Biaryl compounds as serine protease inhibitors

Abstract

Compounds of formula (I) are useful as inhibitors of trypsin like serine protease enzymes such as thrombin, factor VIIa, factor Xa, TF/FVIIa, and trypsin. These compounds could be useful to treat and/or prevent clotting disorders, and as anticoagulating agents.

Description

TECHNICAL FIELD

[0002] The present invention relates to the identification, through synthesis and testing, of heretofore unreported compounds which, in appropriate pharmaceutical compositions, exert a therapeutic effect through reversible inhibition of serine proteases.

BACKGROUND OF INVENTION

[0003] Serine proteases make up the largest and most extensively studied group of proteolytic enzymes. Their critical roles in physiological processes extend over such diverse areas as blood coagulation, fibrinolysis, complement activation, reproduction, digestion, and the release of physiologically active peptides. Many of these vital processes begin with cleavage of a single peptide bond or a few peptide bonds in precursor protein or peptides. Sequential limited proteolytic reactions or cascades are involved in blood clotting, fibrinolysis, and complement activation. The biological signals to start these cascades can be controlled and amplified as well. Similarly, controlled proteolysis can shut down or inactivate proteins or peptides through single bond cleavages.

[0004] While serine proteases are physiologically vital, they also can be hazardous. Their proteolytic action, if uncontrolled, can destroy cells and tissues through degradation of proteins. As a natural safeguard in normal plasma, 10% of the protein matter is composed of protease inhibitors. The major natural plasma inhibitors are specific for serine proteinases. Diseases (associated protease given in the parentheses) such as pulmonary emphysema (cathepsin G), adult respiratory distress syndrome (chymases), and pancreatitis (trypsin, chymotrypsin, and others) are characterized by uncontrolled serine proteases. Other proteases appear to be involved in tumor invasion (plasmin, plasminogen activator), viral transformation, and inflammation (kallikrein). Thus the design and synthesis of specific inhibitors for this class of proteinases could offer major therapeutic benefits.

[0005] Thrombus formation, that is blood coagulation, is normally initiated by tissue injury; its normal purpose is to slow or prevent blood loss and facilitate wound healing. There are other conditions, however, not directly connected with tissue injury that may promote the coagulation process and lead instead to harmful consequences; examples of such conditions are atherosclerosis and inflammation.

[0006] The complex pathways of blood coagulation involve a series of enzyme reactions in which plasma coagulation factors, actually enzyme precursors or zymogens, are sequentially activated by limited proteolysis. Blood coagulation, or the coagulation cascade, is viewed mechanistically as two pathways, the extrinsic and the intrinsic (FIG. 1). Each pathway proceeds through a sequence of the Roman-numeral-designated factors until they converge at the activation of factor X after merger of the pathways. Thrombin generation proceeds stepwise through a common pathway. Thrombin then acts on the solution plasma protein, fibrinogen, to convert it to stable insoluble fibrin clots, thus completing the coagulation cascade.

[0007] The extrinsic pathway is vital to the initiation phase of blood coagulation while the intrinsic pathway provides necessary factors in the maintenance and growth of fibrin. The initiation of the coagulation cascade involves the release of tissue factor (TF) from injured vessel endothelial cells and subendothelium. TF then acts upon factor VII to form the TF/FVIIa complex (where VIIa designates the activated factor rather than the zymogen form). This complex initiates coagulation by activating factors IX and X. The resulting factor Xa forms a prothrombinase complex that activates prothrombin to produce the thrombin that converts fibrinogen to insoluble fibrin. In contrast, the intrinsic system is activated in vivo when certain coagulation proteins contact subendothelial connective tissue. In the sequence that follows, contact factors XII and XI are activated. The resulting factor XIa activates factor IX; then factor IXa activates factor X thereby intersecting with the extrinsic pathway.

[0008] With time, the TF/FVIIIa complex (of the extrinsic pathway) loses activity due to the action of tissue factor pathway inhibitor (TFPI), a Kunitz-type protease inhibitor protein which, when complexed with factor Xa, can inhibit the proteolytic activity of TF/FVIIa. If the extrinsic system is inhibited, additional factor Xa is produced through the thrombin-mediated action in the intrinsic pathway. Thrombin, therefore, exerts a dual catalytic role in (a) the conversion of fibrinogen to fibrin and (b) mediating its own production. The autocatalytic aspect of thrombin production affords an important safeguard against excessive blood loss, and, assuming presence of a threshold level of prothrombinase, ensures that the blood coagulation process will go to completion.

[0009] While the ability to form blood clots is vital to survival, there are disease states wherein the formation of blood clots within the circulatory system can cause death. When patients are afflicted with such disease states, it is not desirable to completely inhibit the clotting system because life-threatening hemorrhage would follow. Thus, it is highly desirable to develop agents that inhibit coagulation by inhibition of factor VIIa without directly inhibiting thrombin.

[0010] Need for the prevention of intravascular blood clots or for anti-coagulant treatment in many clinical situations is well known. Drugs in use today are often not satisfactory. A high percentage of patients who suffer internal injuries or undergo certain surgical procedures develop intravascular blood clots which, if unchecked, cause death. In total hip replacement surgery, for example, it is reported that 50% of the patients develop deep vein thrombosis (DVT). Current approved therapies involve administration of heparin in various forms, but results are not entirely satisfactory; 10-20% of patients suffer DVT and 5-10% have bleeding complications. Along these lines, see International Publication No. WO 00/15658.

[0011] Other examples of clinical situations for which better anticoagulants would be of great value are when patients undergo transluminal coronary angioplasty and treatment for myocardial infarction or crescendo angina. The present therapy for these conditions is administration of heparin and aspirin, but this treatment is associated with a 6-8% abrupt vessel closure rate within 24 hours of the procedure. Transfusion therapy due to bleeding complications is required in approximately 7% of cases following the use of heparin. Occurrences of delayed vessel closures are also significant, but administration of heparin after termination of the procedure affords little beneficial effect and can be detrimental.

[0012] Heparin and certain derivatives thereof are the most commonly used anti-clotting agents. These substances exert their effects mainly through inactivation of thrombin, which is inactivated 100 times faster than factor Xa. Two other thrombin-specific anticoagulants, hirudin and hirulog, are in clinical trials (as of September 1999). However, bleeding complications are associated with these agents.

[0013] In preclinical studies in baboons and dogs, the targeting of enzymes involved in earlier stages of the coagulation cascade, such as factor VIIa or factor Xa, prevents clot formation and does not produce bleeding side effects observed with direct thrombin inhibitors.

[0014] Several preclinical studies reveal that inhibition of TF/FVIIa offers the widest window of therapeutic effectiveness and safety with respect to bleeding risk of any anticoagulant approach tested including thrombin, platelet, and factor Xa inhibition.

[0015] A specific inhibitor of factor VIIa would provide clinicians with a valuable and needed agent that would be safe and effective in situations where the present drugs of choice, heparin and related sulfated polysaccharides, are no better than marginally effective.

[0016] There exists a need for a low molecular weight specific serine protease inhibitors specific toward various enzymes, particularly for factor VIIa that does not cause unwanted side effects.

[0017] The FIGURE illustrates the extrinsic and intrinsic pathways of blood coagulation.

SUMMARY OF INVENTION

[0018] An aspect of the present invention relates to compounds represented by the formula: 1

[0019] pharmaceutically acceptable salts thereof, and prodrugs thereof.

[0020] Each E1 and L individually is a 5 to 7 membered saturated or unsaturated carbon ring, 5 to 7 membered saturated or unsaturated hetero ring, bicyclic saturated or unsaturated carbon ring, bicyclic saturated or unsaturated hetero ring, or 1-8 hydrocarbon chain which may be substituted with one or more hetero groups selected from N, O, S, S(O), and S(O2) which may be saturated or unsaturated. The bicyclic rings typically contain 7-13 atoms in the ring.

[0021] R is —CH═CH—R2, —C≡C—R2, —C(R2)═CH2, —C(R2)═C(R3), —CH═NR2, —C(R2)═N—R3, 4-7 membered saturated or unsaturated carbon ring system with or without substitution, 4-7 membered saturated or unsaturated hetero ring system with or without substitution, or chain of 2 to 8 carbon atoms having 1 to 5 double or triple bonds with substitutions selected from R1, R2, or R3.

[0022] R1 is H, —R, —NO2, —CN, -halo, —N3, —C1-8 alkyl, —(CH2)nCO2R2, —C2-8 alkenyl-CO2R2, —O(CH2)nCO2R2, —C(O)NR2R3, —P(O)(OR2)2, alkyl substituted tetrazol-5-yl, —(CH2)nO(CH2)n aryl, —NR2R3, —(CH2)n OR2, —(CH2)n SR2, —N(R2)C(O)R3, —S(O2)NR2R3, —N(R2)S(O2)R3, —(CHR2)n NR2R3, —C(O)R3, (CH2)n N(R3)C(O)R3, —N(R2)CR2R3 substituted or unsubstituted (CH2)n-cycloalkyl, substituted or unsubstituted (CH2)n-phenyl, or substituted or unsubstituted (CH2)n-heterocycle which may be saturated or unsaturated.

[0023] m is 1 except that when E1 is a cyclic ring of more than 5 atoms, then m is 1 or higher, depending upon the size of the ring.

[0024] R2 is H, -halo, -alkyl, -haloalkyl, —(CH2)n-phenyl, —(CH2)1-3-biphenyl, —(CH2)1-4—Ph—N(SO2-C1-2-alkyl)2, —CO(CHR1)n—OR1, —(CHR1)n-heterocycle, —(CHR1)n—NH—CO—R1, —(CHR1)n—NH—SO2R1, —(CHR1)n—Ph—N(SO2—C1-2-alkyl)2, —(CHR1)n—C(O)(CHR1)—NHR1, —(CHR1)n—C(S)(CHR1)—NHR1, —(CH2)nO(CH2)nCH3, —CF3, —C2-5 acyl, —(CHR1)nOH, —(CHR1)nCO2R1, —(CHR1)n—O-alkyl, —O(CHR1)n—O—(CH2)n—O-alkyl, —(CHR1)n—S-alkyl, —(CHR1)n—S(O)-alkyl, —(CHR1)n—S(O2)-alkyl, —(CHR1)n—S(O2)—NHR3, —(CHR3)n—N3, —(CHR3)nNHR4, 2 to 8 carbon atom alkene chain having 1 to 5 double bonds, 2 to 8 carbon atom alkyne chain having 1 to 5 triple bonds, substituted or unsubstituted-(CHR3)n heterocycle, or substituted or unsubstituted-(CHR3)n cycloalkyl which may be saturated or unsaturated.

[0025] When n is more than 1, the substitutions R1 and R3 may be same or different.

[0026] R3 is H, —OH, —CN, substituted alkyl, —C2-8 alkenyl, substituted or unsubstituted cycloalkyl, —N(R1)R2, or 5-6 membered saturated substituted or unsubstituted hetero ring.

[0027] —NR2R3 may form a ring system having 4 to 7 atoms or may be bicyclic ring. The ring system may be of carbon or hetero atoms and further it may saturated or unsaturated and also may be substituted or unsubstituted.

[0028] W is a direct bond, —CHR2—, —CH═CR2—, —CR2═CH—, —CR2═CR2—, —C≡C—, —O—CHR2—, —CHR2—O—, —N(R2)—C(O)—, —C(O)—N(R)—, —N(R2)—CH—(R3)—, —CH2—N(R2)—, —CH(R1)—N(R2)—, —S—CHR2—, —CHR2—S—, —S(O2)—N(R2)—, —C(O)N(R2)—(CHR2)n-, —C(R1R2)n-NR2—, —N(R2)—S(O2)—, —R2C(O)NR2—, —R2NC(O)NR2—, —CONR2CO—, —C(═NR2)NR2—, —NR2C(═NR2)NR2—, —NR2O—, —N═NCHR2—, or —C(O)NR2SO2—.

[0029] E2 is 5 to 7 membered saturated or unsaturated carbon ring, 5 to 7 membered saturated or unsaturated hetero ring, bicyclic ring system, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, alkylaryl, aralkyl, aralkenyl, aralkynyl, alkoxy, alkylthio, or alkylamino.

[0030] each X individually is a direct bond, substituted or unsubstituted C1-4 methylene chain; O, S, NR2, S(O), S(O2), or N(O) containing one or two C1-4 substituted or unsubstituted methylene chains. X at different places may be same or different.

[0031] B is H, -halo, —CN, —NH2, —(CH2)n—C(═NR4)NHR5, —(CH2)n—NHR4, —(CH2)nNHC(═NR4)NR5, —(CH2)n—OR4, C1-8 substituted or unsubstituted alkyl, substituted or unsubstituted ring system having 4 to 7 carbon or hetero atoms which may be saturated or unsaturated.

[0032] B1 is selected from B; B1 and B may be same or different.

[0033] There may be more than one similar or different R2 groups present on E2, when E2 is a cyclic group of more than 5 atoms. In particular, p is 1 except that when E2 is a cyclic ring of more than 5 atoms, p is 1 or higher depending upon the size of the ring.

[0034] n is 0-4

[0035] A is selected from R1.

[0036] o is 1 except that when L is a cyclic ring of more than 5 atoms, o is 1 or higher depending upon the size of the ring.

[0037] Each V and V1 individually is selected from R1 and N-alkyl substituted carboxamidyl (—CONHR) where the alkyl group may be straight, branched, cyclic, or bicyclic; N,N-disubstituted carboxamidyl (—CONR1R2 where R1 and R2 may be substituted or unsubstituted alkyl or aryl and may be the same or different); mono- or disubstituted sulfonamides (SO2NHR or —SO2NR1R2); and methylene- or polymethylene chain-extended variants thereof.

[0038] Each R4 and R5 individually is H, —(CH2)nOH, —C(O)OR6, —C(O)SR6, —(CH2)n C(O)NR7R8, —O—C(O)—O—R7, an amino acid or a dipeptide,

[0039] Each R6 is H, R7, —C(R7)(R8)—(CH2)n—O—C(O)—R9, —(CH2)n—C(R7)(R8)—O—C(O)R9, —(CH2)n—C(R7)(R8)—O—C(O)—O—R9, or —C(R7)(R8)—(CH2)n—O—C(O)—O—R9,

[0040] Each R7, R8 and R9 individually is H, alkyl, substituted alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, heterocycle, substituted heterocycle, alkylaryl, substituted alkylaryl, cycloalkyl, substituted cycloalkyl, or CH2CO2alkyl.

[0041] The present invention also relates to pharmaceutical compositions containing at least one of the above disclosed compounds and their prodrugs.

[0042] A further aspect of the present invention relates to a method for inhibiting trypsin-like serine protease enzymes, such as thrombin, factor Xa, factor VIIa, TF/VIIa, and trypsin in a patient which comprises administering to the patient an effective serine protease inhibiting amount of at least one of the above disclosed compounds.

[0043] Still other objects and advantages of the present invention will become readily apparent by those skilled in the art from the following detailed description, wherein it is shown and described preferred embodiments of the invention, simply by way of illustration of the best mode contemplated of carrying out the invention. As will be realized the invention is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, without departing from the invention. Accordingly, the description is to be regarded as illustrative in nature and not as restrictive.

BEST AND VARIOUS MODES FOR CARRYING OUT INVENTION

[0044] An aspect of the present invention relates to compounds represented by the formula: 2

[0045] pharmaceutically acceptable salts thereof; and prodrugs thereof.

[0046] Each E1 and L individually is a 5 to 7 membered saturated or unsaturated carbon ring, 5 to 7 membered saturated or unsaturated hetero ring, bicyclic saturated or unsaturated carbon ring, bicyclic saturated or unsaturated hetero ring, or 1-8 hydrocarbon chain which may be substituted with one or more hetero groups selected from N, O, S, S(O), and S(O2) which may be saturated or unsaturated.

[0047] R is —CH═CH—R2, —C≡C—R2, —C(R2)═CH2, —C(R2)═C(R3), —CH═NR2, —C(R2)═N—R3, 4-7 membered saturated or unsaturated carbon ring system with or without substitution, 4-7 membered saturated or unsaturated hetero ring system with or without substitution, or chain of 2 to 8 carbon atoms having 1 to 5 double or triple bonds with substitutions selected from R1, R2, or R3. Preferably, these R, R1, R2, or R3 do not include —(C2-4 alkenyl)-CO2—C1-8 alkyl, —(C2-4 alkenyl)-CO2—C1-8 alkyl-phenyl, and —(C2-4 alkenyl)—CO2—C1-8 alkyl-O—C1-4 alkyl.

[0048] R1 is H, —R, —NO2, —CN, -halo, —N3, —C1-8 alkyl, —(CH2)nCO2R2, —C2-8 alkenyl-CO2R2, —O(CH2)nCO2R2, —C(O)NR2R3, —P(O)(OR2)2, alkyl substituted tetrazol-5-yl, —(CH2)nO(CH2)n aryl, —NR2R3, —(CH2)n OR2, —(CH2)n SR2, —N(R2)C(O)R3, —S(O2)NR2R3, —N(R2)S(O2)R3, —(CHR2)n NR2R3, —C(O)R3, (CH2)n N(R3)C(O)R3, —N(R2)CR2R3 substituted or unsubstituted (CH2)n-cycloalkyl, substituted or unsubstituted (CH2)n-phenyl, or substituted or unsubstituted (CH2)n-heterocycle which may be saturated or unsaturated.

[0049] m is 1 except that when E1 is a cyclic ring of more than 5 atoms, then m is 1 or higher, depending upon the size of the ring. For instance if the ring is 6 atoms, m can be 1 or 2.

[0050] R2 is H, -halo, -alkyl, -haloalkyl, —(CH2)n-phenyl, —(CH2)1-3-biphenyl, —(CH2)1-4—Ph—N(SO2—C1-2-alkyl)2, —CO(CHR1)n—OR1, —(CHR1)n-heterocycle, —(CHR1)n—NH—CO—R1, —(CHR1)n-NH—SO2R1, —(CHR1)n—Ph—N(SO2—C1-2-alkyl)2, —(CHR1)n—C(O)(CHR1)—NHR1, —(CHR1)n—C(S)(CHR1)—NHR1, —(CH2)nO(CH2)nCH3, —CF3, —C2-5 acyl, —(CHR1)nOH, —(CHR1)nCO2R1, —(CHR1)n—O-alkyl, —(CHR1)n—O—(CH2)n—O-alkyl, —(CHR1)n—S-alkyl, —(CHR1)n—S(O)-alkyl, —(CHR1)n—S(O2)-alkyl, —(CHR1)n—S(O2)—NHR3, —(CHR3)n—N3, —(CHR3)nNHR4, 2 to 8 carbon atom alkene chain having 1 to 5 double bonds, 2 to 8 carbon atom alkyne chain having 1 to 5 triple bonds, substituted or unsubstituted-(CHR3)n heterocycle, or substituted or unsubstituted-(CHR3)n cycloalkyl which may be saturated or unsaturated.

[0051] When n is more than 1, the substitutions R1 and R3 may be same or different.

[0052] R3 is H, —OH, —CN, substituted alkyl, —C2-8 alkenyl, substituted or unsubstituted cycloalkyl, —N(R1)R2, or 5-6 membered saturated substituted or unsubstituted hetero ring.

[0053] —NR2R3 may form a ring system having 4 to 7 atoms or may be bicyclic ring. The ring system may be of carbon or hetero atoms and further it may saturated or unsaturated and also may be substituted or unsubstituted.

[0054] W is a direct bond, —CHR2—, —CH═CR2—, —CR2═CH—, —CR2═CR2—, —C≡C—, —O—CHR2—, —CHR2—O—, —N(R2)—C(O)—, —C(O)—N(R2)—, —N(R2)—CH—(R3)—, —CH2—N(R2)—, —CH(R1)—N(R2)—, —S—CHR2—, —CHR2—S—, —S(O2)—N(R2)—, —C(O)N(R2)—(CHR2)n-, —C(R1R2)n-NR2—, —N(R2)—S(O2)—, —R2C(O)NR2—, —R2NC(O)NR2—, —CONR2CO—, —C(═NR2)NR2—, —NR2C(═NR2)NR2, —NR2O—, —N═NCHR2—, or —C(O)NR2SO2—.

[0055] E is 5 to 7 membered saturated or unsaturated carbon ring, 5 to 7 membered saturated or unsaturated hetero ring, bicyclic ring system, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, alkylaryl, aralkyl, aralkenyl, aralkynyl, alkoxy, alkylthio, or alkylamino.

[0056] each X individually is a direct bond, substituted or unsubstituted C1-4 methylene chain; O, S, NR2, S(O), S(O2), or N(O) containing one or two C1-4 substituted or unsubstituted methylene chains. X at different places may be same or different.

[0057] B is H, -halo, —CN, —NH2, —(CH2)n—C(═NR4)NHR5, —(CH2)n—NHR4, —(CH2)nNHC(═NR4)NR5, —(CH2)n—OR4, C1-8 substituted or unsubstituted alkyl, substituted or unsubstituted ring system having 4 to 7 carbon or hetero atoms which may be saturated or unsaturated.

[0058] B1 is selected from B; B1 and B may be same or different.

[0059] There may be more than one similar or different R2 groups present on E2, when E2 is a cyclic system of more than 5 atoms. p is 1 or higher if E2 is a cyclic ring of more than 5 atoms. For example, if the ring is 6 atoms, p can be 1 or 2.

[0060] n is 0-4

[0061] A is selected from R1.

[0062] o is 1 except that when L is a cyclic ring of more than 5 atoms, o is 1 or higher depending upon the size of the ring. For instance, if the ring is 6 atoms, o can be 1 or 2.

[0063] Each V and V1 individually is selected from R1 and N-alkyl substituted carboxamidyl (—CONHR) where the alkyl group may be straight, branched, cyclic, or bicyclic; N,N-disubstituted carboxamidyl (—CONR1R2 where R1 and R2 may be substituted or unsubstituted alkyl or aryl and may be the same or different); mono- or disubstituted sulfonamides (SO2NHR or —SO2NR1R2); and methylene- or polymethylene chain-extended variants thereof.

[0064] Each R4 and R5 individually is H, —(CH2)nOH, —C(O)OR6, —C(O)SR6, —(CH2), C(O)NR7R8, —O—C(O)—O—R7, an amino acid or a dipeptide, Each R6 is H, R7, —C(R7)(R8)—(CH2)n—O—C(O)—R9, —(CH2)n—C(R7)(R8)—O—C(O)R9, —(CH2)n—C(R7)(R8)—O—C(O)—O—R9, or —C(R7)(R8)—(CH2)n—O—C(O)—O—R9,

[0065] Each R7, R8 and R9 individually is H, alkyl, substituted alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, heterocycle, substituted heterocycle, alkylaryl, substituted alkylaryl, cycloalkyl, substituted cycloalkyl, or CH2CO2alkyl.

[0066] R substituent groups employed pursuant to the present invention contribute to significantly enhanced activity of the compounds of the present invention.

[0067] Listed below are definitions of various terms used to describe this invention. These definitions apply to the terms as they are used throughout this specification, unless otherwise limited in specific instances, either individually or as part of a larger group.

[0068] The term “alkyl” refers to straight or branched chain unsubstituted hydrocarbon groups of 1 to 20 carbon atoms, preferably 1 to 8 carbon atoms. The expression “lower alkyl” refers to unsubstituted alkyl groups of 1 to 4 carbon atoms.

[0069] The terms “alkenyl” and “alkynyl” refer to straight or branched chain unsubstituted hydrocarbon groups typically having 2 to 8 carbon atoms.

[0070] The terms “substituted alkyl”, “substituted alkenyl” or substituted alkynyl” refer to an alkyl, alkenyl or alkynyl group substituted by, for example, one to four substituents, such as halo, trifluoromethyl, trifluoromethoxy, hydroxy, alkoxy, cycloalkyloxy, heterocyclooxy, oxo, alkanoyl, aryloxy, alkanoyloxy, amino, alkylamino, arylamino, aralkylamino, cycloalkylamino, heterocycloamino, disubstituted amines in which the 2 amino substituents are selected from alkyl, aryl or aralkyl, alkanoylamine, aroylamino, aralkanoylamino, substituted alkanolamino, substituted arylamino, substituted aralkanoylamino, thiol, alkylthio, arylthio, aralkylthio, cycloalkylthio, heterocyclothio, alkylthiono, arylthiono, aralkylthiono, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, sulfonamido (e.g. SO2NH2), substituted sulfonamido, nitro, cyano, carboxy, carbamyl (e.g. CONH2), substituted carbamyl (e.g. CONH alkyl, CONH aryl, CONH aralkyl or cases where there are two substituents on the nitrogen selected from alkyl, aryl or aralkyl), alkoxycarbonyl, aryl, substituted aryl, guanidino and heterocyclos, such as indolyl, imidazolyl, furyl, thienyl, thiazolyl, pyrrolidyl, pyridyl, pyrimidyl and the like. Where noted above where the substituent is further substituted it will be with halogen, alkyl, alkoxy, aryl or aralkyl.

[0071] The term “halogen” or “halo” refers to fluorine, chlorine, bromine and iodine.

[0072] The term “aryl” refers to monocyclic or bicyclic aromatic hydrocarbon groups having 6 to 12 carbon atoms in the ring portion, such as phenyl, naphthyl, biphenyl and diphenyl groups, each of which may be substituted.

[0073] The term “aralkyl” or “alkylaryl” refers to an aryl group bonded directly through an alkyl group, such as benzyl or phenethyl.

[0074] The term “substituted aryl” or “substituted alkylaryl” refers to an aryl group or alkylaryl group substituted by, for example, one to four substituents such as alkyl; substituted alkyl, halo, trifluoromethoxy, trifluoromethyl, hydroxy, alkoxy, azido, cycloalkyloxy, heterocyclooxy, alkanoyl, alkanoyloxy, amino, alkylamino, aralkylamino, hydroxyalkyl, aminoalkyl, azidoalkyl, alkenyl, alkynyl, allenyl, cycloalkylamino, heterocycloamino, dialkylamino, alkanoylamino, thiol, alkylthio, cycloalkylthio, heterocyclothio, ureido, nitro, cyano, carboxy, carboxyalkyl, carbamyl, alkoxycarbonyl, alkylthiono, arylthiono, alkysulfonyl, sulfonamido, aryloxy and the like. The substituent may be further substituted by halo, hydroxy, alkyl, alkoxy, aryl, substituted aryl, substituted alkyl or aralkyl. “Substituted benzyl” refers to a benzyl group substituted by, for example, any of the groups listed above for substituted aryl.

[0075] The term “cycloalkyl” refers to optionally substituted, saturated cyclic hydrocarbon ring systems, preferably containing 1 to 3 rings and 3 to 7 carbons per ring which may be further fused with an unsaturated C3-C7 carbocyclic ring. Exemplary groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl, cyclododecyl and adamantyl. Exemplary substituents include one or more alkyl groups as described above, or one or more groups described above as alkyl substituents.

[0076] The term “cycloalkenyl” refers to optionally substituted, unsaturated cyclic hydrocarbon ring systems, preferably containing 1 to 3 rings and 3-7 carbons per ring. Exemplary groups include cyclopentenyl and cyclohexenyl.

[0077] The terms “heterocycle”, “heterocyclic” and “heterocyclo” refer to an optionally substituted, fully saturated or unsaturated, aromatic or nonaromatic cyclic group, for example, which is 4 to 7 membered monocyclic, 7 to 11 membered bicyclic, or 10 to 15 membered tricyclic ring system, which has at least one heteroatom in at least one carbon atom-containing ring. Each ring of the heterocyclic group containing a heteroatom may have 1, 2 or 3 heteroatoms selected from nitrogen atoms, oxygen atoms and sulfur atoms, where the nitrogen and sulfur heteroatoms may also optionally be oxidized and the nitrogen heteroatoms may also optionally be quaternized. The heterocyclic group may be attached at any heteroatom or carbon atoms.

[0078] Exemplary monocyclic heterocyclic groups include pyrrolidinyl, pyrrolyl, indolyl, pyrazolyl, oxetanyl, pyrazolinyl, imidazolyl, imidazolinyl, imidazolidinyl, oxazolyl, oxazolidinyl, isoxazolinyl, isoxazolyl, thiazolyl, thiadiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, furyl, tetrahydrofuiryl, thienyl, thiophenyl, oxadiazolyl, piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxazepinyl, azepinyl, 4-piperidonyl, pyridyl, dihydropyridyl, N-oxo-pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrothiopyranyl sulfone, morpholinyl, thiomorpholinyl, thiomorpholinyl sulfoxide, thiomorpholinyl sulfone, 1,3-dixolane and tetrahydro-1,1-dioxothienyl, dioxanyl, isothiazolidinyl, thietanyl, thiiranyl, triazinyl and triazolyl and the like.

[0079] Exemplary bicyclic heterocyclic groups include benzothiazolyl, benzoxazolyl, benzothienyl, quinuclidinyl, quinolinyl, quinolinyl-N-oxide, tetrahydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzopyranyl, indolizinyl, benzofuryl, chromonyl, cournarinyl, cinnolinyl, quinoxalinyl, indazolyl, pyrrolapridyl, furopyridinyl (such as furo[2,3-c]pyridinyl, furo[3,1-b]pyridinyl, or furo[2,3-b]pyridinyl), dihydroisoindolyl, diyhydroquinazolinyl (such as 3,4-dihydro-4-oxo-quinazolinyl), benzisothiazolyl, benzisoxazolyl, benzodiazinyl, benzofurazanyl, benzothiopyranyl, benzothiazolyl, benzpyrasolyl, dihydrobenzofuryl, dihydrobenzothienyl, dihydrobenzothiopyranyl, dihydrobenzothiopyranyl sulfone, dihydrobenzopyranyl, indolinyl, isochromanyl, isoindolinyl, naphthyridinyl, phthalazinyl, piperonyl, purinyl, pyridopyridyl, quinazolinyl, tetrahydroquinolinyl, theinofuryl, thienopyridyl, thienothienyl, and the like.

[0080] Exemplary substituents include one or more alkyl groups as described above or one or more groups described above as alkyl substituents.

[0081] Within the above-described definitions, certain embodiments are preferred. Preferred alkyl groups are lower alkyl groups containing 1 to about 8 carbon, and more preferably 1 to about 5 carbon atoms, and can be straight, branched-chain or cyclic saturated aliphatic hydrocarbon groups.

[0082] Examples of suitable alkyl groups include methyl, ethyl and propyl. Examples of branched alkyl groups include isopropyl and t-butyl. An example of a suitable alkylaryl group is phenethyl. Examples of suitable cycloalkyl groups typically contain 3-8 carbon atoms and include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The aromatic or aryl groups are preferably phenyl or alkyl substituted aromatic groups (aralkyl) such as phenyl C1-3 alkyl such as benzyl.

[0083] The N-heterocyclic rings preferably contain 3-7 atoms in the ring and a heteroatom such as N, S or O in the ring. Examples of suitable preferred heterocyclic groups are pyrrolidino, azetidino, piperidino, 3,4-didehydropiperidino, 2-methylpiperidino and 2-ethylpiperidino. In addition, the above substitutions can include halo such as F, Cl, Br, lower alkyl, lower alkoxy and halo substituted lower alkoxy.

[0084] Examples of some preferred B groups include —NHC(═NH)NH2, —C(═NH)NH2, NH2, various N-substituted variants, and assorted prodrug derivatives.

[0085] Prodrug forms of the compounds bearing various nitrogen functions (amino, hydroxyamino, hydrazino, guanidino, amidino, amide, etc.) may include the following types of derivatives where each R group individually may be hydrogen, substituted or unsubstituted alkyl, aryl, alkenyl, alkynyl, heterocycle, alkylaryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, or cycloalkenyl groups as defined beginning on page 7.

[0086] (a) Carboxamides, —NHC(O)R

[0087] (b) Carbamates, —NHC(O)OR

[0088] (c) (Acyloxy)alkyl carbamates, —NHC(O)OROC(O)R

[0089] (d) Enamines, —NHCR(═CHCRO2R) or —NHCR(═CHCRONR2)

[0090] (e) Schiff bases, —N═CR2

[0091] (f) Mannich bases (from carboximide compounds), RCONHCH2NR2

[0092] Preparations of such prodrug derivatives are discussed in various literature sources (examples are: Alexander et al., J. Med. Chem. 1988, 31, 318; Aligas-Martin et al., PCT WO pp/41531, p. 30). The nitrogen function converted in preparing these derivatives is one (or more) of the nitrogen atoms of a compound of the invention.

[0093] Prodrug forms of carboxyl-bearing compounds of the invention include esters (—CO2R) where the R group corresponds to any alcohol whose release in the body through enzymatic or hydrolytic processes would be at pharmaceutically acceptable levels. Another prodrug derived from a carboxylic acid form of the invention may be a quaternary salt type 3

[0094] of structure described by Boder et al., J. Med. Chem. 1980, 23, 469.

[0095] Examples of some preferred groups for W are —CH2CH2—, —CH═CH—, —C≡C—, —CH2CH2CH2—, —CH2CH═CH—, —CH2C≡C—, —CONH, —CH2CONH—, —NHCONH—, —CONHCO—, —CONHCH2—, —C(═NH)NH—, —CH2C(═NH)NH—, —NHC(═NH)NH—, —NHNH—, —NHO—, —CONHSO2—, —SO2NH—, —NHSO2CH2—, —SO2NHCH2—, —CH2O—, —CH2OCH2—, —OCH2CH2—, —CH2NH—, —CH2CH2NH—, —CH2NHCH2—, —CH2S—, —SCH2CH2, —CH2SCH2—, —CH2SO2CH2—, —CH2SOCH2—, —CH(CO2H)O and —CH(CO2H)OCH2.

[0096] Examples of some preferred groups for V and V1 are N-alkyl substituted carboxamidyl (—CONHR) where the alkyl group may be straight, branched, cyclic, or bicyclic, and typically containing up to ten carbons; N,N-disubstituted carboxamidyl (—CONR1R2 where R1 and R2 may be substituted or unsubstituted alkyl or aryl and may be the same or different); mono- or disubstituted sulfonamides (SO2NHR or —SO2NR1R2); methylene—or polymethylene chain—extended variants thereof such as —(CH2)nCONHR1, —(CH2)nCONR1R2, —(CH2)nSO2NHR1, —(CH2)nSO2NR1R2 (where n=1-4), —NHC(O)R, N(R1)C(O)R2, NHSO2R, CH2NHR, CH2NR1R2.

[0097] Pharmaceutically acceptable salts of the compounds of the present invention include those derived from pharmaceutically acceptable, inorganic and organic acids and bases. Examples of suitable acids include hydrochloric, hydrobromic, sulphuric, nitric, perchloric, fumaric, maleic, phosphoric, glycollic, lactic, salicyclic, succinic, toluene-p-sulphonic, tartaric, acetic, citric, methanesulphonic, formic, benzoic, malonic, naphthalene-2-sulphonic, trifluoroacetic and benzenesulphonic acids.

[0098] Salts derived from appropriate bases include alkali such as sodium and ammonia.

[0099] It is of course understood that the compounds of the present invention relate to all optical isomers and stereo-isomers at the various possible atoms of the molecule.

[0100] The synthetic routes leading to the compounds in formula (I) are described in the following schemes. 45678910

[0101] Conversion of 1$24\mathrm{ab}\stackrel{K,I-1}{\to }25\mathrm{ab}$$24\mathrm{ac}\stackrel{K,I-1}{\to }25\mathrm{ac}$$24\mathrm{ac}\stackrel{K,I-1}{\to }25\mathrm{ac}$$24\mathrm{ad}\stackrel{K,I-1}{\to }25\mathrm{af}$

[0102] The reduction of the formyl group of 24ab, 24ac, 24ae, and 24ad was accomplished with NaBH4 to give corresponding alcohols 24ab-i, 24ac-i, 24ae-i, and 24ad-i, respectively. Later, the MEM group was removed under acidic conditions to give 25ab, 25ac, 25ae, and 25af, respectively.

[0103] Conversion of 2$24\mathrm{ad}\stackrel{E,H,I-1}{\to }25\mathrm{ad}$

[0104] The aldehyde 24ad was oxidized to acid 24ad-i which was protected as benzyl ester to give 24ad-ii. MEM deprotection under acidic conditions produced 25ad.

[0105] Conversion of 3$24\mathrm{ah}\stackrel{L,I-1}{\to }25\mathrm{ah}$

[0106] The vinyl compound 24ah was oxidized with OsO4 to give diol 24ah-i, followed by acidic hydrolysis of the MEM group to produce 25ah.

[0107] Conversion of 4$24\mathrm{ah}\stackrel{L,M,K,N,O,I-1}{\to }25\mathrm{ai}$

[0108] The vinyl compound 24ah on dihydroxylation with OsO4 gave diol 24ah-i. Oxidative cleavage of the diol with NaIO4 produced aldehyde 24ah-ii. The aldehyde on reduction gave alcohol 24ah-iii, which on further reaction with methane sulfonyl chloride yielded mesylate 24ah-iv. The mesylate on further reaction with sodium azide gave the corresponding azide 24ah-v, which on acidic hydrolysis produced 25ai.

[0109] Conversion of 5$24w\stackrel{I-1,Q}{\to }25w$1112

[0110] Conversion of 6$29g\stackrel{K,N,O,I-1}{\to }30g$

[0111] Aldehyde 29g was converted to alcohol 29g-i by reduction with NaBH4, followed by the reaction of methanesulfonyl chloride to give mesylate 29g-ii. The mesyl group was displaced with azide to give 29g-iii and finally, the MEM group was removed under acidic conditions to give 30g.

[0112] Conversion of 7$29h\stackrel{K,I-1}{\to }30h$$29i\stackrel{K,I-1}{\to }30i$

[0113] The reduction of the formyl group of 29h and 29i was accomplished with NaBH4 to give corresponding alcohols 29h-i and 29i-i, respectively. Later, the MEM group was removed under acidic conditions to give 30h and 30i, respectively.

[0114] Compounds of the type 23 and 28, where X═—Sn(Bu)3, are prepared using the methods AG-1 or AG-2 1314151617181920212223242526272829303132333435363738394041424344454647484950515253545556

[0115] It was prepared the same way as 229 using propylamine in method A-3 575859606162

[0116] It was prepared the same way as 257 starting from 253 and 63646566

General Methods of Preparation

[0117] The following abbreviations have been used:

[0118] THF: Tetrahydrofuran; DMF: Dimethylformamide

[0119] DME: 1,2-Dimethoxyethane; DMAP: 4-(Dimethylamino)pyridine

[0120] Boc anhydride: Di-tert-butyl dicarbonate; TIPS: Triisopropylsilyl

[0121] MEM: Methoxyethoxymethyl; Bn: Phenylmethyl or Benzyl

[0122] The organic extracts were dried over sodium sulfate or magnesium sulfate.

[0123] The general methods for the preparation of the compounds of formula (I) are given below:

[0124] A-1: Conversion of Acid to Amide

[0125] To derivative (1 mmol), was added thionyl chloride (12.6 mmol) and a few drops of DMF. The reaction mixture was refluxed for 2 h and concentrated in vacuo to obtain an oily residue. The residue was dissolved in dichloromethane (3 mL); cooled with ice water and amine (5 mmol) was added. The reaction mixture was stirred at room temperature overnight, washed with 1N HCl, saturated sodium hydrogen carbonate, water, brine, dried and concentrated in vacuo. The product obtained was purified by crystallization or flash column chromatography to furnish the desired amide.

[0126] A-2: Conversion of Acid to Amide

[0127] To a solution of acid derivative (1 mmol) in dichloromethane (10 mL) at 0° C. was added triethylamine (3 mmol) and ethyl chloroformate (3 mmol). The reaction mixture was stirred at the same temperature for 30 min and the corresponding amine (6 mmol) was added. The reaction mixture was stirred at room temperature overnight and quenched with 1N HCl. The organic layer was separated washed with water, brine, dried and concentrated in vacuo. The product obtained was purified by crystallization or flash column chromatography to furnish the desired amide.

[0128] A-3: Conversion of Acid to Amide

[0129] To a solution of acid (1 mmol) in dichloromethane (5 mL) was added 2M oxalyl chloride in dichloromethane (2.5 mmol), followed by a drop of DMF. The reaction mixture was stirred for 2h at room temperature and concentrated in vacuo. The residue was co-evaporated once with dichloromethane (5 mL) and then dried in vacuo. To the residue in dichloromethane (10 mL) were further added triethylamine (3 mmol) and the corresponding amine (1.2 mmol). The reaction mixture was stirred for 16 h and washed with water, brine, dried and concentrated in vacuo. The product obtained was purified by crystallization or flash column chromatography to furnish the desired amide.

[0130] A-4: Conversion of Acid to Amide

[0131] To a solution of acid (1 mmol) in dichloromethane or THF (10 mL) cooled with an ice bath was added triethylamine (1.2 mmol) and ethyl chloroformate or isobutyl chloroformate (1.2 mmol). The reaction mixture was stirred at 0° C. for 30 min and the corresponding amine (2.5 mmol) was added. The reaction mixture was stirred at room temperature overnight and quenched with 1N HCl. The organic layer was separated,washed with water, brine, dried and concentrated in vacuo. The product obtained was purified by crystallization or flash column chromatography to furnish the desired amide.

[0132] A-5: Conversion of Acid to Amide

[0133] A mixture of carboxylic acid (1 mmol), amine (1.1 mmol), 1-hydroxybenzotriazole (1 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide methiodide (1.1 mmol) in pyridine (10 mL) was stirred overnight at room temperature and was concentrated in vacuo to dryness. The residue obtained was purified by column chromatography or used as such for the next step.

[0134] A-6: Reduction of Acid to Alcohol

[0135] To a solution of acid (1 mmol) in dichloromethane or THF (10 mL) at 0° C. was added triethylamine (1.2 mmol) and ethyl chloroformate or isobutyl chloroformate (1.2 mmol). The reaction mixture was stirred at 0° C. for 30 min and sodium borohydride (1.25 mmol) was added. The reaction mixture was stirred at room temperature overnight and quenched with 1N HCl. The reaction mixture was extracted with ethyl acetate. The organic layers were combined, washed with water, brine, dried and concentrated in vacuo to furnish the desired alcohol. This can be purified further, if needed, by crystallization or column chromatography.

[0136] A-7: Conversion of Acid to Amide

[0137] A mixture of carboxylic acid (1 mmol), amine (1 mmol), and 4-dimethylaminopyridie (0.12 mmol) in xylene (10 mL) was stirred at 80° C. for 10 min. Phosphorus trichloride (1 mmol) was added and the reaction mixture was heated with stirring at 150° C. for 2 hr. After cooling, the product was extracted with EtOAc. The organic layers were combined, washed with water, brine, dried and concentrated in vacuo. The product obtained was purified by flash column chromatography to furnish the desired amide.

[0138] B-1: Conversion of Phenolic Hydroxyl to Triflate

[0139] To a phenol (1 mmol) in dichloromethane (2.5 mL) was added pyridine (5 mmol) under a nitrogen atmosphere and cooled to −10 C. To the cold reaction mixture was added dropwise triflic anhydride (2 mmol) in dichloromethane (2.5 mL) over a period of 10 mins and allowed to warm to room temperature and stirred for 16 h. The reaction mixture was quenched with saturated aqueous sodium hydrogen carbonate solution and the organic layer was separated. The organic layer was washed with 1N HCl, saturated sodium hydrogen carbonate, water, brine, dried and concentrated in vacuo. The product obtained was purified by crystallization or flash column chromatography to furnish the desired triflate.

[0140] B-2: Conversion of Phenolic Hydroxyl to Triflate

[0141] To a solution of substituted phenol (1 mmol) in DMF (10 mL) was added N-phenylbis(trifluoromethanesulphonimide) (1.1 mmol), and triethylamine (2 mmol) and stirred at room temperature overnight. The reaction mixture was quenched with ice water and extracted twice with ether. The organic layers were combined, washed with brine, dried and concentrated in vacuo to furnish the desired triflate.

[0142] C: Conversion of Acid to MEM Ester

[0143] To a solution of acid derivative (1 mmol) in DMF (10 mL) was added sodium bicarbonate (1.05 mmol), and MEM-Cl (1.05 mmol) and was stirred at room temperature for 24 h. The reaction mixture was quenched with ice water and extracted twice with ether. The organic layers were combined, washed with brine, dried and concentrated in vacuo to furnish crude product. Purification by flash column chromatography or crystallization gave the desired MEM ester.

[0144] D-1: Coupling of Boronic Acid with Triflate

[0145] A mixture of triflate (1 mmol), aryl boronic acid (1.5 mmol), potassium phosphate (3 mmol), potassium bromide (2.4 mmol) and tetrakis(triphenylphosphine)palladium (0.05 mmol) in dioxane (10 mL) was heated at reflux overnight under an argon atmosphere. The reaction mixture was cooled, quenched with water and was extracted with ethyl acetate. The organic layers were combined, dried and concentrated in vacuo. Purification by flash column chromatography or crystallization gave the coupled product.

[0146] D-2: Coupling of Boronic Acid with Triflate

[0147] A mixture of triflate (1 mmol), aryl boronic acid (2 mmol), sodium hydrogen carbonate (3 mmol) and tetrakis(triphenylphosphine)palladium (0.05 mmol) or bis(triphenylphosphine)palladium(II)chloride (0.05 mmol) in DME/water (9:1, 10 mL) was heated at reflux overnight. The reaction mixture was cooled, quenched with water and extracted with ethyl acetate. The organic layer was dried and concentrated in vacuo. Purification by flash column chromatography or crystallization gave the coupled product.

[0148] D-3: Coupling of Tributyltin Derivative with Triflate

[0149] A mixture of triflate (1 mmol), tributyltin derivative (3 mmol), tetraethylammonium chloride (6 mmol), and bis(triphenylphosphine)palladium(II)-chloride (0.05 mmol) in DMF (10 mL) was heated at 70° C. overnight under an argon atmosphere. The reaction mixture was cooled, quenched with water (20 mL) and extracted with ethyl acetate (2×10 mL). The organic layers were combined, dried and concentrated in vacuo. Purification by flash column chromatography or crystallization gave the coupled product.

[0150] D-4: Coupling of Trimethyltin Derivative with Triflate

[0151] A mixture of triflate (1 mmol), trimethyltin derivative (3 mmol), and bis(triphenylphosphine)palladium(II)chloride (0.05 mmol) in THF (10 mL) was heated at 70° C. overnight under an argon atmosphere. The reaction mixture was cooled, quenched with water and extracted with ethyl acetate (2×10 mL). The organic layers were combined, dried and concentrated in vacuo. Purification by flash column chromatography or crystallization gave the coupled product.

[0152] D-5: Coupling of Alkyne with Triflate

[0153] A mixture of triflate (1 mmol), triethylamine (4.5 mmol), substituted alkyne (3.5 mmol), and bis(triphenylphosphine)palladium(II)chloride (0.05 mmol) in DMF (10 mL) was heated at 70° C. overnight under an argon atmosphere. The reaction mixture was cooled, quenched with water (20 mL) and extracted with ethyl acetate (2×10 mL). The organic layers were combined, dried and concentrated in vacuo. Purification by flash column chromatography or crystallization gave the coupled product.

[0154] D-6: Coupling of Boronate Ester with Aryl Bromides

[0155] A mixture of boronate ester (2 mmol), aryl bromide (1 mmol), potassium phosphate (3 mmol) and bis(diphenylphosphinoferrocene)palladium(II)chloride (0.05 mmol) in DMF (10 mL) was heated at 100° C. for overnight under an argon atmosphere. The reaction mixture was cooled, quenched with water (20 mL) and extracted with ethyl acetate (2×10 mL). The organic layers were combined, dried and concentrated in vacuo. Purification by flash column chromatography or crystallization gave the desired product.

[0156] D-7: Coupling of Boronate Ester with Aryl Bromides

[0157] A mixture of boronate ester (2 mmol), aryl bromide (1 mmol), sodium hydrogen carbonate (3 mmol) and bis(diphenylphosphinoferrocene)palladium(II)chloride (0.05 mmol) in DME/water (9:1, 10 mL) was heated at 50-70° C. for overnight under an argon atmosphere. The reaction mixture was cooled, quenched with water (20 mL) and was extracted with ethyl acetate (2×10 mL). The organic layers were combined, dried and concentrated in vacuo. Purification by flash column chromatography or crystallization gave the coupled product.

[0158] D-8: Coupling of Phenol with Boronic Acid

[0159] A mixture of phenol (1 mmol), aryl boronic acid (3 mmol), molecular sieves (4A°), pyridine (5 mmol), copper(II)acetate (1 mmol) and bis(triphenylphosphine)-palladium(II)chloride (0.05 mmol) in dichloromethane (10 mL) was stirred at room temperature overnight under an argon atmosphere. The reaction mixture was cooled, filtered through a pad of Celite and concentrated in vacuo. Purification of the crude by flash column chromatography gave the coupled aryl ether.

[0160] D-9: Coupling of Trimethyltin Derivative with Triflate

[0161] To a solution of triflate (1 mmol), LiCl (4 mmol), PPh3 (0.15 mmol), CuBr (0.2 mmol), and bis(triphenylphosphine)palladium(II)chloride (0.07 g) in DMF (10 mL) under an atmosphere of argon was added trimethylstannyl compound (0.8 mmol) and a crystal of 2,6-di-t-butyl-4-methylphenol. After the mixture was stirred at 90° C. for 3 h, a second portion of aryl-trimethylstannyl compound (0.5 mmol) was added. The reaction mixture was stirred at 90° C. overnight. Water was added and extracted with ethyl acetate. The organic layer was dried (MgSO4), concentrated and purified by flash column chromatography or crystallization to furnish the desired coupled product.

[0162] D-10: Coupling of Amine with Triflate

[0163] A mixture of triflate (0.75 mmol), amine (0.9 mmol), potassium phosphate (1.1 mmol), 2-(di-t-butylphosphino)biphenyl (0.015 mmol) and tris(dibenzylideneacetone) dipalladium(0) (10 mg) in DME (10 mL) was heated at reflux overnight under an argon atmosphere. The reaction mixture was concentrated in vacuo and the residue was purified by flash column chromatography to furnish the desired coupled product.

[0164] D-11: Conversion of Triflate to Cyano Compound

[0165] To a solution of triflate (0.84 mmol), zinc cyanide (0.54 mmol), Palladium acetate (0.016 mmol), 2-(di-tert-butylphosphine)biphenyl (0.016 mmol) and N-methyl pyrrolidine (10 mL) was heated under argon at 160° C. for 48 h. The reaction mixture was cooled to room temperature and quenched with water (50 mL). The reaction mixture was extracted with ethyl acetate (2×25 mL). The organic layers were combined, dried, filtered and concentrated in vacuo. The residue obtained was purified by flash column chromatography to furnish the desired cyano compound.

[0166] D-12: Coupling of Tetravinyltin with Triflate or Halide

[0167] To a solution of aryl triflate or bromide (1 mmol) in DMF (5 mL) were added LiCl (5 mmol), tetravinyltin (2 mol), and dichlorbis(triphenylphosphine)palladium (II) (0.01 mmol). The reaction mixture was stirred at 70° C. under nitrogen for 5 h and then diluted with ethyl acetate and filtered. The organic layer was washed with water and brine and dried (MgSO4). After evaporating the solvent in vacuo, the compound was purified by flash-column chromatography to give the desired product.

[0168] E: Oxidation of Aryl Aldehyde to Acid

[0169] A mixture of aldehyde (1 mmol), tert-butanol (5 mL), water (2 mL) and acetonitrile (1 mL, additional amount may be added until the reaction mixture was homogenous) was stirred at room temperature. The solution was cooled in ice-bath and 2-methyl-2-butene (1 mL), sodium chlorite (6 mmol) and sodium dihydrogenphosphate (1.6 mmol) were added. The reaction mixture was stirred at room temperature for 2 h. If the solid separated out, the mixture was filtered to collect the solid, the desired product. If no solid separated out, then the reaction mixture was concentrated in vacuo to remove acetonitrile, diluted with water (10 mL) and extracted with ethyl acetate (2×10 mL). The organic layers were combined, washed with water, brine, dried and concentrated in vacuo to furnish crude acid. Purification was achieved, if needed, by crystallization or using flash column chromatography to obtain pure acid.

[0170] E-2: Oxidation of Vinyl Compound to Acid

[0171] To a solution of vinyl compound (1 mmol) in acetone (5 mL) was added KMnO4 (4 mmol). The reaction mixture was stirred for 3 h (the reaction is exothermic, and refluxed on its own during the addition of KMnO4). The reaction mixture was diluted with methanol and water and filtered. The organic solvents were evaporated in vacuo and the aqueous layer was acidified to pH 1 and extracted several times with ethyl acetate/DME. The combined organic layers were dried (MgSO4) to furnish the desired acid.

[0172] F: Conversion of Aromatic Acid to MEM Ester

[0173] To a solution of aromatic acid (1 mmol) in THF (10 mL) was added diisopropylethylamine (2 mmol) and 2-methoxyethoxymethylchloride (1.1 mmol). The reaction mixture was stirred a room temperature for 3 h and diluted with ether (25 mL). The reaction mixture was washed with water (10 mL), brine (10 mL), dried and concentrated in vacuo to obtain product as colorless oil. The product was purified by flash column chromatography to furnish desired product.

[0174] G: Conversion of Aromatic Benzyl Ether to Aromatic Phenol, Benzyl Ester to Acid, Benzyl Carbamate to Amine, Alkene to Alkane, Azide to Amine, Nitro to Amine, and Oxime to Amine

[0175] To a solution of appropriate substrate (1 mmol) in ethanol (10 mL) was added 10% palladium on carbon (10-wt %). The reaction mixture was hydrogenated at 50 psi for 2 to 24 h (until all starting material disappeared as confirmed by MS and TLC analysis). The catalyst was removed by filtration through a pad of Celite under nitrogen. The filtrate was concentrated in vacuo to furnish the product, which was purified by flash column chromatography or crystallization.

[0176] H: Conversion of Aromatic Acid to Benzyl Ester

[0177] To a solution of aromatic acid (1 mmol) in DMF (10 mL) was added sodium bicarbonate (1.05 mmol), and benzyl bromide (1.05 mmol) and stirred at room temperature for 24 h. The reaction mixture was quenched with ice water and extracted twice with ethyl acetate. The organic layers were combined, washed with water and brine, dried and concentrated in vacuo to furnish crude product. Purification by crystallization or flash column chromatography gave the desired ester.

[0178] I-1: Hydrolysis of MEM Ester to Acid

[0179] To a solution of MEM ester (1 mmol) in DME (8 mL) was added 6 N HCl (2 mL) and stirred at room temperature overnight. The reaction mixture was neutralized with solid sodium hydrogen carbonate (18 mmol) and concentrated in vacuo. The reaction mixture was acidified with 0.5 N HCl (20 mL) and extracted with ethyl acetate (2×20 mL). The organic layers were combined, washed with brine (20 mL), dried and concentrated in vacuo to furnish crude product. Purification of the crude by flash column chromatography gave the product. Alternatively the crude reaction mixture was diluted with water (10 mL) and concentrated in vacuo to remove DME. The solid obtained was collected by filtration and dried in vacuo to furnish pure acid.

[0180] I-2: Hydrolysis of Ester to Acid

[0181] To a solution of ester (1 mmol) in MeOH (10 mL) was added 1 N NaOH (10 mmol). The reaction mixture was stirred at room temperature for 2-3 h, filtered through a plug of cotton, and concentrated in vacuo to remove MeOH. The pH of the aqueous layer was adjusted to below 7. The solid that separated, was collected by filtration, washed with water and dried in vacuo to furnish the desired acid.

[0182] J: Coupling of Acid with Amino Compounds

[0183] To a solution of acid (1 mmol) in DMF (5 mL) was added corresponding amine (1.1 mmol) and stirred at room temperature until homogenous. Pyridine (5 mL) was added to the reaction mixture followed by 1,3-dicyclohexylcarbodiimide (1.2 mmol) and stirred overnight at room temperature. The mixture was quenched with 6 N HCl (10 mL), diluted with ice cold water (10 mL) and extracted with chloroform (2×10 mL). The organic layers were combined washed with brine (10 mL), dried and filtered. Purification of the crude by flash column chromatography gave the product as a solid. If the product was soluble in water, then the reaction mixture was concentrated in vacuo to remove pyridine and DMF and purified by flash column chromatography.

