Nitrilases Catalyze Key Step to Conformationally Constrained GABA Analogous γ-Amino Acids in High Optical Purity

Abstract

Five- and six-membered carbocyclic gamma-amino acids were prepared in high enantiomeric purity by nitrilase-mediated transformation of hitherto unreported gamma-amino nitriles. The nitrilases investigated reveal a strong enantiopreference for cis-isomers (up to 99% ee), whereas trans-isomers were available in up to 86% ee. The biocatalytic enantioselective syntheses of cis-3-aminocyclohexanecarboxylic acid (3b), trans-3-aminocyclohexanecarboxylic acids (4b, 6b, 8b) as well as trans-3-aminocylopentanecarboxylic acid (2b) are hereby reported for the first time.