Quantitative analyses of biochemical kinetic resolutions of enantiomers

Chen, Ching Shih; Fujimoto, Yoshitaka; Girdaukas, Gary; Sih, Charles J.

doi:10.1021/ja00389a064

Cited by 2,659 publications

(1,246 citation statements)

References 4 publications

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“…The extreme difference in enantioselectivity that CALB displays for these compounds is remarkable since the E value observed in transesterification and hydrolysis normally are of the same by 1 H NMR. e) Calculated from conversion and ee prod according to Sih's formula [18] . f) Conversion was calculated based on ee OAc and ee OH [18] .…”

Section: Resultsmentioning

confidence: 99%

Investigation of the Impact of Water on the Enantioselectivity Displayed by CALB in the Kinetic Resolution of δ‐Functionalized Alkan‐2‐ol Derivatives

Yang

Lihammar

Bäckvall

2014

Chemistry A European J

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It is shown that the low enantioselectivity of Candida antarctica lipase B (CALB)‐catalyzed transesterification of a δ‐functionalized alkan‐2‐ol to its acetate does not correlate at all with the high enantioselectivity of the CALB‐catalyzed hydrolysis of the corresponding acetate in water. This lack of correlation is unusual and for unfunctionalized alkan‐2‐ol derivatives there is a very good correlation between the enantioselectivity of transesterification of the alcohol and hydrolysis of the corresponding acetate (E>200 in both cases). The results confirm previous predictions from molecular modeling. The water effect was mimicked by CALB variant Ala281Ser, which showed an enhanced enantioselectivity in transesterification of δ‐functionalized alkan‐2‐ols compared to wild‐type CALB.

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Section: Resultsmentioning

confidence: 99%

Investigation of the Impact of Water on the Enantioselectivity Displayed by CALB in the Kinetic Resolution of δ‐Functionalized Alkan‐2‐ol Derivatives

Yang

Lihammar

Bäckvall

2014

Chemistry A European J

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“…As predicted by molecular modeling, enantioselectivity towards 3 was not changed by A400I, while mutation G105A lead to a 6-fold increase of enantioselectivity from E = 3 (BsubpNBE WT) to E = 19 (BsubpNBE G105A) ( (ee) can be experimentally determined with high precision (± 2%) via gas chromatographic analysis. However, due to the approximations in the formula used to calculate enantioselectivity from ee values, [33] the error margin…”

Section: Modeling Of Achesmentioning

confidence: 99%

A Molecular Mechanism of Enantiorecognition of Tertiary Alcohols by Carboxylesterases

et al. 2003

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“…An increase in alcohol concentration has been shown to reduce both the reaction rate and the enantioselectivity in the esterification of 2-methyldecanoic acid. The apparent enantiomeric ratio of the lipase (Chen et al, 1982), Es = (k,.,,/K,)S/(kL. (II/K,n)Rr decreased from Es = 83 to Es = 37 when the heptanol concentration was increased from 90 mM to 900 mM in the esterification reaction (Berglund et al, 1995).…”

Section: A Molecular Basis F O R Enantioselective Substrate Inhibitionmentioning

confidence: 99%

“…The free energy of the ground state is the same for the two enantiomeric substrates. Therefore, the difference in free energy between the diastereomeric lipase-transition states is a measure of the enantioselectivity (Chen et al, 1982) Es = (k,,,/K,)s/(k,,,/K,)R of the enzyme. The simulations were performed in vacuum with a distance-dependent dielectric function (E = r ) .…”

Section: Calculation Of the Geometry And Energies Of Lipase-transitiomentioning

confidence: 99%

A structural basis for enantioselective inhibition of Candida rugosa lipase by long‐chain aliphatic alcohols

et al. 1996

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Molecular modeling showed that the enantiomers of heptyl2-methyldecanoate are productively bound to the active site of Candida rugosa lipase in quite different conformations. The fast-reacting S-enantiomer may well occupy the previously identified acyl-binding tunnel in the active site of the lipase. By contrast, the slow-reacting R-enantiomer must be bound to the active site, leaving the tunnel empty to allow the formation of two catalytically essential hydrogen bonds between His 449 of the catalytic triad and the transition state of the catalyzed reaction. This information enables us to propose a molecular mechanism explaining how long-chain aliphatic alcohols act as enantioselective inhibitors of this lipase in the resolution of 2-methyldecanoic acid. Long-chain aliphatic alcohols may coordinate to the acyl-binding tunnel of the C. rugosa lipase, thereby selectively inhibiting the turnover of the fast-reacting S-enantiomer, thus resulting in a lowered enantioselectlvity in the resolution.

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Quantitative analyses of biochemical kinetic resolutions of enantiomers

Cited by 2,659 publications

References 4 publications

Investigation of the Impact of Water on the Enantioselectivity Displayed by CALB in the Kinetic Resolution of δ‐Functionalized Alkan‐2‐ol Derivatives

Investigation of the Impact of Water on the Enantioselectivity Displayed by CALB in the Kinetic Resolution of δ‐Functionalized Alkan‐2‐ol Derivatives

A Molecular Mechanism of Enantiorecognition of Tertiary Alcohols by Carboxylesterases

A structural basis for enantioselective inhibition of Candida rugosa lipase by long‐chain aliphatic alcohols

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