pro- stenoic acid1883 41 9-oxo-3,3-dimethyl- 15-methoxy-13-trans- prostenoic acid1884 46 9-oxo-3-oxa-15-methoxy- 13-trans-prostenoic acid1885 53 9-oxo-7-nor-15-methoxy- 13-trans-prostenoic acid1886 70 9-oxo-2-fluoro-15- methoxy-13-trans- prostenoic acid1887 74 9-oxo-7a-homo-15- methoxy-13-trans-pro- stenoic acid1888 79 9-oxo-2-phenyl-15- methoxy-13-trans-pro- stenoic acid1889 99 9-oxo-2-methyl-15- methoxy-13-trans-pro- stenoic acid1890 111 9-oxo-10a-homo-15- methoxy-13-trans- prostenoic acid1891 118 9-oxo-3-thia-15- methoxy-13-trans- prostenoic acid1892 900 9-oxo-15-methoxy-5- cis,13-trans-pro- stadienoic acid1893 1144 9-oxo-4-nor-15-methoxy- 13-trans-prostadienoic acid1894 1145 9-oxo-4-homo-15- methoxy-5-cis,13- trans-prostadienoic acid1895 1146 9-oxo-4a,4b-bishomo- 15-methoxy-13-trans- prostadienoic acid______________________________________

EXAMPLES 1896-1910

Treatment of the 9-oxo-15-methoxy-13-trans-prostenoic acids listed in Table 48 below with lithium perhydro-9b-boraphenalylhydride by the procedure described in Example 737 furnishes the 9.alpha.-hydroxy-15-methoxy-13-trans-prostenoic acids of the Table.

TABLE 48______________________________________ Starting 9-oxo- 15-methoxy-13- trans-prosten- Product 9.alpha.-hydroxy-15-Ex- oic acid of methoxy-13-trans-ample Example prostenoic acid______________________________________1896 1881 9.alpha.-hydroxy-7a,7b-bis- homo-15-methoxy-13- trans-prostenoic acid1897 1882 9.alpha.-hydroxy-2-ethyl- 15-methoxy-13-trans- prostenoic acid1898 1883 9.alpha.-hydroxy-3,3-dimethyl- 15-methoxy-13-trans- prostenoic acid1899 1884 9.alpha.-hydroxy-3-oxa-15- methoxy-13-trans- prostenoic acid1900 1885 9.alpha.-hydroxy-7-nor-15- methoxy-13-trans-pro- prostenoic acid1901 1886 9.alpha.-hydroxy-2-fluoro- 15-methoxy-13-trans- prostenoic acid1902 1887 9.alpha.-hydroxy-7a-homo- 15-methoxy-13-trans- prostenoic acid1903 1888 9.alpha.-hydroxy-2-phenyl- 15-methoxy-13-trans- prostenoic acid1904 1889 9.alpha.-hydroxy-2-methyl- methoxy-13-trans- prostenoic acid1905 1890 9.alpha.-hydroxy-10a-homo- 15-methoxy-13-trans- prostenoic acid1906 1891 9.alpha.-hydroxy-3-thia-15- methoxy-13-trans- prostenoic acid1907 1892 9.alpha.-hydroxy-15-methoxy- 5-cis,13-trans-prosta- dienoic acid1908 1893 9.alpha.-hydroxy-4-nor-15- methoxy-5-cis,13- trans-prostadienoic acid1909 1894 9.alpha.-hydroxy-4-homo-15- methoxy-5-cis,13-trans- prostadienoic acid1910 1895.beta. 9.alpha.-hydroxy-4a,4b-bis- homo-15-methoxy-13- trans-prostenoic acid______________________________________

EXAMPLE 1911

Preparation of 2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanol

A solution of 5.0 g. (35 mmoles) of 5-hydroxy-2,3-oxidocyclopentylacetaldehyde-.gamma.-lactol (isomeric mixture; E. J. Corey and R. Noyori, Tetrahedron Letters, 1970, 311) in 25 ml. of DMSO is added during 0.5 minutes at 20.degree. C. to a stirred solution of the Withig reagent [E.J. Corey et al., JACS, 91 5675 (1969); also Example 1108] and dimsyl sodium prepared from 23.5 g. (53 mmoles) of 4-carboxybutyltriphenylphosphonium bromide, 6.1 g. (140 mmoles) of 57% sodium hydride dispersion, and 230 ml. of DMSO (dimethylsulfoxide).

