Repository logo
 

Selective Functionalisation of 5-Methylcytosine by Organic Photoredox Catalysis.

Published version

Published version
Peer-reviewed

Repository DOI


Change log

Authors

Goodman, Jonathan M  ORCID logo  https://orcid.org/0000-0002-8693-9136
Balasubramanian, Shankar  ORCID logo  https://orcid.org/0000-0002-0281-5815

Abstract

The epigenetic modification 5-methylcytosine plays a vital role in development, cell specific gene expression and disease states. The selective chemical modification of the 5-methylcytosine methyl group is challenging. Currently, no such chemistry exists. Direct functionalisation of 5-methylcytosine would improve the detection and study of this epigenetic feature. We report a xanthone-photosensitised process that introduces a 4-pyridine modification at a C(sp3)-H bond in the methyl group of 5-methylcytosine. We propose a reaction mechanism for this type of reaction based on density functional calculations and apply transition state analysis to rationalise differences in observed reaction efficiencies between cyanopyridine derivatives. The reaction is initiated by single electron oxidation of 5-methylcytosine followed by deprotonation to generate the methyl group radical. Cross coupling of the methyl radical with 4-cyanopyridine installs a 4-pyridine label at 5-methylcytosine. We demonstrate use of the pyridination reaction to enrich 5-methylcytosine-containing ribonucleic acid.

Description

Funder: Herchel Smith Fund


Funder: Trinity College, University of Cambridge; Id: http://dx.doi.org/10.13039/501100000727


Funder: Krishnan-Ang Studentships Programme

Keywords

C−H Functionalization, Nucleic Acids, Photocatalysis, Radicals, Reaction Mechanisms

Journal Title

Angew Chem Weinheim Bergstr Ger

Conference Name

Journal ISSN

0044-8249
1521-3757

Volume Title

Publisher

Wiley
Sponsorship
Wellcome Trust (209441/Z/17/Z)