Biocatalytic Amine Synthesis

Abstract

Nature has developed an arsenal of enzymes for the synthesis of amino acids and amines in high optical purity. Modern protein engineering techniques such as directed or structural guided evolution have enabled researchers to greatly expand the substrate scope of these enzymes, improve their catalytic activities and stability under synthetically relevant conditions, and evolve new-to-nature activities. The biocatalytic synthesis of amines has reached a level of maturity that allows it to compete with and even surpass other catalytic methodologies. This book chapter provides a comprehensive, yet concise, overview of the available enzyme families and related methods for the synthesis of amines, amino acids and amino alcohols. This toolbox of enzymes comprises hydrolases, amine oxidases, transaminases, amine dehydrogenases, imine reductases, reductive aminases, ammonia lyases, Pictet-Spenglerases and engineered cytochromes P450 (the latter called cytochromes P411 upon substitution of the axially coordinated cysteine to heme with a serine). Depending on the catalyzed reaction, these enzymes can be applied in kinetic resolution (KR), dynamic kinetic resolution (DKR) and deracemization of racemic amine moieties. Another method is the asymmetric synthesis of the amine starting from a prochiral molecule such as a ketone, an α,β-unsaturated carboxylic acid, an olefin or an alkane.