SELECTED DERIVATIVES OF K-252a

Abstract: Disclosed herein are selected indolocarbazole derivatives which are represented by general formula (I). The compounds are useful for enhancing the function and/or survival of a trophic factor responsive cell. They inhibit interleukin-2 production and have immunosuppressive activity.

Description: SELECTED DERIVATIVES OF K-252a This application is a coπtinuation-in-part of Senal No. 08/657,366, filed June 3, 1996. HELD OF INVENTION This invention features selected ring-substituted deπvatives of K-252a and their use for treatment of neurological disorders. BACKGROUND OF THE INVENTION K-252a is a compound having an lndolocarbazole skeleton represented by the following formula [Japanese Published Unexamined Patent Applicanon No.41489/85 (US No.4555402)]. It has been reported that K-252a strongly inhibits protein kinase C (PKC) which plays a central role m regulating cell funcnons, and has vanous acnvines such as the action of inhibiting smooth muscle contraction (Jpn. J. Pharmacol.43(suppl.): 284, 1987), the acnon of inhibiting serotonin secretion (Biochem. Biophys. Res. Commun., 144: 35, 1987), the acnon of inhibiting elongation of neuraxone (J. Neuroscience, 8: 715, 1988), the acnon of inhibiting histamine release (Allergy, 43- 100, 1988), the acnon of inhibiting smooth muscle MLCK (I. Biol. Chem., 263: 6215, 1988), ann-inflammatory acnon (Acta Physiol. Hung., 80: 423, 1992), the acnvity of cell survival (J. Neurochemistry, 64: 1502, 1995), etc. It has also been disclosed in Experimental Cell Research, 193: 175-182, 1991 that K-252a has the activity of inhibiting IL-2 production. Also the complete synthesis of K-252a has been achieved (J. Am. Chem. Soc, 117: 10413, 1995). On the other hand, it has been disclosed that derivanves of K-252a have PKC inhibitory activity, the activity of inhibiting histamme release (Japanese Published Unexamined Patent Application No. 295588/88), antitumor activity [Japanese Published Unexamined Patent Application No. 168689/89 (US 4,877,776), WO 88/07045 (US 4,923,986)] etc., the action of increasing blood platelets [WO94/06799 (EP 630898A)], vasodepressor activity (Japanese Published Unexamined Patent Application No. 120388/87), the action of accelerating cholinergic neuron funcnons [WO 94/02488 (US 5,461,146)], curanve effect on prostate cancer [WO 94/27982 (US 5,516,771)], etc. SUMMARY OF THE INVENTION The present invention relates to selected derivanves of K-252a represented by the general formula: Constituent members are disclosed in detail, infra. Preferred methods for preparing these compounds and methods for using them are also disclosed. DETAILED DESCRIPTION I. Drawings Figures 1 and 3 depict the structure of the substituted K-252a denvanves of the mvennon. Figure 2 depicts the structure of K-252a. Figure 4 is a schematic drawing showmg the synthesis of a πng-subsnruted K-252a derivative from a nng-unsubstituted starting material. Figure 5 is a schematic drawing showing the synthesis of a compound which contains at least one ring substituent. Figure 6 is a schematic drawing showmg the synthesis of a compound which contains at least one nng subsntuent. Figure 7 is a schematic drawing showmg the synthesis of a compound which contams at least one -(CHj) k R 7 or nng substituent. Figure 8 is a schematic drawing showmg the synthesis of a compound which contams a halogen or nitro nng substituent Figure 9 depicts the structures of certain known K-252a denvanves which are used as starting matenals to prepare compounds of the invention. π. Selected Ring-Substituted K-252a Derivatives Disclosed herein are the selected nng-subsntuted denvanves of K-252a which are represented by the following formula: • wherein: one of R 1 and R 2 is selected from the group consisting of: a) -CO(CH 2 ),R 4 , wherein j is 1 to 6, and K* is selected from the group consisting of. 1 ) hydrogen and a halogen; 5 2) -NR 5 R 6 , wherein R 5 and R 6 independently are hydrogen, substituted lower alkyl, unsubstituted lower alkyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted aralkyl, unsubstituted aralkyl, lower alkylaminocarboπyl, or lower alkoxycarbonyl; or R 5 and R 6 are combined with a nitrogen atom to form 10 a heterocyclic group; 3) N 3 ; 4) -SR 27 , wherein R 27 is selected from the group consisting of: i) hydrogen; ii) substituted lower alkyl; ! 5 iii) unsubstituted lower alkyl; iv) substituted aryl; v) unsubstituted aryl; vi) substituted heteroaryl; vii) unsubstituted heteroaryl; 20 viii) substituted aralkyl; ix) unsubstituted aralkyl; x) thiazolinyl, xi) -(CH J J.COJR 2 ', wherein a is 1 or 2, and R 2 ' is selected from the group consisting of: hydrogen and lower alkyl; and xii) -(CH 2 ),CONR 5 R 6 ; and 5) OR 2 (wherein R 2 ' is hydrogen, substituted lower alkyl, unsubstituted lower alkyl, or COR 30 (wherein R 30 is hydrogen, lower alkyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, or unsubstituted heteroaryl)), b) -CH(OH)(CH 2 ) b R 4A , wherein b is 1 to 6 and R 4A is hydrogen or the same as R 4 , c) -(CH 2 ) d CHR 3 'C0 2 R 32 wherein d is 0 to 5, R 31 is hydrogen, -CONR 5 R 6 , or -C0 2 R 33 (wherein R" ts hydrogen or lower alkyl), and R 32 is hydrogen or lower alkyl, d) -(CH2) d CHR 3 'CONR 5 R\ e) -(CH 2 ) k R " wherein k is 2 to 6, and R 7 is haiogen, C0 2 R' (wherein R* is hydrogen, lower alkyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, or unsubstituted heteroaryl), CONR 5 R 6 , substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, OR 9 (wherein R 9 is hydrogen, substituted lower alkyl, unsubstituted lower alkyl, acyl, substituted aryl, or unsubstituted aryl), SR 27B (wherein R™ is the same as R 27 ), NR I0 R" (wherein R 10 and R 1 ' are the same as R 5 and R 6 ) or N 3 ; f) -CH=CH(CH 2 ) n R 12 wherein m is 0 to 4, and R 12 is hydrogen, lower alkyl, C0 2 R ,A (wherein R" is the same as R*), -CONR 5 R 6 , substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, OR A (wherein R ,A is the same as R 9 ), or NR 10A R l ,A (wherein R 10A and R HA are the same as R 3 and R 6 ), g) -CH=C(C0 2 R 33A ) 2 , wherein R 33A is the same as R 33 , h) -C"C(CH 2 ).R l \ wherein n is 0 to 4, and R 13 is the same as R 12 , 0 -CH 2 OR" , wherein R 44 is substituted lower alkyl, and the other of R' or R 2 is selected from the group consisting of j) hydrogen, lower alkyl, halogen, acyl, nitro, NR 14 R 15 (wherein R 14 or R l! is hydrogen or lower alkyl, and the other is hydrogen, lower alkyl, acyl, carbamoyi, lower alkylammocarbonvi, substituted arylaminocarbonyl or unsubstituted arylammocarbonyl), k) -CH(SR 34 ) 2 , wherein R 34 is lower alkyl or alkylene; 1) -CH 2 R 35 , wherein R 33 is OR 36 (wherein R 36 is tri-lower alkyl silyl in which the three lower alkyl groups are the same or different, or is the same as R 29 ), or SR 37 (wherein R 37 is the same as R 2 '), ) -CO(CH 2 ),R 16 , wherein q is 1 to 6, and R 16 is the same as R 4 ; n) -CH(OH)(CH 2 ),R J, 1 wherein e is I to 6, an R 3 ' is the same as R 4A ; o) -(CH 2 )rCHR 39 C0 2 R 40 , wherein f is 0 to 5, R 39 is the same as R JI and R 40 is the same as R 32 ; p) -(CH 2 )-R 17 , wherein r is 2 to 6, and R 17 is the same as R 7 ; q) -CH-C^CHΛ ' 1 , wherein t is 0 to 4, and R 1 * is the same as R 12 ; r) -CH=C(C0 2 R 33B ) 2> wherein R 33B is the same as R 33 ; s) -C"C(CH 2 ) 1I R 19 , wherein u is 0 to 4, and R 19 is the same as R 13 ); R >-' i :s hydrogen, acyl, or lower alkyl; X is selected from the group consisting of: a) hydrogen; b) formyi; c) lower alkoxycarbonyl; d) -CONR 20 R 21 , wherein: R 20 and R 21 independently are: hydrogen; lower alkyl; -CH2R 22 , wherein R 22 is hydroxy, or -NR^R 24 (wherein R 23 or R 24 is hydrogen or lower alkyl, and the other is hydrogen, lower alkyl, or the residue of an α-amino acid in which the hydroxy group of the carboxyl group is excluded, or R 23 and R 24 are combined with a nitrogen atom to form a heterocyclic group); and e) -CH-N-R 25 , wherein R 25 is hydroxy, lower alkoxy, amino, guanidino, or imidazoiyiamino; γ is hydroxy, lower alkoxy, aralkyloxy, or acyioxy; or X and Y combined represent, -X-Y-, -0, -CH 2 0(C=0)0-, -CH 2 OC(=S)0-, -CH 2 NR 26 C( « 0)- (wherein R 26 is hydrogen or lower alkyl), -CH 2 NHC(=S)0-, -CH 2 0S(=O)0-, or -CH 2 OC(CH 3 ) 2 0-; and W and W 2 are hydrogen, or W' and W 2 together represent oxygen; or a pharmaceutically acceptable salt thereof. The compounds represented by formula (I) are hereinafter referred to as Compound (I), and the same applies to the compounds of other formula numbers In the definitions of the groups in formula (I), lower alkyl means a straight-chain or branched alkyl group having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isoamyl, neopentyl, 1-ethylpropyl and hexyl. The lower alkyl moiety of lower alkoxy, lower alkoxycarbonyl, lower alkylarmnocarbonyl and tn-lower aikylsilyl has the same meaning as lower alkyl defined above. The acyi moiety of the acyl and the acyloxy groups means a straight-chain or branched alkanoyl group having 1 to 6 carbon atoms, such as formyL, acetyl, propanoyl, butyryl, valeryl, pivaloyl and hexanoyl, an arylcarbonyl group described below, or a heteroarylcarbonyl group described below The aryl moiety of the aryl, the arylcarbonyl and the arylaminocarbonyl groups means a group having 6 to 12 carbon atoms such as phenyl, biphenyl and naphthyl. The heteroaryl moiety of the heteroaryl and.the heteroarylcarbonyl groups contain at least one hetero atom selected from O, S, and N, and include pyπdyl, pynmidyl, pyrrolyl, furyl, thienyl, lmidazolyl, triazolyL, tetrazoly quinolyL, isoquinolyl, benzoimidazoiyl, thiazolyl and benzothiazolyl. The aralkyl moiety of the aralkyl and the aralkyioxy groups means an aralkyl group having 7 to 15 carbon atoms, such as benzyi, phenethyl, benzhydryl and naphthylmethyl The substituted lower alkyl group has 1 to 3 independently-selected substituents, such as hydroxy, lower alkoxy, carboxyl, lower alkoxycarbonyl, nitro, amino, mono- or di-lower alkylamino, dioxolane, dioxane, dithiolane, and dithionc The lower alkyl moiety of the substituted lower alkyl, and the lower alkyl moiety of the lower alkoxy, the lower alkoxycarbonyl, and the mono- or di-lower alkylamino in the substituents of the substituted lower alkyl group have the same meaning as lower alkyl defined above. The substituted aryl, the substituted heteroaryl and the substituted aralkyl groups each has 1 to 3 independently-selected substituents, such as lower alkyl, hydroxy, lower alkoxy, carboxy, lower alkoxycarbonyl, nitro, amino, mono- or di-lower alkylamino, and halogen The lower alkyl moiety of the lower alkyl, the lower alkoxy, the lower alkoxycarbonyl, and the mono- or d i -lower alkylamino groups among the substituents has the same meaning as lower alkyl defined above The heterocycuc group formed with a nitrogen atom includes pyrrolidinyl, pφeπd i nyl, p i peπdino, morpho nyl, morpholino, thiomorphohno, N-methylpiperazinyl, indolyl, and t so i ndoiyl The α-amino acid groups include glycine, alanine, prohne, glutamic acid and lysine, wh i ch may be in the L-form, the D-form or in the form of a racemate Halogen includes fluorine, chlorine, bromine and iodine Preferably, one of R' and R 2 is selected from the group consisting of -(CH J HR 7 , -CH=CH(CH 2 ) tB R 12 , -CsqCH^R 13 , -CO(CH 2 ). SR 27 , and -CH . 0R 44 wherein R 44 is methoxymethyl, ethoxymethyl, or methoxyethyl, and the other of R 1 and R 2 is selected from the group cons i sting of -(CH_) r R 17 , -CH=CH(CH . λR", -C--.C(CH_) g R", NR'-R 15 , hydrogen, halogen, n i tro, - CH 2 0-(substituted or unsubstituted) lower alkyl, -CO(CH 2 ), SR 27 , - CH . R 35 , - CH j OH, and -CH j SR wherein R 57 is selected from the group consisting of lower alkyl, pyndyl, and benziπudazole Preferably, R 35 is OR 34 wherein R 36 , preferably, is selected from the group consisting of methoxymethyl, etiioxymethyl, and methoxyethyl Preferably, R is selected from the group consisting of substituted or unsubstituted lower alkyl, subst i tuted or unsubstituted phenyl, pyndyl, pyππudiπyl, thiazole, and tetrazole Preferably, k and r, independently, are each 2, 3, or 4 Preferably, j and q, independendy, are 1 or 2 Preferably, R 7 and R 17 , independently, are selected from the group consisting of (1) CO j R* and CO-.R A , where R 1 and R ,A , independently, are hydrogen, methyl, ethyl, or phenyl, (2) phenyl, pyndyl, i πudazolyl, thazoiyl, or tetrazolyl,(3) OR 9 and 0R 9A where R' and R 9A , independently, are hydrogen, methyl, ethyl, phenyl, or acyl, (4) SR 27B where R 173 is selected from the group consisting of unsubst i tuted lower alkyl, 2-thιazouπe, and pyndyl, and (5) NR ,0 R" and NR I R' S , where R 10 , R , R , and R , independently, are selected from the group consisting of hydrogen, methyl, ethyl, phenyl, carbamoyi, and lower alkylaminocarbonyl Preferably, m, n, t and u, independently, are 0 or 1 Preferably, R 12 , R", R". and R' 9 , in-fcpαidently. are selected from the group cα i sisung of hydrogen, methyl, ethyl, phenyl. pyndyl, iir.idae.le, thiazole, tetrazole, CO j R\ OR 9 , and NR ,0 R n where R', R 9 , R 10 , and R" have the preferred values shown above. Preferably, R 1 is hydrogen or acetyL moit preferably hydrogen. Prefer-U-ly, X u hvctorocyrii.rώyl or 1^ particularly preferred. Preferably, Y is hydioxy or acctyloxy, most preferably hydroxy. Preferably, each W* and W 3 is hydrogen. More preferred are tic actual substituent value shown on the ∞mpouiiώ ώ T^ ^ Crαmpounds 1-157 bang especially preferred. πL Utilities The selected ring substituted K-252a ώsivatives have evidenced important factional phaππacological ctivmes iuch f.nd utility therapeutic arenas. and or survival of trophic factor responsive cells. Effect on the funcuoo and or survival of trophic factor responsive cells, e.g., cells of a neαronal lineage, can be established using any of the following assays: (1) cultured spinal cord cltioline - U -βtyltransferase ("ChAT") assay; or (2) cultured basal rorcbrain neuron ("BFN") ChAT acnvity assay. As used lierein, the terra "effect" when used to inαiify the terms "funcuon" and "surv i val" means a positive or negative a l teration or change. An effect which is positive can be referred to herem as an "cmlianceπient" or "en IJ ancing ,, and an effect which is negative can be referred to here i n as "inhibition" or "inhibiting " As used herein, the l eπns "enhance" or "enhancing" when used to mαiify the terms •function" or "survival" means that the presence of a substituted K-252a denvatrve has a pos i t i ve effect on the function and or survival of a trophic factor responsive cell compared with a cell i n the absence of the derivative. Fsr example, and not by way of limitation, with respect to the surv i val of. c.g., a cholinergic neuror, the denvative would evidence enhancement of survival of a cholinergic neuronal populaiion at nsk of dying (due to, e.g., injury, a disease cond i tion, a degenexative condition or natural progression) when compared to a cholmergic neuronal population not presented with such denvative, if the treated population has a comparatively greater penod of functionality than the non-treated population As used herein, "inhibit" and "inhibition" mean that a specified response of a designated mateπal (e g , enzymatic activity) is comparatively decreased in the presence of a substituted K- 252a denvative As used herein the term "neuron," "cell of neuronal lineage" and "neuronal cell" mcludes, but is not limited to, a heterogeneous population of neuronal types having singular or multiple transmitters and or singular or multiple functions, preferably, these are cholmergic and sensory neurons As used herein, the phrase "cholmergic neuron" means neurons of the Central Nervous System (CNS) and Peπpheral Nervous System (PNS) whose neurotransmitter is acetylcholine, exemplary are basal forebrain, stπatal, and spinal cord neurons As used herein, the phrase "sensory neuron" includes neurons responsive to environmental cues (e.g., temperature, movement) from, e.g., skin, muscle and joints, exemplary is a neuron from the dorsal root ganglion A "trophic factor-responsive cell," as defined herein, is a cell which mcludes a receptor to which a trophic factor can specifically bind, examples include neurons (e g , cholinergic and sensory neurons) and non-neuronal cells (e.g , monocytes and neoplastic cells) The disclosed aromatic nng substituted K-252a deπvatives can be used to enhance the function and or survival of cells of neuronal lineage They can also be used to enhance the function and/or survival of cells of neuronal lineage in a mammal, e g., a human In these contexts, the deπvatives can be utilized individually or with other deπvatives, or in combination with other beneficial molecules which also evidence the ability to effect the function and or survival of a designated cell A vanety of neurological disorders are characterized by neuronal cells which are dying, injured, functionally compnsed, undergoing axonal degeneration, at πsk of dying, etc These disorders include, but are not limited to. Alzheimer's disease, motor neuron disorders (e g amyotrophic lateral sclerosis), Parkinson's; cerebrovascular disorders (e g , stroke, ischaemia), Huntington's, AIDS dementia, epilepsy; multiple sclerosis; peπpheral neuropathies (e g., those affecting DRG neurons in chemotherapy-associated peπpheral neuropathy) including diabetic neuropathy; disorders induced by excitatory amino acids; disorders associated with concussive or penetrating mjunes of the brain or spinal cord. ChAT catalyzes the synthesis of the neurotransmitter acetylcholine, and it is considered an enzymatic marker for a functional cholmergic neuron. A functional neuron is also capable of survival Neuron survival is assayed by quanάtation of the specific uptake and enzymatic conversion of a dye (e.g., calcein AM) by living neurons. Because of their varied utilities, the K-252a derivatives disclosed herein find utility in a vaπety of settings . The compounds can be used in the development of in vitro models of neuronal cell survival, function, identification, or for the screening of other synthetic compounds which have activities similar to that of the K-252a derivatives. The compounds can be utilized in a research environment to investigate, define and determine molecular targets associated with functional responses For example, by radiolabelling a K-252a derivative associated with a specific cellular function (e.g., mitogenesis), the target entity to which the derivative binds can be identified, isolated, and purified for characterization. The pharmaceutically acceptable salts of Compounds (I) include pharmaceutically acceptable acid addition salts, metal salts, ammonium salts, organic amine addition salts, and ammo acid addition salts. Examples of the acid addition salts are inorganic acid addition salts such as hydrochloride, sulfate and phosphate, and organic acid addition salts such as acetate, maleate, fumarate, tartrate, citrate and lactatc; examples of the metal salts are alkali metal salts such as lithium salt, sodium salt and potassium salt alkaline earth metal salts such as magnesium salt and calcium salt, aluminum salt and zinc salt examples of the ammonium salts are ammonium salt and tetramethylammonium salt; examples of the organic amine addition salts are salts with morpholine and piperidine; and examples of the ammo acid addition salts are salts with glycine, phenylalanine, glutamic acid and lysine. Compounds provided herein can be formulated into pharmaceutical compositions by admixture with pharmaceutically acceptable nontoxic excipients and earners. Such compositions can be prepared for use in parenteral adrninistration, particularly in the form of liquid solutions or suspensions; or oral administration, particularly in the form of tablets or capsules; or intranasally, particularly in the form of powders, nasal drops, or aerosols; or dermally, via, for example, trans- dermal patches The composition can be conveniently administered in unit dosage form and may be prepared by any of the methods well known in the pharmaceutical art, for example, as descπbed in Remington's Pharmaceutical Sciences (Mack Pub Co., Easton, PA, 1980) Formulations for parenteral administration may contain as common excipients sterile water or saline, polyaikylene glycols such as polyethylene glycol. oils and vegetable oπgin, hydrogenated naphthalenes and the like In particular, biocompatible, biodegradable lactide polymer, lacQde/glycolide copolymer, or polyoxyethylene-polyoxypropylene copoiymers may be useful excipients to control the release of the active compounds Other potentially useful parenteral delivery systems for these active compounds include ethylene-vmyl acetate copolymer particles, osmotic pumps, implantable infusion systems, and hpOSOmeS Formulauπn?; for inhalation aHminnmnnn rnntain fl«i mtKipients, for exam le lactose, or may be aqueous solutions containing, for example, polyoxyethylene-9-lauryl ether, glycocholate and deoxycholate, or ody solutions for adrrunistration m the form of nasal drops, or as a gel to be applied mtranasally Formulations for parenteral administration may also include glycocholate for buccal administration, a saiicylate for rectal adrrunistration, or citnc acid for vaginal adrrunistration Formulations for trans-dermal patches are preferably bpophihc emulsions The compounds of this mvennon can be employed as the sole active agent in a pharmaceutical composition Alternatively, they can be used in combination with other active ingredients, e.g., other growth factors which facihtate neuronal survival or axonal regeneration in diseases or disorders Compound (I) and pharmaceutically acceptable salts thereof can be administered orally or non-orally, e.g., as an ointment or an injection The concentrations of the compounds of this invention in a therapeutic composition can vary The concentration will depend upon factors such as the total dosage of the drug to be administered, the chemical characteristics (e.g , hydrophobicity) of the compounds employed, the route of administration, the age, body weight and symptoms of a patient etc The compounds of this mvenuon typically are provided in an aqueous physiological buffer solution containing about 0.1 to 10% w/v compound for parenteral administration Typical dose ranges are from about 1 μg/kg to about 1 g/kg of body weight per day, a preferred dose range is from about 0 01 mg/kg to 100 mg/kg of body weight per day, and preferably about 0 1 to 20 mg/kg once to four times per day A preferred dosage of drug to be administered is likely to depend on vanables such as the type and extent of progression of the disease or disorder, the overall health stanis of the particular patient the relative biological efficacy of the compound selected, and formulation of the compound excipient and its route of administration Compound (I) and pharmaceutically acceptable salts thereof can be administered as they are, or in the form of vaπous pharmaceutical compositions, according to the pharmacological activity and the purpose of administration. The pharmaceutical compositions in accordance with the present invention can be prepared by uniformly mixing an effective amount of Compound (I) or a pharmaceutically acceptable salt thereof as an active ingredient with a pharmaceutically acceptable earner. The earner may take a wide range of forms according to the forms of composition suitable for administration It is desired that such pharmaceutical compositions are prepared in a unit dose form suitable for oral or non-oral administration The forms for non-oral administration include ointment and injection Tablets can be prepared using excipients such as lactose, glucose, sucrose, manmtol and methyl cellulose, disintegrating agents such as starch, sodium alginate, calcium carboxymethyl cellulose and crystalline cellulose, lubneants such as magnesium stearate and talc, binders such as gelatin, polyvinyl alcohol, polyvinyl pyrrolidone, hydroxypropyi cellulose and methyl cellulose, surfactants such as sucrose fatty acid ester and sorbitol ratty acid ester, and the like in a conventional manner It is preferred that rach tablet contains 15-300 mg of the active ingredient Granules can be prepared usmg excipients such as lactose and sucrose, disintegrating agents such as starch, binders such as gelatin, and the like in a conventional manner. Powders can be prepared usmg excipients such as lactose and mannitol, and the like in a conventional manner. Capsules can be prepared usmg gelatin, water, sucrose, gum arabic, sorbitol, glycerin, ciystalline cellulose, magnesium stearate, talc, and the Like in a conventional manner It is preferred that each capsule contains 15-300 mg of the active ingredient. Syrup preparations can be prepared using sugars such as sucrose, water, ethanol, and the like in a conventional manner. Ointment can be prepared using ointment bases such as vaseline, liquid paraffin, ianoun and macrogol, emulsifiers such as sodium lauryl lactate, benzalkonium chloride, sorbitan mono-fatty acid ester, sodium carboxymethyl cellulose and gum arabic, and the like in a conventional manner In ectable preparations can be prepared using solvents such as water, physiological saline, vegetable oils (e.g., ohve oil and peanut oil), ethyl oleate and propylene giycol, solubilizmg agents such as sodium benzoate, sodium sahcylate and urethanc, isotomcity agents such as sodium chlonde and glucose, preservatives such as phenol, cresol, p-hydroxybenzoic ester and chlorobutanol, antioxidants such as ascorbic acid and sodium pyrosulfite, and the like in a conventional manner rV. General Description of the Synthetic Processes The processes for preparing Compound (I) are descπbed below Me, Et Ph, Ac, Bn, Boc, and t-Bu in the structural formulae and tables represent methyl, ethyl, phenyl, acetyl, benzyl, tert-butoxycarbonyl, and tert-butyl, respectively The compounds of the present invention can be usually obtained from optically active K- 252a as the starting compound, but ail possible stereoisomers and their mixtures are also within the scope of the present invention In the processes shown below, if the defined groups are converted under the conditions of the processes or are not suitable for carrying out the processes, the desired compounds can be obtamed by employing means for mtroducQon or elimination of protective groups conventionally used m organic synthetic chemistry [See, e.g. T.W. Greene, Protective Groups m Organic Synthesis, John Wiley & Sons Inc. (1981)] Oxidation, reduction, addition, elimination, condensation, or hydrolysis, which is conventionally used in organic synthetic chemistry, may be earned out and if necessary, the order of the reaction steps for the introduction of substituents, and the like, may be vaπed Further, conversion of the functional groups may be earned out more than one time Process 1 Compound (1-1), i.e , Compound (I) wherem at least one of R 1 and R 2 is -CO(CH2)jR 4 (wherem j and R 4 have the same significances as defined above), can be prepared accordmg to the following reaction steps Fig. 4 [In the formulae, R^, w', 2 , X and Y have the same significances as defined above, and at least one of R* a and R 2a is -CO(CH2) j R 4 (wherem j and R 4 have the same significances as defined above) ] Step 1-1: Compound (I-la), ι e , Compound (1-1) wherem R 4 is halogen, can be obtamed by subjecting Compound (IT) which is a known compound descπbed below to the Fπedel-Crafts reaction with Compound (TH) represented by formula (HI) R 4j 4CH2) j C0-Hal (III) (wherem j has the same significance as defined above, R 4a is halogen as defined above, and Hal is chloπne or bromme) or acryloyl.chlonde in a solvent such as methylene chlonde and chloroform in the presence of a Lewis acid such as aluminum chlonde Compound (HI) and the Lewis acid are respectively used in an amount of 1 to 20 equivalents based on Compound (H) The reaction is usually earned out at 0 to 80°C for 1 to 24 hours The starting Compound (H) can be prepared according to the processes disclosed m Japanese Published Unexamined Patent Applications Nos. 295588/88, 295589/88 and 807045/88 ?tep 1-2: Compound (I-lb), i.e., Compound (1-1) wherein R 4 is NR 5 R 6 (wherem R 5 and R 6 have the same significances as defined above), N3, OR 29 (wherein R 29 has the same significance as defined above) or SR 7 _(whereιn R 27 has the same significance as defined above) can be obtamed by subjecting Compound (I- 1 a) to reaction with a metallic salt of Compound (TVa) represented by formula (TVa): HNR 5 R 6 (TVa) (wherem R 5 and R 6 have the same significances as defined above), sodium azide, Compound (TVb) represented by formula (Ivb) R 29 OH (TVb) (wherem R 29 has the same significance as defined above), or Compound (TVc) represented by formula (Ivc) R 27 SH (TVc) (wherem R 27 has the same significance as defined above) in a solvent such as methylene chloride, chloroform, d i methylsulfoxide or N,N-dιmethylformamide, or reaction with Compound (TVa), (TVb) or (TVc) in the presence of a base such as potassium carbonate and tπethylamine. Compound (TVa), sodium azide, Compound (TVb), Compound (TVc) or.a metallic salt thereof is used m an amount of 1 equivalent to excess amount based on Compound (I-la), preferably 1 to 20 equivalents based on Compound (I-la). A base is used m an amount of 1 to 20 equivalents. The reaction is usually earned out at 0 to 100°C for 1 to 24 hours Process 2 Compound (1-2), i.e., Compound (I) wherein at least one of R 1 and R 2 is - CH=CH(CH2)mR 12 (wherem m and R* have the same significances as defined above) or - CH=C(C02R 33A )2 (wherem R 33A has the same significance as defined above) can be prepared accordmg to the following reaction steps: Fig.5 [In the formulae, R 3 , W*, W 2 , X and Y have the same significances as defined above; at least one of R B1 and R B2 is formyl, hydroxymethyl, halogen or -G»C(CH2)m Rl2 (wherem m and R 12 have the same.significances as defined above); and at least one of R 1 D and R 2b is - CH=CH(CH2)mR (wherem m and R 2 have the same significances as defined above) or - CH=C(C02R 3 A )2 (wherem R A has the same significance as defined above).] Step 2-1 : Compound (1-2) can be obtained by subjecting Compound (Va).where at least one of R and R B2 is formyl to reaction with Compound (Via) represented by formula (Via): (Ph) 3 P=CH(CH2)mR 12 (Via) (wherein m and R' 2 have the same significances as defined above, and Ph is phenyl) in a solvent such as methylene chloride and chloroform. Alternatively, Compound (1-2) can be obtained by subjecting Compound (Va) to reaction with Compound (VIb) represented by formula (VIb). (Ph)3P + CH2(CH2)mR 12 HaJ- (VIb) (wherem m, R 12 , Ph and Hal have the same significances as defined above) m a solvent such as methylene chloride and chloroform m the presence of a base such as potassium carbonate and butyllithium. When a base which has poor solubihty m the solvent e.g. potassium carbonate, is used, the reaction is preferably earned out in the presence of a phase transfer catalyst such as 18- crown-6 Compound (Via), Compound (VIb) and the base are respectively used in an amount of 1 to 20 equivalents based on Compound (Va), and the phase transfer catalyst is used in an amount of 0.01 to 1 equivalent based on Compound (Va). The reaction is usually earned out at -10 to 100°C for 1 to 100 hours. Compound (Va) can be prepared according to the process disclosed in Japanese Published Unexamined Patent Apphcation No. 295588/88. Step 2-2: Compound (1-2) can be obtained by subjecting a phosphonium salt obtained from Compound (Vb) wherem at least one of R B * and R B2 is hydroxymethyl and tπpheπylphosphine hydrobromidc to reaction with Compound (Vic) represented by formula (Vic) R 12 (CH2)mCHO (Vic) (wherein m and R* have the same significances as defined above) in a solvent such as methylene chloride in the presence of a base such as potassium carbonate and butylhthium. Compound (Vb) can be prepared according to the processes disclosed in Japanese Published Unexamined Patent Apphcation No. 295588/88, WO94/02488,etc. When a base which has poor solubihty in the solvent e.g. potassium carbonate, is used, the reaction is preferably earned out m the presence of a phase transfer catalyst such as 18-crown-6. Each of Compound (Vic) and the base is used in an amount of 1 to 20 equivalents based on the phosphonium salt (Vb), and the phase transfer catalyst is used in an amount of 0.01 to 1 equivalent based on the phosphonium salt (Vb). The reaction is usually earned out at -10 to 100°C for 1 to 100 hours. Step 2-3: Compound (1-2) can be obtained by subjecting Compound (Vc) wherem at least one of R * and R 2 is halogen to Heck reaction with Compound (Vld) represented by formula (Vld): H2C=CH(CH2) m R 12 (Vld) (wherem m and R 2 have the same significances as defined above) in a solvent such as N,N- dimethylformamide in the presence of a palladium compound such as palladium (II) acetate and bistπpbenylphosphine paralhum (ϋ) chlonde, a phosphorus compound such as tπphenylphosphine and tπs(2-methylphenyi)phosphιne and a base such as tπethylaπune Based on Compound (Vc), Compound (VΙd)ιs used m an amount of 1 to 40 equivalents, each of the palladium compound and phosphorus compound is used in an amount of 0 1 to 5 equivalents based on Compound (Vc), and the base is used in an amount of 1 to 500 equivalents When the palladium compound used contains a phosphorus compound as a hgand as the case of bιs(tπphenylphosphme)palladιum (II) chlonde, it is sometimes unnecessary to add the phosphorus compound The reaction is usuallv arned out at 0 to 100°C for 1 to 10 hours Step 2-4: Compound (1-2) can be obtained by subjecting Compound (1-3) synthesized accordmg to Step 3 desenbed below to catalytic reduction m a solvent such as N,N-dιmethylformamιde m a stream of hydrogen the presence of a reduction catalyst such as palladium carbon The reduction catalyst is used in an amount of 10 to 100% by weight based on Compound (1-3) The reaction is usually earned out at 0 to 100°C for 1 to 72 hours Step 2-5: Compound (1-2) can be obtamed by subjecting Compound (Va) to reaction with a compound represented by formula (Vie) CH2(C0 2 R 33A ) (Vie) (wherem R • ' A has the same significance as defined above) in a solvent such as chloroform and methylene chlonde m the presence of a base such as pipeπdine Compound (Vie) is used in an amount of 1 to 40 equivalents based on Compound (Va), and the base is used in an amount of 0 1 equivalent based on Compound (Va) to an amount equivalent to the solvent The reaction is usually earned out at 20 to 100 β C for 1 to 24 hours Process 3 Compound (1-3), i.e., Compound (I) wherem at least one of R 1 and R 2 is -CeC(CH2) n R 13 (wherem n and R 13 have the same significances as defined above), can be prepared accordmg to the following reaction steps Fig.6 (VII) (1-3) [In the formulae, R 3 , 1 , W 2 , X and Y have the same significances as defined above; at least one of R C 1 and R C2 is iodine, and at least one of R lc and R 2c is -OC(CH2)nR 13 (wherein n and R 13 have the same significances as defined above).] Step 3: Compound 0-3) can be obtamed by subjecting Compound (VH) to the Sonogasira reaction with Compound (Vrff) represented by formula (VlTf) HC-C(CH2)nR 13 (Vffl) (wherem n and R* 3 have the same significances as defined above) in a solvent such as methylene chloride and chloroform in the presence of a copper compound such as cuprous iodide, a palladium compound such as palladiumfll) acetate and bis(tπphenylphosplune)palladιum(ID chloride, a phosphorus compound such as tnphenyiphosphine, and a base such as diethylamine and tnethylamine Compound (VlTf) is used in an amount of 1 to 40 equivalents based on Compound (VTf), the copper compound, the palladium compound and the phosphorus compound are respectively used in an amount of 0.1 to 5 equivalents, and the base is used in an amount of 1 to 500 equivalents. When the palladium compound contains the phosphorus compound as a hgand as in the case of bis(tnphenyiphosphine)paliadium(IT) chloride, it is not necessary to add the phosphorus compound The reaction is usually earned out at 0 to 100°C for 1 to 10 hours Compound (\TJ) can be obtamed by subjecting Compound (H) to reaction with iodine in a solvent such as methylene chloπde methanol mixture (4/1) in the presence of a mercury compound such as mercunc mtrate and mercunc chlonde The mercury compound and iodine are respectively used in an amount of 1 to 3 equivalents based on Compound (IT) The reaction is usually earned out at 0 to 50°C for 1 to 24 hours Process 4 Compound (1-4), i e , Compound (I) wherem at least one of R 1 and R 2 is -(CH2)kR 7 (wherem k and R 7 have the same significances as defined above) or -CH2CH(Cθ2R 33A )2 (wherem R JJ A has the same significance as defined above), can be prepared accordmg to the following reaction steps ig 7 [In the formulae, R!°, R2b, R lc > R2c t 3^ W 1_ ^2 and Y have the same significances as defined above, and at least one of R lα and R 2α" is -(CH2)kR 7 (wherem k and R 7 have the same significances as defined above) or -CH2CH(Cθ2R 33A )2 (wherem R 33A has the same significance as defined above).] 23 Step 4-1: Compound (1-4) can be obtamed by subjecting Compound (1-2) or Compound 0-3) to catalytic reduction m a solvent such as N,N-dιmethylformamιde m a stream of hydrogen the presence of a reduction catalyst such as 10% palladium/carbon and plutinum oxide The reduction catalyst is used m an amount of 10 to 100% (wt wt) based on Compound (I- 2) or Compound 0-3) The reaction is usually earned out at 0 to 100 β C for 1 to 72 hours Step 4-2: Compound 0-4) can be obtamed by subjecting Compound 0-1) to reaction with alkylsilane such as ethylsilane m tnfiuoroacetic acid . Trifluoroaceuc acid is used in an amount equivalent to a solvent for Compound 0-1), and alkylsilane is used m an amount of 1 to 20 equivalents based on Compound 0-1) The reaction is usually earned out at -10 to 20°C for 1 to 24 hours Process 5 Compound 0-5), I e , Compound 0) wherem either of R* and R 2 is halogen or nitro, can be prepared by subjecting Compound (DC) to the reactions in Steps 1-4 in Processes 1-4 descnbed above Compound (DC) can be prepared according to the processes descnbed in Japanese Published Unexamined Patent Applications Nos 120388/87 and 295588/88 Fig 8 [In the formulae, R 3 , Wl, W 2 , X and Y have the same significances as defined above; either of REI and R" is halogen or nitre and the other is hydrogen; and either of R* e and R e is halogen, mtro or amine, and the other is -CO(CH2)jR 4 (wherein j and R 4 have the same significances as defined above), -(CH2) R 7 (wherem k and R 7 have the same significances as defined above), - CH=CH(CH2)mR (wherem m and R* 2 have the same significances as defined above), - CH=C(C02R 3 )2 (wherem R 3B has the same significance as defined above) or - C β C(CH2)n (wherem n and R! 3 have the same significances as defined above) ] Process 6 Compound (1-6), i e , Compound 0) wherem either of R 1 and R 2 is NR1 4 R 15 (wherem R 14 and R 15 have the same significances as defined above), and the other is -CO(CH2)jR 4 (wherem j and R 4 have the same significances as defined above), -(CH2)kR 7 (wherem k and R 7 have the same significances as defined above), -CH=CH(CH2)mR 12 (wherem m and Rl 2 have the same significances as defined above), -CH=C(C02R 33A )2 (wherem R 33A has the same significance as defined above) or -OC(CH2)nR 13 (wherem n and R 13 have the same significances as defined above), can be prepared from Compound 0-5) wherem either of R* e and R 2e is nitro according to the process descnbed in Japanese Published Unexamined Patent Apphcation No. 295588/88 Process 7 Compound b), i.e., Compound 0) wherein R 3 is hydrogen, can also be prepared from Compound 0a), i.e., Compound 0) wherem R 3 is acyl as defined above, according to the process described m Japanese Published Unexamined Patent Apphcation No 295588/88 Process 8 Compound 0-7), i.e.. Compound (I) wherein at least one of R^ and R 2 is - CH(OH)(CH2)bR A (wherem b and R 4A have the same significances as defined above) can be obtamed by reduction of a compound which can be synthesized accordmg to the above Step 1-1 or 1-2, for example, reaction with a reducmg agent such as sodium borohydride a solvent such as methanol and methanol/chloroform The reducmg agent is used in an amount of 1 to 20 equivalents based on the raw ateπal. The reaction is usually carried out at -10 to 50°C for 0.5 to 24 hours Process 9 Compound 0-8), i e.. Compound 0) wherem either of R^ and R 2 is formyl, and the other is -<CH2)kR 7 (wherem k and R 7 have the same significances as defined above), -CH=CH(CH2)mR 2 (wherem m and R! 2 have the same significances as defined above), or -C-»C(CH2)nR (wherem n and R' 3 have the same significances as defined above), can be prepared accordmg to Processes 2 to 4 after formyiation of K-252a denvative (which can be prepared accordmg to the process descnbed in Reference Examples) wherem either of R^ and R 2 is hydrogen and the other is bromme or iodine or both R' and R 2 are bromine or iodine Process 10 Compound 0-9), I e , Compound 0) wherem either of R 1 and R 2 is -CH(SR 3 )2 (wherem R 34 has the same significance as defined above), and the other is -(CH2)kR 7 (wherem k and R 7 have the same significances as defined above), -CH*CH(CH2)mR 12 (wherem m and R 12 have the same significances as defined above), or -C«C(CH2)nR 13 (wherem n and R 13 have the same significances as defined above), can be obtamed by subjecting Compound 0-8) to reaction with Compound (X) represented by formula (X) R 34 SH (X) (wherem R 34 has the same significance as defined above) m the presence of an acid catalyst such as BF3 OEt2 Each of Compound (X) and the acid catalyst is used in an amount of 1 to 20 equivalents based on Compound 0-8) The reaction is usually earned out at 0 to 80°C for 1 to 24 hours ProcβBB 11 Compound 0-10), i.e., Compound (I) wherem either of R 1 and R 2 is -CH2R 35A (wherem R35A h s the same significance as R 35 except tri-lower alkylsilyloxy), and the other is -(CH2)kR 7 (wherem k and R 7 have the same significances as defined above), -CH=CH(CH2)mR 12 (wherem m and R 12 have the same significances as defined above), or -C-C(CH2)nR 13 (wherem n and R 3 have the same significances as defined above), can be obtamed by reduction of Compound 0-9) with a reducmg agent such as soώum borohvdride to form a compound wherem either of R' and R 2 is - CH2OH, and then reaction with Compound (XT) represented by formula (XT) 27 SH (XI) (wherem R 27 has the same significance as defined above) or Compound (XII) represented by formula (XIT) R 29 OH (XT!) (wherem R 29 has the same significance as defined above) in the presence of an acid catalyst such as camphorsulfomc acid The acid catalyst is used m an amount of 0 1 to 5 equivalents base on Compound 0-9), and Compound (XT) or (XH is used m an amount of 1 to 20 equivalents based on Compound 0-9) The reaction is usually earned out at 0 to 80 β C for 1 to 100 hours Conversion of the functional groups in the substituents R 1 and R 2 may be earned out accordmg to the above steps or by known methods [see, e g R.C Larock, Comprehensive Organic Transformations (1989)] For example, conversion of the functional groups can be earned out by reacting Compound (I) containing a leaving group (e g , chloπne, bromme, iodine or sulfonyloxy such as methylsulfonyoxy, tπfluoromethanesulfonyloxy and p-toluenesulfonyloxy) R 1 or R 2 with a nucleophihc reagent such as amine, alcohol, thiol and azide in the presence of a base such as pottasium carbonate to give new Compound (T) Alternatively, when Compound 0) contains an azide groups R* or R 2 , the functional groups can be converted mto ammo groups by using a reducmg agent such as tπphenylphosphine, or the ammo groups can be reacted with lower alkyl isocyanate or di-lower alkyl carbonate to obtain an urea denvative or carbamate The desired compounds m the processes descnbed above can be isolated and punfied by appropπate combinations of purification methods conventionally used m organic synthetic chemistry, for example, filtration, extraction, washing, drymg, concentration, crystallization, and vanous lands of chromatography The intermediates may be subjected to the subsequent reaction without purification There may be stereoisomers such as geometrical isomers and optical isomers for Compound (I), and the present invention covers all possible isomers and their mixtures m any proportions k ώe case where a salt of Compound 0) « desired and it is produced m the form of the desired salt it can be subjected to purification as such In the case where Compound (J) is produced in the free state and its salt is desired, Compound 0) is dissolved or suspended m a suitable solvent followed by addition of an acid to form a salt Compound (l) and pharmaceutically acceptable salts thereof may be m the form of adducts with water or vanous solvents, which are also within tie scope of the present invention Examples of Compound 0) are shown m Table 1 and the mtermediates are shown Table 2 Table 1 (1) Table 1(2) Pyr * Pyridyi Table 1(3) Pip = Pipeπdine Moφh = Moφholine Table 1(4) Table 1(5) Compound ~ W Table 1(6) Table 1(7) Table 1(8) (Benz)lmιd = Benzimidazole Table 1(9) The C0 2 CH 3 group is replaced with CH 2 OH. Tab.2 Table 2 EXAMPLES Certain embodiments of the invention are illustrated in the following Examples and Reference Examples Compounds a-e and g which are known compounds used as the starting compounds are descnbed in Japanese Published Unexamined Patent Apphcation No. 295588/88 Compounds f and h are descnbed in WO94/02488 The structures are shown below m Figure 9 Fig . 9 Exam p le 1 Synthesis of Compound 1 Step A: To a solution of 50 0 mg (0.0824 mmol) of Compound a (Japanese Published Unexamined Patent Application No 295588/88) m 5 ml of chloroform was added 198 mg (0.592 mmol) of methyl(tπphenylphosphoranyhdene)acetate, followed by stirring under reflux for 4 hours After cool i ng, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column ch j omatography (chloroform/methanol = 98 2) to give diacetylated Compound 1 FAB-MS (m/z) , 720 (M+l) + Step B: 5 To a solution of 71.0 mg of diacetylated Compound 1 in a mixture of 4 mi of 1 ,2- dichloromethane and 1 ml of methanol was added 18 ml (0.09 mmol) of 5.1 N sodium methoxidc methanol solution, and the mixture was stirred at room temperature for 30 mmutes. The react i on mixture was poured into water, followed by extraction with tetrahydrofuran. The organic layer was washed with a saturated aqueous soluuon of sodium chloride and dπed over magnesium j 0 sulfate After evaporation of the solvent under reduced pressure, the residue was crystallized from chloroform-methanol to give 16 3 mg (yield from Compound a: 31%) of Compound 1. iH-NMR (DMSO-d6) δ, 2 04 (dd, 1H, J - 4.9, 14.1 Hz), 2.12 (s, 3H), 3.42 (dd, 1H, J = 7.5, 14.1 Hz), 3 77 (s, 6 H), 3.93 (s, 3H), 5.10 (s, 2H),6 43 (s, 1H), 6.59 (d, 1H, J 15 = 15.9 Hz), 6.78 (d, 1H, J - 15.9 Hz), 7.21 (dd, 1H, J - 4.9, 7.5 Hz), 7.85 (d, 1H, J = 15.9 Hz), 7.95 (d, 1H, J =15.9 Hz), 7.88 - 8 00 (m, 4 H), 8 40 (d, 1H, J = 1.2 Hz), 8 79 (s, 1H), 9.48 (d, 1H, J = 1.7 Hz) FAB-MS (m z) ; 636 (M+l) + 20 Exam p le 2 Synthesis of Compound 2 The same procedure as in Example 1, Step A was repeated usmg 55.7 mg (0.0962 mmol) of Compound b (Japanese Published Unexamined Patent Apphcation No 295588/88) and 92.1 mg (0.264 mmol) of ethyl(tnphenylphosphoranylidene)acetate to give diacetylated Compound 2. 5 FAB-MS (m/z) ; 650 (M+l) + The same procedure as in Example 1, Step B was repeated using diacetylated Compound 2 to give 27.5 mg (yield from Compound b: 51%) of Compound 2. -NMR (DMSO-d 6 ) δ; 1.31 (t, 3H, J = 7.1 Hz), 2.05 (dd, IH, J - 4.9, 14.1 Hz), 2.15 (s, 3H), 3 . 41 (dd, IH, J = 7.3, 14.1 Hz), 3.93 (s, 3H), 4.23 (q, 2H, J = 7.1 Hz), 5.00 (d, IH, J = 1 .5 Hz), 5.06 (d, IH, J - I7.5Hz), 6.36 (s, IH), 6.56 (d, IH, J = 15.9 Hz), 7.19 (dd, IH, J - 4.9, 7.3 Hz), 7.84 (d, IH, J = 15.9 Hz), 7.36 - 8.08 (m, 6 H), 8.69 (s, IH), 9 . 