Claims
- 1. A process for the preparation of a .DELTA..sup.17(20) -steroid of the formula ##STR19## which comprises starting with a 16-unsaturated corticoid of the formula ##STR20## and (1) contacting the 16-unsaturated corticoid (I) with a methylating agent in the presence of a copper catalyst and
- (2) contacting the product of step (1}with a silylating agent where
- R.sub.20 is alkyl of 1 thru 4 carbon atoms or phenyl, the R.sub.20 's can be can be the same or different;
- R.sub.21 is a hydrogen atom, -CO-R.sub.21, or -Si(R.sub.121).sub.3 ;
- R.sub.21 ' is alkyl of 1 thru 4 carbon atoms or phenyl;
- R.sub.121 is alkyl of 1 thru 4 carbon atoms or phenyl, the R.sub.121 's can be the same or different.
- 2. A process according to claim 1 where the 16-unsaturated corticoid (I) is selected from the group consisting of ##STR21## and the C.sub.3 protected forms of the 3.beta.-hydroxy-.DELTA..sup.5 -(C)-steroid ##STR22## where R.sub.3 is alkyl of 1 thru 3 carbon atoms, a TMS, THP, or EEE group;
- R.sub.3 ' is alkyl of 1 thru 5 carbon atoms or phenyl;
- R.sub.6 is a hydrogen or fluorine atom or methyl group;
- R.sub.9 is nothing, a hydrogen, fluorine or oxygen atom which makes the C ring
- (a) .DELTA..sup.9(11) when R.sub.9 is nothing and
- (b) 9.beta.,11.beta.-epoxide when R.sub.9 and R.sub.11 taken together are an oxygen atom;
- R.sub.11 is a hydrogen or oxygen atom, two hydrogen atoms, or .alpha.- or .beta.-hydroxyl group or trimethylsilyl ether thereof which makes the C-ring
- (a) .DELTA..sup.9(11) when R.sub.11 is a hydrogen atom,
- (b) 9.beta.,11.beta.-epoxide when R.sub.9 and R.sub.11 taken together are an oxygen atom and between C.sub.11 and R.sub.11 is a single bond, and
- a ketone when R.sub.11 is an oxygen atom and between C.sub.11 and R.sub.11 is a double bond;
- R.sub.20 is alkyl of 1 thru 4 carbon atoms or phenyl, the R.sub.20 's can be the same or different;
- R.sub.21 is a hydrogen atom, -CO-R.sub.21 ' or -Si(R.sub.121).sub.3 ;
- R.sub.21 ' is alkyl of 1 thru 4 carbon atoms or phenyl;
- R.sub.121 is alkyl of 1 thru 4 carbon atoms or phenyl, the R.sub.121 's can be the same or different;
- .about. indicates that the attached group can be in either the .alpha. or .beta. configuration;
- is a single or double bond;
- TMS refers to trimethylsilyl;
- THP refers to tetrahydropyranyl;
- EEE refers to (1-ethoxy) ethyl ether [-O-CH(CH.sub.3)OCH.sub.2 CH.sub.3 ].
- 3. A process according to claim 1 where the methylating agent is selected from the group consisting of compounds of the formula CH.sub.3 Cu, (CH.sub.3).sub.2 CuM or CH.sub.3 MgQ where M is a lithium or magnesium ion and Q is a chlorine, bromine or iodine atom.
- 4. A process according to claim 1 where the methylating agent is CH.sub.3 MgQ.
- 5. A process according to claim 1 where the copper catalyst is a cupric salt selected from the group consisting of cupric acetate, cupric chloride, cupric sulfate, or a cuprous salt selected from the group consisting of cuprous chloride, cuprous bromide, cuprous iodide and cuprous cyanide and complexes thereof.
- 6. A process according to claim 1 where the copper catalyst is cupric acetate.
- 7. A process according to claim 1 where the silylating agent is selected from the group consisting of (R.sub.20).sub.3 -Si-E, bistrimethylsilylacetamide, where E is a chlorine, bromine or iodine atom or -NR.alpha.R.beta. where R.alpha. and R.beta. may be the same or different and are alkyl of 1 thru 5 carbon atoms or phenyl and where R.alpha. and R.beta. can be connected or cyclized in a ring with or without an oxygen or additional nitrogen atom and where R.sub.20 is defined in claim 12.
- 8. A process according to claim 1 where the silylating agent is trimethylsilyl chloride.
- 9. A process according to claim 1 where the 16-unsaturated corticoid (1) is selected from the group consisting of 21-hydroxypregna-1,4,9(11),16-tetraene-3,20-dione 21-acetate or 9.beta.,11.beta.-epoxy-21-hydroxypregna-1,4,16-triene-3,20-dione 21-acetate.
