Asymmetric Synthesis of <i>N</i>‐Substituted α‐Amino Esters from α‐Ketoesters via Imine Reductase‐Catalyzed Reductive Amination
Peiyuan Yao, James R. Marshall, Zefei Xu, Jesmine Lim, Simon J. Charnock, Dunming Zhu, Nicholas J. Turner
Abstract
N-Substituted α-amino esters are widely used as chiral intermediates in a range of pharmaceuticals. Here we report the enantioselective biocatalyic synthesis of N-substituted α-amino esters through the direct reductive coupling of α-ketoesters and amines employing sequence diverse metagenomic imine reductases (IREDs). Both enantiomers of N-substituted α-amino esters were obtained with high conversion and excellent enantioselectivity under mild reaction conditions. In addition >20 different preparative scale transformations were performed highlighting the scalability of this system.
Topics & Concepts
ImineReductive aminationEnantioselective synthesisChemistryEnantiomerCatalysisCombinatorial chemistryAminationEnantiomeric excessAmino acidStereoisomerismOrganic chemistryStereochemistryBiochemistryAsymmetric Hydrogenation and CatalysisCyclopropane Reaction MechanismsSynthesis and Catalytic Reactions