An Alternative Formal Synthesis of (S)-(+)-Vigabatrin

Abstract

An improved synthesis of chirally pure advanced pyrrolidone intermediate of the (S)-(+)-vigabatrin, an antiseizure active pharmaceutical ingredient (API) is reported. The synthesis is developed using commercially available, cheaper amino acid (R)-methionine. Meldrum’s acid served as a two-carbon homologation unit to access the pyrrolidone intermediate in a short synthetic sequence. The sequence to pyrrolidone intermediate is scalable and eludes the use of organometallic pyrophoric reagents on a large scale.