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

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(R), CAL-B)-catalysed hydrolysis of the ethoxycarbonylmethyl ester of 1,4-dihydroisonicotinic acid was enantioselective. In water-saturated diisopropyl ether at 45degreesC the enantioselectivity of CAL-B toward the ethoxycarbonylmethyl ester was rather moderate (E = 13.8), but it was enhanced at rt and +4degreesC (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. (C) 2002 Elsevier Science Ltd. All rights reserved.