Imine Reductases and Reductive Aminases in Organic Synthesis

Abstract

Imine reductases (IREDs) and reductive aminases (RedAms) are NADPH-dependent oxidoreductases catalyzing C–N redox reactions. These include the enantioselective reduction of preformed/cyclic imines and enantioselective formal reductive amination of carbonyl compounds with ammonia or alkyl/aryl/cyclic amines to allow the asymmetric synthesis of structurally diverse primary, secondary, and tertiary chiral amines from various precursors. In the oxidative direction, IREDs/RedAms can catalyze the enantioselective deamination of chiral amines, thereby enabling their application in kinetic resolution and deracemisation of racemic amines. Members of the IRED/RedAm family can also catalyze the asymmetric four-electron reduction of CN and the conjugated CC bonds of α,β-unsaturated imines, as well as the conjugate reduction and reductive amination of α,β-unsaturated carbonyl compounds to the corresponding saturated amines. This review discusses IRED/RedAm enzyme panels and the enzyme discovery strategies that have unearthed them. The expanding synthetic capabilities of IREDs/RedAms, their substrate scope, and their synthetic limitations are discussed. Enzyme engineering efforts are examined with a particular focus on hotspot mapping to establish sequence-activity relationships for this enzyme family.