Asymmetric Reductive Alkylation of Alanylproline by the Ethyl Esters of 4‐Substituted 2‐Oxobutenoic Acids.

Abstract

Acids. -A new method for the synthesis of enalapril (III), a highly effective ACE inhibitor, by reductive alkylation of alanylproline (I) with 2-oxo-4-phenylbutenoate (II) is developed. Alkylation using the corresponding saturated α-oxo acid occurs with diminished diastereoselectivity. Reductive alkylation of alanylproline (I) with the 2-thienyl analogue of (II) also takes place asymmetrically, however, strong poisoning of the catalyst by the sulfur-containing compound is observed. -(SLAVINSKA, V.; SILE, D.; CHIPENS, G. I.; BALODIS, Y.; ROZENTHAL, G.; VENTERIS, K.; LUKEVICS, E.; Chem. Heterocycl.