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

Publisher Website
Google Scholar
Abstract
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 .alpha.-hydroxyester ((RS)-4) with a lipase and also by asymmetric reduction of the .alpha.-oxoester (3) with baker''s yeast. The enantiomeric excess (ee) of the .alpha.-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.