Optimization of Lipase-Catalyzed Enantioselective Production of 1-Phenyl 1-Propanol Using Response Surface Methodology

Abstract

Optically active 1-phenyl 1-propanol is used as a chiral building block and synthetic intermediate in the pharmaceutical industries. In this study, the enantioselective production of 1-phenyl 1-propanol was investigated systematically using response surface methodology (RSM). Before RSM was applied, the effects of the enzyme source, the type of acyl donor, and the type of solvent on the kinetic resolution of 1-phenyl 1-propanol were studied. The best results were obtained with Candida antartica lipase (commercially available as Novozym 435), vinyl laurate as the acyl donor, and isooctane as the solvent. In the RSM, substrate concentration, molar ratio of acyl donor to the substrate, amount of enzyme, temperature, and stirring rate were chosen as independent variables. The predicted optimum conditions for a higher enantiomeric excess (ee) were as follows: substrate concentration, 233 mM; molar ratio of acyl donor to substrate, 1.5; enzyme amount, 116 mg; temperature, 47 °C; and stirring rate, 161 rpm. A verification experiment conducted at these optimized conditions for maximum ee yielded 91% for 3 hr, which is higher than the predicted value of 83%. The effect of microwave on the ee was also investigated and ee reached 87% at only 5 min.

How the mode of Candida antarctica lipase B immobilization affects the continuous-flow kinetic resolution of racemic amines at various temperatures

“…Occasionally, temperature had no effect on enantioselectivity [28], whereas in other cases a maximum of enantioselectivity at a certain temperature was found [29]. Effect of the temperature on selectivity in CaLB-catalyzed hydrolysis [30][31][32][33], ammonolysis [34], direct esterification [35,36], enantioselective acylation of prochiral diols [37] and kinetic resolution of alcohols [29,38,39] has already been reported. In most of the quoted examples the enzyme-catalyzed reactions were performed in batch mode (in stirred or shaken flasks).…”

Factors screening to statistical experimental design of racemic atenolol kinetic resolution via transesterification reaction in organic solvent using free Pseudomonas fluorescens lipase

“…The R 2 for ee model is only 89.63%. As a comparison, Soyer et al obtained the R 2 for ee of 80.05% during enzymatic racemic 1‐phenyl 1‐propanol resolution, while Cunha et al described that the R 2 of 91% was adequate for accuracy and applicability of the polynomial model used to describe the optimized conditions in the kinetic resolution of racemic 1,2‐ O ‐isopropylidene‐3,6‐di‐ O ‐benzyl‐myo‐inositol. The predicted values match the experimental data reasonably well, with the R 2 of 95.13% (conversion) and 90.95% (substrate ee ).…”

“…The R 2 for ee model is only 89.63%. As a comparison, Soyer et al 40 obtained the R 2 for ee of 80.05% during enzymatic racemic 1-phenyl 1-propanol resolution, while Cunha et al 41 described that the R 2 of 91% was adequate for accuracy and applicability of the polynomial model used to describe the optimized conditions in the kinetic resolution of…”

Highly selective anti-Prelog synthesis of optically active aryl alcohols by recombinant Escherichia coli expressing stereospecific alcohol dehydrogenase

“…[3,4] The asymmetric reduction of prochiral carbonyl compounds to their corresponding alcohols is potentially one of the most useful ways of introducing chirality in a molecule. For those chiral auxiliaries production from their corresponding prochiral ketones, alcohol dehydrogenases have the inherent advantages over chemo-catalysts in terms of their highly chemo-, enantio-and regioselectivity.…”