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Synlett 2005(11): 1746-1748  
DOI: 10.1055/s-2005-871548
LETTER
© Georg Thieme Verlag Stuttgart · New York

Improved Process for the Enantioselective Hydrolysis of Prochiral Diethyl Malonates Catalyzed by Pig Liver Esterase

Pablo Domínguez de Maríaa, Beate Kossmannb, Nicole Potgraveb, Stefan Buchholzc, Harald Trauthweinc, Oliver Maya, Harald Gröger*a
a Degussa AG, Service Center Biocatalysis, Rodenbacher Chaussee 4, 63457 Hanau-Wolfgang, Germany
b Degussa AG, Creavis Technologies & Innovation, Paul-Baumann-Straße 1, 45764 Marl, Germany
c Degussa AG, Project House Proferm, Rodenbacher Chaussee 4, 63457 Hanau-Wolfgang, Germany
Fax: +49(6181)592961; e-Mail: harald.groeger@degussa.com;
Further Information

Publication History

Received 22 February 2005
Publication Date:
14 June 2005 (online)

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Abstract

An improved process for the enantioselective hydrolysis of prochiral 2-aryl-2-alkyl-disubstituted diethyl malonates catalyzed by pig liver esterase (PLE) was developed. With diethyl 2-phenyl-2-methylmalonate as a model substrate, the highest enantioselectivities (96% ee; R-isomer) were achieved when carrying out the process in the presence of a suitable mixture of cosolvents ­(buffer-i-PrOH-t-BuOH, 8:1:1). The process also works efficiently at higher substrate concentrations. The reaction was carried out on a multi-gram preparative scale, leading to a conversion of >95%, an enantioselectivity of 96% ee, and a yield of 83% at a substrate concentration of 200 mM.

Key words

asymmetric synthesis - enzymes - hydrolyses - malonates - solvent effects

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