Journals Proceedings

Abstract

Chiral, β,γ-Unsaturated carboxylic acids derivatives are important intermediates in the synthesis of many biologically active compounds; for example anti-microtubule agents [1], Bisnorvernolepin [2] and Vineomycinone B2 [3]. Recently we have performed studies on enzymatic kinetic resolution based on esterification of carboxylic acids with orthoestres, used as a donor of alkoxy group [4,5]. As a compound for our studies, we choose 2-benzyl-2-methylbut-3-enic acid, which contains stereogenic quaternary carbon center. This compound is a substrate for the synthesis of irreversible inhibitors of a carboxypeptidase A, a representative zinc-containing proteolytic enzyme [6]. 2-Benzyl-2-methylbut-3-enic acid was synthesized in 4-step synthesis, containing enzymatic hydrolysis of benzylmethylmalonic dimethylester [6]. We propose short, two step synthesis of optically active 2-benzyl-2-methylbut-3-enic acid from commercially available tiglic acid. The results of optimization of the kinetic resolution of 2-benzyl-2-methylbut-3-enic acid, containing enzyme screening, influence of solvent and reaction conditions will be demonstrated.[7].