Biocatalytic enantioselective hydroaminations enabling synthesis of N-arylalkyl-substituted l-aspartic acids

Abstract

N-Substituted L-aspartic acids are important chiral building blocks for pharmaceuticals and food additives. Here we report the asymmetric synthesis of various N-arylalkyl-substituted L-aspartic acids using ethylenediamine-N,N′-disuccinic acid lyase (EDDS lyase) as a biocatalyst. This C–N lyase shows a broad non–natural amine substrate scope and outstanding enantioselectivity, allowing the efficient addition of structurally diverse arylalkylamines to fumarate to afford the corresponding N-arylalkyl-substituted L-aspartic acids in good isolated yield (up to 79%) and with excellent enantiopurity (>99% ee). These results further demonstrate that C–N lyases working in reverse constitute an extremely powerful synthetic tool to prepare difficult noncanonical amino acids.