An improved synthesis of the new angiotensin converting enzyme inhibitor CV-5975 via a chemoenzymatic process.

A chemoenzymatic synthesis of the new angiotensin converting enzyme inhibitor CV-5975 (1) is described. The optically active key intermediate for the synthesis of 1, ethyl (R) -6- (1-benzyloxycarbonyl-4-piperidyl) -2-hydroxyhexanoate ((R) -4), was prepared by kinetic resolution of the racemic α-hydroxyester ((RS) -4) with a lipase and also by asymmetric reduction of the α-oxoester (3) with baker's yeast. The enantiomeric excess (ee) of the α-hydroxyester ((R) -4) produced by these enzymatic procedures exceeded 60%. This optically active alcohol ((R) -4) was converted to its mesylate ((R) -5), which was then subjected to SN2 reaction with the aminobenzothiazepine derivative (2) followed by deprotection to yield 1.