Formal synthesis of the ACE inhibitor benazepril·HCl via an asymmetric aza-Michael reaction

Abstract

A formal enantioselective synthesis of benazepril·HCl (4), an antihypertensive drug, is reported. Our synthesis employed an asymmetric aza-Michael addition of L-homophenylalanine ethyl ester (LHPE, 1) to 4-(2-nitrophenyl)-4-oxo-but-2-enoic acid methyl ester (6) as the key step to prepare (2S,3′S)-2-(2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-ylamino)- 4-phenylbutyric acid ethyl ester (8), which is the key intermediate leading to benazepril·HCl (4). © 2006 by MDPI.