Applications of vinylogous Mannich reactions. Total synthesis of the angiotensin converting enzyme inhibitor (−)-A58365A

Abstract

A concise enantiospecific synthesis of the angiotensin converting enzyme inhibitor (−)-A58365A ( 7 ) has been achieved following a strategy in which a vinylogous Mannich reaction and a lactone–lactam rearrangement served as the key transformations. The trimethylsilyloxyfuran derived from 25 , which was prepared from the known sulfoxide 16 , served as the nucleophilic partner in a vinylogous Mannich reaction with the chiral N-acyliminium ion that was generated in situ from the aminal 26 . Addition of a further quantity of TMSOTf cleaved the N-Boc group from the adducts 27 to give a mixture of diastereomeric amino butenolides 28 . Treatment of this mixture with LiOMe/MeOH furnished 10 , and acid-catalyzed hydrolysis of the methyl ester groups delivered (−)-A58365A in 37% overall yield over the longest linear sequence of eight steps.