[0184] K: Reduction of Aldehyde to Alcohol

[0185] To a solution of aldehyde (1 mmol) in THF (10 mL) was added sodium borohydride (0.4 mmol). The reaction mixture was stirred for 30 mins and quenched with glacial acetic acid (0.3 mL). The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (2×10 mL). The organic layers were combined and washed with brine (10 mL), dried, filtered and concentrated in vacuo to obtain crude product which was purified by flash column chromatography.

[0186] L: Conversion of Vinyl Group to Diol

[0187] To a solution of vinyl compound (1 mmol) in THF/tert-butanol (1:1, 10 mL) and water (2 mL) was added 4-methylmorpholine N-oxide (2.5 mmol) and osmium tetraoxide (1 mL, 2.5 wt % in tert-butanol, 0.1 mmol). The reaction mixture was stirred at room temperature for 2 h and quenched with saturated aqueous solution of sodium sulfite (5 mL). The reaction was stirred at room temperature for 30 mins and diluted with brine (10 mL) and ethyl acetate (10 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (10 mL). The organic layers were combined and washed with brine (10 mL), dried, filtered and concentrated in vacuo. The crude product was purified by flash column chromatography to furnish the desired diol.

[0188] M: Conversion of Diol to Aldehyde

[0189] To a solution of diol (1 mmol) in DME/water (9:1, 10 mL) was added sodium metaperiodate (3 mmol) and stirred at room temperature for 30 min. The reaction mixture was quenched with water (10 mL) and extracted with ethyl acetate (2×10 mL). The organic layers were combined and washed with brine (10 mL), dried, filtered and concentrated in vacuo. The crude product was purified by flash column chromatography to furnish the desired aldehyde.

[0190] N: Conversion of Alcohol to Mesylate

[0191] To a solution of alcohol (1 mmol) in DME (10 mL) was added dimethylaminopyridine (0.1 mmol), methane sulfonyl chloride (3 mmol) and diisopropylethylamine or triethylamine (5 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with brine, dried, filtered and concentrated in vacuo. The residue obtained, was purified by column chromatography to furnish the desired mesylate.

[0192] O: Conversion of Mesylate to Azide

[0193] To a solution of mesylate (1 mmol) in DMSO (10 mL) was added sodium azide (25 mmol) and heated at 100° C. overnight. The reaction mixture was cooled and diluted with cold water (25 mL). The reaction mixture was extracted with ethyl acetate (2×15 mL). The combined organic layers were washed with water (10 mL), brine (10 mL), dried, filtered and concentrated in vacuo The residue obtained was purified by column chromatography to furnish the desired azido compound.

[0194] P: Protection of Amine as Benzyl Carbamate

[0195] A mixture of amino compound (1 mmol), benzyl chloroformate (2 mmol) and triethylamine (10 mL) in pyridine (10 mL) was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo to remove organic solvents and diluted with 0.1 N HCl (10 mL). The product was extracted with chloroform (2×10 mL), dried, filtered and concentrated in vacuo. The residue obtained was purified by column chromatography to furnish the desired carbamate.

[0196] Q: Conversion of Silyl Protected Amine to Amine

[0197] A mixture of silyl protected amine (1 mmol), tetrabutylammonium fluoride (1.0 M in THF, 2 mmol) in THF (10 mL) was stirred at room temperature for 1.5 h. The reaction mixture was concentrated in vacuo and purified by column chromatography to obtain the desired product.

[0198] R: Protection of Amine as Tert-Butyl Carbamate

[0199] To a solution of amino compound (1 mmol) in acetonitrile (5 mL) was added triethylamine (2 mmol) and BOC anhydride (1.2 mmol). The reaction mixture was stirred for 2 h and concentrated in vacuo. Water was added to the residue and extracted with ethyl acetate. The organic layer was washed with brine, dried (MgSO4), and the solvent was evaporated in vacuo to furnish tert-butyl carbamate. If needed, the product was purified by crystallization or column chromatography.

[0200] S: Conversion of Tert-Butyl Carbamate to Amine

[0201] To a solution of tert-butyl carbamate (1 mmol) in dichloromethane (10 mL) was added trifluoroacetic acid (2 mL). The solution was stirred at room temperature for 4 h and concentrated in vacuo. The residue was purified by column chromatography or crystallization to give the desired amine.

[0202] S-2: Conversion of Tert-Butyl Carbamate to Amine

[0203] To a solution of tert-butyl carbamate (1 mmol) in methanol (13 mL) was added 6 N HCl (8.75 mL, 52 mmol) and water (4.25 mL). The reaction mixture was stirred at room temperature for 2 days. The pH was adjusted to 7 using conc. ammonium hydroxide and the solid that separated out, was collected by filtration, washed with ether, dried in vacuo to furnish the desired product. If no solid separated out, the product was isolated by extraction with chloroform and evaporating the organic layer.

[0204] T: Protection of Aldehyde as Acetal

[0205] To a solution of aldehyde (1 mmol) in ethanol (5 mL) was added triethyl orthoformate (1.4 mmol), ammonium nitrate (0.2 mmol) and stirred at room temperature overnight (if reaction was not complete by TLC and NMR analysis of an aliquot, the reaction mixture was heated at 50° C. until complete). After completion of the reaction, the mixture was quenched with triethylamine (0.2 mmol) and concentrated in vacuo to remove ethanol. The residue was dissolved in ether, filtered to remove any insoluble inorganic impurities, and evaporated to dryness. The product obtained was used as such without further purification.

[0206] U-1: Conversion of Bromide to Boronic Acid

[0207] To a mixture of bromo compound (1 mmol) in ether (10 mL), cooled to −78° C., n-butyl lithium (1.2 mmol) was added dropwise and the reaction mixture was stirred for 30 mins after the addition was completed. Tributyl borate (1.3 mmol) in ether (10 mL) was added to the reaction and stirred at −78° C. for 2 h. The reaction mixture was allowed to warm to 0° C. and quenched with 2 M HCl (10 mL). The reaction mixture was stirred at room temperature for 1 h and cooled with ice. The aqueous layer was separated and the organic layer was extracted twice with 1N NaOH (2×10 mL). The basic extracts were combined and washed with ether (10 mL). The basic layer was acidified to pH 4 using 6 N HCl and the solid that separated out was collected by filtration, washed with water and hexane and dried in vacuo to furnish boronic acid as a solid. If no solid product is obtained then the basic layer was extracted with ether (2×10 mL). The organic layers were combined, dried and concentrated in vacuo to furnish boronic acid.

[0208] U-2: Synthesis of Boronic Acid by Ortho Lithiation of Aryl Aldehyde

[0209] To a solution of N,N,N′-trimethylethylenediamine (1 mmol) in THF/ether (10 mL, 1:1) cooled to −20° C. was added dropwise, over a period of 15 mins, n-butyl lithium (1 mmol) and stirred at −20° C. for 15 mins. Aldehyde (1 mmol) at −20° C. was added dropwise over a period of 10 mins to this mixture. The reaction mixture was further stirred for 15 mins at −20° C. followed by the addition of n-butyl lithium (2.8 mmol) dropwise over a period of 15 mins and stirred at 4° C. overnight. The reaction mixture was cooled to −40° C. and tributyl borate (5.6 mmol) in ether (20 mL) was added to the reaction and stirred at 4° C. for 12 h. The reaction mixture was allowed to warm to 0° C. and quenched with 2 M HCl (3 mmol) and heated at reflux for 2 h and added to ice water (25 mL). The aqueous layer was separated and the organic layer extracted twice with 1N NaOH (2×10 mL). The basic extracts were combined and washed with ether (10 mL). The basic layer was acidified to pH 3 using 6 N HCl and the solid that separated out was collected by filtration, washed with water and hexane and dried in vacuo to furnish boronic acid as a solid. If no solid product was obtained, then the basic layer was extracted with ether (2×10 mL). The organic layers were combined, dried and concentrated in vacuo to furnish boronic acid.

[0210] U-3: Synthesis of Boronic Acid by Ortho Lithiation of Aryl Acetal

[0211] To a solution of aryl acetal compound (1 mmol) in ether (10 mL) at −78° C., tert-butyl lithium (1.1 mmol) was added dropwise and the reaction mixture was stirred for 3 h at −20° C. after the addition was completed. Tributyl borate (1.2 mmol) in ether (10 mL) was added to the reaction and stirred at −20° C. for 1 h. The reaction mixture was allowed to warm to 0° C. and quenched with 2 M HCl (10 mL). The reaction mixture was stirred at room temperature for 1 h. The aqueous layer was separated and the organic layer was extracted twice with 1N NaOH (2×10 mL). The basic extracts were combined and washed with ether (10 mL). The basic layer was acidified to pH 4 using 6 N HCl and the solid that separated out was collected by filtration, washed with water and hexane and dried in vacuo to furnish boronic acid as a solid. If no solid product was obtained then the mixture was extracted with ether (2×10 mL). The organic layers were combined, dried and concentrated in vacuo to furnish boronic acid.

[0212] V-1: Demethylation of Aryl Methyl Ether to Phenol

[0213] In a round bottom flask (50 mL), pyridine hydrochloride (10 g) was heated in an oil bath at 180° C. After the entire solid had melted, the corresponding aryl methyl ether (1 mmol) was added in small portions over a period of 20 min. The reaction mixture was heated at 180° C. for 4 h, cooled and quenched with water (100 mL). The reaction mixture was extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with brine, dried over MgSO4, concentrated to give phenol. This can be further purified if needed by crystallization or column chromatography.

[0214] V-2: Demethylation of Aryl Methyl Ether to Phenol

[0215] To a solution of aryl ether (1 mmol) in dichloromethane (10 mL) cooled to −78° C. was added boron tribromide (3 mmol). The reaction mixture was allowed to warm to room temperature overnight and quenched with water (10 mL). The solid obtained was collected by filtration to give the desired product. More product was obtained after evaporation of the organic layer and washing the residue with water. Alternatively, if a homogenous biphasic mixture was obtained on addition of water, the organic layer was separated, washed with brine, dried over MgSO4, and concentrated to give the desired phenol. This can be further purified if needed by crystallization or column chromatography.

[0216] V-3: Demethylation of Aryl Methyl Ether to Phenol

[0217] To a solution of aryl methyl ether (1 mmol) in dichloromethane (5 mL) was added AlCl3 (8.5 mmol). The reaction mixture was heated to reflux for 12 h under nitrogen. To this mixture was added 12 mL of 1 N HCl slowly and the organic layer was separated. The aqueous layer was re-extracted several times with ethyl acetate/DME. The combined organic layers were washed with brine, dried (MgSO4), and evaporated in vacuo to furnish the desired phenol, which was purified by column chromatography.

[0218] V-4: Demethylation of Aryl Methyl Ether to Phenol

[0219] To a stirred slurry of NaH (2 mmol) in anhydrous toluene (5 mL) under nitrogen atmosphere was added para-thiocresol (2 mmol) dissolved in toluene (40 mL). The mixture was stirred at room temperature for 30 min and hexamethylphosphoric triamide (2 mmol) in toluene (5 mL) was added dropwise over a period of 30 min. A solution of aryl ether (1 mmol) in toluene (5 mL) was added in one portion. The reaction mixture was stirred at reflux for 9.5 h, cooled to room temperature and diluted with ethyl acetate (40 mL). The organic layer was extracted with 1 N aqueous NaOH solution (2×20 mL). The basic layer was acidified to pH 5 and extracted with ethyl acetate (2×20 mL). The organic layers were combined, washed with water, dried (MgSO4) and concentrated in vacuo. The residue obtained was purified by flash column chromatography to afford the desired phenol compound.

[0220] W: Conversion of Acid to Methyl Ester

[0221] A mixture of acid (1 mmol), conc. H2SO4 or conc HCl (0.5 mL) and methanol (10 mL) was heated at reflux for 16 h. The mixture was concentrated to half of its volume and the residue poured into a saturated sodium bicarbonate solution. The precipitate was collected by filtration, washed with water and dried to give the desired ester. If the ester did not come as solid, it was extracted with ethyl acetate. The organic layer was dried, filtered and concentrated to give the desired ester.

[0222] W-2: Conversion of Acid to Ester

[0223] A solution of methanolic HCl or ethanolic HCl was prepared by the addition of acetyl chloride (1 mL) to methanol/ethanol (9 mL) at 0° C. and stirred for 30 mins. To the solution of anhydrous methanolic HCl was added acid (1 mmol) and stirred at room temperature (or reflux if needed) overnight. The reaction mixture was concentrated to dryness in vacuo and the residue was purified by column chromatography or crystallization to furnish the desired ester.

[0224] X: Conversion of Phenol to Alkyl Aryl Ethers or Alkylation of Amines

[0225] To a solution phenol or amine (1 mmol) in DMF (10 mL) was added cesium carbonate (1.25 mmol) and corresponding bromide (1.1 mmol). The reaction mixture was stirred at room temperature overnight and quenched with water (25 mL). The product was extracted with ether (2×25 mL), the organic layers were combined and washed with water (25 mL), brine (25 mL), dried and concentrated in vacuo to furnish crude product. The crude was purified by crystallization or flash column chromatography.

[0226] Y: Conversion of Nitrile to Hydroxycarbamimidoyl

[0227] To a solution of nitrile compound (1 mmol) in ethyl alcohol (10 mL) was added hydroxylamine (50% aqueous solution, 5 mmol). The mixture was stirred at reflux for 2-5 h. The reaction mixture was concentrated in vacuo to furnish the desired hydroxycarbamimidoyl compound.

[0228] Z: Opening of Aromatic Methylene Dioxy Compound with Alcohol

[0229] A solution of potassium tert-butoxide (2.25 mmol) in DMSO (1.25 mL) was heated at 50° C. for 30 min. Methanol (1.25 mL) was added to it and continued heating at 50° C. for 30 min. To the reaction mixture was added 1,2-methylenedioxy aromatic compound (1 mmol) and continued heating at 50° C. for 30 min. The reaction mixture was cooled to room temperature and quenched with water (10 mL) and 1 N sodium hydroxide (16 mL). The reaction m mixture was washed with ether (2×10 mL) and acidified to pH 4 using conc HCl. The solid obtained was collected by filtration to furnish the desired product.

[0230] Z-1: Opening of Aromatic Methylene Dioxy Compound with Alcohol

[0231] To a mixture of methylene dioxy compound (1 mmol) in HMPA (2.5 mL) were added sodium methoxide (2.5 mmol) and heated with stirring at 150° C. for 12 min. The mixture was cooled and poured into ice water (20 mL), NaOH (30 mg) and stirred for 10 min. It was then extracted with ether and the aqueous layer was acidified to pH 4 with HCl and extracted with ether. The later ethereal extracts were combined, dried and concentrated. The residue was purified by crystallization or column chromatography.

[0232] AA: Conversion of Amine to Amide in the Presence of a Phenol

[0233] To a solution of amino compound (1 mmol) in pyridine (5 mL) was added, dropwise, acid chloride (2 mmol) at 0° C. under N2. The mixture was stirred for 45 min and was then poured into ice water and acidified with 1 N HCl. The precipitated solid was collected by filtration, washed with 1N HCl, hexane, and then dried in vacuo to give crude product. The crude product was added to freshly prepared sodium methoxide solution (0.1 M, 10 mL) and stirred for 30 min at room temperature. The reaction mixture was quenched with acetic acid (1 mmol) and concentrated in vacuo. The residue was dissolved in ethyl acetate and washed with water. The water layer was extracted with ethyl acetate, and the combined organic layers were washed with brine, dried (MgSO4) and evaporated to yield a solid. The solid was washed with hexane and dried in vacuo to furnish the desired amide.

[0234] AB-1: Conversion of Amino of Amidine to Amino Carbamate

[0235] To amidine compound (1 mmol) was added 0.1N NaOH (10 mL) and stirred at room temperature for 5 min. The reaction mixture was concentrated in vacuo and to the residue was added alkyl or aryl 4-nitrophenyl carbonate (2 mmol) in 20 mL of hexamethylphosphoramide and stirred at 45° C. for 24 h. The reaction was quenched with water (100 mL) and extracted with ethyl acetate (2×100 mL). The combined extracts were washed with water (100 mL) and brine (100 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue obtained was purified by flash column chromatography to furnish the desired product.

[0236] AB-2: Conversion of Amino of Amidine to Amino Carbamate

[0237] To a solution of amidine compound (1 mmol) in acetonitrile (25 mL) was added triethylamine (5 mL) and aryl/alkyl chloroformate (2 mmol) or dialkyl/aryl carbonate. The reaction mixture was stirred at room temperature for 16 h and quenched with water (100 mL). The reaction mixture was extracted with ethyl acetate (2×100 mL). The combined extracts were washed with brine (100 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue obtained was purified by flash column chromatography to furnish the desired product.

[0238] AC: Conversion of Aldehyde to Oxime

[0239] To a stirred solution of aldehyde (1 mmol) in ethanol (10 mL) was added pyridine (10 mL) and hydroxylamine hydrochloride (1.25 mmol). The reaction mixture was stirred overnight at room temperature under nitrogen and then concentrated in vacuo to one third of its original volume. Water (10 mL) was added and the precipitated solid was collected by filtration and dried in vacuo. The product was used as such for next step without further purification.

[0240] AD: Debenzylation in the Presence of Aldehyde

[0241] To a solution of phenyl methoxyaryl aldehyde (1 mmol) in dichloromethane (10 mL) cooled to −78° C. was added dropwise under a nitrogen atmosphere boron tribromide (1M solution in dichloromethane, 1.2 mmol). The reaction mixture was allowed to warm to room temperature and stirred at room temperature overnight. The reaction mixture was quenched with water (10 mL) and the layers were separated. The aqueous layer was extracted with chloroform (10 mL). The organic layers were combined, washed with brine (10 mL), dried, filtered and concentrated in vacuo to furnish crude product. Purification of the crude by flash column chromatography furnished the desired phenolic aldehyde

[0242] AE-1: Reductive Amination of Aldehyde

[0243] To a stirred solution of aldehyde (1 mmol) in methanol (40 mL) was added amine (3.3 mmol) followed by the addition of glacial acetic acid (0.3 mL). The reaction mixture was stirred for 30 min under nitrogen at room temperature, and then sodium cyanoborohydride (1.5 mmol) was added. After stirring for 20 min, the solvent was evaporated in vacuo, and the residue was taken in ethyl acetate. The organic layer was washed with water, and the insoluble material was removed from the organic layer by filtration. The pH of the aqueous phase was adjusted to 7 with 1N NaOH and was extracted twice with ethyl acetate. The combined organic layers were washed with brine and dried (MgSO4). The solvent was evaporated in vacuo to furnish crude product. The crude product was purified by crystallization or flash column chromatography.

[0244] AE-2: Reductive Amination of Aldehyde

[0245] To a mixture of aminoarylamidine (1.2 mmol), 4A° molecular sieves, and sodium hydroxide (1 N solution in anhydrous methanol, 1.2 mL, 1.2 mmol) in methanol (10 mL) was added a solution of aldehyde (1 mmol) in THF (10 mL). The reaction mixture was heated for 15 mins at reflux temperature and was cooled to room temperature. Acetic acid (1%) and sodium cyanoborohydride (1 M solution in THF, 5 mmol) was added to the reaction mixture and stirred at room temperature overnight. The reaction mixture was quenched with 1 N NaOH (30 mmol) and stirred for additional 2 h and concentrated in vacuo to remove methanol. The mixture was diluted with water (15 mL) and washed with ether (2×10 mL). The aqueous layer was acidified to pH 2 using 6 N HCl and the solid that separated out was collected by filtration, washed with ether, dried in vacuo to furnish product, which was purified by flash column chromatography, if needed.

[0246] AE-3: Reductive Amination of Aldehyde

[0247] A mixture of aminoarylamidine (2 mmol), 4A° molecular sieves, pyridine (6 mL) in methanol (9 mL) was heated at 50° C. for one hour. A solution of aldehyde (1 mmol) in methanol (7.5 mL) containing acetic acid (1%) was added and continued heating for 4 h to 12 h. The reaction mixture was cooled and sodium cyanoborohydride (1 M solution in THF, 5 mmol) was added to the reaction mixture and stirred at room temperature overnight. The reaction mixture was quenched with 5 N NaOH (30 mmol) and stirred for additional 2 h. The reaction mixture was filtered through Celite (to remove molecular sieves) and concentrated to remove methanol. The mixture was diluted with water (15 mL) and washed with ether (2×10 mL). The aqueous layer was filtered and solid obtained was kept aside (mainly product). The aqueous layer was acidified to pH 2 using 6 N HCl and the solid that separated out was collected by filtration. The combined solid materials were purified, if needed, by flash column chromatography.

[0248] AE-4: Reductive Amination of Aldehyde

[0249] To a mixture of aldehyde (1 mmol) and aminoarylamidine (1.1 mmol) in MeOH at room temperature was added triethyl amine (2.75 mmol), sodium cyanoborohydride (0.83 mmol) and zinc chloride (0.9 mmol). The reaction mixture was stirred at room temperature overnight and concentrated to remove methanol. The reaction mixture was quenched with 1 N NaOH (10 mL), diluted with water (10 mL), and extracted with EtOAc (5×20 mL). The combined organic extracts were washed with brine (15 mL), dried (MgSO4), filtered through Celite and concentrated to give the product. Purification of the crude by flash column chromatography gave the desired product.

[0250] AE-5: Reductive Amination of Aldehyde

[0251] To a solution of amine (1.2 mmol) in MeOH (10 mL) was added aldehyde (1 mmol) in THF (10 mL) containing acetic acid (0.1 mL) drop-wise. The mixture was stirred at 50° C. for 4-12 h and then cooled to room temperature. Sodium cyanoborohydride (1.5 mmol) was added to the reaction mixture and stirred at room temperature overnight. Water was added and pH of the solution was adjusted to 7. The solution was extracted with ethyl acetate. The organic layer was dried (MgSO4) and evaporated in vacuo. The residue was purifeid by flash column chromatography to furnish the desired amine.

[0252] AF-1: Synthesis of Amidine from Nitrile

[0253] Acetyl chloride (5 mL) was added to methanol (5 mL) at 0° C. drop-wise and stirred at room temperature for 15 mins. To this solution of methanolic HCl was added nitrile compound (1 mmol) and stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and dried. The residue obtained of the resulting methyl imidate was dissolved in methanol (10 mL). Dry ammonia gas was bubbled into the reaction mixture at reflux temperature for 5 h. The reaction mixture was concentrated to furnish the required amidine.

[0254] AG: Addition of Grignard Reagent to Aryl Aldehyde

[0255] To a solution of aryl aldehyde (1 mmol) in THF (15 mL) cooled to −78° C. was added drop wise under a nitrogen atmosphere, vinyl magnesium bromide (1 M solution in THF, 5 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 48 h. The reaction was quenched carefully with saturated aqueous ammonium chloride solution (10 mL) and extracted with ethyl acetate (2×10 mL). The organic layers were combined, washed with brine (10 mL), dried and concentrated in vacuo. The residue obtained was purified by flash column chromatography to obtain the desired addition product.

[0256] AG-1: Synthesis of Tributylvinyltin Compounds from Vinyl Bromide Containing Hydroxyl

[0257] To a solution of vinyl bromide with hydroxyl (1 mmol) in dichloromethane (20 mL) was added tert-butyldimethylsilyl chloride (1.5 mmol) and DMAP (1.5 mmol) and stirred at room temperature overnight. The reaction mixture was quenched with water (20 mL) and the aqueous layer separated. The organic layer was washed with 0.1 N aqueous HCl (10 mL), brine (20 mL), dried and concentrated in vacuo to furnish corresponding tert-butyldimethylsilyloxy compound as an oil which was used as such for the next step.

[0258] To a solution of the above oily residue (1 mmol) in diethyl ether (20 mL) cooled to −78° C. was added dropwise tert-butyllithium (1.7 M in pentane, 2 mmol) over a period of 15 mins. The reaction mixture was stirred at −78° C. for 3 h and quenched at −78° C. with 2 N aqueous sulfuric acid (2 mL) and water (18 mL). The reaction mixture was neutralized using 2 N NaOH and the organic layer was separated. The organic layer was washed with water (20 mL), brine (20 mL), dried and concentrated in vacuo. Purification of the crude residue obtained by flash column chromatography furnished the desired tributyltin compound.

[0259] AG-2: Synthesis of Tributylmethyltin Compounds from Arylmethyl Bromides or Allyl Bromides

[0260] To lithium clippings (10 mmol) in THF (10 mL) cooled to −40° C. was added dropwise tributyltin chloride (0.27 mL, 1 mmol) in THF (5 mL) over a period of 15 min. The reaction mixture was allowed to warm to room temperature and stirred for 16 h. The reaction mixture was filtered through glass wool to remove insoluble impurities and cooled to −40° C. A freshly prepared solution of arylmethyl bromide or allyl bromide (1 mmol) was added dropwise over a period of 10 mins and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous ammonium chloride solution (10 mL) and extracted with ether (2×10 mL). The organic layers were combined, washed with brine (10 mL), dried, filtered and concentrated in vacuo to furnish desired tributyltinalkyl and was used as such without further purification.

[0261] AG-3: 4-Bromo-5-formyl-benzo[1,3]dioxole-2-carboxylic acid methyl ester

[0262] To a mixture of 2-bromo-3,4-dihydroxy-benzaldehyde (2.17 g, 10.0 mmol) and K2CO3 (5.56 g, 40.2 mmol) in n-propanol (25 mL) was added dibromoacetic acid (2.18, 10.0 mmol) and the mixture was heated at reflux temperature for 24 h. After cooling to room temperature, another portion of dibromoacetic acid (1.75 g, 8.0 mmol) was added. The mixture was stirred at reflux for 46 h. n-Propanol was evaporated and water (30 mL) was added. The resulting aqueous solution was acidified to pH 2 by adding 1 N HCl and extracted with ethyl acetate (3×100 mL). The combined organic layers were dried (MgSO4) and evaporated in vacuo to afford crude 4-bromo-5-formyl-benzo[1,3]dioxole-2-carboxylic acid (1.34 g) as a brownish solid. This crude product was dissolved in anhydrous methanol (50 mL) and conc. H2SO4 (5 mL) was added drop by drop. The resulting mixture was refluxed overnight and cooled to room temperature. Water (50 mL) was added and the resulting aqueous solution was extracted with ethyl acetate (100 mL×3). The combined organic layers were dried (MgSO4) and evaporated in vacuo. The residue was purified by flash column chromatography (ethyl acetate:hexane=5:95) to furnish 4-bromo-5-formyl-benzo[1,3]dioxole-2-carboxylic acid methyl ester as a white solid.

[0263] AH: Synthesis of Tert-Butyl Ester of Phenol

[0264] To a solution of phenol (1 mmol) in pyridine (10 mL) was added 2,2-dimethyl-propionyl chloride (1.2 mmol) dropwise. The mixture was stirred at room temperature for overnight and diluted with water (100 mL). The reaction mixture was extracted with ethyl acetate (3×50 mL). The organic layers were combined and washed with aqueous 0.5 N HCl (100 mL), water, brine, dried (MgSO4) and concentrated in vacuo. The crude residue was purified by flash column chromatography to furnish the desired ester.

[0265] AI: Preparation of 2-bromo-5-hydroxy benzaldehyde

[0266] To a solution 3-hydroxybenzaldehyde (Aldrich, 101.39 g, 805 mmol) in chloroform (1000 mL), was added bromine (45 mL, 845 mmol) in chloroform (200 mL) drop wise over a period of 2 h at room temperature. The reaction mixture was stirred at room temperature overnight and filtered to collect crude 2-bromo-5-hydroxy benzaldehyde (32 g) as a dark brown solid. The filtrate was concentrated to 200 mL, filtered through a pad of Celite and silica gel (40 g) and washed with ether (1000 mL). The filtrate was concentrated in vacuo to give a second crop of the crude desired aldehyde (60 g) as a dark brown solid. The above solids were combined and dissolved in glacial acetic acid (360 mL) by heating. Water (840 mL) was added and the solution was filtered hot. The solution was allowed to attain room temperature and kept in a refrigerator overnight. The crystals obtained were collected by filtration and washed with water, dried overnight in vacuo to furnish (60 g, 37%) of the desired product as a purplish brown crystalline solid, mp: 135° C.

[0267] AJ-1: Amidine from Nitrile

[0268] A mixture of nitrile (1 mmol) and hydroxylamine (aqueous 50%, 1.8 mL) in EtOH (15 mL) was refluxed for 3 h and concentrated in vacuo. To the residue obtained was added EtOH (20 mL), acetic acid (2 mL) and a small amount of Raney nickel. The reaction mixture was hydrogenated (50 psi) for 14-24 h, filtered and concentrated in vacuo. The residue obtained, was purified by flash column chromatography to obtain the corresponding amidine.

[0269] AJ-2: Amidine from Nitrile

[0270] A mixture of nitrile (1 mmol) and saturated methanolic HCl solution (freshly prepared by bubbling HCl gas or prepared in-situ by premixing methanol and acetyl chloride at ice cold temperature) was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo to furnish methyl imidate. To the residue of methyl imidate was added MeOH (40 mL) and ammonia gas was bubbled at reflux temperature for 16 h or till the reaction was complete. The reaction mixture was concentrated in vacuo and dried to furnish the desired amidine. Alternatively, the methyl imidate was dissolved in methanol and ammonium acetate (10 mmol) was added. The reaction mixture was concentrated in vacuo and purified by flash column chromatography to obtain the corresponding amidine.

[0271] AJ-3: Amidine from Nitrile

[0272] To a solution of nitrile (1 mmol) dissolved in methanol (5 mL) was added N-acetyl cystein (0.1 or 1 mmol) and ammonium acetate (5 mmol) and heated at reflux till the reaction was complete. The reaction mixture was concentrated in vacuo and purified by flash column chromatography to obtain the corresponding amidine.

[0273] AK: Conversion of Aryl Triflates or Halides to Boronate Ester

[0274] To dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloro-methane adduct (0.75 mmol) under argon in dioxane (100 mL) was added aryl triflate (25 mmol), pinacolborane (31.5 mmol) and triethylamine (75 mmol). The reaction mixture was heated under argon at 100° C. for 3 h or until complete as evidenced from TLC analysis. The reaction mixture was concentrated in vacuo. The residue obtained was purified by flash column chromatography to furnish the desired boronate ester. Alternatively, the following method can be used.

[0275] To dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloro-methane adduct (0.03 mmol), 1,1′-bis(diphenylphosphino)ferrocene (0.03 mmol) under argon in dioxane (100 mL) was added aryl triflate (1 mmol), bis(pinacolata)diboron (1.1 mmol) and potassium acetate (3 mmol). The reaction mixture was heated under argon at 100° C. for 3 h or until complete as evidenced from TLC analysis. The reaction mixture was concentrated in vacuo. The residue obtained was purified by flash column chromatography to furnish the desired boronate ester.

[0276] The examples of the compounds prepared are given in the following tables. The tables describe the compounds, their method of preparation, the starting material, and the analytical data. In some cases, where analytical data have not been given, those compounds were characterized at the later step in the synthesis.

[0277] AL: Deprotection of the Benzyl Ester

[0278] The aldehyde (1 mmol) was mixed with ammonium nitrate (0.2 mmol) in 10 mL of EtOH. The mixture was treated with HC(OEt)3 (1.5 mmol) and stirred at 70° C. for 2 h. The reaction mixture was diluted with 30 mL of EtOH and dried with molecular sieves followed by filtration.

[0279] The above filtrate (40 mL) was treated with 1 drop of concentrated HCl and 10% Pd/C (0.1 g) followed by hydrogenation for 5 h. The reaction mixture was filtered and concentrated. The residue was treated with 10 mL of DME and 1 mL of 1N HCl followed by stirring at room temperature for 0.5 h. Water (5 mL) was added and the mixture was extracted with EtOAc (2×10 mL). The combined extracts were washed with water (2×10 mL) and brine (10 mL), dried over MgSO4, filtered, and concentrated. The residue was purified by flash column chromatography (EtOAc/Hex/MeOH, 1:1:0 to 1:1:0.2) to afford the desired product.

[0280] AM: Preparation of α-Amino Esters:

[0281] A mixture of methyl 2′-formyl-4-[(isobutylamino)carbonyl]-5′-methoxy-1,1′-biphenyl-2-carboxylate (1 mmol) and 4-aminobenzonitrile (1 mmol) in toluene (5 mL) was heated at reflux for 16 h. The reaction mixture was concentrated and the residue taken in dry methanol (5 mL), cooled in an ice bath and tosylmethyl isocyanide (1.1 mmol) added to it followed by BF3.ethereate (3.0 mmol) over a period of 5 min. The reaction mixture was stirred for 0.5 h in ice-bath and then at room temperature for 1.5 h. Water (90 μL) was added to the reaction and further stirred for 16 h. The reaction mixture was taken in ethyl acetate (50 mL), washed with water and brine, and dried over MgSO4. After filtration, the filtrate was concentrated and the residue was purified on silica gel using ethyl acetate: hexane as an eluent to give 0.37 g (67%) of the desired product, 2′-{1-[4-cyanophenyl)amino]-2-methoxy-2-oxoethyl}-4-[(isobutylamino)carbonyl]-5′-methoxy-1,1′-biphenyl-2-carboxylate.

67
Cpd.			Starting	Method
No.	—R	—R′	From	Used	Analytical Data
2a	—OH	68	1	A-1 or A-2	1H NMR (DMSO-d6): δ 10.26 (s, 1 H), 9.84 (s, 1H), 8.15 (d, J=3.0 Hz, 1H), 7.64 (dd, J=2.0 Hz and 8.9 Hz, 1H), 6.94 (d, J=8.9 Hz, 1H), 3.90 (s, 3H), 2.15 (d, J=6.9 Hz, 2H), 2.06 (m, J=6.9 Hz, 1H), 0.93 (d, J=6.9 Hz, 1H), 0.93 (d, J=6 Hz, 6H); MS (ES+): 252.12
2b	—OH	69	1	A-1 or A-2	Characterized in the next step
2c	—OH	70	1	A-1 or A-2	MS (ES+): 294.54
2d	—OH	71	1	A-1 or A-2	MS (ES+): 288.49 (M + Na)+
2e	—OH	72	1	A-1 or A-2	Characterized in the next step
2f	—OH	73	1	A-1 or A-2	MS (ES+): 300.40 (M + Na)+
2g	—OH	74	1	A-1 or A-2	MS (ES+): 272.48 (M + Na)+; MS (ES−): 248.66
2h	—OH	75	1	A-1 or A-2	MS (ES+): 286.48 (M + Na)+
2i	—OH	76	1	A-1 or A-2	MS (ES+): 224.54
2j	—OH	77	1	A-1 or A-2	Characterized in the next step
3a	—OSO2CF3	78	2a	B-1 or B-2	MS (ES+): 384.37
3b	—OSO2CF3	79	2b	B-1 or B-2	MS (ES+): 370.36
3c	—OSO2CF3	80	2c	B-1 or B-2	MS (ES+): 426.37
3d	—OSO2CF3	81	2d	B-1 or B-2	Characterized in the next step
3e	—OSO2CF3	82	2e	B-1 or B-2	1H NMR (CDCl3): δ 8.41 (d, J=2.3 Hz, 1H), 8.10 (dd, J=8.5, 2.4 Hz, 1H), 7.37 (d, J=8.5 Hz, 1H), 6.48 (broad, 1H), 3.98 (s, 3H), 3.46 (q, J=7.2 Hz, 2H), 1.62 (m, 2H), 1.42 (m, 2H), 0.96 (t, J=7.2 Hz, 3H); MS (ES+): 384.1
3f	—OSO2CF3	83	2f	B-1 or B-2	1H NMR (CDCl3): δ 8.45 (d, J=2.4 Hz, 1H), 8.14 (dd, J=8.7, 2.4 Hz, 1H), 7.42 (d, J=8.7 Hz, 1H), 6.52 (broad, 1H), 4.14 (m, 2H), 4.00 (s, 3H); MS (ES+): 410.2
3g	—OSO2CF3	84	2g	B-1 or B-2	1H NMR (CDCl3): δ 8.42 (d, J=2.3 Hz, 1H), 8.12 (dd, J=8.5, 2.3 Hz, 1H), 7.39 (d, J=8.7 Hz, 1H), 6.31 (broad, 1H), 4.00 (s, 3H), 3.34 (dd, J=7.2, 5.5 Hz, 2H), 1.07 (m, 1H), 0.59 (m, 2H), 0.30 (m, 2H); MS (ES+): 382.2
3h	—OSO2CF3	85	2h	B-1 or B-2	MS (ES+): 396.36
3i	—OSO2CF3	86	2i	B-1 or B-2	1H NMR (DMSO-d6): δ 8.85 (t, J=5.5 Hz, 1H), 8.49 (d, J=2.3 Hz, 1H), 8.23 (dd, J=8.7, 2.3 Hz, 1H), 7.70 (d, J=8.7 Hz, 1H), 3.92 (s, 3H), 3.31 (m, 2H), 1.14 (t, J=7.2 Hz, 3H); MS (ES+): 356.1
3j	—OSO2CF3	87	2j	B-1 or B-2	1H NMR (DMSO-d6): δ 8.81 (t, J=6.0 Hz, 1H), 8.49 (d, J=2.3 Hz, 1H), 8.24 (dd, J=8.7, 2.4 Hz, 1H), 7.71 (d, J=8.7 Hz, 1H), 3.92 (s, 3H), 3.15 (m, 2H), 1.64 (m, 1H), 1.41 (m, 1H), 1.12 (m, 1H), 0.88 (m, 6H); MS (ES+): 398.2
5	—OSO2CF3	—CO2MEM	4	B-1 or B-2	1H NMR (DMSO-d6): δ 8.52 (d, J=2.0 Hz, 1H),
					8.32 (dd, J=2.0 and 8.9 Hz, 1H), 7.72 (d, J=7.9
					Hz, 1H), 5.50 (s, 2H), 3.88 (s, 3H), 3.78 (t, J=4.9
					Hz, 2H), 3.44 (d, J=4.9 Hz, 2H), 3.17 (s, 3H);
					MS (ES+): 439.1 (M + Na)+
6a	88	89	3a	AK	1HNMR (CDCl3): δ 8.29 (d, J=1.6 Hz, 1H), 7.96 (dd, J=7.5 & 1.6 Hz, 1H), 7.58 (d, J=7.5 Hz, 1H), 6.24 (bs, 1H), 3.94 (s, 3H), 3.30 (t, J=6.5 Hz, 2H), 1.92 (m, 1H), 1.43 (s, 12H), 0.99 (d, J=6.5 Hz, 6H); MS (ES+) 362.2
139	—OH	90	138	AA	1H NMR (DMSO-d6): δ 10.26 (s, 1H), 9.84 (s, 1H), 8.15 (d, J=3.0 Hz, 1H), 7.64 (dd, J=2.0 Hz and 8.9 Hz, 1H), 6.94 (d, J=8.9 Hz, 1H), 3.90 (s, 3H), 2.15 (d, J=6.9 Hz, 2H), 2.06 (m, J=6.9 Hz, 1H), 0.93 (d, J=6.9 Hz, 6H); MS (ES+): 252.12
140	—OSO2CF3	91	139	B-2	1H NMR (DMSO-d6): δ 10.38 (s, 1H), 8.36 (d, J=2.8 Hz, 1H), 7.99 (dd, J=2.6 and 8.9 Hz, 1H), 7.52 (d, J=9.0 Hz, 1H), 3.89 (s, 3H), 2.23 (d, J=7.0 Hz, 2H), 2.09 (m, J=6.6 Hz, 1H), 0.94 (d, J=6.6 Hz, 6H); MS (ES+): 384.0
169	—OH	92	168	AC	1H NMR (CDCl3): δ 8.08 (s, 1H), 8.00 (d, J=2.3 Hz, 1H), 7.75 (dd, J=2.3 and 8.7 Hz, 1H), 7.01 (d, J=8.7 Hz, 1H), 3.97 (s, 3H), 3.50 (s, 1H); MS (ES+): 196.1
170	—OH	—CH2NH2	169	G	1H NMR (DMSO-d6): δ 7.79 (d, J=2.0 Hz, 1H),
					7.51 (dd, J=2.3 and 8.5 Hz, 1H), 6.95 (d, J=8.5
					Hz, 1H), 7.01 (d, J=8.7 Hz, 1H), 3.90 (s, 3H),
					3.72 (s, 2H), 3.50 (bs, 2H); MS (ES+): 182.12
171	—OH	93	170	AA	MS (ES−): 250.50; MS (ES+): 274.50 (M + Na)+
172	—OSO2CF3	94	171	B-2	1H NMR (CDCl3): δ 7.96 (d, J=2.3 Hz, 1H), 7.55 (d, J=2.3 and 8.3 Hz, 1H), 7.26 (d, J=8.3 Hz, 1H), 5.90 (br s, 1H), 4.50 (d, J=4.1 Hz, 2H), 3.97 (s, 3H), 2.44 (sep, J=7.0 Hz, 1H), 1.20 (d, J=7.0 Hz, 6H); MS (ES+): 384.1
177	—OH	95	168	AE-1	1H NMR (DMSO-d6): δ 10.62 (s, 1H), 8.88 (m, 2H), 7.99 (d, J=2.3 Hz, 1H), 7.70 (dd, J=2.3 and 8.5 Hz, 1H), 7.06 (d, J=8.7 Hz, 1H), 4.09 (m, 2H), 3.91 (s, 3H), 2.70 (m, 2H), 1.98 (m, 1H, J=6.8 Hz), 0.93 (d, J=6.8 Hz, 6H); MS (ES+): 238.1
178	—OSO2CF3	96	177	B-2	1H NMR (CDCl3): δ 8.05 (d, J=2.3 Hz, 1H), 7.63 (dd, J=2.3 and 8.3 Hz, 1H), 7.25 (d, J=8.3 Hz, 1H), 3.96 (s, 3H), 3.85 (s, 2H), 2.43 (d, J=6.8 Hz, 2H), 1.77 (m, J=6.6 Hz, 1H), 0.93 (d, J=6.6 Hz, 1H); MS (ES+): 370.2
179	—OSO2CF3	97	178	R	1H NMR (DMSO-d6): δ 7.93 (m, 1H), 7.47 (m, 1H), 7.26 (m, 1H), 4.48 (m, 2H), 3.96 (s, 3H), 3.03 (m, 2H), 1.91 (m, 1H), 1.52 (m, 9H), 0.89 (d, J=6.6 Hz, 6H); MS (ES+): 492.2 (M + Na)+

[0282]

98
Cpd.			Starting	Method
No.	—R	—R′	From	Used	Analytical Data
7	—OBn	—CHO	6 + 3a	D-2	1 H NMR (DMSO-d6): δ□9.78 (s, 1H), 8.85 (t, J=5.7 Hz, 1H),
					8.50 (d, J=2.0 Hz, 1H), 8.20 (dd, J=8.2, 1.9 Hz, 1H), 7.55 (m,
					9H), 5.35 (s, 2H), 3.69 (s, 3H), 3.23 (t, J=6.5 Hz, 2H), 1.98 (m,
					1H), 1.02 (d, J=6.8 Hz, 6H); MS (ES+): 446.3
8	—OBn	—CO2H	7	E	MS (ES+): 484.33 (M + Na)+
9	—OBn	—CO2MEM	8	F	MS (ES+): 572.2 (M + Na)+
10	—OH	—CO2MEM	9	G	MS (ES+): 482.33 [(M-MBM) + Na]+
11	—OSO2CF3	—CO2MEM	10	B-2	1 H NMR (DMSO-d6): δ□8.75 (t, J=5.6 Hz, 1H), 8.44 (d, J=1.6
					Hz, 1H), 8.11 (dd, J=8.0, 1.9 Hz, 1H), 8.01 (d, J=2.9 Hz, 1H),
					7.84 (dd, J=8.4, 2.6 Hz, 1H), 7.47 (d, J=8.5 Hz, 1H), 7.41 (d, J=
					8.0 Hz, 1H), 5.23 (q, AB system, 2H), 3.59 (s, 3H), 3.44 (m, 2H),
					3.30 (m, 2H), 3.18 (s, 3H), 3.13 (t, J=6.6 Hz, 2H), 1.88 (m, 1H),
					0.91 (d, J=6.7 Hz, 6H); MS (ES+): 614.3 (M + Na)+
29a	99	—CO2MEM	11	D-3	Characterized in the next step
29b	100	—CO2MEM	11	D-3	MS (ES+): 520.2 (M + Na)+
29c	101	—CO2MEM	11	D-3	MS (ES+): 482.3
29d	102	—CO2MEM	11	D-3	MS (ES+): 562.3 (M + Na)+
29e	103	—CO2MEM	11	D-3	MS (ES+): 556.4 (M + Na)+
29f	104	—CO2MEM	11	D-3	1 H NMR (DMSO-d6): δ□8.50 (t, J=5.6 Hz, 1H), 8.18 (d, J=1.9 Hz, 1H), 7.86 (dd, J=7.9, 1.9 Hz, 1H), 7.78 (d, J=1.7 Hz, 1H), 7.56 (dd, J=8.0, 1.8 Hz, 1H), 7.13 (d, J=8.0 Hz, 1H), 7.00 (d, J=7.9 Hz, 1H), 6.67 (dd, J=17.6, 11.1 Hz, 1H), 5.76 (d, J=17.6 Hz, 1H),
# 5.19 (d, J=11.1 Hz, 1H), 4.99 (q, AB system, 2H), 3.37 (s, 3H), 3.20 (m, 2H), 3.11 (m, 2H), 2.97 (s, 3H), 2.91 (t, J=6.7 Hz, 2H), 1.67 (m, 1H), 0.70 (d, J=6.6 Hz, 6H); MS (ES+): 492.3 (M + Na)+
29g	105	—CO2MEM	11	D-2	MS (ES+): 576.2 (M + Na)+; MS (ES−): 552.2
29h	106	—CO2MEM	11	D-2	MS (ES+): 538.2
29i	107	—CO2MEM	11	D-2	MS (ES+): 560.4 (M + Na)+
30a	108	—CO2H	29a	I-1	MS (ES+): 398.3; MS (ES−): 396.3
30b	109	—CO2H	29b	I-1	Characterized in the next step
30c	110	—CO2H	29c	I-1	MS (ES−): 392.1
30d	111	—CO2H	29d	I-1	MS (ES+): 452.1
30e	112	—CO2H	29e	I-1	MS (ES+): 446.2
30f	113	—CO2H	29f	I-1	MS (ES−): 380.1
30g	114	—CO2H	29g	K, N, O, I-1	MS (ES+): 515.3 (M + Na)+; MS (ES−): 491.2
30h	115	—CO2H	29h	K, I-1	MS (ES−): 450.1
30i	116	—CO2H	29i	K, I-1	MS (ES−): 450.3
33	—OSO2CF3	—CO2H	11	I-1	Characterized in the next step
41	117	—CO2MEM	10	D-8	MS (ES−): 534.30
42	118	—CO2H	41	I-1	MS (ES−): 446.30
48	—OCH3	—CHO	47 + 3a	D-2	MS (ES+): 392.2 (M + Na)+
49	—OCH3	—CO2H	48	E	MS (ES+): 386.1; 408.1 (M + Na)+

[0283]

119
Cpd.			Starting	Method
No.	—R	—R′	From	Used	Analytical Data
14	—OSO2CF3	—CHO	13	B-2	Characterized in the next step
15	—OSO2CF3	—CO2H	14	E	MS (ES−): 403.58
16	—OSO2CF3	120	15	A-3 or A-4	1 HNMR (DMSO-d6): δ□ 8.83 (t, J=6 Hz, 1H), 8.49 (d, J=2.6 Hz, 1H), 8.23 (dd, J=8.6 Hz, 1H), 7.72 (d, J=8.6 Hz, 1H), 7.49 (m, 2H), 7.41 (m, 3H), 5.43 (s, 2H), 3.1 (t, J=6.9 Hz, 2H), 2.29 (m, 1H), 0.89 (d, J=6.9 Hz, 6H).