47 (d, lH, J - 1.5 Hz). FAB-MS (m z) ; 565 (M) + , 566 (M+l) + Exam p le 3 Synthesis of Compound 3 The same procedure as in Example 1, Step A was repeated using 50.0 mg (0.0824 mmol) of Compound a and 225 mg (0.645 mmol) of ethyl (triphenylphosphoranyUdene)acetate to give diacetylated Compound 3. FAB-MS (m z) ; 747 (M) + , 748 (M+l) + The same procedure as in Example 1, Step B was repeated using diacetylated Compound 3 to give 29.7 mg (yield from Compound a: 54%) of Compound 3 -NMR (DMSO i6) δ; 1.31 (t, 6 H, J - 7.1 Hz), 2.04 (dd, IH, J = 4.9, 14.2 Hz), 2.15 (s, 3H), 3.42 (dd, IR J = 7.4, 14.2 Hz), 3.93 (s, 3H), 4.23 (q, 2H, J = 7.1 Hz), 4.23 (q, 2H, J = 7 1 Hz), 5.10 (s, 2H), 6.43 (s, IH), 6.58 (d, IH, J = 15.9 Hz), 6.77 (d, IH, J = 16.0 Hz), 7.21 (dd, IH, J = 4.9, 7.4 Hz), 7.83 (d, IH, J = 15.9 Hz), 7.93 (d, IH, J = 16.0 Hz), 7.88 - 8.00 (m, 4 H), 8.40 (d, IH, J - 1.5 Hz), 8.78 (s, IH), 9.47 (d, lH, J = i .6 Hz). FAB-MS (m z) ; 664 (M+l) + Exam p le 4 Synthesis of Compound 4 The same procedure as in Example 1, Step A was repeated using 50.0 mg (0.0824 mmol) of Compound b and 104 mg (0.311 mmol) of methyl (triphenylphosphoraπylidene)-acetate to give diacetylated Compound 4 FAB-MS (m z) , 636 (M+l) + The same procedure as in Example 1, Step B was repeated usmg diacetylated Compound 4 o give 14 6 mg (yield from Compound b 31%) of Compound 4 !H-NMR (DMSO-d6) δ, 2 05 (dd, IH, J = 4 9, 14 2 Hz), 2 15 (s, 3H), 3 41 (dd, IH, J = 7 5, 14 2 Hz), 3 77 (s, 3 H), 3.93 (s, 3H), 5 00 (d, IH, J = 17 6 Hz), 5 06 (d, IH, J = 17 6 Hz), 6 36 (s, IH), 6 59 (d, IH, J = 15 8 Hz), 7 19 (dd, IH, J = 4 9, 7 5 Hz), 7 85 (d, IH, J = 15 8 Hz), 7 36 - 8 08 (m, 6 H), 8 70 (s, IH), 9 47 (d, IH, J = 1 5 Hz) FAB-MS (m/z) , 552 (M+l) + Exam p le 5 Synthesis of Compound 5 To a solution of 215 mg (0 553 mmol) of benzyltnphenylphosphomum chlonde in 2 ml of dichloromethane were added 165 mg (1 19 mmol) of potassium carbonate and 12 mg (0 045 mmol) of 18-crown-6, followed by stirring at room temperature for 5 minutes After addition of a solution of 80 0 mg (0 138 mmol) of Compound b in 8 ml of dichloromethane, the mixture was stirred overmght at room temperature Insoluble matenals m the reaction mixture were filtered off, and the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (chloroform) and then by preparative TLC (chloroform/methanol = 99/1) to give 80 0 mg (89%) of diacetylated Compound 5 FAB-MS (m/z) , 564 (M+l) + The same procedure as in Example 1, Step B was repeated usmg 80 0 mg (0 123 mmol) of diacetylated Compound 5 to give 26 1 mg (37%) of Compound 5 (E/Z = 3/7) -NMR (DMSO-d6) δ, 2 00 - 2 57 (m, IH), 2 13 (s, 2 IH), 2 14 (s, 0 9H), 3 37 (dd, 0 7H, J = 7 5, 14 2 Hz), 3 40 (dd, 0 3H, J = 7 6, 13 7 Hz),3 90 (s, 2 IH), 3 92 (s, 0 9H), 4 93 - 5 60 (m, 2H), 6 33 (s, 0 7H), 6 34 (s, 0 3H), 6 621 (d, 0 7H, J = 12 4 Hz), 6.849 (d, 0.7H, J = 12.4 Hz), 7.072 (dd, 0.7H, J - 4.9, 7.5 Hz), 7.132 - 8 064 (m, 11.9H), 8.58 (s, 0.7H), 8.63 (s, 0.3H), 9.15 (m, 0 7H), 9.38 (d, 0.3H, J = 1 7 Hz) FAB-MS (m/z) ; 570 (M+l) + Example 6 Synthesis of Compound 6 The same procedure as in Example 5 was repeated using 250 mg (0.643 mmol) of benzyltnphenylphosphonium chloride and 50.0 mg (0.0824 mmol) of Compound a to give 63.5 mg of diacetylated Compound 6 FAB-MS (m/z) ; 756 (M+l) + The same procedure as in Example 1, Step B was repeated using 63.5 mg (0.0841 mmol) of d i ace t ylated Compound 6 to give 49.9 mg (yield from Compound a: 90%) of Compound 6 (Rl, R2 cis, trans / Rl, R^ : CU! , C1S R l R 2 : ^^^ cis , R l ( R 2. tranS) XnBS = j imil) 1H-NMR (DMSO-d6) δ, 1.99 - 2.08 (m, IH), 2.10, 2.12, 2.15, 2.17 (4xs, 3H), 3.35 - 3 45 (m, IH), 3.89, 3.92, 3.92, 3.93 (4xs, 3H), 4.50 - 5.03 (m, 2H), 6.35, 6.36, 6.40, 641 (4xs, IH), 6.61 - 8.23 (m, 20H), 8.59, 8.57, 8 67, 8 72 (m, IH), 9.13, 9 17, 9-36, 9 40 (m, IH) FAB-MS (m/z) ; 672 (M+l) + Example 7 Synthesis of Compound 7 The same procedure as in Example 5 was repeated using 61.8 mg (0 142 mmol) of 2- pynd i nemethyl-tnphenylphosphonium bromide and 26.5 mg (0.0458 mmol) of Compound b to give 47.3 mg of diacetylated Compound 7. FAB-MS (m/z) ; 655 (M+l) + The same procedure as in Example 1, Step B was repeated using 47.3 mg of diacetylated Compound 7 to give 13.3 mg (yield from Compound b: 51 ) of Compound 7 1H-NMR (DMSO-d6) δ, 2.05 (dd, IH, J = 5.0, 14.1 Hz), 2.16 (s, 3H), 3.42 (dd, IH, J = 7.3, 14.1 Hz), 3.94 (s, 3H), 5.00 (d, IH, J = 18.0 Hz), 5.06 (d, IH, J = 18.0 Hz), 6.35 (s, 1 H), 7.17 (dd, IR J = 5.0, 7.3 Hz),7.23 - 7.97 (m, 8 H), 7.30 (d, IH, J = 16.0 Hz), 7.89 (d, IH, J = 16.0 Hz), 8.07 (d, IH, J = 7.3 Hz), 8.59 (m, IH), 8.67 (s, IH), 9 46 (d, lH, J = 1.2 Hz). FAB-MS (m/z) ; 571 (M+l) + Example 8 Synthesis of Compound 8 The same procedure as in Example 5 was repeated using 244 mg (0.561 mmol) of 2- pyridmemethyl-tπphenylphosphonium bromide and 50.0 mg (0.0824 mmol) of Compound a to give 75.3 mg of diacetylated Compound 8. FAB-MS (m z) ; 757 (M) + The same procedure as in Example 1, Step B was repeated using 75.3 mg of diacetylated Compound 8 to give 22.6 mg (yield from Compound - 41%) of Compound 8 iH-NMR (DMSO-d6) δ; 2.06 (dd, IH, J = 5.0, 14.4 Hz), 2.18 (s, 3H), 3 43 (dd, IH, J = 7.6, 14.4 Hz), 3.95 (s, 3H), 5.08 - 5.17 (m, 2H), 6.42 (s, 1 H), 7.19 (dd, IH, J = 5.0, 7.6 Hz), 7.30 (d, IH, J = 16.0 Hz), 7.42 (d, IH, J = 16.0 Hz), 7.22 - 9 46 (m, 17 H). FAB-MS (m/z) ; 674 (M+l) + Exam p le 9 Synthesis of Compound 9 To a soluuon of 36.9 mg (0.0550 mmol) of Compound 6 in 4 ml of N,N- dimethylformarmde was added 25 mg of 10% Pd/C, followed by stimng at 60°C for 2 houπ m an atmosphere of hydrogen. After insoluble materials in the reacuon mixture were filtered off, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform) to give 31.1 mg (84%) of Compound 9. !H-NMR (DMSO-d6) δ; 1.98 (dd, IH, J = 5.1, 14.1 Hz), 2.12 (s, 3H), 2.99 - 3.14 (m,8H), 3.36 (dd, IH, J = 7.5, 14.1 Hz), 3.92 (s, 3H), 4.92 (d,lR J = 17.6 Hz), 4.97 (d, IR J = 17.6 Hz), 6.28 (s, 1 H), 7.08 (dd, IR J = 5.1, 7.5 Hz), 7.17 - 7.38 (m, 12 H), 7.78 - 7.84 (m, 3H), 8.59 (s, IH), 9.09 (m, IH). FAB-MS (m/z) ; 676 (M+l) + Exam p le 10 Synthesis of Compound 10 The same procedure as in Example 9 was repeated using 43.6 mg (0.0766 mmol) of Compound 5 to give 24.2 mg (55%) of Compound 10. -NMR φMSO-i δ; 2.00 (dd, IR J = 4.9, 14.1 Hz), 2.15 (s, 3H), 2.99 - 3.11 (m, 4 H), 3.37 (dd, IR J = 7.3, 14.1 Hz), 3.92 (s, 3H), 4.97 (d, IR J - 17.9 Hz), 5.03 (d, IR J = 17.9 Hz), 6.32 (s, 1 H), 7.10 (dd, IR J = 4.9, 7.3 Hz), 7.17 - 8.06 (m, 11 H), 8.58 (s, lH), 9.11 (m, lH). FAB-MS (m/z) ; 572 (M+l) + Exam p le 11 Synthesis of Compound If The same procedure as in Example 9 was repeated using 15.0 mg (0.0223 mmol) of Compound 8 to give 9.8 mg (65%) of Compound 11. iH-NMR (CDCI3) δ; 2.19 (s, 3H), 2.42 (dd, IR J = 4.8, 14.4 Hz), 3.21 - 3.29 (m, 8H), 3 -31 (dd, IR J = 7.5, 14.4 Hz), 4.08 (s, 3H), 4.19 (br, lH), 4.83 (d, IR J = 16.2 Hz), 4.88 (d, IR J = 16.2 Hz), 5.98 (s, 1 H), 6.84 (dd, IR J - 4.8, 7.5 Hz), 7.11 - 7.33 (m, 7 H), 7.56 - 7.62 (m,2H), 7.68 (s, IH), 7.73 (d, IR J = 8.6 Hz), 8.58 - 8.61 (m, 2H), 9.08 (m, IH). FAB-MS (m z) ; 678 (M+l) + Example 12 Synthesis of Compound 12 The same procedure as in Example 1, Step A was repeated using 25.0 mg (0.0432 mmol) of Compound C obtained in Reference Example 3 and 52.0 mg (0.156 mmol) of ethyl (tπphenylphosphoraπyhdene)acetate to give 17.2 mg (63%) of diacetylated Compound 12 FAB-MS (m/z) ; 650 (M+l) + The same procedure as in Example 1, Step B was repeated using diacetylated Compound 12 to give 8.1 mg (54%) of Compound 12. !H-NMR (DMSO-d6) δ, 1.31 (t, 3 R J = 7.1 Hz), 2.00 (dd, IR J - 4.9, 14 1 Hz), 2.15 (s, 3H), 3.41 (dd, IR J = 7.3, 14.1 Hz), 3.93 (s, 3H), 4.23 (q, 2R J = 7.1 Hz), 5.08 (s, 2H), 6 41 (s, IH), 6.76 (d, IR J = 15.9 Hz), 7.16 (dd, IR J = 4.9, 7.3 Hz), 7.93 (d, IR J -= 15.9 Hz), 7.28 - 7.96 (m,4H), 8.39 (s, IH), 8.71 (s, IH), 9.23 (d, IR J = 7.8 Hz) FAB-MS (m/z) ; 566 (M+l) + Exam p le 13 Synthesis of Compound 13 The same procedure as in Example 5 was repeated using 118 mg (0.855 mmol) of 2- pyridmemetbyl-tnphenyiphosphonium bromide and 39.6 mg (0.0684 mmol) of Compound C obtamed in Reference Example 3 to give diacetylated Compound 13 FAB-MS (m/z) ; 655 (M+l) + The same procedure as in Example 1, Step B was repeated usmg diacetylated Compound 13 to give 30.0 mg (yield from Compound C: 77%) of Compound 13 (E/Z = 8/2). tø-NMR (DMSO-dβ) δ, 2.02 (dd, IR J = 4.9, 14.1 Hz), 2.13 (s, 0.6H), 2.17 (s, 2.4H), 3.41 (dd, IR J - 7.3, 14.1 Hz), 3.92 (s, 0.6 H), 3.94 (s, 2.4H), 5.03 (d, 0.8R J = 18 8 Hz), 5 13 (d, 0.8R J - 18 8 Hz), 6.35 (s, 0.2H), 6 39 (s, 0 8 H), 6.69 (d, 0.2R J = 12.9 Hz), 6 98 (d, 0.2R J = 12.9 Hz), 7 15 (dd, IR J - 4.9, 7.3 Hz), 7.24 - 7 97 (m, 8 H), 7.42(d, 0.8R J - 16.0 Hz), 7.96 (d, 0.8R J = 16.0 Hz), 8.23 (s, 0.2H), 8 30 (s, 0.8H), 8.60 (m, IH), 8 70 (s, IH), 9.18 (d, 0.2R J = 7 8 Hz), 9.23 (d, 0 8R J =7 8 Hz) FAB-MS (m/z) , 571 (M+l) + Exam p le 14 Synthesis of Compound 14 The same procedure as in Example 9 was repeated using 19 9 mg (0 0349 mmol) of Compound 13 to give 16 4 mg (82%) of Compound 14. RNMR (CDCI3) δ, 1.99 (dd, IR J = 4 9, 14.2 Hz), 2.13 (s, 3H), 3 16 - 3.24 (m, 4H), 3.38 (dd, IR J = 7.4, 14.2 Hz), 3.92 (s, 3H), 4.30 (d, IR J - 17 4 Hz), 4 98 (d, IR J - 17 4 Hz), 6.29 (s, 1 H), 7.12 (dd, IR J - 4 9, 7 4 Hz), 7.21 - 7 89 (m, 9H), 8.55 (m, IH), 8 61 (s, IH), 9.21 (d, IR J = 7.6 Hz) FAB-MS (m/z) , 573 (M+l) + Exam p le 15 Synthesis of Compound 15 The same procedure as in Example 5 was repeated usmg 144 mg (0.331 mmol) of 2- pynd i nemethyl-tnphenylphosphotuum bromide and Compound E obtained in Reference Example 5 to give 36.3 mg (yield from Compound D 62%) of Compound 15 (E Z = 9/1) 1H-NMR (CDCI3) δ, 1 81 (s, 0.3H), 1 84 (s, 2.7H), 2.25 (dd, IR J = 5.2, 14 7 Hz), 2.29 (s, 0 3H), 2.33 (s, 2.7H), 2.65 (s, 2.7H), 2 68 (s, 0.3H), 4 01 (s, 0 3H), 4 04 (s, 2.7H), 4 07 (dd, IR J = 7.6, 14 7 Hz), 5.08 (m, 0.2H), 5.34 (m, 1 8H), 6 81 (d, 0.1R J = 12.6 Hz), 6 98 (dd, 1RJ = 5.2, 7.6 Hz), 7 19 (m, IH), 7.32 (d, 0.9R J = 16 1 Hz), 7.87 (d, IR J - 16.1 Hz), 7 95 (d, IR J = 8 8 Hz), 8 13 (m, IH), 8 35 (m, IH), 8 66 (m, IH), 9.93 (m, IH). FAB-MS (m/z) . 700 (M+l) + Example 16 Synthesis of Compound 16 The same procedure as in Example 1, Step B was repeated usmg 33 1 mg (0 0474 mmol) of Compound 15 to give 24 5 mg (84%) of Compound 16 (E/Z = 9/1) FAB-MS (m/z) , 616 (M+ 1 ) + iH-NMR (DMSO-d6) δ, 2 13 (dd, IR J - 5 0, 14 3 Hz), 2 18 (s, 3H), 3 47 (dd, IR J = 7.5, 14 3 Hz), 3 93 (s, 0 3 H), 3.95 (s, 2 7H), 5.13 (d, 0.9R J = 18 1 Hz), 5 18 (d, 0 9R J = 18 1 Hz), 6 45 (s, 0.1 H), 6 49 (s, 0.9 H), 6 71 (d, 0.1R J - 12.6 Hz), 6 99 (d, 0 IR J = 12.6 Hz), 7.30 (dd, IR J - 5.0, 7.5 Hz), 7.24 - 8 60 (m, 9 H), 7 43 (d, 0.9R J = 16 0 Hz), 7.96 (d, 0.9R J = 16.0 Hz), 8 74 (s, 0 IH), 8.88 (s, 0.9H), 10 14 (d, 0.1R J = 2 4 Hz), 10.17 (d, 0.9R J = 2 4 Hz) Example 17 Synthesis of Compound 17 Compound 15 (133 mg, 0 190 mmol) was subjected to catalytic reduction in the same manner as in Example 9 to give 93.2 mg (73%) of Compound 17 -NMR (DMSO-d6) δ, 1.68 (s, 3H), 2.09 (dd, IR J « 4 9, 14 6 Hz), 2.18 (s, 3H). 2.71 (s, 3H), 3.15 - 3.21 (m, 2H), 3.82 (dd, IR J = 7 4, 14 6 Hz), 3.93 (s, 3H), 4 97 (br, 2H), 5 35 (s, 2H), 7.11 (dd, IR J - 4 2,7 4 Hz), 6 90 - 7 87 (m, 8H), 8 32 (d, lR J = 2 2 Hz), 8 55 (m, IH) FAB-MS (m/z) , 672 (M+l) + Exam p le 18 Synthesis of Compound 18 The same procedure as in Example 1, Step B was repeated using 23.6 mg (0.0352 mmol) of Compound 17 to give 16.3 mg (79%) of Compound 18. FAB-MS (m/z) ; 588 (M+l) + Exam p le 19 Synthesis of Compound 19 To a solution of 66.2 mg (0.0987 mmol) of Compound 17 in 4 ml of chloroform were added 0.02 ml of triethylamine and 0.1 ml of ethyl isocyanate, followed by stimng at room temperature for 10 2 hours. After addition of water, the reaction mixture was extracted with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform/methanol = 99/1 - 98/2) to give 68.7 mg (94%) of diacetylated Compound 19. 15 FAB-MS (m/z) ; 743 (M+l)+ The same procedure as in Example 1, Step B was repeated using 25.5 mg (0.0344 mmol) of diacetylated Compound 19 to give 17.7 mg (78%) of Compound 19 20 lH-NMR (DMSO-d6) δ, 1.08 (t, 3R J = 7.1 Hz), 1.94 (dd, IR J = 4.6, 14.1 Hz), 2.11 (s, 3H), 3.10 - 3.22 (m, 4H), 3.34 (dd, IR J = 7.2, 14.1 Hz), 3.90 (s, 3H), 4.90 (d, IR J = 17.5 Hz), 4.96 (d, IR J = 17.5 Hz),6.00 (t, IR J = 5.4 Hz), 6.26 (s, IH), 7.03 (dd, IR J = 4.6, 7.2 Hz),7.22 - 7.86 (m, 8 H), 8.43 (s, IH), 8.55 (m, IH), " 8 58 (s, IH), 8.84 (d, IR J = 2.2 Hz). FAB-MS (m/z) ; 659 (M+l) + Exam p le 20 Synthesis of Compound 20 To a solution of 40 mg (0.05 mmol) of Compound F obtained in Reference Example 6 in 3 30 ml of a mcWoromethane/memylamine mixture (2/1) were added 26 mg (0.025 mmol) of palladιum(ll) acetate, 13 mg (0 05 mmol) of tnphenylphosphme and 9.5 mg (0 05 mmol) of cuprous iodide in a stream of argon, followed by stimng at room temperature for 10 minutes After addition of 0 16 ml (1.5 mmol) of N,N-dιmethylpropargylamιne, the mixture was stirred at room temperature for one hour The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (chlorofoim/methanol ■ 96/4) to give 15 1 mg (42%) of diacetylated Compound 20 FAB-MS (m/z) , 714 (M+l) + The same procedure as in Example 1, Step B was repeated usmg 6 5 mg (0 0091 mmol) of diacetylated Compound 20 to give 2 0 mg (35%) of Compound 20 IH-NMR (CDCI3) δ , 2 14 (s, 3H), 2.46 (s, 6H), 2.48 (s, 6H), 3 05 (dd, IR J = 4.5, 14 4 Hz), 3 55 (s, 2H), 3.56 (s, 2H), 3.62 (dd, IR J = 7.5,14 4 Hz), 4 08 (s, 3H), 4.54 (d, IR J = 16 9 Hz), 4 70 (d, IR J = 16.9 Hz), 5.33 (m, 2H), 6.76 (dd, IR J - 4.5, 7.5 Hz), 7 15 (d, IR J - 8.5 Hz), 7.34 (dd, IR J = 1.3, 8 5 Hz), 7.61 (dd, IR J = 1.3, 8.5 Hz), 7 91 (d, IR J = 8 8 Hz), 7 96 (d, IR J = 0 97 Hz), 8 85 (s, IH) FAB-MS (m/z) , 630 (M+l) + Exam p le 21 Synthesis of Compound 21 and Compound 22 A mixture of 2 2 mg (0 01 mmol) of palladium(II) acetate, 5 0 mg (0 02 mmol) of tnphenylphosphme and 1 ml of dichloromethane was stirred at room temperature for 5 mmutes in a stream of argon To the mixture was added a soluuon of 72 mg (0.1 mmol) of Compound G obtamed in Reference Example 7 and 3 8 mg (0.02 mmol) of cuprous iodide m 3 ml of a dichloromethane/diethylarrune mixture (2/1), followed by stimng at room temperature for 10 mmutes After addition of 0.056 ml ( 1 mmol) of l-methoxy-2-propyne, the mixture was stirred at room temperature for 1.5 hours The solvent was evaporated under reduced pressure, and the residue was puπfied by silica gel column chromatography (chloroform) to give 23 0 mg (38%) of Compound 21 and 2.6 mg (4 3%) of Compound 22 Compound 21 1 H-NMR (CDCI3) δ , 2.15 (s, 3H), 3 13 (dd, IR J = 4 5, 14 7 Hz), 3 57 (s, 3H), 3 79 (dd, IR J = 7 7, 14 7 Hz), 4 09 (s, 3H), 4 46 (s, 2H), 4.53 (d, IR J = 6 6 Hz), 4 58 (d, IR J = 6 6 Hz), 5 1 1 (s, IH), 5 69 (s,lH), 6 77 (dd, IR J = 4 5, 7 7 Hz), 7 10 (d, IR J = 8 6 Hz), 7 46 (dd, IR J = 1 7, 8.3 Hz), 7.63 (dd, IR J = 1 5, 8.5 Hz), 7 92 (d, IR J =8 8 Hz), 7 98 (d, IR J = 1 2 Hz), 8 83 (d, IR J = 1 5 Hz) FAB-MS (m/z) , 703 (M+l) + Compound 22 iH-N R (CDCI3) δ , 2 15 (s, 3H), 2 95 (dd, IR J = 4 9, 14 7 Hz), 3 54 (s, 3H), 3 55 (s, 3H), 3 60 (dd, IR J = 7 6, 14 7 Hz), 4 09 (s, 3H), 4 42 (s, 2H), 4 45 (s, 2H), 4 53 (d, IR J = 17 0 Hz), 4 70 (d, IR J = 17 0 Hz), 5.19 (br, IH), 5 32 (br, IH), 6 78 (dd, IR J = 4 9, 7 6 Hz), 7.20 (d, IR J = 8 3 Hz), 7 36 (dd, IR J = 1 5, 8.3 Hz), 7 61 (dd, IR J = 1 7, 8 8 Hz), 7 89 (d, IR J = 8 5 Hz), 7 97 (d, IR J = 1 5 Hz), 8 85 (d, IR J = 1 0 Hz) FAB-MS (m/z) , 603 (M+l) + Exam p le 22 Synthesis of Compound 23 To a soluuon of 40 mg (0 05 mmol) of Compound F obtamed in Reference Example 6 in 3 ml of a d i chloromethane ethylaπune mixture (2/1) were added 126 mg (0 18 mmol) of bιs(tπphenylphosphme)palladιum(II) chlonde and 42 mg (0.22 mmol) of cuprous iodide in a stream of argon, followed by stimng at room temperature for 20 mmutes After addiuon of 0 16 ml ( 1 5 mmol) of propargyl alcohol, the mixture was stirred at room temperature for one hour The reacuon m i xture was filtered through Celite and the solvent was evaporated under reduced pressure The res i due was purified by silica gel column chromatography (chloroform/methanol = 96/4) to give 456 0 mg (23%) of diacetylated Compound 23 FAB-MS (m/z) , 659 (M+l) + The same procedure as in Example 1, Step B was repeated usmg 30.0 mg of diacetylated Compound 23 to give 8 0 mg (33%) of Compound 23. iH-NMR (CD3OD) δ , 1 90 (s, IH), 1.93 (s, IH), 2.14 (dd, IR J = 5.0, 14.2 Hz), 2.19 (s, 3H), 3 41 (dd, IR J = 7.5, 14.2 Hz), 4.01 (s, 3H), 4.78 (m, 4H), 4 98 (d, IR J = 17 6 Hz), 5 03 (d, IR J = 17.6 Hz), 7.02 (dd, IR J = 5 0, 7.5 Hz), 7.35 (dt, IR J = 0 7, 7 8 Hz), 7 49 (m, 2H), 7 63 (d, IR J = 8.3 Hz), 7.97 (d, IR J = 9.2 Hz), 7.99 (d, IR J = 1.1,8.6 Hz), 9.26 (d, lR J = 1.0 Hz) FAB-MS (m/z) , 576 (M+l) + Example 23 Synthesis of Compound 24 Chloroacetyl chloride (0.95 ml, 10 mmol) was added to 5 ml of a suspension of 1 06 g (8 mmol) of aluminum chlonde in dichloromethane, and the mixture was stirred at room temperature for 5 minutes To the mixture was added dropwise 10 ml of a soluuon of 500 mg ( 1 mmol) of Compound c (Japanese Published Unexamined Patent Applicaϋon No. 295588/88) in dichloromethane, followed by sumng at room temperature for 2.5 hours The reaction mixture was poured mto ice-cold water, followed by extraction with chloroform/methanol (9/1) The extract was washed with a saturated aqueous soluuon of sodium chloride and dned over magnesium sutfate After evaporauon of the solvent under reduced pressure, the resulting powder was mixed with 1 N hydrochlonc acid. The mixture was stirred for one hour and then filtered. The filtrate was puπfied by sdica gel column chromatography (chloroform) to give 270 mg (38%) of Compound 24 ^-NMR (CDCI3) δ , 1.82 (s, 3H), 2.20 (dd, IR J = 5.4, 14.5 Hz), 2.32 (s, 3H), 2.81 (s, 3H), 4 05 (s, 3H), 4 06 (dd, IR J = 7.3, 14.5 Hz), 4.87 (dd, IR J = 14.1, 15.6Hz), 5.03 (d, IR J = 14.1, 15.6Hz), 5.45 (m, 2H), 7.03 (dd, IR J =5.1, 7.3 Hz), 7.61 (d, IR J = 8.8 Hz), 8 02 (d, IR J = 8.8 Hz), 8.21 (dd, IR J = 1.7, 8.8 Hz), 8.27 (dd, IR J = 1.7, 8.8 Hz), 8.63 (d, IR J = 1.5 Hz), 9.87 (d, IR J = 1.0 Hz) FAB-MS (m/z) , 704 (M+l) + Exam p le 24 Synthesis of Compound 25 To 1.5 ml of a soluuon of 36 mg (0 05 mmol) of Compound 24 in chloroform was added 0 025 ml (0.25 mmol) of pipeπdme, and the mixture was refluxed for 2 hours The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column 5 chromatography (cUoroform/methanol = 10/1) to give diacetylated Compound 25 FAB-MS (m/z) , 802 (M+l) + The same procedure as in Example 1, Step B was repeated using diacetylated Compound 10 25 to give 16 mg (42%) of Compound 25 iH-NMR (CDCI3) δ , 1.42 (m, 4H), 1.56 (m, 8H), 2.07 (dd, IR J = 4 8, 14.2 Hz), 2.18 (s, 3H), 2.56 (m, 8H), 3.45 (dd, IR J - 7.5, 14.2 Hz), 3.86 (m, 4H), 3.94 (s, 3H), 5.12 (m, 2H), 6 48 (s, IH), 7.25 (dd, IR J = 4.8, 7 5 Hz), 8.02 (d, 2R J = 9.0 Hz), I 5 8 14 (dd, IR J = 1 7, 7.1 Hz), 8.16 (dd, IH, J - 1 7, 7 1 Hz), 8 78 (br, IH), 8.84 (br, lH), 9 99 (d, lR J = 1.5 Hz). FAB-MS (m z) , 718 (M+l) + Exam p le 25 Synthesis of Compound 26 and Compound 27 20 The same procedure as in Example 23 was repeated using 55 mg (0.1 mmol) of Compound c (Japanese Published Unexammed Patent ApphcaUon No. 295588/88) and 3-chloropropιonyl chlonde to give 4 mg (6%) of Compound 26 and 26 mg (36%) of Compound 27 Compound 26 25 FAB-MS (m/z) , 642 (M+ 1 ) + Compound 27 FAB-MS (m/z) , 732 (M+l) + Examnle 26 Synthesis of Compound 28 To 1.5 ml of a soluuon of 200 mg (0.25 mmol) of Compound 26 in chloroform was added 0.025 ml (0.25 mmol) of pipeπdine, and the mixture was refluxed for 2 hours. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform/methanol = 10/1) to give diacetylated Compound 28. FAB-MS (m/z) ; 689 (M+l) + The same procedure as in Example 1, Step B was repeated usmg diacetylated Compound 28 to give 17 mg (11%) of Compound 28. H-NMR (CDCI3) δ ; 1 48 (br, 2H), 1.65 (t, 4R J = 5.2 Hz), 2.18 (s, 3H), 2.47 (br, 4H), 2.60 (br, lH), 3.00(br, IH), 3.57 (dd, IR J = 8.1, 15.4 Hz), 4.07 (s, 3H), 4.15 (d, IR J = 15.4 Hz), 4.40 (d, IR J = 15.8 Hz), 5.73 (br, 2H), 6.71 (dd, J = 4.6, 7.3 Hz), 7.02 (d, IR J = 8.1 Hz), 7.30 (dd, IR J = 5.2. 8.1 Hz), 7.43 (dd, IR J = 5.2, 8.2 Hz), 7.56 (br, IH), 7.63 (br, IH), 7.88 (d, IR J = 8.2 Hz), 8.84 (s, IH). FAB-MS (m/z) ; 605 (M+l) + Example 27 Synthesis of Compound 29 To 1.5 ml of a soluUon of 60 mg (0.03 mmol) of Compound 27 in chloroform was added 0.025 ml (0.25 mmol) of piperidine, and the mixture was refluxed for 2 hours. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column ' chromatography (chloroform/methanol = 10/1) to give d acetylated Compound 29. FAB-MS (m/z) ; 830 (M+l) + The same procedure as in Example 1, Step B was repeated using diacetylated Compound 29 to give 5.1 mg (8.3%) of Compound 29. iH-NMR (DMSO-d6) δ ; 2 06 (dd, 4R J = 4 4, 13.9 Hz), 2.17 (s, 3H), 2.49 (br, 12H), 3.29 (br, 4H), 3 44 (dd, IR J = 7.3, 13.9 Hz), 3.93 (s, 3H), 5.13 (d, IR J = 18.4 Hz), 5.80(d, IR J = 18 4 Hz), 6.48(m, IH), 7.25 (dd, IR J = 5.4, 6.3 Hz), 8.00 - 8.16 ( , 4H), 8 62 (br, IH), 8 77 (br, IH), 9.96 (s, IH) FAB-MS (m/z) ; 746 (M+l) + Exam p le 28 Synthesis of Compound 30 To 1 5 ml of a soluuon of 40 mg (0 05 mmol) of Compound 27 in chloroform was added 0 02 ml (0.23 mmol) of morpholine, and the mixture was refluxed for 2 hours. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform/methanol = 10/1) to give diacetylated Compound 30 FAB-MS (m/z) , 834 (M+l) + The same procedure as m Example 1, Step B was repeated usmg diacetylated Compound 30 to give 35.5 mg (31%) of Compound 30 iH-NMR (DMSO-d6) δ , 2 07 (dd, IR J = 5.0, 14 7 Hz), 2 16 (s, 3H), 2 45 (m, 8H), 2.77 (br, 4H), 3.30 (m, 4H), 3 44 (dd, IR J = 7.5, 14 7Hz), 3 59 (m, 8H), 3.93 (s, 3H), 5 - 16 (m, 2H), 6 48 (s, IH), 7.24 (dd, IR J = 5 0, 7 5 Hz), 8 02 (dd, IR J = 2.2, 5.5 Hz), 8 11 (dd, IR J = 1 7, 5.8 Hz), 8.14 (dd, IR J = 1 7, 5 8 Hz), 8.61 (d, IR J = 1.0 Hz), 8.76 (br, IH), 9.96 (d, IR J = 1.2 Hz) FAB-MS (m/z) ; 750 (M+l) + Exam p le 29 Synthesis of Compound 31 To 3 ml of a soluuon of 100 mg (0 14 mmol) of Compound 24 in chloroform was added 1 ml of morpholine, and the mixture was refluxed for 3 hours. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform methanol = 15/1) to give diacetylated Compound 31 FAB-MS (m/z) ; 806 (M+l) + The same procedure as in Example 1, Step B was repeated using diacetylated Compound 31 to give 27 mg (26%) of Compound 31. iH-NMR (DMSO-Q6) δ ; 2.06 (dd, IR J - 5.0, 14.1 Hz), 2.62 (m, 8H), 3.45(dd, IR J = 7.3, 14.1 Hz), 3.63 (m, 8H), 3.91 (m, 2H), 3.98 (m, 2H), 5.13 (d, 2R J = 7.3 Hz), 6.49 (s, IH), 7.25 (dd, IR J = 5.0, 7.3 Hz), 8.02 (d, IR J = 8.9 Hz), 8.13 (dd, IR J = 1.7, 9.0 Hz), 8.15 (dd, IR J = 1.7, 8.8 Hz), 8.62 (d, IR J = 1.7 Hz), 8.77 (s, lH), 8.78 (d, lR J =1.5 Hz), 10.01 (dd, IR J = 0.49, 1.2 Hz) FAB-MS (m z) , 722 (M+l) + Example 30 Synthesis of Compound 32 To 3 ml of a solution of 110 mg (0.16 mmol) of Compound 24 in N,N-dimethylforrnamide was added 54 ml of a 50% aqueous solution of dimethylamine, and the mixture was refluxed for 3 hours. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform methanol = 10/1) to give 13.7 mg (14%) of Compound 32. iH-NMR (DMSO-d6) δ , 2.06 (dd, IR J = 4.9, 14.1 Hz), 2.18 (s, 3H), 2.35 (s, 6H), 2.36 (s, 6H), 3.40 (dd, IR J = 7.5, 14.1Hz), 3.87 (m, 2H), 3.93 (m, 2H), 3.94 (s, 3H), 5.13 (m, 2H), 6.47 (s, IH), 7.25 (dd, IR J = 4.9, 7.5 Hz), 8.01 (d, 2R J = 9.0 Hz), 8.13 (dd, IR J = 1.7, 5.6 Hz), 8.16 (dd, IR J = 1.7, 5.4 Hz), 8.69 (d, IH, J - 1.7 Hz), 8.76 (br, IH), 9.97 (d, IR J - 1.2 Hz). FAB-MS (m/z) ; 638 (M+l) + Example 31 Synthesis of Compounds 33a and 33b To a suspension of 1.06 g (8.0 mmol) of aluminum chloride in 10 ml of methylene chloride was added 0.48 ml (5.0 mmol) of chloroacetyl chloride, and the mixture was stirred at room temperature for 5 minutes. To the mixture was gradually added a soluuon of 551 mg ( 1.0 mmol) of Compound c in 10 ml of methylene chloride, followed by stimng for 2.5 hours. The reacuon mixture was then poured into ice-cold water, followed by ejctracuon with chloroform/methanol (9/1). The extraα was washed with a saturated aqueous solution of soώum chlonde and dried over soώum sulfate. After evaporauon of the solvent under reduced pressure, the resultmg powder was mixed with 1 N hydrochlonc acid. The mixture was stirred for one hour, and then insoluble matenals were removed by fiitrauon. The filtrate was puπfied by sihca gel column chromatography (chloroform) to give 110 mg (17%) of a mixture of Compounds 33a and 33b. Compound 33a FAB-MS (m/z); 628, 630 (M+l) + Compound 33b FAB-MS (m z); 628, 630 (M+l) + Exam p le 32 Synthesis of Compound 34 To a soluuon of 64 mg (0.1 mmol) of a mixture of Compounds 33a and 33b in 1.5 ml of N,N-dιmethylformamιde were added 30 mg (0.2 mmol) of soώum iodide and 1 ml of a 50% aqueous soluuon of dimethylamine, followed by reflux for 2 hours. The solvent was evaporated under reduced pressure, and the residue was purified by sihca gel column chromatography (chloroform/methanol = 9/ 1 ) to give 3.2 g (5.8%) of Compound 34 H-NMR (CDC1 3 ) δ ; 1.73 (br, IH), 2.20 (s, 3H), 2.44 (s, 6H), 2 85 (dd, IR J = 4.9, 13.7 Hz), 3.61(dd, IR J = 7.8, 13.7 Hz), 3.70 (m, 2H), 4.09 (s, 3H>, 4.50 (d, IR J - 16.6 Hz), 4.70 (d, 1RJ = 16.6 Hz), 5.70 (br, IH), 6.85 (dd, IR J =4 9, 7 3 Hz), 7.29 (d, IR J = 8.3 Hz), 7.39 (t,lR J = 7 6 Hz), 7.51 (t, IR J = 7 6 Hz), 7.83(t, IR J = 7.6 Hz), 7.89 (d, IR J = 8.3 Hz),7.90 (d, IR J = 7.6 Hz), 9.36 (s, IH) FAB-MS (m/z); 553 (M+l) + Example 33 Synthesis of Compound 35 To a soluuon of 63 mg (0 1 mmol) of a mixture of Compounds 33a and 33b in 2 ml of N.N-dimethylformamide was added 90 mg (0 6 mmol) of soώum iodide, and the mixture was then surred at room temperature for 2 hours After the solvent was evaporated under reduced pressure, the residue was treated in the same manner as in Example 1, Step B to give 6 8 mg ( 12%) of Compound 35 iH-NMR (DMSO-dg) δ , 2 00-2 40 (m, 7H), 2 70-2 80 (m,4H), 3 40 (br, IH), 3 94 (s, 3H), 4 22 (br, 2H)),5 02 (d, IR J = 18 0 Hz), 5 07 (d, IR J = 18 0Hz), 6 42 (s, IH), 6 90 (br, IH), 7 38 (t, IR J= 7 5 Hz), 7 51 (dd, IR J = 7 5, 8 5 Hz), 7 95(d, IR J = 8 5 Hz), 8 00 (d, IR J = 8 7 Hz),8 08 (d, IR J = 7 5 Hz), 8 12 (dd, IR J = 1 7,8 7 Hz), 8 69 (s, IH), 9 95 (d, IR J = 1 4 Hz) FAB-MS (m/z), 579 (M+l) + .Tnm le 34 Synthesis of Compounds 36a and 36b The same procedure as m Example 28 was repeated usmg 40 mg (0 064 mmol) of a mixture of Compounds 33a and 33b to give 17 mg (40%) of Compound 36a and 10 mg (23%) of Compound 36b Compound 36a -NMR (CDC1 3 ) δ , 1 80 (s, 3H), 2 18 (dd, IR J = 5 1, 10 2 Hz), 2 29 (s, 3H), 2 77 (s, 3H), 3 07 (br,4H), 3 93 (br, 4H), 4 00 (dd, IR J = 7 5, 10 1 Hz), 4 07 (s, 3H), 4 35 (br, 2H), 5 38 (d, 2R J= 5 4 Hz), 6 90 (m, IH), 7 00 (dd, IR J = 5 1,7 5 Hz), 7 46 (td, IR J = 0 5, 7 5 Hz), 7 56 (d,lR J = 8 5 Hz), 7 57 (to, IH, J - 1 1, 7 5 Hz),7 94 (d, IR J = 8 5 Hz), 8 07 (d, IR J = 7 5 Hz), 8 22 (dd, IR J = 1 6, 7 5 Hz), 9 94 (br,lH) FAB-MS (m/z), 679 (M+l) + Compound 36b H-NMR (CDCI3) δ ; 1.80 (s, 3H), 2.15 (dd, IR J - 5 1, 12.2 Hz), 2.29 (s, 3H), 2.79 (s, 3H), 2.94 (br,4H), 3.92 (t, 4R J = 4.5 Hz), 4.09 (dd, IR J =7.2, 12.2 Hz), 4.02 (s, 3H), 4.35 (br, 2H), 5.38(br, 2H), 7.03 (dd, IR J = 5.1, 7.2 Hz), 7.38(br, IH), 7.56 (br, IH), 7.95 (d, IR J = 8 9Hz), 8.21 (d, IR J = 1 7, 8.9 Hz), 8 78 (br.lH), 9.21 (d, lR J = 8 0 Hz) FAB-MS (m/z), 679 (M+l) + Example 35 Synthesis of Compound 37a The same procedure as in Example 1, Step B was repeated usmg 17 mg (0.025 mmol) of Compound 36a to give 3.2 mg (22%) of Compound 37a iH-NMR (DMSO-d ή ) δ , 2.23 (s, 3H), 2.56 (dd, IR J =4 5, 14.7 Hz), 2.72 (br, 4H), 3.43 (dd, l J =7 6, 14 7 Hz), 3.82 (t, 4R J = 4 6 Hz), 4 01(br, 1H), 4.1 1 (s, 3H), 4.86 (d, IR J = 16.0Hz), 4.95 (d, IR J = 16.0 Hz), 5 96 (br, IH), 6 91 (dd, IR J = 4.8, 7.4 Hz), 7 41 (t, IR J =7.6 Hz), 7.50 (d, IR J = 7 6 Hz), 7.51 (t, IR J= 7.6 Hz), 7 85 (d, IR J = 8.6 Hz), 7.92 (d, 1RJ = 7 6 Hz), 8 11 (d, IR J = 8 6 Hz), 9.8 l (br, lH) FAB-MS (m/z), 595 (M+l) + Example 36 Synthesis of Compound 37b The same procedure as m Example 1, Step B was repeated using 10 mg (0.015 mmol) of Compound 36b to give 1 0 mg ( 11 %) of Compound 37b. 