MARKED DEPENDENCE OF ENZYME PROCHIRAL SELECTIVITY ON THE SOLVENT

Prochiral selectivity of various hydrolytic enzymes (lipases and proteases) in organic solvents was investigated in transformations involving a 2-substituted 1,3-propanediol or its diester. In two instances, a significant dependence of enzyme prochiral selectivity on the solvent was found: transesterification of diol 1 with vinyl butyrate catalyzed by Aspergillus oryzae protease in anhydrous solvents and hydrolysis of diester 3 catalyzed by Pseudomonas sp. lipase in hydrated organic solvents (monoester 2 was a product in both reactions). The latter process, where the pro-S selectivity of the enzyme varied from around 3 in some solvents to greater than 30 in others, was examined in more detail. A mechanistic model was proposed that predicted an inverse correlation between lipase's prochiral selectivity and solvent hydrophobicity, as well as particular effects of substrate structure variation and an additive on the prochiral selectivity; all these predictions were confirmed experimentally. Subtilisin Carlsberg lacked appreciable prochiral selectivity in either transesterification or hydrolysis reactions regardless of the solvent; this was rationalized by means of interactive computer modeling based on the X-ray crystal structure of this serine protease.