[0284]

121
Cpd.			Starting	Method
No.	—R	—R′	From	Used	Analytical Data
17	—OBn	—CHO	16 + 6	D-2	1 HNMR (DMSO-d6): δ□ 0.88 (d, J=6.0 Hz, 6H), 1.85 (m, 1H),
					3.1 (t, J=6.0 Hz, 2H), 5.02 (q, J=13 and 2.5 Hz, 2H), 5.18 (s,
					2H), 6.88 (m, 2H), 7.17 (d, J=8.6 Hz, 1H), 7.26 (m, 4H), 7.35
					(m, 1H), 7.40 (m, 4H), 7.49 (d, J=7.7 Hz, 2H), 8.07 (dd, J=7.7
					and 1.7 Hz, 1H), 8.38 (d, J=1.7 Hz, 1H), 8.72 (t, J=6 Hz, 1H),
					9.63 (s, 1H); MS (ES+): 522.89
18	—OBn	—CO2H	17	E	1 HNMR (DMSO-d6): δ□ 0.86 (d, J=6.9 Hz, 6H), 1.85 (m, 1H),
					3.09 (t, J=6.9 Hz, 2H), 5.01 (d, J=5.01 Hz, 2H), 5.14 (s, 2H),
					7.08 (m, 3H), 7.14 (dd, J=8.6 and 2.6 Hz, 1H), 7.27 (m, 4H),
					7.34 (m, 1H), 7.41 (m, 3H), 7.48 (m, 2H), 7.99 (dd, J=6.9 and
					1.8 Hz, 1H), 8.32 (s, 1H), 8.64 (t, J=6 Hz, 1H), 12.57 (s, 1H);
					MS (ES+): 538.86
19	—OBn	—CO2MEM	18	F	1 HNMR (DMSO-d6): δ 0.90 (d, J=6.8 Hz, 6H), 1.86 (m, 1H),
					3.10 (t, J=6.5 Hz, 2H), 3.16 (s, 3H), 3.28 (dd, J=3 and 6 Hz,
					2H), 3.36 (dd, J=3 and 6 Hz, 2H), 5.02 (d, J=3.8 Hz, 2H), 5.12
					(d, J=15 Hz, 2H), 5.64 (s, 2H), 7.11 (m, 3H), 7.24 (dd, J=8.25
					and 2.75 Hz, 1H), 7.29 (m, 4H), 7.35 (m, 1H), 7.42 (m, 3H),
					7.49 (m, 2H), 8.02 (dd, J=1.7 and 8.2 Hz, 1H), 8.36 (d, 1.7 Hz,
					1H), 8.68 (t, J=6 Hz, 1H); MS (ES+): 626.44
21	—OH	—CO2MEM	19	G, H	1 HNMR (DMSO-d6): δ 0.88 (d, J=6 Hz, 6H), 1.85 (m, 1H) 3.10
					(t, J=6 Hz, 2H) 3.16 (s, 3H), 3.28 (m 2H), 3.35 (m, 2H), 5.04
					(d, J=3.5 Hz, 2H) 5.11 (d, J=14 Hz, 2H), 6.98 (m, 2H), 7.11
					m, 2H), 7.29 (m, 5H), 8.03 (dd, J=8 and 2 Hz, 1H), 8.32 (d,
					J=2 Hz, 1H), 8.67 (t, J=6 Hz, 1H), 9.9 (s, 1H);
					MS (ES+) 536.30 (100%: M+1)
22	—OSO2CF3	—CO2MEM	21	B-2	1 HNMR (DMSO-d6): δ 0.89 (d, J=6.8 Hz, 6H), 1.86 (m, 1H),
					3.12 (t, J=6.5 Hz, 2H), 3.16 (s, 3H), 3.29 (m, 2H), 3.40 (m,
					2H), 5.04 (s, 2H), 5.16 (dd, J=18 and 6 Hz, 2H), 7.15 (m, 2H),
					7.31 (m, 3H), 7.36 (d, J=8.5 Hz, 1H), 7.41 (d, J=8.5 Hz, 1H),
					7.73 (dd, J=8.6 and 2.6 Hz, 1H), 7.85 (d, J=2.6 Hz, 1H), 8.07
					(dd, J=7.7 and 1.7 Hz, 1H), 8.45 (d, J=1.7 Hz, 1H), 8.73 (t,
					J=6 Hz, 1H); MS (ES+) 668.15
24a	122	—CO2MEM	22 + 23	D-1	1 HNMR (DMSO-d6): δ 0.89 (d, J=6.8 Hz, 6H), 1.87 (m, 1H), 3.12 (t, J=6 Hz, 2H), 3.16 (s, 3H), 3.29 (m, 2H), 3.39 (m, 2H), 5.05 (d, J=2.6 Hz, 2H), 5.16 (d, J=17 Hz, 2H), 7.08 (m, 2H), 7.21 (m, 4H), 7.24 (d, J=7.7 Hz, 1H), 7.35
# (d, J=7.7 Hz, 1H), 7.62 (d, J=3.5 Hz, 1H), 7.64 (d, J=5 Hz, 1H), 7.86 (d, J=8.6 Hz, 1H), 8.06 (m, 2H), 8.42 (s, 1H), 8.73 (t, J=6 Hz, 1H); MS (ES+) 602.52
24b	123	—CO2MEM	22 + 23	D-1	1 HNMR (DMSO-d6): δ 0.89 (d, J=6.8 Hz, 6H), 1.87 (m, 1H), 3.12 (t, J=6 and 6.8 Hz, 2H), 3.16 (s, 3H), 3.30 (m, 2H), 3.39 (dd, J=5.2 and 3.4 Hz, 2H), 5.04 (d, J=4.3 Hz, 2H), 5.16 (d, J=16 Hz, 2H), 7.08 (m, 2H), 7.20 (m, 3H), 7.24
# (d, J=8.6 Hz, 1H), 7.35 (d, J=8.6 Hz, 1H), 7.61 (d, J=5 Hz, 1H), 7.71 (dd, J=4.8 and 3 Hz, 1H), 7.91 (dd, J=1.7 and 7.7 Hz, 1H), 8.00 (m, 1H), 8.06 (dd, J=2 and 8 Hz, 1H), 8.14 (d, J=1.7 Hz, 1H), 8.41 (d, J=1.7 Hz, 1H), 8.68 (t, J=6 Hz, 1H); MS (ES+) 602.27
24c	124	—CO2MEM	22 + 23	D-1	1 HNMR (DMSO-d6): δ 0.89 (d, J=6.8 Hz, 6H), 1.87 (m, 1H), 3.12 (t, J=6 and 6.8 Hz, 2H), 3.16 (s, 3H), 3.30 (m, 2H), 3.40 (m, 2H), 5.05 (d, J=5 Hz, 2H), 5.17 (d, J=17 Hz, 2H), 7.09 (m, 2H), 7.21 (m, 3H), 7.30 (d, J=7.7 Hz, 1H), 7.37
# (d, J=7.7 Hz, 1H), 7.44 (m, 1H), 7.54 (t, J=7.7 Hz, 2H), 7.73 (d, J=6.8 Hz, 2H), 7.88 (dd, J=1.7 and 7.7 Hz, 1H), 8.07 (dd, J=7.7 and 1.7 Hz, 1H), 8.11 (d, J=1.7 Hz, 1H), 8.42 (d, J=1.7 Hz, 1H), 8.72 (t, J=6 Hz, 1H); MS (ES+) 596.45
24d	125	—CO2MEM	22 + 23	D-1	MS (ES+) 616
24e	126	—CO2MEM	22 + 23	D-1	MS (ES+) 586.4
24f	127	—CO2MEM	22 + 23	D-1	MS (ES+): 586.39
24g	128	—CO2MEM	22 + 23	D-1	MS (ES+): 616.63
24h	129	—CO2MEM	22 + 23	D-1	MS (ES+): 597.25
24i	130	—CO2MEM	22 + 23	D-1	MS (ES+): 597.4
24j	131	—CO2MEM	22 + 23	D-1	MS (ES+): 597.4
24k	132	—CO2MEM	22 + 23	D-1	MS (ES+): 644.3
24l	133	—CO2MEM	22 + 23	D-3	Characterized at the next step
24m	134	—CO2MEM	22 + 23	D-10	Characterized at the next step
24n	135	—CO2MEM	22 + 23	D-3	MS (ES+): 560.74
24o	136	—CO2MEM	22 + 23	D-4	MS (ES+): 603.72
24p	137	—CO2MEM	22 + 23	D-5	MS (ES+): 558.3
24q	138	—CO2MEM	22 + 23	D-5	Characterized in the next step
24r	139	—CO2MEM	22 + 23	D-5	MS (ES+): 610.4 (M + Na)+
24aa	140	—CO2MEM	22 + 23	D-11	Characterized in the next step
24ab	141	—CO2MEM	22 + 23	D-2	MS (ES+): 630.55
24ac	142	—CO2MEM	22 + 23	D-2	MS (ES+): 630.74
24ad	143	—CO2MEM	22 + 23	D-2	MS (ES+): 652.3
24ae	144	—CO2MEM	22 + 23	D-2	Characterized in the next step
24ag	145	—CO2MEM	22 + 23	D-1	MS (ES+): 685.01
24ah	146	—CO2MEM	22 + 23	D-3	MS (ES+): 546.49
25a	147	CO2H	24a	I-1	1 HNMR (DMSO-d6): δ 0.91 (d, J=6.9 Hz, 6H), 1.88 (m, 1H), 3.13 (t, J=6.9 and 6 Hz, 2H), 5.07 (d, J=11.2 Hz, 2H), 7.09 (m, 2H), 7.22 (m, 5H), 7.35 (d, 7.7 Hz, 1H), 7.63 (d, 2.6 Hz, 1H), 7.65 (d, J=5.2 Hz, 1H), 7.82 (dd, J=7.7 and 1.7 Hz, 1H),
# 8.05 (d, J=1.7 Hz, 1H), 8.07 (s, 1H), 8.40 (s, 1H), 8.72 (t, J=6 Hz, 1H), 12.77 (brs, 1H); MS (ES+) 514.19
25b	148	CO2H	24b	I-1	1 HNMR (DMSO-d6): δ 0.92 (d, J=6.9 Hz, 6H), 1.88 (m, 1H), 3.12 (t, J=6.9 and 6 Hz, 2H), 5.07 (d, J=13 Hz, 2H), 7.09 (m, 2H), 7.22 (m, 4H), 7.35 (d, J=8.6 Hz, 1H), 7.63 (d, J=5.2 Hz, 1H), 7.70 (dd, J=2.6 and 4.3 Hz, 1H), 7.88
# (dd, J=7.2 and 1.7 Hz, 1H), 8.02 (d, J=1.7 Hz, 1H), 8.07 (dd, J=1.7 and 7.7 Hz, 1H), 8.15 (m, 1H), 8.39 (d, J=1.7 Hz, 1H), 8.72 (t, J=6 Hz, 1H), 12.70 (brs, 1H); MS (ES+) 514.06
25c	149	CO2H	24c	I-1	1 HNMR (DMSO-d6): δ 12.73 (bs, 1H), 8.73 (t, J=6 Hz, 1H), 8.41 (d, J=1.7 Hz, 1H), 8.12 (d, J=1.7 Hz, 1H), 8.07 (dd, J=7.7 & 1.7 Hz, 1H), 7.83 (dd, J=7.7 & 1.7 Hz, 1H), 7.72 (d, J=6.9 Hz, 2H), 7.54 (t, J=7.7, 2H), 7.44 (t, J=7.7 Hz, 1H),
# 7.37 (d, J=7.7 Hz, 1H), 7.28 (d, J=7.7 Hz, 1H), 7.21 (m, 3H), 7.09 (m, 2H), 5.08 (d, J=14 Hz, 2H), 3.13 (t, J=6.5 Hz, 2H), 1.88 (m, 1H), 0.91 (d, 6.8 Hz, 6H); MS (ES+) 507.93
25d	150	CO2H	24d	I-1	1 HNMR (DMSO-d6): δ 12.75 (bs, 1H), 8.71 (t, J=6 Hz, 1H), 8.39 (d, J=1.7 Hz, 1H), 8.05 (dd, J=1.7 & 7.7 Hz, 1H), 8.01 (d, J=2.5 Hz, 1H), 7.75 (dd, J=2.5 & 7.7 Hz, 1H), 7.42 (d, 3.4 Hz, 1H), 7.34 (d, J=7.7 Hz, 1H), 7.22 (m, 3H), 7.19 (d,
# J=8.6 Hz, 1H), 7.09 (m, 2H), 6.95 (d, J=3.4 Hz, 1H), 5.06 (d, J=11 Hz, 2H), 3.12 (t, J=6.5 Hz, 2H), 2.52 (s, 3H), 1.89 (m, 1H), 0.81 (d, 6.8 Hz, 6H); MS (ES+) 528.51
25e	151	CO2H	24e	I-1	1 HNMR (DMSO-d6): δ 0.89 (d, J=6 Hz, 6H), 1.86 (m, 1H), 3.12 (t, J=6.8 and 6.0 Hz, 2H), 5.03 (d, J=10 Hz, 2H), 7.02 (s, 1H), 7.06 (m, 2H), 7.16 (d, J=8.6 Hz, 1H), 7.21 (m, 3H), 7.31 (d, J=7.7 Hz, 1H), 7.75 (dd, J=8.5 and 1.7 Hz, 1H), 7.78 (t, J=1.7 Hz, 1H),
# 8.04 (m, 2H), 8.29 (s, 1H), 8.36 (d, J=1.7 Hz, 1H), 8.66 (t, J=6 and 5.2 Hz, 1H), 12.58 (bs, 1H); MS (ES+) 498.49
25f	152	CO2H	24f	I-1	MS (ES+): 498.36
25g	153	CO2H	24g	I-1	1 HNMR (DMSO-d6): δ 12.72 (bs, 1H), 8.69 (t, J=6 Hz, 1H), 8.39 (d, J=1.7 Hz, 1H), 8.06 (m, 2H), 7.79 (dd, J=1.7 & 7.7 Hz, 1H), 7.45 (s, 1H), 7.35 (d, J=7.7 Hz, 1H), 7.21 (m, 5H), 7.1 (m, H), 5.07 (d, J=8.6 Hz, 2H), 3.12 (t, J=6.5 Hz,
# 2H), 2.29 (s, 3H), 1.89 (m, 1H), 0.91 (d, 6.8 Hz, 6H); MS (ES+) 528.38
25h	154	CO2H	24h	I-1	1 HNMR (DMSO-d6): δ 12.74 (bs, 1H), 8.73 (m, 2H), 8.63 (d, J=1.7 Hz, 1H), 8.41 (d, J=1.7 Hz, 1H), 8.23 (dd, J=1.7 and 7.7 Hz, 1H), 8.08 (dd, J=1.7 & 7.7 Hz, 1H), 8.05 (d, J=7.7 Hz, 1H), 7.96 (dt, J=7.7 & 1.7 Hz, 1H), 7.43 (dd, J=6 & 7 Hz,
# 1H), 7.37 (d, J=7.7 Hz, 1H), 7.29 (d, J=8.6 Hz, 1H), 7.18 (m, 3H), 7.08 (m, 2H), 5.01 (q, J=10 & 25 Hz, 2H), 3.13 (t, J=6.9 and 6 Hz, 2H), 1.89 (m, 1H), 0.92 (d, J=6.9 Hz, 6H); MS (ES+) 509.58
25i	155	CO2H	24i	I-1	1 HNMR (DMSO-d6): δ 12.70 (bs, 1H), 8.91 (d, J=2.6 Hz, 1H), 8.68 (t, J=6 & Hz, 1H), 8.62 (d, J=2 Hz, 1H), 8.4 (d, J=1.7 Hz, 1H), 8.12 (m, 2H), 8.05 (dd, J=8.6 & 1.7 Hz, 1H), 7.88 (d, 8.5 & 1.7 Hz, 1H), 7.53 (dd, J=8.6 & 5.2 Hz, 1H), 7.34
# (d, J=7.7 Hz, 1H), 7.28 (d, J=8.6 Hz, 1H), 7.18 (m, 3H), 7.08 (m, 2H), 5.04 (d, J=12 Hz, 2H), 3.11 (t, J=6.5 Hz, 2H), 1.87 (m, 1H), 0.9 (d, 6.8 Hz, 6H); MS (ES+) 509.11
25j	156	CO2H	24j	I-1	1 HNMR (DMSO-d6): δ 0.90 (d, J=6.9 Hz, 6H), 1.88 (m, 1H), 3.11 (t, J=6.9 and 6 Hz, 2H), 5.03 (s, 2H), 7.06 (m, 2H), 7.18 (m, 3H), 7.33 (d, 8.4 Hz, 1H), 7.30 (d, J=8.4 Hz, 1H), 7.75 (d, J=6.2 Hz, 2H), 7.85 (m, 1H), 8.05 (dd, J=7.6 and 1.7 Hz,
# 1H), 8.18 (s, 1H), 8.40 (d, J=2 Hz, 1H), 8.71 (m, 4H); MS (ES+) 509.49
25k	157	CO2H	24K	I-1	Characterized in the next step
25l	158	CO2H	24l	I-1	MS (ES+): 511.54
25m	159	CO2H	24m	I-1	MS (ES+): 501.66
25n	160	CO2H	24n	I-1	MS (ES+): 472.4
25o	161	CO2H	24o	I-1	MS (ES+): 515.65
25p	162	CO2H	24p	I-1	Characterized in the next step
25q	163	CO2H	24q	I-1	MS (ES+): 536.3 (M + Na)+
25r	164	CO2H	24r	I-1	MS (ES−): 500.4
25s	165	CO2H	24s	I-1	Characterized in the next step
25t	166	CO2H	24t	I-1	Characterized in the next step
25u	167	CO2H	24u	I-1	MS (ES−): 486.4
25v	168	CO2H	24v	I-1	MS (ES+): 524.3 (M + Na)+
25w	169	CO2H	24w	I-1, Q	Characterized in the next step
25x	170	CO2H	24x	I-1	MS (ES−): 498.3
25y	171	CO2H	24y	I-1	MS (ES−): 484.3
25z	172	CO2H	24z	I-1	MS (ES+): 488.3
25aa	173	CO2H	24aa	I-1	Characterized in the next step
25ab	174	CO2H	24ab	K, I-1	MS (ES+): 544.27
25ac	175	CO2H	24ac	K, I-1	MS (ES+): 544.2
25ad	176	CO2H	24ad	E, H, I-1	MS (ES+): 670.3 (M + Na)+
25ae	177	CO2H	24ae	K, I-1	1 HNMR (DMSO-d6): δ 9.1 (bs, 2H), 8.8 (bs, 2H), 8.5 (t, J=6 Hz, 1H), 8.02 (s, 1H), 7.68 (s, 1H), 7.62 (m, 6H), 7.53 (d, J=5.8 Hz, 1H), 7.15 (d, J=6 Hz, 1H),), 7.13 (m, 1H), 7.01 (s, 1H), 5.5 (t, J=5 Hz, 1H), 4.7 (d, J=5 Hz, 2H), 3.01 (m, 2H), 1.8 (m, 1H), 0.85 (d, J=6.8 Hz, 6H)
25af	178	CO2H	24ad	K, I-1	MS (ES+): 566.2 (M + Na)+
25ag	179	CO2H	24ag	I-1	MS (ES+): 597.7
25ah	180	CO2H	24ah	L, I-1	MS (ES+): 492.54
25ai	181	CO2H	24ai	L, M, K, N, O, I-1	Characterized in the next step

[0285]

182
Cpd.		Starting	Method
No.	—R	From	Used	Analytical Data
26a	183	25a	J	1 HNMR(DMSO-d6): δ 0.88 (d, J = 6.9 Hz, 6 H), 1.84 (m, 1 H), 3.07 (t, J = 6.9 and 6.0 Hz, 2 H), 5.05 (s, 2 H), 7.04 (d, J = 6.9 Hz, 2 H), 7.20 (m, 4 H), 7.35 (d, J = 7.7 Hz, 1 H), 7.43 (d, J = 7.7 Hz, 1 H), 7.66 (d, J = 5.2 Hz, 1 H), 7.70 (d, J = 4.3 Hz, 1 H), 7.75 (m, 4 H), 7.82 (dd, J = 7.7 and 1.7 Hz, 1 H), 7.94 (d,
#J = 1.7 Hz, 1 H), 8.03 (dd, J = 7.7 and 1.7 Hz, 1 H), 8.26 (dd, J = 7.7, and 1.7 Hz, 1 H), 8.69 (t, J = 6 Hz, 1 H), 8.80 (s, 2 H), 9.17 (s, 2 H), 10.76 (s, 1 H); MS (ES+) 631.05
26b	184	25b	J	1 HNMR (DMSO-d6): δ 0.88 (d, J = 6.9 Hz, 6 H), 1.84 (m, 1 H), 3.07 (t, J = 6.8 and 6.0 Hz, 2 H), 5.04 (s, 2 H), 7.02 (d, J = 6.8 Hz, 2 H), 7.20 (m, 3 H), 7.34 (d, J = 7.7 Hz, 1 H), 7.43 (d, J = 8.6 Hz, 1 H), 7.72 (m, 6 H), 7.90 (dd, J = 1.7 and 7.7 Hz, 1 H), 8.05 (m, 3 H), 8.23 (d, J = 1.7 Hz, 1 H), 8.68 (t, J = 6 and 5.2
#Hz, 1 H), 8.82 (s, 2 H), 9.17 (s, 2 H), 10.73 (s, 1 H); MS (ES+)631.82
26c	185	25c	J	1 HNMR (DMSO-d6): δ 10.75 (s, 1 H), 9.19 (s, 2 H), 8.89 (s, 2 H), 8.69 (t, J = 6 Hz, 1 H), 8.29 (d, J = 1.7 Hz, 1 H), 8.07 (dd, J = 7.7 & 1.7 Hz, 1 H), 7.99 (d, J = 1.7 Hz, 1 H), 7.87 (dd, J = 7.7 & 1.7 Hz, 1 H), 7.83 (d, J = 7.7 Hz, 2 H), 7.77 (m 5 H), 7.54 (t, J = 7.7, 2 H), 7.43 (m, 3 H), 7.19 (m, 3 H), 7.03 (d, J = 6.9 Hz,
#2 H), 5.04 (bs, 2 H), 3.09 (t, J = 6.5 Hz, 2 H), 1.84 (m, 1 H), 0.89 (d, 6.8 Hz, 6 H); MS (ES+) 625.81
26d	186	25d	J	1 HNMR (DMSO-d6): δ 10.7 (s, 1 H), 9.14 (s, 2 H), 8.82 (s, 2 H), 8.64 (t, J = 6 Hz, 1 H), 8.21 (s, 1 H), 7.98 (dd, J = 7.8 & 2 Hz, 1 H), 7.8 (d, J = 2 Hz, 1 H), 7.7 (m, 4 H), 7.68 (dd, J = 2 & 7.8 Hz, 1 H), 7.44 (d, J = 3 Hz, 1 H), 7.37 (d, Hz, 1 H), 7.27 (d, J = 7.7 Hz, 1 H), 7.16 (m, 3H), 7.0 (s, 1 H), 6.99 (s, 1 H), 6.86 (d, J = 3
#Hz, 1 H), 5.0 (s, 2 H), 3.03 (t, J = 6.5 Hz, 2 H), 2.46 (s, 3 H), 1.78 (m, 1 H), 0.83 (d, 6.8 Hz, 6 H); MS (ES+) 645.77
26e	187	25e	J	1 HNMR (DMSO-d6): δ 0.87 (d, J = 6.2 Hz, 6 H), 1.73 (m, 1 H), 3.07 (t, J = 6.7 and 6.2 Hz, 2 H), 5.05 (s, 2 H), 7.03 (dd, J = 1.7 and 8 Hz, 2 H), 7.11 (d, J = 1.7 Hz, 1 H), 7.21 (m, 3 H), 7.31 (d, J = 8 Hz, 1 H), 7.42 (d, J = 8 Hz,1 H), 7.78 (m, 5 H), 7.92 (d, J = 1.7 Hz, 1 H), 8.02 (dd, J = 8 and 1.7 Hz, 1 H), 8.25 (d, J =
# 1.9 Hz, 1 H), 8.33 (s, 1 H), 8.63 (t, J = 6 and 5 Hz, 1 H), 8.80 (bs, 2 H), 9.14 (bs, 2 H), 10.67 (s, 1 H); MS (ES+) 615.75
26f	188	25f	J	1 HNMR (DMSO-d6): δ 0.87 (d, J = 6.7 Hz, 6 H), 1.83 (m, 1 H), 3.06 (t, J = 6.7 and 6.2 Hz, 2 H), 5.04 (s, 2 H), 6.67 (m, 1 H), 7.03 (m, 2 H), 7.16 (m, 3 H), 7.35 (d, J = 8.6 Hz, 1 H), 7.42 (d, J = 8 Hz, 1 H), 7.74 (m, 4H), 7.85 (m, 2H), 7.98 (d, J = 1.2 Hz, 1 H), 8.03 (dd, J =1.7 and 8 Hz, 1 H), 8.25 (d, J = 1.8 Hz, 1 H), 8.67 (t,
#J = 6.2 and 5.5 Hz, 1 H), 8.88 (bs, 2 H), 9.12 (bs, 2 H), 10.772 (bs, 1 H); MS (ES+) 615.75
26g	189	25g	J	1 HNMR (DMSO-d6): δ 10.67 (s, 1 H), 9.12 (s, 2 H), 8.78 (s, 2 H), 8.61 (t, J = 6 Hz, 1 H), 8.21 (s, 1 H), 7.98 (dd, J = 7.8 & 2 Hz, 1 H), 7.84 (d, J = 2 Hz, 1 H), 7.7 (m, 5 H), 7.46 (s, 1 H), 7.39 (d, 7.8 Hz, 1 H), 7.29(d, J = 7.7 Hz, 1 H), 7.16 (m, 4H), 7.01(s, 1 H), 6.99 (s, 1 H), 5.0 (s, 2 H), 3.03 (t, J = 6.5 Hz, 2 H), 2.23 (s, 3 H), 1.79
#(m, 1 H), 0.83 (d, 6.8 Hz, 6 H); MS (ES+) 645.77
26h	190	25h	J	1 HNMR (DMSO-d6): δ 10.77 (bs, 1 H), 8.95 (bs, 4 H), 8.76 (d, J = 4.3 Hz, 1 H), 8.69 (t, J = 6Hz, 1 H), 8.4 (s, 1 H), 8.29 (m, 2 H), 8.15 (d, J = 7.7 Hz, 1 H), 8.07 (dd, J = 1.7 and 7.7 Hz, 1 H), 7.99 (dt, J = 1.7 & 7.7 Hz, 1 H), 7.76 (m, 4 H), 7.46 (m, 2 H), 7.18 (m, 3 H), 7.05 (s, 1 H), 7.03 (s, 1 H), 5.06 (s, 2 H), 3.10 (t, J = 6.9 and
#6 Hz, 2 H), 1,86 (m, 1 H), 0.89 (d, J = 6.9 Hz, 6 H); MS (ES+) 626.69
26i	191	25i	J	1 HNMR (DMSO-d6): δ 10.73 (bs, 1 H), 9.16 (bs, 2 H), 9.05 (d, J = 1.9 Hz, 1 H), 8.79 (s, 2H), 8.69 (t,J = 6 & Hz, 1 H), 8.64 (dd, J = 1.2 & 5 Hz, 1H), 8.29 (d, J = 1.7 Hz,1 H), 8.24 (d, J = 8 Hz, 1H), 8.05 (m, 2 H), 7.93 (dd, 8 & 1.8 Hz, 1 H), 7.76 (m, 5 H), 7.56 (dd, J = 8 & 4.3 Hz, 1 H), 7.44 (d, J = 7.4 Hz, 2 H), 7.18 (m, 3 H), 7.0 (m,
#2 H), 5.0 (s, 2 H), 3.08 (t, J = 6.5 Hz, 2 H), 1.82 (m, 1 H), 0.88 (d, 6.8 Hz, 6 H);; MS (ES+) 626.44
26j	192	25j	J	1 HNMR (DMSO-d6): δ 0.87 (d, J = 6.9 Hz, 6 H), 1.75 (m, 1 H), 3.08 (t, J = 6.9 and 6.0 Hz, 2 H), 5.03 (s, 2 H), 7.03 (m, 1 H), 7.18 (m, 3 H), 7.45 (f, J = 7.8 and 7 Hz, 2H), 7.76 (s, 4H), 7.87 (d, J = 6 Hz, 2H), 7.94 (dd, J = 8 and 2 Hz, 1 H), 8.05 (dd, J = 8 and 2 Hz, 1 H), 8.08 (d, J = 2 Hz,1 H), 8.29 (d, J = 2 Hz, 1 H), 8.70 (m, 3 H),
#8.84 (s, 2 H), 9.11 (s, 2 H), 10.76 (s, 1H); MS (ES+) 626.76
26k	193	25k	J	1 HNMR (DMSO-d6): δ 10.72 (bs, 1 H), 9.15 (bs, 2 H), 8.81 (bs, 2 H), 8.86 (t, J 6 Hz, 1 H), 8.28 (s, 1 H), 8.03 (m,3 H), 7.91 (d, J = 7.9 Hz, 1 H),7.81 (d, J = 4 Hz, 1 H), 7.74 (s, 4 H), 7.42 (d, J = 7.9 Hz, 1 H), 7.38 (d, J = 7.9 Hz, 1 H), 7.18 (m, 3 H), 7.04 (m, 2 H), 5.04 (bs, 2 H), 3.07 (t, J = 6 Hz, 2 H), 2.57 (s, 3 H), 1.83 (m, 1 H), 0.87 (d,
#J = 6.8 Hz, 6 H); MS (ES+) 673.7
26l	194	25l	J	1 HNMR (DMSO-d6): δ 10.66 (s, 1 H), 9.20 (s, 2 H), 8.86 (s, 2 H), 8.66 (t, J = 6 Hz, 1 H), 8.24 (d, J = 2 Hz, 1 H), 8.15 (dd, J = 7.8 & 2Hz, 1 H), 7.69 (m, 4 H), 7.68 (d, J = Hz, 1 H), 7.63 (d, J = 7.9 Hz, 1 H), 7.43 (d, J = 7.9 Hz, 1 H), 7.37 (d, J = 7.9 Hz, 1 H), 7.24 (m, 3 H), 7.09 (m, 2 H), 6.92 (s, 1 H), 6.40 (s, 1 H), 6.17 (t,
#J = 4 Hz, 1 H), 5.10 (bs, 2 H), 3.74 (s, 3 H), 3.09 (t, J = 6 Hz, 2 H), 1.83 (m, 1 H), 0.88 (d, J = 6.8 Hz, 6 H); MS (ES+) 628.65
26m	195	25m	J	MS (ES+); 618.91
26n	196	25n	J	1 HNMR (DMSO-d6): δ 10.56 (s, 1 H), 9.15 (bs, 2 H), 8.84 (bs, 2 H), 8.64 (t, J =6 Hz, 1 H), 8.19 (d, J = 2 Hz, 1 H), 7.99 (d, J = 7 Hz, 1 H), 7.70 (m, 4 H), 7.46 (s, 1 H), 7.36 (m, 2 H), 7.24 (m, 3 H), 7.05 (s, 1 H), 7.00 (s, 1 H), 6.0 (m, 1 H), 5.18 (d, J = 16 Hz, 1 H), 5.10 (d, J = 11 Hz, 1 H), 5.0 (s, 2 H), 3.47 (d, J =6 Hz, 1 H), 3.03
#(t, J = 6 Hz, 2 H), 1.79 (m, 1 H), 0.83 (d, J = 6.8 Hz, 6 H); MS (ES+) 589.5
26o	197	25o	J	1 HNMR (DMSO-d6): δ 10.84 (s, 1 H), 9.16 (s, 2 H), 8.78 (s, 2 H), 8.69 (t, J = 6 Hz, 1 H), 8.27 (d, J = 2Hz, 1 H), 8.19 (s, 1 H), 8.09 (dd, J = 2 & 7.7 Hz, 1 H), 8.04 (dd, J = 2 & 7.7 Hz, 1 H), 8.01 (d, J = 4 Hz, 1 H), 7.89 (d, J = 3 Hz, 1 H), 7.73 (m, 4 H), 7.44 (dd, J = 3 & 7.8 Hz, 2 H), 7.16 (m, 3 H), 7.30 (s, 1 H), 7.05 (s, 1 H),
#5.03 (bs, 2 H), 3.06 (t, J = 6.5 Hz, 2 H), 1.82 (m, 1 H), 0.86 (d, 6.8 Hz, 6 H); MS (ES+) 632.4
26p	198	25p	J	MS (ES+): 609.3 (M + Na)+
26q	199	25q	J	MS (ES+) 631.5
26r	200	25r	J	1 HNMR (DMSO-d6): δ 10.71 (s, 1 H), 9.16 (s, 2 H), 8.81 (s, 2 H), 8.68 (t, J = 6 Hz, 1 H), 8.25 (s, 1 H), 8.03 (d, J = 7.8 Hz, 1 H), 7.73 (m, 5 H), 7.69 (s, 1 H), 7.55 (d, J = 7.8 Hz, 1 H), 7.39 (d, J = 8.9 Hz, 1 H), 7.26 (m, 3 H), 7.03 (m, 2 H), 5.02 (bs, 2 H), 4.95 (t, J = 5 Hz, 1 H), 3.62 (q, J = 6 & 12.8 Hz, 2 H), 3.07 (t, J = 6 Hz,
#2 H), 2.62 (t, J = 6 Hz, 2 H), 1.83 (m, 1 H), 0.88 (d, J = 6.8 Hz, 6 H); MS (ES+) 617.4
26s	201	25s	J	1 HNMR (DMSO-d6): δ 0.89 (d, J = 6.8 Hz, 6 H), 1.84 (m, 1 H), 1.99 (s, 3 H), 3.09 (t, J = 6 Hz, 2 H), 5.04 (s, 2 H), 5.18 (s, 1 H), 5.28 (s, 1 H), 6.73 (d, J = 16 Hz, 1 H), 7.04 (d, J = 6 Hz, 2 H), 7.23 (m, 5 H), 7.42 (d, J = 9 Hz, 1 H), 7.73 (m, 5 H), 7.85 (s, 1 H), 8.03 (dd, J = 9 and 2 Hz, 1 H), 8.26 (d, J = 2 Hz, 1 H), 8.69(t,J = 6 Hz,
#1 H), 8.87 (bs, 4 H), 10.91 (s, 1 H); MS (ES+)615.4
26t	202	25t	J	1 HNMR (DMSO-d6): δ 10.8 (br s, 1 H), 9.1 and 8.9 (2 br s, 4 H), 8.6 (m, 1 H), 8.2 (s, 1 H), 8.0 (m, 1 H), 7.8-7.6 (m, 6 H), 7.40 (,J = 6.9 Hz, 1 H), 7.3 (m, 4 H), 7.0 (d, 1 H), 5.6 (m, 1 H), 5.2 (m, 1 H), 5.0 (br s, 1 H), 3.1 (t, J = 6.8 Hz, 2 H), 2.2 (s, 3 H), 1.8 (m, 1 H), 0.95 (d, 6 H); MS (ES+) 589.4, MS (ES−) 587.5
26u	203	25u	J	1 HNMR (DMSO-d6): δ 0.88 (d, J = 6.8 Hz, 6 H), 1.84 (m, 1 H), 3.09 (t, J = 6 Hz, 2 H), 4.33 (t, J = 5.5 Hz, 2 H), 5.02 (s, 2 H), 5.01 (t, J = 5.5 Hz, 1 H), 5.95 (m, 1 H), 6.57 (d, J = 11.5 Hz, 1 H), 7.04 (d, J = 6.7 Hz, 2H), 7.25 (m, 3 H), 7.31 (d, J = 7.8 Hz, 1 H), 7.43 (m, 2 H), 7.54 (s, 1 H), 7.74 (s, 4 H), 8.05 (dd, J =7.8 and
#2 Hz, 1 H), 8.23 (d, J = 2 Hz, 1 H), 8.69 (t, J = 6 Hz, 1 H), 8.83 (bs, 2 H), 9.18 (bs, 2 H), 10.66 (s, 1 H); MS (ES+) 605.3
26v	204	25v	J	1 HNMR (DMSO-d6): δ 0.88 (d, J = 6.8 Hz, 6 H), 1.84 (m, 1 H), 2.75 (t, J = 7 Hz, 2 H), 3.09 (t, J = 6 Hz, 2 H), 3.60 (m, 2 H), 4.65 (t, J = 5 Hz, 1 H), 5.05 (s, H), 7.05 (d, J = 7 Hz, 2 H), 7.29 (m, 5 H), 7.42 (d, J = 7.8 Hz, 1 H), 7.66 (dd, J = 7.8 and 2 Hz, 1 H), 7.75 (m, 6 H), 8.03 (dd, J = 7.8 and 2 Hz, 1 H), 8.25 (s, 1 H), 8.68
#(t, J = 6 Hz, 1 H), 8,82 (bs, 2 H), 9.18 (bs, 2 H), 10.68 (s, 1 H); MS (ES+) 619.4
26w	205	25w	J	1 HNMR (DMSO-d6): δ 0.88 (d, J = 6.8 Hz, 6 H), 1.84 (m, 1 H), 3.09 (t, J = 6 Hz, 2 H), 4.41 (s, 1 H), 5.04 (d, J = 11 Hz, 2 H), 7.05 (d, J = 5.5 Hz, 2 H), 7.29 (m, 3 H), 7.34 (d, J = 8 Hz, 1H), 7.40 (d,J = 8 Hz, 1H), 7.65 (dd, J = 8 and 2 Hz, 1 H), 7.75 (s, 4 H), 7.79 (s, 1 H), 8.05 (dd, J = 8 and 2 Hz, 1 H), 8.28 (d, J =2
#Hz, 1 H), 8.71 (t, J = 6 Hz, 1 H), 8,82 (bs, 2 H), 9.17 (bs, 2 H), 10.73 (s, 1 H); MS (ES+) 573.3
26x	206	25x	J	1 HNMR (DMSO-d6): δ 0.86 (d, J = 6.8 Hz, 6 H), 1.47 (s, 3 H), 1.74 (s, 3 H), 1.85 (m, 1 H), 3.06 (t, J = 6 Hz, 2 H), 3.43 (d, J = 8 Hz, 1 H), 5.04 (s, 2 H), 5.11 (m, 1 H), 7.03 (m, 2 H), 7.23 (m, 5 H), 7.52 (m, 2 H), 7.72 (m, 5 H), 8.02 (m, 1 H), 8.21 (s, 1 H), 8.66 (t, J = 6 Hz, 1 H), 8.81 (bs, 2 H), 9.23 (bs, 2 H), 10.52 (s, 1 H); MS (ES+) 617.6
26y	207	25y	J	1 HNMR (DMSO-d6): δ 0.87 (d, J = 6.8 Hz, 6 H), 1.72 (m, 1 H), 3.07 (t, J = 6 Hz, 2 H), 4.36 (d, J = 6 Hz, 2 H), 5.0 (m, 2 H), 5.42 (t, J = 6 Hz, 1 H), 7.03 (d, J = 7 Hz, 2 H), 7.25 (m, 3 H), 7.31 (d, J = 8 Hz, 1 H), 7.39 (d, J = 8 Hz, 1 H), 7.58 (d, J = 8 Hz, 1 H), 7.73 (m, 5 H), 8.02 (dd, J = 10 and 2 Hz, 1 H), 8.23 (s, 1 H),
#8.68 (t, J = 6 Hz, 1 H), 8,76 (bs, 1 H), 9.15 (bs, 2H), 10.71 (s, 1H); MS (ES+) 603.4
26z	208	25z	J	1 HNMR (DMSO-d6): δ 10.6 (s, 1 H), 9.17 (s, 1 H), 8.85 (s, 1 H), 8.68 (d, J =5.9 Hz, 2 H), 8.25 (d, 1.98 Hz, 1 H), 8.05 (d, J = 1.96 Hz, 1 H), 8.03 (d, J = 1.9 1 H), 7.75 (m, 4 H), 7.65 (m, 4 H), 7.41 (d, J = 7.87 Hz, 4 H), 7.25 (m, 1 H) 5.4 (s, 1 H), 5.2 (d, J = 5.9 Hz, 2 H), 4.44 (d, J = 5.9 Hz, 1 H), 3.09 (d, J =6.89 Hz, 2 H), 1.89 (d,
#J = 6.89 Hz, 2 H), 0.88 (d, J = 5.9 Hz, 6 H); MS (ES +) 605.69
26aa	—≡N	25aa	J	Characterized in the next step
26ab	209	25ab	J	1 HNMR (DMSO-d6): δ 10.70 (s, 1 H) 9.15 (bs, 2 H), 8.77 (bs, 2 H), 8.67 (t, J =Hz, 1 H), 8,25 (s, 1 H), 8.04 (d, J = 7 Hz, 1 H), 7.77 (d, J = 2 Hz, 1 H), 7.71 (m 4H), 7.70 (d, J = 2 Hz, 1 H), 7.59 (d, J= 6 Hz, 1 H), 7.46 (d, J = 8 Hz, 1 H), 7.41 (d, J = 8 Hz, 1 H), 7.22 (m, 3 H), 7.05 (s, 1 H), 7.03 (d, J = 2 Hz, 1 H), 5.31 (t,
#J = 6 Hz, 1 H), 5.04 (bs, 2 H), 4.51 (d, J = 6 Hz, 2 H), 3.07 (t, J =6 Hz, 2 H), 1.82 (m, 1 H), 0.86 (d, J = 6.8 Hz, 6 H); MS (ES+) 661.74
26ac	210	25ac	J	1 HNMR (DMSO-d6): δ 0.87 (d, J = 6.8 Hz, 6 H), 1.83 (m, 1 H), 3.07 (t, J = 6 Hz, 2 H), 4.71 (d, J = 5 Hz, 2 H), 5.04 (bs, 2 H), 5.69 (t, J = 5 Hz, 1 H), 7.03 (d, J = 5.8 Hz, 2 H), 7.21 (m, 3H), 7.35 (d, J = 5 Hz, 1 H), 7.38 (d, J = 8 Hz, 1 H), 7.44 (m, d, J = 8 Hz, 1 H), 7.58 (d, J = 5 Hz, 1 H), 7.74 (m, 6 H), 8.03 (d, J =8 Hz,
#1 H), 8.24 (s, 1 H), 8.67 (t, J = 6 Hz, 2 H), 8.79 (bs, 2 H), 9.14 (bs, 2 H), 10.64 (s, 1 H); MS (ES+)661.74
26ad	211	25ad	J	1 HNMR (DMSO-d6): δ 9.65 (s, 1H), 8.71 (t, J = 5.15 Hz, 1 H) 8.39 (d, J =2.57 Hz, 4 H), 8.09 (d, J = 1.79 Hz, 4 H), 8.05 (d, J = 1.79 Hz, 4 H), 7.43 (d, J =7.77 Hz, 2 H), 7.29 (s, 2 H), 7.19 (m, 2 H), 7.08 (m, 2 H), 5.03 (d, J = 2.58 Hz, 2 H) 3.29 (m, 2 H), 3.12 (s, 4 H), 2.49 (m, 2 H), 1.87 (m, 2 H), 0.90 (d, J =6.87 Hz, 6 H); MS (ES+) 765.4
26ae	212	25ae	J	1 HNMR (DMSO-d6): δ 9.1 (bs, 2 H), 8.8 (bs, 2 H), 8.5 (t, J = 6 Hz, 1 H), 8.02 (s; 1 H), 7.68 (s, 1 H), 7.62 (m, 6 H), 7.53 (d, J = 5.8 Hz, 1 H), 7.15 (d, J = 6 Hz, 1 H), ), 7.13 (m, 1 H), 7.01 (s, 1 H), 5.5 (t, J = 5 Hz, 1 H), 4.7 (d, J = 5 Hz, 2 H), 3.01 (m, 2 H), 1.8 (m, 1 H), 0.85 (d, J = 6.8 Hz, 6 H); MS (ES+) 571.2
26af	213	25af	J	1 HNMR (DMSO-d6): δ 10.6 (s, 1 H), 9.17 (s, 1 H), 8.85 (s, 1 H), 8.68 (d, J =5.9 Hz, 2 H), 8.25 (d, 1.98 Hz, 1 H), 7.75 (m, 4 H), 7.65 (m, 4 H), 7.41 (d, J =7.87 Hz, 4 H), 7.25 (m, 4 H), 5.4 (s, 1 H), 5.2 (a, J = 5.9 Hz, 2 H), 4.44 (d, J =5.9 Hz, 1 H), 3.09 (d, J = 6.89 Hz, 2 H), 1.89 (d, J = 6.89 Hz, 2 H), 0.88 (d, J =5.9 Hz, 6 H).
26ag	214	25ag	J	1 HNMR (DMSO-d6): δ 0.90 (d, J = 6.9 Hz, 6 H), 1.41 (s, 9 H), 1.87 (m, 1 H), 3.11 (t, J = 6.9 and 6Hz, 2 H), 5.07 (s, 2 H), 6.37 (t, J = 3.4 Hz, 1 H), 6.51 (s, 1 H), 7.11 (m, 2 H), 7.26 (m, 3 H), 7.33 (d, 7.7 Hz, 1 H), 7.41 (d, J = 8.6 Hz, 1 H), 7.45 (d, J = 1.7 Hz, 1 H), 7.61 (dd, J = 1.7 and 7.7, 1 H), 7.74 (m, 5 H), 8.05 (dd, J = 8.6
#and 1.7 Hz, 1 H), 8.26 (d, J = 1.7 Hz, 1 H), 8.66 (t, J = 5 and 6 Hz, 1 H), 8.77 (bs, 2 H), 9.15 (bs, 2 H), 10.58 (s, 1 H); MS (ES+) 714.78
26ah	215	25ah	J	MS (ES+): 609.6
26ai	216	25ai	J	1 HNMR (DMSO-d6): δ 10.8 (s, 1 H), 6.2 and 8.9 (2 br s, 2 H each, 4H), 8.7 (t, 1 H), 8.2 (s, 1 H), 8.0 (d, J = 6 Hz, 1 H), 7.7 (m, 5 H), 7.6 (d, J = 5 Hz, 1 H), 7.4 (d, J = 5.8 Hz, 1 H), 7.35 (d, J = 6.9 Hz, 1 H), 7.29 (m, 3 H), 7.0 (m, 2 H), 5.0 (m, 2 H), 4.6 (s, 2 H), 3.01 (t, J = 6.8 Hz, 2 H), 1.81 (m, 1 H), 0.95 (d, J =6.8 Hz, 6 H);
#MS (ES+)604.3

[0286]

