Oxidoreductase-Catalyzed Synthesis of Chiral Amines

Chiral amines are valuable constituents of many important pharmaceutical compounds and their intermediates. It is estimated that similar to 40%-45% of small molecule pharmaceuticals contain chiral amine scaffolds in their structures. The major challenges encountered in the chemical synthesis of enantiopure amines are the use of toxic chemicals, the formation of a large number of byproducts, and multistep syntheses. To address these limitations, cost-effective biocatalytic methods are maturing and proving to be credible alternatives for the synthesis of chiral amines in enantiomerically pure forms. Herein, we report the recent progress achieved and current perspectives in the enzymatic synthesis of chiral amines using four important enzymes, i.e., imine reductases, amine dehydrogenases, monoamine oxidases, and cytochrome P450s. Applications to the industrial synthesis of chiral amines are highlighted. Protein engineering approaches, which play a critical role in improving or altering enzyme activity and substrate scope, are also addressed, along with the discovery of pioneering enzymatic activities from nature. This survey of recent work demonstrates that enzymatic approaches to the synthesis of chiral amines will continue to be a major focus of research in biocatalytic chemistry in the years to come.