Chemoenzymatic approach to optically active 1,4-dihydropyridine derivatives

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.

Graphical abstractDownload high-res image (88KB)Download full-size image