A Practical and Diastereoselective Synthesis of Angiotensin Converting Enzyme Inhibitors

Abstract

The diastereoselective synthesis of a series of potent angiotensin converting enzyme (ACE) inhibitors is described. The optically active intermediate, N-carbamyl (/?)-2-amino-4-phenylbutyric acid (2) leading to (l?)-2-halogeno or (/f)-2-hydroxy-4-phenylbutyric acid was prepared by asymmetric hydrolysis of dl -5-phenethylhydantoin (1) by microbial hydantoinase. The halogenoester was subjected to 5N2 reaction with L-amino acid derivatives to afford N-substituted amino acids, which were easily converted to ACE inhibitors or intermediates by deprotection. © 1989, The Pharmaceutical Society of Japan. All rights reserved.