217
Cpd.			Starting	Method
No.	—R	—R′	From	Used	Analytical Data
27a	218	219	26a	I-2	1 H NMR (DMSO-d6): δ 14.95 (s, 1 H), 8.97 (s, 4 H), 8.5 (t, J = 6 Hz, 1 H), 7.97 (d, J = 2 Hz, 1 H), 7.80 (d, J = 2 Hz, 1 H), 7.73 (dd, J = 7.9 and 2 Hz, 1 H), 7.61 (m, 7 H), 7.18 (t, J = 3.9 Hz, 1 H), 7.05 (d, J = 7.9 Hz, 1 H), 6.93 (d, J = 7.9 Hz, 1 H), 3.01 (t, J = 6.9 and 6.0 Hz, 2 H), 1.81
# (m, 1 H), 0.84 (d, J = 6.9 Hz, 6 H); MS (ES+): 541.17
27b	220	221	26b	I-2	1 H NMR (DMSO-d6): δ 13.24 (s, 1 H), 9.05 (s, 2 H), 8.9 (s, 2 H), 8.49 (t, J = 6 and 5.2 Hz, 1 H), 7.97 (s, 1 H), 7.99 (s, 1 H), 7.87 (s, 1H), 7.75 (d, J = 7.7 Hz, 1 H), 7.65 (m, 1 H), 7.62 (m,6 H), 7.05 (d, J = 7.7 Hz, 1 H), 6.93 (d, J =7.7 Hz, 1 H), 3.01 (t, J = 6.9 and 6.0 Hz, 2 H), 1.81 (m, 1
#H), 0.85 (d, J = 6.9 Hz, 6 H); MS (ES+): 541.42
27c	222	223	26c	I-2	1 H NMR (DMSO-d6): δ 13.28 (s, 1 H), 9.04 (s, 4 H), 8.5 (t, J = 6 Hz, 1 H), 7.97 (s, 1 H), 7.82 (s, 1 H), 7.74 (m, 3 H), 7.62 (m, 5 H), 7.5 (t, J = 7.7 Hz, 2 H), 7.4 (t, J = 7.7, 1 H),7.1 (d, J = 7.7 Hz,2 H), 6.97 (d, J = 7.7. Hz, 1 H), 3.01 (t, J = 6.5 Hz, 2 H), 1.8 (m, 1 H), 0.85 (d, 6.8 Hz, 6 H); MS
#(ES+): 535.48
27d	224	225	26d	I-2	1 H NMR (DMSO-d6): δ 9.03 (s, 2 H), 8.89 (s, 2 H), 8.49 (t, J = 6 Hz, 1 H), 7.99 (s, 1 H), 7.65 (m, 8 H), 7.37 (d, J =3 Hz, 1 H), 7.04 (d, J = 7.7 Hz, 1 H), 6.98 (s, 1 H), 6.82 (d, J = 3 Hz, 1 H), 2.98 (t, J = 6.5 Hz, 2 H), 2.46 (s, 3 H), 1.76 (m, 1 H), 0.81 (d, 6.8 Hz, 6 H); MS (ES+):555.61
27e	226	227	26e	I-2	1 H NMR (DMSO-d6): δ 14.10 (s, 1 H), 9.05 (bs, 2 H), 8.79 (bs, 2 H), 8.47 (t, J = 5.6 Hz, 1 H), 8.3 (s, 1 H), 7.96 (d, J = 2 Hz, 1 H), 7.78 (m, 1 H), 7.63 (m, 7 H), 7.05 (m, 1 H),7.01 (d, J = 7.7 Hz, 1 H), 6.92 (d, J = 7.7 Hz, 1 H), 3.02 (t, J = 4.9 Hz, 2 H), 1.81 (m, 1 H), 0.85 (d, J = 6.3 Hz, 6 H); MS
#(ES+): 525.36
27f	228	229	26f	I-2	1 H NMR (DMSO-d6): δ 9.07 (s, 2 H), 8.86 (s, 2 H), 8.53 (t, J = 5 Hz, 1 H), 8.03 (s, 1H),7.89 (d, J = 1.4 Hz, 1 H), 7.78 (m, 2 H), 7.65 (m, 6 H), 7.1 (m, 2 H), 7.08 (d, J = 7 Hz, 1 H), 6.64 (dd, J = 3.5 and 2 Hz, 1 H), 3.03 (t, J = 6.9 and 6.0 Hz, 2 H), 1.81 (m, 1 H), 0.86 (d, J = 6.9 Hz, 6 H); MS
#(ES+); 525.43
27g	230	231	26g	I-1	1 H NMR (DMSO-d6): δ 13.81 (s, 1 H), 8.74 (bs, 4 H), 8.43 (t, J = 6 Hz, 1 H), 7.92 (d, J = 2 Hz, 1 H), 7.69 (d, J =Hz, 1 H), 7.62 (dd, J = 7.7 & 2 Hz, 1 H), 7.54 (m, 5 H), 7.38 (s, 1 H), 7.15 (s, 1 H), 6.99 (d, J = 7.8 Hz, 1 H), 6.89 (d, J = 6.8 Hz, 1 H), 2.97 (t, J = 6.5 Hz, 2 H), 2.20 (s, 3 H), 1.76
#(m, 1 H), 0.8 (d, 6.8 Hz, 6 H); MS (ES+): 555.67
27h	232	233	26h	I-2	1 H NMR (DMSO-d6): δ 13.95 (bs, 1 H), 8.99 (bs, 2 H), 8.79 (bs, 2 H), 8.65 (d, J = 5 Hz, 1 H), 8.43 (t, J = 6 Hz, 1 H), 8.25 (s, 1 H), 8.09 (d, J = 7.8 Hz, 1 H), 8.00 (d, J =7.8 Hz, 1 H), 7.94 (s, 1 H), 7.87 (t, J = 7.8 Hz, 1 H), 7.58 (m, 5 H), 7.34 (dd, J = 7.8 & 5Hz, 1 H), 7.09 (dd, J = 7.7 Hz, 1 H), 6.90
#(d, J = 7.8 Hz, 1 H), 2.97 (t, J = 5 Hz, 2 H), 1.76 (m, 1 H), 0.81 (d, 6.8 Hz, 6 H); MS (ES+): 268.64 (m/2)
27i	234	235	26i	I-2	1 H NMR (DMSO-d6): δ 9.05 (bs, 2 H), 8.95 (d, J = 2.1 Hz, 1 H), 8.75 (s, 2 H), 8.65 (dd, J = 5 & 1.4 Hz, 1 H), 8.5 (t, J = 5.6 Hz, 1 H), 8.2 (dt, J = 1.8 & 7.7 Hz, 1 H), 7.99 (d, J = 2.1 Hz, 1 H), 7.9 (d, J = 2.1 Hz, 1 H), 7.85 (dd, J =7.7 & 2.2 Hz, 2 H), 7.65 (m, 5 H), 7.55 (dd, J = 7.7 & 4.5 Hz, 1 H),
#7.15 (d, J =7.7 Hz, 1 H), 6.95 (d, J = 7.7 Hz, 1 H), 3.08 (t, J = 5 Hz, 2 H), 1.82 (m, 1 H), 0.9 (d, 6.8 Hz, 6 H); MS (ES+): 268.85 (m/2)
27j	236	237	26j	I-2	1 H NMR(DMSO-d6): δ 14.19 (s, 1 H), 9.06 (bs, 2 H), 8.67 (bs, 2 H), 8.67 (d, J = 6 Hz, 2 H), 8.50 (t, J = 6 Hz, 1 H), 7.97 (m, 2 H), 7.91 (dd, J = 7.7 and 2 Hz, 1 H), 7.80 (d, J = 6 Hz, 2 H), 7.64 (m, 6 H), 7.18 (d, J = 7.7 Hz, 1 H), 6.95 (d, J = 7.7 Hz, 1 H), 3.02 (t, J = 5.0 Hz, 2 H), 1.82 (m, 1 H), 0.80
#(d, J = 6.9 Hz, 6 H); MS (ES+): 536.43
27k	238	239	26k	I-2	1 H NMR (DMSO-d6): δ 9.04 (bs, 2 H), 8.78 (bs, 2 H), 8.55 (t, J = 6 Hz, 1 H), 8.1 (s, 1 H), 7.98 (d, J = 4 Hz, 1 H), 7.95 (s, 1 H), 7.87 (d, J = 7.9 Hz, 1 H), 7.75 (d, J =6.9 Hz, 1 H), 7.66 (m, 4 H), 7.2 (m, 2 H), 7.09 (s, 1 H), 3.03 (t, J = 6 Hz, 2 H), 2.55 (s, 3 H), 1.81 (m, 1 H), 0.85 (d, J = 6.8 Hz, 6 H);
#MS (ES+): 583.59
27l	240	241	26l	I-2	1 H NMR (DMSO-d6): δ 9.1 (s, 2 H), 8.84 (s, 2 H), 8.56 (t, J = 6 Hz, 1 H), 8.08 (bs, 1 H), 7.67 (m, J = 7 H), 7.58 (d, J =7.9 Hz, 1 H),7.11 (m, 2H), 6.91 (bs, 1 H),6.31 (bs, 1 H), 6.11 (t, J = 3 Hz, 1 H), 3.74(s, 3 H), 3.05 (t, J = 6 Hz, 2 H), 1.83 (m, 1 H), 0.88 (d, J = 6.8 Hz, 6 H); MS (ES+): 538.64
27m	242	243	26m	I-2	1 H NMR (DMSO-d6): δ 9.04 (s, 2 H), 8.94 (s, 2 H), 8.46 (t, J = 6 Hz, 1 H), 7.96 (s, 1 H), 7.63 (m, 6 H), 6.94 (s, 1 H), 6.83 (d, J = 7.7 Hz, 1 H), 6.7 (d, J = 2, 1 H), 6.62 (dd, J = 7.7 and 2 Hz, 1 H), 3.28 (m, 4 H), 3.02 (t, J = 6.5 Hz, 2 H), 1.98 (m, 4 H), 1.82 (m,1H), 0.82 (d, 6.8 Hz, 6 H); MS (ES+): 528.76
27n	244	245	26n	I-2	1 H NMR (DMSO-d6): δ 13.96 (s, 1 H), 9.02 (s, 2 H), 8.85 (s, 2 H), 8.46 (t, J = 6 Hz, I H), 7.91 (s, 1 H), 7.58 (m, 4 H), 7.39 (s, 1 H), 7.25 (d, J = 7.8 Hz, 1 H), 6.92 (d, J =7.7, 1 H), 6.87 (d, J = 7.7 Hz, 1 H), 6.01 (m, 1 H), 5.17 (d, J = 16.7 Hz, 1 H), 5.08 (d, J = 10 Hz, 1 H), 3.45 (d, J = 6 Hz, 2H),
#2.99 (t, J = 6 Hz, 2 H), 1.78 (m, 1 H), 0.83 (d, J =6.8 Hz, 6 H); MS (ES+): 499.3
27o	246	247	26o	I-2	1 H NMR (DMSO-d6): δ 14.08 (bs, 1 H), 9.06 (s, 2 H), 8.79 (s, 2 H), 8.51 (t, J = 6 Hz, 1 H), 8.11 (d, J = 2 Hz, 1 H), 8.01 (m, 3 H), 7.85 (d, J = 3 Hz, 1 H), 7.63 (m, 6 H), 7.17 (d, J = 7.8 Hz, 1 H), 6.97 (d, J = 7.8 Hz, 1 H), 3.02 (t, J = 6.5 Hz, 2 H), 1.81 (m, 1 H), 0.86 (d, 6.8 Hz, 6 H); MS (ES+): 542.2)
27p	248	249	26p	I-2	1 H NMR (DMSO-d6): δ 9.1 and 9.2 (2 br s, 4 H, NH proton), 8.6 (m, 1 H), 8.3 (m, 1 H), 8.0-7.6 (m, 8 H, aromatic proton), 7.3 (m, 2 H), 3.1 (t, 2 H), 2.2 (s, 3 H), 1.8 (m, 1 H), 0.9 (2s, 6 H); JR (KBr Pellets) 2957, 1676, 1480, 1324, 844 cm−1. MS (ES+): 497
27q	250	251	26q	I-2	1 H NMR (DMSO-d6): δ 9.06 (s, 2 H), 8.77 (s, 2 H), 8.53 (t, J = 6 Hz, 1 H), 8.03 (m, 1 H), 7.64 (m, 6 H), 7.46 (d, J =6.9 Hz, 1 H), 7.05 (s, 2 H), 6.96 (s, 1 H), 5.52 (s, 1 H), 3.02 (t, J = 6.8 Hz, 2 H), 1.81 (m, 1 H), 1.48 (s, 6 H),0.85 (d, J = 6.8 Hz, 6 H); MS (ES−): 539.4
27r	252	253	26r	I-2	1 H NMR (DMSO-d6): δ 9.06 (s, 2 H), 8.78 (s, 2 H), 8.52 (t, J = 6 Hz, 1 H), 8.01 (d, J = 6.8 Hz, 1 H), 7.62 (m, 7 H), 7.46 (d, J = 6.8 Hz, 1 H), 7.0 (m, 2 H), 4.94 (t, J = 6 Hz, 1 H), 3.60 (q, J = 6 & 12.8 Hz,2 H), 3.01 (t, J = 6 Hz, 2 H), 2.58 (t, J = 6 Hz, 2 H), 1.82 (m, 1 H), 0.85 (d, J = 6.8 Hz, 6 H); MS
#(ES−): 525.4
27s	254	255	26s	I-2	1 H NMR (DMSO-d6): δ 9.01 (s, 2 H), 8.88 (s, 2 H), 8.5 (t, J = 6 Hz, 1 H), 8.07 (m, 1 H), 7.73 (m, 1 H), 7.63 (m, 7 H),7.11 (d, J = 17 Hz, 1 H),7.01 (d,J = 17 Hz, 1 H),6.97 (m, 1 H), 6.69 (d, J = 17 Hz, 1 H), 5.24 (s, 1H), 5.14 (s, 1H), 3.03 (t, J = 6.9 and 6.0 Hz, 2 H), 1.92 (s, 3 H), 1.81 (m, 1 H), 0.84 (d, J = 6.9
#Hz,6 H); MS (ES+):525.4
27t	256	257	26t	I-2	1 H NMR (DMSO-d6): δ 9.08 (s, 2 H), 8.82 (s, 2 H), 8.53 (t, J = 6 Hz, 1 H), 8.04 (m, 1 H), 7.67 (m, 7 H), 7.04 (m, 2 H), 5.55 (s, 1H), 5.20 (s, 1H), 3.04 (t, J = 6.9 and 6.0 Hz, 2 H), 2.19 (s, 3 H), 1.81 (m, 1 H), 0.87 (d, J = 6.9 Hz, 6 H); MS (ES+): 499.4
27u	258	259	26u	I-2	1 H NMR (DMSO-d6): δ 9.11 (s, 2 H), 8.86 (s, 2 H), 8.57 (t, J = 6 Hz, 1 H), 8.13 (m, 1 H), 7.53 (m, 2 H), 7.74 (m, 6 H), 7.37 (d, J = 7 Hz, 1 H), 7.17 (m, 2 H), 6.54 (d, J = 12 Hz, 1 H), 5.91 (m, 1 H), 4.99 (m, 1 H), 4.31 (m, 2 H), 3.06 (t, J = 6.9 and 6.0 Hz, 2 H), 1.83 (m, 1 H), 0.87 (d, J =6.9 Hz, 6 H);MS (ES+): 515.4
27v	260	261	26v	I-2	1 H NMR (DMSO-d6): δ 9.08 (s, 2 H), 8.82 (s, 2 H), 8.54 (t, J = 6 Hz, 1 H), 8.05 (m, 1 H), 7.63 (m, 8 H), 7.06 (m, 2 H), 5.52 (s, 1 H), 5.2 (s, 1 H), 4.63 (t, J = 5 Hz, 1 H), 3.56 (m, 2 H), 3.05 (t, J = 6.9 and 6.0 Hz, 2 H), 2.71 (t, J = 7 Hz, 2 H), 1.82 (m, 1 H), 0.87 (d, J = 6.9 Hz, 6 H); MS (ES+): 529.4
27w	262	263	26w	I-2	1 H NMR (DMSO-d6): δ 9.08 (s, 2 H), 8.86 (s, 2 H), 8.54 (t, J = 6 Hz, 1 H), 8.03 (m, 1 H), 7.62 (m, 7 H), 7.08 (d, J =7.5 Hz, 1 H), 6.99 (m, 1 H), 4.32 (s, 1 H), 3.03 (t, J =6.9 and 6.0 Hz, 2 H), 2.71 (t, J = 7 Hz, 2 H), 1.82 (m, 1 H), 0.87 (d, J = 6.9 Hz, 6 H); MS (ES+): 483.3
27x	264	265	26x	I-2	1 H NMR (DMSO-d6): δ 13.8 (s, 1 H), 9.04 (s, 2 H), 8.96 (s, 2 H), 8.47 (t, J = 6 Hz, 1 H), 7.93 (s, 1 H), 7.61 (m, 6 H), 7.42 (m, 1 H), 6.91 (m, 2 H), 6.07 (dd, J = 17 and 9 Hz, 1 H), 5.35 (m, 1 H), 5.09 (dd, J = 17 and 11 Hz, 1 H), 3.38 (d, J = 6.5 Hz, 1 H), 3.0 (t, J = 7 Hz, 2 H), 1.78 (m, 1 H), 1.72 (s, 3 H), 1.41 (s, 3 H),
#0.84 (d, J = 6.9 Hz, 6 H); MS (ES+): 527.5
27y	266	267	26y	I-2	1 H NMR (DMSO-d6): δ 8.99 (s, 2 H), 8.86 (s, 2 H), 8.52 (t, J = 6 Hz, 1 H), 8.03 (m, 1 H), 7.63 (m, 6 H), 7.50 (d, J =7 Hz, 1 H), 7.07 (d, J = 7 Hz, 1 H), 7.12 (m, 1 H), 5.40 (t, J = 6 Hz, 1 H), 4.33 (d, J = 6.0 Hz, 2H), 3.01 (t, J = 7 Hz, 2 H), 1.80 (m, 1 H), 0.84 (d, J = 6.9 Hz, 6 H); MS (ES+): 513.4
27z	268	269	26z	I-2	1 H NMR (DMSO-d6): δ 9.50 (bs, 1 H), 8.77 (bs, 2 H), 8.49 (t, J = 6 Hz, 1 H), 7.98 (m, 1 H), 7.63 (m, 6 H), 7.55 (d, J = 6.9 Hz, 1 H), 7.01 (d, J = 7.9 Hz, 1 H), 6.99 (m, 1 H), 5.55 (s, 1 H), 5.38 (s, 1 H), 5.13 (t, J = 5 Hz, 1 H), 4.39 (d, J = 5 Hz, 2 H), 3.02 (t, J = 6.9 and 6.0 Hz, 2 H), 1.81 (m, 1 H), 0.86 (d,
#J =6.9 Hz, 6 H); MS (ES+): 515.4
27aa	270	271	26aa	I-2	1 H NMR (DMSO-d6): δ 9.08 (s, 2 H), 8.73 (s, 2 H), 8.53 (t, J = 6 Hz, 1 H), 8.06 (s, 1 H), 8.02 (bs, 1 H), 7.94 (d, J =7.8 Hz, 1 H), 7.62 (m, 6 H), 7.24 (d, J = 7.8 Hz, 1 H), 6.95 (d, J = 7.8 Hz, 1 H), 3.03 (t, J = 6 Hz, 2 H), 1.82 (m, 1 H), 0.87 (d, J = 6.8 Hz, 6 H); MS (ES+): 484.3
27ab	272	273	26ab	I-2	1 H NMR (DMSO-d6): δ 9.05 (bs, 2 H), 8.81 (bs, 2 H), 8.49 (t, J =6 Hz, 1 H), 8.02 (s, 1 H), 7.68 (s, 1 H), 7.62 (m, 6H), 7.53 (d, J = 6 Hz, 1 H),7.21 (d, J = 6 Hz, 1 H), 7.13 (d, J = 7 Hz, 1 H), 7.01 (s, 1 H), 5.25 (t, J = 5 Hz, 1 H), 4.51 (d, J = 5 Hz, 2 H), 3.01 (t, J = 6 Hz, 2 H), 1.81 (m, 1 H), 0.85 (d,
#J = 6.8 Hz, 6 H); MS (ES+): 571.64
27ac	274	275	26ac	I-2	1 H NMR (DMSO-d6): δ 9.05 (bs, 2 H), 8.78 (s, 2 H), 8.52 (t, J = 6 Hz, 1 H), 8.02 (bs, 1 H), 7.65 (m, 6 H), 7.53 (d, J =1 H), 7.54 (d, J = 5 Hz, 1 H), 7.26 (d, J = 5 Hz, 1 H), 7.10 (m, 1 H), 6.99 (m, 1 H), 5.64 (t, J = 5 Hz, 1 H), 4.71 (d, J = 5 Hz, 2H), 3.07 (t, J = 6.9 and 6.0 Hz, 2 H), 1.73 (m, 1 H), 0.84
#(d, J = 6.9 Hz, 6 H); MS (ES+): 571.56
27ad	276	277	26ad	I-2	MS (ES+): 585.4
27ae	278	279	26ae	I-2	1 H NMR(DMSO-d6): δ 14.11 (bs, 1 H), 9.05 (bs, 2 H), 8.75 (bs, 2 H), 8.5 (m, 1 H), 8.0 (s, 1 H), 7.8-7.6 (m, 8 H), 7.49 (d, J = 3 Hz, 1 H),7.1 (d, J = 6.9 Hz, 1 H), 7.0 (m, 1 H), 5.5 (m,1 H), 4.7 (m, 2 H), 3.09 (m, 2 H), 1.74 (m, 1 H) 0.86 (d, J = 6.9 Hz, 6 H); MS (ES+) 571.2
27af	280	281	26af	I-2	1 H NMR (DMSO-d6): δ 14.11 (bs, 1 H), 9.05 (bs, 2 H), 8.75 (bs, 2 H), 8.49 (t, J = 6 Hz, 1 H), 7.97 (s, 1 H), 7.67 (d, J =3 Hz, 1 H), 7.61 (m, 7 H), 7.54 (d, J = 3 Hz, 1 H), 7.06 (d, J = 6.9 Hz, 1 H), 6.89 (d, J = 6.9 Hz, 1 H), 5.23 (t, J = 5 Hz, 1 H), 5.42 (d, J = 5 Hz, 2 H), 3.09 (t, J = 26.9 and 6.0
#Hz, 2H), 1.74 (m, 1 H) 0.86 (d, J = 6.9 Hz, 6 H); MS (ES+): 571.3
27ag	282	283	26ag	I-2	1 H NMR (DMSO-d6): δ 11.45 (s, 1 H), 9.08 (bs, 2 H), 8.88 (bs, 2 H), 8.75 (t, J = 6 Hz, 1 H), 8.04 (bs, 1 H), 7.88 (m, 1 H), 7.7 (m, 7 H), 7.03 (m, 2 H), 6.9 (m, 1 H), 6.62 (m, 1 H), 6.17 (m, 1 H), 3.07 (t, J = 6.9 and 6.0 Hz, 2 H), 1.84 (m, 1 H), 0.86 (d, J = 6.9 Hz, 6 H); MS (ES+): 524.65
27ah	284	285	26ah	I-2	1 H NMR (DMSO-d6): δ 13.83 (s, 1 H), 8.9 (bs, 4 H), 8.47 (t, J = 6 Hz, 1 H), 7.95 (s, 1 H), 5.3 (s, 1 H), 7.61 (m, 6 H), 7.4 (m, 1 H), 6.95 (d, J = 7.7 Hz, 1 H), 6.85 (d, J = 7.7 Hz, 1 H), 6.64 (d, J = 9 Hz, 1 H), 6.22 (s, 1 H), 4.6 (t, J =5.1 Hz, 1 H), 3.51 (d, J = 5.6 Hz, 2 H), 3.01 (t, J = 7 Hz, 2 H),
#1.8 (m, 1 H), 0.85 (d, J = 6.9 Hz, 6 H); MS (ES+): 519.52
27ai	286	287	26ai	I-2	MS (ES+) 514.25
27aj	288	289	26n	G	1 H NMR (DMSO-d6): δ 9.05 (s, 2 H), 8.67 (s, 2 H), 8.47 (t, J = 6 and 5 Hz, 1 H), 7.95 (m, 1 H), 7.95 (m, 1 H), 7.63 (m, 5H), 7.40 (s, 1 H), 7.38 (d, J = 7.7 Hz, 1 H), 6.92 (m, 2 H), 3.02 (t, J = 6.8 Hz, 2 H), 2.64 (m, 2 H), 1.80 (m, 1 H), 1.66 (m, 2 H), 0.96 (t, J = 8 and 6.5 Hz, 3 H), 0.85 (d, J = 6.8 Hz, 6 H); MS
#(ES−) 499.31
27ak	290	291	32f	G	1 H NMR (DMSO-d6): δ 14.3 (bs, 1 H), 9.05 (bs, 2 H), 8.75 (bs, 2 H), 8.5 (m, 1 H), 8.0 (s, 1 H), 7.8-7.6 (m, 8 H), 7.49 (d, J = 3 Hz, 1 H), 7.1 (d, J = 6.9 Hz, 1 H), 7.0 (m, 1 H), 5.5 (m,1 H), 4.7 (m, 2 H), 3.09 (m, 2 H), 1.74 (m, 1 H), 0.86 (d, J = 6.9 Hz, 6 H); MS (ES+) 487.2
27al	292	293	26ai	G	MS (ES+) 488.3 (100%: M+1)
27am	294	295	26u	G	1 H NMR (DMSO-d6): δ 13.9 (bs, 1 H), 9.05 (2 bs, 4 H), 8.5 (m, 1 H), 7.9 (s, 1 H), 7.7-7.5 (m, 8 H), 7.3 (d, J = 3 Hz, 1 H), 6.9 (m, 2 H), 4.6 (m, 1H), 3.5 (m, 2 H), 3.09 (m, 2 H), 2.6 (m, 2 H), 1.8 (m, 1 H) 0.85 (d, J = 6.9 Hz, 6 H);□MS (ES+) 517.3
32a	296	297	31a	I-2	1 H NMR (DMSO-d6): δ 9.84 (bs, 1 H), 9.07 (bs, 2 H), 8.87 (bs, 2 H), 8.51 (t, J = 6 and 5 Hz, 1 H), 8.13 (m, 1 H), 8.03 (m, 2 H), 7.65 (m, 5 H), 7.20 (d, J = 7.7 Hz, 1 H), 6.94 (d, J = 7.7.Hz, 1 H), 3.04 (t, J = 6.8 Hz, 2 H), 2.66 (s, 3 H), 1.83 (m, 1 H), 0.86 (d, J = 6.8 Hz, 6 H); MS (ES−) 499.4, (ES+) 501.4
32b	298	299	31b	I-2	Characterized in the next step
32c	300	301	31c	I-2	1 H NMR (DMSO-d6): δ 14.24 (s, 1 H), 9.29 (bs, 2 H), 9.01 (bs, 2 H), 8.73 (t, J = 6 Hz, 1 H), 8.2 (d, J = 2 Hz, 1 H), 7.85 (m, 5 H), 7.74 (d, 2 Hz, 1 H), 7.4 (d, J = 8 Hz, 1 H), 7.22 (d, J = 7.4 Hz, 1 H), 7.13 (d, J = 7.5, 1 H), 6.73 (t, J = 6.8 Hz, 1 H), 5.59 (d, J = 6.8 Hz, 2 H), 3.25 (t, J =6.8 Hz,
#2 H), 2.04 (m, 1 H), 1.08 (d, J = 6.8 Hz, 6 H); MS (ES−) 495.1, (ES+) 497.2
32d	302	303	31d	I-2	MS (ES−) 553.3
32e	304	305	31e	I-2	1 H NMR (DMSO-d6): δ 13.642 (bs, 1 H), 9.06 (s, 2 H), 8.89 (s, 2 H), 8.50 (t, J = 6 and 5 Hz, 1 H), 7.98 (s, 1 H), 7.62 (m, 7 H), 7.43 (s, 1 H), 7.33 (m, 4 H), 6.95 (m, 2 H), 4.04 (s, 2 H), 3.02 (t, J = 6.8 Hz, 2 H), 1.80 (m, 1 H), 0.86 (d, J = 6.8 Hz, 6 H); MS (ES−) 547.4
32f	306	307	31f	I-2	1 H NMR (DMSO-d6): δ 0.85 (d, J = 6.9 Hz, 6 H), 1.81 (m, I H), 3.03 (t, J = 7 Hz, 2 H), 5.35 (d, J = 11 Hz, 1 H), 5.94 (d, J = 17 Hz, 1 H), 6.84 (dd, J = 17 and 11 Hz, 2 H), 7.0 (m, 2 H), 7.64 (m, 8 H), 8.01 (s, 1 H), 8.54 (t, J = 6 Hz, 1 H), 8.77 (s, 2 H), 9.06 (s, 2 H); MS (ES+) :485.57
32g	308	309	31g	I-2	MS (ES+) 596..2
32h	310	311	31h	I-2	1 H NMR (DMSO-d6): δ 14.2 (bs, 1 H), 9.1 (bs, 4 H), 8.6 (m, 1 H), 8.15 (s, 1 H), 7.9-7.6 (m, 8 H), 7.2 (m, 2 H), 6.7 (s, 1 H), 5.3 (br s, 1 H), 4.6 (m, 2 H), 3.1 (m, 2 H), 1.9 (m, 1 H), 0.9 (d, J = 6.7 Hz, 6 H); MS (ES+) 555.1
32i	312	313	31i	I-2	1 H NMR (DMSO-d6): δ 13.84 (bs, I H), 9.01 (bs, 2 H), 8.80 (bs, 2 H), 8.46 (t, J = 6 and 5 Hz, 1 H), 8.03 (s, 1 H), 7.95 (s, 1 H), 7.77 (s, 1 H), 7.67 (m, 2 H), 7.61 (m, 5 H), 7.02 (d, J = 7.7 Hz, 1 H), 6.94 (m, 1 H), 5.13 (t, J = 5 Hz, 1 H), 4.47 (m, 2 H), 2.97 (t, J = 6.8 Hz, 2 H), 1.78 (m, 1 H), 0.80 (d,
#J = 6.8 Hz, 6 H); MS (ES−) 553.3, (ES+) 555.3
40	314	315	39	I-2	MS (ES+) 524.3
44	316	317	43	I-2	1 H NMR (DMSO-d6): δ 13.82 (s, 1 H), 9.20 (bs, 1 H), 9.10 (bs, 1 H), 8.51 (t, J = 6 Hz, 1 H), 7.97 (s, 1 H), 7.73-7.45 (m, 5 H), 7.43-7.39 (m, 2 H), 7.20 (t, J = 8 Hz, 1 H), 7.10 (m, 6 H), 6.96 (d, J = 8 Hz, 1 H), 3.0 (t, J = 6 Hz, 2 H), 1.80 (m, 1 H), 0.68 (d, J = 6.8 Hz, 6 H); MS (ES+) 551.30
46	318	319	45	I-2	1 H NMR (DMSO-d6): δ 9.21 (2 bs, 2 H each, 4 H), 8.61 (m, 1 H), 8.1 (s, 1H), 7.8-7.4 (m, 10 H), 7.3 (s, 1 H), 7.2 (d, J = 7 Hz, 1 H),7.1 (m, 2H), 5.2 (s, 2H), 3.1 (m, 2H), 1.8 (m, 1 H), 0.91 (d, J = 6.8 Hz, 6 H); MS (ES+) 565.27
51	—OCH3	320	50	I-2	1 H NMR (CF3CO2D): δ 8.43 (s, 1 H), 8.01 (d, J = 7.5 Hz, 1 H), 7.67 (q, J = 24 and 8.4 Hz, 4 H), 7.56 (d, J = 7.7 Hz, 1 H), 7.38 (s, 1 H), 7.23 (s, 2 H), 3.98 (s, 3 H), 3.43 (d, J =7 Hz, 2 H), 2.01 (m, 1 H), 1.01 (d, J = 6.8 Hz, 6 H); MS (ES−) 487., (ES+) 489.3
53	321	322	52	I-2	1 H NMR (DMSO-d6): δ 14.00 (bs, 1 H), 8.52 (t, J = 6 and 5 Hz, 1 H), 7.98 (s, 1 H), 7.63 (m, 8 H), 7.07 (d, J = 7.7 Hz, 1 H), 6.96 (d, J = 7.7 Hz, 1 H), 3.83 (s, 2 H), 3.02 (t, J =6.8 Hz, 2 H), 1.81 (m, 1 H), 0.86 (d, J = 6.8 Hz, 6 H); MS (ES−) 568.1
70a	323	324	68a	I-2, S	1 H NMR (DMSO-d6): δ 13.84 (br s, 1 H), 9.05 (s, 2 H), 8.94 (s, 2 H), 8.48 (t, J = 5.7 Hz, 1 H), 7.97 (d, J = 1.9 Hz, 1 H), 7.70 (m, 7 H), 7.00 (d, J = 7.9 Hz, 1 H), 6.92 (d, J = 7.9 Hz, 1 H), 6.84 (dd, J = 10.9 and 17.7 Hz, 1 H), 5.93 (d, J = 17.7 Hz, 1 H), 5.34 (d, J = 10.9 Hz, 1 H), 3.19 (m, 2 H),
#1.46 (qui, J = 7.0 Hz, 2 H), 1.29 (sex, J =7.0 Hz, 2 H), 0.87 (t, J = 7.3 Hz, 3 H); MS (ES+): 485.2
70b	325	326	68b	I-2, S	1 H NMR (DMSO-d6): δ 12.71 (br s, 1 H), 9.12 (s, 2 H), 8.93 (s, 2 H), 8.20 (m, 2 H), 7.86 (m, 1 H), 7.70 (m, 6 H), 7.20 (m, 2 H), 6.87 (dd, J = 10.9 and 17.7 Hz, 1 H), 5.99 (d, J = 17.7 Hz, 1 H), 5.40 (d, J = 10.9 Hz, 1 H), 3.97 (m, 1 H), 1.50-1.20 (m, 8 H) 0.86 (t, J = 7.2 Hz, 6 H); MS (ES+): 527.3
70c	327	328	68c	I-2, S	1 H NMR (DMSO-d6): δ 12.84 (br s, 1 H), 9.08 (m, 3 H), 8.36 (d, J = 7.7 Hz, 1 H), 8.18 (s, 1 H), 7.83 (m, 1 H), 7.67 (m, 6 H), 7.15 (m, 3 H), 6.86 (dd, J = 10.9 and 17.7 Hz, 1 H), 5.98 (d, J = 17.7 Hz, 1 H), 5.39 (d, J = 10.9 Hz, 1 H), 3.74 (m, 1 H), 1.84-1.55 (m, 5 H), 1.38-1.04 (m, 5 H); MS (ES+): 511.3
70d	329	330	68d	I-2, S	1 H NMR (DMSO-d6): δ 9.11 (s, 2 H), 8.89 (s, 2 H), 8.81 (t, J = 5.7 Hz, 1 H), 8.21 (s, 1 H), 7.85 (m, 1 H), 7.68 (m, 7 H), 7.17 (m, 3 H), 6.87 (dd, J = 10.9 and 17.7 Hz, 1 H), 5.99 (d, J = 17.7 Hz, 1 H), 5.88 (m, 1 H), 5.39 (d, J = 10.9 Hz, 1 H), 5.12 (m, 2 H), 3.88 (t, J = 5.0 Hz, 1 H); MS (ES+): 469.2
70e	331	332	68e	I-2, S	1 H NMR (DMSO-d6): δ 9.11 (s, 2 H), 9.01 (s, 2 H), 8.38 (d, J = 7.5 Hz, 1 H), 8.18 (s, 1 H), 7.83 (m, 1 H), 7.67 (m, 6 H), 7.16 (m, 3 H), 6.86 (dd, J = 10.9 and 17.7 Hz, 1 H), 5.98 (d, J 17.7 Hz, 1 H), 5.39 (d, J 10.9 Hz, 1 H), 4.09 (m, 1 H), 1.15 (d, J = 6.6 Hz, 6 H); MS (ES+): 471.3
70f	333	334	68f	I-2, S	1 H NMR (DMSO-d6): δ 9.11 (s, 2 H), 9.05 (s, 2 H), 8.31 (d, J = 8.1 Hz, 1 H), 8.20 (s, 1 H), 7.85 (d, J = 7.7 Hz, 1 H), 7.69 (m, 6 H), 7.17 (m, 3 H), 6.86 (dd, J = 10.9 and 17.7 Hz, 1 H), 5.98 (d, J = 17.7 Hz, 1 H), 5.39 (d, J =10.9 Hz, 1 H),3.91 (m, 1 H), 1.50 (m,2 H), 1.12 (d,J =6.6 Hz, 3 H). 0.85
#(t, J = 7.3 Hz, 3 H); MS (ES+): 485.3
70g	335	336	68g	I-2, S	1 H NMR (DMSO-d6): δ 12.82 (br s, 1 H), 9.25 (m, 1 H), 9.12 (s, 2 H), 8.91 (s, 2 H), 8.23 (s, 1 H), 7.87 (m, 1 H), 7.68 (m, 7 H), 7.18 (m, 3 H), 6.87 (dd, J = 10.9 and 17.7 Hz, 1 H), 5.99 (d, J = 17.7 Hz, 1 H), 5.40 (d, J = 10.9 Hz, 1 H), 4.07 (m, 2 H); MS (ES+): 511.2
70h	337	338	68h	I-2, S	1 H NMR (DMSO-d6): δ 10.34 (s, 1 H), 9.05 (m, 4 H) 8.18 (s, 1 H), 7.71 (m, 11 H), 7.34 (t, J = 7.8 Hz, 2 H), 7.09 (m, 3 H), 6.86 (ad, J = 10.9 and 17.7 Hz, 1 H), 5.98 (d, J =17.7 Hz, 1 H), 5.39 (d, J = 10.9 Hz, 1 H); MS (ES+): 505.3
70i	339	340	68i	I-2, S	1 H NMR (DMSO-d6): δ 12.64 (br s, 1 H), 9.09 (m, 4 H), 8.56 (m, 1 H), 8.09 (s, 1 H), 7.66 (m, 9 H), 7.08 (m, 3 H), 6.86 (dd, J = 10.9 and 17.7 Hz, 1 H), 5.96 (d, J = 17.7 Hz, 1 H), 5.37 (d, J = 10.9 Hz, 1 H), 4.40 (m, 2 H) 3.39 (m, 2 H), 3.22 (m, 2 H), 1.48 (m, 4 H); MS (ES+): 501.3 (100%: Me+1)
70j	341	342	68j	I-2, S	1 H NMR (DMSO-d6): δ 9.08 (m, 4 H), 8.69 (t, J = 6.0 Hz, 1 H), 8.16 (s, 1 H), 7.69 (m, 5 H), 7.13 (d, J = 7.7 Hz, 2 H), 7.09 (m, 3 H), 6.86 (dd, J = 10.9 and 17.7 Hz, 1 H), 5.97 (d, J = 17.7 Hz, 1 H), 5.38 (d, J = 10.9 Hz, 1 H), 3.11 (t, J = 6.0 Hz, 2 H), 1.01 (m, 1 H), 0.41 (m, 2H), 0.21 (m, 2 H);
#MS (ES+): 483.3
70k	343	344	68k	I-2, S	1 H NMR (DMSO-d6): δ 9.11 (s, 2 H), 8.97 (s, 2 H), 8.54 (m, 1 H), 8.12 (s, 1 H), 7.68 (m, 7 H), 7.17 (m, 4 H), 6.86 (dd, J = 10.9 and 17.7 Hz, 1 H), 5.97 (d, J = 17.7 Hz, 1 H), 5.38 (d, J = 10.9 Hz, 1 H), 2.75 (d, J = 4.3 Hz, 1 H); MS (ES+): 443.26
70l	345	346	68l	I-2, S	1 H NMR (DMSO-d6): δ 9.07 (s, 2 H), 8.92 (s, 2 H), 8.53 (t, J = 5.5 Hz, 1 H), 8.02 (s, 1 H), 7.62 (m, 7 H), 7.01 (m, 2 H), 6.85 (dd, J = 10.9 and 17.7 Hz, 1 H), 5.95 (d, J =17.7 Hz, 1 H), 5.36 (d, J = 10.9 Hz, 1 H), 3.24 (qui, J =6.7 Hz, 2 H), 1.08 (t, J = 7.2 Hz, 3 H); MS (ES+): 457.2
70m	347	348	68m	I-2, S	1 H NMR (DMSO-d6): δ 12.53 (br s, 1 H), 9.10 (m, 3 H), 8.38 (d, J = 7.9 Hz, 1 H), 8.11 (s, 1 H), 7.68 (m, 7 H), 7.12 (m, 3 H), 6.86 (dd, J = 10.9 and 17.7 Hz, 1 H), 5.96 (d, J = 17.7 Hz, 1 H), 5.37 (d, J = 10.9 Hz, 1 H), 3.94 (m, 1 H), 1.88-1.33 (m, 12 H); MS (ES+): 525.3
70n	349	350	68n	I-2, S	1 H NMR (DMSO-d6): δ 9.09 (m, 4 H), 8.59 (t, J = 5.2 Hz, 1 H), 8.17 (s, 1 H), 7.70 (m, 7 H), 7.16 (m, 4 H), 6.87 (dd, J = 10.9 and 17.7 Hz, 1 H), 5.98 (d, J = 17.7 Hz, 1 H), 5.39 (d, J = 10.9 Hz, 1 H), 3.20 (q, J = 6.7 Hz, 2 H), 1.52 (sex, J = 7.2 Hz, 2 H),
#0.87 (t, J = 7.3 Hz, 3 H); MS (ES+): 471.3
70o	351	352	68o	I-2, S	1 H NMR (DMSO-d6): δ 12.97 (hr s, 1 H), 9.08 (s, 2 H), 8.99 (s, 2 H), 8.53 (t, J = 5.1 Hz, 1 H), 8.06 (s, 1 H), 7.64 (m, 7 H), 7.06 (m, 2 H), 6.85 (dd, J = 10.9 and 17.7 Hz, 1 H), 5.96 (d, J = 17.7 Hz, 1 H), 5.36 (d, J = 10.9 Hz, 1 H), 3.20 (q, J = 6.5 Hz, 2 H), 1.49 (qui, J = 6.6 Hz, 2 H), 1.27 (m,
#4 H), 0.86 (t, J = 6.6 Hz, 3 H); MS (ES+): 499.3
70p	353	354	68p	I-2, S	1 H NMR (DMSO-d6): δ 9.10 (s, 2 H), 8.91 (s, 2 H), 8.55 (t, J = 5.5 Hz, 1 H), 8.13 (s, 1 H), 7.68 (m, 7 H), 7.12 (m, 2 H), 6.86 (dd, J = 10.9 and 17.7 Hz, 1 H), 5.98 (d, J =17.7 Hz, 1 H), 5.38 (d, J = 10.9 Hz, 1 H), 3.10 (m, 2 H), 1.62 (m, 1 H), 1.39 (m, 1 H), 1.10 (m, 1 H), 0.86 (m, 6 H); MS (ES+): 499.3
70q	355	356	68q	I-2, S	1 H NMR (DMSO-d6): δ 9.06 (s, 2 H), 8.82 (s, 2 H), 8.11 (t, J = 7.9 Hz, 1 H), 8.00 (s, 1 H), 7.62 (m, 7 H), 6.99 (m, 2 H), 6.85 (dd, J = 10.9 and 17.7 Hz, 1 H), 5.95 (d, J =17.7 Hz, 1 H), 5.35 (d, J = 10.9 Hz, 1 H), 3.81 (q, J = 7.5 Hz, 1 H), 1.45 (m, 4 H), 1.24 (m, 4.H), 0.82 (m, 6 H); MS (ES+): 527.3
70r	357	358	68r	I-2, S	1 H NMR (DMSO-d6): δ 13.81 (s, 1 H), 8.44 (m, 4 H), 7.97 (s, 1 H), 7.61 (m, 7 H), 6.90 (m, 3 H), 5.93 (d, J =17.7 Hz, 1 H), 5.34 (d, J = 10.9 Hz, 1 H), 3.22 (m, 5 H), 2.73 (m, 2 H), 1.52 (m, 4 H); MS (ES+): 500.3
70s	359	360	68s	I-2, S	1 H NMR (DMSO-d6): δ 9.09 (s, 2 H), 8.86 (s, 2 H), 8.42 (d, J = 7.5 Hz, 1 H), 8.11 (s, 1 H), 7.68 (m, 8 H), 7.10 (m, 4 2 H), 6.86 (dd, J = 10.9 and 17.7 Hz, 1 H), 5.97 (d, J =17.7 Hz, 1 H), 5.38 (d, J = 10.9 Hz, 1 H), 4.20 (q, J = 7.2 Hz, 1 H), 1.93-1.44 (m, 8 H); MS (ES+): 497.2
70t	361	362	68t	I-2, S	1 H NMR (DMSO-d6): δ 13.78 (br s, 1 H), 9.07 (s, 2 H), 8.87 (s, 2 H), 8.25 (d, J = 8.1 Hz, 1 H), 8.00 (s, 1 H), 7.62 (m, 7 H), 6.98 (m, 2 H), 6.85 (dd, J = 10.9 and 17.7 Hz, 1 H), 5.94 (d, J = 17.7 Hz, 1 H), 5.35 (d, J = 10.9 Hz, 1 H), 4.55 (d, J = 4.1 Hz, 1 H), 3.68 (m, 1 H), 3.39 (m, 1 H), 1.79 (m, 4 H),
#1.28 (m, 4 H); MS (ES+): 527.2
70u	363	364	68u	I-2, S	1 H NMR (DMSO-d6): δ 13.36 (br s, 1 H), 9.05 (m, 3 H), 8.49 (s, 1 H), 7.98 (s, 1 H), 7.61 (m, 8 H), 6.92 (m, 3 H), 5.94 (d, J = 17.7 Hz, 1 H), 5.35 (d, J = 10.9 Hz, 1 H), 2.81 (m, 1 H), 0.69-0.48 (m, 4 H); MS (ES+): 469.3
70v	365	366	68v	I-2, S	1 H NMR (DMSO-d6): δ 9.05 (m, 4 H), 8.75 (d, J = 7.5 Hz, 1 H), 8.15 (s, 1 H), 7.70 (m, 7 H), 7.14 (d, J = 7.9 Hz, 2 H), 6.86 (dd, J = 10.9 and 17.7 Hz, 1 H), 5.97 (d, J =17.7 Hz, 1 H), 5.39 (d, J = 10.9 Hz, 1 H), 4.40 (q, J = 8.2 Hz, 1 H), 2.12 (m, 4 H) 1.65 (m, 2 H); MS (ES+): 483.3
70w	367	368	68w	I-2, S	1 H NMR (DMSO-d6): δ 13.17 (hr s, 1 H), 9.05 (m, 4 H), 8.51 (t, J = 5.8 Hz, 1 H), 8.06 (s, 1 H), 7.64 (m, 7 H), 7.03 (m, 2 H), 6.85 (dd, J = 10.9 and 17.7 Hz, 1 H), 5.95 (d, J =17.7 Hz, 1 H), 5.36 (d, J = 10.9 Hz, 1 H), 4.72 (t, J =5.4 Hz, 1 H) 3.47 (q, J = 5.7 Hz, 2 H), 3.28 (m, 2 H); MS (ES+): 473.2
70x	369	370	68x	I-2, S	1 H NMR (DMSO-d6): δ 9.07 (s, 2 H), 8.90 (s, 2 H), 8.50 (t, J = 5.5 Hz, 1 H), 8.04 (s, 1 H), 7.63 (m, 7 H), 7.03 (m, 2 H), 6.85 (dd, J = 10.9 and 17.7 Hz, 1 H), 5.96 (d, J =17.7 Hz, 1 H), 5.36 (d, J = 10.9 Hz, 1 H), 3.23 (q, J = 6.5 Hz, 2 H), 1.59 (m, J = 7.0 Hz, 1 H), 1.39 (q, J = 6.8 Hz, 2 H), 0.88
#(d, J = 6.6 Hz, 6 H).
70y	371	372	68y	I-2,S	1 H NMR (DMSO-d6): δ 13.77 (s, 1 H), 9.48-8.58 (m, 5 H), 7.97 (s, 1 H), 7.61 (m, 6 H), 7.03 (m, 3 H), 6.90 (m, 3 H), 5.93 (d, J = 17.3 Hz, 1 H), 5.34 (d, J = 10.5 Hz, 1 H), 3.22 (m, 2 H), 2.22 (t, J = 7.0 Hz, 2 H), 1.71 (t, J = 7.3 Hz, 2 H); MS (ES−): 513.41.
70z	373	374	68z	I-2,S	1 H NMR (DMSO-d6-DCl): δ 8.31 (s, 1 H), 7.98 (m, 1 H), 7.74 (m, 6 H), 7.30 (m, 2 H), 6.88 (dd, J = 10.5 and 17.3 Hz, 1 H), 6.02 (d, J = 17.3 Hz, 1 H), 5.41 (d, J = 10.5 Hz, 1 H), 3.46 (tJ = 6.8 Hz, 2 H), 2.54 (m, 2 H); MS (ES−): 499.32.
70aa	375	376	68aa	I-2,S	1 H NMR (DMSO-d6): δ 13.78 (s, 1 H), 8.68 (m, 5 H), 8.03 (s, 1 H), 7.61 (m, 7 H), 6.89 (m, 3 H), 5.24 (d, J =17.7 Hz, 1 H), 5.34 (d, J = 10.9 Hz, 1 H), 3.42 (m, 2 H), 2.93 (m, 2 H); MS (ES+): 472.28.
70ab	377	378	68ab	I-2,S	1 H NMR (DMSO-d6): δ 13.41 (br s, 1 H), 9.10 (m, 3 H), 8.47 (m, 1 H), 8.05 (s, 1 H), 7.65 (m, 6 H), 7.08-6.78 (m, 3 H), 6.90 (m, 3 H), 5.95 (d, J = 17.3 Hz, 1 H), 5.36 (d, J =10.5 Hz, 1 H), 4.82 (d, J = 5.3 Hz, 1 H), 4.58 (t, J = 5.7 Hz, 1 H), 3.61 (m, 1 H), 3.33 (m, 2 H), 3.18 (m, 1 H); MS (ES+): 503.34.
70ac	379	380	68ac	I-2,S	1 H NMR (DMSO-d6): δ 9.02 (m, 3 H), 8.58 (m, 1 H), 8.04 (s, 1 H), 7.72-6.78 (m, 12 H, 6.90 (m, 3 H), 5.95 (d, J = 17.3 Hz, 1 H), 5.36 (d, J = 10.5 Hz, 1 H), 3.40 (m, 2 H), 2.32 (t, J = 7.0 Hz, 1 H); MS (ES+): 500.30.

[0287]

381
Cpd.		Starting	Method
No.	-R	From	Used	Analytical Data
31a	382	30a	J	1 HNMR (DMSO-d6): δ 10.85 (s, 1H), 9.21 (s, 2H), 8.91 (s, 2H), 8.71 (t, J=5.9 Hz, 1H), 8.21 (d, J=1.96 Hz, 1H), 8.23 (d, J=1.96 Hz, 1H), 8.19 (d, J=2.19 Hz, 1H), 8.17 (d, J=1.97 Hz, 1H), 8.09 (d, J=1.91 Hz, 1H), 7.77 (s, 4H), 7.53 (d, J=7.53 Hz, 1H), 3.57 (s, 3H), 3.11 (q, J=6.89 Hz, 1H), 2.71 (s, 3H), 1.86 (m, 1H), 3.88 (d, 6.87 Hz, 6H); MS (ES+) 515.3
31b	383	30b	J	MS (ES+): 527.2
31c	384	30c	J	Characterized in the next step
31d	385	30d	J	1 HNMR (DMSO-d6): δ 10.59 (bs, 1H), 9.16 (s, 2H), 8.85 (s, 2H), 8.69 (t, J=6 and 5 Hz, 1H), 8.21 (s, 1H), 8.04 (d, J=1.5 Hz, 1H), 7.73 (m, 4H), 7.58 (s, 1H ), 7.50-7.38 (m, 3H), 7.32 (m, 1H), 7.03 (d, J=7.5 Hz, 2H), 4.31 (s, 2H), 3.55 (s, 2H), 3.07 (t, J=6.8 Hz, 2H), 1.85 (m, 1H), 0.87 (d, J=6.8 Hz, 6H),; MS (ES−) 567.3, (ES+) 569.3
31e	386	30e	J	MS (ES−): 561.4; MS (ES+): 563.4
31f	387	30f	J	1 H NMR (DMSO-d6): δ 10.73 (s, 1H), 9.24 (s, 2H), 9.00 (s, 2H), 8.71 (t, J=5.7 Hz, 1H), 8.24 (d, J=1.9 Hz, 1H), 8.05 (dd, J=8.0, 1.9 Hz, 1H), 7.77 (m, 5H), 7.71 (dd, J=7.9, 1.5 Hz, 1H), 7.42 (d, J=7.9 Hz, 1H), 7.31 (d, J=7.9 Hz, 1H), 6.89 (dd, J=17.6, 11.0 Hz, 1H), 6.04 (d, J=17.6 Hz, 1H), 5.42 (d, J=11.0 Hz, 1H), 3.56 (s, 3H), 3.10 (t, J=6.4 Hz, 2H), 1.85 (m, 1H), 0.89 (d, J=6.7 Hz, 6H):
# MS (ES+): 499.3
31g	388	30g	J	1 HNMR (DMSO-d6): δ 10.73 (s, 1H), 9.19 (bs, 2H), 8.88 (bs, 2H), 8.71 (t, J=6Hz, 1H), 8.27 (d, J=2Hz, 1H), 8.07 (dd, J=7.7 and 2 Hz, 1H), 7.88 (d, 2 Hz, 1H), 7.8 (d, J=2Hz, 1H), 7.83 (m, 4H), 7.72 (dd, J=2 and 7.7 Hz, 1H), 7.46 (d, J=7.7, 1H), 7.41 (d, J=7.7 Hz, 1H), 4.56 (s, 2H), 3.56 (s, 3H), 3.11 (t, J=6.8 Hz, 2H), 1.87 (m, 1H), 0.92 (d, J=6.8 Hz, 6H); MS (ES−) 608.2, (ES+) 610.3
31h	389	30h	J	Characterized at the next step
31i	390	30i	J	1 HNMR (DMSO-d6): δ 10.68 (s, 1H), 9.17 (bs, 2H), 8.82 (bs, 2H), 8.68 (t, J=6Hz, 1H), 8.25 (d, J=2 Hz, 1H), 8.16 (d, J=2 Hz, 1H), 8.05 (dd, J=8 and 2 Hz, 1H), 7.87 (m, 1H), 7.89 (dd, J=8 and 2 Hz, 1H), 7.75 (m, 5H), 7.44 (d, J=9 Hz, 1H), 7.36 (d, J=8 Hz, 1H), 5.22 (t, J=5 Hz, 1H), 4.54 (d, J=5 Hz, 2 H), 3.57 (s, 3H), 3.10 (t, J= 6.8 Hz, 2H), 1.84 (m, 1H), 0.88 (d, J=6.8 Hz, 6 H;
# MS (ES−) 567.4, (ES+) 569.4
43	391	42	J	MS (ES−): 563.4
45	—Obn	8	J	Characterized in the next step
50	—OCH3	49	J	MS (ES+): 503.1
52	392	31g	G	Characterized in the next step

[0288]

393
Cpd.			Starting	Method
No.	-R	-R′	From	Used	Analytical Data
34	—OSO2CF3	394	33	J	MS (ES+): 621.2
35	—OSO2CF3	395	34	P	MS (ES+): 755.2; (ES−) 753.3
37	396	397	35 + 36	D-2	MS (ES+): 828.5
38	398	—H	37	G	MS (ES+): 694.4; (ES−) 692.4
39	399	—H	38	Q	Characterized in the next step

[0289]

400
Cpd.				Starting	Method
No.	-R	-R′	-R″	From	Used	Analytical Data
54	—OBn	13 CHO	—CO2MEM	5 + 6	D-2	1 H NMR (DMSO-d6): δ 9.69 (s, 1H), 8.49 (d, J=2.0 Hz, 1H), 8.22 (d, J=6.9 Hz, 1H), 7.53 (m, 4H), 7.43 (m, 2H), 7.37 (m, 2H), 7.24 (d, J=8.9 Hz, 1H), 5.57 (s, 2H), 5.26 (s, 2H), 3.85 (t, J=4.9 Hz, 2H), 3.60 (s, 3H), 3.51 (t, J=4.9 Hz 2H), 3.32 (s, 3H); MS (ES+): 501.02 (M + Na)+
55	—OBn	—CO2H	—CO2MEM	54	E	1 H NMR (DMSO-d6): δ 12.65 (s, 1H), 8.41 (d, J=2.0 Hz 1H), 8.14 (dd, J=2.0 and 7.9 Hz, 1H), 7.50 (m, 3H), 7.38 (m, 4H), 7.24 (dd, J=3.0 and 8.9 Hz, 1H), 7.11 (d, J=8.9 Hz, 1H), 5.54 (s, 2H), 5.20 (s, 2H), 3.82 (t, J=4.9 Hz, 2H), 3.57 (s, 3H), 3.49 (t, J=4.9 Hz, 2H), 3.23 (s, 3H); MS (ES−): 493.2
141	—OBn	—CHO	401	140 + 6	D-2	1 H NMR (DMSO-d6): δ 10.2 (s, 1H), 9.65 (s, 1H), 8.25 (d, J=2.0 Hz, 1H), 7.85 (dd, J=2.0 and 8.9 Hz, 1H), 7.51 (d, J=7.9 Hz, 2H), 7.45 (m, 2H), 7.35 (m, 3H), 7.29 (d, J=7.9 Hz, 1H) 7.2 (d, J=7.9 Hz, 1H), 5.24 (s, 2H), 33.55 (s, 3H), 2.3 (d, J=6.9 Hz, 2H) 2.1 (m, J==6.9 Hz, 1H), 1.0 (d, J=6.9 Hz, 6H); MS (ES+): 446.31
142	—OBn	—CO2H	402	141	E	1 NMR (DMSO-d6): δ 12.38 (s, 1H), 10.01 (s, 1H), 8.05 (s, 1H), 7.68 (d, J=7.9 Hz, 1H), 7.41 (d, J=7.9 Hz, 2H), 7.35 (m, 5H), 7.27 (m, 1H), 7.11 (d, J=8.9 Hz, 1H), 7.04 (d,J=8.9 Hz, 1H), 6.99 (d, J=8.9 Hz, 1H), 5.11 (s, 2H), 2.13 (d, J=6.9 Hz, 2H), 2.02 (m, J=6.9 Hz, 1H), 0.852 (d, J=6.9 Hz, 6H); MS (ES−): 460.2
143	—OBn	—CO2MEM	403	142	F	1 H NMR (DMSO-d6): δ 10.12 (s, 1H), 8.16 (d, J=1.9 Hz, 1H), 7.80 (dd, J=1.9 and 8.3 Hz, 1H), 7.42 (m, 6H), 7.26 (dd, J=2.8 and 8.3 Hz, 1H), 7.13 (m, 2H), 5.21 (s, 2H), 5.17 (s, 2H), 3.54 (s, 3H), 3.40 (m, 2H), 3.32 (m, 2 H), 2.22 (d, J=7.0 Hz, 2H), 2.10 (m, 4H), 0.95 (d, J=6.4 Hz, 6H); MS (ES+): 572.3 (M + Na)+
144	—OH	—CO2MEM	404	143	G	1 H NMR (DMSO-d6): δ 12.7 (brs, 1H), 9.09 (s, 2H), 8.91 (s, 2H), 8.57 (m, 1H), 8.11 (s, 1H), 7.92 (d, J=1.9 Hz, 1H), 7.81 (m, 3H), 7.67 (m, 5H), 7.14 (m, 3H), 6.66 (m, 1H), 4.40 (t, J=5.3 Hz, 1H), 3.39 (m, 2H), 3.22 (m, 2H), 1.48 (m, 4H); MS (ES−): 592.2.
145	—OSO2CF3	—CO2MEM	405	144	B-2	MS (ES+): 592.2
146a	406	—CO2MEM	407	145	D-2	MS (ES+): 532.5 (M + Na)+
146b	408	—CO2MEM	409	145	D-2	1 HNMR (DMSO-d6): δ 10.1 (s, 1H), 8.21 (d, J=2.0 Hz, 1H), 8.10 (d, J=2.0 Hz, 1H), 7.89 (dd, J=2.0 and 7.9 Hz, 1H), 7.84 (d, J=3.0 and 8.9 Hz, 1H), 7.63 (m, 2H), 7.25 (d, J=7.9 Hz, 1H), 7.19 (m, 2H), 5.22 (d, J=14.8 Hz, 2H), 3.57 (s, 3H), 3.43 (t, J=4.9 Hz, 2H), 3.34 (t, J=4.9 Hz, 2H), 3.20 (s, 3H), 2.23 (d, J=6.9 Hz, 2H), 2.11 (m, J=6.9 Hz, 1H), 0.96 (d, J=5.9 Hz, 6H);
# MS (ES+): 526.48
146c	—CH═CH2	—CO2MEM	410	145	D-3	MS (ES+): 470.2 (M + Na)30
147a	411	—CO2H	412	146a	I-1	MS (ES−): 420.29
147b	413	—CO2H	414	146b	I-1	1 H NMR (DMSO-d6): δ 12.65 (s, 1H), 10.12 (s, 1H), 8.18 (d, J=1.9 Hz, 1H), 8.07 (d, J=3.0 Hz, 1H), 7.83 (m, 2H), 7.61 (m, 2H), 7.19 (m, 3H), 3.56 (s, 3H), 2.22 (d J=6.9 Hz, 2 H), 2.11 (m, J=6.9 Hz, 1H), 0.96 (d,J=6.9 Hz, 6H); MS (ES+): 438.52
147c	—CH═CH2	—CO2H	415	146c	I-1	MS (ES−): 380.32
173	—H	—CHO	416	172 + 130	D-2	1 H NMR (DMSO-d6): δ 9.70 (s, 1H), 8.42 (t, J=6.2 Hz, 1H), 7.90 (dd, J=1.1 & 6.6 Hz, 1H), H), 7.82 (d, J=1.9 Hz, 1H), 7.72-7.50 (m, 3H), 7.34 (d, J=7.7 Hz, 1H), 7.27 (dd, J=1.3 & 6.2 Hz, 1H), 4.38 (d, J=6.0 Hz, 2H), 3.53 (s, 3H), 2.47 (m, 1H),, 1.07 (d, J=7.0 Hz, 6H); H); MS (ES+): 340.05
174	—H	—CO2H	417	173	E	1 H NMR (DMSO-d6): δ 12.35 (brs, 1H), 8.31 (t, J=7.5 Hz, 1H), 7.80-7.31 (m, 5H), 7.06 (m, 2H), 4.25 (d, J=6.0 Hz, 2H), 3.41 (s, 3H), 2.37 (m, 1H), 0.97 (d, J=7.0 Hz, 6H); MS (ES−): 353.83
180	—H	—CHO	418	179 + 130	D-2	1 H NMR (DMSO-d6): δ 9.70 (s, 1H), 7.87 (m, 2H), 7.69 (m, 1H), 7.55 (m, 2H), 7.35 (d, J=7.9 Hz, 1H), 7.27 (d, J=7.5 Hz, 1H), 4.51 (s, 2H), 3.52 (s, 3H), 3.05 (m, 2H), 1.92 (m, 1H), 1.40 (m, 9H), 0.85 (d, J=6.8 Hz, 6H); MS (ES+): 448.3 (M + Na)+
181	—H	—CO2H	419	180	E	1 H NMR (DMSO-d6): δ 7.81 (m, 2H), 7.56 (m, 1H), 7.44 (m, 2H), 7.16 (m, 2H), 4.47 (s, 2H), H), 3.51 (s, 3H), 3.02 (m, 2H), 1.92 (m, J=7.0 Hz, 1H), 1.41 (m, 9H), 0.85 (d, J=6 Hz, 6H); MS (ES−): 440.2
184a	—OBn	—CHO	420	3a + 6	D-2	1 H NMR (DMSO-d6): δ□9.78 (s, 1H), 8.85 (t, J=5.7 Hz, 1H), 8.50 (d, J=2.0 Hz, 1H), 8.20 (dd, J=8.2, 1.9 Hz, 1H), 7.55 (m, 9H), 5.35 (s, 2H), 3.69 (s, 3H), 3.23 (t, J=6.5 Hz, 2H), 1.98 (m, 1H), 1.02 (d, J=6.8 Hz, 6H); MS (ES+): 446.3
184b	—OBn	—CHO	421	3f + 6	D-2	MS (ES31 ): 470.2
184c	—OBn	—CHO	422	3i + 6	D-2	MS (ES−): 418.3
184d	—OBn	—CHO	423	3j + 6	D-2	MS (ES+): 460.3
185a	—OH	—CHO	424	184a	AD	1 HNMR (DMSO-d6): δ 10.06 (s, 1H), 9.63 (s, 1H), 8.73 (t, J=6.5 Hz, 1H), 8.36 (d, J=2 Hz, 1H), 8.09 (dd J=2 and 8 Hz, 1H), 7.45 (d, J=8 Hz, 1H), 7.28 (s, 1H), 7.11 (s, 2H), 3.58 (s, 3H), 3.13 (d, J=7 Hz, 2H), 1.87 (m, 1H), 0.91 (d, J=6.8 Hz, 6H); MS (ES−): 354.2 and (ES+) 378.2 (M + Na)+)
185b	—OH	—CHO	425	184b	AD	MS (ES−): 380.1
185c	—OH	—CHO	426	184c	AD	1 HNMR (DMSO-d6): δ 10.21 (s, 1H), 9.78 (s, 1H), 8.87 (t, J=5.80 Hz, 1H), 8.51 (s, 1H), 8.23 (d, J=7.92 Hz, 1H), 7.60 (d, J=7.9 Hz, 1H), 7.43 (s, 1H), 7.25 (s, 2H), 3.74 (s, 3H), 3.46 (q, J=5.65, 2H), 1.32 (t, J=7.8 Hz, 3H)
185d	—OH	—CHO	427	184d	AD	1 HNMR (DMSO-d6): δ 10.06 (s, 1H), 9.62 (s, 1H), 8.69 (t, J=5.90 Hz, 1H), 8.36 (s, 1H), 8.08 (d, J=7.92 Hz, 1H), 7.45 (d, J=8.1 Hz, 1H), 7.28 (s, 1H), 7.10 (s, 2H), 3.58 (s, 3H), 3.22 (m, 1H), 3.11 (m, 1H), 1.66 (m, 1H), 1.44 (m, 1H), 1.18 (m, 1H), 0.89 (t, J=6.4 Hz, 6H).
186a	—OSO2CF3	—CHO	428	185a	B-2	MS (ES+): 488.24
186b	—OSO2CF3	—CHO	429	185b	B-2	1 HNMR (DMSO-d6): δ 9.74 (s, 1H), 9.44 (t, J=5.90 Hz, 1H), 8.51 (s, 1H), 8.11 (d, J=7.91 Hz, 1H), 7.54 (m, 4H), 4.18 (m, 2H), 3.59 (s, 3H).
186c	—OSO2CF3	—CHO	430	185c	B-2	1 HNMR (DMSO-d6): δ 9.45 (s, 1H), 8.59 (t, J=5.90 Hz, 1H), 8.28 (s, 1H), 7.94 (d, J=8.10 Hz, 1H), 7.79 (d, J=2.8 Hz, 1H), 7.67 (d, J=7.9 Hz, 1H), 7.32 (d, J =7.9 Hz, 2H), 3.40 (s, 3H), 3.12 (q, J=7.1 Hz, 2H), 0.97 (t, J=7.16 Hz, 3H).
186d	—OSO2CF3	—CHO	431	185d	B-2	1 HNMR (DMSO-d6): δ 9.71 (s, 1H), 8.78 (t, J=5.90 Hz, 1H), 8.49 (s, 1H), 8.18 (d, J=7.92 Hz, 1H), 8.00 (s, 1H), 7.88 (d, J=8.51 Hz, 1H), 7.52 (q, J=8.1 Hz, 2H), 3.67 (s, 3H), 3.22 (m, 1H), 3.16 (m, 1H), 1.68 (m, 1H), 1.44 (m, 1H), 1.18 (m, 1H), 0.89 (t, J=6.4 Hz, 6H).
187a	—CH═CH2	—CHO	432	186a	D-3	1 HNMR (DMSO-d6): δ9.74 (s, 1H), 8.76 (t, J=6.5 Hz, 1H), 8.42 (d, J=2 Hz, 1H), 8.11 (dd, J=2 and 8 Hz, 1H), 8.00 (d, J=1.7 Hz, 1H), 7.84 (dd, J=8 and 2 Hz, 1H), 7.47 (d, J=8 Hz, 1H), 7.27 (d, J=8 Hz, 1H), 6.90 (dd, J=11 and 17.7 Hz, 1H), 6.01 (d, J=17.7 Hz, 1H), 5.42 (d, J=11 Hz, 1H), 3.59 (s, 3H), 3.14
# (d, J=7 Hz, 2H), 1.88 (m, 1H), 0.92 (d, J=6.8 Hz, 6H); MS (ES−): 364.2 and (ES+) 388.2 (M + Na)+
187b	—CH═CH2	—CHO	433	186b	D-3	MS (ES−): 390.1
187c	—CH═CH2	—CHO	434	186c	D-3	MS (ES−): 336.2
187d	—CH═CH2	—CHO	435	186d	D-3	MS (ES−): 378.2

[0290]

436
Cpd.				Starting	Method
No.	-R	-R′	-R″	From	Used	Analytical Data
56	—OBn	—H	—CO2MEM	55	J	1 H NMR (DMSO-d6): δ 10.67 (s, 1H), 9.2 (s, 2H), 8.87 (s, 2H), 8.33 (d, J=2.0 Hz, 1H), 8.17 (dd, J=2.0 and 7.9 Hz, 1H), 7.77 (s, 4H), 7.49 (m, 4H), 7.39 (m, 2H), 7.30 (s, 2H), 5.54 (s, 2H), 5.27 (s, 2H), 3.83 (t, J=4.9 Hz, 2H), 3.57 (s, 3H), 3.49 (t, J=4.9 Hz, 2H), 3.23 (s, 3H); MS (ES+): 612.4
57	—OBn	—Boc	—CO2MEM	56	R	MS (ES+): 712.4
58	—OH	—Boc	—CO2MEM	57	G	1 H NMR (DMSO-d6): δ 10.4 (s, 1H), 10.0 (s, 1H), 8.9 (s, 1H), 8.28 (d, J=2.0 Hz, 1H), 8.12 (dd, J=2.1 and 7.7 Hz, 1H), 7.89 (d, J=8.4 Hz, 2H), 7.61 (d, J=8.4 Hz, 2H), 7.45 (d, J=7.7 Hz, 1H), 7.13 (d, J=8.4 Hz, 1H) 7.06 (s, 1H), 6.98 (dd, J=2.8 and 8.4 Hz, 1H), 5.52 (s, 2H), 3.81 (t, J=4.9 Hz, 2H), 3.56 (s, 3H), 3.46 (t,
# J=4.9 Hz, 2H), 3.20 (s, 3H), 1.43 (s, 9H); MS (ES−): 620.5
59	—OSO2CF3	—Boc	—CO2MEM	58	B-2	1 H NMR (DMSO-d6): δ 10.55 (s, 1H), 8.38 (d, J=2.0 Hz, 1H), 8.18 (dd, J= 2.0 and 7.9 Hz, 1H), 7.86 (m, 4 H), 7.75 (dd, J=2.0 and 8.9 Hz, 1H), 7.54 (m, 5H), 5.51 (s, 2H), 3.77 (t, J=4.9 Hz, 2H), 3.55 (s, 3H), 3.46 (t, J=4.9 Hz, 2H), 3.18 (s, 3H) 1.41 (s, 9H); MS (ES+): 754.3
60	437	—Boc	—CO2MEM	59	D-2	1 H NMR (DMSO-d6): δ 10.61 (s, 1H), 8.94 (s, 1H), 8.37 (s, 1H), 8.19 (dd, J=2.0 and 7.9 Hz, 1H), 8.02 (s, 1H), 7.89 (m, 5H), 7.65 (d, J=8.9 Hz, 2H), 7.54 (d, J=7.9 Hz, 1H), 7.39 (d, J=7.9 Hz, 1H), 7.17 (d, J=3.9 Hz, 1H), 6.68 (m, 1H), 5.54 (s, 2H), 3.82 (t, J=4.9 Hz, 2H), 3.58 (s, 3H), 3.49 (t, J=4.9 Hz, 2H), 3.22 (s, 3H), 1.45 (s, 9H); MS (ES+): 582.4
61	438	—Boc	—CO2H	60	I-1	1 H NMR (DMSO-d6): δ 10.50 (s, 1H), 8.96 (s, 1H), 8.32 (s, 1H), 8.07 (d, J=7.9 Hz, 1H), 7.98 (s, 1H), 7.87 (m, 5H), 7.63 (d, J=8.9 Hz, 2H), 7.38 (m, 2H), 7.15 (d, J=3.0 Hz, 1H), 6.67 (m, 1H), 3.57 (s, 3H), 1.45 (s, 9H); MS (ES1): 582.4
66	—CH═CH2	—Boc	—CO2MEM	59	D-3	1 H NMR (DMSO-d6): δ 10.56 (s, 1H), 9.02 (br s, 1H), 8.35 (d, J=1.7 Hz, 1H), 8.18 (dd, J=1.9 and 6.0 Hz, 1H), 7.88 (d, J=9.0 Hz, 2H), 7.80 (d, J=1.3 Hz, 1H), 7.71 (dd, J=1.7 and 6.2 Hz, 1H), 7.63 (d, J=8.9 Hz, 2 H), 7.50 (d, J=8.3 Hz, 1H), 7.32 (d, J=8.1 Hz, 1H), 6.89 (dd, J=10.7 and 17.7 Hz, 1H), 6.04 (d, J=17.4 Hz, 1H), 5.54 (s, 2H), 5.43 (d,
# J=11.7 Hz, 1H), 3.82 (t, J=4.5 Hz, 2H), 3.57 (s, 3H), 3.48 (t, J=4.5 Hz, 2H), 3.22 (s, 3H), 1.44 (s, 9H); MS (ES+): 632.1
67	—CH═CH2	—Boc	—CO2H	66	I-1	H NMR (DMSO-d6): δ 10.49 (s, 1H), 8.99 (br s, 1H), 8.31 (s, 1H), 8.07 (d, J=8.3 Hz, 1H), 7.87 (d, J=9.0 Hz, 2H), 7.77 (m, 2H), 7.66 (m, 3H), 7.38 (d, J=7.7 Hz, 1H), 7.29 (d, J=7.7 Hz, 1H), 6.88 (dd, J=10.7 and 17.7 Hz, 1H), 6.03 (d, J=17.4 Hz, 1H), 5.41 (d, J=10.9 Hz, 1H), 3.56 (s, 3H), 1.43 (s, 9H); MS (ES−): 542.1

