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

A concise enantiospecific synthesis of the angiotensin converting enzyme inhibitor (−)-A58365A () 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 , which was prepared from the known sulfoxide , served as the nucleophilic partner in a vinylogous Mannich reaction with the chiral N-acyliminium ion that was generated in situ from the aminal . Addition of a further quantity of TMSOTf cleaved the N-Boc group from the adducts to give a mixture of diastereomeric amino butenolides . Treatment of this mixture with LiOMe/MeOH furnished , and acid-catalyzed hydrolysis of the methyl ester groups delivered (−)-A58365A in 37% overall yield over the longest linear sequence of eight steps.