SYNTHESIS OF OPTICALLY-ACTIVE 3(R)-[(ALKYLSULFONYL)OXY]THIOLANES FROM 2(R)-HYDROXY-4-(METHYLTHIO)BUTANOIC ACID OR D-METHIONINE

The highly active penem antibiotic CP-70,429 featured a l(R)-oxo-3(S)-(thiolanylthio) substituent at carbon 2. The side-chain precursor, l(R)-oxo-3(S)-(acetylthio)-thiolane (A), was synthesized initially by Volkmann et al.1 2starting from L-aspartic acid and through the intermediacy of 3(R)-[(methylsulfonyl)oxy]- or 3(R)-[(p-tolylsulfonyl)-oxy]thiolanes, (R)-6 and (R)-9. An alternate approach to the synthesis of these optically active thiolanes is presented (Scheme I). We started from 2CR)-hydroxy-4-(methylthio)butanoic acid ((R)-l), which was prepared from D-methionine or, more efficiently, by a novel lipase hydrolysis of racemic ethvl 2-hvdroxv-4-(methvlthio)butvrate (rac-2). © 1990, American Chemical Society. All rights reserved.