SYNTHESIS AND ENANTIOSELECTIVE LIPASE-CATALYZED KINETIC RESOLUTION OF METHYL 6-(METHOXYCARBONYL-METHYL)SULFANYL-l,4-DIHYDROPYRIDINE-3-CARBOXYLATES

摘要

A series of methyl 6-(methoxycarbonylmethyl)sulfanyl-l,4-dihydropyridine-3-carboxy-lates as more lipophilic derivatives of biologically active 6-methylsulfanyl-l,4-dihydro-pyridine-3-carboxylic acid esters have been prepared by alkylation of 6-thioxo-l,4-dihydro-pyridines with methyl bromoacetate. Kinetic resolution catalyzed by Candida antarctica lipase В (Novozym 435~?) has been investigated; enantiomeric excess of the target products reached 70%. The experiments revealed that 6-(methoxycarbonylmethyl)sulfanyl group is an essentially new activating group, which being removed by 5 bonds from chiral center undergoes easy enzymatic hydrolysis and could be used for kinetic resolution of racemic 1,4-dihydropyridines.