[0291]

439
Cpd.			Starting	Method
No.	-R	-R′	From	Used	Analytical Data
62a	—CH3	440	61	A-4	1 H NMR (DMSO-d6): δ 10.57 (s, 1H), 8.92 (s, 1H), 8.64 (t, J=5.4 Hz, 1H), 8.24 (d, J=2.0 Hz, 1H), 8.02 (dd, J=2.0 and 7.9 Hz, 1H), 7.98 (s, 1H), 7.88 (m, 3H) 7.84 (s, 1H), 7.64 (d, J=8.9 Hz, 2H), 7.42 (d, J=7.9 Hz, 1H), 7.36 (d, J=7.9 Hz, 1H), 7.14 (d, J=3.0 Hz, 1H), 6.67 (m, 1H), 3.55 (s, 3H), 3.26 (m, 2H) 1.50 (m, J=7.4 Hz, 2H), 1.43 (s, 9H), 1.32 (m, J=7.4 Hz, 2H), 0.89 (t, 3H);
# MS (ES−): 639.5
62b	—CH3	441	61	A-4	MS (ES+): 625.5
62c	—CH3	442	61	A-4	MS (ES+): 623.4
62d	—CH3	443	61	A-4	MS (ES+): 687.4
62e	—CH3	444	61	A-4	MS (ES+): 625.4
62f	—CH3	445	61	A-4	MS (ES+): 653.5
62g	—CH3	446	61	A-4	MS (ES+): 653.5
62h	—CH3	447	61	A-4	MS (ES+): 667.3
62i	—CH3	448	61	A-4	MS (ES+): 681.5
62j	—CH3	449	61	A-4	MS (ES+): 637.3
62k	—CH3	450	61	A-4	MS (ES+): 640.3
62l	—CH3	451	61	A-4	MS (ES+): 665.4
62m	—CH3	452	61	A-4	MS (ES+): 597.3
62n	—CH3	453	61	A-4	MS (ES+): 639.4
62o	—CH3	454	61	A-4	MS (ES+): 695.4 (M + Na)+
62p	—CH3	455	61	A-4	MS (ES−): 665.4
62q	—CH3	456	61	A-4	MS (ES+): 653.4
62r	—CH3	457	61	A-4	MS (ES+): 567.3
62s	—CH3	458	61	A-4	MS (ES+): 667.5
62t	—CH3	459	61	A-4	MS (ES+): 641.3
62u	—CH3	460	61	A-4	MS (ES+): 655.3
62v	—CH3	461	61	A-4	MS (ES+): 663.1
62w	—CH3	462	61	A-4	MS (ES−): 577.2
62x	—CH3	463	61	A-4	MS (ES+): 679.2
62y	—CH3	464	61	A-4	MS (ES+): 621.1
62z	—CH3	465	61	A-4	MS (ES+): 611.1
62aa	—CH3	466	61	A-4	MS (ES+): 657.1
62ab	—CH3	467	61	A-4	MS (ES+): 659.1
62ac	—CH3	468	61	A-4	MS (ES+): 679.3
62ad	—CH3	469	61	A-4	MS (ES−): 695.3
62ae	—CH3	470	61	A-4	MS (ES+): 651.3
62af	—CH3	471	61	A-4	MS (ES+): 679.4
62ag	—CH3	472	61	A-4	MS (ES−) 667.32

[0292]

473
Cpd.			Starting	Method
No.	-R	-R′	From	Used	Analytical Data
64a	474	475	62a	I-2, S	1 H NMR (DMSO-d6): δ 12.80 (s, 1H), 9.09 (s, 2H), 8.91 (s, 2H), 8.57 (m, 1H), 8.15 (s, 1H), 7.91 (s, 1H), 7.80 (m, 3H), 7.67 (m, 4H), 7.20 (m, 2H), 7.07 (s, 1H), 6.63 (s, 1H) 3.21 (m, J=5.9 Hz, 2H), 1.46 (m, J=7.4 Hz, 2H), 1.28 (m, J=7.4 Hz, 2H) 0.86 (t, J=7.4 Hz, 3H); MS (ES+): 525.3
64b	476	477	62b	I-2, S	1 H NMR (DMSO-d6): δ 12.76 (s, 1H), 9.10 (s, 2H), 8.82 (s, 2H), 8.59 (m, 1H), 8.20 (s, 1H), 7.95 (s, 1H), 7.83 (m, 3H), 7.70 (s, 4H), 7.25 (m, 2H), 7.10 (s, 1H), 6.65 (s, 1H), 3.20 (q, J=6.0 Hz, 2H), 1.51 (m, J=7.4 Hz, 2H), 0.87 (t, J=7.4 Hz, 3H); MS (ES+): 511.2
64c	478	479	62c	I-2, S	1 H NMR (DMSO-d6): δ 12.84 (s, 1H), 9.11 (s, 2H), 8.84 (m, 2H), 8.26 (m, 1H), 7.94 (m, 2H), 7.83 (m, 3H), 7.71 (s, 4H), 7.28 (m, 2H), 7.12 (s, 1H), 6.65 (s, 1H), 5.87 (m, 1H), 5.15 (d, J=17.2 Hz, 1H), 5.07 (d, J=10.3 Hz, 1H) 3.88 (t, J=5.2 Hz, 2H); MS (ES+): 509.2
64d	480	481	62d	I-2, S	1 H NMR (DMSO-d6): δ 12.78 (s, 1H), 9.11 (m, 2H), 8.85 (s, 2H), 8.22 (s, 1H), 7.93 (s, 1H), 7.83 (m, 3H), 7.68 (s, 4H), 7.19 (m, 3H), 7.10 (m, 5H), 6.65 (s, 1H), 4.41 (s, 2H), 2.27 (s, 3H); MS (ES+): 573.3
64e	482	483	62e	I-2, S	1 H NMR (DMSO-d6): δ 12.82 (s, 1H), 9.11 (s, 2H), 8.86 (s, 2H), 8.39 (d, J=7.7 Hz, 1H), 8.24 (s, 1H), 7.95 (s, 1H), 7.90 (m, 1H), 7.84 (m, 2H), 7.71 (s, 4H), 7.28 (m, 2H), 7.11 (m, 1H), 6.65 (s, 1H), 4.08 (m, J=6.9 Hz, 1H), 1.14 (d, J=6.9 Hz, 6H); MS (ES+): 511.3
64f	484	485	62f	I-2, S	1 H NMR (DMSO-d6): δ 13.28 (br s, 1H), 9.05 (m, 2H), 8.84 (s, 2H), 8.46 (m, 1H), 7.99 (s, 1H), 7.88 (s, 1H), 7.77 (m, 2H), 7.63 (m, 5H), 7.07 (m, 2H), 6.96 (m, 1H), 6.63 (s, 1H), 3.16-2.96 (m, 2 H), 1.65-1.03 (m, 3H), H), 0.85 (m, 6H); MS (ES+): 539.3
64g	486	487	62g	I-2, S	1 H NMR (DMSO-d6): δ 13.37 (s, 1H), 9.06 (s, 2H), 8.84 (s, 2H), 8.47 (m, 1H), 8.00 (s, 1 H), 7.88 (s, 1H), 7.78 (m, 2H), 7.70 (m, 5H), 7.08 (m, 2H), 6.97 (s, 1H), 6.63 (s, 1H), 3.22 (m, 2H), 1.58 (m, J=6.0 Hz, 1H), 1.38 (m, J=6.9 Hz, 2H), 0.87 (d, J=6.9 Hz, 6H); MS (ES+): 539.3
64h	488	489	62h	I-2, S	1 H NMR (DMSO-d6): δ 12.71 (br s, 1H), 9.13 (s, 1H), 8.75 (m, 3H), 8.31 (m, 1H), 7.97 (m, 2H), 7.86 (m, 2H), 7.73 (m, 4H), 7.64 (m, 2H), 7.33 (m, 2H), 7.13 (m, 1H), 6.67 (m, 1H), 3.98 (m, 1H), 3.77 (q, J=6.9 Hz, 1H), 3.62 (q, J=6.9 Hz, 1H), 3.29 (m, 2H), 1.86 (m, 3H), 1.59 (m, 1H); MS (ES+): 553.3
64i	490	491	62i	I-2, S	1 H NMR (DMSO-d6): δ 12.81 (br s, 1 H), 9.13 (s, 2 H), 8.85 (s, 2H), 8.26 (m, 2H), 7.96 (m, 2H), 7.86 (m, 2H), 7.74 (m, 5H), 7.32 (m, 1H), 7.13 (m, 1H), 6.67 (m, 1H), 3.99 (m, 1H), 1.5-0.85 (m, 14H); MS (ES+): 567.3
64j	492	493	62j	I-2, S	1 H NMR (DMSO-d6): δ 13.74 (br s, 1H), 9.07 (s, 2H), 8.92 (s, 2H), 8.62 (t, J=5.6 Hz, 1H), 8.03 (s, 1H), 7.89 (d, J=1.7 Hz, 1H), 7.79 (m, 2H), 7.64 (m, 4H), 7.10 (m, 3H), 6.99 (d, J=8.5 Hz, 1H), 6.64 (m, 1H), 3.08 (t, J=6.0 Hz, 2H), 1.00 (m, 1H), 0.40 (m, 2H), 0.20 (m, 2H); MS (ES+): 523.4
64k	494	495	62k	I-2, S	1 H NMR (DMSO-d6): δ 9.12 (s, 2H), 8.88 (s, 2H), 8.52 (m, 1H), 8.12 (m, 1H), 7.92 (m, 2H), 7.81 (m, 3H), 7.67 (m, 4H), 7.14 (m, 3H), 6.66 (m, 1H), 4.75 (d, J=4.5 Hz, 1H), 3.77 (m, 1H), 3.17 (m, 1H), 1.04 (d, J=6.0 Hz, 3H); MS (ES+): 527.2
64l	496	497	62l	I-2, S	1 H NMR (DMSO-d6): δ 13.91 (br s, 1H), 9.07 (s, 2H), 8.90 (s, 2H), 8.29 (d, J=8.1 Hz, 1H), 8.00 (s, 1H), 7.89 (m, 1H), 7.78 (m, 2H), 7.64 (m, 5H), 7.08 (m, 2H), 6.96 (d, J=7.7 Hz 1H), 6.64 (m, 1H), 3.71 (m, 1H), 1.82-1.03 (m, 10H)p; MS (ES+): 551.33
64m	498	499	62m	I-2, S	1 H NMR (DMSO-d6): δ 13.87 (br s, 1H), 9.07 (s, 2H), 8.90 (s, 2H), 8.48 (m, 1H), 7.99 (s, 1H), 7.89 (m, 1H), 7.79 (m, 2H), 7.62 (m, 5H), 7.10 (m, 2H), 6.97 (d, J=7.9 Hz 1H), 6.64 (m, 1H), 2.73 (d, J=4.5 Hz, 3H); MS (ES+): 483.2
64n	500	501	62n	I-2, S	1 H NMR (DMSO-d6): δ 9.08 (s, 2H), 8.85 (s, 2H), 8.26 (d, J=8.7 Hz, 1H), 8.07 (s, 1H), 7.91 (s, 1H), 7.80 (m, 2H), 7.67 (m, 5H), 7.09 (m, 3H), 6.65 (m, 1H), 3.89 (m, J=7.0 Hz, 1H), 1.49 (m,J=6.9 Hz, 2H), 1.10 (d, J=6.6 Hz, 3H), 0.85 (t, J=7.2 Hz, 3H); MS (ES+): 525.2
64o	502	503	62o	I-2, S	1 H NMR (DMSO-d6): δ 9.19 (m, 2H), 9.10 (s, 2H), 8.82 (s, 2H), 8.19 (m, 1H), 7.94 (s, 1H), 7.83 (m, 2H), 7.68 (m, 4H), 7.33-7.10 (m, 8H), 6.66 (m, 1H), 4.45 (d, J=5.7 Hz, 2 Hz); MS (ES+): 559.2
64p	504	505	62p	I-2, S	1 H NMR (DMSO-d6): δ 9.22 (m, 2H), 9.09 (s, 2H), 8.81 (s, 2H), 8.17 (m, 1H), 7.95 (s, 1H), 7.82 (m, 2H), 7.68 (m, 4H), 7.16 (m, 4H), 6.66 (m, 1H), 4.06 (m, 2H); MS (ES+): 551.22
64q	506	507	62q	I-2, S	1 H NMR (DMSO-d6): δ 9.10 (s, 2H), 8.86 (s, 2H), 8.56 (m, 1H), 8.13 (m, 1H), 7.93 (s, 1H), 7.82 (m, 2H), 7.67 (m, 5H), 7.15 (m, 3H), 6.66 (m, 1H), 3.19 (m, 2H), 1.50 (m, 2H), 1.28 (m, 4H), 0.87 (t, J=7.0 Hz, 3H); MS (ES+): 539.3
64r	508	509	62r	I-2, S	1 H NMR (DMSO-d6): δ 9.09 (s, 2H), 8.90 (m, 2H), 8.15 (m, 2H), 7.93 (s, 1H), 7.81 (m, 3H), 7.68 (m, 4H), 7.13 (m, 3H), 6.66 (m, 1H), 3.83 (m, 1H), 1.47 (m, 4H), 1.25 (m, 4H), 0.83 (m, 6H); MS (ES+): 567.3
64s	510	511	62s	I-2, S	1 H NMR (DMSO-d6): δ 9.08 (s, 2H), 8.86 (s, 2H), 8.48 (m, 1H), 8.03 (m, 1H), 7.90 (s, 1H), 7.79 (m, 2H), 7.65 (m, 5H), 7.12 (m, 2H), 7.02 (m, 1H), 6.65 (m, 1H), 3.22 (m, 2H), 1.42 (t, J= 8.2 Hz, 2H), 0.91 (s, 9H); MS (ES+): 553.4
64t	512	513	62t	I-2, S	1 H NMR (DMSO-d6): δ 13.61 (br s, 1H), 9.07 (s, 2H), 9.00 (s, 2H), 8.52 (t, J=5.5 Hz, 1H), 8.02 (s, 1H), 7.90 (d, J=1.9 Hz, 1H), 7.79 (m, 2H), 7.64 (m, 5H), 7.10 (m, 2H), 7.00 (d, J= 7.7 Hz, 1H), 6.64 (m, 1H), 4.47 (t, J=5.3 Hz, 1H), 3.43 (m, 2H), 3.27 (m, 2H), 1.64 (qui, J=6.8 Hz, 2H); MS (ES+): 527.23
64u	514	515	62u	I-2, S	1 H NMR (DMSO-d6): δ 12.7 (br s, 1H), 9.09 (s, 2H), 8.91 (s, 2H), 8.57 (m, 1H), 8.11 (s, 1H), 7.92 (d, J=1.9 Hz, 1H), 7.81 (m, 3H), 7.67 (m, 5H), 7.14 (m, 2H), 6.66 (m, 1H), 4.40 (t, J=5.3 Hz, 1H), 3.39 (m, 2H), 3.22 (m, 2H), 1.48 (m, 4H); MS (ES+): 541.34
64v	516	517	62v	I-2, S	1 H NMR (DMSO-d6): δ 9.16-8.89 (m, 4H), 8.16 (m, 1H), 7.93 (s, 1H), 7.81 (m, 3H), 7.67 (m, 4H), 7.56 (s, 1H), 7.15 (m, 5H), 6.65 (m, 1H), 6.38 (m, 1H), 6.26 (m, 1H), 4.42 (d, J=4.9 Hz, 2H); MS (ES+): 549.27
64w	518	519	62w	I-2, S	1 H NMR (DMSO-d6): δ 11.59 (br s, 1H), 9.14 (s, 2H), 8.98 (s, 2H), 8.70 (t, J=5.7 Hz, 1H), 8.24 (s, 1H), 7.99 (m, 2H), 7.87 (m, 3H), 7.71 (m, 3H), 7.36 (s, 1H), 7.27 (m, 2H), 7.10 (m, 2H), 6.67 (m, 1H), 4.07 (t, J=6.9 Hz, 2H), 3.24 (q, J=6.5 Hz, 2H), 1.98 (qui, J=6.7 Hz, 2H); MS (ES+): 577.17
64x	520	521	62x	I-2, S	1 H NMR (DMSO-d6): δ 13.72 (br s, 1H), 9.13 (s, 2H), 9.06 (s, 2H), 8.50 (t, J=5.7 Hz, 1H), 8.00 (d, J=1.3 Hz, 1H), 7.89 (d, J=1.9 Hz, 1H), 7.78 (m, 2H), 7.62 (m, 4H), 7.08 (m, 2H), 6.96 (d, J=7.9 Hz, 1H), 6.64 (m, 1H), 3.04 (t, J=6.5 Hz, 2H), 1.72-1.43 (m, 6H), 1.25-1.08 (m, 3H), 0.88 (m, 2H); MS (ES+): 565.25
64y	522	523	62y	I-2, S	1 H NMR (DMSO-d6): δ 9.16-8.87 (m, 4H), 8.09 (s, 1H), 7.91 (s, 1H), 7.80 (m, 2H), 7.65 (m, 5H), 7.12 (m, 5H), 6.65 (m, 1H), 4.01 (m, 2H), 3.10 (m, 1H); MS (ES+): 507.2
64z	524	525	62z	I-2, S	1 H NMR (DMSO-d6): δ 9.10 (s, 2H), 8.97 (s, 2H), 8.59 (t, J=5.7 Hz, 1H), 8.13 (s, 1H), 7.93 (s, 1H), 7.80 (m, 3H), 7.68 (m, 4H), 7.16 (m, 4H), 6.65 (m, 1H), 3.26 (qui, J=6.0 Hz, 2H), 1.10 (t, J=7.2 Hz, 3H); MS (ES+): 497.2
64aa	526	527	62aa	I-2, S	1 H NMR (DMSO-d6): δ 14.1 (br s, 1H), 9.08 (s, 2H), 8.79 (s, 2H), 8.45 (m, 1H), 8.01 (s, 1H), 7.90 (s, 1H), 7.79 (m, 3H), 7.63 (m, 5H), 7.09 (m, 2H), 6.98 (m, 1H), 6.65 (m, 1H), 4.80 (d, J=4.7-Hz, 1H), 4.56 (t, J=6.8 Hz, 1H), 3.60 (m, 1H), 3.32-2.90 (m, 3H); MS (ES+): 543.2
64ab	528	529	62ab	I-2, S	1 H NMR (DMSO-d6): δ 10.34 (s, 1H), 9.07 (s, 2H), 8.85 (s, 2H), 8.18 (s, 1H), 7.93 (s, 1H), 7.80 (m, 6H), 7.66 (m, 4H), 7.34 (m, 2H), 7.11 (m, 4H), 6.65 (m, 1H); MS (ES+): 545.2
64ac	530	531	62ac	I-2, S	1 H NMR (DMSO-d6): δ 9.07 (m, 4H), 8.38 (d, J=8.5 Hz, 1H), 8.10 (s, 1H), 7.92 (s, 1H), 7.84-7.62 (m, 7H), 7.11 (m, 3H), 6.66 (m, 1H), 3.94 (m, 1H), 1.88-1.35 (m, 12H); MS (ES+): 565.3
64ad	532	533	62ad	I-2, S	1 H NMR (DMSO-d6): δ 13.71 (m, 2H), 9.36-8.57 (m, 4H), 8.50 (m, 1H), 7.98 (s, 1H), 7.89 (s, 1H), 7.78 (2H), 7.61 (m, 5H), 7.08 (m, 2H), 6.95 (d, J=7.9 Hz, 1H), 6.63 (m, 1H), 3.19 (m, 2H), 2.16 (t, J=7.2 Hz, 2H), 1.48 (m, 4H), 1.28 (m, 2H); MS (ES−): 581.2
64ae	534	535	62ae	I-2, S	1 H NMR (DMSO-d6): δ 9.12 (s, 2H), 8.89 (s, 2H), 7.91 (m, 1H), 7.81 (m, 2H), 7.70 (d, J=8.7 Hz, 2H), 7.62 (d, J=8.9 Hz, 2H), 7.48 (m, 1H), 7.22 (m, 2H), 7.11 (d, J=3.4 Hz, 1H), 7.05 (d, J=7.2 Hz, 1H), 6.65 (m, 1H), 3.53 (m, 2H), 3.08 (m, 2H), 1.62-1.21 (m, 6H); MS (ES+): 537.20
64af	536	537	62af	I-2, S	1 H NMR (DMSO-d6): δ 12.81 (br s, 1H), 9.13 (s, 2H), 8.82 (s, 2H), 7.95 (s, 1H), 7.85 (m, 2H), 7.71 (m, 5H), 7.43 (m, 1H), 7.29 (m, 2H), 7.13 (m, 1H), 6.67 (m, 1H), 3.49-2.97 (m, 4H), 1.67-1.37 (m, 2H), 1.08 (m, 1H), 0.90 (m, 3H), 0.61-0.26 (m, 4H); MS (ES+): 565.3
64ag	538	539	62ag	I-2, S	1 H NMR (DMSO-d6): δ 13.78 (s, 1H), 9.09-8.22 (m, 5H), 7.97 (s, 1H), 7.89 (s, 1H), 7.77 (m, 2H), 7.61 (m, 5H), 7.03 (m, 3H), 6.64 (m, 1H), 3.22 (m, 2H), 2.20 (t, J=7.0 Hz, 2H), 1.71 (t, J=7.3 Hz, 2H); MS (ES−): 553.24.

[0293]

540
Cpd.			Starting	Method	Analytical
No.	-R	-R′	From	Used	Data
65	541	542	61	A-4, I-2, S	1 H NMR (DMSO-d6, D2O): δ 13.87 (br s, 1 H), 9.56 (m, 2 H) 9.21 (s, 1 H), 8.74 (s, 1 H), 8.47 (m, 1 H), 7.97 (m, 1 H), 7.88 (s, 1 H), 7.78 (m, 3 H), 7.58 (m, 7 H), 7.09 (m, 3 H), 6.96 (m, 1 H), 6.65 (m, 1 H), 3.14 (m, 4 H), 1.77-0.80 (m, 18 H); MS (ES+): 609.4
71a	—CH═CH2	543	67	A-4, I-2, S	1 H NMR (DMSO-d6): δ 13.80 (br s, 1 H), 9.91 (s, 1 H), 9.41 (s, 1 H), 8.63 (m, 2 H), 8.07 (s, 1 H), 7.98 (s, 1 H), 7.60 (m, 8 H), 6.90 (m, 3 H), 5.94 (d, J=17.7 Hz, 1 H), 4.37 (m, 1 H), 4.16 (m, 1 H), 2.41-1.58 (m, 12 H); MS (ES+): 537.4
71b	—CH═CH2	544	67	A-4, I-2, S	1 H NMR (DMSO-d6): δ 9.76 (s, 1 H), 9.41 (s, 1 H), 8.95 (s, 1 H), 8.53 (m, 1 H), 8.07 (s, 1 H), 7.65 (m, 8 H), 7.08 (m, 2 H), 6.85 (dd, J 10.9 and 17.7 Hz, 1 H), 6.92 (m, 3 H), 5.97 (d, J=17.7 Hz, 1 H), 5.37 (d, J=10.9 Hz, 1 H), 2.84 (m, 1 H), 2.70 (m, 1 H), 0.98-0.51 (m, 8H); MS (ES+): 509.4
71c	—CH═CH2	545	67	A-4, I-2, S	1 H NMR (DMSO-d6): δ 12.51 (br s, 1 H), 9.59 (s, 1 H), 9.22 (s, 1 H), 8.79 (s, 1 H), 8.58 (t, J=5.5 Hz, 1 H), 8.17 (s, 1 H), 7.67 (m, 8 H), 7.12 (m, 2 H), 6.86 (dd, J=10.9 and 17.7 Hz, 1 H), 5.98 (d, J=17.7 Hz, 1 H), 5.38 (d, J=10.9 Hz, 1 H), 3.27 (m, 4 H), 1.20 (t, J=7.2 Hz, 1 H), 1.09 (t, J=7.2 Hz, 1 H); MS (ES+): 485.3

[0294]

546
Cpd.			Starting	Method	Analytical
No.	-R	-R′	From	Used	Data
68a	—CH3	547	67	A-4	MS (ES+): 599.4
68b	—CH3	548	67	A-4	MS (ES+): 641.4
68c	—CH3	549	67	A-4	MS (ES+): 625.3
68d	—CH3	550	67	A-4	MS (ES+): 583.3
68e	—CH3	551	67	A-4	MS (ES+): 585.3
68f	—CH3	552	67	A-4	MS (ES+): 599.4
68g	—CH3	553	67	A-4	MS (ES+): 625.2
68h	—CH3	554	67	A-4	MS (ES+): 619.2
68i	—CH3	555	67	A-4	MS (ES+): 615.3
68j	—CH3	556	67	A-4	MS (ES+): 597.3
68k	—CH3	557	67	A-4	MS (ES+): 557.3
68l	—CH3	558	67	A-4	MS (ES+): 571.4
68m	—CH3	559	67	A-4	MS (ES+): 639.4
68n	—CH3	560	67	A-4	Characterized in the next step
68o	—CH3	561	67	A-4	MS (ES+): 613.5
68p	—CH3	562	67	A-4	MS (ES+): 613.5
68q	—CH3	563	67	A-4	MS (ES+): 641.5
68r	—CH3	564	67	A-4	MS (ES+): 714.5
68s	—CH3	565	67	A-4	MS (ES+): 611.4
68t	—CH3	566	67	A-4	MS (ES+): 641.4
68u	—CH3	567	67	A-4	MS (ES+): 583.3
68v	—CH3	568	67	A-4	MS (ES+): 597.4
68w	—CH3	569	67	A-4	MS (ES+): 587.4
68x	—CH3	570	67	A-4	MS (ES+): 613.5
68y	—CH3	571	67	A-4	MS (ES+): 627.3
68z	—CH3	572	67	A-4	MS (ES+): 613.2
68aa	—CH3	573	67	A-4	MS (ES+): 686.2
68ab	—CH3	574	67	A-4	MS (ES+): 617.3
68ac	—CH3	575	67	A-4	MS (ES+): 614.3

[0295]

	-R (Position with
Cpd.	Respect to Phenyl				Starting	Method
No.	Ring)	-R′	-R″	X	From	Used	Analytical Data
74	—OCH3 (3)	—CHO	—CH3	CH	73 + 3a	D-2	MS (ES−): 368.2
75a	—OH (3)	—CHO	—CH3	CH	74	V-2, W	MS (ES−): 354.1
75b	—OH (3)	—CHO	—Bn	CH	74	V-1, H	MS (ES−): 430.2
76a	—OSO2CF3 (3)	—CHO	—CH3	CH	75a	B-2	MS (ES+): 488.1
76b	—OSO2CF3 (3)	—CHO	—Bn	CH	75b	B-2	MS (ES·): 562.3 ; MS (ES+): 586.3 (M + Na)+
77a	—CHCH2 (3)	—CHO	—CH3	CH	76a	D-3	MS (ES+): 366.38
77b	—OCH2CO2C2H5 (3)	—CHO	—Bn	CH	75b	X	Characterized in the next step
77c	—OCH2CONH2 (3)	—CHO	—Bn	CH	75b	X	MS (ES+): 487.3; MS (ES+): 511.35 (M + Na)+
77d	576	—CHO	—Bn	CH	76b	D-2	Characterized in the next step
77e	577	—CHO	—Bn	CH	75b	D-8	MS (ES+): 530.3 (M + Na)+); MS (ES−):506.3
77f	578	—CHO	—Bn	CH	75b	X	MS (ES+): 496.3 (M + Na)+
77g	579	—CHO	—Bn	CH	75b	X	MS (ES +): 482.4 (M + Na)+
77h	580	—CHO	—Bn	CH	75b	X	MS (ES+): 510.4 (M + Na)+
77i	581	—CHO	—Bn	CH	75b	X	1 HNMR (CDCl3): δ9.59 (s, 1 H), 8.39 (d, J=2 Hz, 1 H), 8.03 (m, 2 H), 7.84 (d, J=8.9 Hz, 1 H), 7.35 (d, J=8 Hz, 1 H), 7.28 (m, 2 H), 7.12 (m, 2 H), 6.93 (dd, J=2.5 and 8.8 Hz, 1 H), 6.64 (d, J=2.5 Hz, 1 H), 6.31 (t, J=6 and 5 Hz, 1 H), 5.06 (m, 2 H), 4.42 (t, J=4.5 Hz, 2 H), 4.13 (m, 2 H), 3.34 (t, J=6.8 Hz, 2 H), 2.11 (s, 3 H),
# 1.94 (m, 1H), 1.01 (d, J=6.8 Hz, 6 H)
78a	—CH═CH2 (3)	—CO2H	—CH3	CH	77a	E	MS (ES−): 380.1
78b	—OSO2CF3 (3)	—CO2H	—Bn	CH	76b	E	Characterized in the next step
78c	—OCH2CO2C2H5 (3)	—CO2H	—Bn	CH	77b	E	Characterized in the next step
78d	—OCH2CONH2 (3)	—CO2H	—Bn	CH	77c	E	MS (ES+): 527.35 (M + Na)+
78e	582	—CO2H	—Bn	CH	77d	E	MS (ES+): 536.4 (M + Na)+
78f	583	—CO2H	—Bn	CH	77e	E	MS (ES−): 522.3
78g	—OCH3 (3)	—CO2H	—CH3	CH	74	E	MS (ES−): 384.1
78h	584	—CO2H	—Bn	CH	77f	E	MS (ES−): 488.3
78i	585	—CO2H	—Bn	CH	77g	E	MS (ES−): 474.4
78j	586	—CO2H	—Bn	CH	77h	E	MS (ES−): 502.4
78k	587	—CO2H	—Bn	CH	77i	E	Characterized in the next step
90	—OBn (5)	—CHO	—CH3	CH	89 + 3a	D-2	1 HNMR (CDCl3): δ 10.47 (s, 1 H), 8.36 (d, J=2 Hz, 1 H), 7.96 (dd, J=2.2 and 7.7 Hz, 1 H), 7.68 (m, 2 H), 7.46 (m, 5 H), 7.23 (d, J=8 Hz, 1 H), 7.12 (d, J=8.7 Hz, 1 H), 6.73 (d, J=7.2 Hz, 1 H), 5.23 (q,J=11 and 15 Hz, 2 H), 3.67(s, 3 H), 3.31 (t, J=6.8 Hz, 2 H), 1.94 (m, 1 H), 1.01 (d, J=6.8 Hz, 6 H), MS (ES+)
# 468.2 (M +Na)+(ES−) 444.2
91	—OBn (5)	—CO2H	—CH3	CH	90	E	1 HNMR (CDCl3): δ 8.22 (s, 1 H), 7.83 (d, J=7.2 Hz, 1 H), 7.34 (m, 8 H), 7.02 (d, J=8.1 Hz, 1 H), 6.75 (d, J=7.4 Hz, 1 H), 5.16 (s, 2 H), 3.66 (s, 3 H), 3.21 (t, J=6.8 Hz, 2 H), 1.85 (m, 1 H), 0.94 (d, J=6.8 Hz, 6 H), MS (ES +) 484.1 (M + Na)+
92	—OBn (5)	—CO2MEM	—CH3	CH	91	F	MS (ES+): 572.2 (M + Na)+
93	—OH (5)	—CO2MEM	—CH3	CH	92	G	MS (ES+): 482. (M + Na)+
94	—OSO2CF3 (5)	—CO2MEM	—CH3	CH	93	B-2	MS (ES+): 614.3 (M + Na)+
95a	588	—CO2MEM	—CH3	CH	94	D-3	MS (ES+) 562.3 (M + Na)+
96a	589	—CO2H	—CH3	CH	95a	I-1	MS (ES+) 452.1 (M + Na)+
101	—OCH3 (2)	—CHO	—CH3	CH	100 + 3a	D-2	MS (ES+) 370.1
102	—OCH3 (2)	—CO2H	—CH3	CH	101	E	MS (ES−) 384.2; MS (ES+) 386.2
108	—OBn (2)	—CHO	—CH3	CH	107 + 3a	D-2	MS (ES+): 446.2
109	—OBn (2)	—CO2H	—CH3	CH	108	E	MS (ES−): 460.1
131	—H	—CHO	—CH3	CH	130 + 3a	D-2	1 HNMR (CDCl3-d1): δ 9.79 (s, 1 H), 8.39 (d, J=1.88 Hz, 1 H), 8.02 (t, J=6.0 Hz, 2 H), 7.59 (m, 2 H), 7.38 (d, J=7.9 Hz, 1 H), 7.22 (d, J=8.1 Hz, 1 H), 6.30 (b, 1 H), 3.72 (s, 3 H), 3.36 (t, J=6.6 Hz,2 H), 1.96 (m, 1 H), 1.02 (d, J=6.8 Hz, 6 H), MS (ES+): 340.1
132	—H	—CO2H	—CH3	CH	131	E	HNMR (DMSO-d6): δ 12.28 (b, 1 H), 8.52 (d, J=6.03 Hz, 1 H), 8.12 (s, 1 H), 7.86 (d, J=8.1 Hz, 1 H), 7.74 (d, J=7.74 Hz, 1 H), 7.41 (t, J=8.67 Hz, 1 H), 7.31 (t, J=7.9 Hz, 1 H), 7.12 (d, J=8.1 Hz, 1 H), 6.97 (d, J=7.5 Hz, 1 H), 3.39 (s, 3 H), 2.92 (t, J=6.0 Hz, 2 H), 1.66 (m, 1 H), 0.78 (d, J=7.4 Hz, 6 H), MS (ES−): 354.1
193a	—H	590	—CH3	CH	192a + 6a	D-7	MS (ES+): 560.5
193b	—H	591	—CH3	CH	192b + 6a	D-7	MS (ES+): 574.5)
194a	—H	592	—CH3	CH	193a	S-2	MS (ES+): 460.3
194b	—H	593	—CH3	CH	193b	S-2	MS (ES+): 474.3
195a	—H	594	—H	CH	194a	I-2	1 HNMR (DMSO-d6): δ 8.79 (bs, 4 H), 8.63 (t, J=6.5 Hz, 1 H), 8.35 (s, 1 H), 7.85 (d, J=6 Hz, 1 H), 7.62 (d, J=8.2 Hz, 2 H), 7.26 (m, 5 H), 7.06 (m, 1 H), 5.0 (m, 2 H), 3.09 (t, J=6.2 Hz, 2 H), 1.86 (m, 1 H), 0.89 (d, J=6.6 Hz, 6 H); MS (ES−): 444.3 and (ES+) 446.3
195b	—H	595	—H	CH	194b	I-2	1 HNMR (DMSO-d6/DCl): δ8.24 (d, J=1.6 Hz, 1 H), 7.91 (dd, J=7.7 and 1.6 Hz, 1 H), 7.56 (d, J=8.7 Hz, 1 H), 7.48 (d, J=8.7 Hz, 1 H), 7.32 (t, J=8 Hz, 1 H), 7.16 (m, 3 H), 6.91 (t, J=7.5 Hz, 1 H), 6.76 (d, J=8.5 Hz, 1 H), 6.66 (d, J=8.5 Hz, 1 H), 4.99 (m, 1 H), 2.92 (d, J=6.9 Hz, 2 H), 1.68 (m, 1 H), 1.33 (d, J=6 Hz, 1.2H), 1.27 (d, J=6 Hz, 1.8 H),
# 0.71 (d, J=6.5 Hz, 6 H); MS (ES−): 458.2 and (ES+) 460.3
200	—H	596	—CH3	CH	199 + 6a	D-7	MS (ES+): 573.5
201	—H	597	—H	CH	200	I-2	1 HNMR (DMSO-d6/DCl): δ8.49 (t, J=5.6 Hz, 1 H), 8.18 (d, J=6.9 Hz, 1 H), 7.84 (t, J=7.8 Hz, 1 H), 7.23 (m, 4 H), 7.01 (m, 2 H), 6.82 (d, J=7 Hz, 1 H), 6.22 (d, J=8.5 Hz, 1 H), 6.15 (d, J=8.5 Hz, 1 H), 3.95 (m, 1 H), 2.85 (t, J=5.8 Hz, 1 H), 1.62 (m, 1 H), 1.23 (s, 9H), 1.1 (d, J=6.7 Hz, 1.2 H), 1.05 (d, J=6.7 Hz, 1.8 H), 0.67 (d, J=6.6 Hz,
# 6 H); MS (ES+): 559.4
202	—H	598	—H	CH	201	S	MS (ES+): 459.3
203	—OBn (4)	599	—CH3	CH	45	R	MS (ES+): 679.4
204	—OBn (4)	600	—H	CH	203	I-2	MS (ES−): 663.4
209a	—H	601	—CH3	CH	132	A-7	MS (ES−): 454.3
209b	—CH═CH2 (4)	602	—CH3	CH	30f	A-7	1 HNMR (DMSO-d6): δ 10.72 (s, 1 H), 8.65 (d, J=6.03 Hz, 1 H), 8.24 (s, 1 H), 8.03 (d, J=8.1 Hz, 1 H), 7.75 (m, 6 H), 7.40 (d, J=7.90 Hz, 1 H), 7.34 (d, J=8.1 Hz, 1 H), 6.88 (q, J=11.2 Hz, 1 H), 6.04 (d, J=7.5 Hz, 1 H), 5.41 (d, J=11.1 Hz, 1 H), 3.55 (s, 3 H), 3.10 (t, J=6.6 Hz, 2 H), 1.86 (m, 1 H), 0.88 (d, J=6.6 Hz,
# 6 H); MS (ES+): 480.3
209c	—CH═CH2 (4)	603	—CH3	N	227	A-7	MS (ES+) 481.4
210b	—CH═CH2 (4)	604	—CH3	CH	209b	Y	1 HNMR (DMSO-d6): δ 10.12 (s, 1 H), 9.37 (b, 1 H), 8.48 (t, J=6.1 Hz, 1 H), 8.05 (d, J=1.9 Hz, 1 H), 7.85 (d, J=7.9 Hz, 1 H), 7.56 (d, J=7.8 Hz, 1 H), 7.49 (d, J=7.9 Hz, 1 H), 7.36 (s, 4 H), 7.21 (d, J=7.9 Hz, 1 H), 7.10 (d, J=2.8 Hz, 1 H), 6.69 (m, 1 H), 5.84 (d, J=15.5 Hz, 1 H), 5.60 (b, 1 H), 5.22 (d, J=11.4 Hz, 1 H), 3.38
# (s, 3 H), 2.91 (t, J=6 Hz, 2 H), 1.66 (m, 1 H), 0.71 (d, J=6.8 Hz, 6 H); MS (ES+) 515.40
210c	—CHCH2 (4)	605	—CH3	N	209c	Y	1 H NMR (DMSO-d6): δ 10.50 (s, 1 H), 9.54 (s, 1 H), 8.58 (t, J=6.4 Hz, 1 H), 8.21-7.34 (m, 9H), 6.90 (dd,J=11.1 and 17.3 Hz, 1 H), 6.07 (d, J=17.3 Hz, 1 H), 5.74 (s, 2 H), 5.45 (d, J=11.1 Hz, 1 H), 3.60 (s, 3 H), 3.16 (t, J=6.2 Hz, 2 H), 1.88 (m, 1 H), 0.88 (d, J=6.4 Hz, 6 H); MS (ES+): 516.40
211b	—CH═CH2 (4)	606	—H	CH	210b	I-2	1 HNMR (DMSO-d6): δ 12.62 (bs, 1H), 10.24 (s, 1 H), 8.48 (t, J=5.65 Hz, 1 H), 8.15 (s, 1 H), 7.81 (d, J=10.9 Hz, 1 H), 7.61 (s, 1 H), 7.50 (d, J=7.9 Hz, 1 H), 7.49 (s, 6 H), 7.16 (d, J=8.1 Hz, 1 H), 7.08 (d, J=8.1 Hz, 1 H), 6.72 (m, 1 H), 5.85 (d, J=13.7 Hz, 1 H), 5.24 (d, J=11.5 Hz, 1 H), 2.93 (t, J=6 Hz, 2 H), 1.68 (m, 1 H), 0.72 (d,
# J=6.8 Hz, 6 H); MS (ES+) 501.40, (ES+) 499.2
211c	—CH═CH2 (4)	607	—H	N	210c	I-2	1 H NMR (DMSO-d6): δ 9.50 (s, 1 H), 8.68 (m, 1 H), 7.93-7.40 (m, 10 H), 7.13 (m, 2 H), 6.86 (dd, J=11.1 and 17.3 Hz, 1 H), 5.99 (d, J=17.3 Hz, 1 H), 5.69 (s, 1 H), 5.38 (d, J=11.1 Hz, 1 H),3.14 (t, J=6.2 Hz, 2 H), 1.86 (m, 1 H), 0.88 (d, J=6.4 Hz, 6 H); MS (ES−): 500.36.
212	—CH═CH2 (4)	608	—CH3	CH	187a	AE-5	1 HNMR (DMSO): δ 8.70 (t, J=5.6 Hz, 1 H), 8.36 (d, J=1.7 Hz, 1 H), 8.07 (dd, J=8.1, 1.9 Hz, 1 H), 7.42 (m, 4H), 7.09 (d, J=5.5 Hz, 1 H), 7.04 (d, J=7.7 Hz, 1 H), 6.74 (dd, J=17.5, 10.9 Hz, 1 H), 6.49 (d, J=8.8 Hz, 2 H), 5.79 (d, J=17.7 Hz, 1 H), 5.27 (d, J=10.9 Hz, 1 H), 4.0 (t, J=6.0 Hz, 2 H), 3.62 (s, 3 H), 3.11 (t, J=6.2.
# 2H), 1.86 (m, 1 H), 0.90 (d, J=6.6 Hz, 6 H)
212a	—CH═CH2 (4)	609	—CH3	N	247	AE-5	MS (ES+) 469.3
212b	—CHαCH2 (4)	610	—CH3	CH	187a	AE-5	characterized in the next step
213	—CH═CH2 (4)	611	—CH3	CH	212	Y	1 HNMR (DMSO): δ 9.23 (s, 1 H), 8.71 (t, J=6.2 Hz, 1 H), 8.36 (d, J=1.9 Hz, 1 H), 8.09 (dd, J=7.9, 1.7 Hz, 1 H), 7.49 (d, J=7.9 Hz, 2 H), 7.40 (d, J=8.3 Hz, 1 H), 7.32 (d, J=8.8 Hz, 2 H), 7.04 (d, J=7.9 Hz, 1 H), 6.73 (dd, J=17.7, 11.1 Hz, 1 H), 6.40 (d, J=8.5 Hz, 2 H), 6.33 (t, J=7.0 Hz, 1 H), 5.78 (d, J=17.7 Hz, 1 H), 5.58
# (b, 1 H), 5.26 (d, J=11.1 Hz, 1 H), 3.96 (m. 2 H), 3.64 (s, 3 H), 3.11 (t, J=6.4 Hz, 2 H), 1.86 (m,, 1 H), 0.90 (d, J=6.8 Hz, 6 H); MS (ES+): 501.3
213a	—CH═CH2 (4)	612	—CH3	N	212a	Y	1 H NMR (DMSO-d6): δ 8.98 (s, 1 H), 8.46 (t, J=6.4 Hz, 1 H), 7.96 (d, J=8.0 Hz, 1 H), 7.87 (d, J=8.0 Hz, 1 H), 7.31 (s, 1 H), 7.21 (d, J=8.1 Hz, 2 H), 7.09 (d, J=8.5 Hz, 1 H), 6.88 (d, J=7.9 Hz, 1 H), 6.51 (dd, J=11.1 and 17.3 Hz, 1H), 6.15 (m, 3 H), 5.58 (d, J=17.3 Hz, 1 H), 5.30 (s, 1 H), 5.06 (d, J=11.1 Hz, 1 H), 3.77 (m, 2 H),
# 3.42 (s, 3 H), 2.93 (t, J=7.0 Hz, 2 H), 1.67 (m, 1 H), 0.66 (d, J=6.4 Hz, 6 H); MS (ES+): 502.35
213b	—CH═CH2 (4)	613	—CH3	CH	212b	Y	1 HNMR (DMSO-d6): δ 9.4 (bs, 1 H), 8.70 (k, J=5.5 Hz, 1 H), 8.35 (d, J=1.7 Hz, 1 H), 8.17 (d, J=2.5 Hz, 1 H), 8.47 (dd, J=8.1, 2 Hz, 1 H), 7.58 (dd, J=8.8, 2.5 Hz, 1 H), 7.47 (m, 1H, 2 H), 7.38 (d, J=7.2 Hz, 1 H), 7.07 (t, J=5 Hz, 1 H), 7.03 (d, J=7.7 Hz, 1 H), 6.73 (dd, J=11.17 Hz, 1 H), 6.41 (d, J=8.8 Hz, 1 H),
# 5.80 (d, J=17 Hz, 1 H), 5.78 (bs, 2 H), 5.21 (d, J=11 Hz, 1 H), 4.16 (d, J=5.3 Hz), 3.62 (s, 3 H), 3.15 (t, J=6.78 Hz, 2 H), 1.87 (m, 1 H), 0.91 (d, J=6.7 Hz, 6 H); MS (ES+) 502.46.
214	—CH═CH2 (4)	614	—H	CH	213	I-2	1 HNMR (DMSO): δ 8.76 (t, J=5.8 Hz, 1 H), 8.37 (s, 1 H), 8.04 (d, J=8.7 Hz, 1 H), 7.39 (m, 5 H), 7.06 (d, J=8.3 Hz, 1 H), 6.72 (dd, J=17.9, 11.3 Hz, 1 H), 6.43 (d, J=8.5 Hz, 3 H), 5.76 (d, J=17.9 Hz, 1 H), 5.24 (d, J=11.1 Hz, 1 H), 3.98 (m. 2 H), 3.11 (t, J=6.6 Hz, 2 H), 1.86 (h, J=6.8 Hz, 1 H), 0.90 (d, J=6.8, 6 H); MS (ES+): 487.2
214a	—CH═CH2 (4)	615	—H	N	213a	I-2	1 H NMR (DMSO-d6): δ 9.33 (s, 1 H), 8.98 (t, J=6.4 Hz, 1 H), 8.16 (d, J=8.0 Hz, 1 H), 8.00 (d, J=8.0 Hz, 1 H), 7.51 (s, 1 H), 7.41 (d, J=8.1 Hz, 1 H), 7.31 (d, J=8.5Hz, 2 H), 7.11 (d, J=7.9 Hz, 1 H), 6.75 (dd, J=11.1 and 17.3 Hz, 1 H), 6.46 (m, 3 H), 5.80 (d, J=17.3 Hz, 1 H), 5.72 (s, 2 H), 5.27 (d, J=11.1 Hz, 1 H), 3.97 (s, 2 H), 2.93 (t,
# J=7.0 Hz, 2 H), 1.90 (m, 1 H), 0.90 (d, J=6.4 Hz, 6 H); MS (ES+): 488.36.
214b	—CH═CH2 (4)	616	H	CH	213b	I-2	1 HNMR (DMSO-d6): δ 8.69 (t, J=6 Hz, 1 H), 8.35 (1,1 H), 8.63 (s, 1 H), 8.03 (d, J=8 Hz, 1 H), 7.60 (d, J=9 Hz, 1 H), 7.47 (s, 1 H), 7.41 (m, 3 H), 7.06 (d, J=7.7 Hz, 1 H), 6.75 (dd, J=10.5, 17.5 Hz, 1 H), 6.47 (d, J=7 Hz, 1 H), 5.80 (d, J=17 Hz, 1 H), 5.27 (d, J=10.5 Hz, 1 H), 4.21 (m, 2 H), 3.10 (t, J=6.7 Hz, 2 H), 2.07 (s, 3 H),
# 1.87 (m, 1 H), 0.90 (d, J=6.5 Hz, 6 H); MS (ES+) 488.39.
238	—CH═CH2 (4)	617	—H	CH	237+187a	AE-2	1 HNMR (DMSO-d6): δ 8.68-8.60 (m, 1 H), 8.50 (d, J=2.4 Hz, 1 H), 7.90-7.80 (m, 1 H), 7.76-7.70 (m, 1 H), 7.56-7.50 (m, 1 H), 7.48-7.42 (d, J=7.7 Hz, 1 H), 7.30-7.22 (d, J=7.9 Hz, 1 H), 7.10-7.02 (d, J=7.7 Hz, 1 H), 6.90-6.75 (dd, J=17, 11 Hz, 1 H), 6.5 (bs, 1 H), 5.92-5.80 (d, J=17 Hz, 1 H), 5.40-5.30
# (d, 11 Hz, 1 H), 4.50-4.20 (m, 2 H), 3.20-3.10 (t, J=6.6 Hz, 2 H), 2.10-1.88 (m, 1 H), 1.2-0.94 (d, J=6.6 Hz, 6 H); MS (ES+) 471.3
256	—H	618	—CH3	CH	255 + 6a	D-6	MS (ES+): 573.3
257	—H	619	—H	CH	256	I-2, S	MS (ES+): 459.1

[0296]

