Chemoselectivity of Enzymes in Anhydrous Media is Strongly Solvent Dependent

Kinetics of monoacylation of different aminoalcohols with trifluoroethyl butyrate catalyzed by a dozen of proteases and lipases were investigated in a variety of anhydrous solvents. Chemoselectivity of these transformations (defined as the ratio of the rate of O-butyrylation to the rate of N-butyrylation, μO/μN) was found to be markedly dependent on the solvent under otherwise identical conditions. For example, with N-α-benzoyl-L-lysinol as the aminoalcohol, although Pseudomonas sp. lipoprotein lipase preferred the OH group and Mucor meheii lipase the NH2 group in all solvents tested, the extent of this preference varied up to 20 fold depending on the solvent. Moreover, for porcine pancreatic lipase, a solvent-induced inversion of chemoselectivity was observed. A mechanistic rationale was proposed which related the vO/vN values to physico-chemical properties of the solvent.