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Enantioselective Desymmetrization of Methylenedianilines via Enzyme-Catalyzed Remote Halogenation.

ABSTRACT: Extensive effort has been devoted to engineering flavin-dependent halogenases (FDHs) with improved stability, expanded substrate scope, and altered regioselectivity. Here, we show that variants of rebeccamycin halogenase (RebH) catalyze enantioselective desymmetrization of methylenedianilines via halogenation of these substrates distal to their pro-stereogenic center. Structure-guided engineering was used to increase the conversion and selectivity of these reactions, and the synthetic utility of the halogenated products was shown via conversion of to a chiral ?-substituted indole. These results constitute the first reported examples of asymmetric catalysis by FDHs.

SUBMITTER: Payne JT

PROVIDER: S-EPMC5898188 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Enantioselective Desymmetrization of Methylenedianilines via Enzyme-Catalyzed Remote Halogenation.

Payne James T JT Butkovich Paul H PH Gu Yifan Y Kunze Kyle N KN Park Hyun June HJ Wang Duo-Sheng DS Lewis Jared C JC

Journal of the American Chemical Society 20180108 2

Extensive effort has been devoted to engineering flavin-dependent halogenases (FDHs) with improved stability, expanded substrate scope, and altered regioselectivity. Here, we show that variants of rebeccamycin halogenase (RebH) catalyze enantioselective desymmetrization of methylenedianilines via halogenation of these substrates distal to their pro-stereogenic center. Structure-guided engineering was used to increase the conversion and selectivity of these reactions, and the synthetic utility of ...[more]

PMID: 29294291

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