A thermodynamic study of ketoreductase-catalyzed reactions 5. Reduction of substituted ketones in n-hexane

The equilibrium constants K for the ketoreductase-catalyzed reduction reactions of 1-benzyl-3-pyrrolidinone, ethyl 2-oxo-4-phenylbutyrate, ethyl 4-chloroacetoacetate, 1-benzyl-4-piperidone, and 1-benzyl-3-piperidone were measured in n-hexane at T = 298.15 K by using gas chromatography. The equilibrium constants for the reaction involving 1-benzyl-4-piperidone were also measured as a function of temperature (288.15 to 308.05) K. The calculated thermodynamic quantities for the reaction (1-benzyl-4-piperidone + 2-propanol = 1-benzyl-4-hydroxypiperidine + acetone) reaction carried out in n-hexane at T = 298.15 K are: K = (26.2 ± 1.7); ΔrGm∘=-(8.10±0.16)kJ·mol-1; ΔrHm∘=-(3.44±0.42)kJ·mol-1; and ΔrSm∘=(15.6±1.4)J·K-1·mol-1. The chirality of the hydroxyl products of the reactions (1), (2), (3) and (5)has also been investigated. The results showed that the stereoselectivity of the hydroxyl products formed can be controlled by the selection of the solvent and enzyme used in these reactions. The thermochemical results for these reactions are compared with the results for reactions that have analogous structural features as well as with the results of quantum chemical calculations.