Enzymatic multicomponent reaction for simultaneous synthesis of two important scaffolds, pyridin-2-ones and α-alkylated nitriles

An efficient approach for the synthesis of highly substituted pyridin-2-one derivatives and α-alkylated nitriles through enzymatic multicomponent reaction (MCR) was developed. This MCR involved bio-mimetic reduction between 3,4-dihydropyridin-2-one and activated olefin, both of which were in situ generated in the Acylase Amano (AA)-catalyzed domino reaction starting from benzaldehyde, cyanoacetamide and ketone. A wide range of substituted benzaldehydes and ketones were accepted by this reaction. Both final products (pyridin-2-one derivatives and α-alkylated nitriles) were important skeletons and synthetic intermediates. The synthetic application of prepared α-alkylated nitrile was demonstrated by converting it into the corresponding α-alkyl-β2-amino acid with high yield.