Yuting Gao; Yang Sun; Xianfu Fang; Guixian Zhao; Xufeng Li; Gong Zhang; Yangfeng Li; Yizhou Li
Org. Chem. Front., 2022, 9, 4542-4548
https://doi.org/10.1039/D2QO00881E

Abstract

The DNA-encoded chemical libraries (DELs) technology is a novel drug discovery tool, benefiting from its large number of compound collections with chemical space coverage. Vinyl sulfone is a privileged functional group, eliciting diverse pharmacological activities as the covalent warhead. In this report, we incorporated vinyl sulfone into the DEL chemistry field by developing a mild and efficient DNA-compatible method starting from simple sodium sulfinates and DNA-conjugated alkenes, affording a broad substrate scope with moderate-to-excellent conversions. Further chemical transformations including thiol-Michael addition reaction, together with enzymatic ligation, were also successfully implemented to demonstrate the feasibility of this DNA-compatible synthesis in DEL construction.