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Comparison of different strategies for the lipase-catalyzed preparative resolution of racemic acids and alcohols: Asymmetric hydrolysis, esterification, and transesterification

Authors

  • Bernard Cambou,

    1. Laboratory of Applied Biochemistry, Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
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  • Alexander M. Klibanov

    1. Laboratory of Applied Biochemistry, Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
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Abstract

Lipase from Candida cylindracea has been found to be a highly stereospecific catalyst suitable for preparative resolution of racemic acids and alcohols. Using (R, S)−2-(p-chlorophenoxy) propionic acid (whose R isomer is a herbicide) and (R, S)-sec-butanol (a versatile synthon) as model compounds, three alternative approaches to lipase-catalyzed resolutions—asymmetric hydrolysis, esterification, and transesterification—have been compared. Enzymatic esterification in biphasic systems has been ruled out for preparative resolutions because addition of the acids lowers the pH of the aqueous phase thereby greatly reducing the efficiency of the procedure. Both enzymatic hydrolysis and biphasic transesterification afforded resolution of the racemates on a gram scale. From the standpoint of productivity, ease of product separation, and the amount of steps required, lipasecatalyzed asymmetric hydrolysis has been judged to be superior for the practical resolution of racemic acids, and lipase-catalyzed asymmetric transesterification to be the method of choice for the practical resolution of racemic alcohols.

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