Diastereoselective enzymatic synthesis of highly substituted 3,4-dihydropyridin-2-ones via domino Knoevenagel condensation–Michael addition–intramolecular cyclization

A direct method to construct 3,4-dihydropyridin-2-ones by enzymatic condensation of aldehyde with cyanoacetamide and 1,3-dicarbonyl compounds was developed. One ring and four new bonds (two C–C, one C–N, one Cdouble bond; length as m-dashC) were formed in one pot. And reaction conditions involving hydrolases, solvents, substrate molar ratios, and hydrolase loading were optimized. A series of new compounds based on the 3,4-dihydropyridin-2-one core were synthesized by the unprecedented three-component domino reaction.