Trypsin-catalyzed tandem reaction: One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones by in situ formed acetaldehyde

•A simple, mild, one-pot tandem method catalyzed by trypsin was developed for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones.•Trypsin was found to display dual promiscuous functions to catalyze transesterification and the Biginelli reaction in sequence.•A Biginelli reaction using in situ-produced acetaldehyde was developed.•The 3,4-dihydropyrimidin-2(1H)-ones were synthesized through one-pot tandem reaction.•Trypsin displayed its dual promiscuous functions.

A simple, mild, one-pot tandem method catalyzed by trypsin was developed for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones by the Biginelli reaction of urea, β-dicarbonyl compounds, and in situ-formed acetaldehyde. Trypsin was found to display dual promiscuous functions to catalyze transesterification and the Biginelli reaction in sequence.