'H-NMR (DMSO-d^) δ , 2.23 (s, 3H), 2 42 (dd, IR J = 4 9,14 5 Hz), 2.64 (br, 4H), 3.35 (dd, IR J = 7.6, 14.5 Hz), 3.80 (t, 4R J = 4 6 Hz), 3 85 (d, 2R J = 5.3 Hz), 4.12 (s, 3H), 4.29 (br, IH), 4.80 (d, IR J = 16.5 Hz), 4 90 (d, IR J - 16.5 Hz), 6.21 (br, IH), 6 93 (dd, IR J = 4 9, 74 Hz), 7.30 (br, IH), 7 49 (m, 2H), 7 83 (d, IR J = 8.9 Hz), 8.11 (d, lR J = 8.9 Hz), 8.55 (s, IH), 8.5(s, IH), 9.20 (d, J = 8.1 Hz, IH) FAB-MS (m/z); 595 (M+l) + Example 37 Synthesis of Compound 38 The same procedure as in Example 33 was repeated using 162 mg (0.23 mmol) of Compound 24 to give 32 mg (46%) of Compound 38. !H-NMR (DMSO-d ) δ ; 1.95 (s, 3H), 2.30 (m, 9H), 2.65 (m, 8H), 3 45 (dd, IR J - 7.1, 14.4 Hz), 3 94 (s, 3H), 4.13 (m, 4H), 5.12 (m, 2H)), 6.52 (s.lH), 7.24 (dd, IR J = 4.9, 7.3 Hz), 8 02 (d, 2R J = 8.8 Hz), 8.29 (m, 2H), 8.72 (s, IH), 8.76(br, IH), 9.97 (s, IH) FAB-MS (m z); 689 (M+l) + Example 38 Synthesis of Compound 39 To a solution of 21 1 mg (0.30 mmol) of Compound 24 in 2 ml of N.N-dimeώylforrrtaπude were added 300 mg (3.0 mmol) of N-methylpiperazine and 90 mg (0.6 mmol) of soώum iodide, and the mixture was stirred at room temperature for 2 hours. After the solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography (chloroform/rrΛthanol = 9/1) to give 190 mg (76%) of Compound 3 FAB-MS (m/z); 832 (M+l) + Example 39 Synthesis of Compound 40 The same procedure as in Example 1, Step B was repeated using 17 mg (0.02 mmol) of Compound 39 to give 5.1 mg (34%) of Compound 40. H-NMR (DMSO-d 6 ) δ , 2.06 (dd, J = 4.6, 14.4 Hz, 4H), 2.18 (s, 3H), 2.30 (br, 6H), 2.50 (br, 8H), 2.67 (br, 8H), 3.45 (dd, IR J = 7.1, 14.4 Hz), 3.94 (s, 3H), 3.98 (br, 4H), 5.13 (br, 2H)), 6.49 (s, IH), 7.25 (dd, IR J = 4 6, 7.1 Hz), 8.02 (d, 2RJ = 8.5 Hz), 8 13 (dd, IR J = 1 7, 6.8 Hz), 8.16 (dd, IR J = 1 7, 6 8 Hz), 8 78 (br, 2H), 9.99 (d, IR J = 1 7 Hz) FAB-MS (m/z), 748 (M+l) + Exam p le 40 Synthesis of Compound 41 To a soluuon of 50 mg (0.078 mmol) of a mixture of Compounds 33a and 33b in 2 ml of methylene chlonde was added 66 mg (0 78 mmol) of soώum ethanethiolate, and the mixture was surred at room temperature for 3 hours The reacuon mixture was poured mto ice-cold water, followed by extraction with chloroform/methanol. The extract was washed with a saturated aqueous soluuon of soώum chlonde and dπed over soώum sulfate After evaporauon of the solvent under reduced pressure, the residue was purified by silica gel column chromatography (chlorofoπn/methanol = 99 8/0.2) to give 17.0 mg (33%) of diacetylated compound 41 FAB-MS (m/z), 654 (M+l) + The same procedure as in Example 1, Step B was repeated usmg 17 mg (0.026 mmol) of diacetylated Compound 41 to give 5.3 mg (35%) of Compound 41 iH-NMR (DMSO-d^) δ ,1.23 (t, 3R J = 7.3 Hz), 2.00 (dd, IR J = 4 7, 13.9 Hz), 2.33 (s, 3H), 2.59 (q, 2R J = 7 3 Hz), 3 42 (dd, IR J = 7 3, 13.9 Hz), 3 94 (s, 3H), 4 19 (d, 2R J = 3 4 Hz), 5.10 (d, 2R J = 5.1 Hz), 6 44 (br, IH), 7 18 (dd, IR J =4 9, 7.3 Hz), 8.31 (t, IR J = 8.2 Hz), 7.51 (dt, IR J = 1 4, 8.3 Hz), 7 92 (d, IR J = 8.2 Hz), 8.02 (d, IR J - 9 0 Hz), 8 11 (dd, IR J = 1.9, 9.0 Hz), 8.63 (d, IR J = 1 4 Hz), 8 72 (br, IH), 9.23 (d, IR J = 8.1 Hz) FAB-MS (m/z), 570 (M+l) + Example 41 Synthesis of Compounds 42a and 42b To a soluuon of 100 mg (0 16 mmol) of a mixture of Compounds 33a and 33b in 2 ml of N,N-dimethylformamide were added 100 mg (0 9 mmol) of 4-mercaptopynώne and 22 mg (0 16 mmol) of potassium carbonate, followed by sumng at room temperature for 2 hours The reaction mixture was poured mto ice-cold water, followed by extraction with chloroform/methanol The extract was washed with a saturated aqueous solution of soώum chlonde and dπed over soώum sulfate After evaporauon of the solvent under reduced pressure, the residue was puπfied by sihca gel column chromatography (chloroform methanol = 99 8/0.2) to give 70 mg (63%) of a mixture of diacetylated Compounds 42a and 42b FAB-MS (m/z), 703 (M+l) + The same procedure as in Example 1, Step B was repeated usmg 70 mg (0 10 mmol) of the mature of diacetylated compounds to give 3.3 mg (5.3 %) of Compound 42a and 5.2 mg (8 4%) of Compound 42b Compound 42a iH-NMR (DMSO-ds) δ , 2.09 (dd, IR J = 4.9, 13.9 Hz), 2 19 (s, 3H), 3 44 (dd, IR J = 7.3, 13.9 Hz), 3.94 (s, 3H), 4.99 (s, 2H), 5.05 (d, 2R J = 5 9 Hz), 6.39 (s, IH), 7.25 (dd, IR J = 4 9, 7.3 Hz), 7.39 (t, IR J = 8.6 Hz)7 41 (d, IR J = 6 4 Hz), 7.52 (t, IR J = 8.6 Hz), 7.96 (d, IR J = 8 6 Hz), 8 071 (d, IR J = 8 8 Hz), 8 074 (d, IR J = 8 6 Hz), 8.25 (dd, IR J = 1.7, 8.8 Hz), 8 40 (d, 2R J = 6 4 Hz), 8 71 (s, IH), 9.98 (d, lR J = 1.0 Hz). FAB-MS (m z), 619 (M+l) + Compound 42b iH-NMR (CDCI 3 ) δ , 2.24 (s, 3H), 2.39 (dd, IR J = 5 1, 14 4 Hz), 3 36 (dd, IR J = 7 3, 14 4 Hz), 4 12 (s, 3H), 4 46 (d, 2R J = 3 4 Hz), 4 83 (d, IR J = 16 4 Hz), 4 93 (d, IR J = 16 4 Hz), 6.15 (s.lH), 6 93 (dd, IR J = 4 9, 7.3 Hz), 7.11-7.29 (br, 5H), 7.22-7.58 (br, 2H), 7.86 (d, IR J =8 3 Hz), 8 04 (d, IR J = 8 3 Hz), 8 48 (d, IR J = 2 7 Hz), 8 51 (s, IH), 9.22 (d, IR J = 8.3 Hz) FAB-MS (m z), 619 (M+l) + Example 42 Synthesis of Compound 43 To a soluuon of 21 1 mg (0 30 mmol) of Compound 24 in 4 ml of chloroform/methanol (3/1) was added 56 mg (0 80 mmol) of soώum methanethiolate, followed by stimng at room temperature for 30 mmutes The reacuon mixture was poured mto ice-cold water, followed by extracuon with chloroform/methanol The extract was washed with a saturated aqueous soluuon of soώum chloride and dned over soώum sulfate The solvent was evaporated under reduced pressure to give 125 mg (57%) of diacetylated Compound 43 FAB-MS (m z), 728 (M+l) + The same procedure as in Example 1, Step B was repeated using 125 mg (0.017 mmol) of diacetylated Compound 43 to give 48 mg (44%) of Compound 43 J H-NMR (DMSO-tlg) δ , 2 07 (dd, IR J = 4 9, 14 4 Hz), 2 13 (s, 3H), 2 14 (s, 3H), 2.18 (s, 3H), 3 45 (dd, IR J = 7 3, 14 4 Hz), 3.94 (s, 3H), 4 04 (s, 2H), 4 17 (d, 2R J = 2.9 Hz), 5.14 (d, 2R J = 4.6 Hz), 6.50 (br, IH), 7 26 (dd, IR J = 4 9, 7.3 Hz), 8 03 (d, IR J = 8.8 Hz), 8.04 (d, IR J = 8.8 Hz), 8.13 (dd, IR J = 2 0, 8.8 Hz), 8 17 (dd, IR J = 2.0, 8 8 Hz), 8 65 (d, IR J = 1 7 Hz), 8 78 (br, IH), 9 93 (d, lR J = 1.5 Hz) FAB-MS (m/z), 644 (M+l) + Example 43 Synthesis of Compound 44 To a soluuon of 50 mg (0.07 mmol) of Compound 24 in 2 ml of methylene chloride was added 59 mg (0.7 mmol) of soώum ethanethiolate, followed by stirring at room temperature for 3 hours After the solvent was evaporated under reduced pressure, the residue was purified by sihca gel column chromatography (chloroform/methanol = 99.8/0.2) to give 19.7 mg (36%) of diacetylated Compound 44 FAB-MS (m/z), 756 (M+l) + The same procedure as in Example 1, Step B was repeated using 19 mg (0.025 mmol) of ώacerylated Compound 44 to give 12.5 mg (67%) of Compound 44 iH-NMR (DMSO-dg) δ , 1.22 (t, 3R J - 7.5 Hz), 1.23 (t, 3R J = 7.5 Hz), 2.08 (dd, IR J = 4.9, 13.9 Hz), 2.18 (s, 3H), 2.60 (br, 4H), 3.45 (dd, IR J = 7.3, 13.9 Hz), 3.94 (s, 3H), 4 07 (br, 2H), 4.19 (d, 2R J = 4.2 Hz), 5.14 (br, 2H), 6.49 (br, IH), 7.26 (dd, IR J = 4 9, 7.3 Hz), 8.03 (d, IR J = 9.0 Hz), 8.04 (dd, IR J = 8.8 Hz), 8.13 (dd, IR J = 1.7, 9.0 Hz), 8.16 (dd, IR J = 2.0, 8.8 Hz), 8.65 (d, IR J = 1.7 Hz), 8.79 (br, IH), 9 94 (d, IR J = 1.7 Hz). FAB-MS (m/z), 672 (M+l) + Example 44 Synthesis of Compound 45 To a soluuon of 100 mg (0.16 mmol) of Compound 24 in 3.5 ml of N,N- dimeώylforrriaπucle methanol (6/1) were added 0.038 ml (0.32 mmol) of propanethiol and 44 mg (0.32 mmol) of potassium carbonate, followed by stirring at room temperature for 2 hours. The reacuon mixture was poured into ice-cold water, followed by extracuon with chloroform methanol The extract was washed with a saturated aqueous soluuon of soώum chloride and dried over soώum sulfate. After the solvent was evaporated under reduced pressure, the residue was purified by sihca gel column chromatography (chloroform/meϋ-anol = 95/5) to give 32 mg (23%) of Compound 45 1 H-NMR (DMSO-d 6 ) δ , 0 93 (t, 3R J = 7 3 Hz), 0 94 (t, 3R J « 7 3 Hz), 1 59 (qt, 2R J = 7 2, 7 3 Hz), 1 60 (tq, 2R J = 7 3, 7 2 Hz), 2 07 (dd, IR J = 5 0, 13 1 Hz), 2 18 (s, 3H), 2 57 (t, 2R J = 7 2 Hz), 2 58 (t, 2R J = 7 2 Hz), 3 45 (dd, IR J = 7 6, 13 1 Hz), 3 94 (s, 3H), 4 04 (s, 2H), 4 15 (d, 2R J = 5 1 Hz), 5 14 (d, 2R J = 8 0 Hz), 6 50 (br, IH), 7 26 (dd, IR J = 5 0, 7 3 Hz), 8 03 (d, IR J = 8 9 Hz), 8 04 (d, IR J - 8 7 Hz), 8 12 (dd, IR J = 1 7, 8 9 Hz), 8 16 (dd, J = 1 7, 8 7 Hz), 8 65 (d, IH, J - 1 6 Hz), 8 80 (br, IH), 9 93 (d, IR J - 1 6 Hz) FAB-MS (m/z), 700 (M+l)+ Example 45 Synthesis of Compound 46 To a soluuon of 70 mg (0 10 mmol) of Compound 24 in 3 5 ml of N,N- dimethylformamide methanol (6/1) were ? ^H 23 mg (0 30 mmol) of 2-hyώoxyethanethιol and 50 mg (0 36 mmol) of potassium carbonate, followed by sumng at room temperature for 1 day The reacuon mixture was poured mto ice-cold water, followed by extracuon with chloroform/methanol The extraα was washed with a saturated aqueous soluuon of soώum chlonde and dπed over soώum sulfate The solvent was evaporated under reduced pressure to give 40 mg (51 %) of diacetylated Compound 46 FAB-MS (m/z), 784 (M+l) + The same procedure as in Example 1, Step B was repeated usmg 40 mg (0 051 mmol) of acetvlated Compound 46 to give 20 mg (56%) of Compound 46 l H-NMR (DMSO-d^) δ , 2 07 (dd, IR J = 5 1, 14 3 Hz), 2 18 (s, 3H), 2 67 (br, 4H ), 3 45 (dd, IR J =7 6, 14 3 Hz), 3 59 (br, 4H), 3 94 (s, 3H), 4 10 (s, 2H), 4 22 (d, 2R J = 5 9 Hz), 4 82 (br, 2H), 6 50 (s, IH), 7 26 (dd, IR 5 1, 7 6 Hz), 8 04 (d, IR J = 9 0 Hz), 8 05 (d, IR J = 8 7 Hz), 8 13 (dd, IR J = 1 7, 9 0 Hz), 8 16 (dd, IR J = 1 7, 8 7 Hz), 8 65 (d, IR J = 1 7 Hz), 8 81 (s, IH), 9 93 (d, IR J = 1 7 Hz) FAB-MS (m/z); 700 (M+l) + Example 46 Synthesis of Compound 47 To a soluuon of 100 mg (0.16 mmol) of Compound 24 in 2 ml of N.N-dimeώylfoiroamide were added 100 mg (0 9 mmol) of 4-mercaptopyridine and 44 mg (0.32 mmol) of potassium carbonate, followed by surring at room temperature for 2 hours. The reacuon mixture was poured into ice-cold water, followed by extraction with chloroform/methanol. The extraα was washed with a saturated aqueous soluuon of soώum chloride and dried over soώum sulfate. After the solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography (chloroform/methanol = 99.8/0.2) to give 67 mg (63%) of ώacetylated Compound 47 FAB-MS (m/z); 854 (M+l) + The same procedure as in Example 1, Step B was repeated using 67 mg (0.10 mmol) of diacetylated Compound 47 to give 45 mg (58%) of Compound 47 H-NMR (DMSO-dg) δ ; 2.08 (dd, IR J = 4.8, 14.3 Hz), 2.19 (s, 3H), 3 47 (dd, IR J = 7.5, 14.3 Hz), 3.95 (s, 3H). 4.97 (s, 2H), 5.12 (d, 2R J = 4 9 Hz), 5.18 (s, 2H), 6.53 (s, IH), 7.30 (dd, IR J = 4.8, 7.5 Hz), 7.37 (br, 4H), 8.07 (d, IR J = 9 0 Hz), 8.10 (d, IR J = 8.7 Hz), 8.19 (dd, IR J = 1 7, 9.0 Hz), 8.29 (dd, IR J = 1.8, 8.7 Hz), 8.21-8.57 (br, 4H), 8.76 (d, IR J = 1.7 Hz), 8 86 (s, IH), 9.99 (d, IR J = 1.8 Hz) FAB-MS (m z), 770 (M+l) + Example 47 Synthesis of Compound 48 To a solution of 160 mg (0.26 mmol) of Compound 24 in 2 ml of N.N-dimewylformamide were added 290 mg (2.6 mmol) of 2-mercaptopyridine and 83 mg (0.6 mmol) of potassium carbonate, followed by stirring at room temperature for 2 hours. The reacuon mixture was poured into ice-cold water, followed by extracuon with chloroform methanol. The extraα was washed with a saturated aqueous solution of soώum chloride and dried over soώum sulfate. After the solvent was evaporated under reduced pressure, the residue was purified by sihca gel column chromatography (chloroform/methanol = 99.8/0.2) to give 123 mg (55%) of ώacetylated Compound 48. FAB-MS (m/z); 854 (M+l) + The same procedure as in Example 1, Step B was repeated using 20 mg (0.023 mmol) of diacetylated Compound 48 to give 1 mg (53 %) of Compound 48 -NMR (DMSO-d^) δ ; 2.09 (dd, IR J = 4.8, 14.2 Hz), 2.19 (s, 3H), 3.47 (dd, IR J = 7.3, 14.2 Hz). 3.95 (s, 3H), 4.94 (s, 2H), 5.02 (d, 2R J = 3.4 Hz), 5.10 (d, 2R J = 7.7 Hz), 6.52 (s, IH), 7.01-7.27 (br, 5H), 7.41 (d, 2R J = 8.0 Hz), 7.66 (dt, 2R J = 1.1, 8.0 Hz), 8.06 (d, IR J = 8.8 Hz), 8.29 (d, IR J = 8.8 Hz), 8.37 (ddd, 2R J = 0.8, 4.1, 8.0 Hz), 8.72 (s. IH), 8.81 (s, IH), 10.02 (s, IH). FAB-MS (m/z); 770 (M+l) + Example 48 Synthesis of Compound 49 To a solution of 140 mg (0.10 mmol) of Compound 24 in 3 ml of N,N-dιmethylformarnide were added 70 mg (0.60 mmol) of 2-mercaptopyridine and 50 mg (0.36 mmol) of potassium carbonate, followed by stirring at room temperature for 3 hours The reaction mixture was poured into ice-cold water, followed by extraction with chloroform/methanol. The extraα was washed with a saturated aqueous solution of soώum chloride and dried over soώum sulfate. After the solvent was evaporated under reduced pressure, the residue was purified by sihca gel column chromatography (chloroform/methanol = 95/5) to give 17 mg (16%) of ώacetylated Compound 49 and 15 mg (18%) of monoacetylated Compound 49. Diacetylated Compound FAB-MS (m/z); 856 (M+l) + Monoacetylated Compound FAB-MS (m/z); 814 (M+l) + The same procedure as m Example 1, Step B was repeated using 17 mg (0.020 mmol) of diacetylated Compound 49 to give 8.7 mg (56%) of Compound 49 !H-NMR (DMSO-d ) δ , 2.09 (dd, IR J = 4.9, 14.0 Hz), 2.19 (s, 3H), 3.30 (br, IH), 3.95 (s, 3H), 4 96 (s, 2H), 5.03 (s, 2H), 5.15 (d, 2R J = 2.7 Hz), 6.52 (s, IH), 7.28- 7.30 (m, 3H), 8.08 (d, IR J = 8.8 Hz), 8.09 (d, IR J = 8 8 Hz), 8.19 (dd, IR J = 1.7, 8.8 Hz), 8.23 (dd, IR J = 1.7, 8.8 Hz), 8.59 (d, 2R J = 4 9 Hz), 8.61 (d, 2R J = 4.9 Hz), 8.74 (d, IR J = 1.7 Hz), 8.80 (br, IH), 10.0 (d, IR J = 1.7 Hz). FAB-MS (m z), 772 (M+l) + r.Tnm lf 49 Synthesis of Compound 50 To a soluuon of 105 mg (0.15 mmol) of Compound 24 in 1.8 ml of N,N- dimeώylforrnamide/methanol (5/1) were added 38 mg (0.30 mmol) of 4-hyώoxymercaptobeπzene and 50 mg (0.36 mmol) of potassium carbonate, followed by stirring at room temperature for 12 hours The reacuon mixture was poured into ice-cold water, followed by extracuon with chloroform/methanol. The extraα was washed with a saturated aqueous solution of soώum chloride and dned over soώum sulfate After the solvent was evaporated under reduced pressure, the residue was purified by sihca gel column chromatography (chloroform/methanol = 9/1) to give 76 mg (63%) of Compound 50 iH-NMR (DMSO-dg) δ ; 2.08 (s,3H), 2.09 (dd, IR J = 2.7, 7.6 Hz), 3.45 (dd, IR J = 7.6, 14.2 Hz), 3.94 (s, 3H), 4 44 (br, 2H), 4.56 (d, 2R J = 5.1 Hz), 5.1 1 (d, 2R J = 4.4 Hz)6.50 (s, IH), 6.73 (td, 4R J = 2.2, 8.9 Hz), 7.27 (m, 3H), 8.02 (d, IR J = 8 9 Hz), 8 04 (d, IR J = 1 7, 8 9 Hz), 8 09 (dd, IR J - I 7, 8 9 Hz), 8 14 (dd, IR J = 1 9, 8 9 Hz), 8 61 (d, IR J = 1 7 Hz), 8 77 (s,lH), 9 58 (s, 2H), 9 92 (d, IR J = 1 4 Hz) FAB-MS (m/z), 800 (M+l) + Example 50 Synthesis of Compound 51 To a soluuon of 70 mg (0 10 mmol) of Compound 24 in 2 ml of N,N-dιmethylformaπude were added 25 mg (0 21 mmol) of 2-mercaptothιazohne and 28 mg (0 20 mmol) of potassium carbonate, followed by surnng at room temperature for 1 hour To the mixture was added a soluuon ofsoώum methoxide in methanol, followed by starring for 30 mmutes The reaction mixture was poured mto ice-cold water, followed by extraction with chloroform/methanol The extraα was washed with a saturated aqueous soluuon of soώum chlonde and dned over soώum sulfate After the solvent was evaporated under reduced pressure, the residue was puπfied by sihca gel column chromatography (chloroform/methanol = 9/1) to give 30 mg (38%) of Compound 51 iH-NMR (DMSO-d^) δ , 2 07 (br, IH), 2 18 (s, 3H), 3 48 (br, 5H), 3 95 (s, 3H), 4 11 (t, 2R J = 8 0 Hz), 4 15 (t, 2R J = 8 0 Hz), 4.96 (s, 2H), 5 02 (s, 2H), 5 16 (d, 2R J = 2 7 Hz), 6 51 (s, IH), 7 27 (dd, IR J = 4 9, 7.2 Hz), 8 06 (d, 2R J = 8 8 Hz), 8 13 (dd, IR J = 1 7, 8 8 Hz), 8 17 (dd, IR J = 1 7, 8 8 Hz), 8 68 (d, IR J = 1 7 Hz), 8 82 (s, IH), 9 96 (d, IR J = 1 7 Hz) FAB-MS (m/z), 786 (M+l) + Example 51 Synthesis of Compound 52 To a soluuon of 160 mg (0.26 mmol) of Compound 24 in 2 ml of N,N-dmewylfo.mamide were added 290 mg (2.6 mmol) of 5-mercaptc-l-methyltetrazole and 83 mg (0.6 mmol) of potassium carbonate, followed by sumng at room temperature for 2 hours. The reacuon m i xture was poured into ice-cold water, and precipitates were removed by fiitrauon. The filtrate was purified by sihca gel column chromatography (chloroform/methanol = 9/1) to give 50 mg (23%) of diacetylated Compound 52. FAB-MS (m/z); 864 (M+l) + The same procedure as in Example 1, Step B was repeated using 50 mg (0.058 mmol) of ώacetylated Compound 52 to give 20 mg (44%) of Compound 52. iH-NMR (DMSO^ifi) δ ; 2.10 (dd, IR J = 4.8, 14.2 Hz), 2.19 (s, 3H), 3.47 (dd, IR J = 7.5, 14.2 Hz), 3.95 (s, 3H), 4.05 (s, 6H), 5.20 (s, 2H), 5.24 (s, 2H), 5.33 (s, 2H), 6.54 (s, IH), 7.30 (dd, IR J = 4.8, 7.5 Hz), 8.08 (d, IH, J « 9.0 Hz), 8.10 (d, IR J = 9.0 Hz), 8.16 (d, IR J = 9.0 Hz), 8.21 (d, IR J = 9.0 Hz), 8.72 (s, IH), 8.84 (s, IH), 9.98 (s, IH) FAB-MS (m/z); 780 (M+ 1 ) + Example 52 Synthesis of Compound 53 To a solution of 211 mg (0.30 mmol) of Compound 27 in 5 ml of chloroform/methanol (1/1) was added 56 mg (0.80 mmol) of soώum methanethiolate, followed by surring at room temperature for 3 hours. The reacuon mixture was poured into ice-cold water, followed by extraction with chloroform/methanol. The extraα was washed with a saturated aqueous solution of soώum chloride and dried over soώum sulfate. The solvent was evaporated under reduced pressure to give 52 mg (26%) of Compound 53. iH-NMR (DMS0-d 6 ) δ , 2 07 (dd, IR J = 4 9, 14 1 Hz), 2 16 (s, 3H), 2.17 (s, 3H), 2 18 (s, 3H), 2 87 (dd, IR J = 7 4, 14 1 Hz), 2 88 (t, 2R J = 7 I Hz), 2.89 (t, 2R J = 7 1 Hz), 3 44 (t, 2R J = 7 1 Hz), 3.53 (t, 2R J = 7 1 Hz), 3 94 (s, 3H), 5 16 (d, 2R J = 3 9 Hz), 6 49 (s, IH), 7 25 (dd, IR J = 4 9, 7 4 Hz), 8 03 (d, IR J = 9 0 Hz), 8 04 (d, IR J = 8 8 Hz), 8 12 (dd, IR J = 1 7, 9 0 Hz), 8 14 (dd, IR J = 1 7, 8 8 Hz), 8 61 (d, IR J = 1 7 Hz), 8 77 (br, IH), 9 96 (d, IR J = 1 5 Hz) FAB-MS (m/z), 672 (M+1 ) T Example S3 Synthesis of Compound 54 To a soluuon of 1 10 mg (0 2 mmol) of Compound c in 5 ml of methylene chlonde was added 0 16 ml (2 mmol) of acryloyi chlonde, followed by sumng at room temperature for 5 minutes To the mixture was gradually added 0 40 g (3 mmol) of alummum chlonde, followed by sumng for 2.5 hours The reacuon mixture was poured into ice-cold water, followed by extracuon with chloroform methanol The extraα was washed with a wnyr? twri aqueous soluuon of soώum chlonde and dried over soώum sulfate The solvent was evaporated under reduced pressure to give diacetylated Compound 54 The same procedure as in Example 1, Step B was repeated usmg the diacetylated Compound 54 to give 32 mg (25%) of Compound 54 H-NMR (DMSO-d 6 ) δ , 2 07 (dd, IR J - 4 9, 14 4 Hz), 2 17 (s, 3H). 2.50 (s, 6H), 3.37 (t, 2R J = 6 2 Hz), 3 45 (br, IH), 3 46 (t, 2R J = 6 2 Hz), 3 80 (dt, 4R J = 1 2, 6.2 Hz), 3 94 (s, 3H), 5 16 (d, 2R J = 3.9 Hz), 6 49 (s, IH), 7 25 (dd, IR J = 4 9, 7.2 Hz), 8.03 (dd, 2R J = 1 9, 9.0 Hz), 8 11 (dd, IR J = 1 5, 9 0 Hz), 8 13 (dd, IR J = 1 5, 9 0 Hz), 8 62 (d, IR J = 1.6 Hz), 8 77 (br, IH), 9.96 (d, IR J = 1 7 Hz) FAB-MS (m/z), 640 (M+l) + Exam p le 54 Synthesis of Compound 55 To a soiuuon of 126 mg (0 2 mmol) of Compound A in 5 ml of methylene chlonde was added 0 21 ml (2 0 mmol) of n-butyryl chlonde, followed by stirring at room temperature for 5 rrunutes. To the mixture was gradually added 0.40 g (3 mmol) of aluminum chloride, followed by stimng for 2.5 hours The reacuon mixture was poured into ice-cold water, followed by extraction with chloroform methanol. The extraα was washed with a saturated aqueous solution of soώum chlonde and dried over soώum sulfate. The solvent was evaporated under reduced pressure to give diacetylated Compound . The same procedure as in Example 1, Step B was repeated using the diacetylated compound to give 21 mg (25%) of Compound 55. H-NMR (DMSO-d6) δ , 1.01 (t, 2R J = 7.3 Hz), 1.74 (tq, 2R J = 7.1, 7.3 Hz), 2.01 (dd, IR J = 4 9, 14.2 Hz), 2.17 (s, 3H), 2.19 (t, 2R J = 7.1 Hz), 3.41 (dd, IR J = 7 3, 14.2 Hz), 3.93 (s, 3H), 5.13 (d, 2R J = 3.9 Hz), 6.45 (s, IH), 7.19 (dd, IR J = 4.9, 7.3 Hz), 7 64 (dd, IR J = 2.0, 8.8 Hz), 7.95 (d, IR J = 8.8 Hz), 8.02 (d, IR J = 9.0 Hz), 8.12 (dd, IR J = 1.7, 9.0 Hz), 8.59 (d, IR J = 1.5 Hz), 8.78 (s, IH), 9.41 (d, lR J = 1 7 Hz). FAB-MS (m/z); 616, 618 (M+l) + Exam p le 55 Synthesis of Compound 56 To a soluuon of 82 mg (0.15 mmol) of Compound c in 2 ml of methylene chloride was added 0.18 ml ( 1.5 mmol) of valeroyl chloride, followed by stirring at room temperature for 5 mmutes. To the mixture was gradually added 0.27 g (2.0 mmol) of aluminum chloride, followed by sumng for 3 hours The reacuon mixture was poured into ice-cold water, followed by extracuon with chloroform methanol. The extraα was washed with a saturated aqueous solution of soώum chlonde and dried over soώum sulfate. After the solvent was evaporated under reduced pressure, the residue was purified by sihca gel column chromatography (chloroform/methanol = 99/1) to give 59 mg (45%) of Compound 56 iH-NMR (CDC1 3 ) δ ; 1.01 (t, 3R J = 7.6 Hz), 1.02 (t, 3R J = 7.6 Hz), 1.51 (br, 4H), 1.80 (s, 3H), 1.82 (br, 4H), 2.17 (dd, IR J = 5.1, 14.7 Hz), 2.31 (s, 3H), 2.77 (s, 3H), 3.15 (br, 4H), 4.02 (dd, IR J = 7.4, 14.7 Hz), 4 03 (s, 3H), 5.38 (d, 2R J = 2.32 Hz), 6.99 (dd, IR J = 5.1, 7.4 Hz), 7.52 (d, IR J = 8.7 Hz), 7.96 (d, IR J = 8 8 Hz), 8.18 (dd, IR J = 1.7, 8.7 Hz), 8 19 (dd, IR J = 1.8, 8.8 Hz), 8.57 (d, IR J = 1.5 Hz), 9.82 (d, IR J = 1 6 Hz). FAB-MS (m/z), 720 (M+l) + Example 56 Synthesis of Compound 57 To a soluuon of 127 mg (0.2 mmol) of Compound g in 3.0 ml of chloroform were added 48 mg (0 1 mmol) of tetrabutylammonium bromide and 1 ml of methanol, followed by reflux for 5 hours The reaction mixture was poured mto ice-cold water, followed by extracuon with chloroform methanol (9/1) The extraα was washed with a saturated aqueous soluuon of soώum chlonde and dπed over soώum sulfate After the solvent was evaporated under reduced pressure, the residue was purified by sihca gel column chromatography (chloroform/methanol = 99/1) to give 21 mg (13%) of Compound 57 ^-NMR (CDC1 3 ) δ , 1.82 (s, 3H), 2.18 (dd, IR J = 5.1, 14.5 Hz), 2.33 (s, 3H), 2 77 (s, 3H), 4 04 (s, 3H), 4.05 (dd, IR J = 7.3, 14.5 Hz), 4 62 (d, 2R J = 4.9 Hz), 4.76 (d, 2R J = 1 0 Hz), 5.41 (d, 2R J = 1.5 Hz), 7.02 (dd, IR J - 5.1, 7.3 Hz), 7.58 (d, IR J = 8.8 Hz), 8 01 (d, IR J = 8 8 Hz), 8.23 (dd, IR J = 1.7, 8.8 Hz), 8.25 (dd, IR J = 1.7, 8.8 Hz), 8.64 (d, IR J = 1 7 Hz), 9 88 (d, IR J = 1.7 Hz) FAB-MS (m/z);794 , 796, 798(M+1) + Exam p le 57 Synthesis of Compound 58 To a solution of 105 mg (0.18 mmol) of Compound d m 3 ml of methanol/chloroform (1/1) was added 6.8 mg (0.18 mmol) of soώum borohydride, followed by stimng under ice cooling for 30 mmutes The reaction mixture was then poured mto ice-cold water, followed by extracuon with chloroform/methanol (9/ 1 ) The extraα was washed with a saturated aqueous soluuon of soώum chlonde and dπed over soώum sulfate. After the solvent was evaporated under reduced pressure, the residue was purified by sihca gel column chromatography (chloroform/methanol = 99/1) to give 85 mg (81%) of Compound 58 FAB-MS (m/z), 596 (M+I) + Exam p le 58 Synthesis of Compound 59 The same procedure as in Example 1, Step B was repeated usmg the produtt obtamed by repeating the same procedure as in Example 57 usmg 73 mg (0 1 mmol) of Compound 27 to give 37 mg (65%) of Compound 59 iH-NMR (DMSO-de) δ , 1 98 (br, IH), 2 10 (br, 2H), 2 14 (s, 3H), 2 22 (br, 2H), 3 37 (dd, IR J = 7 3, 13 9 Hz), 3 65 (br, 2H), 3 80 (br, 2H), 3 93 (s, 3H), 4 85 (br, 2H), 5 10 (br, 2H), 5 43 (br, IH), 5 48 (br, IH), 6 31 (s, IH), 7 12 (dd, IR J = 6 8, 7 3 Hz), 7 48 (br, 2H), 7 85 (br, 2H). 