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 Nov. 2021
Accepted
29 Janv. 2022
First published
01 Febr. 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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