Chemoenzymatic approach to optically active 1,4-dihydropyridine derivatives

Abstract A series of racemic (2-methyl)propanoyloxymethyl 4-aryl-6-chloro-5-methanoyl-2-methyl-1,4-dihydropyridine-3-carboxylates [(±)- 5a – h ] have been prepared by a four step sequence including a multicomponent Hantzsch process and a Vilsmeier–Haack reaction. The subsequent resolution of (±)- 5a – h was carried out by means of lipase-catalyzed hydrolysis, the most adequate enzymes being lipases from Candida rugosa (CRL) and Candida antarctica (CAL-B). The moderate to high enantioselectivities values ( E up to >200) obtained in most cases allowed us to obtain the corresponding optically active 1,4-dihydropyridine derivatives with high enantiomeric excesses (ee≥94%) and yields.