7 96 (d, 0 5 R J = 1 5 Hz), 7 97 (d, 0 5 R J = 1 5 Hz), 8 59 (s, IH), 9 16 (d, 0 5 R J = 1 5 Hz), 9 19 (d, 0 5 R J = 1 5 Hz) FAB-MS (m/z), 652 (M+l) + Exam p le 59 Synthesis of Compound 60 The same procedure as m Example 57 was repeated usmg 100 mg (0 12 mmol) of Compound 40 to give 47 mg (51%) of Compound 60 FAB-MS (m/z), 640 (M+l) + Exam p le 60 Synthesis of Compound 61 The same procedure as m Example 20 was repeated usmg 68 mg (0 10 mmol) of Compound H to give 8 7 mg (16%) of Compound 61 !RNMR (DMSO-ds) δ , 2 18 (s, 3H), 2 46 (s, 6H), 2 83 (dd, IR J = 4 9, 14 4 Hz), 3 52 (dd, IR J = 7 3, 144 Hz), 3 56 (s, 2H), 4 08 (s, 3H), 4 71 (d, IR J = 15 9 Hz), 4 80 (d, 1R J = 15 9 Hz), 4 90 (br, IH), 5 46 (br, IH), 6 80 (dd, 1R J = 4 9, 7 3 Hz), 7 24 (d, IR J = 8 3 Hz), 7 41 (br, 2H), 7 53 (dt, IR J = 1 1, 7 1 Hz), 7 93 (br, 2H), 9 06 (s, IH) FAB-MS (m/z), 549 (M+l) + Example 61 Synthesis of Compound 62 In a 30-ml two-necked flask were placed 12 6 mg (0 018 mmol) of bistπphenyiphosphine palladium (II) chlonde and 4 2 mg (0 022 mmol) of CuJ, and the atmosphere was replaced with argon To the mixture was added a soluuon of 40 mg (0 059 mmol) of Compound I in 3 ml of methvlene cholonde/diethvlamine (2/1), followed by stirπng at room temperature for 20 mmutes To the mixture was added 0 16 ml ( 1 5 mmol) of N-methyl-N-propargylbenzylamme, followed by sumng at room temperature for 3 hours After insoluble matenals were removed by fiitrauon, the filtrate was evaporated under reduced pressure The residue was puπfied by suica gel column chromatography (methanol/chloroform = 1/25) to give 12 3 mg (Z-form, 30%) of Compound 62 iH-NMR (DMSO-ώ5) , 2 02 (dd, IR J = 4 9, 13 7 Hz), 2 14 (s, 3H), 2 34 (s, 3H), 3 28 (d, 2R J = 9 5 Hz), 3 40 (dd, IR J = 7 3, 13 7 Hz), 3 57 (s, 2H), 3 66 (s, 2H), 3 93 (s, 3H), 5 05 (d, IR J = 18 2 Hz), 5 10 (d, IR J = 18 2 Hz), 6 42 (s,lH), 7 17 (dd, IR J = 4 9, 7 3), 7.29 (br, IH), 7 37 (br, 4H), 7 58 (d, IR J = 1 5, 8 8 Hz), 7 63 (d, IR J = 2 2, 8 8 Hz), 7 94 (d, 2R J = 8 8 Hz), 8 11 (d, IR J = 1 5 Hz), 8 74 (s, IH), 9 40 (d, IR J = 2 2 Hz) FAB-MS (m/z), 704, 706 (M+l) + Exam p le 62 Synthesis of Compound 63 To a soluuon of 71 4 mg (0 1 mmol) of diacetylated Compound 20 in 3 ml of methanol was added 25 mg of 10% Pd/C, followed by reflux in a hyώogeπ atmosphere for 1 hour Insoluble matenals were removed by fiitrauon, and the filtrate was evaporated under reduced pressure The residue was puπfied by sihca gel column chromatography (chloroform) to give 23 0 mg (Z-form, 33%) of Compound 63 FAB-MS (m/z), 718 (M+l) + Example 63 Synthesis of Compound 64 The same procedure as in Example 1, Step B was repeated usmg 23 mg (0 033 mmol) of Compound 63 to give 8 7 mg (41 %) of Compound 64 iH-NMR (CD 3 OD) δ , 2 11 (dd, IR J = 5 0, 14 1 Hz), 2.21 (s, 3H), 2 34 (s, 6H), 2 44 (s, 6H), 3 43 (dd, IR J = 7 7, 14 4 Hz), 3 55 (dd, 2R J =1 5, 6 5 Hz), 3 67 (dd, 2R J = 1 5, 6 5 Hz), 4 02 (s, 3H), 5 03 (d, 2R J = 5 8 Hz), 5 74 (dt, lR J = 6 5, 11 7 Hz), 5 80 (s, IH), 6 87 (d, 1RJ = 11 7 Hz), 6 88 (d, IR J = 11 7 Hz), 7 05(dd, IR J = 5 0, 7 7 Hz), 7 20-7 58 (m, 2H),7 68 (d, IR J = 8 4 Hz), 7 86 (s, IH), 7 95 (d,lR J = 8 8 Hz), 9 16 (s, IH) FAB-MS (m/z), 634 (M+l) + Example 64 Synthesis of Compound 65 To a soluuon of 1 16 g (0 64 mmol) of Compound e in 100 ml of acetonitnle was added 823 mg (2 4 mmol) of tnphenyiphosphine hydrobromide, followed by stirring at 80_C for 1 hour To the mixture was added ethyl acetate, and the precipitated phosphomum salt was collected by filtration, and dned under reduced pressure to give 1.22 g (67%) of crude phosphomum salt To a soluuon of 91 mg (0 1 mmol) of the phosphomum salt m 3 ml of methylene chlonde were added 16 5 mg (1 3 mmol) of potassium carbonate and 3.0 mg (0 011 mmol) of 18-crown-6, followed by sumng at room temperature for 30 mmutes To the mixture was added 2 3 ml (5 0 mmol) of propionaldehyde, followed by stimng at room temperature for 4 days The reaction mixture was the poured mto a saturated aqueous solution of ammonium chlonde, followed by extraction with chloroform The extraα was washed with a saturated aqueous solution of soώum chlonde, and dned over soώum sulfate After the solvent was evaporated under reduced pressure, the residue was purified by sihca gel column chromatography (chloroform/methanol = 200/1) to give 22 6 mg (E Z = 1/1, 37%) of Compound 65 FAB-MS (m s), 606 (M+l) + Exam p le 65 Synthesis of Compound 66 The same procedure as in Example 1, Step B was repeated usmg 22 6 mg (0 037 mmol) of Compound 65 to give 13 1 mg (E/Z « 1/1, 68%t of Compound 66 FAB-MS (m/s), 522 (M+l) + Exam p le 66 Synthesis of Compound 67 The same procedure as in Example 64 was repeated usmg 450 mg (0 64 mmol) of Compound K to give 367 mg (E Z = 1/1, 78%) of Compound 67 FAB-MS (m/s), 732 (m+l) + Exam p le 67 Synthesis of Compound 68 To a soluuon of 120 mg (0 02 mmol) of Compound f in 100 ml of acetonitπle was added 823 mg (2 4 mmol) of tnphenylphosphme hydrobromide, followed by stimng at 80_C for 1 hour To the mixture was then added ethyl acetate, and the precipitated phosphomum salt was coUected by fiitrauon, and dπed under reduced pressure to give crude phosphomum salt To a solution of the phosphomum salt in 3 ml of methylene chlonde were added 26 mg (0 2 mmol) of potassium-t- butoxide and 6.0 mg (0 022 mmol) of 18-crown-6, followed by sumng at room temperature for 30 mmutes To the mixture was added 0 12 ml (0.25 mmol) of propionaldehyde, followed by stimng at room temperature for 4 days The reacuon mixture was the poured mto a saturated aqueous soluuon of ammonium chlonde, followed by extraction with chloroform The extraα was washed with a saturated aqueous solution of soώum chlonde, and dned over soώum sulfate The solvent was evaporated under reduced pressure to give ώacetylated Compound 68 The same procedure as in Example 1, Step B was repeated using the ώacetylated compound to give 17 0 mg (mixture of E and Z, 13%) of Compound 68 FAB-MS (m/s); 576 (M+l) + Example 68 Synthesis of Compound 69 To a solution of 21 1 mg (0.3 mmol) of Compound 24 in 2 ml of trifluoroaceuc acid was added 0.19 ml (1.5 mmol) of tπethylsilane, followed by surring under ice coohng for 2 hours. The reaction mixture was the poured mto ice-cold water, and the resulting precipitates were collected by fiitrauon, and washed with hexane The produtt was then purified by silica gel column chromatography (chloroform) to give 150 mg (73%) of diacetylated Compound 69. The same procedure as in Example 1, Step B was repeated using 68 mg (0.1 mmol) of ώacetylated Compound 69 to give 48 mg (81 %) of Compound 69. iH-NMR (DMSO-c-6) δ ; 1.98 (dd, IR J = 3.8, 5.5 Hz), 2.13 (s, 3H). 3.24 ( , 5H), 3.92 (s, 3H), 3.93 (t, 2R J = 7.2 Hz), 3.97 (t, 2R 7.5 Hz), 5.01 (br, 2H), 6.30 (s, IH), 7.11 (dd, IR J = 3.8, 7.2 Hz), 7.40 (dd, IR J = 1.5, 8.3 Hz), 7.42 (dd, IR J = 1.5, 8.3 Hz), 7.84 (d, IR J = 8.3 Hz), 7.86 (d, IR 8.3 Hz), 7.97 (d, IH. J - 1.2 Hz), 8.63 (br, IH), 9.08 (d, IR J = 1.2 Hz) FAB-MS (m/s); 592, 594, 596(M+1) + Example 69 Synthesis of Compounds 70a, 70b and 70c To a solution of 679 mg (1.2 mmol) of Compound 69 in 10 ml of N,N-dιmeώylformamide was added 380 mg (23 mmol) of potassium iodide, followed by stirring at 90_C for 3 hours. The reaction mixture was poured into ice-cold water, followed by extraction with chloroform methanol (9/1). The extraα was washed with a saturated aqueous solution of soώum chloride and then dried over soώum sulfate. After evaporation under reduced pressure, the residue was purified by sihca gel column chromatography (chloroform) to give 300 mg (67%) of Compound 70a, 89 mg (15%) of Compound 70b, and 42 mg (5%) of Compound 70c Compound 70a ΪH-NMR (CDC1 3 ) δ, 2.20 (s, 3H), 2 47 (dd, IR J = 4 8, 8.3 Hz), 3 40 (br, 9H), 4.10 (s, 3H), 4.26 (br,lH), 4.86 (d, IR J - 16.7 Hz), 4 93 (d, IR J =16 7 Hz), 5.91 (br, IH), 6.85 (dd, IR J = 4.8,7.5 Hz), 7.28 (br, 2H), 7 37 (d, IR J = 8 3 Hz),7.72 (br, IH), 7.78 (d, IR J = 8.6 Hz), 8.97(br, IH) FAB-MS (m/s), 776 (M+l) + Compound 70b iH-NMR (DMSO-d 6 ) δ, 2.20 (s, 3H), 2.43 (dd, IR J = 4 8, 14.3 Hz), 3.17 (t, 2R J = 7.1 Hz), 3.21 (t,2R J = 7.1 Hz), 3.32 (dd, IR J = 7 4, 14.3 Hz),4 00 (s, 3H), 4.23 (br, IH), 4.50 (br, 4H), 4 84(d, IR J = 15.9 Hz), 4 93 (d, IR J = 15.9 Hz),6 00 (br, IH), 6.87 (dd, IR J = 4.8, 7.4 Hz),7.32 (dd, IR J = 1 7, 8.3 Hz), 7.34 (dd, IR J =1 7, 8 4 Hz), 7.39 (d, IR J = 8 3 Hz), 7.72 (s,lH), 7 76 (d, IR J = 8 4 Hz), 8 08 (s, IH), 8.09(s, IH), 9.04 (br, IH) FAB-MS (rn/s); 612 (M+l) + Compound 70c ^- MR (CDCI3) δ, 1.95 (dd, IR J = 4.8, 14 0 Hz), 2 13 (s, 3H), 2 92 (t, 2R J = 7.1 Hz), 3.16 (t, 2R J = 7.1 Hz), 3 34 (dd, IR J = 7 4, 14.0Hz), 3 70 (m, 4H), 3.92 (s, 3H), 4.67 (t, 2R J = 5.3 Hz), 4.99 (d, IR J = 5 8 Hz), 6.28 (br, IH), 7 08 (dd, IR J = 4.8, 7.4 Hz), 7.32 (dd, IR J =1 7, 8 4 Hz), 7 34 (dd, IR J = 1.7, 8 4 Hz), 7.78 (d, IR J = 8.4 Hz), 7.82 (d, IR J = 8 4 Hz), 8.59 (s, IH), 9 03 (br, IH) FAB-MS (m/s); 556 (M+l) + Example 70 Synthesis of Compound 71 To a solution of 55 mg (0.1 mmol) of Compound 70c in 5 ml of methylene chlonde were added 0.5 ml of tnethylaπune and 71 mg (0 4 mmol) of isonicotinoyl chlonde hydrochloride, followed by stimng at room temperature for 3 hours. The reacuon mixture was poured into ice- cooled 1 N hydrochlonc acid, followed by extraction with chloroform/methanol The extract was washed with a saturated aqueous solution of soώum chloride and dried over soώum sulfate. After the solvent was evaporated under reduced pressure, the residue was purified by sihca gel column chromatography (chloroform/methanol = 20/1) to give 32 mg (42%) of Compound 71. H-NMR (CDC1 3 ) δ; 1.97 (dd, IR J = 4.9, 13.9 Hz), 2.12 (s, 3H), 3.30 (br, 5H), 3.91 (s, 3H), 4.58 (dt, 2R J = 2.2, 6.7 Hz), 4.65 (t, 2R J = 6.7 Hz), 4.97 (br, 2H), 6.29 (s, IH), 7.09 (dd, IR J= 4.9, 7.1 Hz), 7.45 (d, 2R J = 8.6 Hz), 7.85 (br. 5H), 8.66 (s, IH), 8.77 (d, 4R J = 6.1 Hz),8.81 (d, 4R J = 6.1 Hz), 9.01 (d, IR J = 1.5Hz). FAB-MS (m s); 766 (M+l) + Example 71 Synthesis of Compounds 72a and 72b The same procedure as in Example 23 was repeated using 110 mg (0.2 mmol) of Compound c and 0.32 ml (2.0 mmol) of methyloxalyl chloride give a produtt. The same procedure as in Example 68 was repeated using the obtained produtt to give 12.2 mg (11%) of Compound 72a and 37.2 mg (31%) of Compound 72b. Compound 72a iH-NMR (CDC.3) δ; 2.16 (s, 3H), 2.72 (dd, IR J = 4.8, 14.4 Hz), 3.43 (dd, IR J = 7.6, 14.4 Hz), 3.77 (s, 3H), 3.78 (s, 2H), 4.09 (s, 3H), 4.64 (d, 1RJ = 16.3 Hz), 4.75 (d, IR J = 16.3 Hz), 4.85 (br, IH), 5.54 (br, IH), 6.80 (dd, IR J = 4.8, 7.6 Hz), 7.36 (d, IR J = 7.3 Hz), 7.39 (dt, IR J = 0.8, 7.3 Hz), 7.50 (s, 2H), 7.88 (d, IR J = 7.3 Hz), 7.91 (d, IR J = 8.3 Hz), 8.82 (br, IH). FAB-MS (m/s); 540 (M+l) + Compound 72b H-NMR (CDCI3) δ; 2.00 (dd, IR J = 4.7, 14.0 Hz), 2.15 (s, 3H), 3.30 (s, IH), 3.65 (s, 6H), 3.84 (s, 2H), 3.90 (s, 2H), 3.93 (s, 3H), 5.00 (d, 2RJ = 5.4 Hz), 6.33 (s, IH), 7.12 (dd, IR J = 4.7,7.1 Hz), 7.36 (d, IR J = 7.3 Hz), 7.85 (d, IR J= 7.3 Hz), 7.94 (d, IR J = 7.3 Hz), 7.95 (s.lH), 8.05 (d, IR J = 7.3 Hz), 8.62 (br, IH), 9.08 (s, IH). FAB-MS (m/s); 612 (M+l) + Example 72 Synthesis of Compounds 73a, 73b and 73c The same procedure as in Examples 68 and 69 was repeated using 141 mg (0.2 mmol) of Compound 27 to give 56 mg (67%) of Compound 73a, 3.0 mg (2.4%) of Compound 73b and 27 mg (23%) of Compound 73c Compound 73 a FAB-MS (m/s); 804 (M+l) + Compound 73b iH-NMR (CDCl ) δ ; 2.10-2.18 (m, 4H), 2.21 (s, 3H), 2.29 (dd, IR J = 4.9, 14.3 Hz), 2.92 (t, 2R J =7 4 Hz), 2.94 (t, 2R J = 7.4 Hz), 3.27 (dd, 1RJ = 7.5, 14.3 Hz), 4.24 (s, 3H), 4.26 (t, 2R J =7.4 Hz), 4.28 (t, 2R J = 7 4 Hz), 5 02 (d, 2R = 6.4 Hz), 6.09 (br, IH), 6.88 (dd, IR J = 2.7,4.7 Hz), 7.30 (d, IR J = 8.0 Hz), 7.37 (d, IR J= 8.3 Hz), 7.42 (d, IR J = 8.0 Hz), 7.71 (d, 1RJ = 1 7 Hz), 7.72 (d, J = 8.3 Hz), 8.12 (s, 1H),8.14 (s, IH), 9.14 (d, IR J = 1.2 Hz) FAB-MS (m/s); 640 (M+l) + Compound 73c 1 H-NMR (CDCI3) δ; 1.85 (s, 4H), 1.97 (dd, IR J = 4.9, 14.1 Hz), 2.17 (s, 3H), 2.81 (dt, 4R J = 10.0, 16.0 Hz), 3.33 (dd, IR J = 7.1, 14 1 Hz), 3.50 (t, 4R J = 6.4 Hz), 3.92 (s, 3H), 4.49 (br, 2H),4.99 (d, IR J = 5.4 Hz), 6.27 (S, IH), 7.07 (dd,lR J = 4.9, 7.3 Hz), 7.32 (d, 2R J = 8.4 Hz),7.78 (d, IR J = 8 4 Hz), 7 82 (s, IH), 7.83 (d,lR J = 8.4 Hz), 9.03 (d, IR J = 1.2 Hz). FAB-MS (m/s); 584 (M+l) + Example 73 Synthesis of Compound 74 To a solution of 31 mg (0.05 mmol) of Compound 22 in 3 ml ofN,N-ώmethylformamιde was added 15 mg of 10% Pd/C, followed by stirring in a hydrogen atmosphere at 60_C for 5 hours After insoluble matenals were removed by filtration, the filtrate was evaporated under reduced pressure The residue was purified by sihca gel column chromatography (chloroform) to give 12 mg (20%) of Compound 74 -NMR (CDC1 3 ) δ, 2.05 (br, 4H), 2.20 (s, 3H), 2.44 (dd, IR J = 4 9, 14.4 Hz), 2.88 (t, 2R J = 7 4 Hz), 2.92 (t, 2R J = 7.4 Hz), 3.32 (dd, IR J = 7.4, 14.4 Hz), 3.47 (t, 2R J = 7 4 Hz), 3 48 (t,2R J - 7.4 Hz), 3.78 (s, 6H), 4.00 (s, 3H), 4.12(br, IH), 4.85 (d, IR J = 15.8 Hz), 4.92 (d, 1RJ = 15.8 Hz), 5.93 (br, IH), 6.85 (dd, IR J =4.9, 7.4 Hz), 7.30 (br, 2H), 7.34 (d, IR J = 8.0Hz), 7.70 (d, IR J = 1.3 Hz), 7.74 (d, IR J =7.3 Hz), 8.98 (d, IR J = 1.0 Hz) FAB-MS (m/s); 612 (M+l) + Example 74 Synthesis of Compound 75 To a solution of 50 mg (0.06 mmol) of Compound 70a in 3 ml of N,N-dιmethylformamιde was added 0.5 ml of pipcπdine, followed by stirring at room temperature overnight. Water was added to the reaction mixture, followed by extraction with chloroform/methanol (9/1). The extract was washed with a saturated aqueous solution of soώum chloride, and dπed over soώum sulfate. After the solvent was evaporated under reduced pressure, the residue was puπfied by sihca gel column chromatograpby (chloroform/methanol = 10/1) to give 10 mg (15%) of Compound 75 iH-NMR (CDCI3) δ; 1.55 (br, 10H)§ 2.19 (s, 3H), 2.31 (dd, IR J = 4.9, 7.6 Hz), 2.53 (br, 8H), 2.66 (br, 2H), 2.74 (br, 2H), 3.02 (br, 2H), 3.26 (dd, IR J = 6.8, 7.5 Hz), 4.09 (s, 3H), 4.93 (d, 2R J = 10.2 Hz), 6.09 (br, IH), 6.86 (dd, IR J = 4.9, 7.3 Hz), 7.35 (br, 3H), 7.71 (d, IR J - 8.6 Hz), 7.74 (d, IR J = 1.5 Hz), 9.08 (br, IH). FAB-MS (m/s); 690 (M+l) + Example 75 Synthesis of Compound 76 The same procedure as in Example 74 was repeated using 50 mg (0.06 mmol) of Compound 70a and 0.5 ml of morpholine to give 24 mg (59%) of Compound 76 iH-NMR (CDC1 3 ) δ, 2.20 (s, 3H), 2.29 (dd, IR J = 4.9, 14 4 Hz), 2.69 (br, 8H), 2.71 (br, 4H), 3 01 (br, 4H), 3.26 (dd, IR J = 7 4, 14 4 Hz), 3 78 (br, 8H), 3.89 (br, IH), 4 09 (s, 3H), 4 98 (d, 2R J = 4.9 Hz), 6 11 (s, IH), 6 87 (dd, IR J = 4 9, 7.4 Hz), 7.34 (br, 2H), 7 70 (d, IR J = 8 5 Hz), 7 71 (d, IR J = 8.5 Hz), 7 74 (d, IR J = 1.2 Hz), 9 12 (s, IH) FAB-MS (m/s), 694 (M+l) + Example 76 Synthesis of Compound 77 The same procedure as in Example 74 was repeated usmg 50 mg (0.06 mmol) of Compound 70a and 0.5 ml of ώethylamine to give 7.3 mg (18%) of Compound 77 iH-NMR (CDCI3) δ, 1 12 (t, 6R J = 7.2 Hz), 1.14 (t, 6R J = 7.2 Hz), 2.19 (s, 3H), 2.37 (dd, IR J = 4.9, 14 4 Hz), 2.68 (q, 4R J = 7.2 Hz), 2.72 (q, 4R J = 7.2 Hz), 2.83 (br, 4H), 2.95 (br, 4H), 3.29 (dd, IR J = 7 4, 14 4 Hz), 4 09 (s, 3H), 4 88 (d, IR J = 16 4 Hz), 4 96 (d, IR J = 16.4 Hz), 6 05 (br, IH), 6 86 (dd, IR J = 4.9, 7 4 Hz), 7.29 (br, 2H), 7.36 (d, IR J = 8 3 Hz), 7 70 (s, IR), 7.73 (d, IR J = 8.3 Hz), 9.03 (s, IH) FAB-MS (m/s), 666 (M+l) + Example 77 Synthesis of Compound 78 The same procedure as in Example 74 was repeated usmg 50 mg (0.06 mmol) of Compound 70a and 1 ml of N-methylethanolamine to give 8.3 mg (21%) of Compound 78 iH-NMR (CDCI3) δ; 1.60 (br, 2H), 2.18 (s, 3H), 2.31 (dd, IR J = 4 9, 14.4 Hz), 2.40 (s, 3H), 2.41 (s, 3H), 2 64 (t, 2R J = 5.1 Hz), 2.66 (t, 2R J = 5.1 Hz), 3.01 (br, 4H), 3.26 (br, 5H), 3.59 (t, 2R J = 5.1, 14.4 Hz), 3.61 (t, 2R J = 5 1, 14 4 Hz), 4 08 (s, 3H), 4 89 (d, IR J = 16.4 Hz), 4.98 (d, IR J = 16 4 Hz), 6 19 (br, IH), 6 85 (dd, IR J = 4 9, 7.3 Hz), 7.28 (d, IR J = 8.3 Hz), 7.31 (d, IR J = 8.3 Hz), 7 38 (d, IR J - 8 3 Hz), 7 69 (br, IR), 7 72 (d, IR J = 8 3 Hz), 9 09 (s, IH) FAB-MS (m/s), 670 (M+l) + Example 78 Synthesis of Compound 79 The same procedure as in Example 74 was repeated using 50 mg (0 06 mmol) of Compound 70a and 0.5 ml of a 1.0 N solution of methylaπune in ethanol to give 12 mg (34%) of Compound 79 iH-NMR (CDC1 3 ) δ, 2.15 (s, 3H), 2.23 (br, IH), 2 47 (s, 3H), 2 49 (s, 3H), 2.94 (br, 2H), 3.00 (br, 6H), 3.25 (dd, IR J = 7.3, 14 4 Hz), 4 08 (s, 3H), 4.88 (d, IR J = 16 6 Hz), 4 95 (d, IR J = 16.6 Hz), 6.21 (br, IH), 6.85 (dd, IR J = 4 9, 7 1 Hz), 7.29 (d, IR J = 8 3 Hz), 7.31 (d, IR J = 8.3 Hz), 7 39 (d, IR J = 8 3 Hz), 7 69 (s, IH), 7 71 (d, IR J = 8.3 Hz), 9.08 (s, IH) FAB-MS (m/s), 582 (M+l) + Example 79 Synthesis of Compound 80 To a solution of 78 mg (0.1 mmol) of Compound 70a in 3 ml of methylene chlonde was added 0 78 ml (6 0 mmol) of p-methoxybenzylamine, followed by reflux for 1 day Water was added to the reaction mixture, followed by extraction with chloroform/methanol (9/1) The extract was washed with a saturated aqueous solution of soώum chlonde, and dπed over soώum sulfate After the solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography (chloroform/methanol = 10/1) to give 47 mg (59%) of Compound 80 iH-NMR (CDCI3) δ, 2.16 (s, 3H), 2.33 (dd, IR J = 4 9, 7.3 Hz), 3 02 (br, 8H), 3.25 (dd, IR J = 7 3, 14 4 Hz), 3 764 (s, 3H), 3 769 (s, 3H), 3 773 (s, 4H), 4 08 (s, 3H), 4 79 (d, IR J = 16.7 Hz), 4.87 (d, IR J = 16.7 Hz), 6.10 (br, IH), 6 63- 7 03 (br, 5H), 7.10-7.34 (br. 7H), 7.67 (s, IH), 7 71 (d, IR J = 8.5 Hz), 9.05 (s, IH) FAB-MS (m/s), 794 (M+l) + Example 80 Synthesis of Compound 81 To a solution of 20 mg (0.026 mmol) of Compound 70a in 3 ml of dimethylsulfoxidc was added 9 8 mg (0.15 mmol) of soώum azide, followed by stirring at room temperature overmght Water was added to the reacuon mixture, and precipitates were removed by filtration. After the filtrate was evaporated under reduced pressure, the residue was purified by sihca gel column chromatography (chloroform/methanol « 20/1) to give 14 mg (89%) of Compound 81 iH-NMR (DMSO-dg) 5; 1.97 (dd, IR J = 4.9, 13.9 Hz), 2.13 (s, 3H), 3.05 (t, 2R J = 7 0 Hz), 3.09 (t, 2R J = 7.0 Hz), 3.36 (dd, IR J = 7.3, 13.9 Hz), 3.66 (t, 2R J = 7 0 Hz), 3.69 (t, 2R J = 7 0 Hz), 3.92 (s, 3H), 5.00 (br, 2H), 6 30 (s, IH), 7.10 (dd, IR J = 4 9, 7.3 Hz), 7.39 (dd, IR J = 1.7, 8.3 Hz), 7 41 (dd, IR J = 1 7, 8.3 Hz), 7.84 (d, IR J = 8.3 Hz), 7.86 (d, IR J - 8.3 Hz), 7 95 (dd, IR J = 1.5 Hz), 8.62 (br, IH), 9.09 (dd, IR J = 1.5 Hz). FAB-MS (m/s); 606 (M+l) + Example 81 Synthesis of Compound 82 The same procedure as in Example 74 was repeated usmg 50 mg (006 mmol) of Compound 73a and 2.0 ml of piperidine to give 16 mg (36%) of Compound 82 1 H-NMR (CDCI3) δ;1.43 (br, 4H), 1.60 (br, 12H), 1.90 (br, 4H), 2.20 (s, 3H), 2.31 (dd, IR J = 4.9, 14.4 Hz), 2.38-2.50 (br, 8H), 2.78-2.86 (br, 4H), 3.27 (dd, IR J = 7.3, 14 4 Hz), 4.09 (s, 3H), 4.97 (d, 2R J = 6 4 Hz), 6 07 (br, IH), 6.86 (dd, IR J = 4.9, 7.3 Hz), 7.30 (m, 2H), 7.38 (d, IR J = 8.3 Hz), 7 700 (d, IR J = 8 3 Hz), 7.703 (d, IR J « 1.5 Hz), 9 07 (br, IH) FAB-MS (m/s); 718 (M+I) + Example 82 Synthesis of Compound 83 The same procedure as in Example 74 was repeated usmg 50 mg (0.06 mmol) of Compound 73a and 0.3 ml of morpholine to give 11 mg (26%) of Compound 83. HNMR f MSO^ δ .β l fbr^H), 1.97 (dd, IR J = 4 6, 14.9 Hz), 2.19 (br, 12H), 2.21 (s, 3H), 2.83 (br, 4H), 3.59 (br, 9H), 3.92 (s, 3H), 4.98 (d, 2R J = 4.6 Hz), 6.28 (br, IH), 7.07 (dd, IR J = 4.6, 7.3 Hz), 7.32 (d, IR J = 2.0, 8.8 Hz), 7.33 (d, IR J = 2.0, 8.8 Hz), 7.77 (d, IR J = 8.8 Hz), 7.81 (d, IR J = 8.8 Hz), 7.83 (d, IR J = 1.0 Hz), 8.57 (s, IH), 9.04 (d, IR J = 1.0 Hz). FAB-MS (m s), 722 (M+I) + Example 83 Synthesis of Compound 84 The same procedure as in Example 74 was repeated using 50 mg (0.06 mmol) of Compound 73a and 0.5 ml of ώethylamine to give 7.9 mg (19%) of Compound 84 iH-NMR (DMSO-d^) δ; 0.97 (t, 6R J = 7.1 Hz), 0.98 (t, 6R J = 7.1 Hz), 1 81 (br, 12H), 1.97 (dd, IR J = 4.9, 14.5 Hz), 2.12 (s, 3H), 2.28 (t, 2R J = 8.8 Hz), 2.30 (t, 2R J = 8.8 Hz), 2.41-2.49 (br, 4H), 3.30 (br, IH), 3.92 (s, 3H), 4.99 (d, 2R J = 5.4 Hz), 6.28 (s, IH), 7.07 (dd, IR J = 4.9, 7.3 Hz), 7.32 (dd, IR J = 1.9, 8.5 Hz), 7.33 (dd, IR J = 1.9, 8.5 Hz), 7.77 (d, IR J = 8.5 Hz), 7.81 (s, IH), 7.83 (d, IR J = 8.5 Hz), 8.56 (s, IH), 9.04 (d, IR J = 1.5 Hz) FAB-MS (m/s); 694 (M+l) + Example 84 Synthesis of Compound 85 Step A To a solution of 1.0 g (1.25 mmol) of Compound 73a in 10 ml of dimethylsulfoxide was added 488 mg (7.5 mmol) of soώum azide, followed by sti ng at room temperature overnight. Water was added to the reacuon mixture, and precipitates were collected by filtration. To a soluuon of 310 mg (about 0.43 mmol) of the obtained produtt m 5.0 ml of chloroform/methanol (9/1) was added 2 6 g (10 mmol) of tnphenylphosphme, followed by stimng at room temperature overnight To the reacuon mixture was added water, followed by extracuon with chloroform/methanol (9/1) The extract was washed with a saturated aqueous solution of soώum chloride, and dπed over sodium sulfate The solvent was evaporated under reduced pressure to give 497 mg (quantitative) of a diamino compound Step B To a soluuon of 58 mg (0 1 mmol) of the diamino compound in 2.0 mi of methylene chlonde was added 0 075 ml (0 5 mmol) of ethyl isocyanate, followed by stirring at room temperature overnight To the reacuon mixture was added water, followed by extraction with chloroform/methanol The extraα was washed with a saturated aqueous solution of soώum chlonde, and dned over soώum sulfate After the solvent was evaporated under reduced pressure, the residue was puπfied by sdica gel column chromatography (chloroform/methanol = 10/1) to give 2.0 mg (2 7%) of Compound 85 iH-NMR (DMSO-dg) δ, 0 99 (t, 3R J = 7.2 Hz), 1 00 (t, 3R J = 7 2 Hz), 1.78 (br, 4H), 1 97 (dd, IR J = 4 8, 14 1 Hz), 2.12 (s, 3H), 2 76 (br, 4H), 3 10 (br, 8H),3.37 (br, IH), 3.92 (s, 3H), 5.00 (br, 2H), 5 74 (br, 2H). 5 86 (br, 2H), 6.28 (br, IH), 7 07 (dd, IR J = 4 8, 7.3 Hz), 7.31 (d, 2R J = 8 4 Hz), 7 78 (d, IR J = 8 4 Hz), 7 82 (s, IH), 7.83 (d, IR J = 8 4 Hz), 8 58 (s, IH), 9 03 (d, IR J = 1 5 Hz) FAB-MS (m/s), 724 (M+l) + Example 85 Synthesis of Compound 86 To a soluuon of 58 mg (0.1 mmol) of the diamino compound obtamed in Example 84, Step A in 2.0 ml of methylene chlonde were added 0.5 ml of pynώne and 91 mg (0.5 mmol) of ώ-t-butyl ώcarbonate, followed by stimng at room temperature overnight To the reaction mixture was added water, followed by extracuon with chloroform/methanol(9/l) The extract was washed with a saturated aqueous solution of soώum chlonde, and dπed over soώum sulfate. After the solvent was evaporated under reduced pressure, the residue was purified by sihca gel column chromatography (chloroform/methanol = 10/1) to give 8 0 mg (10%) of Compound 86 iH-NMR (CDCI3) δ, 1 45 (s, 18H), 1.92 (br, 4H), 2 19 (s, 3H), 2 40 (dd, lR J = 4 6, 14 4 Hz), 2 80 (br, 4H), 3 23 (br, 4H), 3.31 (dd, IR J = 7.3, 14 4 Hz), 4 09 (s, 3H), 4 67 (br, 2H), 4 79 (d, IR J = 16.4 Hz), 4 89 (d, IR J = 16 4 Hz), 5 98 (br, IH), 6 85 (dd, IR J = 4 6, 7 3 Hz), 7.25- 7.29 (m, 2H), 7 35 (d, IR J = 8 3 Hz), 7 65 (br, IH), 7 73 (d, IR J = 8.3 Hz), 8.95 (s, IH) FAB-MS (m/s), 782 (M+l) + Example 86 Synthesis of Compound 87 The same procedure as in Example 68 was repeated usmg 45 mg (0 070 mmol) of Compound 43 to give 20 mg (46%) of Compound 87. iH-NMR (CDCI 3 ) δ, 1 97 (dd, IR J - 4 9, 13.8 Hz), 2.14 (s, 6H), 2.16 (s, 3H), 2 79-2 89 (br, 4H), 2 97-3 09 (br, 4H), 3.35 (dd, IR J = 7.3, 13.8 Hz), 3.92 (s, 3H), 5.00 (br, 2H), 6 29 (s, IH), 7.09 (dd, IR J = 4 9, 7.3 Hz), 7.36 (dd, IH, J = I 7, 8.5 Hz), 7 38 (dd, IR J = 1 7, 8.5 Hz), 7 80 (d, IR J = 8 5 Hz), 7 83 (d, IR J = 8 5 Hz), 7 90 (d, IR J = 1.5 Hz), 8 59 (br, IH), 9 05 (d, IR J = 1.2 Hz) FAB-MS (m/s), 616 (M+l) + Example 87 Synthesis of Compound 88 The same procedure as in Example 68 was repeated usmg 886 mg (1.3 mmol) of Compound 44 to give 710 mg (85%) of Compound 88 iH-NMR (CDCI3) δ, 1.31 (t, 3R J = 73 Hz), 1.33 (t, 3R J = 7.3 Hz), 2.18 (s, 3H), 2.60- 2.68 (m, 5H), 2.86 (br, 2H), 2.94 (br, 2H), 3.06 (br, 2H), 3.12 (br, 2H), 3 37 (dd, IR J = 7.3, 14.1 Hz), 4 09 (s, 3H), 4 75 (d, IR J = 16.1 Hz), 4 83 (d, IR J = 16.1 Hz), 5.73 (s, IH), 6.82 (dd, IR J = 4.9, 7 3 Hz), 7.24 (dd, IR J = 1 7, 8 3 Hz), 7.29 (d, IR J = 8.3 Hz), 7.33 (dd, IR J = 1 7, 8.5 Hz), 7.71 (d, IR J = 1.2 Hz), 7.80 (d, IR J = 8.5 Hz), 8.85 (br, IH) FAB-MS (m s), 644 (M+l) + Exam p le 88 Synthesis of Compound 89 To a solution of 77 mg (0 1 mmol) of Compound 70a in 2 ml of N,N-ώmethylformamιde were added 0.025 ml (0 24 mmol) of methyl 2-mercaptoacetate and 138 mg (1.0 mmol) of potassium carbonate, followed by stimng at room temperature for 2 hours To the reaction mixture was added water, followed by extraction with chloroform/methanol(9/l) The extract was washed with a saturated aqueous solution of soώum chlonde, and dried over soώum sulfate. After the solvent was evaporated under reduced pressure, the residue was puπfied by sihca gel column chromatography (chloroform methanol = 20/1) to give 37 mg (51%) of Compound 89 iH-NMR (CDC1 3 ) δ, 1 96 (dd, IR J = 5.3, 14 0 Hz), 2.13 (s, 3H), 3.00 (br, 8H), 3 30 (br, IH), 3 43 (s, 2H), 3 46 (s, 2H), 3.67 (s, 3H), 3 68 (s, 3H), 3.91 (s, 3H), 5.01 (br, 2H), 6.31 (br, IH), 7.09 (dd, IR J = 5.3, 7.7 Hz), 7 35 (dd, IR J = 1.6, 8.7 Hz), 7.37 (dd, IR J « 1.6, 8 7 Hz), 7.81 (d, IR J = 8 7 Hz), 7 84 (d, IR J = 8 7 Hz), 7.89 (s. IH), 8.62 (s, IH), 9 04 (s, IH) FAB-MS (m/s), 732 (M+l) + Example 89 Synthesis of Compound 90 The same procedure as in Example 88 was repeated usmg 77 mg (0 1 mmol) of Compound 70a and 0.027 ml (0.24 mmol) of ethyl 3-mercaptopropιonate to give 43 mg (55%) of Compound 90 iH-NMR (CDCI3) δ, 1.23 (t, 3R J = 7 1 Hz), 1.26 (t, 3R J = 7 1 Hz), 2 18 (br, 3H), 2.59-3.62 (br, 5H), 2.83-2 89 (m, 6H), 2.96 (br, 2H), 3 02-3.07 (br, 2H), 3.10- 3.16 (m, 2H), 3.37 (dd, IR J = 7.6, 14 4 Hz), 4 08 (s, 3H), 4 15 (m, 4H), 4 73 (d, IR J - 16.6 Hz), 4 75 (br, IH), 4 83 (d, IR J = 16 6 Hz), 5 76 (br, IH), 6 83 (dt, IR J = 4 9, 7.6 Hz), 7.23 (dd, IR J = 8.7 Hz), 7 27 (d, IR J = 8 8 Hz), 7 32 (dd, IR J = 1 7, 8.8 Hz), 7 70 (s, IH), 7.80 (d, IR J = 8 8 Hz), 8 83 (s, IH) FAB-MS (m/s), 788 (M+l) + Example 90 Synthesis of Compound 91 The same procedure as in Example 68 was repeated usmg 65 mg (0.081 mmol) of Compound 50 to give 42 mg (67%) of Compound 91 iH-NMR (DMSO-d^) δ, 1 97 (dd, IR J = 4 7, 7.9 Hz), 2.08 (s, 3H), 3 00-3 05 (br, 4H), 3.15-3 21 (br, 4H), 3.39 (br, IH), 3.91 (s, 3H), 5.00 (br, 2H), 6.30 (s, IH), 6 79 (dt, 4R J = 2.2, 8.8 Hz), 7.32 (br, lOH), 7 79 (d, IR J = 8 6 Hz), 7.83 (d, IR J = 8 6 Hz), 7 86 (s, IH), 9 04 (d, IR J = 1.2 Hz), 9 54 (s, IH), 9 55 (s, IH) FAB-MS (m/s), 772 (M+l) + Example 91 Synthesis of Compound 92 The same procedure as in Example 68 was repeated using 38 mg (0.05 mmol) of Compound 51 to give 22 mg (56%) of Compound 92 iH-NMR (DMSO-ώs) δ, 1 97 (dd, IR J = 4 9, 13 8 Hz), 2 06 (s, 8H), 2 13 (s, 3H), 3.21- 3.25 (m, 4H), 3 36 (dd, IR J = 7 3, 13.8 Hz), 3 92 (s, 3H), 3.94 (t, 2R J = 7 3 Hz), 3 97 (t, 2R J = 7.3 Hz), 5.01 (br, 2H), 6 30 (br, IH), 7 10 (dd, IR J = 4.9, 7.3 Hz), 7 40 (d, IR J = 1 7, 8.3 Hz), 7 42 (dd, IR J = 1 7, 8.3 Hz), 7 84 (d, IR J = 7 3 Hz), 7 86 (d, IR J = 8 3 Hz), 7.98 (d, IR J = 1 4 Hz), 8 63 (br, IH), 9 08 (d, IR J = 1 2 Hz) FAB-MS (m s), 756 (M+l) + Example 92 Synthesis of Compound 93 The same procedure as in Example 46 was repeated usmg 31 mg (0 05 mmol) of Compound 69 to give 10 mg (26%) of Compound 93 iH-NMR (CDCI3) δ, 2.28 (s, 3H), 2.30 (dd, IR J = 4.9, 14 2 Hz), 3 17-3.21 (br, 2H), 3.33 (t, 2R J = 7 3 Hz), 3 42-3 46 (m, 3H), 3 48-3 52 (m, 2H), 3 63 (t, 2R J = 7.2Hz), 4.09 (s, 3H),4.99(br, IH), 6.27(br, IH), 6.88 (dd, IR J =4.9, 7.0Hz), 7.09 (d, 2RJ = 64 Hz), 7.12 (d, 2R J =64Hz), 7.31 (dd, IR J = 1.5, 8.3 Hz), 7.33 (dd, IRJ = 1.7, 8.3Hz), 7.43 (d, IRJ =8.3 Hz), 7.68 (s, IH), 7.76(d, IR J= 8.4 Hz), 8.21 (d,2R J=64Hz), 8.34 (d, 2R J =64 Hz), 9.19 (s, IH). FAB-MS (m/s), 742 (M+l) + Example 93 Synthesis of Compound 94 The same procedure as in Example 47 was repeated usmg 77 mg (0.1 mmol) of Compound 70a to give 21 mg (28%) of Compound 94 lH-NMR (CDCl 3 ) δ, 2.16 (s, 3H), 2.78 (dd, IR J = 4.7, 14 4 Hz), 3.14 (br, 2H), 3.27 (t, 2R J = 7.2 Hz), 3 41 (dd, IR J = 7.4, 14.4 Hz), 3.50 (br, 2H), 3.63 (t, 2R J = 7.2 Hz), 4.03 (s, 3H), 4 69 (br, IH), 5.08 (br, IH), 5 45 (br, 3H), 6.79 (dd, IR J = 4.7, 7.4 Hz), 6.99 (br, 2H), 7.25 (br, 4H), 7 40 (dd, IR J = 1.7, 8.5 Hz), 7.48 (br, 2H), 7.75 (s, IR), 7.85 (d, IR J = 8.5 Hz), 8.52 (br, 2H), 8.78 (s, IH). FAB-MS (m/s); 742 (M+l) + Example 94 Synthesis of Compound 95 The same procedure as in Example 68 was repeated usmg 60 mg (0.089 mmol) of Compound 53 to give 