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Enzymatic desymmetrization of 3-(4-fluorophenyl)glutaric anhydride through enantioselective alcoholysis in organic solvents

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Abstract

The enzymatic desymmetrization of 3-(4-fluorophenyl)glutaric anhydride (3-FGA) was investigated through lipase-catalyzed enantioselective alcoholysis in organic solvents. An immobilized Lipase B from Candida Antarctica (Novozym 435) was found to be an efficient biocatalyst for the enantioselective alcoholysis of 3-FGA. Methyl tert-butyl ether (MTBE) and methanol were chosen as the suitable reaction medium and acyl acceptor, respectively. The optimum reaction temperature, molar ratio of methanol to 3-FGA and 3-FGA concentration were 25°C, 2:1 and 100 mM, respectively. Under these conditions, complete conversion was achieved and methyl (S)-3-(4-fluorophenyl)glutarate ((S)-MFG) was obtained in a moderate ee value of 80%. Furthermore, the reaction was performed on a gram scale and the ee value of (S)-MFG was enriched to 96% after treatment with a toluene/hexane (2/1, v/v) mixture.

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Authors and Affiliations

  1. College of Biotechnology and Pharmaceutical Engineering, State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing University of Technology, Nanjing, 210-009, China

    Weiming Liu, Yi Hu, Yang Zhang, Yan Ma & He Huang

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  1. Weiming Liu
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Correspondence to He Huang.

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Liu, W., Hu, Y., Zhang, Y. et al. Enzymatic desymmetrization of 3-(4-fluorophenyl)glutaric anhydride through enantioselective alcoholysis in organic solvents. Biotechnol Bioproc E 19, 449–455 (2014). https://doi.org/10.1007/s12257-014-0110-9

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