Solvent-dependent reactivity in porcine pancreatic lipase (PPL)-catalyzed hydrolysis

The solvent-dependent enzyme reactivity of porcine pancreatic lipase (PPL)-catalyzed hydrolysis was investigated using trans-3 and cis-(3-(benzyloxymethyl)oxiran-2-yl)methyl acetate 4 as substrates. The conversion efficiency and enantioselectivity of the hydrolysis of these compounds were measured in three different types of enzymatic media: neat organic solvents, organic–aqueous mixture solvent systems, and an aqueous buffer solution. Comparison of the catalytic hydrolysis that occurred in 12 different organic solvents with log P values in the range of −1.10 to 3.50 revealed that the reactivity and selectivity of PPL-catalyzed hydrolysis toward (+)- and (−)-isomers were strongly affected by the solvent system. In neat organic solvents and organic–aqueous biphasic systems, (+)-cis oxirane acetate (+)-4 was selectively hydrolyzed by PPL over the (−)-cis isomer. In contrast, hydrolysis of the (+)-trans substrate (+)-3 was preferred in monophasic organic–aqueous systems and buffer solutions. The addition of water to the organic solvent increased the overall hydrolysis rate. However, hydrolysis in the aqueous buffer solution was considerably retarded since the organic substrates were insoluble in water. Therefore, control of the solvent system can result in the successful kinetic resolution of oxirane esters and their corresponding alcohols.

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((2S,3S)-3-(Benzyloxymethyl)oxiran-2-yl)methanolC11H14O3Ee = 92.3%[α]24 = +21.65 (c 0.56, EtOAc)Source of chirality: enzyme reactionAbsolute configuration: (2S,3S)

((2R,3S)-3-(Benzyloxymethyl)oxiran-2-yl)methanolC11H14O3Ee = 99.5%[α]24 = +20.5 (c 0.45, EtOAc)Source of chirality: enzyme reactionAbsolute configuration: (2R,3S)