20 mg (35%) of Compound 95. iH-NMR (DMSO-d 6 ) δ, 1.95 (m, 5H), 2.08 (s, 3H), 2.09 (s, 3H), 2.13 (s, 3H), 2.55 (t, 4R J = 7.6 Hz), 2.86 (t, 2R J = 7.6 Hz), 2.88 (t, 2R J = 7 6 Hz), 3.34 (dd, IR J = 7.3, 14.1 Hz), 3.92 (s, 3H), 4.99 (d, 2R J = 4.9 Hz), 6.28 (s, IH), 7.08 (dd, IR J = 4.9, 7.3 Hz), 7.32 (dd, IR J = 2.7, 8.5 Hz), 7.38 (dd, IR J = 1.7, 8.5 Hz), 7.79 (d, IR J = 8.5 Hz), 7.83 (d, IH, J - 1.2 Hz), 7.84 (d, IR J = 8.5 Hz), 8.57 (br, IH), 9 04 (s, IH). FAB-MS (m/s); 644 (M+l) + Exampte 95 Synthesis of Compound 96 The same procedure as in Example 88 was repeated using 80 mg (0.1 mmol) of Compound 73a and 34 mg (0.20 mmol) of 2-mercaptobenzothιazole to give 35 mg (40%) of Compound 96 iH-NMR (DMSO-dg) δ, 1.97 (dd, IR J = 4.9, 14.0 Hz), 2.12 (s, 3H), 2.18-2.22 (m, 4H), 2.96-3.00 (m, 4H), 3.33 (br, 3H), 3.44 (t, 2R J = 2.8 Hz), 3.91 (s, 3H), 4.97 (br, 2H), 6.29 (s, IH), 7.08 (dd, IR J = 4.9, 7.3 Hz), 7.26-7.52 (m, 6H), 7.80-8.00 (m, 7H), 8.56 (br, IH), 9.07 (d, IR J = 1.2 Hz). FAB-MS (m/s), 882 (M+l) + Example 96 Synthesis of Compound 97 To a soluuon of 335 mg (1.5 mmol) of palladium (II) acetate in 5 ml of N,N- ώmethylformamide was added 1.82 mg (6.0 mmol) of bis(o-tolyl)phosphine, followed by sumng in an argon stream at room temperature for 30 mmutes. To the mixture were added a solution of 3.29 g (5.0 mmol) of Compound B in 30 ml of N,N-oimethylformamide, 0.60 ml (80 mmol) of tnethyiamine and 0.28 ml (2.1 mmol) of 2-vinylpyridine, followed by stimng at 60_C for 3 hours. After the solvent was evaporated under reduced pressure, the residue was purified by sihca gel column chromatography (chloroform methanol = 50/1) to give 2.24 g (66%) of Compound 97. iH-NMR (DMSO-dg) δ; 1.79 (s, 3H), 2.13 (dd, IR J = 5.1, 15.4 Hz), 2.32 (s, 3H), 2.77 (s,3H), 3.99(dd, IRJ=7.3, 15.4 Hz), 4.02 (s, 3H), 5.35 (br, 2H), 6.98 (dd, IR J=5.1,7.3 Hz), 7.15(ddd, IRJ= 1.0,4.8, 7.8Hz), 7.47(d, IR J =8.8Hz), 7.48(d, IR J= 7.8 Hz), 7.69(dt, IRJ= 1.7, 8.8Hz),7.78 (dd, IR J = 1.7, 8.8 Hz),7.83 (d, IR J= 16.1 Hz), 8.01 (br,2H), 8.08 (dd, IRJ= 1.7, 7.8Hz), 8.46 (d, IR J= 1.5 Hz), 8.63 (ddd, IRJ =0.7, 1.7, 4.9Hz), 9.29 (d, IH.J - 1.5 Hz), 10.20(s, IH). FAB-MS (m/s); 683 (M+l) + Example 97 Synthesis of Compound 98 The same procedure as in Example 57 was repeated usmg 1.0 g (1 4 mmol) of Compound 97 to give 870 mg (87%) of Compound 98 FAB-MS (m/s), 685 (M+l) + Example 98 Synthesis of Compound 99 The same procedure as in Example 1, Step B was repeated using 174 mg (0 25 mmol) of Compound 98 to give 150 mg (98%) of Compound 99 iH-NMR (DMSO-d^) δ, 2.04 (dd, IR J - 4 9,13.9 Hz), 2.15 (s, 3H), 3 42 (dd, IR J = 7.3, 13.9 Hz), 4 72 (s, 2H), 5.02 (d, IR J = 5 4 Hz), 6.34 (s, IH), 7.17 (dd, IR J = 4 9, 7.3 Hz), 7.26-7.29 (m, 2H), 7.30 (d, IR J - 16.1 Hz), 7 46 (dd, IR J = 1.5, 8 1 Hz), 7.65 (d, IR J = 8.1 Hz), 7 85-7 89 (m, 6H), 8.61 (dd, IR J = 1 0, 3.9 Hz), 9 46 (d, IR J - 1.2 Hz).FAB-MS (m/s), 685 (M+l) + Example 99 Synthesis of Compound 100 To a solution of 100 mg (0 15 mmol) of Compound 98 in 5 ml of methylene chlonde were added 54 mg (0.36 mmol) of t-butylώmetfaylsilyl chlonde, 75 mg (0 75 mmol) of imidazole and 0.5 ml of tnethylaπune, followed by stimng for 1 hour. The reacuon mixture was poured mto ice-cold water, followed by extraction with chloroform. The extract was washed with a saturated aqueous solution of soώum chloride, and dπed over soώum sulfate After the solvent was evaporated under reduced pressure, the residue was tnturated with hexane to give 110 mg (92%) of Compound 100 FAB-MS (m/z), 799 (M+l) + Example 100 Synthesis of Compound 101 The same procedure as in Example 1, Step B was repeated usmg 40 mg (0.25 mmol) of Compound 100 to give 27 mg (68%) of Compound 101 iRNMR (CDCI3) δ; 0.21 (s, 6H), 1.03 (s, 9H), 2.15 (s, 3H), 2.84 (dd, IR J = 4.9, 14.4 Hz), 3.50 (dd, IR J = 7.5, 14.4 Hz), 4.03 (s, 3H), 4 46 (d, IR J = 16.4 Hz), 4.63 (d, IR J = 16.4 Hz), 4.94 (s, 2H), 5.52 (br, IH), 6.73 (dd, IR J = 4.9, 7.5 Hz), 7.14 (br, 2H), 7.16 (d, IR J = 8.5 Hz), 7.42 (d, IR J = 7.5 Hz), 7.44 (dd, IR J = 1.5, 8.5 Hz), 7.50 (dd, IR J = 1.5, 8.5 Hz), 7.66 (dt, IR J = 1.7, 7.5 Hz), 7.71 (d, IR J = 16.1 Hz), 7.74 (s, IH), 7.88 (d, IR J = 8.5 Hz), 8.61 (d, IR J = 3.9 Hz), 8.95 (s, IH ). FAB-MS (m/z); 715 (M+l) + Example 101 Synthesis of Compound 102 To a solution of 90 mg (0.15 mmol) of Compound 99 in 3.0 ml of chloroform/methanol (5/1) was added 104 mg (0.45 mmol) of camphor sulfonic acid, followed by sύπing at room temperature for 1 day. The reaction mixture was poured into a saturated aqueous solution of soώum hyώogen carbonate, followed by extraction with chloroform/methanol (9/1). The extraα was washed with a saturated aqueous solution of soώum chloride, and dried over soώum sulfate. After the solvent was evaporated under reduced pressure, the residue was purified by sihca gel column chromatography (chloroform/methanol = 20/1) to give 64 mg (52%) of Compound 102. iH-NMR (DMSO-dg) δ, 2.04 (dd, IR J = 4.9,14.1 Hz), 2.15 (s, 3H), 3.37 (s, 3H), 3.41 (dd, IRJ=7.5, 14.1 Hz),3.93 (s, 3H), 4.63 (s,2H), 5.01 (d, IR J= 17.2Hz), 5.06 (d, IR J= 17.2Hz), 6.38 (s, IH), 7.17 (dd, IR J =4.9,7.3Hz), 7.24 (m, IH), 7.29(d, IRJ= 16.0Hz), 7.46(dd, IRJ = 1.7, 8.7Hz), 7.61 (d, IRJ= 7.6 Hz), 7.79 (dt, IRJ= 1.7, 7.6Hz), 7.87 (dd, IRJ = 1.7, 8.7Hz), 7.88 (d, IR J= 16.0Hz), 7.92 (d, IRJ=8.7Hz), 7.99(d, IRJ= 1.0Hz), 8.59 (d, IR J =3.8 Hz), 8.69(s, IH), 9.45 (d, IRJ= 1.4Hz). FAB-MS (m/s); 615 (M+l) + Exam p le 102 Synthesis of Compound 103 The same procedure as in Example 101 was repeated using a solution of 60 mg (0.10 mmol) of Compound 99 in 3.0 ml of methylene chloride/ethanoi (2 1) and 255 mg (1.1 mol) of camphorsulfonic acid to give 23 mg (41%) of Compound 103. iH-NMR (CDC1 3 ) δ; 1.33 (t, 3R J = 6.9 Hz), 2.18 (s, 3H), 2.62 (dd, IR J = 4.9, 14.5 Hz), 3.44 (dd, IR J = 7 4, 14.5 Hz), 3.66 (q, 2R J = 6.9 Hz), 4.08 (s, 3H), 4.67 (d, IR J = 15.9 Hz), 4.71 (s, 2H), 4.82 (d, IR J = 15.9 Hz), 5.77 (s, IH), 6.82 (dd, IR J = 4.9, 7.4 Hz), 7.14 (ddd, IR J = 1.0, 4.9, 7.6 Hz), 7.21 (d, IR J = 16.1 Hz), 7.32 (d, IR J = 8.8 Hz), 7.46 (d, IR J = 8 8 Hz), 7.47 (d, IR J = 8.6 Hz), 7.64 (dd, IR J = 1.7, 7.6 Hz), 7.68 (dt, IR J = 1.7, 7.6 Hz), 7.80 (d, IR J = 16.1 Hz), 7.83 (d, IR J = 1.2 Hz), 7.83 (d, IR J = 8.3 Hz), 8.63 (dd, IR J = 0 7, 3.9 Hz), 9.21 (d, lR J = 1.2 Hz). FAB-MS (m s); 629 (M+l) + Example 103 Synthesis of Compound 104 To a solution of 137 mg (0.20 mmol) of Compound 98 in 3.0 ml of methylene chloride was added 0.13 ml (2.0 mmol) of N,N-dimethylethanolaπune and 510 mg (2.2 mol) of camphorsulfonic acid, followed by reflux for 1 day. The reaction was poured mto a saturated aqueous solution of soώum hydrogen carbonate, followed by extraction with chloroform/methanol (9/1). The extraα was washed with a saturated aqueous solution of soώum chloride, and dried over soώum sulfate The solvent was evaporated under reduced pressure to give ώacetylated Compound 104. The same procedure as in Example 1, Step B was repeated using the obtamed ώacetylated compound to give 21 mg (16%) of Compound 104. llH-NMR (DMSO-d 6 ) δ; 2.03 (dd, IR J = 4.9, 14.2 Hz), 2.15 (s, 3H), 2.21 (m, 8H), 3.42 (m, IH), 3.60 (t, 2R J = 5.9 Hz), 3.93 (s, 3H), 4 69 (s, 2H), 4.99 (d, IR J = 17.1 Hz), 5.05 (d, IR J = 17.1 Hz), 6.37 (s, IH), 7.17 (dd, IR J = 4 9, 7.3 Hz), 7.24 (m, IH), 7.30 (d, IR J = 16.0 Hz), 7.46 (dd, IR J = 1.5, 8.7 Hz), 7.61 (d, IR J = 7.9 Hz), 7.67-7.97 (rn, 5H), 8.00 (s, IH), 8.58 (m, IH), 8.69 (s, IH), 9.45 (d, lR J = 1.6 Hz). FAB-MS (m/s); 672 (M+l) + Example 104 Synthesis of Compound 105 To a solution of 60 mg (0.10 mmol) of Compound 99 in 2 ml of methylene chloride was added 0.042 ml (0.3 mmol) of trifluoroacetic anhydride, followed by stirring for 20 minutes. To the mixture was added 0.022 ml (0.3 mmol) of ethanethiol, followed by stirring overnight. The reaction mixture was poured into a saturated aqueous solution of soώum hydrogencarbonate, followed by extraction with chloroform/methanol. The extract was washed with a saturated aqueous soluuon of soώum chloride, and dried over soώum sulfate. After the solvent was evaporated under reduced pressure, the residue was purified by sihca gel column chromatography (chloroform/methanol = 20/1) to give 26 mg (25%) of Compound 105. iH-NMR (CDC1 3 ) δ; 1.33 (t, 3R J = 7.3 Hz), 2.18 (s, 3H), 2.56 (q, 2RJ = 7.3 Hz), 2.68 (dd, IR J = 4.9, 14.4 Hz), 3.46 (dd, IR J = 7.3, 14.4 Hz), 3.85 (s, 2H), 4.08 (s, 3H), 4.65 (d, IR J = 16.4 Hz), 4.69 (d, IR J - 16.4 Hz), 5.75 (s, 2H), 6.81 (dd, IR J - 4.9, 7.3 Hz), 7.18 ( , IH), 7.19 (d, IR J = 15.9 Hz), 7.28 (dd, IR J = 1.7. 8.8 Hz), 7.43 (dd, IR J = 1.7, 8.8 Hz), 7.46 (d, IR J = 7.6 Hz), 7.60 (d, IR J - 8.8 Hz), 7.68 (dt, IR J = 1.5, 7.6 Hz), 7.79 (br, 3H), 8.62 (dd, IR J = 0.4, 3.7 Hz), 9.13 (s, IH). FAB-MS (m/s); 645 (M+ 1) + Example 105 Synthesis of Compound 106 The same procedure as in Example 103 was repeated using a solution of 137 mg (0.20 mmol) of Compound 98 in 3.0 ml of methylene chloride, 113 mg (0.8 mmol) of N,N- dimethylethanethiol hyώochloride and 510 mg (2.2 mmol) of camphorsulfonic acid to give 6.1 mg (4.3%) of Compound 106. iH-NMR (DMSO-dg) δ; 2.03 (dd, IR J = 4.9, 14.2 Hz), 2.14 (s, 3H), 2.19 (s, 6H), 2.52 (br, 4H), 3 40 (br, IH), 3.93 (s, 3H), 3.99 (s, 2H), 4.99 (d, IR J = 17.1 Hz), 5.03 (d, IR J = 17.1 Hz), 6.37 (s,lH), 7.17 (dd, IR J =49, 74 Hz),7.23 (m, IH), 7.30(d, IR J= 15.9Hz), 7.47(dd, IRJ= 1.7, 8.9Hz), 7.60(d, IRJ =76Hz), 7.79(dd, IRJ= 18, 8.9Hz),7.87(dd, IRJ= 1.7, 8.9Hz), 7.88 (d, IRJ= 15.9Hz), 7.90(d, IRJ =8.7Hz), 7.95 (d, IRJ= 8.7Hz), 7.97(d, IRJ= 15 Hz), 8.58 (m, IH), 8.70 (s, IH), 9.45 (d, IRJ= 1.5Hz) FAB-MS (m/s), 688 (M+I) + Example 106 Synthesis of Compound 107 The same procedure as in Example 103 was repeated usmg a soluuon of 137 mg (0.20 mmol) of Compound 98 in 3.0 ml of methylene chlonde. 111 mg (1.0 mmol) of 2-mercaptopyriώne and 510 mg (2.2 mmol) of camphorsulfonic acid to give 33 mg (24%) of Compound 107 iH-NMR (DMSO-dg) δ; 2.00 (dd, IR J = 4 9, 14.5 Hz), 2.13 (s,3H), 3 40 (br, IH), 3.92 (s, 3H), 4.66 (s, 2H), 4.95 (d, IR J = 17.6 Hz), 4 99 (d, IR J = 17.6 Hz), 6.32 (s, IH), 7.16 (dd, 2R J = 4.9, 7.6 Hz), 7.24 (br, IH), 7.29 (d, IH). 7.36 (d, IR J « 7.6 Hz), 7.54 (dd, IR J = 1.7, 8.7 Hz), 7.60 (d, IR J = 7 6 Hz), 7 67 (dt, IR J = 1.7, 7.6 Hz), 7.79 (dt, IR J « 1.7, 7.6 Hz), 7.88 (br, 3H), 7.94 (d, IR J - 8.8 Hz), 8.10 (d, IR J - 1.5 Hz), 8.53 (br, IH), 8.58 (br, IH), 8.67 (s, IH), 9 44 (d, lR J = 1.2 Hz). FAB-MS (m/s), 694 (M+l ) + Example 107 Synthesis of Compound 108 The same procedure as in Example 103 was repeated using a solution of 68 mg (0.10 mmol) of Compound 98 in 3.0 ml of methylene chlonde, 150 mg (1.0 mmol) of 2- mercaptobenzimidazole and 510 mg (2.2 mmol) of camphorsulfonic acid to give 22 mg (30%) of Compound 108 iH-NMR (DMSO-dg) δ, 1.99 (dd, IR J = 4.9, 14.1 Hz), 2.12 (s, 3H), 3.38 (dd, IR J = 4.9, 6.9 Hz), 3.92 (s, 3H), 4.79 (d, 2R J = 3 4 Hz), 4 84 (d, IR J = 16.4 Hz), 4.93 (d, IR J - 16.4 Hz), 6.30 (s, IH), 7.18 (br, 5H), 7.24 (d, IR J = 15.9 Hz), 7.28 (dd, IR J = 15.9 Hz), 7.38 (dd, J = 1.9, 7.6 Hz), 7.60 (br, 2H), 7.79 (dt, IR J - 1.9, 7.6 Hz), 7.87 (br, 2H), 7.94 (d, IR J = 8.6 Hz), 8.15 (s, IH), 8.59 (d, IR J = 1.8 Hz), 9.21 (s, IH), 9.43 (s, IH), 12.2 (s, IH). FAB-MS (m/s), 733 (M+l) + Example 108 Synthesis of Compound 109 To a suspension of 68 mg (0.10 mmol) of Compound 97 in 3.0 ml of methylene chloride were added 0.016 ml (0.22 mmol) of ethanethiol, and 0.018 ml (0.15 mol) of boron trifluoride etherate, followed by stirring at room temperature for 1 hour. The reaction mixture was poured into a saturated aqueous solution of soώum hydrogencarbonate, followed by extraction with chloroform. The extract was washed with a saturated aqueous solution of soώum chloride, and dried over soώum sulfate. After the solvent was evaporated under reduced pressure, the residue was purified by sihca gel column chromatography (chloroform/methanol = 20/1) to give 21 mg (27%) of Compound 109. FAB-MS (m/s); 789 (M+l) + Example 109 Synthesis of Compound 110 The same procedure as in Example 1, Step B was repeated using 21 mg (0.25 mmol) of Compound 109 to give 15 mg (88%) of Compound 110. iH-NMR (DMSO-dg) δ; 1.22 (dt, 6R J = 2.5, 7.3 Hz), 2.03 (dd, IR J = 4.9, 14.1 Hz), 2.15 (s, 3H), 2.58 (br, 4H), 3.41 (dd, IR J = 7.3, 14.1 Hz), 3.93 (s, 3H), 4.98 (d, IR J = 17.1 Hz), 5.04 (d, IR J = 17.1 Hz), 5.43 (s, IH), 6.35 (s, IH), 7.18 (dd, IR J = 4.9, 7.3 Hz), 7.25 (br, IH), 7.30 (d, IR J = 16.1 Hz), 7.61 (br, 2H), 7.80 (dt, IR J = 1.7, 7.6 Hz), 7.88 (d, IR J = 16.1 Hz), 7.89 (d, IR J = 16.1 Hz), 7.93 (d, IR J = 8.8 Hz), 7.96 (d, IR J = 8.8 Hz), 8.09 (d, IR J = 1.4 Hz), 8.59 (dd, IR J = 0.8, 3.2 Hz), 8.71 (s, IH). 9.45 (d, IR J = 0.6 Hz). FAB-MS (m/s); 705 (M+l) + Example 110 Synthesis of Compound 111 The same procedure as in Example 96 was repeated using 1.5 g (2.1 mmol) of Compound J to give 893 mg (62%) of Compound 111. iR-NMR (CDC1 3 ) δ, 1.81 (s, 3H), 2.16 (dd, IR J = 5.1, 14 6 Hz), 2.34 (s, 3H), 2.75 (s, 3H), 4.01 (dd, IR J = 7.3, 14.6 Hz), 4.03 (s, 3H), 5.31 (d, 2R J = 2.0 Hz), 6.99 (dd, IR J = 5 1, 7.3 Hz), 7.18 (ddd, IR J = 1.0, 4.9, 7.6 Hz), 7.30 (d, IR J = 16.1 Hz), 7.52 (d, IR J = 7.6 Hz), 7.56 (d, IR J = 8.8 Hz), 7.72 (dt, IR J = 1 7, 7.6 Hz), 7.82 (dd, IR J = 1.7, 8.8 Hz), 7.85 (d, IH), 7.93 (d, IR J = 8.8 Hz), 8.03 (dd, IR J = 1.5, 8.8 Hz), 8.09 (d, IR J = 1.3 Hz), 8.66 (dd, IR J = 1.0, 4.6 Hz), 9.57 (d, IR J = 1.6 Hz), 10.16 (s, IH) FAB-MS (m/z); 683 (M+l) + Example 111 Synthesis of Compound 112 The same procedure as in Example 57 was repeated usmg 750 mg (1 1 mmol) of Compound 111 to give 620 mg (82%) of Compound 112. FAB-MS (m/z); 685 (M+l) + Example 112 Synthesis of Compound 113 The same procedure as in Example 1, Step B was repeated usmg 620 mg (0.91 mmol) of Compound 112 to give 450 mg (83%) of Compound 113. iH-NMR (CDCI3) δ, 1.99 (dd, IR J - 5.0, 13.7 Hz), 2.16 (s, 3H), 3.17 (s, IH), 3.30 (m, IH), 3.93 (s, 3H),467 (s, 2H),5.09(d, 2R J= 3.5Hz), 7.13 (dd, IR J-5.0, 7.3 Hz),7.25(dd, IRJ= 5.0,7.6Hz), 7.41 (d, IRJ= 161Hz), 748(dd, IRJ= 1.5, 8.7Hz), 7.60(d, IRJ=7.6Hz), 7.80 (dt, IRJ= 1.6, 7.6Hz), 7.84 (dd, IR J= 1.2, 8.7Hz), 7.85 (d, IRJ= 8.7Hz), 7.94(d, IR J = 8.7Hz), 7.95 (d, IR J = 16.1 Hz), 8.29 (d, IR J - 0.9 Hz), 8.59 (d, IR J - 4.0 Hz), 8.69 (s, IH), 9.16 (s, IH). FAB-MS (m/z), 601 (M+l) + Example 113 Synthesis of Compound 114 The same procedure as in Example 99 was repeated using 82 mg (0.12 mmol) of Compound 112 to give 110 mg (72%) of Compound 114. FAB-MS (m/z); 798 (M+l) + Example 114 Synthesis of Compound 115 The same procedure as in Example 1, Step B was repeated using 30 mg (0.038 mmol) of Compound 114 to give 12 mg (44%) of Compound 115. iH-NMR (CDC1 3 ) δ; 0.13 (s, 3H), 0.15 (s, 3H), 0.97 (s, 9H), 2.19 (s, 3H), 2.73 (dd, IR J = 4.6, 14.4 Hz). 3.48 (dd, IR J = 7.3, 14.4 Hz), 4.09 (s, 3H), 4.45 (d, IR J = 16.5 Hz). 4.68 (d, IR J - 16.5 Hz), 4.74 (d, IR J = 12.2 Hz), 4.80 (d, IR J = 12.2 Hz), 5.69 (br, IH), 6.81 (dd, IR J = 4.6, 7.3 Hz), 7.08 (d, IR J = 16.1 Hz), 7.19 (ddd, IR J = 0.7, 4.9, 7.3 Hz), 7.29 (d, IR J = 8.5 Hz), 7.38 (d, IR J = 7.8 Hz), 7.40 (dd, IR J = 1.4, 8.5 Hz), 7.62 (br, 2H), 7.71 (d, IR J = 16.1 Hz), 7.80 (s, IH), 7.84 (d, IR J = 8.5 Hz), 8.60 (d, IR J = 3.9 Hz), 8.75 (s, IH ). FAB-MS (m/z); 715 (M+l) + Example 115 Synthesis of Compound 116 The same procedure as in Example 1, Step B was repeated using 60 mg (0.10 mmol) of Compound 113 to give 37 mg (40%) of Compound 116. iH-NMR (CDCI3) δ; 2.20 (s, 3H), 2.65 (d, IR J = 15.0 Hz), 3.33 (s, 3H), 3.49 (dd, IR J = 7.4, 15.0 Hz), 4.08 (s, 3H), 4.32-4.66 (m, 4H), 5.86 (s, IH), 6.85 (dd, IR J = 4 6, 7 3 Hz), 6 99 (d, IR J - 16 1 Hz), 7 10 (dd, IR J = 4 9, 7 4 Hz), 7 36 (br, 2H), 7 39 (dd, IR J = 0 5, 8 8 Hz),7 60 (br, 4H), 7 72 (s, IH), 7 80 (d, IR J = 8 8 Hz), 8 57 (d, IR J = 3 9 Hz), 8 72 (s, IH) FAB-MS (m s), 615 (M+l) + Example 116 Synthesis of Compound 117 The same procedure as m Example 102 was repeated usmg 60 mg (0 10 mmol) of Compound 113 to give 32 mg (51%) of Compound 117 iH-NMR (CDC1 3 ) δ, 1 26 (t, 3R J = 7 2 Hz), 2 21 (s, 3H), 2 63 (dd, IR J = 4 6, 14 4 z), 3 34 (dd, IR J = 7 4, 14 4 Hz), 3 55 (q, 2R J = 7 2 Hz), 4 10 (s, 3H), 4 50 (d, IR J = 1 1 5 Hz), 4 57 (d, IR J = 16 6 Hz), 4 58 (d, IR J = 11 5 Hz), 4 77 (d, IR J = 16 6 Hz), 5 81 (s, IH), 6 86 (dd, IR J = 4 6, 7 5 Hz), 7 15 (br, 2H), 7 36 (d, IR J = 8 6 Hz), 7 40 (d, IR J = 7 8 Hz), 7 45 (dd, IR J = 1 7, 8 6 Hz), 7 64 (br, 3H), 7 74 (d, IR J = 16 1 Hz), 7 84 (d, IR J = 8 5 Hz), 7 87 (s, IH), 8 61 (d, IR J = 3 6 Hz), 8 86 (s, IH) FAB-MS (m s), 629 (M+I) + Example 117 Synthesis of Compound 118 The same procedure as in Example 104 was repeated using 60 mg (0 10 mmol) of Compound 113 to give 30 mg (46%) of Compound 118 iH-NMR (CDCI3) δ, 1 24 (t, 3R J = 7 3 Hz), 2 22 (s, 3H), 2 45 (q, 2R J = 7 3 Hz), 2 62 (dd, IR J = 4 6, 14 5 z), 3 50 (dd, IR J = 7 3, 14 5 Hz), 3 71 (d, IR J = 14 9 Hz), 3 77 (d, IR J = 14 9 Hz), 4 10 (s, 3H), 4 46 (d, IR J = 16 6 Hz), 4 71 (d, IR J = 16 6 Hz), 5 80 (s, IH), 6 87 (dd, IR J = 4 6, 7 3 Hz), 7 04 (d, IR J = 16 7 Hz), 7 12 (ddd, IR J = 0 7, 5 2, 7 6 Hz), 7 37 (br, 2H), 7 43 (dd, IR J = 1 7, 8 6 Hz), 7 62 (br. 3H), 7 78 (s, IH), 7 81 (d, IR J = 8 6 Hz), 8 59 (d, IR J = 3 9 Hz), 8 75 (s, IH) FAB-MS (m/s); 645 (M+l) + Example 118 Synthesis of Compound 119 The same procedure as in Example 106 was repeated using 60 mg (0.10 mmol) of Compound 1 13 to give 28 mg (40%) of Compound 1 19 . iH-NMR (CDC1 3 ) δ, 2.00 (dd, IR J = 4.9, 13.9 Hz), 2.16 (s, 3H), 3.32 (br, IH), 3.93 (s, 3H), 4 62 (s, 2H), 5.10 (s, 2H), 6.40 (s, IH), 7.12 (br, 2H), 7.26 (br, IH), 7.34 (d, IR J = 7 9 Hz), 7.41 (d, IR J = 16.1 Hz), 7.54 (dd, IR J = 2.0, 8.6 Hz), 7.65 (br, 2H), 7 81 (br, 3H), 7.94 (s, IH), 7.97 (d, IR J = 6.9 Hz), 8.29 (s, IH), 8.60 (s, IH), 8 65 (d, IR J = 7.1 Hz),8.70 (s, IH), 9.28 (s, IH). FAB-MS (m/s), 694 (M+l) + Example 119 Synthesis of Compound 120 To a solution of 90 mg (0.15 mmol) of Compound 113 in 3.0 ml of methylene chloride was added 225 mg (1.0 mmol) of 2-mercaptobenzimidazole and 695 mg (3.0 mmol) of camphorsulfonic acid, followed by reflux for 1 day. The reaction mixture was poured into a saturated aqueous solution of soώum hydrogencarbonate, followed by extraction with chloroform methanol (9/1) The extraα was washed with a saturated aqueous solution of soώum chloride, and dried over soώum sulfate. The solvent was evaporated under reduced pressure to give 26 mg (24%) of Compound 120 iH-NMR (DMSO-ώ j ) δ; 2.00 (dd, IR J = 4.8, 13.9 Hz), 2.16 (s, 3H), 3.92 (m, IH), 3.93 (s, 3H), 4 79 (s, 2H), 5.10 (s, 2H), 6.40 (s, IH), 7.13 (br, 5H), 7.26 (dd, IR J = 5.4, 6.9 Hz), 7.41 (d, IR J = 16.1 Hz), 7.59 (br, 3H), 7.84 (br, 3H), 7.94 (d, IR J = 8.9 Hz), 7.95 (d, IR J = 16.1 Hz), 8.29 (s, IH), 8.59 (d, IR J = 4 0 Hz), 8.71 (s, IH), 9.30 (d, IH, J - 1.4 Hz), 12.6 (br, IH). FAB-MS (m/s), 733 (M+l) + Example 120 Synthesis of Compound 121 The same procedure as in Example 96 was repeated using 146 mg (0.20 mmol) of Compound 67 to give 57 mg (mixture of E and Z, 40%) of Compound 121. FAB-MS (m/s), 709 (M+l) + Example 121 Synthesis of Compound 122 The same procedure as in Example 1, Step B was repeated using 57 mg (0.080 mmol) of Compound 121 to give 32 mg (64%) of Compound 122. FAB-MS (m/s); 625 (M+l) + Example 122 Synthesis of Compound 123 The same procedure as in Example 62 was repeated using 68 mg (0.1 mmol) of Compound 100 to give 34 mg (50%) of Compound 123. FAB-MS (m/z); 802 (M+l) + Example 123 Synthesis of Compound 124 The same procedure as in Example 1, Step B was repeated usmg 40 mg (0.050 mmol) of Compound 123 to give 11 mg (31%) of Compound 124. iH-NMR (CDC1 3 ) δ; 0.19 (s, 6H), 1.02 (s, 9H), 2.19 (s, 3H), 2.51 (dd, IR J = 4.9, 14.4 Hz), 3.23 (br, 4H), 3.34 (dd, IR J = 7.3, 14.4 Hz), 4.08 (s, 3H), 4.38 (br, IH), 4.80 (d, IR J = 16.4 Hz), 4.88 (d, IR J = 16.4 Hz), 4.96 (s, 2H), 5.89 (br, IH), 6.83 (dd, IR J = 4.9. 7.3 Hz), 7.11 (ddd, IR J = 1.0, 4.9, 7.3 Hz), 7.16 (d, IR J = 7.6 Hz), 7.28 (br, 2H), 7.42 (dd, IR J - 1.7, 8.8 Hz), 7.56 (dt, IR J = 2.0, 7.6 Hz), 7.80 (d, IR J = 8.8 Hz), 7.87 (d, IR J = 1.0 Hz), 8.58 (ddd, IR J « 0.73, 1.7, 3.9 Hz), 9.02 (s, IH). FAB-MS (m/z), 716 (M+1) + Example 124 Synthesis of Compounds 125a and 125b To a solution of 80 mg (0 1 mmol) of Compound 123 in 6 ml of chloroform methanol (5/1) was added 104 mg (0 45 mmol) of camphorsulfomc acid, followed by stimng at 40_C for 1 day The reaction mixture was poured mto a saturated aqueous solution of soώum hydrogencarbonate, followed by extraction with chloroform/methanol The extract was washed with a saturated aqueous solution of soώum chlonde, and dned over sodium sulfate. After the solvent was evaporated under reduced pressure, the residue was puπfied by suica gel column chromatography (chlorofoπn/methanol = 20/1) to give 12 mg (17%) of Compound 125a and 38 mg (58%) of Compound 125 b Compound 125 a FAB-MS (m/s), 701 (M+l) + Compound 125b FAB-MS (m/z), 659 (M+l) + Example 125 Synthesis of Compound 126 The same procedure as in Example 1, Step B was repeated using 38 mg (0 057 mmol) of Compound 125b to give 21 mg (60%) of Compound 126 iH-NMR (CDC1 3 ) δ, 2.14 (s, 3H), 2.49 (dd, IR J = 4 9, 14 4 Hz), 3 19 (br, 4H), 3.34 (dd, IR J = 7.3, 14 4 Hz), 3.50 (s, 3H), 4.07 (s, 3H), 4 64 (d, IR J = 16 7 hz), 4.65 (s, 2H), 4.75 (d, IR J = 16.6 Hz), 6.04 (br, IH), 6 82 (dd, IR J = 4 6, 7.3 Hz), 7.10 (dd, IR J = 4 6, 7.3 Hz), 7.14 (d, IR J = 7 6 Hz), 7.22 (dd, IR J = 1 7, 8.5 Hz), 7.28 (d, IR J = 8.5 Hz), 7.42 (dd, IR J = 1 5, 8 8 Hz), 7.56 (dt, IR J = 1 7, 7.6 Hz), 7 79 (s, IH), 7 82 (d, IR J = 8 8 Hz), 8 57 (d, IR J = 4 8 Hz), 8 93 (d, IR J = 1 0 Hz) FAB-MS (m/z), 617 (M+l)+ Example 126 Synthesis of Compounds 127a and 127b The same procedure as in Example 102 was repeated usmg 80 mg (0 1 mmol) of Compound 123 to give diacetylated Compounds 127a and 127b The same procedure as in Example 1, Step B was repeated usmg ώacetylated Compounds 127a and 127b to give 14 6 mg (23%) of Compound 127a and 11 0 mg (18%) of Compound 127b Compound 127a iH-NMR (CDC1 3 ) δ, 1 33 (t, 3R J = 7 1 Hz), 2 12 (s, 3H), 2 58 (dd, IR J = 4 8, 144 Hz), 3 17 (br, 4H), 3 37 (dd, IR J = 7 3, 14 4 Hz), 3 65 (q, 2R J = 7 1 Hz), 4 05 (s, 3H), 4 58 (d, IR J = 16.6 Hz), 4 67 (d, IR J = 16 6 Hz), 4 69 (s, 2H), 5 95 (s, IH), 6 80 (dd, IR J = 4 8, 7.3 Hz), 7 11 (ddd, IR J = 1 0, 4 9, 7 6 Hz), 7 15 (d, IR J = 7 6 Hz), 7 17 (dd, IR J = 1 8, 8 6 Hz), 7 23 (d, IR J = 8 5 Hz), 7 43 (dd, IR J = 1 5, 8 5 Hz), 7 56 (dt, IR J = 1 8, 7 6 Hz), 7 78 (s, IH), 7 83 (d, IR J = 8.5 Hz), 8 57 (br, IH), 8 83 (d, IR J = 1 0 Hz) FAB-MS (m/z), 631 (M+l) + Compound 127b iH-NMR (CDCI3) δ, 1 98 (dd, IR J = 4 9, 14 4 Hz), 2 14 (s, 3H), 3 29 (br, 4H), 3 36 (dd, IR J = 7 3, 14 4 Hz), 3 92 (s, 3H), 4 71 (d, 2R J = 5 7 Hz), 4 98 (d, 2R J = 4 9 Hz), 5 21 (t, IR J = 5 7 Hz), 6 30 (s, IH), 7 08 (dd, IR J = 4 9, 7 3 Hz), 7 21 (ddd, IR J = 1 0, 4 9, 7 3 Hz), 7.32 (d, IR J = 7 6 Hz), 7 35 (dd, IR J = 1 7, 8 6 Hz), 7 44 (dd, IR J = 1 4, 8 6 Hz), 7 69 (dt, IR J = 1 7, 7 6 Hz), 7 78 (d, IR J = 8 6 Hz), 7 88 (d, IR J = 8 6 Hz), 7 96 (s, IH), 8 53 (ddd, IR J = 0 7, 1 7, 4 5 Hz), 8 59 (s, IH), 9 10 (d, IR J = 1 4 Hz) FAB-MS (m/z), 603 (M+l) + Example 127 Synthesis of Compound 128 The same procedure as in Example 106 was repeated usmg 80 mg (0 1 mmol) of Compound 123 to give 42 mg (54%) of Compound 128 FAB-MS (m/z), 780 (M+l) + Example 128 Synthesis of Compound 129 The same procedure as in Example 1, Step B was repeated using 42 mg (0 057 mmol) of Compound 128 to give 13 mg (33%) of Compound 129 iH-NMR (CDC1 3 ) δ, 2 14 (s, 3H), 2 66 (dd, IR J = 4 9, 14 4 Hz), 3 18 (br, 4H), 3 39 (dd, IR J = 7 6, 14 4 Hz), 4 06 (s, 3H), 4 58 (s, 2H), 4 63 (d, IR J = 13 4 Hz), 4 70 (d, IR J = 13 4 Hz), 5 71 (br, IH), 6 77 (dd, IR J = 4 9, 7 6 Hz), 7 02 (ddd, IR J = 1 1, 1 2, 7 3 Hz), 7 12 (ddd, IR J = 1 2, 4 9, 7 6 Hz), 7 15 (d, IR J = 8 8 Hz), 7 22 (d, 2R J = 7 3 Hz), 7 55 (br, 4H), 7 81 (d, IR J = 8 8 Hz), 7 92 (d, IR J = 1 5 Hz), 8 52 (ddd, IR J = 1 0, 1 7, 4 9 Hz), 8 59 (ddd, IR J = 1 0, 1 9, 4 9 Hz), 8 78 (s, IH) FAB-MS (m/z), 679 (M+l) + Example 129 Synthesis of Compound 130 The same procedure as in Example 62 was repeated usmg 600 mg (0 057 mmol) of Compound 1 14 to give 423 mg (71%) of Compound 130 FAB-MS (m/z), 801 (M+l) + Example 130 Synthesis of Compound 131 The same procedure as in Example 1, Step B was repeated usmg 30 mg (0 037 mmol) of Compound 130 to give 9 0 mg (34%) of Compound 131 iH-NMR (CDC1 3 ) δ, 0 17 (s, 3H), 0.18 (s, 3H), 1 00 (s, 9H), 2.15 (s, 3H), 2 70 (dd, IR J = 4.9, 14 3 Hz), 3.26-3.36 (m, 4H), 3.39 (dd, IR J = 7.3, 14 3 Hz), 4 08 (s, 3H), 4 67 (d, IR J = 16 4 Hz), 4.73 (d, IR J = 16 4 Hz), 4 92 (s, 2H), 5 70 (br, 2H), 5 70 (br, IH), 6 79 (dd, IR J = 4 9, 7 3 Hz), 7 16 (ddd, IH, J - 1.2, 4 9, 7 1 Hz), 7.20 (dt, IR J = 1 0, 7 6 Hz), 7 28 (br, 2H), 7 41 (dd, IR J = 1 7, 8.5 Hz), 7 62 (dt, IR J = 1 9, 7 6 Hz), 7 68 (d, IR J = 1.5 Hz), 7 78 (d, IR J = 8 5 Hz), 8 60 (ddd, IR J = 1 0, 2.0, 4 8 Hz), 8 90 (s, IH) FAB-MS (m/z), 717 (M+l) + Exam p le 131 Synthesis of Compounds 132 The same procedure as in Example 101 was repeated using 80 mg (0 1 mmol) of Compound 130 to give diacetylated Compound 132. The same procedure as in Example 1, Step B was repeated usmg diacetylated Compound 132 to give 36 5 mg (59%) of Compound 132 1 H-NMR (CDCI3) δ, 2.12 (s, 3H), 2 86 (dd, IR J = 4 9, 14 4 Hz), 3 28-3 45 (m, 4H), 3 43 (s, 3H), 3 47 (dd, IR J = 7 3, 14 4 Hz), 4 06 (s, 3H), 4 43-4 59 (m, 4H), 5 70 (br, IH), 5 75 (br, IH), 6 73 (dd, IR J = 4 9, 7 3 Hz), 7 15 (ddd, IR J = 1 2, 4 9, 7 3 Hz), 7 17 (d, IR J = 8 5 Hz), 7 20 (d, IR J = 7 6 Hz), 7 21 (dd, IR J = 1 7, 8 5 Hz), 7 60 (d, IR J = 1 7 Hz), 7 61 (dt, IH, J - I 7, 7 6 Hz), 7 82 (d, IR J = 8 5 Hz), 8 56 (ddd, IR J = 1 0, 1 7, 4 9 Hz), 8 72 (d, IR J = 1 2 Hz) FAB-MS (m z), 617 (M+l) + Example 132 Synthesis of Compounds 133 The same procedure as in Example 102 was repeated using 80 mg (0 1 mmol) of Compound 130 to give diacetvlated Compound 133 The same procedure as in Example 1, Step B was repeated using diacetylated Compound 133 to give 4 9 mg (7 8%) of Compound 133 lH-NMR (CDCl 3 ) δ, 1 31 (t, 3R J = 7 0 Hz), 2 13 (s, 3H), 2 78 (dd, IR J = 5 1, 14 6 Hz), 3 48 (br, 4H), 3 71 (q, 2R J = 7 0 Hz), 4 07 (s, 3H), 4 55-5 13 (m, 4H), 5 71 (br, IH), 5 75 (br, IH), 6 76 (dd, IH, J - 5 1, 7 3 Hz), 7 15 (ddd, IR J = 1 0, 4 9, 7 3 Hz), 7 22 (br, 3H), 7 36 (dd, IR J = 1 7, 8 8 Hz), 7 61 (dd, IR J = 1 7, 7 8 Hz), 7 64 (d, IR J = 0 8 Hz), 7 80 (d, IR J = 8 8 Hz), 8 57 (ddd, IR J = 0 9, 1 9, 4 9 Hz), 8 83 (d, IR J = 1 0 Hz) FAB-MS (m z), 631 (M+l) + Example 133 Synthesis of Compounds 134 The same procedure as m Example 104 was repeated usmg 80 mg (0 1 mmol) of Compound 130 to give diacetylated Compound 134 The same procedure as in Example 1, Step B was repeated usmg diacetylated Compound 134 to give 16 mg (23%) of Compound 134 'H-NMR (CDC1 3 ) δ, 1 30 (t, 3R J = 7 3 Hz), 2 14 (s,3H), 2 54 (q, 2R J = 7 3 Hz), 2 78 (dd, IR J = 4 9, 14 4 Hz), 3 18-3 34 (rn, 4H), 3 52 (dd, IR J = 7 3, 14 4 Hz), 3 88 (s, 3H), 4 08 (s, 3H), 4 53 (d, IR J = 16 6 Hz), 4 63 (d, IR J = 16 6 Hz),5 68 (s, IH), 6 78 (dd, IR J = 4 9, 7 3 Hz), 7 15 (ddd, IR J = 1 0, 4 8, 7 8 Hz), 7 22 (br,3H), 7 36 (dd, IR J = 1 7, 8 5 Hz), 7 61 (dd,lR J = 1 7, 7 8 Hz), 7 63 (s. IH), 7 80 (d, IR J = 8 5 Hz), 8 58 (ddd, IR J = 0 9, 1 7, 4 9 Hz), 8 76 (d, lR J = 1.2 Hz) FAB-MS (m/z), 647 (M+l) + Example 134 Synthesis of Compound 135 The same procedure as in Example 105 was repeated usmg 80 mg (0 10 mmol) of Compound 130 to give 16 mg (23%) of Compound 135 iRNMR (CDC1 3 ) δ, 1 99 (dd, IR J = 4 9, 14 1 Hz), 2 12 (s, 3H), 2 13 (s, 6H), 2 50 (br, 4H), 3 20 (br, 4H), 3 34 (dd, IR J = 7 1, 14 1 Hz), 3 92 (s, 3H), 3 95 (s, 2H), 4 91 (d, IH, J = 17 5 Hz), 4.98 (d, IR J = 17.5 Hz), 6.29 (s, IH), 7 09 (dd, IR J = 4 9, 7 1 Hz), 7 23 (ddd, IR J = 0 7, 4 9, 7 5 Hz). 