Enantioselective lipase-catalysed kinetic resolution of acyloxymethyl and ethoxycarbonylmethyl esters of 1,4-dihydroisonicotinic acid derivatives

• Published in: Tetrahedron: Asymmetry
• Main Authors: Sobolev, A., Franssen, M.C.R., Poikans, J., Duburs, G., de Groot, Æ.
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2002
• Subjects: Life Science; Antarc*; Antarctica
• Online Access: https://research.wur.nl/en/publications/enantioselective-lipase-catalysed-kinetic-resolution-of-acyloxyme; https://doi.org/10.1016/S0957-4166(02)00655-9

The lipase-catalysed kinetic resolution of four derivatives of 4-[(acyloxy)methyl] and 4-ethoxycarbonylmethyl 3-methyl 5-propyl 2,6-dimethyl-1,4-dihydro-3,4,5-pyridinetricarboxylates has been investigated. Whereas the enantioselectivity of lipases towards the acyloxymethyl derivatives was rather low, the Candida antarctica lipase B (Novozym 435?, CAL-B)-catalysed hydrolysis of the ethoxycarbonylmethyl ester of 1,4-dihydroisonicotinic acid was enantioselective. In water-saturated diisopropyl ether at 45°C the enantioselectivity of CAL-B toward the ethoxycarbonylmethyl ester was rather moderate (E=13.8), but it was enhanced at rt and 4°C (E=21.5 and E=28.9, respectively). A high enantiomeric ratio (E=45.3) was reached at subzero temperatures, although at the expense of the reaction rate.