Biocatalytic Synthesis of Chiral N-Functionalized Amino Acids

Abstract

N-Functionalized amino acids are important building blocks for the preparation of diverse bioactive molecules, including peptides. The development of sustainable manufacturing routes to chiral N-alkylated amino acids remains a significant challenge in the pharmaceutical and fine-chemical industries. Herein we report the discovery of a structurally diverse panel of biocatalysts which catalyze the asymmetric synthesis of N-alkyl amino acids through the reductive coupling of ketones and amines. Reactions have been performed on a gram scale to yield optically pure N-alkyl-functionalized products in high yields.

Keywords: N-methyl amino acid dehydrogenases; biocatalysis; ketimine reductases; reductive amination; α-keto amino acids.