Issue 9, 2022

In-solution direct oxidative coupling for the integration of sulfur/selenium into DNA-encoded chemical libraries

Abstract

Sulfur/selenium-containing electron-rich arenes (ERAs) exist in a wide range of both approved and investigational drugs with diverse pharmacological activities. These unique chemical structures and bioactive properties, if combined with the emerging DNA-encoded chemical library (DEL) technique, would facilitate drug and chemical probe discovery. However, it remains challenging, as there is no general DNA-compatible synthetic methodology available for the formation of C–S and C–Se bonds in aqueous solution. Herein, an in-solution direct oxidative coupling procedure that could efficiently integrate sulfur/selenium into the ERA under mild conditions is presented. This method features simple DNA-conjugated electron-rich arenes with a broad substrate scope and a transition-metal free process. Furthermore, this synthetic methodology, examined by a scale-up reaction test and late-stage precise modification in a mock peptide-like DEL synthesis, will enable its utility for the synthesis of sulfur/selenium-containing DNA-encoded libraries and the discovery of bioactive agents.

Graphical abstract: In-solution direct oxidative coupling for the integration of sulfur/selenium into DNA-encoded chemical libraries

Supplementary files

Article information

Article type
Edge Article
Submitted
11 11 2021
Accepted
29 1 2022
First published
01 2 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2022,13, 2604-2613

In-solution direct oxidative coupling for the integration of sulfur/selenium into DNA-encoded chemical libraries

S. Yang, G. Zhao, Y. Gao, Y. Sun, G. Zhang, X. Fan, Y. Li and Y. Li, Chem. Sci., 2022, 13, 2604 DOI: 10.1039/D1SC06268A

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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