Lipase-mediated kinetic resolution of rigid clofibrate analogues, with lipid-modifying activity

The lipase-catalysed kinetic resolution of methyl (+/-)-6-chloro-2.3-dihydro-4H-1-benzopyran-2-carboxylic acid. and (+/-)-6-chloro-2,3-dihydro-4H-1-benzopyran-3-carboxylic acid, rigid analogues of clofibrate. was effected with fair to moderate enantioselectivities (E = 1.0-4.8), enantiomeric excesses of up to 86%, and workable reaction rates. Enantiomerically pure (R)- and ( S)-5-chloro-2,3-dihydro-1-benzofuran-2-carboxylic acids were obtained by fractional crystallisation of the diastereomeric salts of the corresponding racemic acid with (+)- and (-)-amphetamine from ethanol; the absolute configuration of the products were established by chemical correlation.