Enzyme-Catalyzed Remote Halogenation

  • Author: ChemistryViews.org
  • Published: 10 January 2018
  • Copyright: Wiley-VCH Verlag GmbH & Co. KGaA
  • Source / Publisher: Journal of the American Chemical Society/ACS Publishing
  • Associated Societies: American Chemical Society (ACS), USA
thumbnail image: Enzyme-Catalyzed Remote Halogenation

Enzymatic halogenation is a promising tool for inserting halogen substituents due to the high selectivity, mild conditions, and environmentally benign reagents associated with halogenase catalysis. Many flavin-dependent halogenases (FDHs) selectively functionalize C–H bonds on aromatic substrates, often at electronically disfavored positions. Therefore, engineering FDHs with improved stability, expanded substrate scope, and altered regioselectivity is of great interest. To date, however, no examples of enantioselective halogenation catalyzed by FDHs have been reported.


Jared C. Lewis, University of Chicago, Il, USA, and colleagues have engineered the rebeccamycin halogenase (RebH) variant 4-V to halogenate large, biologically active indoles and carbazoles. Recent studies showed that the enzyme also catalyzes remote desymmetrization of methylenedianinelines with high enantioselectivity. This is the first report of an FDH catalyzing an enantioselective halogenation reaction.

The team generated a small group of 4-V variants based on docking simulations of methylenedianiline binding in the enzyme active site. These variants provided improved activity and selectivity on a number of methylenedianiline substrates. This shows how targeted mutagenesis can be used to improve halogenase enantioselectivity in analogy to previous efforts focused on substrate scope and regioselectivity.

The team converted one of the resulting enantioenriched, halogenated methylenedianiline products to 5-substituted indole (pictured) with no loss in enantioselectivity at the α-stereogenic center. According to the researchers, future research will further expand the potential applications of these halogenases in the preparation of useful, bioactive compounds.


Article Views: 1226

Sign in Area

Please sign in below

Additional Sign In options

Please note that to comment on an article you must be registered and logged in.
Registration is for free, you may already be registered to receive, e.g., the newsletter. When you register on this website, please ensure you view our terms and conditions. All comments are subject to moderation.

Article Comments - To add a comment please sign in

Bookmark and Share

If you would like to reuse any content, in print or online, from ChemistryViews.org, please contact us first for permission. more


CONNECT:

ChemistryViews.org on Facebook

ChemistryViews.org on Twitter ChemistryViews.org on YouTube ChemistryViews.org on LinkedIn Sign up for our free newsletter


A product of ChemPubSoc Europe (16 European Chemical Societies)and Wiley-VCH