Kinetic and thermodynamic analysis for lipase-catalyzed hydrolytic resolution of (R,S)-alcohols though their azolyl carbamates

Abstract

A new approach to the lipase-catalyzed hydrolytic resolution of (R,S)-azolyl carbamates for obtaining chiral azolyl carbamates and alcohol is described. With (R,S)-1-phenylethyl azolyl carbamates as the model substrates, the best reaction condition of using (R,S)-1-phenylethyl 4-bromopyrazole carbamate (1) as the substrate in water-saturated diisopropyl ether at 45 °C is selected. The kinetic constants, and hence enantiomeric ratio of 124, are then estimated from the kinetic analysis by considering the alcohol inhibition effect, with which theoretical time-course conversions for both enantiomers are numerically solved and agree with the experimental data. The thermodynamic parameters -ΔΔH and -ΔΔS satisfying a linear enthalpy-entropy compensation relationship of -ΔΔS = -38.84 + 3.29(-ΔΔH) are further estimated. An extension of the resolution platform to (R,S)-4-bromopyrazole carbamates derived from other (R,S)-alcohols (4, 5, 7) is also addressed.

Enzyme Biocatalysis for Sustainability Applications in Reactors: A Systematic Review

“…63 In the pharmaceutical industry, Novozym 435 have been deeply discussed for its application in the synthesis of selected isomers of chiral drugs. 65 Siodmiak et al reports due to the displacement of the biocatalyst in solvents, multiple reuse cycles of Novozym 435 are unfeasible. 66 However, based on the reviews conducted, several of the reusability studies exhibit outstanding results, where in one study the biocatalyst could be reused up to 100 cycles.…”

“…Ortiz et al reports that the lipase preparation method is found to be the most extensive method used in literature reports . In the pharmaceutical industry, Novozym 435 have been deeply discussed for its application in the synthesis of selected isomers of chiral drugs …”