Mercaptoketones and mercaptoalcohols and a process for their preparation

A process for the preparation of a diastereomerically and enantiomerically pure compound according to the formula ##STR9## where R.sup.1 is C.sub.1 -C.sub.12 alkyl, straight or branched and optionally substituted by halogen, hydroxy, C.sub.1 -C.sub.6 alkoxy, amino, carboxyl, C.sub.1 -C.sub.6 alkoxycarbonyl, carboxamido, nitrile, mono- or di-(C.sub.1 -C.sub.6)alkylamino, thio, C.sub.1 -C.sub.6 alkylthio, aryl, --Oaryl or --OCH.sub.2 aryl where aryl is optionally substituted with C.sub.1 -C6 alkyl, C.sub.1 -C.sub.6 alkoxy, carboxy, halogen, cyano, nitro, carboxamido, or hydroxy;

• and C.sub.1 -C.sub.6 alkanesulfonyloxy where aryl is a 5 to 10 membered carbocyclic or heterocyclic mono or bicyclic aromatic group selected from the benzene, furan, thiophene, imidazole, naphthalene, quinoline, indole, benzothiophene, benzimidazole, pyridine, pyrimidine, and benzofuran;
• R.sup.2 is (S)--OH and R.sup.6 is H, which comprises:
• (1) reacting a (3R,5S)-5-iodomethyl-3-R.sup.1 -dihydrofuran-2-one with the anion of HSW, where W is defined as phenyl, --C(O)aryl and --C(O)-substituted aryl where aryl is a 5 to 10 membered carbocyclic or heterocyclic mono or bicyclic aromatic group selected from the benzene, furan, thiophene, imidazole, naphthalene, quinoline, indole, benzothiophene, benzimidazole, pyridine, pyrimidine, and benzofuran, optionally substituted with C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, carboxy, halogen, cyano, nitro, carboxamido, or hydroxy;
• --C(O)--C.sub.1 -C.sub.12 alkyl and --CR.sup.3 R.sup.4 R.sup.5 where R.sup.3, R.sup.4, and R.sup.5 are independently selected from H, methyl, --O---C.sub.1 -C.sub.12 alkyl, O-tetrahydrophyranyl, --S-benzyl and phenyl optionally substituted with methoxy, hydroxy, nitro, or methyl, to provide lactone iiia,
• (2) deprotection of the sulfur of lactone iiia of step (1) under reducing conditions, acid hydrolysis or base hydrolysis to provide compound iva (Z.dbd.H),
• (3) protection of the free thiol of step (2) above to provide compound iva where Z is H, phenyl, --CR.sup.3 R.sup.4 R.sup.5 where R.sup.3, R.sup.4 and R.sup.5 are independently H, methyl, --O--C.sub.1 -C.sub.12 alkyl, O-tetrahydropyranyl, --S-benzyl, phenyl optionally substituted with methoxy, hydroxy, nitro, or methyl;
• disulfides or any other group suitable for protecting sulfur,
• (4) hydrolysis of the furanone of step (3) with aqueous acid or base to give compound va, a thiol-protected (2R)-2-R.sup.1 -(4R)-4-hydroxy-5-mercaptopentanoic acid, where
• Z is as defined above,
• (5) protection of the hydroxy group of compound va of step (4) with a protecting group Y to give compound via where Y is selected from trimethylsilyl, tert-butyldimethylsilyl, triethylsilyl, isopropyldimethylsilyl, trityldimethylsilyl, tert-butyldiphenylsilyl, methyldiisopropylsilyl, methyldi-tert-butylsilyl, triisopropylsilyl, triphenylsilyl, benzyl optionally substituted with methoxy, nitro, halogen or cyano;
• substituted methyl or ethyl ethers including triphenylmethyl, methoxymethyl, methoxyethoxymethyl, tetrahydropyranyl, or allyl,
• (6) amidation of carboxylic acid via of step (5) with (2S)-t-butylglycine N-methylamide and a peptide coupling reagent, to provide compound viia where Y and Z are as defined above,
• (7) removal of the protecting group Y from the hydroxyl group of compound viia of step (6) to provide alcohol viiia, where Z is as defined above,
• (8) removal of the thiol protecting group of compound viiia of step (7) to provide a compound of the above formula.