Enantioselective Desymmetrization of Methylenedianilines via Enzyme-Catalyzed Remote Halogenation

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 α-substituted indole. These results constitute the first reported examples of asymmetric catalysis by FDHs.


Publication Date:
Jan 08 2018
Date Submitted:
Jun 28 2019
Pagination:
546-549
Citation:
Journal of the American Chemical Society
140
2
External Resources:




 Record created 2019-06-28, last modified 2019-07-24


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