The solution is stirred at ambient temperatures for 2 hours and poured into a stirred mixture of methylene chloride, ice, and hydrochloric acid. The reaction mixture is worked up as described in Example 1105, and the crude product is purified by dry column chromatography on silica gel to provide the title compound (mixture of two stereoisomers) as an oil, IR (film) 3450, 1710, and 832 cm.sup.-1.

EXAMPLE 1912

Preparation of 2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanone

A stirred solution of 2.98 g. (13.2 mmoles) of 2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentaol (Example 1911) in 66 ml. of acetone is treated dropwise with 3.30 ml. of 8N chromic acid in 8M N.sub.2 SO.sub.4 during 20 minutes at -10.degree. to -5.degree. C. The solution is stirred at -5.degree. C. for 10 minutes and treated successively with a few drops of isopropanol and 12 ml. of water. The mixture is filtered, and the filtrate is concentrated saturated with sodium chloride, and extracted with ethyl acetate. The extract is washed with brine, dried over MgSO.sub.4, and evaporated to give an oil, IR (film) 1740, 1710, and 840 cm.sup.-1.

EXAMPLE 1913

Preparation of 2-(6-carboxy-2-cis-hexenyl)-4-hydroxycyclopent-2-en-1-one

A solution of (pH or 10.2-10.5) of 2.42 g. (10.8 mmoles) of 2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanone (Example 1912) 4.58 g. (43.2 mmoles) of sodium carbonate, and 216 ml. of water is allowed to stand at room tempertures under nitrogen for 24 hours. The solution is acidified at 15.degree. C. with hydrochloric acid and extracted with ethyl acetate. The extract is washed with brine, dried over MgSO.sub.4, and evaporated to give an oil; IR (film) 1700 (carbonyl groups) and 1630 cm.sup.-1 (conjugated oelfin); NMR 7.11 (1), 5.54 (2), and 4.95 (1).delta..

Claims

1. A compound selected from the group consisting of an optionally active compound of the formula: ##STR38## and a racemic compound of that formula and the mirror image thereof wherein m is an integer from 2 to 5, inclusive, and n is an integer from 3 to 6, inclusive, R is selected from the group consisting of hydrogen and C.sub.1 -C.sub.4 alkyl; and the pharmacologically acceptable cationic salts thereof.

2. A compound according to claim 1, wherein n and m are as previously defined; and R is hydrogen.

3. A compound according to claim 1, wherein n and m are as previously defined; and R is selected from the group consisting of C.sub.1 -C.sub.4 alkyl.

4. A compound according to claim 2, wherein n and R as previously defined; and m is the integer 3.

5. A compound according to claim 3, wherein m and R are as previously defined; and m is the integer 3.

6. The enantiomer according to claim 1, l-9-oxo-11.alpha.,15-dihydroxy-5-cis,13-cis-prostadienoic acid.

7. The racemate according to claim 1, dl-9-oxo-11.alpha.,15-dihydroxy-5-cis,13-cis-prostadienoic acid.

8. The enantiomer according to claim 1, l-9-oxo-11.alpha.,15-dihdyroxy-4,20-bisnor-5-cis,13-cis-prostadienoic acid.

9. The racemate according to claim 1, dl-9-oxo-11.alpha.,15-dihdroxy-4,20-bisnor-5-cis,13-cis-prostadienoic acid.