Chemoenzymic Production of Lactams from Aliphatic α,ω-Dinitriles

Abstract

Five- and six-membered ring lactams have been prepared by first converting an aliphatic α,ω-dinitrile to an ω-cyanocarboxylic acid ammonium salt, using a microbial cell catalyst having an aliphatic nitrilase activity (Acidovorax facilis 72W, ATCC 55746) or a combination of nitrile hydratase and amidase activities (Comamonas testosteroni 5-MGAM-4D, ATCC 55744). The ω-cyanocarboxylic acid ammonium salt was then directly converted to the corresponding lactam by hydrogenation in aqueous solution, without isolation of the intermediate ω-cyanocarboxylic acid or ω-aminocarboxylic acid. Only one of two possible lactam products was produced from α-alkyl-substituted α,ω-dinitriles, where the nitrilase of A. facilis 72W regioselectively hydrolyzed only the ω-cyano group to produce a single cyanocarboxylic acid ammonium salt in greater than 98% yield.