Lipase-catalyzed enantioselective hydrolysis of methyl 2-fluoro-2-arylpropionates in water-saturated isooctane

Abstract

Lipases from Candida rugosa, Candida antartica B and Carica papaya are employed as the biocatalyst for the hydrolytic resolution of methyl 2-fluoro-2-arylpropionates in water-saturated isooctane, in which excellent to good enantioselectivity without the formation of byproducts is obtained for the papaya lipase when using ( R, S)-2-fluoronaproxen methyl ester ( 1) and methyl ( R, S)-2-fluoro-2-(4-methoxyphenyl)propionate ( 2), but not methyl ( R, S)-2-fluoro-2-(naphth-1-yl)propionate ( 3) as the substrates. The thermodynamic analysis indicates that the enantiomer discrimination for the papaya lipase is driven by the difference in activation enthalpy for compound 1, 2 or ( R, S)-naproxen methyl ester ( 4). The kinetic analysis also demonstrates that in comparison with ( S)- 4, the insertion of the 2-fluorine moiety in ( R)- 1 has increased k 2, but not K m, and consequently the lipase activity.