Stereocomplementary Synthesis of Pharmaceutically Relevant Chiral 2-Aryl-Substituted Pyrrolidines Using Imine Reductases

Abstract

Exploring a collection of naturally occurring imine reductases (IREDs) identified two stereocomplementary IREDs with reducing activity toward sterically hindered 2-aryl-substituted pyrrolines. Using (<i>R</i>)-selective <i>Sc</i>IR and (<i>S</i>)-selective <i>Sv</i>IR, various chiral 2-aryl-substituted pyrrolidines with excellent enantioselectivity (>99% ee) were stereocomplementarily synthesized in good yield (60-80%), demonstrating the feasibility of IREDs for generating pharmaceutically relevant chiral 2-aryl-substituted pyrrolidine intermediates.