Enzyme-catalyzed asymmetric domino aza-Michael/aldol reaction for the synthesis of 1,2-dihydroquinolines using pepsin from porcine gastric mucosa

An unprecedented enzyme-catalyzed asymmetric domino aza-Michaelialdol reaction of 2-aminobenzaldehyde and alpha,beta-unsaturated aldehydes is achieved. Pepsin from porcine gastric mucosa provided mild and efficient access to diverse substituted 1,2-dihydroquinolines in yields of 38%-97% with 6%-24% enantiomeric excess (ee). This work not only provides a novel method for the synthesis of dihydroquinoline derivatives, but also promotes the development of enzyme catalytic promiscuity. (C) 2016 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.