Biocatalytic Route to Chiral Precursors of β-Substituted-γ-Amino Acids

Abstract

In this work, we utilized commercial lipases (from Thermomyces lanuginosa, Rhizopus delemar, and Mucor miehei) as biocatalysts for the efficient synthesis of precursors of β-substituted-γ-amino acids. This biocatalytic route provides a practical and efficient synthesis of a wide range of optically active compounds by accepting a number of aliphatic and aromatic 3-substituted-3-cyano-2-(ethoxycarbonyl)propanoic acid ethyl esters (2) without compromising enantioselectivity or yields. The resolution step allows for the nearly quantitative recovery of the unreacted enantiomer of R-(2) as well as the newly formed 3-substituted-3-cyano-2-(ethoxycarbonyl)propanoic acid (3) in high enantio and diastereoselectivity. The use of a facile thermal decarboxylation of (3) in aqueous solution to produce 3-substituted-3-cyanopropanoic acid ethyl esters (4) enable us to prepare a wide range of optically active precursors of β-Substituted-γ-Amino Acids.