Synthesis of a Homostatine-Containing Renin Inhibitor Which Incorporates a Sulfonemethylene Isostere at Its <i>N</i>-Terminus

Abstract

Abstract A homostatine analogue, (2RS,4S,5S)N-isobutyl-5-amino-2-ethyl-4-hydroxy-7-methyloctanamide, was synthesized starting from natural statine. The modified Horner–Wadsworth–Emmons reaction of (4S,5R)-3-benzyloxycarbonyl-5-formyl-4-isobutyl-2,2-dimethyloxazolidine is a key reaction for the synthesis of a homostatine analogue. Stereoselective and stereospecific syntheses of a N-terminal precursor, N-[(2R)-3-hydroxy-2-(1-naphthylmethyl)propionyl]-l-norleucine t-butyl ester and a total synthesis of a highly active renin inhibitor, (2RS,4S,5S)-N-isobutyl-5-[[N-[(2S)-2-(1-naphthylmethyl)-3-(2-pyrimidinylsulfonyl)propionyl]-l-norleucyl]amino]-2-ethyl-4-hydroxy-7-methyloctanamide are described.