BioChem - DOS

Enantioselective Desymmetrization of Methylenedianilines via Enzyme-Catalyzed Remote Halogenation

Journal of the American Chemical Society

Payne, James T.; Butkovich, Paul H.; Gu, Yifan; Kunze, Kyle N.; Park, Hyun June; Wang, Duo-Sheng; Lewis, Jared C.

<P>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 &alpha;-substituted indole. These results constitute the first reported examples of asymmetric catalysis by FDHs.</P><P><B>Graphic Abstract</B><BR><IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/2018/jacsat.2018.140.issue-2/jacs.7b09573/production/images/medium/ja-2017-09573b_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja7b09573'>ACS Electronic Supporting Info</A></P>

2018

American Chemical Society

0002-7863

1520-5126

140

2

pp.546-549

10.1021/jacs.7b09573.s001

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART79511566

https://europepmc.org/articles/pmc5898188?pdf=render