620
Cpd.			Starting	Method
No.	—R	—R′	From	Used	Analytical Data
79a	—CH═CH2 (3)	—CH3	78a	J	MS (ES+): 499.2
79b	—OSO2CF3 (3)	—CH2C6H5	78b	J	Characterized in the next step
79c	—OCH2CO2C2H5 (3)	—CH2C6H5	78c	J	Characterized in the next step
79d	—OCH2CONH2 (3)	—CH2C6H5	78d	J	MS (ES+): 622.4; (ES−) 620.4
79e	621	—CH2C6H5	78e	J	Characterized in the next step
79f	622	—CH2C6H5	78f	J	Characterized in the next step
79g	—OCH3 (3)	—CH3	78g	J	1 HNMR (DMSO-d6): δ 10.6 (bs, 1H), 9.29-9.32 (bs, 1H),
					9.06 (bs, 1H), 8.82-8.75 (t, J=5.84 Hz, 1H), 8.32 (d,
					J=1.88 Hz, 1H), 8.13 (d, J=1.7 Hz, 1H), 7.83 (s, 4H), 7.78
					(d, J=8.67 Hz, 1H), 7.50 (d, J=7.9 Hz, 1H), 7.20-7.15 (dd,
					J=8.67, 2.3 Hz, 1H), 6.92 (d, J=2.4Hz, 1H), 3.94 (s, 3H),
					3.64 (s, 3H), 3.21-3.14 (t, J=6 Hz, 2H), 2.0-1.86 (m, 1H),
					1.0-0.94 (d, J=6.5 Hz, 6H); MS (ES+) 503.3
79h	623	—Bn	78h	J	MS (ES+): 607.3
79i	624	—Bn	78i	J	MS (ES+): 593.4
79j	625	—Bn	78j	J	MS (ES+): 621.4
79k	—O—CH2—CH2—OAc (3)	—Bn	78h	J	MS (ES+): 651.4
80a	—CH═CH2 (3)	—H	79a	I-2	1 HNMR (DMSO-d6): δ 9.1 (s, 2H), 8.87 (s, 2H), 8.53 (t,
					J=6 Hz, 1H), 8.02 (s, 1H), 7.64 (m, 7H), 7.1 (s, 1H), 6.98
					(d, 7.4 Hz, 1H), 6.80 (dd, J=11 Hz, J=17.6 Hz, 1H), 5.90 (d,
					J=17.6 Hz, 1H), 5.35 (d, J=12 Hz, 1H), 3.03 (t, 6 Hz, 2H),
					1.83 (m, 1H), 0.86 (d, J=6.7 Hz, 6H); MS (ES+) 485.2
80b	—OH (3)	—H	79b	I-2	1 HNMR (DMSO-d6): δ 10.37 (s, 1H), 9.20 (m, 3H), 8.72 (t,
					J=6 Hz, 1H), 8.2 (s, 1H), 8.85 (m, 6H), 7.65 (d, J=8 Hz,
					1H), 7.12 (d, 8 Hz, 1H), 7.02 (dd, J=2.5 Hz, J=8 Hz, 1H),
					6.60 (d, J=2.5 Hz, 1H), 3.25 (t, J=6.5 Hz, 2H), 2.0 (m,
					1H), 1.07 (d, J=6.8 Hz, 6H); MS (ES+) 475.2
80c	—OCH2CO2H (3)	—H	79c	I-2	1 H NMR (DMSO-d6): δ 12.7 (2H, bs, 1H), 9.01, 8.87 (2 bs,
					4H), 8.36 (m, 1H), 7.83 (s, 1H), 7.44 (m, 6H), 6.75 (m, 2H),
					6.31 (d, J=2.2 Hz, 1H), 4.42 (s, 2H), 2.84 (m, 2H), 1.63 (m,
					1H), 0.67 (d, J=6.5 Hz, 6H); MS (ES+): 533.4
80d	—OCH2CONH2 (3)	—H	79d	G	1 H NMR (DMSO-d6): δ 9.13 (bs, 5H), 8.59 (t, J=6.28 Hz,
					1H), 8.14 (d, J=1.7 Hz, 1H), 7.63 (m, 9H), 7.42 (s, 1H), 7.09
					(d, J=7.5 Hz, 1H), 7.03 (dd, J=2.5, 12.7 Hz, 1H), 6.70 (d,
					J=2.5 Hz, 1H), 4.48 (s, 2H), 3.05 (t, J=6.6 Hz, 2H), 1.83 (m,
					1H), 0.87 (d, J=6.8 Hz, 6H); MS (ES+): 532.4
80e	626	—H	79e	I-2	1 H NMR (DMSO-d6): δ 12.6 (1H, bs, COOH), 8.98, 8.67 (2 bs, 4H), 8.46 (m, 1H), 8.08 (m, 1H), 7.76 (m, 1H), 7.53 (m, 6H), 7.39 (m, 2H), 7.06 (m, 1H), 7.04 (m, 1H), 2.89 (m, 2H), 1.66 (m, 1H), 0.69 (d, J=6.5 Hz, 6H); MS (ES+): 541.4
80f	627	—H	79f	I-2	1 HNMR (DMSO-d6): δ 9.14 (d, J=10 Hz, 4H), 8.60 (t, J=6 Hz, 1H), 8.22 (bs, 1H), 7.87-7.62 (m, 7H), 7.47 (t, J=8 Hz, 2H), 7.26 (t, 7 Hz, 1H), 7.22 (m, 4H), 6.70 (bs, 1H), 3.09 (t, J=6 Hz, 2H), 1.83 (m, 1H), 0.91 (d, J=6.8 Hz, 6H); MS (ES+) 551.4
80g	—OCH3 (3)	—H	79g	I-2	1 HNMR (DMSO-d6): δ 9.13 (bs, 2H), 8.78 (bs, 2H), 8.65 (t,
					J=6 Hz, 1H), 8.25 (bs, 1H), 7.78 (m, 1H), 7.76 (m, 5H),
					7.25 (s, 1H), 7.17 (m, 1H), 6.73 (bs, 1H), 3.83 (s, 3H), 3.10
					(t, J=6 Hz, 2H), 1.80 (m, 1H), 0.88 (d, J=6.8 Hz, 6H);
					MS (ES+) 489.3
80h	628	—H	79h	I-2	MS (ES+): 517.7
80i	629	—H	79i	I-2	MS (ES+): 503.4; MS (ES−): 501.4
80j	630	—H	79j	I-2	MS (ES+): 531.4; MS (ES−): 529.4
80k	—O—CH2—CH2—OH (3)	—H	79k	I-2	1 HNMR (DMSO-d6): δ 13.52 (bs, 1H), 9.16 (bs, 2H), 9.03
					(bs, 2H), 8.50 (t, J=6 Hz, 1H), 7.96 (d, J=1.7 Hz, 1H),
					7.56 (m, 6H), 7.00 (dd, J=2.5 and 8.5 Hz, 1H), 6.90 (d,
					J=8 Hz, 1H), 6.48 (d, J=2.5 Hz, 1H), 4.91 (t, J=5.5 Hz, 1H),
					4.00 (t, J=4.5 Hz, 2H), 3.69 (q, J=5.5 and 10 Hz, 2H),
					3.05 (t, J=6.8 Hz, 2H), 1.80 (m, 1H), 0.84 (d, J=6.8 Hz,
					6H); MS (ES+): 519.3, (ES−) 517.3
86a	—CH(OH)CH2OH (3)	—H	82	S, I-2	1 HNMR (DMSO-d6): δ 9.15 (bs, 3H), 8.65 (t, J=6 Hz, 1H),
					8.12 (s, 2H), 7.82-7.56 (m, 7H), 7.55-6.96 (m, 4H), 5.5 (bs,
					1H), 4.90 (bs, 1H), 4.65 (bs, 1H), 3.10 (t, J=6 Hz, 2H),
					1.90 (m, 1H), 0.92 (d, J=6.8 Hz, 6H); MS (ES+) 519.3
86b	—CH2OH (3)	—H	84	S, I-2	1 HNMR (DMSO-d6): δ 8.82 (bs, 2H), 8.68 (bs, 2H), 8.40 (t,
					J=6 Hz, 1H), 7.88 (bs, 1H), 7.53 (m, 5H), 7.45 (d, 8 Hz,
					1H), 7.25 (d, J=8 Hz, 1H), 6.81 (m, 2H), 5.22 (d, J=5.5 Hz,
					1H), 4.41 (d, J=5.5 Hz, 2H), 2.88 (t, J=6 Hz, 2H), 1.65 (m,
					1H), 0.71 (d, J=6.8 Hz, 6H); MS (ES+) 489.2
86c	—CO2H (3)	—H	85	S, I-2	1 HNMR (DMSO-d6.D2O): δ 13.7 (bs, 1H), 8.32 (t, J=6 Hz,
					1H), 7.63-7.17 (m, 7H), 6.72 (d, 7.0 Hz, 1H), 2.81 (t, J=6
					Hz, 2H), 1.53 (m, 1H), 0.64 (d, J=6.8 Hz, 6H);
					MS (ES+) 503.2
97a	631	—CH3	96a	J	MS (ES+): 569.2
97b	—OBn (5)	—CH3	91	J	1 HNMR (DMSO-d6): δ 10.62 (s, 1H), 9.15 (bs, 2H), 8.82
					(bs, 2H), 8.67 (t, J=6 Hz, 1H), 8.25 (d, J=2 Hz, 1H), 7.99
					(dd, J=8.1 and 2 Hz, 1H), 7.69 (q, 8.8 and 16.2 Hz, 4H),
					7.44 (m, 3H), 7.28 (m, 3H), 6.89 (d, J=7.7 Hz, 1H), 5.5 (s,
					2H), 3.6 (s, 3H), 3.08 (t, J=5.8 and 6.8 Hz, 2H), 1.83 (m,
					1H), 0.87 (d, J=6.8 Hz, 6H); MS (ES−) 577.2, (ES+) 579.3
98a	632	—H	97a	I-2	1 HNMR (DMSO-d6): δ 13.45 (bs, 1H), 9.06 (s, 2H), 8.99 (s, 2H), 8.51 (t, J=6 and 5 Hz, 1H), 7.99 (s, 1H), 7.62 (m, 5H), 7.47 (s, 1H), 7.36 (m, 2H), 6.99 (m, 4H), 4.26 (s, 2H), 3.02 (t, J=6.8 Hz, 2H), 1.80 (m, 1H), 0.86 (d, J=6.8 Hz, 6H); MS (ES−) 553.2, (ES+) 555.2
98b	—OBn (5)	—H	97b	I-2	1 HNMR (DMSO-d6): δ 13.52 (bs, 1H), 9.09 (bs, 2H), 9.04
					(bs, 2H), 8.48 (t, J=6 Hz, 1H), 7.94 (s, 1H), 7.61 (m, 4H),
					7.49 (s, 1H), 7.46 (s, 1H), 7.34 (m, 5H), 7.15 (d, J=8.2 Hz,
					1H), 7.00 (d, J=8.2, 1H), 6.02 (d, J=7.4 Hz, 1H), 5.21 (s,
					2H), 3.01 (t, J=6.8 Hz, 2H), 1.80 (m, 1H), 0.85 (d, J=6.8
					Hz, 6H); MS (ES−) 563.2, (ES+) 565.2
98c	—OH (5)	—H	98b	G	1 HNMR (DMSO-d6): δ 9.85 (s, 1H), 9.07 (s, 2H), 8.98 (s,
					2H), 8.50 (t, J=6 and 5 Hz, 1H), 7.99 (d, J=1.7 Hz, 1H),
					7.63 (m, 5H), 7.20 (t, J=8 Hz, 2H), 6.90 (d, J=7.9 Hz,
					1H), 6.49 (d, J=7.2 Hz, 1H),3.21 (t, J=6.8 Hz, 2H), 1.80
					(m, 1H), 0.85 (d, J=6.8 Hz, 6H); MS (ES+) 475.2; (ES−) 473.2
103	—OCH3 (2)	—CH3	102	J	MS (ES+) 503.1
104	—OCH3 (2)	—H	103	I-2	1 HNMR (DMSO-d6): δ 9.08 (bs, 2H), 8.80 (bs, 2H), 8.52 (t,
					J=6 Hz, 1H), 8.02 (s, 1H), 7.64 (m, 5H), 7.16 (m, 2H),
					7.03 (m, 2H), 3.84 (s, 3H), 3.03 (t, J=6.8 Hz, 2H), 1.81 (m,
					1H), 0.86 (d, J=6.8 Hz, 6H); MS (ES−) 487.3, (ES+) 489.3
110	—OBn (2)	—CH3	109	J	MS (ES+): 579.3
111	—OH (2)	—CH3	110	G	MS (ES+): 489.3
	—OC 2H 5 (3)
126		{close oversize brace}	both	—CH3	118b	J	Characterized in the next step
	—OBn (4)
							1 H NMR (DMSO-d6): δ 9.06-9.09 (m, 3H), 8.56-8.50 (m,
	—OC 2H 5 (3)						1H), 8.05 (s, 1H), 7.71-7.58 (m, 6H), 7.55-7.28 (m, 6H),
127		{close oversize brace}	both	—H	126	I-2	7.10-7.01 (m, 1H), 6.63 (s, 1H), 5.19 (s, 2H), 4.05-3.97 (m, 2H),
	—OBn (4)						3.05-3.01 (m, 2H), 1.86-1.77 (m, 1H), 1.29 (t, J=6.7 Hz, 3H),
							0.87 (d, J=6.8 Hz, 6H)
							1 H NMR (DMSO-d6): 13.64 (br s, 1H), 8.99 (br s, 2H), 8.49 (t,
	—OCH 3 (3)						J=5.1 Hz, 1H), 7.99 (s, 1H), 7.73-7.56 (m, 5H), 7.32-6.83 (m,
129		{close oversize brace}	both	—H	128	I-2, S	5H), 6.50 (s, 1H), 5.17 (d, J=4.3 Hz, 1H), 5.01 (m, 1H), 3.75
	—CH(OH)CH 3 (4)						(s, 3H), 3.03 (t, J=6.0 Hz, 1H), 1.81 (m, 1H), 1.32 (d, J=6.2
							Hz, 3H), 0.86 (d, J=6.6 Hz, 6H); MS (ES+): 533.4 (100% M+)

[0297]

633
Cpd.	—R (With Respect to	Starting	Method
No.	Phenyl Ring)	From	Used	Analytical Data
81	—CH═CH2 (3)	79a	R	MS (ES−):
				597.2
82	—CH(OH)CH2OH (3)	81	L	MS (ES−1):
				631.3
83	—CH═O (3)	82	M	MS (ES+):
				601.3
84	—CH2OH (3)	83	K	MS (ES−1):
				601.4
85	—CO2H (3)	83	E	MS (ES−1):
				615.3
	—OCH 3 (3)
128		{close oversize brace}	both	124a	R	MS (ES+):
	—CH═CH 2 (4)					629.4

[0298]

634
Cpd.						Starting	Method
No.	—R	—R1	—R2	—R3	—R4	From	Used	Analytical Data
88	—Br	—H	—H	—H	—OBn	87	X	1 HNMR (CDCl3): δ 10.48 (s, 1 H),
								7.42-7.25 (m, 7H), 7.00 (dd, J=2 and 7.4
								Hz, 1H), 5.19 (s, 2H); IR (KBr) 1701,
								1585, 1452, 1262, 1009 cm−1; MS
								(ES+) 313.0, 315.0 (M + Na)+
89	—B(OH)2	—H	—H	—H	—OBn	88	T, U-1	1 HNMR (CDCl3): δ 10.61 (s, 1H), 7.65
								(d, J=7.2 Hz, 1H), 7.60 (t, J=7.9 and
								7.2 Hz, 1H), 7.41 (m, 5H), 7.19 (d, J=7.9
								Hz, 1H), 6.81 bs, 2H), 5.20 (s, 2H)
100	—B(OH)2	—OCH3	—H	—H	—H	99	T, U-3	1 HNMR (DMSO-d6): δ 10.2 (s, 1H),
								8.34 (s, 2H), 7.92 (d, J=9.4 Hz, 1H),
								7.13 (m, 2H), 3.92 (s, 3H);
								MS (ES−) 179.0
107	—B(OH)2	—OBn	—H	—H	—H	106	T, U-1	1 HNMR (DMSO-d6): δ 10.1 (s, 1H),
								7.3-7.6 (m, 8H), 5.3 (m, 2H)
114a	—Br	—H	—OCH3	—OH	—H	113	Z	MS (ES−): 229.0 and 231.0)
114b	—Br	—H	—OC2H5	—OH	—H	113	Z-1	MS (ES−): 242.9 and 244.9
114c	—Br	—H	—OCH(CH3)2	—OH	—H	113	Z-1	MS (ES−): 257.0 and 259.0
115a	—Br	—H	—OCH3	—OBn	—H	114a	X	MS (ES+): 321.0 and 323.0
115b	—Br	—H	—OC2H5	—OBn	—H	114b	X	MS (ES+): 335.0 and 337.0
115c	—Br	—H	—OCH(CH3)2	—OBn	—H	114c	X	MS (ES+): 349.0 and 351.0
115d	—Br	—H	635	—OBn	—H	115a	X, V-4, AH	Characterized in the next step
116a	—B(OH)2	—H	—OCH3	—OBn	—H	115a	T, U-1	Characterized in the next step
116b	—B(OH)2	—H	—OC2H5	—OBn	—H	115b	T, U-1	Characterized in the next step
116c	—B(OH)2	—H	—OCH(CH3)2	—OBn	—H	115c	T, U-1	Characterized in the next step

[0299]

636
Cpd.	Starting	Method
No.	From	Used	Analytical Data
112	111	I-2	1 HNMR (DMSO-d6): δ 11.28 (s, 1H), 9.31
			(s, 2H), 9.0 (s, 2H), 8.88 (d, J=11.30 Hz,
			1H), 8.82 (d, J=1.88 Hz, 1H), 8.25 (d,
			J=1.88 Hz, 1H), 8.18 (d, J=1.88 Hz, 1H),
			8.04 (d, J=8.47 Hz, 1H), 7.92 (m, J=24.48 Hz,
			2H), 7.75 (m, J=15.82, 1H), 7.75 (m,
			J=8.28 Hz, 1H), 7.55 (m, J=8.66 Hz, 1H), 3.10
			(m, J=12.6 Hz, 1H), 2.5 (m, J=3.5 Hz, 1H), 1.8
			(m, J=19.9 Hz, 2H), 0.88 (m, J=6.6 Hz, 6H).

[0300]

637
Cpd.					Starting	Method
No.	—R	—R′	—R″	—R′′′	From	Used	Analytical Data
117a	—CH3	—OBn	—CHO	638	3a +116a	D-2	MS (ES−): 474.2
117b	—C2H5	—OBn	—CHO	639	3a +116b	D-2	MS (ES−): 488.2
117c	—CH(CH3)2	—OBn	—CHO	640	3a +116c	D-2	MS (ES−): 502.3
117d	—CH3	—OBn	—CHO	641	3a +116a	D-2	1 H NMR (CDCl3): δ 9.56 (s, 1H), 8.34 (d, J=1.7 Hz, 1H), 8.5 (s, 1H), 8.01 (dd, J=7.9 and 1.9 Hz, 1H), 7.40 (m, 7H), 6.9 (s, 1H), 5.24 (m, 2H), 4.2 (m, 1H), 3.80 (s, 3H), 3.52 (s, 3H), 1.02 (d, J=7 Hz, 6H); MS (ES+): 484.3 (M + Na)+
117e	—CH3	—OBn	—CHO	642	3c +116a	D-2	1 HNMR (DMSO-d6): δ 8.43 (d, J=1.65 Hz, 1H), 8.31 (d, J=8.66 Hz, 1), 8.12 (dd, J=1.69 Hz, 1H), 7.98 (s, 1H), 7.41 (d, J=8 and 10 Hz, 1H), 7.19 (d, J=8.1 Hz, 1H), 5.20 (dd, J=6.2 Hz, 1H), 3.98 (dd, J=7.75 Hz, 3H), 3.94 (s, 3H),
# 3.42 (m, 3H), 3.32 (m, 3H), 3.19 (s, 3H), 2.5 (m, 3H), 2.0 (s, 4H), 1.5 (m, 2H), 1.28 (m, 3H), 0.88 (d, J=6.59 Hz, 3H); MS (ES+): 664.3
117f	—CH3	—OBn	—CHO	643	3d +116a	D-2	1 H NMR (CDCl3): δ 9.50 (s, 1H), 8.40 (d, J=2.1 Hz, 1H), 8.04 (dd, J=8.1, 2.1 Hz, 1H), 7.57 (s, 1H), 7.48 (m, 5H), 7.38 (m, 5H), 6.67 (s, 1H), 6.50 (broad, 1H),) 5.27 (d, J=11.9 Hz, 1H), 5.22 (dd, J=11.7, 1H), 4.63, (m, 3H)
# 4.17 (m, 4H), 3.92 (s, 3H), 3.66 (s, 3H); MS (ES−): 488.3
117g	—CH3	—OBn	—CHO	644	3f +116a	D-2	1 H NMR (CDCl3): δ 9.50 (s, 1H), 8.40 (d, J=2.1 Hz, 1H), 8.04 (dd, J=8.1, 2.1 Hz, 1H), 7.57 (s, 1H), 7.48 (m, 2H), 7.38 (m, 3H), 6.67 (s, 1H), 6.50 (broad, 1H), 5.27 (d, J=11.9 Hz, 1H), 5.22 (dd, J=11.7, 2H), 4.17 (m, 2H), 3.92 (s, 3H), 3.66 (s, 3H); MS (ES−): 500
117h	—CH3	—OBn	—CHO	645	3e +116a	D-2	1 H NMR (CDCl3): δ 9.56 (s, 1H), 8.34 (d, J=1.7 Hz, 1H), 8.01 (dd, J=7.9, 1.9 Hz, 1H), 7.57 (s, 1H), 7.50 (dd, J=7.2, 1.5, 2H), 7.40 (m, 4H), 6.67 (s, 1H), 6.21 (broad, 1H), 5.24 (d, J=2.8 Hz, 2H), 3.92 (s, 3H), 3.65 (s, 3H), 3.52 (m, 2H), 1.65 (m, 2H),
# 1.46 (m, 2H), 0.99 (t, J=7.3 Hz, 3H).
117i	—CH3	—OBn	—CHO	646	3g +116a	D-2	1 H NMR (CDCl3): δ 9.57 (s, 1H), 8.37 (d, J=1.9 Hz, 1H), 8.03 (dd, J=7.9, 1.9 Hz, 1H), 7.58 (s, 1H), 7.50 (d, J=7.2 Hz, 2H), 7.38 (m, 3H), 6.68 (s, 1H), 6.33 (broad, 1H), 5.26 (d, J=11.5 Hz, 1H), 5.21 (d, J=11.9 Hz, 1H), 3.92 (s, 3H), 3.65 (s, 3H), 3.37
# (dd, J=7.2, 5.3 Hz, 2H), 1.09 (m, 1H), 0.60 (m, 2H), 0.32 (m, 2H); MS (ES+): 474.2
117j	—CH3	—OBn	—CHO	647	3h +116a	D-2	1 H NMR (CDCl3): δ 9.55 (s, 1H), 8.32 (d, J=1.9 Hz, 1H), 8.00 (dd, J=1.9 and 7.9 Hz, 1H), 7.59-7.30 (m, 7H), 6.67 (s, 1H), 5.23 (m, 2H), 4.45 (q, J=7.0 Hz, 1H), 3.91 (s, 3H), 3.64 (s, 3H), 2.21-1.46 (m, 8 H); MS (ES+): 510.3 (M + Na)+
117k	—CH3	—OBn	—CHO	648	3i +116a	D-2	1 H NMR (CDCl3): δ 9.56 (s, 1H), 8.35 (d, J=1.9 Hz, 1H), 8.02 (dd, J=1.9 and 7.9 Hz, 1H), 7.58-7.33 (m, 7H), 6.68 (s, 1H), 5.24 (m, 2H), 3.92 (s, 3H), 3.65 (s, 3H), 3.56 (m, 2H), 1.30 (t, J=7.2 Hz, 3H); MS (ES+): 470.3 (M + Na)+
117l	—CH3	—OBn	—CHO	649	3j +116a	D-2	1 H NMR (CDCl3): δ 9.56 (s, 1H), 8.35 (d, J=1.9 Hz, 1H), 8.02 (dd, J=1.9 and 7.9 Hz, 1H), 7.58-7.33 (m, 7H), 6.68 (s, 1H), 5.24 (m, 2H), 3.92 (s, 3H), 3.65 (s, 3H), 3.40 (m, 2H), 1.80-0.94 (m, 9H); MS (ES+): 512.2 (M + Na)+
117m	650	—OBn	—CHO	651	6a +115d	D-6	1 HNMR (DMSO-d6): δ 9.73 (s, 1H), 8.86 (t, J=5.7 Hz, 1H), 8.52 (d, J=1.5 Hz, 1H), 8.22 (dd, J=8 and 2 Hz, 1H), 7.79 (s, 1H), 7.60 (d, J=8 Hz, 1H), 7.5(m, 5H), 7.22 (s, 1H), 5.35 (q, J=11 and 17 Hz, 1H), 3.70 (s, 3H), 3.23 (t, J=6.5 Hz, 2H), 1.98
# (m, 1H), 1.3 (s, 9H), 1.01 (d, J=6.8 Hz, 6H); MS (ES+): 546.4
118a	—CH3	—OBn	—CO2H	652	117a	E	MS (ES−): 490.2
118b	—C2H5	—OBn	—CO2H	653	117b	E	MS (ES−): 504.2
118c	—CH(CH3)2	—OBn	—CO2H	654	117c	E	MS (ES−): 518.2
118d	—CH3	—OBn	—CO2H	655	117d	E	Characterized in the next step
118e	—CH3	—OBn	—CO2H	656	117e	E	MS (ES+): 534.3
118f	—CH3	—OBn	—CO2H	657	117f	E	MS (ES+): 506.3
118g	—CH3	—OBn	—CO2H	658	117g	E	Characterized in the next step
118h	—CH3	—OBn	—CO2H	659	117h	E	MS (ES−1): 490.2
118i	—CH3	—OBn	—CO2H	660	117i	E	MS (ES−1): 488.3
118j	—CH3	—OBn	—CO2H	661	117j	E	1 H NMR (DMSO-d6): δ 12.19 (br s, 1H), 8.50 (d, J=7.4 Hz, 1H), 8.31 (d, J=1.9 Hz, 1H), 8.02 (dd, J=1.7 and 7.9 Hz, 1H), 7.58-7.29 (m, 7H), 6.71 (s, 1H), 5.17 (s, 2H), 4.27 (q, J=6.4 Hz, 1H), 3.80 (s, 3H), 3.57 (s, 3H), 1.97-1.51 (m, 8H)
118k	—CH3	—OBn	—CO2H	662	117k	E	MS (ES−): 462.3
118l	—CH3	—OBn	—CO2H	663	117l	E	1 H NMR (CDCl3): δ 8.30 (d, J=1.9 Hz, 1H), 7.95 (dd, J=1.7 and 7.9 Hz, 1H), 7.66 (s, 1H), 7.52-7.27 (m, 6H), 6.62 (s, 1H), 6.49 (m, 1H), 5.21 (s, 2H), 3.88 (s, 3H), 3.61 (s, 3H), 3.38 (m, 2H), 1.79-0.94 (m, 9H); MS (ES−): 504.4
118m	664	—OBn	—CO2H	665	117m	E	Characterized in the next step
119a	—CH3	—OBn	—CO2MEM	666	118a	F	MS (ES−): 578.3
119b	—C2H5	—OBn	—CO2MEM	667	118b	F	MS (ES−): 592.3
119c	—CH(CH3)2	—OBn	—CO2MEM	668	118c	F	MS (ES−): 606.3
119d	—CH3	—OBn	—CO2MEM	669	118d	F	MS (ES−): 564.2
119e	—CH3	—OBn	—CO2MEM	670	118e	F	MS (ES−): 620.1
119f	—CH3	—OBn	—CO2MEM	671	118f	F	MS (ES−): 592.3
119g	—CH3	—OBn	—CO2MEM	672	118g	F	Characterized in the next step
119h	—CH3	—OBn	—CO2MEM	673	118h	F	1 H NMR (CDCl3): δ 8.32 (d, J=1.9 Hz, 1H), 7.96 (dd, J=7.9, 1.9 Hz, 1H), 7.68 (s, 1H), 7.50 (m, 2H), 7.35 (m, 4H), 6.62 (s, 1H), 6.33 (t, J=5.4 Hz, 1H), 5.24 (m, 4H), 3.88 (s, 3H), 3.63 (s, 3H), 3.46 (m, 6 H), 3.34 (s, 3H), 1.63 (m, 2H), 1.44 (m, 2H), 0.98 (t, J=7.3 Hz, 3H)
119i	—CH3	—OBn	—CO2MEM	674	118i	F	1 H NMR (CDCl3): δ 8.34 (d, J=1.9 Hz, 1H), 8.00 (dd, J=7.9, 2.1 Hz, 1H), 7.68 (s, 1H), 7.50 (m, 2H), 7.36 (m, 4H), 6.63 (s, 1H), 6.42 (broad, 1H), 5.24 (m, 4H), 3.89 (s, 3H), 3.64 (s, 3H), 3.45 (s, 3H), 3.35 (m, 5H), 1.07 (m, 1H), 0.58 (m, 2H), 0.30 (m, 2H)
119j	—CH3	—OBn	—CO2MEM	675	118j	F	1 H NMR (DMSO-d6): δ 8.55 (d, J=7.4 Hz, 1H), 8.39 (d, J=1.9 Hz, 1H), 8.10 (dd, J=1.7 and 7.9 Hz, 1H), 7.63-7.35 (m, 7H), 6.81 (s, 1H), 5.25-5.12 (m, 4H), 4.31 (q, J=6.4 Hz, 1H), 3.86 (s, 3H), 3.62 (s, 3H), 3.3 (s, 3H), 3.23 (s, 3H) 1.99-1.53
# (m, 8H); MS (ES+): 614.3 (M + Na)+
119k	—CH3	—OBn	—CO2MEM	676	118k	F	1 H NMR (DMSO-d6): δ 8.70 (t, J=5.5 Hz, 1H), 8.35 (d, J=1.9 Hz, 1H), 8.05 (dd, J=1.7 and 7.9 Hz, 1H), 7.59-7.30 (m, 7H), 6.77 (s, 1H), 5.21-5.08 (m, 4H), 3.82 (s, 3H), 3.58 (s, 3H), 3.40-3.29 (m, 6H), 3.18 (s, 3H), 1.14 (t, J=7.2 Hz, 3H); MS (ES+): 574.3 (M + Na)+
119l	—CH3	—OBn	—CO2MEM	677	118l	F	1 H NMR (DMSO-d6): δ 8.68 (t, J=5.8 Hz, 1H), 8.35 (d, J=1.9 Hz, 1H), 8.05 (dd, J=1.7 and 7.9 Hz, 1H), 7.63-7.33 (m, 7H), 6.77 (s, 1H), 5.22-5.08 (m, 4H), 3.82 (s, 3H), 3.58 (s, 3H), 3.39-3.22 (m, 6H), 3.18 (s, 3H), 1.56 (qui, J=7.0 Hz, 2H), 1.27 (m, 1H), 0.94-0.75
# (m, 6H); MS (ES+): 616.3 (M + Na)+
119m	678	—OBn	—CO2MEM	679	118m	F	1 H NMR (DMSO-d6): δ 8.72 (t, J=5.6 Hz, 1H), 8.38 (d, J=1.8 Hz, 1H), 8.70 (dd, J=1.8 and 8.1 Hz, 1H), 7.71 (s, 1H), 7.40 (m, 6H), 7.02 (s, 1H), 5.20 (m, 4H), 3.59 (s, 3H), 3.37 (m, 2H), 3.31 (m, 2H), 3.17 (s, 3H), 3.12 (t, J=6.5 Hz, 2H), 1.87 (m, 1H), 1.21 (s, 9H), 0.91 (d,
# J=6.8 Hz, 6H); MS (ES+): 650.4 and 672.3 (M + Na)+
120a	—CH3	—OH	—CO2MEM	680	119a	G	MS (ES−): 488.1
120b	—C2H5	—OH	—CO2MEM	681	119b	G	MS (ES−): 502.2
120c	—CH(CH3)2	—OH	—CO2MEM	682	119c	G	MS (ES−): 516.3
120d	—CH3	—OH	—CO2MEM	683	119d	G	MS (ES−): 474.3
120e	—CH3	—OH	—CO2MEM	684	119e	G	MS (ES−): 530.4
120f	—CH3	—OH	—CO2MEM	685	119f	G	MS (ES−): 502.3
120g	—CH3	—OH	—CO2MEM	686	119g	G	Characterized in the next step
120h	—CH3	—OH	—CO2MEM	687	119h	G	Characterized in the next step
120i	—CH3	—OH	—CO2MEM	688	119i	G	MS (ES−): 486.3
120j	—CH3	—OH	—CO2MEM	689	119j	G	MS (ES+): 524.3 (M + Na)+
120k	—CH3	—OH	—CO2MEM	690	119k	G	MS (ES+): 484.2 (M + Na)+
120l	—CH3	—OH	—CO2MEM	691	119l	G	MS (ES−): 502.3
120m	692	—OH	—CO2MEM	693	119m	G	1 HNMR (DMSO-d6): δ 10.83 (bs, 1H), 8.77 (t, J=5.6 Hz, 1H), 8.42 (d, J=1.8 Hz, 1H), 8.12 (dd, J=1.8 and 8.1 Hz, 1H), 7.68 (s, 1H), 7.41 (d, J=8.1 Hz, 1H), 6.73 (s, 1H), 5.21 (q, J=21 and 6 Hz, 2H), 3.65 (s, 3H), 3.48 (m, 2H), 3.37 (m, 2H),
# 3.24 (s, 3H), 3.18 (t, J=6.5 Hz, 2H), 1.94 (m, 1H), 1.39 (s, 9H), 0.97 (d, J=6.8 Hz, 6H); MS (ES+): 560.5 and 582.4 (M + Na)+, (ES−) 558.4
121a	—CH3	—OSO2CF3	—CO2MEM	694	120a	B-2	MS (ES+): 644.1 (M + Na)+
121b	—C2H5	—OSO2CF3	—CO2MEM	695	120b	B-2	MS (ES+): 658.2 (M + Na)+
121c	—CH(CH3)2	—OSO2CF3	—CO2MEM	696	120c	B-2	MS (ES+): 672.2 (M + Na)+
121d	—CH3	—OSO2CF3	—CO2MEM	697	120d	B-2	1 HNMR (DMSO-d6): δ 8.43 (d, J=1.9 Hz, 1H), 8.31 (s, 1H), 8.12 (d, J=1.69 Hz, 1H), 7.98 (s, 1H), 7.41 (d, J=8.1 Hz, 1H), 7.19 (s, 1H), 5.20 (m, 2H), 3.98 (m, 1H), 3.94 (s, 3H), 3.42 (s, 3H), 3.19 (s, 3H), 2.50 (m, 2H), 1.08 (d, J=6.59, 6H); MS (ES+) 608.3
121e	—CH3	—OSO2CF3	—CO2MEM	698	120e	B-2	1 HNMR (DMSO-d6): δ 8.49 (s, 1H), 8.34 (d, J=1.8 Hz, 1H), 8.2 (d, J=1.8 Hz, 1H), 7.97 (s, 1H), 7.4 (d, J=7.8 Hz, 1H), 7.2 (s, 1H), 5.2 (q, J=6 and 10 Hz, 2H), 4.0 (m, 3H), 3.6 (s, 3H), 3.4 (m, 4H), 3.2 (s, 3H), 1.5 (m, 4H), 1.3 (m, 4H), 0.85 (m, 6H); MS (ES+): 664.3
121f	—CH3	—OSO2CF3	—CO2MEM	699	120f	B-2	1 HNMR (DMSO-d6): δ 8.83 (d, J=5.46, 1H), 8.55 (d, J=1.88 Hz, 1H), 8.23 (dd, J=1.88 Hz, 1H), 8.19 (s, 1H), 7.73 (d, J=7.93 Hz, 1H), 7.29 (s, 1H), 5.29 (dd, J=6.217 Hz, 2H), 4.06 (s, 3H), 3.71 (s, 2H), 3.54 (m, 5H),
# 2.62 (t, J=3.57 Hz, 3H), 1.66 (t, J=6.59 Hz, 2H), 1.42 (m, 6H), 0.99 (t, J=6.79 Hz, 3H); MS (ES+) 636.6
121g	—CH3	—OSO2CF3	—CO2MEM	700	120g	B-2	1 H NMR (CDCl3): δ 8.43 (d, J=1.9 Hz, 1H), 8.03 (dd, J=7.9 Hz, 2.1 Hz, 1H), 8.00 (s, 1H), 7.35 (d, J=7.9 Hz, 1H), 6.79 (m, 2H), 5.29 (d, J=6.2 Hz, 1H), 5.26 (d, J=6.2 Hz, 1H), 4.16 (m, 2H), 3.94 (s, 3H), 3.67 (s, 3H), 3.48 (m, 4H), 3.36 (s, 3H); MS (ES−): 646.3
121h	—CH3	—OSO2CF3	—CO2MEM	701	120h	B-2	1 H NMR (CDCl3): δ 8.41 (s, 1H), 7.96 (d, J=8.3 Hz, 2H), 7.8 (m, 1H), 6.80 (s, 1H), 6.34 (m, 1H), 5.32 (m, 2H), 3.90 (s, 3H), 3.66 (s, 3H), 3.55 (m, 6H), 3.4 (s, 3H), 1.7 (m, 2H), 1.45 (m, 2H), 0.98 (t, J=7.3 Hz, 3H); MS (ES−): 620
121i	—CH3	—OSO2CF3	—CO2MEM	702	120i	B-2	1 H NMR (CDCl3): δ 8.41 (d, J=2.1 Hz, 1H), 8.03 (dd, J=7.9, 1.9 Hz, 1H), 8.00 (s, 1H), 7.32 (d, J=7.9 Hz, 1H), 6.43 (t, J=4.9 Hz, 1H), 5.30 (q, J=6.0 Hz, 2H), 3.94 (s, 3H), 3.67 (s, 3H), 3.55 (m, 2H), 3.48 (m, 2H),
# 3.35 (m, 5H), 1.09 (m, 1H), 0.59 (m, 2H), 0.31 (m, 2H); MS (ES−): 618.4
121j	—CH3	—OSO2CF3	—CO2MEM	703	120j	B-2	1 H NMR (CDCl3): δ 8.35 (d, J=1.9 Hz, 1H), 8.00 (m, 2H), 7.31 (d, J=7.9 Hz, 1H), 6.77 (s, 1H), 6.27 (m, 1H), 5.28 (m, 2H), 4.44 (q, J=7.0 Hz, 1H), 3.94 (s, 3H), 3.66 (s, 3H), 3.57-3.45 (m, 4H), 3.35 (s, 3H), 2.19-1.45 (m, 8H); MS (ES+): 656.3 (M + Na)+
121k	—CH3	—OSO2CF3	—CO2MEM	704	120k	B-2	1 H NMR (CDCl3): δ 8.38 (s, 1H), 8.00 (m, 2H), 7.31 (d, J=7.9 Hz, 1H), 6.78 (s, 1H), 6.37 (m, 1H), 5.27 (m, 2H), 3.94 (s, 3H), 3.66 (s, 3H), 3.59-3.43 (m, 6H), 3.35 (s, 3H), 1.28 (t, J=7.2 Hz, 3H); MS (ES+): 616.3 (M + Na)+
121l	—CH3	—OSO2CF3	—CO2MEM	705	120l	B-2	1 H NMR (CDCl3): δ 8.38 (s, 1H), 8.00 (m, 2H), 7.31 (d, J=7.9 Hz, 1H), 6.78 (s, 1H), 6.37 (m, 1H), 5.27 (m, 2H), 3.94 (s, 3H), 3.66 (s, 3H), 3.57-3.25 (m, 9H), 1.78-0.92 (m, 9H); MS (ES+): 658.4 (M + Na)+
121m	706	—OSO2CF3	—CO2MEM	707	121m	B-2	1 HNMR (DMSO-d6): δ 8.75 (t, J=5.6 Hz, 1H), 8.45 (d, J=1.8 Hz, 1H), 8.11 (dd, J=1.8 and 8.1 Hz, 1H), 8.04 (s, 1H), 7.57 (s, 1H), 7.42 (d, J=8.1 Hz, 1H), 5.23 (q, J=21 and 6 Hz, 2H), 3.60 (s, 3H), 3.41 (m, 2H), 3.32 (m, 2H), 3.17 (s, 3H), 3.13
# (t, J=6.5 Hz, 2H), 1.87 (m, 1H), 1.37 (s, 9H), 0.91 (d, J=6.8 Hz, 6H); MS (ES−): 690.4
122a	—CH3	—CH═CH2	—CO2MEM	708	121a	D-3	Characterized in the next step
122b	—C2H5	—CH═CH2	—CO2MEM	709	121b	D-3	MS (ES+): 536.3 (M + Na)+
122c	—CH(CH3)2	—CH═CH2	—CO2MEM	710	121c	D-3	MS (ES+): 550.3 (M + Na)+
122d	—CH3	—CH═CH2	—CO2MEM	711	121d	D-3	MS (ES+): 486.2
122e	—CH3	—CH═CH2	—CO2MEM	712	121e	D-3	MS (ES+): 564.5 (M + Na)+
122f	—CH3	—CH═CH2	—CO2MEM	713	121f	D-3	MS (ES+): 514.4 (M + Na)+
122g	—CH3	—CH═CH2	—CO2MEM	714	121g	D-3	Characterized in the next step
122h	—CH3	—CH═CH2	—CO2MEM	715	121h	D-3	Characterized in the next step
122i	—CH3	—CH═CH2	—CO2MEM	716	121i	D-3	Characterized in the next step
122j	—CH3	—CH═CH2	—CO2MEM	717	121j	D-3	MS (ES−): 422.3 [(M-MeM)-1]
122k	—CH3	—CH═CH2	—CO2MEM	718	121K	D-3	MS (ES+): 494.2 (M + Na)+
122l	—CH3	—CH═CH2	—CO2MEM	719	121l	D-3	MS (ES+): 536.42 (M + Na)+
122m	720	—CH═CH2	—CO2MEM	721	121m	D-3	1 HNMR (DMSO-d6): δ 8.73 (t, J=5.6 Hz, 1H), 8.43 (d, J=1.8 Hz, 1H), 8.11 (dd, J=1.8 and 8.1 Hz, 1H), 7.61 (s, 1H), 7.57 (s, 1H), 7.42 (d, J=8.1 Hz, 1H), 6.72 (dd, J=11 and 17.5 Hz, 1H), 6.03 (d, J=17.5 Hz,
# 1H), 5.5 2(d, J=11 Hz, 1H), 5.19(q, J=18 and 6 Hz, 2H), 3.60 (s, 3H), 3.41 (m, 2H), 3.32 (m, 2H), 3.18 (s, 3H), 3.13 (t, J=6.5 Hz, 2H), 1.89 (m, 1H), 1.38 (s, 9H), 0.91 (d, J=6.8 Hz, 6H); MS (ES−): 480.4 [(M-MEM)-1]
123a	—CH3	—CH═CH2	CO2H	722	122a	I-1	MS (ES−): 410.2
123b	—C2H5	—CH═CH2	CO2H	723	122b	I-1	MS (ES−): 424.2
123c	—CH(CH3)2	—CH═CH2	CO2H	724	122c	I-1	MS (ES−): 438.2
123d	—CH3	—CH═CH2	CO2H	725	122d	I-1	MS (ES−): 396.2
123e	—CH3	—CH═CH2	CO2H	726	122e	I-1	MS (ES+): 454.3
123f	—CH3	—CH═CH2	CO2H	727	122f	I-1	MS (ES+): 426.3
123g	—CH3	—CH═CH2	CO2H	728	122g	I-1	1 H NMR (DMSO): δ 12.37 (s, 1H), 9.35 (t, J=6.0 Hz, 1H), 8.42 (d, J=1.7 Hz, 1H), 8.10 (dd, J=8.1 Hz, 1.9 Hz, 1H), 8.06 (s, 1H), 7.40 (d, J=7.9 Hz, 1H), 6.98 (dd, J=17.9, 11.5 Hz, 1H), 6.77 (s, 1H), 5.89 (dd,
# J=17.7, 1.3 Hz, 1H), 5.37 (dd, J=11.1, 1.3 Hz, 1H), 4.14 (m, 2H), 3.84 (s, 3H), 3.61 (s, 3H); MS (ES−): 436.3
123h	—CH3	—CH═CH2	CO2H	729	122h	I-1	1 H NMR (DMSO): δ 8.66 (t, J=5.5 Hz, 1H), 8.35 (d, J=1.7 Hz, 1H), 8.05 (s, 1H), 8.03 (dd, J=8.1, 1.9 Hz, 1H), 7.34 (d, J=7.9 Hz, 1H), 6.98 (dd, J=17.9, 11.3 Hz, 1H), 6.75 (s, 1H), 5.88 (dd, J=17.7, 1.3, 1H),
# 5.36 (dd, J=11.3, 1.3 Hz, 1H), 3.84 (s, 3H), 3.60 (s, 3H), 3.30 (q, J=5.6 Hz, 2H), 1.52 (m, 2H), 1.33 (m, 2H), 0.96 (t, J=7.3 Hz, 3H); MS (ES−): 410.4
123i	—CH3	—CH═CH2	CO2H	730	122i	I-1	1 H NMR (DMSO): δ 12.34 (s, 1H), 8.80 (t, J=6.1 Hz, 1H), 8.37 (d, J=1.9 Hz, 1H), 8.06 (dd, J=9.8, 7.9 Hz, 1H), 8.05 (s, 1H), 7.36 (d, J=7.9 Hz, 1H), 6.98 (dd, J=17.9, 11.3 Hz, 1H), 6.76 (s, 1H), 5.89
# (dd, J=17.9, 1.5 Hz, 1H), 5.36 (dd, J=10.9, 1.5 Hz, 1H), 3.84 (s, 3H), 3.60 (s, 3H), 3.18 (t, 6.2, 2H), 1.06 (m, 1H), 0.45 (m, 2H), 0.25 (m, 2H); MS (ES−): 408.4
123j	—CH3	—CH═CH2	CO2H	731	122j	I-1	1 H NMR (DMSO): δ 12.31 (br s, 1H), 8.52 (d, J=7.3 Hz, 1H), 8.34 (d, J=1.7 Hz, 1H), 8.05 (m, 2H), 7.34 (d, J=7.9 Hz, 1H), 6.97 (dd, J=11.5 and 17.9 Hz, 1H), 6.74 (s, 1H),
# 5.89 (d, J=17.9 Hz, 1H), 5.37 (d, J=11.5 Hz, 1H), 4.27 (q, J=7.3 Hz, 1H), 3.84 (s, 3H), 3.60 (s, 3H), 1.98-1.50 (m, 8H); MS (ES−): 422.3
123k	—CH3	—CH═CH2	CO2H	732	122k	I-1	1 H NMR (DMSO-d6): δ 12.27 (br s, 1H), 8.58 (m, 1H), 8.23 (s, 1H), 7.92 (m, 2H), 7.47 (m, 1H), 7.22 (m, 1H), 6.84 (m, 1H), 6.63 (s, 1H), 5.76 (d, J=17.9 Hz, 1H), 5.24 (d, J=11.5 Hz, 1H), 3.71 (s, 3H), 3.47 (s, 3H), 1.02 (m, 3H); MS (ES−): 382.2
123l	—CH3	—CH═CH2	CO2H	733	122l	I-1	1 H NMR (DMSO-d6): δ 12.30 (br s, 1H), 8.52 (d, J=6.0 Hz, 1H), 8.33 (d, J=1.7 Hz, 1H), 8.02 (m, 2H), 7.31 (d, J=7.9 Hz, 1H), 6.95 (dd, J=11.5 and 17.9 Hz, 1H), 6.73 (s, 1H), 5.86 (d, J=17.9 Hz, 1H), 5.33
# (d, J=11.5 Hz, 1H), 3.81 (s, 3H), 3.57 (s, 3H), 3.14 (m, 2H), 1.65 (m, 1H), 1.39(m, 1H), 1.11 (m, 1H), 0.87 (m, 6H)
123m	734	—CH═CH2	—CO2H	735	122m	I-1	1 H NMR (DMSO-d6): δ 12.81 (bs, 1H), 8.72 (t, J=5.6 Hz, 1H), 8.38 (d, J=1.8 Hz, 1H), 8.08 (dd, J=1.8 and 8.1 Hz, 1H), 7.61 (s, 1H), 7.57 (s, 1H), 7.39 (d, J=8 Hz, 1H), 6.72 (dd, J=11 and 17.5 Hz, 1H), 5.99 (d, J=17.5
# Hz, 1H), 5.49 (d, J=11 Hz, 1H), 3.57 (s, 3H), 3.13 (t, J=6.5 Hz, 2H), 1.87 (m, 1H), 1.37 (s, 9H), 0.91 (d, J=6.8 Hz, 6H); MS (ES−): 480.3

[0301]

736
Cpd.				Starting	Method
No.	—R	—R′	R″	From	Used	Analytical Data
124a	—CH3	—CH3	737	123a	J	MS (ES+): 529.3
124b	—C2H5	—CH3	738	123b	J	MS (ES+): 543.3
124c	—CH(CH3)2	—CH3	739	123c	J	MS (ES+): 557.3
124d	—CH3	—CH3	740	123d	J	Characterized in the next step
124e	—CH3	—CH3	741	123e	J	MS (ES+): 571.6
124f	—CH3	—CH3	742	123f	J	MS (ES+): 543.6
124g	—CH3	—CH3	743	123g	J	1 H NMR (DMSO): δ 10.62 (s, 1H), 9.35 (t, J=6.6 Hz, 1H), 9.20 (s, 2H), 8.90 (s, 2H), 8.30 (d, J=1.9 Hz, 1H), 8.11 (dd, J=8.1, 1.9 Hz, 1H), 7.86 (s, 1H), 7.76 (s, 4H), 7.50 (d, J=8.1 Hz, 1H), 7.04 (dd, J=17.9, 11.5 Hz, 1H), 6.94 (s, 1H), 6.01 (dd, J=17.7, 1.3, 1H), 5.42 (dd, J=11.3, 1.3 Hz, 1H), 4.11 (m, 2H), 3.89 (s, 3H), 3.57 (s, 3H)
124h	—CH3	—CH3	744	123h	J	1 H NMR (DMSO): δ 9.03 (broad, 3H), 8.49 (broad, 1H), 8.04 (s, 1H), 7.65 (m, 6 H), 6.99 (m, 2H), 6.61 (s, 1H), 5.90 (d, J=17.5 Hz, 1H), 5.35 (d, J=11.5 Hz, 1H), 3.78 (s, 3H), 3.20 (m, 2H), 1.46 (m, 2H), 1.28 (m, 2H), 0.87 (t, J=7.3 Hz, 3H)
124i	—CH3	—CH3	745	123i	J	MS (ES+): 527.4
124j	—CH3	—CH3	746	123j	J	MS (ES+): 541.4
124k	—CH3	—CH3	747	123K	J	MS (ES+): 501.3
124l	—CH3	—CH3	748	123l	J	MS (ES+): 543.3
124m	749	—CH3	750	123m	J	1 HNMR (DMSO-d6): δ 10.67 (s, 1H), 9.19 (bs, 2H), 8.88 (bs, 2H), 8.71 (t, J=5.6 Hz, 1H), 8.25 (d, J=1.8 Hz, 1H), 8.07 (dd, J=1.8 and 8.1 Hz, 1H), 7.73 (m, 4H), 7.65 (s, 1H), 7.50 (d, J=8 Hz, 1H), 7.45 (s, 1H), 6.73 (dd, J=11 and 17.5 Hz, 1H), 6.03 (d, J=17.5 Hz, 1H), 5.49 (d, J=11 Hz, 1H), 3.56 (s, 3H), 3.09 (t, J=6.5 Hz, 2H), 1.85 (m,
# 1H), 1.37 (s, 9H), 0.89 (d, J=6.8 Hz, 6H); MS (ES−): 597.3 and (ES+): 599.5
125a	—CH3	—H	751	124a	I-2	1 HNMR (DMSO): δ 13.40 (bs, 1H), 9.26 and 9.03 (2s, 4H), 8.53-8.49 (t, J=6 Hz, 1H), 8.02 (d, J=1.28 Hz, 1H), 7.71-7.53 (m, 6H), 7.0-6.9 (m, 2H), 6.5 (s, 1H), 5.89 (d, J=17.6 Hz, 1H), 5.33 (d, J=12.4 Hz, 1H), 3.37 (s, 3H), 3.04-2.99 (m, 2H), 1.85-1.75 (m, 1H), 0.86-0.84 (d, J=76.8 Hz, 6H); MS (ES+): 515.3
125b	—C2H5	—H	752	124b	I-2	1 HNMR (DMSO): δ 9.17 and 8.92 (s, 3H), 8.67-8.63 (m, 1H), 8.28 (s, 1H), 7.95-7.93 (m, 1H), 7.83 (s, 1H), 7.73 (s, 5H), 7.29 (d, J=8.1 Hz, 1H), 7.02 (dd, J=17.7 Hz, 11.3 Hz, 1H), 6.82 (s, 1H), 6.00 (d, 17.7 Hz, 1H), 5.38 (d, 11.3 Hz, 1H), 4.14-4.06 (m, 2H), 3.11-3.04 (q, J=6.8 Hz, 2H), 1.89-1.80
# (m, 1H), 1.35 (t, J=6.8 Hz, 3H), 0.88 (d, J=6.8 Hz, 6H); MS (ES+): 529.2
125c	—CH(CH3)2	—CH3	753	124c	I-2	1 HNMR (DMSO): δ 13.74 (s, 1H), 8.99 (s, 3H), 8.59-8.41 (m, 1H), 7.95 (s, 1H), 7.69 (s, 1H), 7.65-7.53 (m, 6H), 7.06-6.91 (m, 2H), 6.53 (s, 1H), 5.89 (d, J=17.7 Hz, 1H), 5.32 (d, J=11.5 Hz, 1H), 4.62-4.54 (m, 1H), 3.03-2.99 (m, 2H), 1.87-1.71 (m, 1H), 1.25 (d, J=6.1 Hz, 6H), 0.85 (d, J=6.8
# Hz, 6H); MS (ES−): 541.2
125d	—CH3	—H	754	124d	I-2	1 HNMR (DMSO-d6): δ 8.9 (d, J=33.74, 4H), 8.08 (d, J=7.91, 1H), 7.81 (s, 1H), 7.51 (s, 1H), 7.41 (s, 4H), 6.78 (s, 1H), 6.3 (s, 2H), 5.70 (d, J=7.78 Hz, 1H), 5.15 (d, J=11.8 Hz, 2H),) 3.82 (m, J=20.34 Hz, 2H), 3.56 (bs, 3H) 0.92 (d, 6H); MS (ES+) 501.3
125e	—CH3	—H	755	124e	I-2	1 HNMR (DMSO-d6): δ 9.05 (s, 2H), 8.85 (s, 2H), 7.96 (d, J=9.04 Hz, 1H), 7.88 (s, 1H), 6,86 (m, J=17.8 Hz, 3H), 7.62 (m, 1H), 7.24 (d, J=7.8 Hz, 1H), 6.95 (d, J=7.8 Hz, 1H), 7.45 (m, J=28.63 Hz, 5H), 7.55 (s, 1H), 5.75 (d, J=17.5 Hz, 1H); 5.61 (d, J=11.11, 1H) 3.61 (s, 3H) 1.30 (bs,
# 3H) 1.05 (s, 4H) 0.66 (m, 6H); MS (ES+) 555.3 (100% M+1)
125f	—CH3	—H	756	124f	I-2	1 H NMR (DMSO-d6): δ 12.7 (bs, 1H), 9.01 (bs, 2H), 8.87 (bs, 2H), 8.36 (t, J=6 Hz, 1H), 7.83 (s, 1H), 7.44 (m, 6H), 6.75 (m, 2H), 6.31 (d, J=2.2 Hz, 1H), 5.7 (d, J=17 Hz, 1H), 5.1 (d, J=11 Hz, 1H), 3.5 (s, 3H), 2.84 (m, 2H), 1.3 (m, 2H), 1.1 (m, 4H), 0.7 (m, 3H); MS (ES+): 529.4
125g	—CH3	—H	757	124g	I-2	1 H NMR (DMSO): δ 9.22 (broad, 1H), 9.09 (s, 2H), 8.9 (s, 2H), 8.18 (s, 1H), 7.80 (m, 2H), 7.66 (m, 4H), 7.16 (s, 1H), 7.00 (dd, J=17.7, 11.1 Hz, 1H), 6.70 (s, 1H), 5.94 (d, J=17.7 Hz, 1H), 5.37 (d, J=10.9 Hz, 1H), 4.07 (m, 2H), 3.81 (s, 3H); MS (ES−) 539.3
125h	—CH3	—H	758	124h	I-2	1 H NMR (DMSO): δ 9.03 (bs, 4H), 8.49 (bs, 1H), 8.04 (s, 1H), 7.65 (m, 6 H), 6.99 (m, 2H), 6.61 (s, 1H), 5.90 (d, J=17.5 Hz, 1H), 5.35 (d, J=11.5 Hz, 1H), 3.78 (s, 3H), 3.20 (m, 2H), 1.46 (m, 2H), 1.28 (m, 2H), 0.87 (t, J=7.3 Hz, 3H); MS (ES+) 515.4
125i	—CH3	—H	759	124i	I-2	1 H NMR (DMSO): δ 8.86 (s, 2H), 8.78 (s, 2H), 8.44 (broad, 1H), 7.89 (s, 1H), 7.53 (m, 2H), 7.43 (m, 4H), 6.86 (s, 1H), 6.78 (dd, J=17.5, 11.3 Hz, 1H), 6.44 (s, 1H), 5.71 (d, J=17.5 Hz, 1H), 5.14 (d, J=11.1 Hz, 1H), 3.59 (s, 3H), 2.89 (m, 2H), 0.79 (m, 1H), 0.20 (m, 2H), 0.01 (m, 2H); MS (ES−) 513.4
125j	—CH3	—H	760	124j	I-2	1 H NMR (DMSO): δ 13.14 (br s, 1H), 8.84 (m, 3H), 8.12 (d, J=7.3 Hz, 1H), 7.79 (s, 1H), 7.40 (m, 8H), 6.74 (m, 2H), 6.33 (s, 1H), 5.66 (d, J=19.2 Hz, 1H), 5.10 (d, J=11.7 Hz, 1H), 3.94 (m, 1H), 3.54 (s, 3H), 1.66-0.93 (m, 8H); MS (ES+) 527.4
125k	—CH3	—H	761	124k	I-2	1 H NMR (DMSO): δ 9.25 (m, 4H), 8.73 (t, J=5.7 Hz, 1H), 8.28 (s, 1H), 7.86 (m, 7H), 6.84 (s, 1H), 6.10 (d, J=17.7 Hz, 1H), 5.55 (d, J=11.3 Hz, 1H), 3.99 (s, 3H), 3.43 (qui, J=6.2 Hz, 2H), 1.28 (t, J=7.2 Hz, 3H); MS (ES+): 487.2
125l	—CH3	—H	762	124l	I-2	1 H NMR (DMSO): δ 8.91 (m, 4H), 8.38 (t, J=5.5 Hz, 1H), 7.96 (s, 1H), 7.53 (m, 5H), 6.86 (m, 2H), 6.52 (s, 1H), 5.77 (d, J=17.7 Hz, 1H), 5.21 (d, J=11.5 Hz, 1H), 3.65 (s, 3H), 2.94 (m, 1H), 1.57-0.56 (m, 11H); MS (ES+): 529.3
125m	—CH3	—H	763	124m	I-2	1 HNMR (DMSO-d6): δ 10.07 (bs, 1H), 9.05 (bs, 2H), 8.98 (bs, 2H), 8.49 (t, J=5.6 Hz, 1H), 7.96 (s, 1H), 7.62 (m, 5 H), 7.06 (s, 1H), 7.03 (s, 1H), 6.94 (dd, J=11 and 18 Hz, 1H), 5.78 (d, J=18 Hz, 1H), 5.26 (d, J=11 Hz, 1H), 3.02 (t, J=5.7 Hz, 2H), 1.81 (m, 1H), 0.85 (d, J=6.8 Hz, 6H); MS (ES−): 499.2 and (ES+) 501.3

[0302]

