Reversal of regioselectivity in the enzymatic acylation of secondary hydroxyl groups mediated by organic solvents

Abstract

The effect of solvent hydrophobicity on the regioselectivity of acylation of phenyl 6- o-trityl-β- d-glycopyranosides using Pseudomonas cepacia lipase was investigated. In the case of phenyl 6- o-trityl-β- d-glucopyranoside, the ratio of the two products formed, namely the 2-acetate and the 3-acetate, was found to be markedly affected by the nature of the reaction medium. In solvents of low log P, values up to 85% of the 3-acetate was formed compared to less than 40% in solvents of high log P values. These observations were rationalized in terms of a working model based on partition of the trityl group between the solvent and hydrophobic surfaces near the active site of the enzyme. The model was then investigated by comparing the relative rates of acylation of phenyl 6- o-trityl-β- d-glucopyranoside and phenyl 6- o-trityl-β- d-mannopyranoside in which the 2-hydroxyl group is precluded from acylation. As predicted, similar rates for the two substrates were observed in polar solvents whereas in nonpolar solvents, the glucose derivative was acylated approximately seven times faster.