Quantitative insights and improvements of enzyme activity and stereoselectivity for CALB-catalyzed alcoholysis in two-step desymmetrization

[Display omitted] •A generalized analytic solution for the two-step desymmetrization process is derived and employed for obtaining quantitative insights of the process.•A formula is also found for investigating effects of dimensionless parameters on varying the enantiomeric excess of the major enant...

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Bibliographic Details
Published in:Journal of molecular catalysis. B, Enzymatic Enzymatic, 2016-05, Vol.127, p.82-88
Main Authors: Hsiao, Hsu-Ting, Lin, Shin-Yan, Tsai, Shau-Wei
Format: Article
Language:English
Subjects:
Azolides
Biotransformations
Kinetic resolution
Lipases
Two-step desymmetrization
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Summary:[Display omitted] •A generalized analytic solution for the two-step desymmetrization process is derived and employed for obtaining quantitative insights of the process.•A formula is also found for investigating effects of dimensionless parameters on varying the enantiomeric excess of the major enantiomer.•The kinetic and thermodynamic analysis for the alcoholic desymmetrization of di-1,2,4-triazolidyl 3-phenylglutarateis is furthermore demonstrated, showing improvements of the enzyme performance via the substrate engineering approach. A generalized analytical solution for the two-step desymmetrization is recommended for doing the parameter estimation and process simulation in practical applications. A formula is then derived for investigating effects of the dimensionless kinetic parameters and molar fraction of the substrate on varying the enantiomeric excess of the major enantiomer. With the preparation of (R)-3-phenylglutaric 4-(1,2,4-triazolidyl)-butyl ester from 3-phenylglutaric di-1,2,4-triazolide via CALB-catalyzed alcoholysis in anhydrous MTBE as the model system, agreements between the best-fit results and experimental data are demonstrated from the kinetic analysis, in which the lipase performance is largely improved by using the substrate engineering approach in comparison with the previous result via the hydrolytic desymmetrization. Enhancements of the enzyme activity and stereoselectivity with the temperature in both the desymmetrization and subsequent kinetic resolution steps are demonstrated and elucidated from the thermodynamic analysis.
ISSN:1381-1177
1873-3158
DOI:10.1016/j.molcatb.2016.02.013