7 33 (br, 2H), 7 44 (dd, IR J = 1 5, 8 4 Hz), 7 71 (dt, IR J = 1 9, 7 6 Hz), 7 82-7 85 (m, 2H), 8 55 (ddd, IR J = 0 7, 1 0, 4 9 Hz), 8.60 (s, IH), 9 13 (d, IR J = 1 7 Hz) FAB-MS (m/z), 690 (M+l) + Example 135 Synthesis of Compound 136 The same procedure as in Example 106 was repeated usmg 80 mg (0 1 mmol) of Compound 130 to give 45 mg (58%) of Compound 136 FAB-MS (m/z), 780 (M+l) + Example 136 Synthesis of Compound 137 The same procedure as in Example 1, Step B was repeated usmg 45 mg (0 058 mmol) of Compound 136 to give 24 mg (59%) of Compound 137 iH-NMR (CDCI3) δ, 2 14 (s, 3H), 3.23 (dd, IR J = 4 9, 14 4 Hz), 3 22-3 34 ( , 4H), 3.51 (dd, IR J = 7 6, 14 4 Hz), 4 04 (s, 3H), 4 55-4 68 (m, 4H), 5 59 (br, IH), 6 77 (dd, IR J « 4 9, 7.6 Hz), 7.01 (ddd, IR J = 1 0, 4 9, 7 6 Hz), 7 16 (ddd, IR J = 1 0, 2.4, 7 6 Hz), 7 23 (br, 4H), 7.34 (dd, IR J = 1 5, 8 6 Hz), 7 50 (ddd, IR J = 1.9, 7 6, 7 9 Hz), 7 62 (dt, IH, J - 1 8, 7 6 Hz), 7 67 (d, IR J = 1 2 Hz), 7 79 (d, IR J = 8 6 Hz), 8.53 (ddd, IR J = 0 7, 1.7, 4 7 Hz), 8.59 (ddd, IR J = 0.7, 1 7, 4.9 Hz), 8 93 (s, IH). FAB-MS (m/z); 696 (M+l) + Example 137 Synthesis of Compound 138 To a soluuon of 290 mg (0 40 mmol) of Compound G in 3 ml of methanol/methylene chloride (1/1) was added 4.5 mg (0.12 mmol) of soώum borohydπde. followed by sumng at room temperature for 1 hour The reacuon mixture was poured mto ice-cold water, followed by extracuon with chloroform/methanol. The extraα was washed with a saturated aqueous soluuon of soώum chloride, and dned over soώum sulfate. After the solvent was evaporated under reduced pressure, the residue was purified by sihca gei column chromatography (chloroform) to give 120 mg (75%) of a hydroxymethyl compound. The same procedure as m Example 21 was repeated using 210 mg (0.29 mmol) of the obtamed hydroxymethyl compound to give 60 mg (39%) of Compound 138. iRNMR (DMSO-d^) δ; 1.95 (br, 2H), 2.15 (s, 3H), 3.20 (br, 2H), 3.80 (br, 3H), 4.39 (s, 4H), 5 05 (d, IR J = 7.8 Hz), 5.15 (t, IR J = 6.03 Hz), 5.46 (s, IH), 6.98 ( , IH), 7.53 (dd, IR J = 1.7, 8.6 Hz), 7.55 (dd, IR J = 1.7, 8.8 Hz), 7.82 (d, IR J = 8.6 Hz), 7.96 (d, IR J = 8.8 Hz), 8.13 (d, IH, J - 1.2 Hz), 8.70 (br, IH), 9.33 (d, lR J = 1.5 Hz). FAB-MS (m s), 576 (M+l) + Example 138 Synthesis of Compound 139 The same procedure as in Example 9 was repeated using 48.2 mg (0.0630 mmol) of Compound 1 to give 29.0 mg (60%) of Compound 139. iH-NMR (DMSO-d$) δ; 1.96 (dd, IR J = 4.9, 13.9 Hz), 2.12 (s, 3H), 2.70-2.79 ( , 4H), 3.04-3.10 (m, 4H), 3.35 (dd, IR J = 7.3, 13.9 Hz), 3.62 (s, 3H), 3.63 (s, 3H), 3.91 (s, 3H), 4.96 (d, IR J = 17.6 Hz), 5.01 (d, IR J = 17.6 Hz), 6.28 (s, IH), 7 08 (dd, IR J = 4 9, 7.3 Hz), 7.33-7.37 (m, 2H), 7 80 (d, IR J = 8 5 Hz), 7.83 (d, IR J = 8 6 Hz), 7.88 (rn, IH), 8 60 (br, IH), 9 04 (m, IH) FAB-MS (m z) ; 640 (M+l) + Example 139 Synthesis of Compound 140 The same procedure as in Example 9 was repeated using 41.8 mg (0 0962 mmol) of Compound 3 to give 27.0 mg (64%) of Compound 140 iH-NMR (DMSO-d ) δ; 1.19 (t, 3R J = 7.1 Hz), 1.20 (t, 3R J = 7 1 Hz), 1.96 (dd, IR J = 4 9, 13.9 Hz), 2 12 (s, 3H), 2.68-2.77 (m, 4H), 3.03-3 09 (m, 4H), 3.35 (dd, IR J = 7.2, 13.9 Hz), 3.91 (s, 3H), 4 08 (q, 2R J = 7 1 Hz), 4 09 (q, 2R J = 1 Hz), 4.96 (d, IR J = 17.7 Hz), 5.01 (d, IR J = 17 7 Hz), 6.28 (s, IH), 7 08 (dd, IR J = 4 9, 7.2 Hz), 7.33-7.37 (m, 2H), 7.79 (d, IR J = 8 6 Hz), 7 83 (d, IR J = 8 5 Hz), 7.88 (d, IR J = 1.5 Hz), 8.60 (br, IH), 9.04 (d, IR J = 1.0 Hz) FAB-MS (m/z) ; 668 (M+l) + Exam p le 140 Synthesis of Compound 141 The same procedure as in Example 5 was repeated usmg 3 mg (0.536 mmol) of 2- pyπdyhnethyltnphenylphosphomum bromide and 82.8 mg (0.126 mmol) of Compound B to give 62.0 mg (EZ = 9/1, 67%) of Compound 141. FAB-MS (m/z) , 733 (M+l) + , 735 (M+l) + Example 141 Synthesis of Compound 142 The same procedure as in Example 1, Step B was repeated using 62.0 mg (0 0846 mmol) of Compound 141 to give 36 6 mg (E Z = 9/1, 67%) of Compound 142 FAB-MS (m/z) , 649 (M+l) + , 651 (M+l) + Example 142 Synthesis of Compound 143 To a soluuon of 28 1 mg (0.0433 mmol) of Compound 142 in 0.5 ml of N,N- dimemylformamide was added 2.6 mg of platinum oxide, followed by sumng in a hyώogen atmosphere at room temperature for 2 days. Insoluble materials m the reacuon mixture were removed by filtration, and the filtrate was evaporated under reduced pressure. The residue was purified by sihca gel column chromatography (chloroform/methanol = 95/5) to give 10.6 mg (38%) of Compound 143 iH-NMR (DMSO-d ) δ, 2.00 (dd, IR J = 4.9, 14.2 Hz), 2.12 (s, 3H), 3.16-3.26 (m, 4H), 3.38 (dd, IR J = 7.3, 14.2 Hz), 3.91 (s, 3H), 4.94 (d, IR J = 18.2 Hz), 5.00 (d, IR J = 18.2 Hz), 6.31 (s, IH), 7.14 (dd, IR J = 4 9, 7.3 Hz), 7.23 (m, IH), 7.34 (d, IR J = 7.8 Hz), 7.39 (m, IH), 7.60 (m, IH), 7.71 (m, IH), 7.83-7.85 (m, 2H), 7.92 (d, IR J = 8.8 Hz), 8.55 (m, IH), 8.72 (s, IH), 9.38 (d, IR J = 2.0 Hz). FAB-MS (m/z) ; 651 (M+l) + , 653 (M+l) + Example 143 Synthesis of Compound 144 The same procedure as in Example 5 was repeated usmg 547 mg (18.2 mmol) of 4- pyridylmethyltriphenylphosphonium chloride and 104 mg (0.171 mmol) of Compound a to give 42.2 mg (33%) of Compound 144 FAB-MS (m/z) ; 758 (M+l) + Example 144 Synthesis of Compound 145 The same procedure as in Example 1, Step B was repeated using 40.0 mg (0.0528 mmol) of Compound 144 to give 16.1 mg (45%) of Compound 145 iRNMR (DMSO-d 6 ) δ; 2.06 (dd, IR J = 5.0, 14.3 Hz), 2.17 (s, 3H), 3.44 (dd, IR J = 7.5, 14.2 Hz), 3.95 (s, 3H), 5.09 (d, IR J = 17.2 Hz), 5.14 (d, IR J = 17.2 Hz), 6.44 (s, IH), 7.20 (dd, IR J = 5.0, 7.5 Hz), 7.23 (d, IR J = 16.3 Hz), 7.36 (d, 1R J = 16.3 Hz), 7.62-7.65 (m, 4H), 7 75 (d, IR J = 16.3 Hz), 7.82 (d, IR J = 16.3 Hz), 7 85 (m, I H), 7.91 (m, IH), 7.97-8.00 (m, 2H). 8.31 (d, IR J = 1 4 Hz), 8.54-8 58 ( , 4H), 8.77 (s, IH), 9.45 (d, IR J - 1.6 Hz) FAB-MS (m/z) , 674 (M+ l) + Example 145 Synthesis of Compound 146 The same procedure as in Example 9 was repeated usmg 21.3 mg (0 0316 mmol) of Compound 145 to give 6 7 mg (31%) of Compound 146 iH-NMR (DMSO-ώj) δ, 1.97 (dd, IR J = 4 9, 14.1 Hz), 2.12 (s, 3H), 3 02-3.16 (m, 8H), 3.35 (dd, IR J = 7.3, 14.1 Hz), 3.91 (s, 3H), 4.93 (d, IR J = 17 6 Hz), 4.97 (d, IR J = 17.6 Hz), 6.30 (s, IH), 7.08 (dd, IR J = 4.9, 7.3 Hz), 7.33-7.38 (rn, 6H), 7 79-7.84 (m, 2H), 7.85 (m, IH), 8.45-7 48 (m, 4H), 8.61 (m, IH), 9.08 (m, IH) FAB-MS (m/z) ; 678 (M+I) + Example 146 Synthesis of Compound 147 To a methylene chloride (1 ml) solution of 70 0 mg (0 0824 mmol) of the coarse phosphonium salt, which was obtamed by repeating the same method as in Example 64 usmg 51.3 mg (0.0883 mmol) of Compound e and 44.1 mg (0.128 mmol) of tπphenylphosphine hydrobromide, were added 11.6 mg (0.0839 mmol) of potassium carbonate and 0 9 mg (0 0034 mmol) of 18- crown-6, followed by stimng at room temperature for 5 minutes To the mixture was added 10.2 mg (0 106 mmol) of 2-ιmidazolccarboxaldehyde, followed by stimng at room temperature for 4 days After insoluble materials m the reaction mixture were removed by filtration, the filtrate was evaporated under reduced pressure The residue was purified by sdica gel column chromatography (chloroform/methanol = 95/5) to give 34.2 mg (69%) of Compound 147 FAB-MS (m/z) ; 644 (M+l) + Example 147 Synthesis of Compound 148 The same procedure as in Example 1, Step B was repeated using 34.2 mg (0.0532 mmol) of Compound 147 to give 22.3 mg (E/Z = 1/3, 75%) of Compound 148. FAB-MS (m/z) ; 560(M+1) + Example 148 Synthesis of Compound 149 The same procedure as in Example 9 was repeated using 10.1 mg (0.0181 mmol) of Compound 148 to give 6.9 mg (69%) of Compound 149. 1 H-NMR (DMSO-d ) δ; 1.99 (dd, IR J = 4.9, 14.1 Hz), 2.15 (s, 3H), 3.04-3.07 (m, 2H), 3.15-3.19 (m, 2H), 3.37 (dd, IR J = 7.4, 14.1 Hz), 3.92 (s, 3H), 4.98 (d, IR J = 17.2 Hz), 5.03 (d, IR J = 17.2 Hz), 6.33 (s, IH), 7.02 (br, 2H), 7.10 (dd, IR J = 4.9, 7.4 Hz), 7.32 (m, IH), 7.36 (m, IH), 7.48 (m, IH), 7.81 ( , IH), 7.94 (m, IH), 8.05 (m, IH), 8.61 (s, IH), 9.09 (d, IR J = 1.0 Hz). FAB-MS (m/z) ; 562 (M+l) + Example 149 Synthesis of Compound 150 To a solution of 75.4 mg (0.124 mmol) of Compound a in 3 ml of chloroform were added 0.15 ml (1.31 mmol) of dimethyl malonate and 0.015 ml of piperidine, followed by stirring under reflux for 12 hours. After coohng, the reaction mixture was poured into 4N hydrochlonc acid, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution of soώum chloride, and dried over soώum sulfate. After the solvent was evaporated under reduced pressure, the residue was purified by tnturation with methanol to give 88.9 mg (86%) of Compound 150. iRNMR (CDC1 3 ) δ; 1.80 (s, 3H), 2.14 (dd, IR J = 5.1, 14.6 Hz), 2.28 (s, 3H), 2.81 (s, 3H), 3.89 (s, 3H), 3.92 (s, 3H), 3.99 (dd, IR J = 7.5, 14.6 Hz), 4.01 (s, 3H), 4.03 (s, 3H), 4.09 (s. 3H), 5.36 (s, 2H), 7.00 (dd, IH. J = 5.1, 7.5 Hz), 7.53 (d, IR J = 9.3 Hz), 7 61-7 65 (m, 2H), 7.92 (d, IR J - 8.8 Hz), 7.98 (s, IH), 8 04 (s, IH), 8 18 (d, IR J = 1.7 Hz), 9.37 (d, IR J = 1 7 Hz). FAB-MS (m/z) ; 836(M+1) + Example 150 Synthesis of Compound 151 The same procedure as in Example 9 was repeated using 81.7 mg (0 0978 mmol) of Compound 150 to give 65 9 mg (80%) of Compound 151 FAB-MS (m/z) , 840(M+1) + Exam p le 151 Synthesis of Compound 152 To a mixed solution of 56.5 mg (0.0673 mmol) of Compound 151 in methylene chloride (3 ml)/methanol (0.6 ml) was added 32.8 mg of potassium carbonate, followed by stimng at room temperature for 6 hours. The reaction mixture was poured into water, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution of soώum chloride, and dπed over soώum sulfate The solvent was evaporated under reduced pressure to give 33 4 mg (66%) of Compound 152 iH-NMR (CDC-3) δ, 2.14 (s, 3H), 2.80 (dd, IR J = 4.8, 14 4 Hz), 3.37 (d, 2R J =7.8 Hz), 3.41-3.47 (m, 2H), 3.53 (dd, IR J = 6 8, 14 2 Hz), 3 73 (s, 3H), 3 75 (s, 3H), 3.75 (m, IH), 3 78 (s, 3H), 3.79 (s, 3H), 3.95 (m, IH), 4.09 (s, 3H), 4 67 (d, IR J = 16.6 Hz), 4 73 (d, IR J - 16.6 Hz), 5.11 (br, IH), 5 42 (s, IH), 6 77 (dd, IR J = 4.8, 7.6 Hz), 7.14 (m, IH), 7.18 (d, IR J = 8.3 Hz), 7.29 (m, IH), 7.82 (d, IR J = 8.8 Hz), 7.88 (d, IR J = 1.5 Hz), 8.69 (m, IH) FAB-MS (m/z) ; 756 (M+ 1 ) + Example 152 Synthesis of Compound 153 To a soluuon of 10 mg (0.016 mmol) of Compound 122 in 3 ml of methanol was added 10 mg of 10% Pd/C, followed by reflux in a hydrogen atmosphere for a day Insoluble matenals were removed by filtration, and the filtrate was evaporated under reduced pressure The residue was purified by silica gel column chromatography (chloroform) to give 2 7 mg (27%) of Compound 153 1HNMR (CDClj) δ ; 0.97 (t, 3R J = 7.3 Hz), 1 40-1 47 (m, 2H), 1.67-1 78 (m, 2H), 2.19 (s, 3H), 2.35 (dd, IR J = 4.7, 14.5 Hz), 2.83 (t, 2R J = 7.8 Hz), 3.23 - 3.31 (m, 5H), 4 08 (s, 3H), 4.88 (d, 2R J = 1.7 Hz), 5.98 (br, IH), 6.84 (dd, IR J = 4 7, 7.3 Hz), 7.16 (d, IR J = 7 7 Hz), 7.26 - 7.36 (m, 4H), 7.60 (ddd, IR J = 2.0, 5.9, 7 7 Hz), 7 68 - 7 73 (m, 3H), 8 61 (d, IR J = 4 0 Hz), 9.04 (br s, IH). FAB-MS (m/z) , 629 (M+ 1 >+ Example 153 Synthesis of Compound 154 To a soluuon of 67 9 mg (0.117 mmol) of Compound e in 3 ml of dichloromethane was added 0.02 ml (0.26 mmol) of chloromethyl methyl ether and 0 02 ml (0.12 mmol) of N,N- dusopropylethylammc, and the mixture was surred at room temperature for 8 hours. After addition of IN aqueous soluuon of soώum hydroxide, the reaction mixture was extracted with chloroform The organic layer was washed with a saturated aqueous solution of soώum chloride and dned over soώum sulfate. The solvent was evaporated under reduced pressure, and the residue was tnturated with methanol to give 53.8 mg (74%) of diacetylated Compound 154 1H-NMR(CDC1 J ) δ ; 1.80 (s, 3H), 2.16 (dd, IR J = 5.0, 14 6 Hz), 2.28 (s, 3H), 2.86 (s, 3H), 3 49 (s, 3H), 3.99 (dd, IR J = 7.5, 14 6 Hz), 4 01 (s, 3H), 4.80 (s, 2H), 4 86 (s, 2H), 5.41 (d, IR J = 17.6 Hz), 5 46 (d, IR J = 17.6 Hz), 7.02 (dd, IR J = 5.0, 7.5 Hz), 7.44 (m, IH), 7.54 (m, 2H), 7.61 (m, IH), 7.94 (d, IR J = 8 6 Hz), 8.09 (m, IH), 9.23 (m, IH). FAB-MS (m/z) ; 625 (M)+ The same procedure as in Example 1, Step B, was repeated usmg 51.2 mg (0 0819 mmol) of ώacetylated Compound 154 to give 39.2 mg (88%) of Compound 154 1H-NMR(CDCI 3 ) δ , 2 18 (s, 3H), 2 74 (dd, IR J = 4 9, 14 4 Hz), 3 46 (dd, IR J = 7 5, 144 Hz), 3 51 (s, 3H), 4 09 (s, 3H), 4 67 (d, IR J = 16 4 Hz), 4 75 (s, 2H), 4 78 (d, IR J = 16 4 Hz), 4 80 (s, 2H), 4 88 (s, IH), 6 46 (s, IH), 6 81 (dd, IR J = 4 9, 7 5 Hz), 7 29 (d, IR J = 8 3 Hz), 7 39 (m,lH), 7 41 (m, IH), 7 51 ( , IH), 7 92 (m, 2H), 8 93 (d, IR J = 1 0 HZ) FAB-MS (m/z) , 541 (M)+ Example 154 Synthesis of Compound 155 The procedure as m Example 153 was repeated usmg 49 1 mg (0 0804 mmol) of Compound f to give 24 8 mg (44%) of diacetylated Compound 155 lH-NMR(CDCIj) δ , 1 81 (s, 3H), 2 17 (dd, IR J = 5 0, 14 4 Hz), 2 26 (s, 3H), 2 87 (s, 3H), 3 49 (s, 3H),@3.50 (s, 3H), 3 99 (dd, IR J = 7 5, 14 4Hz), 4 01 (s, 3H), 4 80 (s, 2H), 4 83 (s, 2H), 4 84 (s, 2H), 4 86 (s, 3H), 5 43 (d, IR J = 17 6 Hz), 5 48 (d, IR J = 17 6 Hz), 7 02 (dd, IR J = 5 0, 7 5 Hz), 7 55 (m, IH), 7 62 (m, IH), 7 92 (m, 2H), 8 06 (d, IR J = 1 2 Hz), 9 23 (d, IR J = 1 0 Hz) FAB-MS (m/z) , 699 (M) + The same procedure as in Example 1, Step B, was repeated usmg 24 8 mg (0 0355 mmol) of diacetylated Compound 155 to give 19 9 mg (71%) of Compound 155 1H-NMR(CDC1 3 ) δ , 2 20 (s, 3H), 245 (dd, IR J = 4 9, 14 4 Hz), 3 34 (dd, IR J = 7 5, 14 4 Hz), 3 49 (s, 3H), 3 50 (s, 3H), 3 50 (s, 3H), 4 10 (s, 3H), 4 18 (s, 3H), 4 18 (s, IH), 4 80 (s, 6H), 4 82 (s, 2H), 4 89 (d, IR J = 15 8 Hz), 4 96 (d, IR J = 15 8 Hz), 5 87 (s, IH), 6 87 (dd, IR J = 4 9, 7 5 Hz), 7 41 (d, IR J = 8 6 Hz), 7 49 (m,2H), 7 82 (d, IR J = 8 8 Hz), 7 90 (d, IR J = 1 5 Hz), 9 16 (d, IR J = 1 0 HZ) FAB-MS (m/z) , 615 (M)+ Example 155 Synthesis of Compound 156 The procedure as in Example 153 was repeate using 46.0 mg (0.0753 mmol) of Compound f and 0.02 ml (0.22 mmol) of chioromethyl ethyl ether to give 50.9 mg (94%) of diacetylated Compound 156 lH-NMR(CDClj) δ , 1 17 (t, 3R J = 7.1 Hz), 1.19 (t, 3R J = 7.1 Hz), 1.81 (s, 3H), 2.17 (dd, IR J = 5 1, 14.4 Hz), 2.26 (s, 3H), 2.86 (s, 3H), 3.74 (q, 2H. J = 7.1 Hz), 3.75 (q, 2R J = 7 1 Hz), 3.98 (dd, IR J = 7.3, 14.4Hz), 4.01 (s, 3H), 4.85 (s, 2H), 4.85 (s, 2H), 4.87 (s, 2H), 4.88 (s, 3H), 5.42 (d, IR J = 17.6 Hz), 5.47 (d, IR J = 17.6 Hz), 7 01 (dd, IR J = 5.1, 7.3 Hz), 7.54 (m, 2H), 7 61 (m, IH), 7.90 (d, IR J = 8 6 Hz), 8.05 (d, IR J = 1.7 Hz), 9.23 (m, IH) FAB-MS (m z) , 727 (M)+ The same procedure as in Example 1, Step B, was repeated usmg 50.9 mg (0 0700 mmol) of ώacetylated Compound 156 to give 23.1 mg (51%) of Compound 156 1H-NMR(CDC1 3 ) δ, 1.30 (t, 6R J = 7 1 Hz), 2.20 (s, 3H), 2.41 (dd, IR J = 4 9, 14 4 Hz), 3.32 (dd, IR J = 7.6, 14.4 Hz), 3.73 (q, 2R J = 7.1 Hz), 3 73 (q, 2R J = 7 1 Hz), 4.08 (s, IH), 4.10 (s, 3H), 4.81 (s, 2H), 4.83 (s, 2H), 4.85 (s, 4H), 4 91 (d, IR J = 16.8 Hz), 4.98 (d, IR J = 16.8 Hz), 5.91 (s, IH), 6.88 (dd, IR J = 4 9, 7.6 Hz), 7 42 (d, IR J - 8.3 Hz), 7.49 (m,2H), 7.81 (d, IR J = 8.5 Hz), 7 90 (d, IR J = 1.2 Hz), 9.18 (d, IR J = 1.0 Hz). FAB-MS (m/z) ; 643 (M)+ Example 156 Synthesis of Compound 157 To a soluuon of 45.0 mg (0.0854 mmol) of Compound h in 2 ml of dichloromethane was added 0.1 ml (1.3 mmol) of 2-methoxyet anoI and 36.2 mg (0.156 mmol) of (±) 10- camphorsulfonic acid, and the mixture was stirred at room temperature for 2 days After addition of saturated aqueous solution of soώum bicarbonate, the reacuon mixture was extracted with chloroform The organic layer was washed with a saturated aqueous solution of soώum chlonde and dned over soώum sulfate The solvent was evaporated under reduced pressure, and the residue was puπfied by preparative TLC (chloroform/methanol = 95/5) to give 19.9 mg (36%) of Compound 157 1H-NMR(CDC1 3 ) δ ; 2.19 (s, 3H), 2.42 (dd, IR J = 4 6, 14.3 Hz), 3.32 (dd, IR J = 7 2, 14.3 Hz), 3.41 (s, 3H), 3.43 (s, 3H), 3.60-3.64 (m, 4H), 4.09 (s, 3H), 4 17 (br, IH), 4.77 (s, 2H), 4.80 (s, 2H), 4.89 (d, IR J = 16.6 Hz), 4 97 (d, IR J = 16.6 Hz), 5.95 (br, IH), 6.87 (dd, IR J = 4.6, 7.2 Hz), 7 43 (d, IR J = 8.5 Hz), 7.47 (m, IH), 7.53 (d, IR J = 8.5 Hz), 7.85 (d, IR J = 8 5 Hz), 7.91 (s, IH), 9.10 (s, IH). FAB-MS (m z) ; 643 (M) + Reference Example 1 Synthesis of Compound A To a solution of 5.00 g (9.07 mmol) of Compound c (Japanese Published Unexamined Patent ApphcaUon No. 295588/88) in 100 ml of a 10% methanol/chloroforrn rruxture'was added 1 62 g (9.10 mmol) of N-bromosuccirύmide under ice cooling, followed by stimng at room temperature for 8.5 hours. The precipitated crystals were separated by fiitrauon and dried to give 3.59 g (63%) of Compound A lH-NMR(CDCl3)δ; 1.82(s, 3H), 2.18 (dd, IRJ=5.1, 14.5 Hz),2.30 (s,3H),2.83 (s, 3H),400(dd, IRJ=7.5, 14.5Hz),4.03 (s,3H), 5.40(d, IRJ= 17.5Hz), 5.44 (d, IRJ = 17.5 Hz), 6.98 (dd, IRJ =5.1, 7.5 Hz), 744(d, IRJ = 8.7Hz), 747 (m, IH),7.57(m, IH), 7.64 (dd, IRJ =2.0, 8.7Hz), 7.96(d, IRJ=84Hz), 8.10(m, IH), 9.39(d, IR J=2.0Hz). FAB-MS (m z) , 630 (M) + . 632 (M+2) + Reference Example 2 Synthesis of Compound B A soluuon of 501 mg (0 794 mmol) of Compound A and 11 1 mg (0 792 mmol) of hexamethylenetetramme m 5 ml of tπfluoroaceuc acid was surred under reflux for 4 hours, followed by adώtion of water Resulting insoluble materials were collected by filtration, purified by silica gel column chromatography (chloroform/methanol = 99/1) and then by methanol tnturation to give 296 mg (57%) of Compound B iH-NMR (DMSO-d6) δ, 1.70 (s, 3H), 2.25 (s, 3H), 2.32 (dd, IR J = 5 0, 14 8 Hz), 2.68 (s, 3H), 3.90 (dd, IR J = 7.5, 14.8Hz), 3.96 (s, 3H), 5 44 (d, IR J = 17.7 Hz), 5 49 (d, IR J = 17 7 Hz), 7.35 (dd, IR J = 5 0, 7 5 Hz), 7 69 (m, IH), 8 05 (d, IR J = 8 8 Hz), 8.13 (m, IH), 8.21 (d, IR J = 8 7 Hz), 8 67 (m, IH), 9 24 (d, IR J = 1.9 Hz), 10.24 (s, lH). FAB-MS (m/z) , 658 (M) + , 660 (M+2) + Reference Example 3 Synthesis of Compound C Compound B (237 mg, 0.360 mmol), 64.2 mg (0 0556 mmol) of tetrakιs(tπphenylphosphιne) palladium and 44.6 mg (0454 mmol) of potassium acetate were dissolved m 2 ml of N.N-dimethylformaπude, and the soluuon was stirred at 100°C for 2 hours. To the reacuon mixture was added water, followed by extraction with chloroform. The extraα was washed with a saturated aqueous solution of soώum chlonde, and dned over anhydrous soώum sulfate After evaporauon of the solvent under reduced pressure, the residue was puπfied by sihca gel column chromatography (chloroform/methanol = 99/1) to give 71 2 mg (34%) of Compound C lH-NMR (CDCl3) δ, 1.79 (s, 3H), 2.15 (dd, IR J = 5 1, 14 7 Hz), 2.25 (s, 3H), 2.71 (s, 3H), 4 00 (dd, IR J = 7 7, 14.7Hz), 4.02 (s, 3H), 5 30 (s, 2H), 7.02 (dd, IR J = 5.1, 7.7 Hz), 7 34 (m, IH), 7.54 (m, 2H), 8 01 (d, IR J = 8 8 Hz), 8.08 (m, IH), 9 43 (d, lR J = 1.2 Hz), 9.16 (d, lR J = 8 1 Hz), 10 19 (s, IH) FAB-MS (m/z) ; 580 (M+l) + Reference Example 4 Synthesis of Compound D To a soluuon of 1.02 g of Compound c (Japanese Published Unexammed Patent Application No. 295588/88) in 50 ml of 1,2-ώchloroethane was added dropwise 0.17 ml of fuming nitπc acid, and the mixture was surred at room temperature for 10 minutes. A saturated aqueous soluuon of soώum hyώogen carbonate was added to the reacuon mixture, followed by extracuon with chloroform The extraα was washed with a saturated aqueous soluuon of soώum chlonde. and dned over anhydrous magnesium sulfate. After evaporation of the solvent under reduced pressure, the residue was purified by sihca gel column chromatography (chloroform/methanol = 99/1) to give 537 mg (49%) of Compound D. iH-NMR (CDC13) δ; 1.82 (s, 3H), 2.26 (dd, IR J = 5 4, 14.6 Hz), 2.31 (s, 3H), 2.70 (s, 3H), 4.03 (s, 3H), 4.07 (dd, IR J = 7.5, 14.6Hz), 5.38 (s, 2H), 6.99 (dd, IR J = 5.4, 7.5 Hz), 7 48 - 7.59 (m, 3H), 7.96 - 8.08 (m, 2H), 8.03 (m, IH), 10.02 (s, IH) FAB-MS (m/z) ; 597 (M+l) + Reference Example 5 Synthesis of Compound E A soluuon of 50 0 mg (0.0839 mmol) of Compound D and 175 mg (1.25 mmol) of hexamethylenetetraπune in 1 ml of trifluoroacetic acid was stirred under reflux for 2 hours. After adώtion of water, the reaction mixture was neutralized with a saturated aqueous solution of soώum hyώogen carbonate, followed by extracuon with chloroform The extract was washed with a saturated aqueous soluuon of soώum chloride, and dried over anhydrous soώum sulfate. Evaporation of the solvent under reduced pressure gave Compound E. iH-NMR (CDCI3) δ, 1.83 (s, 3H), 2.29 (dd, IR J = 5.3, 14 7 Hz), 2.34 (s, 3H), 2.64 (s, 3H), 4.05 (s, 3H), 4.12 (dd, IR J = 7.5, 14.7Hz), 5.34 (d, IR J = 17.6 Hz), 5.40 (d, IR J = 17.6 Hz), 7 02 (dd, IR J = 5.3, 7.5 Hz), 7.54 (d, IR J = 9.3 Hz), 8.07 (d, IR J = 8.6 Hz), 8.15 (m, IH), 8.37 (m, IH), 8.50 (d, IR J = 1.5 Hz), 8.90 (d, IR J = 2.2 Hz), 10.24 (s, IH) FAB-MS (m/z) , 625 (M+l) + Reference Example 6 Synthesis of Compound F Methanol (3 ml) was added to 1.4 g (60-65%, ca. 2.6 mmol) of mercury (IT) nitrate monohydrate, followed by stirring at room temperature for 5 minutes. To the mixture were successively added a soluuon of 551 mg (1.0 mmol) of Compound c (Japanese Published Unexammed Patent Apphcation No. 295588/88) m 12 ml of chloroform and 660 mg (2.6 mmol) of iodine, and the resulting mixture was stirred at room temperature for one hour. The reaction mixture was poured into 150 ml (1 N) of an aqueous solution of soώum thiosulfate, followed by extraction with chloroform The extratt was washed with water, and dried over anhyώous soώum sulfate. After evaporation of the solvent under reduced pressure, the residue was purified by sihca gel column chromatography (chloroform) to give 750 mg (93%) of Compound F iH-NMR (CDCI3) δ; 2.14 (s, 3H), 3.00 (dd, IR J = 4.6, 14.5 Hz), 3.72 (dd, IR J = 4.6, 7.6 Hz), 4.09 (s, 3H), 4.31 (d, IR J = 16.6), 4.59 (d, IR J = 16.6 Hz), 5.39 (br, IH), 5.54 (br, IH), 6.78 (dd, IR J = 6.0,7.6 Hz), 7.13 (d, IR J = 8.5 Hz), 7.45 (dd, IR J = 1.7, 8.5 Hz), 7.72(d, IR J = 8.7 Hz), 7.76 (dd, IR J = 1.7, 8.7 Hz), 8.16 (d, lR J = 1.5 Hz), 8.83 (d, IR J = 1.0 Hz). FAB-MS (m/z) ; 804 (M+l) + Reference Example 7 Synthesis of Compound G The same procedure as m Reference Example 6 was repeated usmg 23 4 mg (0 05 mmol) of K-252a to give 1 1 mg (86%) of Compound G. iH-NMR (CDCI3) δ; 1.80 (s, 3H), 2.11 (dd, IR J = 7.3, 16.2 Hz), 2.24 (s, 3H), 2.79 (s, 3H), 3.97 (dd, IR J - 7.3, 9.3 Hz), 4 00 (s, 3H), 5.32 (m, 2H), 6.93 (dd, IR J = 2.7, 7.6 Hz), 7.27 ( , IH), 7.68 (d, IR J = 8.8 Hz), 7 78 (m, 2H), 8.32 (br, IH), 9.52 (br, IH). FAB-MS (m/z) ; 720 (M+l) + Example 157 Spmal Cord ChAT Activity Assay The effect of selected nng substituted K-252a deπvatives on ChAT activity was assayed in ώssociated spmal cord cultures prepared from fetal rats usmg the procedure descnbed in U S Patent 5,461 , 146, Columns 26 and 27, Examples 6 and 7 ChAT is the enzyme that catalyzes the synthesis of the neurotransmitter acetylcholine, and it is a specific biochemical marker for chohnergic neurons In the spmal cord, the large majonty of chohnergic neurons are motor neurons Assay of this enzyme may thus be used as an mώcation of the effects of a factor, or factors, on the survival of chohnergic neurons and/or regulation of this enzyme The compounds were tested at 0nM and 300nM, and die data are summarized in Table 3 Compounds which increased ChAT activity at least 120% of the control activity are considered active Table 3: Spinal Cord ChAT Activity Example 158: Basal Forebrain ChAT Activity Assay Compounds of the mvenuon were assessed for their ability to promote survival and increase in ChAT activity m basal forebrain cultures. ChAT activity in these cultures is a biochemical marker for the chohnergic neurons (less than 5% of the cells in culture), which represent the major cholinergic put to the hippocampal formation, olfactory nucleus, lnterpeduncular nucleus, cortex, amygdala, and parts of the thalamus. Representative compounds of the mvenuon not only mcreased ChAT activity but in addition mcreased general survival of neurons in basal forebram cultures The basal forebrain was dissected from embryonic day 1 or 18 rat embryos and the cells were dissociated with Dispase™ (neutral protease, Collaborative Research) Neurons were plated at 5 x 10 4 cells well (1.5 x 10 5 cells/cm 2 ) in wells of 96-well plates previously coated with poly-1- ornithine and iarmnin. Cells were cultured in serum-free N 2 medium containing 0.05% bovine serum albumin (BSA) (Bottenstein et al., supra) at 37° in a humidified atmosphere of 5% COj/95% air. ChAT activity was measured in vitro at day six, using a modification of the Fonnum procedure (supra) according to McManaman et al. (supra) and Glicksman et al. (J. Neurochem. 61 :210-221, 1993). The compounds were tested at concentrations between lOnM and 500nM, and the data are summanzed in Table 4. Compounds which mcreased ChAT activity at least 120% of the control activirv are considered active Table 4: Basal Forebrain ChAT Activity Those skilled in the art will appreciate that numerous changes and modifications may be made to the preferred embodiments of the invention and that such changes and modifications may be made without departing from the spirit of the mvenuon. It is therefore intended that the appended claims cover all equivalent vaπations as fall within the true spiπt and scope of the invention. Documents cited throughout this patent ώsclosure are hereby incorporated herein by reference