764
Cpd.				Starting	Method
No.	—R	—R′	—R″	From	Used	Analytical Data
133a	765	—H	—CH3	132	A-5	MS (ES+): 506.4
133b	766	—H	—CH3	132	J	MS (ES+): 499.3
133c	767	—H	—CH3	132	A-5	Characterized in the next step
133d	768	—H	—CH3	132	A-5	Characterized in the next step
133e	769	—H	—CH3	132	A-5	Characterized in the next step
133f	770	—H	—CH3	132	A-5	Characterized in the next step
133g	771	—H	—CH3	132	A-5	Characterized in the next step
133h	772	—H	—CH3	132	A-5	Characterized in the next step
133i	773	—H	—CH3	132	A-5	Characterized in the next step
133j	774	—H	—CH3	132	A-5	Characterized in the next step
133k	775	—H	—CH3	132	J	MS (ES+): 502.3
133l	776	—H	—CH3	132	J	MS (ES+): 470.2
133m	777	—H	—CH3	132	J	MS (ES+): 437.3
133n	778	—H	—CH3	132	J	MS (ES+): 518.2
133o	779	—H	—CH3	132	J	MS (ES+): 501.3
133p	780	—H	—CH3	132	J	MS (ES+): 469.1
133q	781	—H	—CH3	132	J	MS (ES−): 469.1; MS (ES+): 471.2
133r	782	—H	—CH3	132	A-5	Characterized in the next step
133s	783	—H	—CH3	132	A-5	MS (ES+): 483.2 (M + Na)
133u	784	—H	—CH3	132	A-5	MS (ES+): 432.2
133v	785	—H	—CH3	132	A-5	MS (ES+): 432.2
133w	786	—H	—CH3	132	A-5	MS (ES+): 447.2
133x	787	—H	—CH3	132	A-5	Characterized in the next step
133y	788	—H	—CH3	132	A-5	MS (ES+): 446.3
133z	789	—H	—CH3	132	A-5	MS (ES+): 446.2
133aa	790	—H	—CH3	132	A-4	MS (ES+): 475.3
133ab	791	—H	—CH3	132	J	MS (ES+): 499.3 (M + Na)
133ac	792	—H	—CH3	132	A-4	MS (ES−): 483.2; MS (ES+): 485.2
133ad	793	—H	—CH3	132	A-4	MS (ES−): 497.2; MS (ES+): 495.2
133ae	794	—H	—CH3	132	A-4	MS (ES−): 483.2; MS (ES+): 485.2
133af	795	—H	—CH3	132	J	MS (ES+): 511.3 (M + Na)+; MS (ES−): 487.3
133ag	796	—H	—CH3	132	J	MS (ES−): 451.3
133ai	797	—H	—CH3	132	J	MS (ES−): 584.4
134a	798	—H	—H	133a	I-2	1 HNMR (DMSO-d6): δ 13.13 (bs, 1H), 8.76 (t, J=6 and 5Hz, 1H), 8.32 (m, 2H), 8.02 (dd, J=1.9 and 8.1 Hz, 1H), 7.42 (m, 4H), 7.25 (m, 1H), 3.62-3.19 (m, 12H), 3.11 (t, J=6.8 Hz, 2H), 1.87 (m, 1H), 1.76 (m, 2H), 0.90 (d, J=6.8 Hz, 6H); MS (ES−) 490.3; (ES+) 492.3
134b	799	—H	—H	133b	I-2	1 HNMR (DMSO-d6): δ 13.82 (bs, 1H), 10.57 (bs, 2H), 8.50 (t, J=6 and 5 Hz, 1H), 7.99 (d, J=1.5 Hz, 1H), 7.83 (s, 1H), 7.8 (s, 1H), 7.59 (m, 4H), 7.46 (m, 2H), 7.03 (m, 1H), 6.92 (d, J=7.9 Hz, 1H), 3.89 (s, 4H), 3.02 (t, J=6.8 Hz, 2H), 1.81 (m, 1H), 0.8 (d, J=6.8 Hz, 6H); MS (ES−): 483.3; MS (ES+): 485.4
134c	800	—H	—H	133c	I-2	1 HNMR (DMSO-d6): δ 8.71 (t, J=5.5 Hz, 1H), 8.40 (t, J=5.3 Hz, 1H), 8.30 (s, 1H), 8.00 (d, J=7.8 Hz, 1H), 7.63 (d, J=4.3 Hz, 2H), 7.40 (d, J=7.4 Hz, 4H), 7.27 (d, J=8.1 Hz, 1H), 7.18 (s, 1H), 6.91 (d, J=7.1 Hz, 1H), 4.42 (b, 2H), 3.13 (t, J=6.5 Hz, 2H), 1.93 (m, 1H), 0.91 (d, J=6.8 Hz, 6H); MS (ES−) 497.3
134d	801	—H	—H	133d	I-2	1 HNMR (DMSO-d6): δ 10.45 (s, 1H), 8.63 (s, 1H), 8.27 (s, 1H), 7.93 (d, J=8.1 Hz, 1H), 7.67 (t, J=6.8 Hz, 2H), 7.55 (m, 2H), 7.27 (m 3H), 7.12 (m, 2H), 3.06 (t, J=6 Hz, 2H), 1.82 (m, 1H), 0.86 (d, J=6.8 Hz, 6H); MS (ES−) 483.3
134e	802	—H	—H	133e	I-2	1 HNMR (DMSO-d6): δ 12.92 (bs, 1H), 8.71 (t, J=5.8 Hz, 1H), 8.49 (t, J=6.2 Hz, 1H), 8.32 (s, 1H), 8.01 (d, J=7.8 Hz, 1H), 7.52 (m, 5H), 7.27 (d, J=7.9 Hz, 1H), 7.18 (m, 1H), 7.08 (d, J=8.2 Hz, 2H), 4.32 (d, J=4.2 Hz, 2H), 3.12 (t, J=6.5 Hz, 2H), 1.88 (m, 1H), 0.91 (d, J=6.8 Hz, 6H); MS(ES−) 498.2
134f	803	—H	—H	133f	I-2	1 HNMR (DMSO-d6): δ 8.66 (t, J=5.7 Hz, 1H), 8.27 (s, 1H), 7.92 (d, J=8.1 Hz, 1H), 7.45 (m, 7H), 7.18 (m, 3H), 4.32 (d, J=5.9 Hz, 2H), 3.12 (t, J=6 Hz, 2H), 1.89 (m, 1H), 0.91 (d, J=6.8 Hz, 6H); MS (ES−) 497.2
134g	804	—H	—H	133g	I-2	1 HNMR (DMSO-d6): δ 13.1 (s, 1H), 9.58 (s, 1H), 8.65 (s, 1H), 8.29 (s, 1H), 7.98 (d, J=5.9 Hz, 1H), 7.75 (d, J=5.2 Hz, 2H), 7.30 (d, J=8 Hz, 2H), 7.12 (d, J=12.0 Hz, 1H), 7.12 (m, 4H), 3.06 (t, J=6 Hz, 2H), 1.85 (m, 1H), 0.86 (d, J=6.8 Hz, 6H); MS (ES−) 483.2
134h	805	—H	—H	133h	I-2	1 HNMR (DMSO-d6): δ 10.31 (s, 1H), 8.65 (t, J=6.2 Hz, 1H), 8.31 (s, 1H), 7.98 (d, J=7.9 Hz, 1H), 7.66 (m, 1H), 7.53 (m, 3H), 7.27 (m, 4H), 6.85 (m, 1H), 3.09 (t, J=6.5 Hz, 2H), 1.86 (m, 1H), 0.89 (d, J=6.8 Hz, 6H); MS (ES−) 433.1 (M−1)
134i	806	—H	—H	133i	I-2	1 HNMR (DMSO-d6): δ 8.71 (t, J=5.7 Hz, 1H), 8.31 (s, 1H), 8.01 (d, J=7.9 Hz, 1H), 7.46 (m, 2H), 7.39 (m, 2H), 7.24 (s, 1H), 3.38 (b, 8H), 3.11 (t, J=6.5 Hz, 2H), 1.86 (m, 1H), 0.91 (d, J=6.8 Hz, 6H); MS (ES−) 409.3
134j	807	—H	—H	133j	I-2	1 HNMR (DMSO-d6): δ 9.61 (s, 1H), 8.67 (t, J=5.5 Hz, 1H), 8.32 (s, 1H), 7.98 (d, J=7.9 Hz, 1H), 7.71 (m, 2H), 7.54 (m, 2H), 7.29 (d, J=7.9 Hz, 1H), 7.04 (m, 4H), 3.10 (t, J=6.5 Hz, 2H), 1.86 (m, 1H), 0.89 (d, J=6.8 Hz, 6H); MS (ES−) 433.3
134k	808	—H	—H	133k	I-2	1 HNMR (DMSO-d6): δ 8.59 (t, J=6 and 5 Hz, 1H), 8.3 (d, J=5 Hz, 2H), 8.18 (s, 1H), 7.86 (d, J=8 Hz, 1H), 7.36 (m, 5H), 6.6 (t, J=4.7 Hz, 1H), 4.0 (m, 1H), 3.75 (m, 2H), 3.37 (m, 5H), 3.07 (t, J=6.8 Hz, 2H), 1.81 (m, 1H), 0.85 (d, J=6.8 Hz, 6H)
134l	809	—H	—H	133l	I-2	1 HNMR (DMSO-d6): δ 10.92 (bs, 1H), 8.55 (t, J=6 and 5 Hz, 1H), 8.14 (s, 1H), 7.76 (d, J=7 Hz, 1H), 7.68 (m, 1H), 7.62 (m, 1H), 7.45 (m, 2H), 7.24 (t, J=2.6 Hz, 1H), 7.19 (s, 1H), 7.15 (s, 1H), 7.10 (m, 2H), 6.95 (dd, J=1.5 and 8.7 Hz, 1H), 6.28 (s, 1H), 3.04 (t, J=6.8 Hz, 2H), 1.82 (m, 1H), 0.86 (d, J=6.8 Hz, 6H); MS (ES−) 454.3; (ES+) 456.3
134m	810	—H	—H	133m	I-2	1 HNMR (DMSO-d6): δ 13.30 (bs, 1H), 8.62 (t, J=6 and 5 Hz, 1H), 8.18 (s, 1H), 7.87 (d, J=7.9 Hz, 1H), 7.42 (m, 3H), 7.09 (m, 2H), 3.03 (m, 1H), 3.1 (t, J=6.8 Hz, 2H), 1.86 (m, 1H), 1.4 (m, 4H), 1.09 (m, 1H), 0.89 (d, J=6.8 Hz, 6H); MS (ES−) 421.2; (ES+) 423.2
134n	811	—H	—H	133n	I-2	1 HNMR (DMSO-d6): δ 15.89 (bs, 1H), 8.56 (t, J=6 and 5 Hz, 1H), 8.06 (s, 1H), 7.67 (m, 2H), 7.54 (d, J=8.8 Hz, 1H), 7.48 (m, 4H), 7.05 (m, 1H), 6.96 (m, 2H), 3.77 (s, 3H), 3.03 (t, J=6.8 Hz, 2H), 1.81 (m, 1H), 0.84 (d, J=6.8 Hz, 6H); MS (ES−) 502.3; (ES+) 504.3
134o	812	—H	—H	133o	I-2	1 HNMR (DMSO-d6): δ 13.07 (bs, 1H), 8.63 (t, J=6 and 5 Hz, 1H), 8.26 (s, 1H), 8.05 (d, J=4 Hz, 1H), 7.94 (d, J=8 Hz, 1H), 7.43 (m, 5H), 7.28 (m, 1H), 6.72 (d, J=8.8 Hz, 1H), 6.62 (dd, J=5.5 and 6.5 Hz, 1H), 3.34 (m, 8H), 3.07 (t, J=6.8 Hz, 2H), 1.82 (m, 1H), 0.85 (d, J=6.8 Hz, 6H); MS (ES−) 486.3; (ES+) 488.3
134p	813	—H	—H	133p	I-2	1 HNMR (DMSO-d6): δ 12.94 (bs, 1H), 10.20 (bs, 1H), 8.63 (t, J=6 and 5 Hz, 1H), 8.28 (d, J=1.5 Hz, 1H), 7.96 (m, 2H), 7.92 (d, J=8.3 Hz, 1H), 7.68 (m, 1H), 7.52 (m, 2H), 7.4 (m, 1H), 7.3 (m, 2H), 7.24 (m, 1H), 3.08 (t, J=6.8 Hz, 2H), 1.84 (m, 1H), 0.88 (d, J=6.8 Hz, 6H); MS (ES−) 455.2; (ES+) 479.2 (M + Na)
134q	814	—H	—H	133q	I-2	1 HNMR (DMSO-d6): δ 12.84 (bs, 1H), 10.45 (bs, 1H), 8.62 (t, J=6 and 5 Hz, 1H), 8.27 (d, J=,1.5 Hz, 1H), 8.01 (s, 1H), 7.93 (s, 2H), 7.9 (d, J=1.5 Hz, 1H), 7.69 (m, 1H), 7.57 (d, J=8.7 Hz, 1H), 7.52 (m, 2H), 7.29 (d, J=8 Hz, 1H), 7.23 (m, 1H), 7.02 (dd, J=1.5 and 8.7 Hz, 1H), 3.07 (t, J=6.8 Hz, 2H), 1.83 (m, 1H),
# 0.87 (d, J=6.8 Hz, 6H), MS (ES−) 455.2; (ES+) 479.3 (M + Na)
134r	815	—H	—H	133r	I-2	1 HNMR (DMSO-d6): δ 8.64 (t, J=5.5 Hz, 1H), 8.16 (s, 1H), 7.87 (d, J=7.1 Hz, 1H), 7.50 (m, 1H), 7.40 (d, J=4.1 Hz, 2H), 7.19 (b, 3H), 7.07 (m, 2H), 6.51 (m, 2H), 6.35 (d, J=7.8 Hz, 2H), 3.97 (d, J=5.6 Hz, 2H), 3.13 (t, J=6.5 Hz, 2H), 1.90 (m, 1H), 0.91 (d, J=6.8 Hz, 6H)
134s	816	—H	—H	133s	I-2	1 HNMR (DMSO-d6): δ 9.53 (bs, 1H), 8.67 (t, J=4.7 Hz, 1H), 8.32 (s, 1H), 7.99 d, J=8.1 Hz, 1H), 7.70 (d, J=7.6 Hz, 1H), 7.52 (m, 2H), 7.46 (d, J=11.5 Hz, 1H), 7.32 (m, 3H), 7.18 (m, 3H), 4.33 (s, 2H), 3.10 (t, J=6.5 Hz, 2H), 1.86 (m, 1H), 0.89 (d, J=6.8 Hz, 6H); MS (ES−) 445.2
134t	—OH	—H	—H	132	I-2	1 HNMR (DMSO-d6): δ 12.57 (b, 1H), 8.69 (t, J=5.6 Hz, 1H), 8.36 (s, 1H), 7.99 (d, J=7.9 Hz, 1H), 7.92 (d, J=7.7 Hz, 1H), 7.57 (t, J=7.5 Hz, 1H), 7.46 (t, J=7.7 Hz, 1H), 7.23 (d, J=5.2 Hz, 1H), 7.17 (d, J=7.5 Hz, 1H), 3.12 (t, J=6.5 Hz, 2H), 1.88 (m, 1H), 0.91 (d, J=6.8 Hz, 6H); MS (ES−) 340.2
134u	817	—H	—H	133u	I-2	1 HNMR (DMSO-d6): δ 8.56 (t, J=5.0 Hz, 1H), 8.16 (d, J=7.0 Hz, 2H), 7.94 (d, J=8.4 Hz, 1H), 7.75 (d, J=7.4 Hz, 1H), 7.63 (m, 2H), 7.46 (m, 2H), 7.21 (b, 1H), 7.07 (s, 2H), 6.99 (t, J=5.1 Hz, 1H), 3.05 (t, J=6.5 Hz, 2H), 1.83 (m, 1H), 0.86 (d, J=6.8 Hz, 6H); MS (ES−) 416.3
134v	818	—H	—H	133v	I-2	1 HNMR (DMSO-d6): δ 8.60 (t, J=5.6 Hz, 1H), 8.32 (d, J=5.3 Hz, 2H), 8.11 (s, 1H), 7.78 (d, J=7.7 Hz, 1H), 7.65 (d, J=5.5 Hz, 1H), 7.55 (m, 2H), 7.43 (d, J=4.5 Hz, 2H), 7.14 (m, 3H), 3.06 (t, J=6.5 Hz, 2H), 1.83 (m, 1H), 0.86 (d, J=6.8 Hz, 6H); MS (ES−) 416.2
134w	819	—H	—H	133w	I-2	1 HNMR (DMSO-d6): δ 10.10 (bs, 1H), 9.31 (s, 1H), 8.65 (t, J=5.7 Hz, 1H), 8.27 (s, 1H), 7.93 (d, J=8.1 Hz, 1H), 7.62 (d, J=5.3 Hz, 1H), 7.48 (m, 2H), 7.28 (s, 1H), 7.20 (d, J=12.0 Hz, 1H), 7.09 (s, 1H), 6.98 (d, J=7.0 Hz, 1H), 6.81 (d, J=7.3 Hz, 1H), 6.37 (t, J=7.6 Hz, 1H), 3.09 (t, J=6.5 Hz, 2H), 1.85 (m, 1H), 0.90 (d, J=6.8 Hz,
# 6H); MS (ES−) 431.1
134x	820	—H	—H	133x	I-2	1 HNMR (DMSO-d6): δ 10.28 (bs, 1H), 8.63 (t, J=5.3 Hz, 1H), 8.34 (d, J=4.7 Hz, 1H), 8.06 (s, 1H), 7.82 (d, J=6.6 Hz, 1H), 7.53 (m, 1H), 7.42 (m, 2H), 7.34 (t, J=8.6 Hz, 1H), 7.18 (s, 1H), 7.07 (d, J=2.7 Hz, 2H), 6.10 (b; 1H), 4.43 (b; 1H), 4.12 (b, 1H), 3.12 (t, J=6.5 Hz, 2H), 1.89 (m, 1H), 0.90 (d, J=6.8 Hz, 6H); MS (ES+)
# 432.3, (ES−) 430.2
134y	821	—H	—H	133y	I-2	1 HNMR (DMSO-d6): δ 9.79 (bs, 1H), 8.62 (t, J=6.0 Hz, 1H), 8.31 (d, J=4.5 Hz, 1H), 8.20 (s, 1H), 8.08 (s, 1H), 7.78 (d, J=2.1 Hz, 1H), 7.51 (m, 1H), 7.42 (m, 2H), 7.06 (m, 3H), 6.88 (m, 1H), 4.02 (b, 2H), 3.13 (t, J=6.5 Hz, 2H), 1.90 (m, 1H), 0.93 (d, J=6.8 Hz, 6H); MS (ES+) 432.3, (ES−) 430.3
134z	822	—H	—H	133z	I-2	1 HNMR (DMSO-d6): δ 10.71 (bs, 1H), 8.64 (t, J=5.9 Hz, 1H), 8.21 (d, J=5.2 Hz, 2H), 8.05 (s, 1H), 7.81 (d, J=7.7 Hz, 1H), 7.51 (m, 1H), 7.42 (m, 2H), 7.18 (s, 1H), 7.04 (t, J=1.4 Hz, 2H), 6.51 (b, 2H), 4.41 (b, 1H), 4.01 (b, 1H), 3.13 (t, J=6.5 Hz, 2H), 1.91 (m, 1H), 0.91 (d, J=6.8 Hz, 6H); MS (ES+) 432.2, (ES−) 430.2
134aa	823	—H	—H	133aa	I-2	1 HNMR (DMSO-d6): δ 10.02 (bs, □1H), 8.65 (t, J=5.7 Hz, 1H), 8.26 (s, 1H), 7.94 (d, J=7.7 Hz, 1H), 7.66(d, J=5.8 Hz, 1H), 7.51 (m, 2H), 7.36 (d, J=8.4 Hz, 2H), 7.29 (d, J=7.9 Hz, 1H), 7.22 (d, J=5.5 Hz, 1H), 7.07 (d, J=8.3 Hz, 2H), 4.57 (t, J=9.0 Hz, 1H), 3.51 (m, 2H), 3.09 (t,
# J=6.5 Hz, 2H), 2.62 (t, J=6.6 Hz, 2H), 1.85 (m, 1H), 0.90 (d, J=6.8 Hz, 6H), MS (ES−) 459.2
134ab	824	—H	—H	133ab	I-2	1 HNMR (DMSO-d6): δ 9.05 (s, 1H), 8.70 (t, J=5.7 Hz, 1H), 8.56 (s, 1H), 8.36 (s, 1H), 8.12 (m, 2H), 7.79 (m, 1H), 7.60 (m, 1H), 7.44 (s, 2H), 7.09 (m, 2H), 6.56 (d, J=8.9 Hz, 1H), 4.89 (t, J=4.4 Hz, 1H), 4.38 (d, J=5.6 Hz, 2H), 3.11 (t, J=6.5 Hz, 2H), 1.84 (m, 1H), 0.90 (d, J=6.8 Hz, 6H), MS (ES−) 461.1
134ac	825	—H	—H	133ac	I-2	1 HNMR (DMSO-d6): δ 8.60 (t, J=6 and 5 Hz, 1H), 8.13 (s, 2H), 7.85 (d, J=2 Hz, 1H), 7.46 (m, 4H), 7.36 (d, J=7.7 Hz, 1H), 7.16 (m, 4H), 7.10 (m, 1H), 3.17 (s, 3H), 3.08 (t, J=6.8 Hz, 2H), 1.85 (m, 1H), 0.89 (d, J=6.8 Hz, 6H), MS (ES−) 469.2; (ES+) 471.3
134ad	826	—H	—H	133ad	I-2	1 HNMR (DMSO-d6): δ 8.55 (t, J=6 and 5 Hz, 1H), 8.10 (s, 2H), 7.73 (d, J=7.2 Hz, 1H), 7.54 (m, 4H), 7.46 (m, 5H), 7.08 (m, 3H), 3.04 (t, J=6.8 Hz, 2H), 1.82 (m, 1H), 0.86 (d, J=6.8 Hz, 6H), MS (ES−) 481.1; (ES+) 483.3
134ae	827	—H	—H	133ae	I-2	1 HNMR (DMSO-d6): δ 9.66 (bs, 1H), 8.54 (t, J=6 and 5 Hz, 1H), 8.12 (s, 2H), 7.77 (dd, J=8 and 2 Hz, 1H), 7.6 (dd, J=7 and 2 Hz, 1H), 7.45 (m, 5H), 7.10 (m, 4H), 4.36 (bs, 2H), 3.09 (t, J=6.8 Hz, 2H), 1.86 (m, 1H), 0.89 (d, J=6.8 Hz, 6H), MS (ES−) 469.2; (ES+) 471.3
134af	828	—H	—H	133af	I-2	1 HNMR (DMSO-d6): δ 9.76 (s, 1H), 9.17 (s, 1H), 8.63 (t, J=5.0 Hz, 1H), 8.29 (s, 1H), 7.90 (d, J=1.6 Hz, 1H), 7.60 (s, 1H), 7.51 (d, J=8 Hz 1H), 7.30 (d, J=3.6 Hz, 2H), 7.28 (d, J=8.2 Hz, 1H), 7.22 (t, 3H), 6.60 (d, J=8.9 Hz, 1H), 3.06 (t, J=6 Hz, 2H), 1.85 (m, 1H), 0.86 (d, J=6.8 Hz, 6H); MS (ES−) 431.2
134ag	829	—H	—H	133ag	I-2	1 HNMR (DMSO-d6): δ 9.64 (s, 1H), 9.06 (s, 1H), 8.66 (t, J=5.6 Hz, 1H), 8.29 (s, 1H), 7.95 (d, J=7.9 Hz, 1H), 7.63 (m, 1H), 7.50 (m, 2H), 7.29 (d, J=3.1 Hz, 1H), 7.20 (d, J=8.9 Hz, 1H), 7.11 (m, 1H), 7.03 (m, 1H), 6.60 (d, J=8.9 Hz, 1H), 3.08 (t, J=6 Hz, 2H), 2.05 (s, 3H), 1.85 (m, 1H), 0.86 (d, J=6.8 Hz, 6H); MS (ES−) 445.2,
# MS (ES+) 469.3 (M + Na)
134ai	830	—H	—H	133ai	I-2, S	MS (ES+): 472.2; MS (ES−): 470.2
135a	831	—CH═CH2	—CH3	30f	A-4	MS (ES+): 489.3
135b	832	—CH═CH2	—CH3	30f	A-4	MS (ES+): 475.3; MS (ES−): 473.3
135c	833	—CH═CH2	—CH3	30f	J	MS (ES+): 573.5; MS (ES−): 571.3
135d	834	—CH═CH2	—CH3	30f	A-4	MS (ES−): 472.2
135e	835	—CH═CH2	—CH3	30f	J	MS (ES−): 489.1
135f	836	—CH═CH2	—CH3	30f	J	MS (ES−): 498.1
135g	837	—CH═CH2	—CH3	30f	J	MS (ES−): 494.3
135h	838	—CH═CH2	—CH3	30f	J	MS (ES−): 584.2
136a	839	—CH═CH2	—H	135a	I-2	1 HNMR (DMSO-d6): δ 8.66 (t, J=.55 Hz, 1H), 8.35 (t, J=4 and 6.4 Hz, 1H), 8.28 (d, J=2 Hz, 1H), 7.95 (dd, J=7.9 and 2 Hz, 1H), 7.69 (s, 1H), 7.59 (m, 2H), 7.25 (d, J=8.1 Hz, 2H), 7.15 (m, 2H), 6.93 (s, 1H), 6.88 (dd, J=17.7 and 11.5 Hz, 1H), 5.95 (d, J=17.7 Hz, 1H), 5.37
# (d, J=11.5 Hz, 1H), 3.76 (t, J=6.8 Hz, 2H), 3.10 (t, J=6.4 Hz, 2H), 2.96 (m, 2H), 1.86 (m, 1H), 1.67 (m, 2H), 0.89 (d, J=6.8 Hz, 6H); MS (ES−) 473.3; (ES+) 475.3
136b	840	—CH═CH2	—H	135b	I-2	1 HNMR (DMSO-d6): δ 8.64 (t, 1H), 8.51 (s, 1H), 8.21 (s, 1H), 7.88 (d, J=7.8 Hz, 1H), 7.74 (s, 1H), 7.56 (s, 2H), 7.15 (m, 2H), 6.80 (t, 2H), 5.90 (d, J=17 Hz, 1H), 5.36 (d, J=11.0 Hz, 1H), 3.18 (m, 2H), 3.06 (t, J=6 Hz, 2H), 2.43 (m, 2H), 1.85 (m, 1H), 0.86 (d, J=6.8 Hz, 6H); MS (ES+) 461.2, MS (ES−) 459.2
136c	841	—CH═CH2	—H	135c	I-2, S	1 HNMR (DMSO-d6/D2O): δ 8.71 (t, 1H), 8.27 (d, J=3 Hz, 1H), 8.21 (d, J=3 Hz, 1H), 7.96 (q, 1H), 7.79 (q, 1H), 7.72 (s, 1H), 7.63 (d, J=8 Hz 1H), 7.30 (d, J=6 Hz, 1H), 7.24 (d, J=7 Hz, 1H), 6.87 (q, 2H), 6.00 (d, J=8 Hz, 1H), 5.41 (d, J=8 Hz, 1H), 3.06 (t, J=6 Hz, 2H), 1.85 (m,
# 1H), 0.86 (d, J=6.8 Hz, 6H); MS (ES+) 459.2
136d	842	—CH═CH2	—H	135d	I-2	1 HNMR (DMSO-d6): δ 12.86 (bs, 1H), 9.17 (s, 1H), 8.65 (t, J=6 Hz, 1H), 8.29 (d, J=2 Hz, 1H), 8.26 (s, 2H), 7.97 (dd, J=8 and 2 Hz, 1H), 7.76 (s, 1H), 7.63 (d, 8 Hz, 1H), 7.31 (d, J=8 Hz, 1H), 7.24 (d, J=8 Hz, 1H), 6.86 (dd, J=10.7 and 17.5 Hz, 1H), 6.49 (s, 1H), 5.99
# (d, J=17.5, 1H), 5.40 (d, J=10.7 Hz, 1H), 3.10 (t, J=6.8 Hz, 2H), 1.86 (m, 1H), 0.89 (d, J=6.8 Hz, 6H); MS (ES−) 458.2, (ES+) 460.3
136e	843	—CH═CH2	—H	135e	I-2	1 HNMR (DMSO-d6): δ 12.72 (s, broad, 1H), 8.65 (t, J=5.7 Hz, 1H), 8.29 (s, 1H), 7.93 (d, J=7.9 Hz, 1H), 7.74 (m, 2H), 7.65 (d, J=6 Hz 1H), 7.42 (d, J=7.9 Hz, 1H), 7.24 (m, 3H), 7.11 (m, 1H), 6.84 (q, J=11.1, 17.8 Hz, 1H), 5.97 (d, J=18 Hz, 1H), 5.58 (d, 1H), 5.41 (d, 1H),
# 3.08 (t, J=6 Hz, 2H), 1.85 (m, 1H), 0.86 (d, J=6.8 Hz, 6H); MS (ES−) 475.1
136f	844	—CH═CH2	—H	135f	I-2	1 HNMR (DMSO-d6): δ 8.67 (t, J=6.06 Hz, 1H), 8.28 (s, 1H), 7.90 (d, J=7.7 Hz, 1H), 7.67 (m, 4H), 7.32 (m, 5H), 7.09 (d, J=7.9 Hz 1H), 6.89 (q, J=10.9 & 18.0 Hz, 1H), 5.99 (d, J=17.5 Hz, 1H), 5.42 (d, J=11 Hz, 1H), 3.08 (t, J=6.3 Hz, 2H), 1.88 (m, 1H), 0.87 (d, J=6.8 Hz, 6H); MS (ES−) 484.2
136g	845	—CH═CH2	—H	135g	I-2	1 HNMR (DMSO-d6): δ 10.38 (s, 1H), 8.66 (t, J=6.06 Hz, 1H), 8.29 (s, 1H), 7.95 (d, J=6.1 Hz, 1H), 7.75 (s, 1H), 7.63 (d, 2H), 7.43 (d, 2H), 7.26 (m, 3H), 7.00 (d, J=7.7 Hz, 1H), 6.85 (q, J=10.9 & 18.0 Hz, 1H), 5.98 (d, J=17.5 Hz, 1H), 5.40 (d, J=11 Hz, 1H), 3.98 (s, 2H), 3.08
# (t, J=6.3 Hz, 2H), 1.86 (m, 1H), 0.88 (d, J=6.8 Hz, 6H); MS (ES−) 480.2
136h	846	—CH═CH2	—H	135h	S, I-2	1 HNMR (DMSO-d6): δ 8.55 (t, J=6.06 Hz, 1H), 8.02 (s, 1H), 7.60 (m, 4H), 7.21 (t, J=7.1, 2H), 6.99 (m, 2H), 6.83 (d, J=6.8 Hz, 1H), 6.81 (q, J=10.9 & 18.0 Hz, 1H), 5.92 (d, J=17.5 Hz, 1H), 5.35 (d, J=11 Hz, 1H), 3.89 (s, 2H), 3.03 (t, J=6.3 Hz, 2H), 1.36 (m, 1H), 0.86 (d, J=6.8 Hz, 6H)

[0303]

847
Cpd.					Starting	Method
No.	—R′	—R″	R′′′	X	From	Used	Analytical Data
117n	—OBn	—CHO	—CH3	N	116 + 220a	D-2	MS (ES+): 477.2
118n	—OBn	—CO2H	—CH3	N	117n	E	Characterized at the next step
119n	—OBn	—CO2MEM	—CH3	N	118n	F	Characterized at the next step
120n	—OH	—CO2MEM	—CH3	N	119n	G	Characterized at the next step
121n	—OSO2CF3	—CO2MEM	—CH3	N	120n	B-2	Characterized at the next step
122n	—CH═CH2	—CO2MEM	—CH3	N	121n	D-3	Characterized at the next step
123n	—CH═CH2	CO2H	—CH3	N	122n	I-1	MS (ES−): 411.1
124n	—CH═CH2	848	—CH3	N	123n	J	MS (ES+): 530.3
125n	—CH═CH2	849	H	N	124n	I-2	1H NMR (DMSO-d6 + H2O): 8.24 (d, J=7.7 Hz, 1H), 8.0-7.9 (m, 2H), 7.81 (s, 4H), 7.14-6.94 (m, 2H), 6.08 (d, J=17.3 Hz, 1H), 5.48 (d, J=12.05 Hz, 1H), 3.87 (s, 3H), 3.20 (d, J=6.4 Hz, 2H), 2.04-1.75 (1H, m), 0.92 (d, J=6.4 Hz, 6H). MS (ES+): 516.34.
189f	—OH	—CHO	—CH3	CH	117a	AL	MS (ES+): 386.4.
189g	—OH	—CHO	—CH3	N	117n	AL	MS (ES+): 387.38
189h	—OSO2CF3	—CHO	—CH3	CH	189f	B-2	MS (ES+): 518.2
189i	—OSO2CF3	—CHO	—CH3	N	189g	B-2	MS (ES+): 541.1 (M + Na)
189j	—CH═CH2	—CHO	—CH3	CH	189h	D-3	MS (ES+): 418.3 (M + Na)
189k	—CH═CH2	—CHO	—CH3	N	189i	D-3	MS (ES+): 397.3
189l	—CH═CH2	850	H	CH	189j	AE-3	1 HNMR (DMSO-d6): δ 8.63 (t, J=5 Hz, 1H), 8.56 (bs, 4H), 8.33 (s, 1H), 7.90 (d, J=8 Hz, 1H), 7.61 (m, 1H), 7.50 (s, 1H), 7.47 (2, 1H), 7.41 (s, 1H), 7.30 (d, J=7.2 Hz, 1H), 6.94 (dd, J=11 & 17.5 Hz, 1H), 6.67 (m, 3H), 5.62 (d, J=17.5 Hz, 1H), 5.20 (d, J=11 Hz,
# 1H), 4.01 (m, 2H), 3.73 (s, 3H), 3.09 (t, J=6.5 Hz, 2H), 1.86 (m, 1H), 0.80 (d, J=6.5 Hz, 6H); MS (ES+) 501.46
189m	—CH═CH2	851	H	N	189k	AE-3	1 H NMR (DMSOd6 + H2O): 8.20 (d, J=7.9 Hz, 1H), 8.04 (d, J=7.9 Hz, 1H), 7.67-7.45 (m, 4H), 6.94 (dd, J=17.3 and 11.1 Hz, 1H), 6.5 (d, J=8.3 Hz, 1H), 5.73 (d, J=17.9 Hz, 1H), 5.28 (d, J=11.3 Hz, 1H), 4.01 (s, 2H), 3.76 (s, 3H), 3.18 (d, J=6.9 Hz, 2H), 2.0-1.76 (m,
# 1H), 0.91 (d, J=6.6 Hz, 6H); MS (ES+): 502.34
189n	—CH═CH2	852	H	CH	189j	AE-3	1 HNMR [DMSO/DCl (1 drop)]: δ8.34 (m, 3H), 8.3 (d, J=8.3 Hz, 1H), 8.02 (d, J=7.7 Hz, 1H), 7.69 (bs, 1H), 7.43 (d, J=8 Hz, 1H), 6.98 (dd, J=11 & 17 Hz, 1H), 6.75 (s, 1H), 5.88 (d, J=17 Hz, 1H), 5.32 (d, J=11 Hz, 1H), 4.40 (m, 2H), 3.77 (s, 3H), 3.09 (d, J=7 Hz), 1.87 (m, 1H), 0.89 (d, J=7
# Hz, 6H); MS (ES+) 502.39

[0304]

853
Cpd.				Starting	Method
No.	—R	—R′	—R″	From	Used	Analytical Data
148a	854	—CH3	855	147a	J	1 H NMR (DMSO-d6): δ 10.65 (s, 1 H), 10.15 (s, 1 H), 9.19 (s, 2 H), 8.88 (s, 2 H), 8.10 (d, J = 2.1 Hz, 1 H), 7.92 (s, 1 H), 7.93-7.75 (m, 6 H), 7.31 (dd, J = 8.4 and 23.9 Hz, 1 H), 7.12 (d, J = 3.5 Hz, 1 H), 6.67 (m, 1 H), 3.53 (s, 3 H), 2.20 (d, J = 7.0 Hz, 2 H), 2.07 (m, 1 H), 0.94 (d, J = 6.3 Hz, 6 H).
148b	856	—CH3	857	147b	J	1 H NMR (DMSO-d6): δ 10.65 (s, 1 H), 10.09 (s, 1 H), 9.17 (s, 1 H), 8.83 (s, 1 H), 8.10 (d, J = 2.0 Hz, 1 H), 7.85 (d, J = 2.0 Hz, 2 H), 7.81 (d, J = 2.0 and 7.9 Hz, 2 H), 7.76 (m, 5 H), 7.66 (d, J = 3.9 Hz, 1 H), 7.62 d, J = 4.9 Hz, 1 H), 7.31 (d, J = 7.9 Hz, 1 H), 7.26 (d, J = 7.9 Hz, 1 H), 7.19 (t, J = 3.9 Hz, 1 H), 3.53 (s, 1 H), 2.19 (d, J = 6.9
# Hz, 2 H), 2.06 (m, J = 6.9 Hz, 1 H), 0.92 (d, J = 6.9 Hz, 6 H); MS (ES+): 555.67
148c	—CH═CH2	—CH3	858	147c	J	Characterized in the next step
149a	859	—H	860	148a	I-2	MS (ES+): 525.3
149b	861	—H	862	148b	I-2	1 H NMR (DMSO-d6): δ 13.95 (s, 1 H), 9.79 (s, 1 H), 8.87 (s, 4 H), 7.76 (s, 1 H), 7.65 (m, 8 H), 7.46 (dd, J =2.1 and 8.4 Hz, 1 H), 7.16 (t, J = 4.2 Hz, 1 H), 7.04 (d, J = 7.7 Hz, 1 H), 6.76 (d, J = 8.4 Hz, 1 H), 2.13 (d, J =7.0 Hz, 2 H), 2.03 (m, J = 6.3 and 7.0 Hz, 1 H), 0.90 (d, J = 6.3 Hz, 6 H); MS (ES+): 541.62
149c	—CH═CH2	—H	863	148c	I-2	MS (ES+): 485.6
175	—H	—CH2	864	174	J	1 H NMR (DMSO-d6): δ 8.81 (m, 4 H), 8.37 (t, J = 6.0 Hz, 1 H), 7.74-7.23 (m, 11 H), 4.31 (d, J = 6.2 Hz, 2 H), 3.51 (s, 3 H), 2.44 (m, 1 H), 1.04 (d, J = 7.0 Hz, 6 H); MS (ES+): 473.3
176	—H	—H	865	175	I-2	1 H NMR (DMSO-d6): δ 13.79 (br s, 1 H), 9.03 (m, 3 H), 8.25 (m, 1 H), 7.78-7.35 (m, 7 H), 6.99 (m, 2 H), 6.79 (m, 1 H), 4.20 (br s, 2 H), 3.51 (s, 3 H), 2.39 (m, 1 H), 1.00 (d, J = 6.8 Hz, 6 H); MS (ES+): 459.3
182	—H	—CH3	866	178	J	1 H NMR (DMSO-d6): δ 8.96 (m, 2 H), 7.79-7.38 (m, 9 H), 7.29 (dd, J = 7.5 and 1.7 Hz, 2 H), 4.42 (s, 2 H), 3.50 (s, 3 H), 2.97 (s, 2 H), 1.87 (m, 1 H), 1.36 (m, 9 H), 0.81 (d, J = 6.8 Hz, 6 H); MS (ES+): 559.5
183	—H	—H	867	182	I-2, S	1 H NMR (DMSO-d6): δ 9.11 (m, 4 H), 7.86 (s, 1 H), 7.66 (m, 5 H), 7.49 (m, 2 H), 7.38 (m, 1 H), 7.08 (m, 2 H), 4.12 (s, 2 H), 2.59 (m, 2 H), 1.87 (m, 1 H), 0.81 (d, J = 6.6 Hz, 6 H); MS (ES+): 445.32

[0305]

868
	N (in Ring
	With
Cpd.	Respect to	Starting	Method
No.	Phenyl)	—R	—R′	From	Used	Analytical Data
151	3	—CHO	—CH3	150+ 3a	D-9	MS (ES−): 339.3
152	3	—CO2H	—CH3	151	E	1 H NMR (CDCl3): δ 8.69 (t, J = 5.8 Hz, 1 H), 8.50 (d, J = 4.9 Hz, 1 H), 8.33 (d, J = 1.7 Hz, 1 H), 8.24 (s, 1 H), 8.01 (dd, J = 7.9, 1.9 Hz, 1 H), 7.53 (d, J = 5.1 Hz, 1 H), 7.34 (d, J = 8.1 Hz, 1 H), 3.56 (s, 3 H), 3.12 (m, 2 H), 1.87 (m, 1 H), 0.91 (d, J = 6.6 Hz, 6 H)
153	3	869	—CH3	152	J	1 H NMR (CD3OD): δ 8.75 (d, J = 4.7 Hz, 2 H), 8.55 (s, 1 H), 8.42 (d, J = 1.9 Hz, 1 H), 8.07 (dd, J = 8.1, 1.9, 1 H), 7.74 (s, 3 H), 7.70 (d, J = 5.1 Hz, 1 H), 7.51 (d, J = 8.1 Hz, 1 H), 3.69 (s, 3 H), 3.21 (m, 2 H), 1.94 (m, 1 H), 0.98 (d, J = 6.6 Hz, 6 H); MS (ES+): 474
154	3	870	—H	153	I-2	1 H NMR (DMSO): δ 11.18 (s, 1 H), 9.31 (s, 2 H), 9.10 (s, 2 H), 8.92 (d, J = 5.1 Hz, 1 H), 8.78 (m, 2 H), 8.43 (d, J = 1.5 Hz, 1 H), 8.07 (dd, J =7.9, 1.3 Hz, 1 H), 7.97 (d, J = 5.3 Hz, 1 H), 7.82 (d, J = 8.7 Hz, 2 H), 7.72 (d, J = 8.8 Hz, 2 H), 7.50 (d, J = 7.9 Hz, 1 H), 3.10 (t, J = 6.0 Hz, 2 H), 1.86 (m, 1 H), 0.89 (d, J = 6.6 Hz,
# 6 H); MS (ES+) 460
156	4	—CHO	—CH3	155+ 3a	D-9	MS (ES+): 341.4
157	4	—CO2H	—CH3	156	E	1 H NMR (CDCl3): δ 8.80 (s, 1 H), 8.46 (d, J =5.1 Hz, 1 H), 8.29 (s, 1 H), 7.85 (d, J = 7.9 Hz, 1 H), 7.13 (d, J = 7.9 Hz, 1 H), 7.00 (d, J = 5.1 Hz, 1 H), 6.83 (bs, 2 H), 3.45 (s, 3 H), 3.15 (m, 2 H), 1.84 (m, 1 H), 0.90 (d, J = 6.6 Hz, 6 H); MS (ES−): 355.2
158	4	871	—CH3	157	J	1 H NMR (CD3OD): δ 8.85 (s, 1 H), 8.75 (d, J =5.3 Hz, 1 H), 8.41 (d, J = 1.9 Hz, 1 H), 8.07 (dd, J = 8.1, 2.1, 1 H), 7.74 (s, 4 H), 7.48 (d, J = 8.1 Hz, 1 H), 7.45 (d, J = 5.1 Hz, 1 H), 3.69 (s, 3 H), 3.21 (m, 2 H), 1.94 (m, 1 H), 0.97 (d, J = 6.8 Hz, 6 H); MS (ES−): 472.4
159	4	872	—H	158	I-2	1 H NMR (DMSO): δ 10.97 (s, 1 H), 9.24 (s, 2 H), 8.96 (s, 3 H), 8.79 (m, 2 H), 8.40 (d, J = 1.8 Hz, 1 H), 8.06 (d, J = 7.7 Hz, 1 H), 7.77 (s, 4 H), 7.52 (m, 1 H), 7.38 (d, J = 7.5 Hz, 1 H), 3.10 (m, 2 H), 1.85 (m, 1 H), 0.89 (d, J = 5.3, 6 H); MS (ES+) 460.2

[0306]

873
Cpd.			Starting	Method
No.	—R	—R′	From	Used	Analytical Data
161a	—CH3	—CH3	31f	AB-2	1 H NMR (DMSO-d6): δ 10.55 (s, 1H), 9.00 (bs, 2H), 8.68 (t, J = 5.8 Hz, 1H), 8.24 (d, J = 1.9 Hz, 1H), 8.04 (d, J = 8.1 Hz, 1H), 7.91 (d, J =8.8 Hz, 2H), 7.77 (d, J = 1.3 Hz, 1H), 7.67 (m, 3H), 7.40 (d, J = 7.9 Hz, 1H), 7.29 (d, J = 7.9 Hz, 1H), 6.90 (dd, J = 17.7, 11.0 Hz, 1H), 6.03 (d, J = 17.7 Hz, 1H), 5.42 (d, J = 11.0 Hz,
# 1H), 3.61 (s, 3H), 3.56 (s, 3H), 3.10 (t, J = 6.4 Hz, 2H), 1.85 (m, 1H), 0.90 (d, J = 6.5 Hz, 6H); MS (ES+): 557.3
161b	—C2H5	—CH3	31f	AB-2	1 H NMR (DMSO-d6): δ 10.54 (s, 1H), 9.20 (bs, 4H), 8.67 (t, J = 6 Hz, 1H), 8.24 (1H), 8.02 (1H), 7.91 (2H), 7.77 (1H), 7.66 (m, 3H), 7.40 (1H), 7.29 (1H), 6.88 (dd, J = 17.3, 10.7 Hz, 1H), 6.03 (d, J = 17.3 Hz, 1H), 5.42 (d, J = 10.7 Hz, 1H), 3.56 (s, 3H), 3.5 (m, 3H), 3.09 (2H), 1.85 (m, 1H), 0.89 (6H); MS (ES+): 571.3
161c	—CH2C6H5	—CH3	31f	AB-2	1 H NMR (DMSO-d6): δ 10.54 (s, 1H), 9.20 (bs, 2H), 8.68 (t, J = 5.8 Hz, 1H), 8.24 (d, J = 1.9 Hz, 1H), 8.03 (d, J = 8.1 Hz, 1H), 7.92 (d, J =8.8 Hz, 2H), 7.77 (s, 1H), 7.68 (m, 4H), 7.36 (m, 6H), 6.89 (dd, J =17.7, 11.2 Hz, 1H), 5.05 (s, 2H), 6.03 (a, J = 17.7 Hz, 1H), 5.42 (d, J =11.2, Hz, 1H), 3.56 (s, 3H), 3.09
# (t, J = 6.6 Hz, 2H), 1/84 (m, 1H), 0.89 (d, J = 6.6 Hz, 6H); MS (ES+): 633.3
161d	—C(CH3)3	—CH3	31f	AB-2	MS (ES+): 599.3 and 499.3
161e	—CH2—CCl3	—CH3	31f	AB-2	1 H NMR (DMSO-d6): δ □ 10.59 (s, 1H), 9.24 (s, 2H), 8.68 (t, J = 5.6 Hz, 1H), 8.24 (d, J = 1.8 Hz, 1H), 8.03 (dd, J = 8.9, 1.9 Hz, 1H), 7.96 (d, J = 8.9 Hz, 2H), 7.79 (d, J = 1.5 Hz, 1H), 7.69 (m, 3H), 7.41 (d, J =8.1 Hz, 1H), 7.29 (d, J = 8.0 Hz, 1H), 6.89 (dd, J = 17.7, 11.1 Hz, 1H), 6.03 (d, J = 17.7 Hz, 1H), 5.42 (d, J = 11.1
# Hz, 1H), 4.88 (s, 2H), 3.56 (s, 3H), 3.10 (t, J = 6.6 Hz, 2H), 1.85 (m, 1H), 0.89 (d, J = 6.6 Hz, 6H); MS (ES+): 674.97
161f	874	—CH3	31f	AB-2	1 H NMR (DMSO-d6): δ □ 10.58 (s, 1H), 9.15 (s, 2H), 8.69 (t, J = 5.4 Hz, 1H), 8.25 (d, J = 1.8 Hz, 1H), 8.04 (dd, J = 8.1, 1.9 Hz, 1H), 7.95 (d, J = 8.9 Hz, 2H), 7.78 (s, 1H), 7.68 (m, 3H), 7.40 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 8.0 Hz, 1H), 7.07 (d, J = 8.8 Hz, 2H), 6.93 (d, J = 8.8 Hz, 2H), 6.89 (dd, J = 17.7, 11.1 Hz, 1H), 6.03 (d, J = 17.7 Hz,
# 1H), 5.42 (d, J = 11.1 Hz, 1H), 3.75 (s, 3H), 3.57 (s, 3H), 3.10 (t, J = 6.6 Hz, 2H), 1.85 (m, 1H), 0.89 (d, J = 6.6 Hz, 6H); MS (ES+): 649.3
161g	875	—CH3	31f	AB-2	1 H NMR (DMSO-d6): δ 10.59 (s, 1H), 9.19 (s, 2H), 8.68 (t, J = 5.7 Hz, 1H), 8.25 (d, J = 1.8 Hz, 1H), 8.03 (dd, J = 8.1, 1.9 Hz, 1H), 7.95 (d, J =8.9 Hz, 2H), 7.78 (d, J = 1.7 Hz, 1H), 7.70 (m, 3H), 7.41 (d, J = 8.1 Hz, 1H), 7.29 (d, J = 7.9 Hz, 1H), 7.20 (m, 4H), 6.90 (dd, J = 17.9, 11.1 Hz, 1H), 6.03 (d, J = 17.9 Hz, 1H), 5.42 (d, J = 11.1 Hz, 1H),
# 3.57 (s, 3H), 3.10 (t, J = 6.8 Hz, 2H), 1.85 (m, 1H), 0.89 (d, J = 6.6 Hz, 6H); MS (ES+): 637.5
161h	876	—CH3	31f	AB-1	1 H NMR (DMSO-d6): δ 10.58 (s, 1H), 9.00 (bs, 2H), 8.68 (t, J = 5.9 Hz, 1H), 8.24 (d, J = 1.9 Hz, 1H), 8.03 (d, J = 8.1 Hz, 1H), 7.94 (d, J =8.9 Hz, 2H), 7.78 (d, J = 1.5 Hz, 1H), 7.68 (m, 3H), 7.40 (d, J = 8.1 Hz, 1H), 7.29 (d, J = 8.1 Hz, 1H), 6.89 (dd, J = 17.5, 11.0 Hz, 1H), 6.03 (d, J = 17.5 Hz, 1H), 5.71 (s, 2H), 5.42 (d, J = 11.0 Hz, 1H),
# 3.56 (s, 3H), 3.10 (t, J = 6.2 Hz, 2H), 2.07 (s, 3H), 1.85 (m, 1H), 0.89 (d, J = 6.6 Hz, 6H); MS (ES+): 615.3
161i	877	—CH3	31f	AB-1	1 H NMR (DMSO-d6): δ 10.57 (s, 1H), 9.22 (s, 2H), 8.67 (t, J = 5.9 Hz, 1H), 8.24 (d, J = 1.9 Hz, 1H), 8.03 (dd, J = 8.1, 1.9 Hz, 1H), 7.94 (d, J =8.9 Hz, 2H), 7.78 (d, J = 1.5 Hz, 1H), 7.69 (m, 3H), 7.41 (d, J = 7.9 Hz, 1H),7.29 (d, J = 7.9 Hz, 1H), 6.89 (dd, J = 17.7, 11.1 Hz, 1H), 6.03 (d, J = 17.7 Hz, 1H), 5.73 (s, 2H), 5.42 (d, J = 11.1 Hz, 1H),
# 3.56 (s, 3H), 3.09 (t, J = 6.6 Hz, 2H), 1.85 (m, 1H), 1.14 (s, 9H), 0.89 (d, J = 6.7 Hz, 6H); MS (ES+): 657.52
161j	878	—CH3	31f	AB-1	1 H NMR (DMSO-d6): δ □ 10.57 (s, 1H), 9.24 (s, 1 H), 9.17 (s, 1H), 8.68 (t, J = 6.2 Hz, 1H), 8.25 (s, 1H), 8.04 (d, J = 8.2 Hz, 1H), 7.94 (d, J =7.5 Hz, 2H), 7.67 (s, 1H), 7.67 (m, 3H), 7.40 (d, J = 7.9 Hz, 1H), 7.29 (d, J = 7.9 Hz, 1H), 6.90 (dd, J = 17.8, 11.1 Hz, 1H), 6.71 (q, J = 5.5 Hz, 1H), 6.03 (d, J = 17.7 Hz, 1H), 5.42 (d, J = 11.1 Hz, 1H),
# 3.56 (s, 3H), 3.10 (t, J = 6.6 Hz, 2H), 2.00 (s, 3H), 1.85 (m, 1H), 1.43 (d, J = 5.5 Hz, 3H), 0.89 (d, J = 6.7 Hz, 6H); MS (ES+): 629.4
162a	—CH3	—H	161a	I-2	1 H NMR (DMSO-d6): δ 9.04 (bs, 3H), 8.57 (t, J = 5.4 Hz, 1H), 8.16 (s, 1H), 7.86 (d, J = 8.5 Hz, 2H), 7.79 (d, J = 7.9 Hz, 1H), 7.72 (s, 1H), 5.97 (d, J = 17.7 Hz, 1H), 5.37 (d, J = 11.0 Hz, 1H), 5.97 (d, J =17.7 Hz, 1H), 5.37 (d, J =11.0 Hz, 1H), 3.59 (s, 3H), 3.05 (t, J = 6.6 Hz, 2H), 1.83 (m, 1H), 0.87 (d, J = 6.6 Hz, 6H);
# MS (ES+): 543.38
162b	—C2H5	—H	161b	I-2	1 H NMR (DMSO-d6): δ 12.8 (bs, 1H), 10.8 (bs, 1H), 9.20 (bs, 2H), 8.68 (t, J = 5.9 Hz, 1H), 8.24 (d, J = 1.9 Hz, 1H), 7.91 (m, 3H), 7.77 (d, J = 1.5 Hz, 1H), 7.64 (m, 3H), 7.28 (d, J = 8.1 Hz, 1H), 7.22 (d, J = 8.1 Hz, 1H), 6.87 (dd, J = 17.7, 11.4 Hz, 1H), 6.01 (d, J = 17.7 Hz, 1H), 5.42 (d, J = 11.4 Hz, 1H), 4.05 (q, J = 7.2 Hz, 2H), 3.08 (t,
# J = 6.4 Hz, 2H), 1.84 (m, 1H), 1.21 (t, J = 7.2 Hz, 3H), 0.88 (d, J = 6.6 Hz, 6H); MS (ES−): 555.2
162c	—CH2C6H5	—H	161c	I-2	1 H NMR (DMSO-d6): δ 12.7 (bs, 1H), 10.75 (bs, 1H), 9.15 (b, 2H), 8.63 (t, J = 5.8 Hz, 1H), 8.27 (bs, 1H), 7.90 (d, J = 8.3 Hz, 2H), 7.77 (s, 1H), 7.43-7.15 (m, 8H), 7.40 (d, J = 8.1 Hz, 1H), 7.29 (d, J = 8.1 Hz, 1H), 6.87 (dd, J = 17.4, 11.0 Hz, 1H), 6.03 (d, J = 17.5 Hz, 1H), 5.71 (s, 2H), 5.42 (d, J = 11.0 Hz, 1H), 5.09 (s, 2H),
# 3.08 (t, J = 6.4 Hz, 2H), 1.85 (m, 1H), 0.88 (d, J = 6.6 Hz, 6H); MS (ES + 1): 619.2
162d	—C(CH3)3	—H	161d	I-2	1 H NMR (DMSO-d6): δ 12.6 (bs, 1H), 11.0 (bs, 1H), 9.04 (b, 2H), 8.62 (t, J = 5.4 Hz, 1H), 8.24 (s, 1H), 7.86 (m, 3H), 7.77 (s, 1H), 7.62 (m, 3H), 7.24 (d, J = 8.2 Hz, 1H), 7.20 (d, J = 8.0 Hz, 1H), 6.87 (dd, J =17.2, 11.0 Hz, 1H), 6.00 (d, J = 17.7 Hz, 1H), 5.40 (d, J = 11.0 Hz, 1H), 3.07 (t, J = 6.3 Hz, 2H), 1.84 (m, 1H), 1.44 (s, 9H), 0.88 (d, J = 6.6
# Hz, 6H); MS (ES + 1): 585.4

[0307]

879
Cpd.			Starting	Method
No.	—R	—R′	From	Used	Analytical Data
164	—CHO	—CH3	163 + 130	D2	1 HNMR (DMSO-d6): δ 9.58 (s, 1 H), 7.91 (dd, J =1.2, 8.0 Hz, 1 H), 7.71 (dt, J = 1.2 and 7.4 Hz, 1 H), 7.58 (t, J = 7.4 Hz, 1 H), 7.41 (m, 2 H), 7.38 (m, 1 H), 7.32 (d, J = 8 Hz, 1 H), 7.24 (d, J = 7.4 Hz, 1 H), 3.52 (q, J = 16 and 26 Hz, 2 H), 3.35 (s, 3 H); MS (ES+): 255.32
165	—CO2H	—CH3	164	E	Characterized in the next step
166	880	—CH3	165	J	1 HNMR (DMSO-d6): δ 10.34 (s, 1 H), 9.18 (s, 2 H), 8.92 (s, 2 H), 7.72-7.5 (m, 7 H), 7.34-7.14 (m, 5 H), 3.60 (q, J = 17 & 40 Hz, 2 H), 3.48 (s, 3 H); MS (ES+) 388.67
167	881	—H	166	I-2	1 HNMR (DMSO-d6): δ 11.74 (bs, 1 H), 9.90 (s, 1 H), 8.79 (bs, 2 H), 7.64 (m, 1 H), 7.50 (m, 7 H), 7.33 (d, J = 8.6 Hz, 1 H), 7.26 (d, J = 7.4 Hz, 1 H), 7.12 (t, J = 7.4 Hz, 1 H), 7.02 (t, J = 7.4 Hz, 1 H), 6.89 (d, J = 6.8 Hz, 1 H), 3.83 (d, J = 15 Hz, 2 H); MS (ES+) 374.79

[0308]

