Synthesis of novel keto-ACE analogues as domain-selective angiotensin I-converting enzyme inhibitors

Novel analogues of the angiotensin I-converting enzyme (ACE) inhibitor keto-ACE were synthesized via a facile Horner–Emmons olefination of a phosphonoketone precursor with ethyl glyoxylate. Introduction of a bulky aromatic tryptophan at the position of keto-ACE resulted in a significant increase in C-domain-selectivity.