Claims: WHAT IS CLAIMED IS: 1 A compound defined by the general formula (I) wherem one of R 1 and R 2 is selected from the group consisting of a) -CO(CH 2 ) j R\ wherein j is 1 to 6, and R 4 is selected from the group consisting of 1 ) hydrogen and a halogen, 2) -NR 5 R 6 . wherem R 5 and R 6 independentiv are hyώogen, substituted lower alkyl. unsubstituted lower alkyl, substituted ar 1, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted aralkyl, unsubstituted aralkyl, lower aikylammocarbonyl, or lower alkoxycarbonyl; or R 5 and R 6 are combined with a nitrogen atom to form a heterocyclic group, 3) N,, 4) -SR 21 , wnerein R 27 IS selected from the group consisting of i) hydrogen; ii) substituted lower alkyl; iii) unsubstituted lower alkyl; iv) substituted aryl, v) unsubstituted aryl; vi) substituted heteroaryl; vn) unsubstituted heteroaryl, 12 Θ viϋ) substituted aralkyl; ix) unsubstituted aralkyl; x) thiazolinyl; xi) -(CH 2 ),C0 2 R 21 , wherein a is 1 or 2, and R 28 is selected from the group consisting of: hydrogen and lower alkyl; and xii) -(CHj ). CONR'R* ; and 5) OR 2 ' (wherein R 29 is hydrogen, substituted lower alkyl, unsubstituted lower alkyl, or COR 30 (wherein R 30 is hydrogen, lower alkyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, or unsubstituted heteroaryl)); b) -CH(OH)(CH 2 ) R 4A , wherein b is 1 to 6 and R 4A is hydrogen or the same as R 4 ; c) -(CH 2 ) d CHR 31 C0 2 R 32 wherein d is 0 to 5, R 31 is hydrogen, -CONR 5 R< , or C0 2 R 33 (wherein R 33 is hydrogen or lower alkyl), and R 32 is hydrogen or lower alkyl; d) -(CH2) d CHR 3l CONR i R* ; e) -(CH 2 ) k R 7 wherein k is 2 to 6, and R 7 is halogen, C0 2 R* (wherein R* is hydrogen, lower alkyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, or unsubstituted heteroaryl), CONR 5 R 6 , substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, OR 9 (wherem R is hydrogen, substituted lower alkyl, unsubstituted lower alkyl, acyl, substituted aryl, or unsubstituted aryl), SR 27B (wherein R :7B is the same as R :; ), NR 10 R" (wherein R'° and R" are the same as R ! and R 6 ) or N 3 ; f) -CH=CH(CH 2 ) m R ι: wherein m is 0 to 4, and R 12 is hydrogen, lower alkyl, C0 2 R ,A (wherein R ,A is the same as R 8 ), -CONR s R 6 , substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, OR 9A (wherein R 9A is the same as R 9 ), or NR I0A R" Λ (wherein R I0A and R I 1A are the same as R 5 and R 6 ); g) -CH=C(C0 2 R 33A ) 2 , wherein R 33A is the same as R 33 ; h) -CEC(CH 2 )„R 13 , wherein n is 0 to 4, and R 13 is the same as R 12 ; i) -CHj OR" , wherein R 44 is substituted lower alkyl; and the other of R 1 or R 2 is selected from the group consisting of j) hydrogen, lower alkyl, halogen, acyl, nitro, NR , R 13 (wherein R 14 or R 15 is hydrogen or lower alkyl, and the other is hydrogen, lower alkyl, acyl, carbamoyi, lower alkylaminocarbonyl, substituted arylaminocarbonyl or unsubstituted arylaminocarbonyl); k) -CH(SR M ) 2 , wherein R 34 is lower alkyl or alkylene, I) -CH 2 R 35 , wherein R 35 is OR 36 (wherem R 36 is tri-lower alkyl silyl in which the three lower alkyl groups are the same or different, or is the same as R 29 ), or SR (wherein R 37 is the same as R 27 ), m) -CO(CH 2 ) < ,R 16 , wherein q is 1 to 6, and R 16 is the same as R 4 , n) -CH(OH)(CH 2 ) t R 31 , wherem e is 1 to 6, and R 38 is the same as R A , o) -(CH 2 ) f CHR 3S C0 2 R 40 , wherem f is 0 to 5, R 39 is the same as R 31 and p) -(CH 2 ),R 17 , wherem r is 2 to 6, and R' 7 is the same as R 1 , q) -CH=CH(CH 2 ),R", wherein t is 0 to 4, and R 18 is the same as R ι: , r) -CH=C(C0 2 R 33B ) 2 , wherein R 33B is the same as R 33 , s) -CB C(CH 2 )„R 19 , wherein u is 0 to 4, and R" IS the same as R 13 ), R 3 is hydrogen, acyl, or lower alkyl, X is selected from the group consisting of a) hydrogen, b) formyl, c) lower alkoxycarbonyl, d) -CONR 20 R 2 '. wherein R :o and R 21 independently are hydrogen, lower alkyl, -CH2 22 , wherein R 22 is hydroxy, or -NR^R 24 (wherein R 23 or R 24 is hydrogen or lower alkyl, and the other is hydrogen, lower alkyl, or the residue of an α-ammo acid in which the hydroxy group of the carboxy 1 group is excluded, or R 23 and R 24 are combined w.ώ a nitrogen atom to form a heterocyclic group), and e) -CH"N-R 2! , wherein R 2S is hydroxy, iower alkoxy, ammo, guanidino, or imidazolylamino, Y is hydroxy, lower alkoxy, aralkyioxy, or acyloxy; or X and Y combined represent, -X-Y-, =0, -CH 2 0(C=0)0-, -CH 2 OC(=S)0-, -CH 2 NR 26 C(=0)- (wherein R 26 is hydrogen or Iower alkyl), -CH 2 NHC( « S)0-, -CH 2 OS(=0)0-, or -CHjOC(CH 3 ) 2 0-, and 1 and W are hydrogen, or W 1 and 2 together represent oxygen; or a pharmaceutically acceptable salt thereof. 2. The compound of claim 1 wherein: a) one of R' and R 2 is selected from the group consisting of -(CHjJ t R 7 , -CH-CH(CH 1 ) m R' J , -CΞC(CH 1 ) D R , \ -CO(CH 2 ).SR 27 and -CHjOR 44 , wherein R" is methoxymethyl, ethoxymethyl, or methoxyethyl; and the other of R' and R 2 is selected from the group consisting of -(OW 7 , -CH=CH(CH 2 )R", -CSCfCHJ-R", NR ,4 R 1J , hyώogen, halogen, nitro, -CH : 0-, substituted lower alkyl, unsubstituted lower alkyl, -CO(CH 1 ) q SR 27 , -CH 2 R" , wherem R" is OR", and -CH,SR 37 , wherein R' 7 is selected from the group consisting of lower alkyl, pyndyl, and benzimidazole; b) k and r are each 2, 3, or 4; c) j and q are each 1 or 2; d) R 7 and R ,7 are: 1) selected independently from the group consisting of • phenyi, pyndyl, i idazolyl, thiazolyl, or tetrazolyl; or 2) selected pairwise, from the group consisπng of i) -CO,R' and C0 2 R ,A , where R' and R'\ιndependemly, are hyώogen, methyl, ethyl, or phenyl; n) -OR' and -OR" 1 , where R 9 and R'\ independently, are hydrogen, methyl, ethyl, phenyl, or acyl; in) -SR 27B , wnere R I7B is selected from the group consisting of unsubstituted lower alkyl, 2-thιazolιne. and pyndyl; and iv) -NR'V and -NR U R ,S , where R ,c , R", R' 4 , and R' 5 , independently, are selected from the group consistmg of hyώogen, methyl, ethyl, phenyl, carbamoyi, and lower alkylaminocarbonyl; e) R 27 is selected from the group consisπng of subsπtuted lower alkyl, unsubsπtuied lower alkyl, subsntuted phenyl, unsubsntuted phenyl, pyridyi, pynmidinyl, thiazole, and tetrazole; f) R 3i is selected from the group consisting of methoxymethyl, ethoxymeUiyl, and methoxyethyl, g) m, n, t and u each is 0 or 1 ; and h) R 12 , R' 3 , R", and R" are mdependeπtly selected from the group consisting of hyώogen, methyl ethyl, phenyl, pyndyl, imidazole. thiazole, tetrazole, -CO,R\ -OR 4 , and NR ,0 R", wherem R', R R", and R" each is hydrogen, meihyl, ethyl, or phenyl. 3 The compound of claim 2, wherein R 3 is hydrogen or acetyl, X is hydroxymethyl or lower alkoxycarbonyl, Y is hydroxy or aceryloxy, and W 1 and W 2 are hyώogen 4 The compound of claim 3 wherein X is methoxycarbonyl, Y is hvdrox , and R 3 is hydrogen 5 The compound of claim 3 wherein- one of R 1 and R 2 is selected from the group consisting of methoxycarbonylvmyl, ethoxycarbonylvmyl, styryi, 2-pyndylvιnyl, 4-pyndyl vinyl, 2-pyπdylethyl, 4-pyndylethyl, phenylethyl, meuioxypropynyl, hyώoxypropynyl, -COCH j SEt, -CΞCCH,NMeBn, -CH=CHEt, •(CHj) 2 SMe, -(CH 2 ) j S-2-thιazolme, -(CH j ) 3 SMe. -CH=CHEt, -CH=CH-2-ιmιdazole, (CH 2 ) 2 0C(=O)H, methoxymethoxymeuiyl, ethoxymethoxymeuiyl, methoxyethoxymethyl, and 2-hyώoxyethyl, and the other of R 1 and R 2 is selected from the group consisting of hyώogen, halogen, methoxycarbonylvmyl, ethoxycarbonylvmyl, styryi, 2-pyndylvmyl, 4-pyndylvmyl, 2-pyπdylethyl, 4-pyndylethyl, phenyleuiyl, nitro, ammo, N-ethylurea. methoxypropynyl, hyώoxypropynyl, -COCHjSEt, -ClCCHjNMeBn, -CH-CHEt, -(CH : ),SMe, -CH j OMe, -CH 3 OEt, -CHjSEt, pyndylthiomethyl, -CH 2 S-2-benzιmιdazole, -CH-CHEt, -CH-CH-2-ιmιdazole, -(CH 2 ) 2 OC(~0)H, meuioxymetiioxymethyl, ethoxymeu oxymethyl, methoxyethoxymethyl, and 2-hyώoxyeϋiyl 6 A method for enhancing the function of a trophic factor responsive cell, comprising the step of contacting said cell with a compound defined by the general formula (I) wherein one of R' and R 2 is selected from the group consisting of a) -CO(CH 2 ),R 4 , wherein j is 1 to 6, and R 4 is selected from the group consisting of 1 ) hydrogen and a halogen, 2) -NR 5 R 6 , wherein R 5 and R 6 independently are hydrogen, substituted lower alkyl, unsubstituted lower alkyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted aralkyl, unsubstituted aralkyl, lower alkylaminocarbonyl, or lower alkoxycarbonyl; or R 5 and R 6 are combined with a nitrogen atom to form a heterocyclic group; 3) N 3 , 4) -SR 27 , wherein R 27 is selected from the group consisting of 0 hydrogen; ii) substituted lower alkyl, iii) unsubstituted lower alkyl, iv) substituted aryl, v) unsubstituted aryl; vi) substituted heteroaryl; vπ unsubstituted heteroaryl; viti) substituted aralkyl; IX) unsubstituted aralkyl; x) thiazolinyl; xi) -(CH 2 ),C0 2 R 28 , wherein a is 1 or 2, and R 28 is selected from the group consisting of: hydrogen and lower alkyl; and XII) -(CH 2 ). CONR 5 R 6 ; and 5) OR 29 (wherem R 29 is hydrogen, substituted lower alkyl, unsubstituted lower alkyl, or COR 30 (wherein R 3C is hydrogen, lower alkyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, or unsubstituted heteroaryl)), b) -CH(OH)(CH 2 ),,R 4A , wherein b is 1 to 6 and R A is hydrogen or the same as R 4 ; c) -(CH 2 ) <1 CHR , C0 2 R 32 wherein d is 0 to 5, R 31 is hydrogen, -CONR'R 6 , or CO.R 33 (wherein R 33 is hydrogen or lower alkyl), and R 32 is hydrogen or lower alkyl; d) -(CH2) d CHR 3l CONR J R 6 ; e) -(CH 2 XR 7 wherein k is 2 to 6, and R 7 is halogen, C0 2 R 8 (wherein R* is hydrogen, lower alkyl, substituted aryl, unsubstituted aryi, substituted heteroaryl, or unsubstituted heteroaryl), CONR 5 R 6 , substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, OR 9 (wherein R 9 is hydrogen, substituted iower alkyl, unsubstituted iower alkyl, acyl, substituted aryl, or unsubstituted aryl), SR 27B (wherein R 27B is the same as R 27 ), NR I0 R" (wherein R 10 and R' ' are the same as R 5 and R 6 ) or N 3 , f) -CH=CH(CH 2 ) m R 12 wherein m is 0 to 4, and R 12 is hydrogen, lower alkyl, C0 2 R ,A (wherein R ,A is the same as R 8 ), -CONR 5 R 6 , substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, OR A (wherein R 9A is the same as R 9 ), or NR ,θA R , 1A (wherein R 10A and R" A are the same as R 5 and R 6 ), g) -CH=C(C0 2 R 33A ) 2 , wherein R 33A is the same as R 33 ; h) -CsC(CH 2 )„R 13 , wherem n is 0 to 4, and R 13 is the same as R 12 , i) -CHj OR 44 , wherein R 44 is substituted lower alkyl, and the other of R' or R 2 is selected from the group consisting of j) hydrogen, Iower alkyl, halogen, acyl, nitro, NR , R 15 (wherein R 14 or R 13 is hydrogen or iower alkyl, and the other is hydrogen, lower alkyl, acyl, carbamoyi, lower alkvlaminocarbonyl, substituted arylaminocarbonyl or unsubstituted arylaminocarbonyl), k) -CH(SR 34 ) 2 , wherein R 34 is Iower alkyl or alkylene, I) -CH 2 R 3J , wherein R 35 is OR 36 (wherein R 36 is tπ-lower alkyl silyl in which the three lower alkyl groups are the same or different, or is the same as R 29 ), or SR 3 ' (wherein R 37 is the same as R 27 ), m) -CO(CHj) q R 16 , wherein q is 1 to 6, and R 16 is the same as R 4 , n) -CH(OH)(CH 2 ) t R 3 ', wherem e is 1 to 6, and R 38 is the same as R 4A , o) -(CH 2 )rCHR 39 C0 2 R 40 , wherein f is 0 to 5, R 39 is the same as R 31 and R 40 is the same as R 32 , p) -(CH 2 ) r R 17 , wherein r is 2 to 6, and R 17 is the same as R 7 , q) -CH=CH(CH 2 ),R , wherein t is 0 to 4, and R" IS the same as R 12 , r) -CH-C(C0 2 R J1B ) 2 , wherem R 33B is the same as R 33 , s) -C«C(CH 2 ) U R 19 , wherein u is 0 to 4, and R 19 is the same as R 13 ), R 3 is hydrogen, acyl, or lower alkyl, X is selected from the group consisting of a) hydrogen, b) formyl, c) lower alkoxycarbonyl, d) -CONR 20 R 21 , wherein R 20 and R 21 independently are hydrogen, Iower alkyl, -CH2R 22 , wherein R 22 is hydroxy, or -NR^R 24 (wherein R 23 or R 24 is hydrogen or lower alkyl, and the other is hydrogen, lower alkyl, or the residue of an α-amino acid in which the hydroxy group of the carboxyl group is excluded, or R 23 and R :< are combined with a nitrogen atom to form a heterocyclic group), and e) -CH » N-R 23 , wherem R 25 is hydroxy, iower alkoxy, amino, guanidino, or imidazolylamino, Y is hydroxy, lower alkoxy, aralkyioxy, or acyloxy; or X and Y combined represent, -X-Y-, =0, -CH : 0(C=0)0-, -CH 2 OC(-S)0-, -CH 3 NR 24 C(=0)- (wherem R 26 is hydrogen or lower alkyl), -CH 2 NHC(=S)0-, -CH 2 OS(=0)0-, or W l and 2 are hydrogen, or W 1 and W 2 together represent oxygen, or a pharmaceutically acceptable salt thereof. 7. A method for enhancing the function of a trophic factor responsive cell, comprising the step of contacting said cell with at least one compound of claim 2 8. A mediod for enhancing the function of a trophic factor responsive cell, compπsing the step of contacting said cell with at least one compound of claim 5 9. The method of claim 6, wherein said trophic factor responsive cell is in a mammal. 10. The method of claim 6, wherein said trophic factor responsive cell is a neuron 1 1. The method of claim 10, wherein said neuron is selected from the group consisting of cholinergic neurons and sensory neurons. 12. A method for enhancing the survival of a trophic factor responsive cell, comprising the step of contacting said cell with a compound defined by the general formula (I) wherein- one of R' and R 2 is selected from the group consisting of. a) -CO(CH 2 ) j R 4 , wherein j is 1 to 6, and R 4 is selected from die group consisting of 1 ) hydrogen and a halogen; 2) -NR S R 6 , wherem R 5 and R* independently are hydrogen, substituted lower alkyl, unsubstituted Iower alkyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted aralkyl, unsubstituted aralkyl, Iower alkylaminocarbonyl, or lower alkoxycarbonyl; or R 3 and R* are combined with a nitrogen atom to form a heterocyclic group; 3) N 3> 4) -SR 27 , wherein R 27 is selected from die group consisting of i) hydrogen, n) substituted Iower alkyl, ni) unsubstituted Iower alkyl, iv) substituted aryl, v) unsubstituted aryl; vi) substituted heteroaryl, vn) unsubstituted heteroaryl, viu) substituted aralkyl, ix) unsubstituted aralkyl; x) thiazo nyl; xi) -(CH 2 ),C0 2 R 28 , wherein a is 1 or 2, and R 28 is selected from the group consisting of hydrogen and lower alkyl, and xn) -(CH 2 ).CONR 5 R 6 ; and 5) OR 2 ' (wherein R 29 ιs hydrogen, substituted lower alkyl, unsubstituted Iower alkyl, or COR 30 (wherein R 30 is hydrogen, lower alkyl, substituted ary l, unsubstituted aryl, substituted heteroaryl, or unsubstituted heteroaryl)), b) -CH(OH)(CH 2 ) b R 4A , wherem b is 1 to 6 and R 4A is hydrogen or the same as R 4 , c ) -(CH 2 )(,CHR 31 C0 2 R 32 wherem d is 0 to 5, R 31 is hydrogen, -CONR $ R 6 , or C0 2 R 33 (wherein R 33 is hydrogen or iower alkyl), and R 32 is hydrogen or Iower alkyl, d) -(CH2)„CHR 3, C0NR 5 R« , e) -(CH 2 ) k R 7 wherein k is 2 to 6, and R 7 is halogen, C0 2 R 8 (wherem R 8 is hydrogen, lower alkyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, or unsubstituted heteroaryl), CONR J R 6 , substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, OR 9 (wherein R 9 is hydrogen, substituted lower alkyl, unsubstituted lower alkyl, acyl, substituted aryl, or unsubstituted aryl), SR S7B (wherein R 27B is the same as R 27 ), NR I0 R" (wherein R 10 and R" are the same as R 5 and R 6 ) or N 3 ; f) -CH=CH(CH 2 ) m R 12 wherein m is 0 to 4, and R 12 is hydrogen, iower alkyl, C0 2 R ,A (wherein R ,A is the same as R 8 ), -CONR 5 R 6 , substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, OR 9A (wherein R 9A is the same as R 9 ), or NR ,0A R" A (wherein R 10A and R , 1A are the same as R 3 and R 6 ); g) -CH=C(C0 2 R 33A ) 2 , wherein R MA is the same as R 33 ; h) -CεC(CH 2 ).R 13 , wherein n is 0 to 4, and R 13 is the same as R 12 ; i) -CH 2 OR 44 , wherein R 44 is substituted lower alkyl; and the other of R 1 or R 2 is selected from the group consisting of j) hydrogen, lower alkyl, halogen, acyl, nitro, NR I R 15 (wherein R 14 or R 13 is hydrogen or Iower alkyl, and the other is hydrogen, lower alkyl, acyl, carbamoyi, lower alkylaminocarbonyl, substituted arylaminocarbonyl or unsubstituted arylaminocarbonyl); k) -CH(SR 34 ) 2 , wherein R 34 is Iower alkyl or alkylene; 1) -CH 2 R 3) , wherein R 3i is OR 36 (wherein R M is tri-lower alkyl silyl in which the three lower alkyl groups are the same or different, or is the same as R 29 ), or SR 37 (wherein R 37 is the same as R 27 ); m) -CO(CH 2 ) Q R 16 , wherein q is 1 to 6, and R 16 is the same as R 4 ; n) -CH(OH)(CH 2 ) e R 3 ', wherein e is 1 to 6, and R 3 * is the same as R A ; o) -(CH 2 ),CHR 3 'CO.R 40 , wherein f is 0 to 5, R 39 is the same as R 31 and R 40 is the same as R 32 ; p) -(CHAR 17 , wherein r is 2 to 6, and R 17 is die same as R 7 ; q) -CH=CH(CH:),R 18 , wherein t is 0 to 4, and R" is the same as R 12 ; r) -CH=C(C0 2 R 33B ) 2 , wherein R 33B is the same as R 33 ; s) -CsC(CH 2 ) g R 19 , wherein u is 0 to 4, and R 19 is the same as R 13 ); R 5 is hydrogen, acyl, or lower alkyl; X is selected from the group consisting of: a) hydrogen; b) formyl; c) lower alkoxycarbonyl; d) -CONR 20 R 21 , wherein: R 20 and R 2 ' independently are: hydrogen; lower alkyl; -CH2R 22 , wherein R 22 is hydroxy, or -NR U R J4 (wherein R 23 or R 24 is hydrogen or lower alkyl, and the other is hydrogen, lower alkyl, or the residue of an -amino acid in which the hydroxy group of the carboxyl group is excluded, or R 23 and R 24 are combined with a nitrogen atom to form a heterocyclic group); and e) -CH^N-R 23 , wherein R u is hydroxy, iower alkoxy, amino, guanidino, or imidazolylamino; Y is hydroxy, iower alkoxy, aralkyioxy, or acyloxy; or X and Y combined represent, -X-Y-, -O, -CH 2 0(C-0)0-, -CH 2 OC(=S)0-, -CH 2 NR 24 C( « )- (wherein R 2 * is hydrogen or lower alkyl), -CH 2 NHC(=S)0-, -CH 2 OS(=0)0-, or -CHjOC(CH 3 ):0-; and W 1 and W 2 are hydrogen, or W 1 and 2 together represent oxygen; or a pharmaceutically acceptable salt thereof. 13. A method for enhancing the survival of a trophic factor responsive cell, comprising the step of contacting said cell with a compound of claim 2. 14. A method for enhancing the survival of a trophic factor responsive cell, comprising the step of contacting said cell with a compound of claim 5. 15. The method of claim 12, wherein said trophic factor responsive cell is a neuron. 16. The method of claim 15, wherein said neuron is a cholinergic neuron. 17. A method for enhancing the survival of a cell at risk of dying, comprising the step of contacting said cell with a compound defined by the general formula (I): wherein: one of R 1 and R 2 is selected from the group consisting of: a) -CO(CH 2 ),R 4 , wherein j is 1 to 6, and R 4 is selected from die group consisting of: 1) hydrogen and a halogen; 2) -NR 3 R 6 , wherein R 3 and R* independently are hydrogen, substituted lower alkyl, unsubstituted lower alkyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted aralkyl, unsubstituted aralkyl, lower alkylaminocarbonyl, or Iower alkoxycarbonyl; or R 5 and R 6 are combined with a nitrogen atom to form a heterocyclic group; 3) N 3 ; 4) -SR 2" , wherein R 27 is selected from the group consisting of: i) hydrogen; ii) substituted lower alkyl; iii) unsubstituted lower alkyl; iv) substituted aryl; v) unsubstituted aryl; vi) substituted heteroaryl; vii) unsubstituted heteroaryl; viii) substituted aralkyl; ix) unsubstituted aralkyl; x) thiazolinyl, xi) -(CH 2 ),C0 2 R 2, t wherein a is 1 or 2, and R 28 is selected from the group consisting of. hydrogen and lower alkyl; and xn) -(CHj ), CONR } R 4 ; and 5) OR 2 ' (wherein R 29 is hydrogen, substituted lower alkyl, unsubstituted Iower alkyl, or COR 30 (wherein R 30 is hydrogen, lower alkyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, or unsubstituted heteroaryl)); b) -CH(0H)(CH 2 ) R A , wherein b is 1 to 6 and R 4A is hydrogen or the same as R 4 , c) -(CH 2 ) d CHR 3l C0 2 R 32 wherein d is 0 to 5, R 31 is hydrogen, -CONR 5 R 6 , or COjR 33 (wherein R 33 is hydrogen or lower alkyl), and R 3: is hydrogen or Iower alkyl; d) -(CH2) <1 CHR 3I C0NR R\ e) -(CH 2 ) k R 7 wherem k is 2 to 6, and R 7 is halogen, C0 2 R* (wherem R is hydrogen, lower alkyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, or unsubstituted heteroaryl), CONR 5 R 6 , substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, OR 9 (wherein R 9 is hydrogen, substituted iower alkyl, unsubstituted Iower alkyl, acyl substituted aryl, or unsubstituted aryl), SR 27B (wherein R 27B is the same as R 27 ), NR 10 R" (wherein R 10 and R 1 ' are the same as R 5 and R 6 ) or N 3 ; f) wherein m is 0 to 4, and R 12 is hydrogen, lower alkyl, C0 2 R A (wherein R 8A is the same as R 8 ), -CONR s R 6 , substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, OR' A (wherem R 9A is the same as R 9 ), or NR l0A R UA (wherein R 10A and R I IA are the same as R 5 and R 6 ); g) -CH=C(C0 2 R 33A ) 2 , wherein R 33A is the same as R 33 , h) -C«C(CHj)„R 13 , wherem n is 0 to 4, and R 13 is the same as R 12 ; i) -CH } OR 44 , wherein R 44 is substituted lower alkyl, and the other of R 1 or R 2 is selected from the group consisting of j) hydrogen, lower alkyl, halogen, acyl, nitro, NR ,4 R 13 (wherein R 14 or R 15 is hydrogen or lower alkyl, and die other is hydrogen, lower alkyl, acyl, carbamoyi, lower alkylaminocarbonyl, substituted arylaminocarbonyl or unsubstituted arylammocarbonyl); k) -CH(SR M ) 3 , wherein R 34 is lower alkyl or alkylene; I) -CH 2 R 35 , wherein R 35 is OR 3 * (wherein R 3 * is tri-lower alkyl silyl in which the three lower alkyl groups are the same or different, or is the same as R ), or SR (wherein R 37 is die same as R ϊ7 ); m) -CO(CHj)-R", wherein q is 1 to 6, and R 16 is the same as R 4 ; n) -CH(OH)(CH 2 ) t R 3 , wherein e is 1 to 6, andR 38 is the same as R 4A ; o) -(CH 2 ),CHR 39 C0 2 R 40 , wherein f is 0 to 5, R 59 is the same as R 31 and R 40 is the same as R 32 ; p) -(CHjirR 17 , wherein r is 2 to 6, and R 17 is the same as R 7 ; q) wherein t is 0 to 4, and R 1 ' is the same as R 12 ; r) -CH « C(C0 2 R 33B ) 2 , wherein R 3JB is the same as R 33 ; s) -C«C(CH2)v,R 19 , wherein u is 0 to 4, and R" is the same as R 13 ); R 3 is hyώogen, acyl, or lower alkyl; X is selected from the group consisting of: a) hydrogen; b) formyl; c) Iower alkoxycarbonyl; d) -CONR 20 R 21 . wherein: R 2C and R 2 ' independently are: hydrogen; lower alkyl; -CH2R 22 , wherein R 22 is hydroxy, or -NR U R 24 (wherein R 23 or R 24 is hydrogen or Iower alkyl, and the other is hydrogen, lower alkyl, or the residue of an α-amino acid in which the hydroxy group of the carboxy I group is excluded, or R~ and R 24 are combined with a nitrogen atom to form a heterocyclic group); and e) -CH-N-R 25 , wherein R 2S is hydroxy, lower alkoxy, amino, guanidino, or imidazolylamino; Y is hydroxy, lower alkoxy, aralkyioxy, or acyloxy; or X and Y combined represent, -X-Y-, -0, -CH 2 0(C=OP-, -CH 2 OC(=S)0-, -CH 2 NR 2 *C(=0)- (wherein R 26 is hydrogen or Iower alkyl), -CH 2 NHC(=S)0-, -CH 2 OS( « 0)0-, or W 1 and W 2 are hydrogen, or W 1 and W 2 together represent oxygen; or a pharmaceutically acceptable salt thereof. 18. A method for enhancing the survival of a cell at risk of dying, comprising the step of contacting said cell with a compound of claim 2. 19. A method for enhancing the survival of a cell at risk of dying, comprising the step of contacting said cell with a compound of claim 5. 20. The method of claim 17, wherein said cell is at risk of dying due to a process selected from the group consisting of aging, trauma, and disease. 21. The method of claim 20, wherein said cell is a neuron. 22. The method of claim 16, wherein said method is used in the treatment of Huntington's disease.

Inventors: HAMANO MASAMI, HUDKINS ROBERT L, MALLAMO JOHN P, MURAKATA CHIKARA, TANAKA REIKO, HAMANO, MASAMI, HUDKINS, ROBERT, L., MALLAMO, JOHN, P., MURAKATA, CHIKARA, TANAKA, REIKO
Applicants: CEPHALON INC, KYOWA HAKKO KOGYO KK, CEPHALON, INC., KYOWA HAKKO KOGYO CO., LTD.
Application year: 1997
Main classification: C07D498
IPC codes: A61K31, A61P9, A61P25, A61P43, C07D498