882
Cpd.					Starting	Method
No.	—R	—R′	—R″	—R″ ′	From	Used	Analytical Data
188a	—CH═CH2 (4)	883	884	—H	187a	AE-3	MS (ES+): 485.4 (100% M+1)
188b	—CH═CH2 (4)	885	886	—H	187b	AE-3	1 HNMR (DMSO-d6/D2O): δ 8.5 (d, J = 2 Hz, 1 H), 8.17 (dd, J = 8 Hz, 2 H), 7.65 (s, 1 H), 7.63 (s, 1 H), 7.54 (d, J = 8 Hz, 1 H), 7.49 (bs, 2 H), 7.14 (d, J = 7.7 Hz, 1 H), 6.78 (dd, J = 11 and 17 Hz, 1 H), 6.62 (d, J =9 hz, 1 H), 5.83 (d, J = 17 hz, 1 H), 5.33 (d, J = 11 hz, 1 H),
# 4.17 (d, J =9 hz, 1 H), 4.12 (s, 2 H); MS (ES+): 497.3
188c	—CH═CH2 (4)	887	888	—H	187c	AE-3	1 HNMR (DMSO-d6/D2O): δ 8.6 (m, 3 H), 8.3 (m, 3 H), 7.9 (d, J =7.9 Hz, 1 H), 7.45 (d, J = 8.8 Hz, 1 H), 7.3 (m, 3 H), 7.1 (m, 1 H), 7.0 (d, J = 8.1 Hz, 1 H), 6.6 (dd, J = 6 and 28 Hz, 1 H), 6.4 (d, J = 8.8 Hz, 2 H), 5.7 (d, J = 17 Hz, 1 H), 5.15 (d, J = 11 Hz, 1 H), 3.9 (m, 2 H), 3.25 (m, 2 H),
# 1.1 (t, J = & Hz, 3 H); MS (ES+): 443.3
188d	—CH═CH2 (4)	889	890	H	187d	AE-3	1 HNMR (DMSO-d6): δ 8.8 (m, 2 H), 8.7 (m, 1 H), 8.4 (m, 2 H), 8.1 (m, 1 H), 7.6 (m, 2 H), 7.5 (m, 3 H), 7.3 (m, 1 H), 7.2 (m, 1 H), 6.8 (m, 1 H), 6.6 (m, 2 H), 5.8 (m, 1 H), 5.3 (m, 1 H), 4.1 (m, 2 H), 3.31 (m, 1 H), 3.2 (m, 1 H), 1.7 (m, 1 H), 1.6 (m, 1 H), 1.3 (m, 1 H), 1.0 (m, 6 H); MS (ES+): 485
189a	—OCH3 (3)	891	892	—H	74	AE-4, I-2	1 HNMR (DMSO-d6): δ 8.60 (t, J =6 Hz, 1 H), 8.39 (bs, 2 H), 8.28 (bs, 1 H), 7.78 (m, 1 H), 7.56 (m, 1 H), 7.43 (dd, J = 5.8 Hz, 3.8 Hz, 2 H), 7.18 (m, 2 H), 6.80 (m, 3 H), 6.51 (bs, 1 H), 4.10 (m, 1 H), 3.85 (m, 1 H), 3.70 (s, 3 H), 3.17 (t, J = 6 Hz, 2 H), 1.80 (m, 1 H), 0.89 (d,
# J = 6.8 Hz, 6 H); MS (ES+) 475.2
189b	—OBn (4)	893	894	—H	184a	AE-3	1 HNMR (DMSO-d6/D2O): δ 8.24 (d, J = 1.5 Hz, 1 H), 7.86 (d, J = 7 Hz, 1 H), 7.49 (m, 2 H), 7.36 (m, 4 H), 7.26 (d, J = 8.3 Hz, 1 H), 6.94 (m, 3 H), 6.66 (d, J = 8.7 Hz, 2 Hz, 2 H), 5.03 (s, 2 H), 4.06 (q, J = 16 and 21 Hz, 2 H), 3.02 (d, J = 7 Hz, 2 H), 1.86 (m, 1 H), 0.89 (d, J = 6.8 Hz, 6 H);
# MS (ES−): 549.2 and (ES+) 551.4
189c	—OH (4)	895	896	—H	189b	G	1 HNMR (DMSO-d6): δ 11.3 (bs, 1 H), 9.07 (s, 1 H), 8.46 (t, J = 6 Hz, 1 H), 8.27 (bs, 2 H), 8.15 (bs, 2 H), 7.66 (d, J = 7.7 Hz, 1 H), 7.36 (d, J =8.5 Hz, 2 H), 7.03 (d, J = 8.1 Hz, 1 H), 6.77 (m, 2 H), 6.68 (d, J = 8.3 Hz, 2 Hz, 2 H), 6.6 (s, 1 H), 6.47 9d, J = 8.2 Hz, 1 H), 4.05 (d, J = 14 Hz,
# 1 H), 3.09 (d, J = 14 Hz, 1 H), 3.01 (t, J = 7 Hz, 2 H), 1.79 (m, 1 H), 0.82 (d, J = 6.8 Hz, 6 H); MS (ES−): 459.2 and (ES+) 461.4
189d	—H	897	898	—H	131	AE-3	MS (ES+): 445.4; MS (ES−): 443.3
189e	—H	899	900	—H	131	AE-3	MS (ES+): 446.46; MS (ES−): 444.45

[0309]

901
Cpd.			Starting	Method
No.	—R	—R′	From	Used	Analytical Data
205	902	—Boc	204	A-4	1 HNMR (DMSO-d6): δ 11.04 (s, 0.6 H), 10.97 (bs, 0.4 H), 8.66 (t, J = 5.6 Hz, 0.6 H), 8.56 (t, J = 5.6 Hz, 0.4 H), 8.22 (s, 1 H), 8.11 (d, J = 2 Hz, 0.6 H), 8.03 (d, J = 2 Hz, 0.4 H), 7.94 (dd, J = 2 and 8 Hz, 1 H), 7.82 (m, 4 H), 7.40 (m, 8 H), 7.18 (m, 2 H), 7.04 (m, 2 H), 5.21 (s, 0.8 H), 5.11 (s, 1.2 H), 3.11 (t, J = 6.2 Hz, 1.2 H),
# 3.06 (t, J = 6.2 Hz, 0.8 H), 1.84 (m, 1 H), 1.43 (s, 5.4 H), 1.42 (s, 3.6 H), 0.91 (d, J = 6.8 Hz, 3.6 H), 0.88 (d, J = 6.8 Hz, 2.4 H); MS (ES+): 665.5
206	—CH2OH	—Boc	204	A-6	1 HNMR (DMSO-d6): δ 12.15 (bs, 1 H), 11.07 (bs, 1 H), 10.69 (s, 1 H), 10.38 (bs, 1 H), 8.68 (t, J = 5.6 Hz, 1 H), 8.12 (d, J = 1.7 Hz, 1 H), 8.00 (dd, 1.8, 8 Hz, 1 H), 7.68 (m, 4 H), 7.46-7.30 (m, 6 H), 7.16 (d, J = 2.8 Hz, 1 H), 7.01 (d, J =8.5 Hz, 1 H), 6.86 (dd, J = 8.5 and 2.8 Hz, 1 H), 5.07 (s, 2 H), 4.30 (d, J = 7.4 Hz, 2 H),
# 3.15 (t, J = 6.2 Hz, 2 H), 1.86 (m, 1 H), 1.53 (s, 9 H), 0.89 (d, J = 6.8 Hz, 6 H); MS (ES−): 649.4
207	—CH2OH	—H	206	S-2	1 HNMR (DMSO-d6/D2O): δ 10.66 (s, 1 H), 9.19 (bs, 2 H), 8.86 (bs, 2 H), 8.69 (t, J = 5.5 Hz, 1 H), 8.13 (d, J = 2 Hz, 1 H), 8.02 (dd, J = 8 and 2 Hz, 1 H), 7.72 (m, 4 H), 7.38 (m, 6 H), 7.17 (d, J = 2.6 Hz, 1 H), 7.03 (d, J = 8.5 Hz, 1 H), 6.87 (dd, J = 8.5 and 2.5 Hz, 1 H), 5.39 (t, J = 4.7 Hz, 1 H), 5.08 (s, 2 H), 4.30 (m, 2 H),
# 3.13 (t, J = 6.5 Hz, 2 H), 1.87 (m, 1 H), 0.91 (d, J = 6.5 Hz, 6 H); MS (ES+) 551.4
208	903	—H	205	S-2	1 HNMR (DMSO-d6): δ 11.26 (s, 0.6 H), 11.20 (bs, 0.4 H), 9.15 (bs, 1.2 H), 9.11 (bs, 0.8 H), 8.84 (bs, 1.2 H), 8.82 (bs, 0.8 H), 8.67 (t, J = 5.6 Hz, 0.6 H), 8.58 (t, J = 5.6 Hz, 0.4 H), 8.3 (s, 1 H), 8.12 (d, J = 2 Hz, 0.6 H), 8.04 (d, J = 2 Hz, 0.4 H), 7.96 (dd, J = 2 and 8 Hz, 1 H), 7.84 (m, 1 H), 7.70 (m, 2 H), 7.57 (m, 3 H),
# 7.40 (m, 4 H), 7.22 (m, 2 H), 7.02 (m, 2 H), 5.21 (s, 0.8 H), 5.11 (s, 1.2 H), 3.12 (t, J = 6.5 Hz, 1.2 H), 3.06 (t, J = 6.5 Hz, 0.8 H), 1.84 (m, 1 H), 0.90 (d, J = 6.5 Hz, 3.6 H), 0.86 (d, J = 6.5 Hz, 2.4 H); MS (ES+): 564.5

[0310]

904
Cpd.				Starting	Method
No.	—R	—R′	—R″	From	Used	Analytical Data
217	—OCH3	905	—Br	216	A-3	1 H NMR (DMSO-d6): δ 8.48 (t, J = 6.2 Hz, 1 H), 8.06 (d, J = 8.3 Hz, 1 H), 7.69 (d, J = 8.5 Hz, 1 H), 4.01 (s, 3 H), 3.15 (t, J = 6.5 Hz, 2 H), 1.91 (m, 1 H), 0.91 (d, J = 6.6 Hz, 6 H); MS (ES+): 287.1
218	—OCH3	906	—CH═CH2	217	D-12	1 H NMR (CDCl3): δ 8.08 (m, 2 H), 7.20 (m, 2 H), 6.39 (dd, J = 2.0 and 17.3 Hz, 1 H), 5.53 (dd, J = 2.0 and 10.9 Hz, 1 H), 4.01 (s, 3 H), 3.15 (t, J =6.5 Hz, 2 H), 1.91 (m, 1 H), 0.91 (d, J = 6.6 Hz, 6 H)
219	—OH	907	—CO2CH3	218	E-2, V- 3, W-2	1 H NMR (DMSO-d6): δ 11.05 (s, 1 H), 8.48 (t, J =6.2 Hz, 1 H) 8.06 (d J = 8.7 Hz, 1 H) 7.53 (d, J = 8.5 Hz, 1 H), 3.90 (s, 3 H), 3.12 (t, J = 6.6 Hz, 2 H), 1.85 (m, 1 H), 0.86 (d, J = 6.6 Hz, 6 H); MS (ES+): 253.2
220	—OSO2CF3	908	—CO2CH3	219	B-2	MS (ES+): 407.2 (M + Na)+
237	909	—NH2	—H	236	AF-1	MS (ES+): 137.1

[0311]

910
Cpd.				Starting	Method
No.	—R	—R′	—R″	From	Used	Analytical Data
221	—CHO	—OBn	—CH3	220 + 6	D-2	1 H NMR (CDCl3): δ 9.77 (s, 1 H),
						8.40 (d, J = 7.9 Hz, 1 H), 8.13 (d, J =
						6.8 Hz, 1 H), 7.83 (d, J = 7.9 Hz, 1 H),
						7.61 (d, J = 2.60 Hz, 1 H), 7.20 (m, 5
						H), 7.21 (m 1 H), 7.18 (d, J = 8.3 Hz,
						1 H), 5.18 (s, 2 H), 3.72 (s, 3 H), 3.35
						(q, J = 5.8 Hz, 2 H), 1.96 (m, 1 H),
						1.01 (d, J = 6.8 Hz,6 H); MS (ES+):
						447.4
222	—CO2H	—OBn	—CH3	221	E	MS (ES−): 461.3
223	—CO2MEM	—OBn	—CH3	222	F	MS (ES+): 573.33 (M + Na)+
224	—CO2MEM	—OH	—CH3	223	G	MS (ES+): 461.36
225	—CO2MEM	—OSO2CF3	—CH3	224	B-2	MS (ES+): 615.58 (M + Na)+
226	—CO2MEM	—CH═CH2	—CH3	225	D-3 or D-12	MS (ES−): 381.35 [(M-MEM)-1]
227	—CO2H	—CH═CH2	—CH3	226	I-1	MS (ES−): 381.35
228	911	—CH═CH2	—CH3	227	J	MS (ES+): 500.35
229	912	—CH═CH2	—H	228	I-2	MS (ES+): 486.32
245	—CHO	—OH	—CH3	221	AD	MS (ES+): 357.40
246	—CHO	—OSO2CF3	—CH3	245	B-2	Characterized in the next step
247	—CHO	—CH═CH2	—CH3	246	D-3	MS (ES+): 367.42
248	913	—CH═CH2	—H	247	AE-3	MS (ES+): 472.39
249	914	—OBn	—CH3	222	J	MS (ES+): 580.4
250	915	—OBn	—H	249	I-2	MS (ES+): 566.4 MS (ES−): 564.3
251	916	—OH	—H	250	G	MS (ES+): 476.3 MS (ES−): 474.2
252	917	—CH═CH2	—H	247	AE-3	MS (ES+): 473.44 MS (ES−): 471.43

[0312]

918
Cpd.		Starting	Method
No.	—R	From	Used	Analytical Data
231b	—CO2CH3	230	AG-3	1 H NMR (CDCl3): δ 10.17 (d, J = 0.75 Hz, 1 H),
				7.62 (d, J = 8.3 Hz, 1 H), 6.94 (dd, J = 8.3, 0.75
				Hz, 1 H), 6.51 (s, 1 H), 3.90 (s, 3 H)

[0313]

919
Cpd.				Starting	Method
No.	—R	—R′	—R″	From	Used	Analytical Data
232a	—H	—CHO	—CH3	231a + 6a	D-6 or D-7	1 HNMR (CDCl3): δ 9.64 (s, 1 H), 8.44 (d, J =
						2 Hz, 1 H), 8.02 (dd, J = 8 and 2 Hz, 1 H), 7.60
						(d, J = 8.3 Hz, 1 H), 7.40 (d, J = 8 Hz, 1 H),
						6.96 (d, J = 8 Hz, 1 H), 6.32 (t, J = 6 and 5 Hz,
						1 H), 6.01 (s, 2 H), 3.72 (s, 3 H), 3.33 (t, J =
						6.5 Hz, 2 H), 1.93 (m, 1 H), 1.00 (d, J = 6.8
						Hz, 6 H); MS (ES+): 384.3 and 406.3 (M + Na)+
232b	—CO2H	—CHO	—CH3	231b + 6a	D-6 or D-7	1 HNMR (DMSO-d6): δ 9.87 (s, 1 H), 9.49 (s, 1
						H), 8.64 (d, J = 2 Hz, 1 H), 8.3 (s, 1 H), 7.97
						(d, J = 8 Hz, 1 H), 7.43 (dd, J = 8 and 2.6 Hz, 1
						H), 7.35 (m, 2 H), 6.94 (m, 1 H), 6.05 (s, 0.4
						H), 5.98 (s, 0.6 H), 3.55 (s, 1.8 H), 3.52 (s, 1.2
						H), 3.02 (t, J = 6.5 Hz, 2 H), 1.78 (m, 1 H),
						0.81 (d, J = 6.6 Hz, 6 H); MS (ES−): 426.2
233a	—H	—CO2H	—CH3	232a	E	1 HNMR (DMSO-d6): δ 12.29 (bs, 1 H), 8.69 (t,
						J = 5.5 Hz, 1 H), 8.38 (d, J = 2 Hz, 1 H), 8.03
						(dd, J = 8 and 2 Hz, 1 H), 7.58 (d, J = 8.5 Hz, 1
						H), 7.36 (d, J = 8 Hz, 1 H), 7.00 (d, J = 8.5 Hz,
						1 H), 6.02 (s, 2 H), 3.64 (s, 3 H), 3.12 (t, J =
						6.5 Hz, 2 H), 1.87 (m, 1 H), 0.91 (d, J = 6.8
						Hz, 6 H); MS (ES−): 398.2
233b	—CO2H	—CO2H	—CH3	232b	E	1 HNMR (DMSO-d6): δ 8.64 (t, J = 5.5 Hz, 1
						H), 8.38 (d, J = 4 Hz, 1 H), 8.00 (dd, J = 8.5
						and 4 Hz, 1 H), 7.59 (dd, J = 8.5 and 4 Hz, 1
						H), 7.30 (dd, J = 8 and 2.5 Hz, 1 H), 6.52 (s,
						0.5 H), 6.48 (s, 0.5 H), 3.60 (s, 1.5 H), 3.58 (s,
						1.5 H), 3.08 (t, J = 6.5 Hz, 2 H), 1.84 (m, 1 H),
						0.88 (d, J = 6.8 Hz, 6 H)
234a	—H	920	—CH3	233a	J	MS (ES+): 517.4
234b	—CO2H	921	—CH3	233b	J	1 HNMR (DMSO-d6): δ 12.41 (bs, 1 H), 11.09 (s, 1 H), 10.96 (s, 1 H), 9.22 (bs. 2 H), 8.96 (bs, 2 H), 8.70 (m, 1 H), 8.38 (dd, J = 2 and 13 Hz, 1 H), 8.04 (d, J = 8 Hz, 1 H), 7.82 (m, 4 H), 7.65 (dd, J = 8 and 5 Hz, 1 H), 7.39 (dd, J =8 and 2.5 Hz, 1 H), 7.11 (dd, J = 8.5 and 1.7 Hz, 1 H), 6.05 (s, 1 H), 3.67 (s, 1.5 H), 3.50 (s, 1.5 H), 3.10
# (t, J = 6.5 Hz, 2 H), 1.88 (m, 1 H), 0.90 (d, J = 6.8 Hz, 6 H)
235a	—H	922	—H	234a	I-2	1 HNMR (DMSO-d6 + DCl one drop): δ 8.34 (d, J = 2 Hz, 1 H), 7.97 (dd, J = 8 and 2 Hz, 1 H), 7.75 (m, 4 H), 7.33 (dd, J = 3.8 and 8.1 Hz, 2 H), 7.04 (d, J = 8.1 Hz, 1 H), 6.01 (d, J = 6 Hz, 2 H), 3.07 (t, J = 6.5 Hz, 2 H), 1.83 (m, 1 H), 0.86 (d, J = 6.8 Hz, 6 H); MS (ES−) 501.3; (ES+) 503.3

[0314]

923
Cpd.				Starting	Method
No.	—R	—R′	—R″	From	Used	Analytical Data
240	—CH(OH)—CH2OH	—Boc	—CH3	161d	L	1 H NMR (DMSO-d6): δ 10.47 (s, 1H), 9.07 (s,
						2H), 8.72 (t, J = 5.7 Hz, 1H), 8.29 (d, J = 2 Hz,
						1H), 8.08 (dd, J = 8.0, 2 Hz, 1H), 7.95 (s, 1H), 7.92
						(s, 1 H), 7.67 (m, 2 H), 7.62 (d, J = 6.5 Hz, 1 H),
						7.46 (d, J = 8 Hz, 1H), 7.31 (d, J = 8 Hz, 1H), 5.50
						(d, J = 4.5 Hz, 1H), 4.91 (t, J = 5.7 Hz, 1H), 4.74
						(m, 1 H), 4.25 (s, 1 H), 3.63 (s, 3H), 3.15 (t, J = 6.4
						Hz, 2H), 1.91 (m, 1H), 1.50 (s, 9 H), 0.95 (d, J =
						6.7 Hz, 6H)
241	—CHO	—Boc	—CH3	240	M	1 H NMR (DMSO-d6): δ 10.69 (s, 1H), 10.17 (s, 1
						H), 9.10 (bs, 2 H), 8.72 (t, J = 5.7 Hz, 1H), 8.30 (d,
						J = 1.5 Hz, 1H), 8.22 (d, J = 1.5 Hz, 1H), 8.22 (dd,
						J = 1.5 and 8 Hz, 1 H), 8.07 (dd, J = 1.5 and 8 Hz, 1
						H), 7.89 (s, 1H), 7.86 (s, 1 H), 7.65 (s, 1 H), 7.62
						(s, 1 H), 7.57 (d, J = 8 Hz, 1H), 7.44 (d, J = 8 Hz,
						1H), 3.57 (s, 3H), 3.11 (t, J = 6.4 Hz, 2H), 1.85 (m,
						1H), 1.44 (s, 9 H), 0.89 (d, J = 6.7 Hz, 6H)
242	—CH(OH)—CH═CH2	—Boc	—CH3	241	AG	MS (ES+): 629.39
243	—CH(OH)—CH═CH2	—H	—CH3	242	S	MS (ES+): 529.38
244	—CH(OH)—CH═CH2	—H	—H	243	I-2	MS (ES−): 515.35

[0315]

924
Cpd.		Starting	Method
No.	—R	From	Used	Analytical Data
254	925	253	AE-3	MS (ES+): 318.2, 320.2
255	926	254	R	MS (ES+): 418

[0316]

927
Cpd.			Starting	Method
No.	X	—R	From	Used	Analytical Data
258a	H	928	131	AE-3	1 HNMR (DMSO-d6): δ 11.71 (bs, 1 H), 8.57 (t, J = 5.5 Hz, 1 H), 8.44 (s, 1 H), 8.34 (s, 1 H), 7.80 (dd, J = 1.5, 7.5 Hz, 1 H), 7.45 (d, J =12.8 Hz, 1 H), 7.20 (m, 5 H), 6.96 (m, 1 H), 4.13 (m, 2 H), 3.09 (t, J = 6.8 Hz, 2 H), 1.87 (m 1 H), 0.87 (d, J = 6.8 Hz, 6 H); MS (ES+) 463.62.
258b	—CH═CH2	929	187a	AE-3	1 HNMR (DMSO-d6): δ 10.01 (s, 1 H), 8.73 (s, 2 H), 8.39 (d, J = 2 Hz, 1 H), 8.33 (s, 1 H), 8.07 (dd, J = 7.7 & 2 Hz, 1 H), 7.78 (m, 2 H), 7.60 (m, 2 H), 7.40 (m, 2 H), 7.05 (m, 2 H), 6.7 (dd, J = 11 & 17.5, 1 H), 6.34 (t, J = 6 Hz, 1 H), 6.26 (d, J = 8 Hz, 1 H), 5.73 (d, J =17.5 Hz, 1 H), 5.24 (d, J = 11 Hz, 1 H), 4.11 (t,
# J = 5.5 Hz, 2 H), 3.11 (t, J = 6 Hz, 2 H), 1.87 (m, 1 H), 0.90 (t, J = 6.6 Hz, 6 H); MS (ES+) 487.35.
258c	—CH═CH2	930	187a	AE-3	1 HNMR (DMSO-d6): δ 8.78 (s, 2 H), 8.73 (t, J = 5.5 Hz, 1 H), 8.40 (d, J = 2 Hz, 1 H), 8.37 (s, 2 H), 8.08 (s, 1 H), 7.48-7.32 (m, 5 H), 7.28 (d, J = 7.5 Hz, 1 H), 6.68 (m, 1 H), 6.55 (t, J = 5.5 Hz, 1 H), 6.30 (d, J = 8.6 Hz, 1 H), 6.01 (m, 1 H), 5.71 (d, J = 17.5 Hz, 1 H), 5.23 (d, J = 11 Hz, 1 H), 5.11 (m, 2 H), 4.13 (d,
# J = 5.3 Hz, 2 H), 3.11 (t, J = 6.5 Hz, 2 H), 1.87 (m, 1 H), 0.91 (d, J = 6.8 Hz, 6 H); MS (ES+) 511.41.
258d	—CH═CH2	931	187a	AE-3	1 HNMR (DMSO-d6): δ 8.62 (t, J = 5.7 Hz, 2 H), 8.52 (s, 2 H), 8.31 (s, 1 H), 7.88 (s, 1 H), 7.68 (s, 1 H), 7.24 (m, 5 H), 7.00 (d, J = 6.1 Hz, 1 H), 6.72 (q, J = 11.2 Hz, 1 H), 6.48 (s, 1 H), 5.73 (d, J = 16.8 Hz, 1 H), 5.22 (d, J = 10.5 Hz, 1 H), 4.08 (m, 2 H), 3.10 (t, J = 6.1 Hz, 2 H), 1.86 (m, 1 H),
# 0.89 (d, J = 6.8 Hz, 6 H); MS (ES+) 489.39.
258e	—CH═CH2	932	187a	AE-3	1 HNMR (DMSO-d6): δ 8.61 (t, J = 5.3 Hz, 4 H), 8.32 (s, 1 H), 8.18 (s, 1 H), 7.89 (t, J = 8.5 Hz, 2 H), 7.70 (s, 1 H), 7.32 (d, J = 8.1 Hz, 1 H), 7.25 (m, 3 H), 6.97 (d, J = 7.5 Hz, 1 H), 6.68 (q, J = 17.8 & 10.9 Hz, 1 H), 5.67 (d, J = 17.6 Hz, 1 H), 5.18 (d, J = 10.9 Hz, 1 H), 4.24 (m, 2 H), 3.10 (t, J = 6.5 Hz, 2 H),
# 1.88 (m, 1 H), 0.90 (d, J = 6.8 Hz, 6 H); MS (ES+) 472.37.
258f	—CH═CH2	933	187a	AE-3	1 HNMR (DMSO-d6): δ 8.60 (s, 1 H), 8.38 (s, 2 H), 7.81 (s, 1 H), 7.30 (d, J = 7.7 Hz, 2 H), 7.17 (m, 4 H), 7.13 (d, J = 5.7 Hz, 1 H), 7.05 (m, 1 H), 6.69 (m, 2 H), 5.64 (d, J = 16.6 Hz, 1 H), 5.16 (d, J = 11.2 Hz, 1 H), 4.27 (m, 1 H), 3.91 (m, 4 H), 3.10 (t, J = 6.5 Hz, 2 H), 1.86 (m, 1 H), 0.90 (d, J = 6.6 Hz, 6 H);
# MS (ES+) 501.37.
258g	—CH═CH2	934	187a	AE-3	1 H NMR (DMSO-d6): δ 13.84 (br s,2 H), 9.32 (s, 2 H), 9.11 (s, 2 H), 8.56 (t, J = 6.4 Hz, 1 H), 7.81-7.41 (m, 8 H), 7.11 (d, J = 7.9 Hz, 1 H), 6.86 (dd, J = 11.1 and 17.3 Hz, 1 H), 5.97 (d, J = 17.3 Hz, 1 H), 5.38 (d, J =11.1 Hz, 1 H), 3.12 (m, 2 H), 1.87 (m, 1 H), 0.87 (d, J = 6.4 Hz, 6 H); MS (ES+): 520.5.

[0317]

935
Cpd.				Starting	Method
No.	R	R′	Y	From	Used	Analytical Data
259	CH3	CH3	CN	74	AM	MS (ES+): 522.3 (M + Na)
260	H	H	936	259	AJ-1, I-2	1 HNMR (DMSO-d6): δ 8.76 (bs, 2 H), 8.40 (bs, 2 H), 8.35 (m, 1 H), 8.08 (d, J =7 Hz, 1 H), 7.87 (m, 1 H), 7.79 (d, J =6 Hz, 1 H), 7.42-7.64 (m, 5 H), 7.30 (m, 1 H), 7.16 (m, 1 H), 7.05 (m, 1 H), 6.70 (t, J = 3.5 Hz, 1 H), 6.45 (m, 1 H), 3.86 (s, 1.5 H), 3.75 (s, 1.5 H), 3.10 (t, J = 6.7 Hz, 2 H), 1.88
# (m, 1 H), 0.90 (d, J = 6.7 Hz, 6 H); MS (ES+) 519.35

[0318] 937

[0319] It was prepared as shown in Schemes 31 and 31a. Analytical data: 1H NMR (DMSO-d6): δ 13.05 (br s, 1H), 9.09 (s, 2 H), 8.94 (s, 2 H), 8.65 (m, 1 H), 8.26-7.60 (m, 8 H), 7.20 (m, 1 H), 6.90 (dd, J=11.1 and 17.3 Hz, 1 H), 6.00 (d, J=17.3 Hz, 1 H), 5.40 (d, J=11.1 Hz, 1 H), 3.25 (m, 2 H), 1.59 (q, J=6.9 Hz, 2 H), 0.92 (t, J=7.3 Hz, 3 H); MS (ES−): 470.30.

938
Cpd.				Starting	Method
No.	X	Y	R	From	Used	Analytical Data
263a	H	CHO	CH3	261 and	D-1	MS (ES+): 241.2
				262a
263b	939	CHO	CH3	261 and 3a	D-1	MS (ES+): 340.3
264a	H	CO2H	CH3	263a	E	MS (ES−): 255.5
264b	940	CO2H	CH3	263b	E	MS (ES+): 356.3
265a	H	941	H	264a	J, I-2	1HNMR (DMSO-d6, MSA salt): δ10.39 (s, 1 H), 8.6 (s, 2 HO, 8.45 (s, 2 H), 7.12-7.65 (m, 4 H), 7.66-8.2 (m, 8 H), 2.35 (s, 3 H); MS (ES+) 360.33.
265b	942	943	H	264b	J, I-2	1HNMR (DMSO-d6): δ 13.01 (bs, 1 H), 10.74 (s, 1 H), 9.22 (s, 2 H), 8.88 (s, 2 H), 8.61 (t, J = 5.5 Hz, 1 H), 8.1 (dd, J = 8.2 and 2 Hz, 1 H), 8.02 (m, 3 H), 7.86 (m, 1 H), 7.83 (s, 1 H), 7.61 (m, 3 H), 3.19 (t, J = 6.7 Hz, 2 H), 2.32 (s, 3 H), 1.82 (m, 1 H), 0.92 (d, J =6.59 Hz, 6 H); MS (ES+) 459.29.
266a	H	944	H	263a	AE-3	1HNMR (DMSO-d6 MSA salt): δ 8.75 (s, 2H), 8.40 (s, 2 H), 7.15-7.75 (m, 12 H), 4.40 (s, 2 H), 2.5 (s, 3 H); MS (ES+) 346.37.
266b	945	946	H	263b	AE-3	1HNMR (DMSO-d6): δ 8.77 (s, 2 H), 8.39 (s, 2 H), 8.22 (s, 1 H), 7.6-7.2 (m, 10 H), 6.7 (d, J = 4.8 Hz, 2 H), 4.4 (b, 2 H), 2.99 (m, 2 H), 2.49 (s, 3 H), 1.88 (m, 1 H), 0.88 (d, J = 6.58 Hz, 6 H); MS (ES+) 445.32.

[0320] The following non-limiting examples are presented to further illustrate the present invention.

[0321] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-[(isobutylamino)carbonyl]-4′-thien-2-yl-1,1′-biphenyl-2-carboxylic acid

[0322] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-[(isobutylamino)carbonyl]-4′-thien-3-yl-1,1′-biphenyl-2-carboxylic acid

[0323] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-[(isobutylamino)carbonyl]-1,1′:4′,1″-terphenyl-2-carboxylic acid

[0324] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4′-(3-furyl)-4-[(isobutylamino)carbonyl]-1,1′-biphenyl-2-carboxylic acid

[0325] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-[(isobutylamino)carbonyl]-4′-pyridin-4-yl-1,1′-biphenyl-2-carboxylic acid

[0326] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-[(isobutylamino)carbonyl]-4′-(1H-pyrrol-2-yl)-1,1′-biphenyl-2-carboxylic acid

[0327] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4′-[2-(hydroxymethyl)thien-3-yl]-4-[(isobutylamino)carbonyl]-1,1′-biphenyl-2-carboxylic acid

[0328] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4′-[3-(hydroxymethyl)thien-2-yl]-4-[(isobutylamino)carbonyl]-1,1′-biphenyl-2-carboxylic acid

[0329] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-[(isobutylamino)carbonyl]-4′-vinyl-1,1′-biphenyl-2-carboxylic acid

[0330] 4′-Allyl-2′-[({4-[amino(imino)methyl]phenyl}amino)carbonyl]-4-[(isobutylamino)carbonyl]-1,1′-biphenyl-2-carboxylate

[0331] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-[(isobutylamino)carbonyl]-4′-(1,3-thiazol-2-yl)-1,1′-biphenyl-2-carboxylic acid

[0332] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4′-[3-(hydroxymethyl)-2-furyl]-4-[(isobutylamino)carbonyl]-1,1′-biphenyl-2-carboxylic acid

[0333] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-[(isobutylamino)carbonyl]-4′-prop-1-ynyl-1,1′-biphenyl-2-carboxylic acid

[0334] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4′-(3-hydroxy-3-methylbut-1-ynyl)-4-[(isobutylamino)carbonyl]-1,1′-biphenyl-2-carboxylic acid

[0335] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-[(3-methylbutanoyl)amino]-4′-vinyl-1,1′-biphenyl-2-carboxylic acid

[0336] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4′-(4-hydroxybut-1-ynyl)-4-[(isobutylamino)carbonyl]-1,1′-biphenyl-2-carboxylic acid

[0337] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-[(isobutylamino)carbonyl]-4′-[(1E)-3-methylbuta-1,3-dienyl]-1,1′-biphenyl-2-carboxylic acid

[0338] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4′-(3-hydroxyprop-1-ynyl)-4-[(isobutylamino)carbonyl]-1,1′-biphenyl-2-carboxylic acid

[0339] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4′-(2-furyl)-4-[(propylamino)carbonyl]-1,1′-biphenyl-2-carboxylic acid

[0340] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-[(sec-butylamino)carbonyl]-4′-(2-furyl)-1,1′-biphenyl-2-carboxylic acid

[0341] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4′-(2-furyl)-4-{[(2,2,2-trifluoroethyl)amino]carbonyl}-1,1′-biphenyl-2-carboxylic acid

[0342] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4′-(2-furyl)-4-{[(4-hydroxybutyl)amino]carbonyl}-1,1′-biphenyl-2-carboxylic acid

[0343] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-[(ethylamino)carbonyl]-4′-(2-furyl)-1,1′-biphenyl-2-carboxylic acid

[0344] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-[(isobutylamino)carbonyl]-5′-methoxy-4′-vinyl-1,1′-biphenyl-2-carboxylic acid

[0345] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-[(isobutylamino)carbonyl]-4′-(thien-2-ylmethyl)-1,1′-biphenyl-2-carboxylic acid

[0346] 2-{3-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]pyridin-4-yl}-5-[(isobutylamino)carbonyl]benzoic acid

[0347] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-[(cyclopentylamino)carbonyl]-4′-vinyl-1,1′-biphenyl-2-carboxylic acid

[0348] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-5′-ethoxy-4-[(isobutylamino)carbonyl]-4′-vinyl-1,1′-biphenyl-2-carboxylic acid

[0349] Methyl 2′-[({4-[({[(acetyloxy)methoxy]carbonyl}amino)(imino)methyl]phenyl}amino)carbonyl]-4-[(isobutylamino)carbonyl]-4′-vinyl-1,1′-biphenyl-2-carboxylate

[0350] Methyl 2′-[({4-[{[(benzyloxy)carbonyl]amino}(imino)methyl]phenyl}amino) carbonyl]-4-[(isobutylamino)carbonyl]-4′-vinyl-1,1′-biphenyl-2-carboxylate

[0351] N1-{4-[Amino(imino)methyl]phenyl}-N8-isobutyl-6-oxo-6H-benzo[c]chromene-1,8-dicarboxamide

[0352] 2′-[({4-[Amino(imino)methyl]phenyl}amino)methyl]-4-[(isobutylamino)carbonyl]-4′-vinyl-1,1′-biphenyl-2-carboxylic acid

[0353] 2′-({[4-(4,5-Dihydro-1H-imidazol-2-yl)phenyl]amino}carbonyl)-4-[(isobutylamino)carbonyl]-1,1′-biphenyl-2-carboxylic acid

[0354] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-[(isobutylamino)carbonyl]-5′-thien-2-yl-1,1′-biphenyl-2-carboxylic acid

[0355] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-5′-(2-amino-2-oxoethoxy)-4-[(isobutylamino)carbonyl]-1,1′-biphenyl-2-carboxylic acid

[0356] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4′-ethoxy-4-[(isobutylamino)carbonyl]-1,1′-biphenyl-2-carboxylic acid

[0357] 2-{5-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-1,3-benzodioxol-4-yl}-5-[(isobutylamino)carbonyl]benzoic acid

[0358] 2′-[1-({4-[Amino(imino)methyl]phenyl}amino)ethyl]-4-[(isobutylamino)carbonyl]-1,1′-biphenyl-2-carboxylic acid

[0359] 3-[2-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-(benzyloxy)phenyl]-6-[(isobutylamino)carbonyl]pyridine-2-carboxylic acid

[0360] 3-[2-(4-Carbamimidoyl-phenylcarbamoyl)-4-vinyl-phenyl]-6-isobutylcarbamoyl-pyridine-2-carboxylic acid

[0361] 2′-[(5-Carbamimidoyl-pyridin-2-ylamino)-methyl]-4-isobutylcarbanoyl-4′-vinyl-biphenyl-2-carboxylic acid

[0362] 2′-{[4-(N-Hydroxycarbamimidoyl)-phenylamino]-methyl}-4-isobutylcarbamoyl-4′-vinyl-biphenyl-2-carboxylic acid

[0363] 2′-{[4-(N-Hydroxycarbamimidoyl)-phenylamino]-methyl}-4-isobutylcarbamoyl-4′-vinyl-biphenyl-2-carboxylic acid methyl ester

[0364] 3-{2-[(4-Carbamimidoyl-phenylamino)-methyl]-4-vinyl-phenyl}-6-isobutylcarbamoyl-pyridine-2-carboxylic acid

[0365] Methyl 3-{2-[({4-[(hydroxyamino)(imino)methyl]phenyl}amino)methyl]-4-vinylphenyl}-6-[(isobutylamino)carbonyl]pyridine-2-carboxylate

[0366] Methyl 3-{2-[({4-[(hydroxyamino)(imino)methyl]phenyl}amino)carbonyl]-4-vinylphenyl}-6-[(isobutylamino)carbonyl]pyridine-2-carboxylate

[0367] N2-Hydroxy-3-{2-[({4-[(hydroxyamino)(imino)methyl]phenyl}amino)carbonyl]-4-vinylphenyl}-N6-isobutylpyridine-2,6-dicarboxamide

[0368] 3-{2-[({4-[(Hydroxyamino)(imino)methyl]phenyl}amino)carbonyl]-4-vinylphenyl}-6-[(isobutylamino)carbonyl]pyridine-2-carboxylic acid

[0369] 2′-[({4-[Amino(imino)methyl]phenyl}amino)methyl]-4-[(isobutylamino)carbonyl]-5′-methoxy-4′-vinyl-1,1′-biphenyl-2-carboxylic acid

[0370] 2′-[({4-[Amino(imino)methyl]phenyl}amino)(carboxy)methyl]-4-[(isobutylamino)carbonyl]-5′-methoxy-1,1′-biphenyl-2-carboxylic acid

[0371] 2′-[({5-[(Hydroxyamino)(imino)methyl]pyridin-2-yl}amino)methyl]-4-[(isobutylamino)carbonyl]-4′-vinyl-1,1′-biphenyl-2-carboxylic acid

[0372] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-{[(3-carboxypropyl)amino]carbonyl}-4′-(2-furyl)-1,1′-biphenyl-2-carboxylic acid

[0373] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-{[(3-carboxypropyl)amino]carbonyl}-4′-vinyl-1,1′-biphenyl-2-carboxylic acid

[0374] 3-{2-[({4-[Amino(imino)methyl]phenyl}amino)methyl]-5-methoxy-4-vinylphenyl}-6-[(isobutylamino)carbonyl]pyridine-2-carboxylic acid

[0375] 3-{2-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-5-methoxy-4-vinylphenyl}-6-[(isobutylamino)carbonyl]pyridine-2-carboxylic acid

[0376] 2′-(4-Carbamimidoyl-phenylcarbamoyl)-4-(2-carboxy-ethylcarbamoyl)-4′-ethyl-biphenyl-2-carboxylic acid

[0377] 2′-[({5-[Amino(imino)methyl]pyridin-2-yl}amino)methyl]-4-[(isobutylamino)carbonyl]-5′-methoxy-4′-vinyl-1,1′-biphenyl-2-carboxylic acid

[0378] 2′-[({6-[Amino(imino)methyl]pyridin-3-yl}amino)methyl]-4-[(isobutylamino)carbonyl]-4′-vinyl-1,1′-biphenyl-2-carboxylic acid

[0379] 3′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-[(isobutylaminoicarbonyl]-1,1′-biphenyl-2-carboxylic acid

[0380] 3′-[({4-[Amino(imino)methyl]phenyl}amino)methyl]-4-[(isobutylamino)carbonyl]-1,1′-biphenyl-2-carboxylic acid

[0381] 4-{[(2-Aminoethyl)amino]carbonyl}-2′-[({4-[amino(imino)methyl]phenyl}amino)carbonyl]-4′-vinyl-1,1′-biphenyl-2-carboxylic acid

[0382] 2′-[({4-[Amino(imino)methyl]phenyl}amino)carbonyl]-4-{[(2,3-dihydroxypropyl)amino]carbonyl}-4′-vinyl-1,1′-biphenyl-2-carboxylic acid

[0383] 2′-(4-Carbamimidoyl-phenylcarbamoyl)-4-(2-carbamoyl-ethylcarbamoyl)-4′-ethyl-biphenyl-2-carboxylic acid

Biological Assay Methods

[0384] In Vitro Assay for Inhibition of TF/FVIIa

[0385] To assess the inhibition of the test compounds against the target enzyme, TF/FVIIa, an amidolytic assay based upon the absorbance of p-Nitroanalide (pNA) at OD405 was utilized. The IC50 of the test compounds was determined by using KC4A data reduction software (Bio-Tek Instruments) to interpolate percent inhibition from observed Vmax values.

[0386] TF/FVIIa assay reactions were performed in a 200 μL mixture containing 4 nM FVIIa, 10 nM lipidated tissue factor, in an assay buffer containing 100 mM Tris, pH 7.2, 150 mM NaCl, 5 mM calcium chloride, 0.1% bovine serum albumin (BSA), and 10% dimethyl sulfoxide (DMSO). TF and FVIIa were allowed to equilibrate at room temperature for 15 minutes. Test compounds dissolved in DMSO were incubated at varied concentrations with TF/FVIIa for 10 minutes, followed by addition of 500 □M substrate Spectrozyme-FVIIa. Reactions were incubated for 5 minutes at room temperature prior to measuring the change in OD405 run for 10 minutes at 21 second intervals with a Powerwave x (Bio-Tek Instruments) microplate reader.

[0387] In Vitro Assay for Human Thrombin

[0388] This colorimetric assay was used to assess the ability of the test compounds to inhibit the human thrombin enzyme. IC50 of the test compounds was determined by using KC4A data reduction software (Bio-Tek Instruments) to interpolate percent inhibition from observed Vmax values.

[0389] Thrombin assay reactions were performed in a 200 μL mixture containing human thrombin at (1 U/mL) in an assay buffer containing 100 mM HEPES, 10 mM calcium chloride, and 10% DMSO, pH 7.5. Test compounds dissolved in DMSO were added to thrombin enzyme reactions at varied concentrations, followed by the addition of substrate Nao-Benzoyl-Phe-Val-Arg-p-Nitroanilide at a final concentration of 1 mM. Reactions were incubated for 5 minutes at room temperature prior to measuring the change in OD405 nm for 10 minutes at 21 second intervals with a Powerwave x (Bio-Tek Instruments) microplate reader.

[0390] In Vitro Assay for Human Trypsin

[0391] This enzymatic assay was employed to evaluate the ability of the test compounds to inhibit human pancreatic trypsin. IC50 of the test compounds was determined by using KC4A data reduction software (Bio-Tek Instruments) to interpolate percent inhibition from observed Vmax values.

[0392] Trypsin assay reactions were performed in a 200 μL mixture containing human pancreatic trypsin at 1 μg/mL in an assay buffer containing 200 mM triethanolamine (TEA), 10 mM calcium chloride, 10% DMSO, pH 7.8. Test compounds dissolved in DMSO were added to trypsin enzyme reactions at varied concentrations, followed by the addition of substrate Nα-Benzoyl-L-Arginine p-Nitroanilide (L-BAPNA) at a final concentration of (0.25 mg/mL). Reactions were incubated for 5 minutes at room temperature prior to measuring the change in OD405 nm for 10 minutes at 21 second intervals with a Powerwave x (Bio-Tek Instruments) microplate reader.

Biological Data

[0393] IC50 Values of Some Selected Compounds on Different Serine Protease Enzymes

947
R (With Respect to
Phenyl Ring	R′	TF/FVIIa	Trypsin	Thrombin
948	949	++	+	+
950	951	++	+	+
952	953	++	+	+
954	955	++	−	−
956	957	+	−	−
958	959	++	−	−
960	961	+++	++	+
962	963	+++	++	+
964	965	+++	++	+
966	967	+++	++	+
IC50 values: + means > 1 μM; ++ means > 100 nM; +++ means < 100 nM

[0394] A comparison of Examples with R group and without R group illustrates the greatly-enhanced activity achieved pursuant to the present invention.

[0395] Compounds of the present invention are useful as inhibitors of trypsin-like serine protease enzymes such as thrombin, factor VIIa, TF/FVIIa, and trypsin.

[0396] These compounds may be employed to inhibit the coagulation cascade and prevent or limit coagulation.

[0397] These compounds may be used to inhibit the formation of emboli or thromboli in blood vessels.

[0398] These compounds may be used to treat thrombolymphangitis, thrombosinusitis, thromboendocarditis, thromboangitis, and thromboarteritis.

[0399] These compounds may be used to inhibit thrombus formation following angioplasty. These may be used in combination with other antithrombolytic agents such as tissue plasminogen activators and their derivatives, streptokinase and its derivatives, or urokinase and its derivatives to prevent arterial occlusion following thrombolytic therapy.

[0400] These compounds may also be used in metastatic diseases, or for any disease where inhibition of coagulation is indicated.

[0401] These compounds may be used as diagnostic reagents in vitro for inhibiting clotting of blood in the tubes.

[0402] These compounds may be used alone or in combination with other compounds such as heparin, aspirin, or warfarin and any other anticoagulant agents.

[0403] These compounds may be used as anti-inflammatory agents.

[0404] According to a further aspect of the invention, compounds may be employed in preventing ex vivo coagulation such as that encountered in the extracorporeal perfusion of blood through for example artificial valves, prothesis, stents or catheters. According to this aspect of the invention the extracorporeal device may be coated with the compositions of the invention resulting in a lower risk of clot formation due to extrinsic pathway activation.

Dosage and Formulation

[0405] The compounds of this invention can be administered by any means that produces contact of the active agent's site of action with factor VIIa and other serine proteases in the body of a human, mammal, bird, or other animal. They can be administered by any conventional means, such as oral, topical, transdermal, parenteral, subcutaneous, intraperitoneal, intrapulmonary, and intranasal, available for use in conjunction with pharmaceuticals, either as individual therapeutic agents or in a combination of therapeutic agents. Parenteral infusion includes intramuscular, intravenous, and intraarterial. They can be administered alone, but generally administered with a pharmaceutical carrier elected on the basis of the chosen route of administration and standard pharmaceutical practice.

[0406] The dosage administered will, or course, vary depending upon known factors, such as the pharmacodynamic characteristics of the particular agent and its mode and route of administration; the age, health and weight of the recipient; the nature and extent of the symptoms, the kind of concurrent treatment; the frequency of treatment; and the effect desired. A daily dosage of active ingredient can be expected to be about 0.0001 to 1000 milligram (mg) per kilogram (kg) of body weight, with the preferred dose being 0.1 to about 30 mg/kg.

[0407] Dosage forms (compositions suitable for administration) contain from about mg to about 500 mg of compound per unit. In these pharmaceutical compositions, the compound of the present invention will ordinarily be present in an amount of about 0.5-95% by weight based on the total weight of the composition.

[0408] The daily dose of the compounds of the invention that is to be administered can be a single daily dose or can be divided into several, for example, two, three or four, part administrations. The pharmaceutical compositions or medicaments of the invention can be administered orally, for example in the form of pills, tablets, lacquered tablets, coated tablets, granules, hard and soft gelatin capsules, solutions, syrups, emulsions, suspensions or aerosol mixtures. Administration, however, can also be carried out rectally, for example in the form of suppositories, or parenterally, for example intravenously, intramuscularly or subcutaneously, in the form of injection solutions or infusion solutions, microcapsules, implants or rods, or percutaneously or topically, for example in the form of ointments, solutions or tinctures, or in other ways, for example in the form of aerosols or nasal sprays.

[0409] Gelatin capsules contain a compound of the present invention and powdered carriers, such as lactose, starch, cellulose derivatives, biocompatible polymers, magnesium stearate, stearic acid, and the like. Similar diluents can be used to make compressed tablets. Both tablets and capsules can be manufactured as sustained release products to provide for continuous release of medication over a period of hours. Compressed tablets can be sugar coated to mask by unpleasant taste and protect the tablet from the atmosphere, or enteric coated for selective disintegration in the gastrointestinal tract.

[0410] Liquid dosage forms for oral administration can contain coloring and flavoring to increase patient acceptance. They may also contain buffering agents, surfactants and preservatives. Liquid oral products can be developed to have sustained-release properties. They may also contain cyclodextrin derivatives to enhance the solubility of the active ingredient and to promote its oral uptake.

[0411] In general, water, a suitable oil, saline, aqueous dextrose (glucose), and related sugar solutions and glycols such as propylene glycol or polyethylene glycols are suitable carriers for parenteral solutions. Solutions for parenteral administration preferably contain a water-soluble salt of the active ingredient, suitable stabilizing agents, and, if necessary, buffering agents. Antioxidizing agents such as sodium bisulfite, sodium sulfite, or ascorbic acid, either alone or combined, are suitable stabilizing agents. Also used are citric acid and its salts and sodium EDTA. In addition, parenteral solutions can contain preservatives, such as benzalkonium chloride, methyl- or propylparaben, and chlorobutanol.

[0412] Suitable pharmaceutical carriers are described in Remington's Pharmaceutical Sciences, Mack Publishing Company and in the Handbook of Pharmaceuticals Excipients, American Pharmaceutical Association, both standard reference texts in this field.

[0413] Useful pharmaceutical dosage forms for administration of the compounds according to the present invention can be illustrated as follows:

Hard Shell Capsules

[0414] A large number of unit capsules are prepared by filling standard two-piece hard gelatin capsules each with 100 mg of powdered 1500 mg of lactose, 50 mg of cellulose, and 6 mg of magnesium stearate.

Soft Gelatin Capsules

[0415] A mixture of active ingredient in a digestible oil such as soybean oil, cottonseed oil, or olive oil is prepared and injected by means of a positive displacement pump into molten gelatin to form soft gelatin capsules containing 100 mg of the active ingredient. The capsules are washed and dried. The prodrug can be dissolved in a mixture of polyethylene glycol, glycerin and sorbitol to prepare a water miscible medicine mix.

Tablets

[0416] A large number of tablets are prepared by conventional procedures so that the dosage unit was 100 mg of active ingredient, 0.2 mg of colloidal silicon dioxide, 5 mg of magnesium stearate, 275 mg of microcystalline cellulose, 11 mg of starch, and 9.98 mg of lactose. Appropriate aqueous and non-aqueous coatings may be applied to increase palatability improve elegance and stability or delay absorption.

Immediate Release Tablets/Capsules

[0417] These are solid oral dosage forms made by conventional and novel processes. These units are taken orally without water for immediate dissolution and delivery of the medication. The drug is mixed containing ingredient such as sugar, gelatin, pectin, and sweeteners. These liquids are solidified into solid tablets or caplets by freeze drying and solid thermoelastic sugars and polymers or effervescent components to produce porous matrices intended for immediate release, without the need of water.

[0418] Moreover, the compounds of the present invention can be administered in the form of nose drops, metered dose nasal or buccal inhalers. The drug is delivered from a nasal solution as a fine mist or from a powder as an aerosol.

[0419] In another embodiment of the invention, a compound of the invention can be used in an assay to identify the presence of factor VIIa and other serine protease or to isolate factor VIIa and other serine protease in a substantially purified form. For example, the compound of the invention can be labeled with, for example, a radioisotope, and the labeled compound is detected using a routine method useful for detecting the particular label. In addition, a compound the invention can be used advantageously as a probe to detect the location or amount of factor VIIa and other serine protease activity in vivo, in vitro or ex vivo.

[0420] Various modifications of the invention in addition to those shown and described herein will be apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims.

[0421] The foregoing disclosure includes all the information deemed essential to enable those skilled in the art to practice the claimed invention. The foregoing description of the invention illustrates and describes the present invention. Additionally, the disclosure shows and describes only the preferred embodiments of the invention but, as mentioned above, it is to be understood that the invention is capable of use in various other combinations, modifications, and environments and is capable of changes or modifications within the scope of the inventive concept as expressed herein, commensurate with the above teachings and/or the skill or knowledge of the relevant art. The embodiments described hereinabove are further intended to explain best modes known of practicing the invention and to enable others skilled in the art to utilize the invention in such, or other, embodiments and with the various modifications required by the particular applications or uses of the invention. Accordingly, the description is not intended to limit the invention to the form disclosed herein. Also, it is intended that the appended claims be construed to include alternative embodiments.

Claims

1. Compound having the structure (I) shown below:

2. The compound of claim 1 represented by the structure:

3. The compound of claim 1 represented by the structure:

4. The compound of claim 1 represented by the structure:

5. The compound of claim 1 represented by the structure:

6. The compound of claim 1 represented by the structure:

7. The compound of claim 1 represented by the structure:

8. The compound of claim 1 represented by the structure:

9. The compound of claim 1 represented by the structure:

10. The compound of claim 1 represented by the structure:

11. The compound of claim 1 represented by the structure

12. A pharmaceutical composition containing at least one compound according to claim 1.

13. A method for inhibiting serine protease in a patient which comprises administering to the patient an effective serine protease inhibiting amount of at least one compound according to claim 1.

14. A method for inhibiting the coagulation cascade and preventing or limiting coagulation by administering to a patient an effective amount of at least one compound according to claim 1.

15. A method for inhibiting the formation of emboli or thromboli in blood vessels by administering to a patient an effective amount of at least one compound according to claim 1.

16. A method for treating at least one condition selected from the group consisting of thrombolymphangitis, thrombosinusitis, thromboendocarditis, thromboangitis, unstable angina, and thromboarteritis which comprises administering to a patient an effective amount of at least one compound according to claim 1.

17. A method for inhibiting thrombus formation following angioplasty which comprises administering to a patient an effective amount of at least one compound according to claim 1.

18. A method for preventing arteria occlusion following thrombolytic therapy which comprises administering to a patient an effective amount of at least one compound according to claim 1 and an effective amount of at least another antithrombolytic agent.

19. The method of claim 18 wherein said other antithrombolytic agent is selected from the group consisting of tissue plasminogen activators, streptokinase and urokinase, and functional derivatives thereof.

20. A method for treating metastatic diseases which comprises administering to a patient an effective amount of at least one compound according to claim 1.

21. A method of claim 14 which further comprises administering a further anticoagulant agent to said patient.

22. The method of claim 21 wherein said further anticoagulant agent is selected from the group consisting of heparin, aspirin, and warfarin.

23. A methof for treating a patient in need of an anti-inflammatory agent which comprises administering to said patient an effective amount of at least one of the compounds according to claim 1.

24. A method for inhibiting in vitro clotting of blood which comprises contacting said blood with at least one compound according to claim 1.

25. The method of claim 24 which comprises inhibiting said blood in tubes.

26. An extraarpereal device having a coating therein which comprises a compound according to claim 1. cm 27. A method for detecting presence of a serine protease which comprises contacting a sample with a compound according to claim 1.