Lipase Mediated Resolution of γ-Branched Chain Fatty Acid Methyl Esters

Abstract

Kinetic resolution of the branched chain fatty acid (BCFA) esters 4-methylhexanoic acid methyl ester (4) and 4-methyloctanoic acid methyl ester (5) was investigated using a series of hydrolases as catalysts. In the transesterification of these methyl esters to their butyl esters, two enzymes showed good conversion and a moderate enantiomeric ratio (E). In the transesterification of 4, an E of 2 was obtained for the reaction catalysed by Rhizomucor miehei lipase, whereas Candida antarctica lipase B (CALB) showed an E of 5. In the conversion of 5 to the butyl ester, Rhizomucor miehei lipase was unselective whereas CALB gave an E of 8. Apparently, changing from an ethyl group to a butyl group at the chiral centre leads to an improved chiral recognition by CALB. The lipases displayed complementary enantiomeric preference. Rhizomucor miehei lipase favours the S-enantiomer of 4 while CALB preferentially transforms the R-cnantiomer of both substrates. Molecular modelling studies supported the measured stereochemical preference of CALB. A decrease in reaction temperature from 45°C to 27°C led to a significant increase in cnantiomeric ratio (E = 23) in the transesterification of 5. These results offer good perspectives for the production of enantiomerically pure branched chain fatty acids.