Effect of Solvent Polarity on Enantioselectivity in Candida Antarctica Lipase B Catalyzed Kinetic Resolution of Primary and Secondary Alcohols

摘要

The Candida antarctica lipase B (CAL-B) catalyzed kinetic resolution of primary and secondary alcohols via acetylation is dependent on the permittivity (e) of the reaction solvent. For example, the enantiomeric ratio (E) vs epsilon plot for the acetylation of 1-(naphth-2-yl)ethanol (1) exhibits a convex shape, taking the maximum E value at a medium e value (11.2), whereas the same plot for the acetylation of benzyl 3-hydroxybutylate (3) exhibits a concave shape, taking the minimum E value at a similar e value (11.6). Kinetic studies reveal that the difference in shape of the E vs epsilon plots originates from the relative reaction rate between the enantiomers with different Michaelis constants (Km). Thus, when the enantiomer with a larger Km value in the middle e region reacts more slowly than its antipode, the e dependence of E exhibits a convex shape. On the other hand, when the enantiomer reacts more quickly, it exhibits a concave shape. The E vs epsilon plot for the acetylation of 2-methoxy-2-phenylethanol (7) exhibits a convex shape with the maximum E value (20) at epsilon = 14.1. The E value can be further improved to almost reach the efficiency required for industrial applications (E approximate to 30) by the addition of a nitro compound.