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

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.