Development of Compatible Photocatalyst-Enzyme Hybrid System Via Intensifying Enzyme Tolerance for Enhanced Chiral Alcohol Synthesis

Abstract

Photo-enzyme catalysis featuring sustainability and selectivity is attractive, but remains challenges from efficiency and enzyme inactivation. This work provides a compatible and efficient photocatalyst-enzyme hybrid system for chiral alcohol synthesis. A covalent organic framework (COF) possessing broad visible light absorption edge to 554 nm was used for photocatalytic NADPH regeneration, achieving 82% yield in 90 min. Then the influence of photocatalysis on coupled enzyme LbADH was unveiled by fluorescence spectra and circular dichroism. Further a facile and mild strategy of entrapping LbADH into Ca2+/Mn2+ doped alginate gel was carried out. Impressively, enzyme immobilized strategy not only enhances 3.2 times activity, but also protects LbADH from diverse harsh environments, thereby improving photo-enzyme catalytic yield from 26% to 82%. To our delight, this one-pot photo-enzyme catalytic system achieves highly yield (up to 99%) with excellent enantioselectivity (90-99 ee%) for various chiral alcohols, and fulfills semipreparative scale preparation of (R)-1-[3,5-Bis(trifluoromethyl)phenyl] ethanol, prochiral intermediate of Aprepitant. This work sheds light on the new synthetic route of chiral compounds and development of photo-enzyme catalytic field.

Keywords: Covalent organic framework, Photocatalysis, NADPH regeneration, Enzyme immobilization, Photo-enzyme cascade, Alcohol dehydrogenase