- 10. A 17.alpha.-silyl ether of the formula ##STR23## and the C.sub.3 protected forms of the 3.beta.-hydroxy-.DELTA..sup.5 -(C) A-ring where
- R.sub.6 is a hydrogen or fluorine atom or methyl group;
- R.sub.9 is nothing, a hydrogen, fluorine or oxygen atom which makes the C ring
- (a) .DELTA..sup.9(11) when R.sub.9 is nothing and
- (b) 9.beta.,11.beta.-epoxide when R.sub.9 and R.sub.11 taken together are an oxygen atom
- R.sub.11 is a hydrogen or oxygen atom, two hydrogen atoms, or .alpha.- or .beta.-hydroxyl group or trimethylsilyl ether thereof which makes the C-ring
- (a) .DELTA..sup.9(11) when R.sub.9 is nothing and
- (b) 9.beta.,11.beta.-epoxide when R.sub.9 and R.sub.11 taken together are an oxygen atom and between C.sub.11 and R.sub.11 is a single bond, and
- (c) a ketone when R.sub.11 is an oxygen atom and between C.sub.11 and R.sub.11 is a double bond;
- R.sub.20 is alkyl of 1 thru 4 carbon atoms or phenyl, the R.sub.20 's can be the same or different;
- R.sub.21 is a hydrogen atom, -CO-R.sub.21 ' or -Si(R.sub.121).sub.3 ;
- R.sub.21 ' is alkyl of 1 thru 4 carbon atoms or phenyl;
- R.sub.121 is alkyl of 1 thru 4 carbon atoms or phenyl, the R.sub.121 's can be the same or different;
- .about. indicates that the attached group can be in either the .alpha. or .beta. configuration;
- is a single or double bond;
- X is a hydrogen atom or nothing; when X is nothing the at C.sub.3 is a double bond and when X is a hydrogen atom the at C.sub.3 is a single bond.
- 11. A 17.alpha.-silyl ether according to claim 10 where the 17.alpha.-silyl ether (IV A-C) is a .DELTA..sup.4 -3-keto(A) or .DELTA..sup.1,4 -3-keto (B) steroid.
- 12. A 17.alpha.-silyl ether according to claim 10 where the 17.alpha.-silyl ether (Iv A-C) is a 3.beta.-hydroxy-.DELTA..sup.5 (C) steroid in the free form ##STR24## or C.sub.3 protected form selected from the group consisting of ##STR25## where R.sub.3 is alkyl of 1 thru 3 carbon atoms, a TMS, THP or EEE group;
- R.sub.3 ' is alkyl of 1 thru 5 carbon or phenyl;
- TMS refers to trimethylsilyl;
- THP refers to tetrahydropyranyl;
- EEE refers to (1-epoxy) ethyl ether [-O-CH(CH.sub.3)OCH.sub.2 CH.sub.3 ];
- where R.sub.6, R.sub.9, R.sub.11, R.sub.20 are defined in claim 10.
- 13. A 17.alpha.-silyl ether according to claim 10 where R.sub.6 is a hydrogen atom.
- 14. A 17.alpha.-silyl ether according to claim 10 where R.sub.9 is nothing or an oxygen atom and where R.sub.11 is a hydrogen atom or an oxygen atom making the C ring .DELTA..sup.9(11) or a 9.beta.,11.beta.-epoxide.
- 15. A 17.alpha.-silyl ether according to claim 10 where R.sub.20 is selected from group consisting of methyl, isopropyl, t-butyl or phenyl.
- 16. A 17.alpha.-silyl ether according to claim 10 where R.sub.20 is methyl or phenyl.
- 17. A 17.alpha.-silyl ether according to claim 10 where R.sub.21 is -CO-R.sub.21 ' and R.sub.21 ' is selected from the group consisting of methyl, ethyl or phenyl.
- 18. 9.beta.,11.beta.-Epoxy-21-hydroxypregna-4,16-diene-3,20-dione 21-acetate.
- 19. 9.beta.,11.beta.-Epoxy-21-hydroxypregna-1,4,16-triene-3,20-dione 21-acetate.
Parent Case Info
This is a continuation of our co-pending U.S. patent application Ser. No. 724,380 filed Apr. 18, 1985, now U.S. Pat. No. 4,704,455, which is a continuation-in-part patent application of U.S. patent application Ser. No. 618,986, filed June 11, 1984, now abandoned.
US Referenced Citations (11)
Foreign Referenced Citations (2)
Number |
Date |
Country |
2318647 |
Feb 1977 |
FRX |
2001990 |
Feb 1979 |
GBX |
Non-Patent Literature Citations (7)
Entry |
Helv. Chim. Acta, 61, 3068-3071 (1978). |
J. Org. Chem., 40, 3427-3429 (1075). |
Organic Reactions in Steroid Chemistry, vol. II, J. Fried and J. A. Edwards, Van Nostrand Reinhold Co., N.Y. (1972), pp. 75-76. |
J. Am. Chem. Soc. 80, pp. 3160-3161 (1958). |
J. Am. Chem. Soc. 80, p. 4428 (1958). |
E. J. Corey in Tetrahedron Letters 26, p. 6019 (1985). |
A. Alexakis in Tetrahedron Letters 27, p. 1047 (1986). |
Continuations (1)
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Parent |
724380 |
Apr 1985 |
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Continuation in Parts (1)
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618986 |
Jun 1984 |
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