Chemo–enzymic synthesis of optically active α,α-disubstituted α-amino acids

Abstract

A series of α,α-disubstituted α-amino esters was chemically synthesized and then resolved through enantioselective hydrolysis catalysed by a new enzyme isolated from crude Humicola langinosa lipase. This enzyme only accepts free amino esters as substrates with neither lipase activity toward olive oil nor esterase activity toward o-nitrophenyl butyrate. It is unique in that it successfully catalyses the resolution of amino esters with two large α-alkyl groups including aliphatic, aromatic and cyclic amino esters. Examples of resolutions where the alkyl groups differ in size by as little as a single carbon atom have been demonstrated. For determination of absolute configuration, some of the optically active α,α-disubstituted amino acids were also prepared through Schöllkopf's asymmetric synthesis and the structures were verified by X-ray crystallography. A model depicting the substrate binding site of the enzyme is proposed.