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-Michael/aldol reaction of 2-aminobenzaldehyde and α,β-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.

Graphical abstractPepsin from porcine gastric mucosa is used as a catalyst in the domino aza-Michael/aldol reaction for the synthesis of 1,2-dihydroquinolines.Figure optionsDownload full-size imageDownload as PowerPoint slide