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

Abstract

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.

New Concepts for Increasing the Efficiency in Directed Evolution of Stereoselective Enzymes

“…When acylating an alcohol, the assumption that the hydrolysis of its ester (the reverse reaction) will display the same enantioselectivity, may not always be true, although the two reactions share the same transition state . Therefore, for organic synthesis applications, where organic solvents are usually required, it is desirable to mimic the true reaction conditions for future applications.…”

Enzyme‐ and Ruthenium‐Catalyzed Enantioselective Transformation of α‐Allenic Alcohols into 2,3‐Dihydrofurans

“…CALA gave relatively low enantioselectivity and a low reaction rate. By control of the reaction time and temperature with substrate 1 a , the CALB family (CALB wild type and a CALB mutant) afforded moderate E values (ranging from 32 to 44 depending on the variant and the solid support). To our delight, lipase PS on different solid supports displayed excellent enantioselectivity; IL1‐PS (IL1‐supported lipase PS) showed the best enantioselectivity and highest reaction rate.…”

ChemInform Abstract: New Concepts for Increasing the Efficiency in Directed Evolution of Stereoselective Enzymes

“…When acylatinga na lcohol, the assumption that the hydrolysis of its ester (the reversereaction) will display the same enantioselectivity,m ay not always be true, although the two reactions share the same transition state. [26] Therefore, for organic synthesis applications,w here organic solvents are usually required, it is desirable to mimic the true reaction conditions for future applications.U nfortunately,m ost screening assays are designed for buffered systems. This study describes am ethod to screen alipase library in organic solvent.…”