Development of on-DNA vinyl sulfone synthesis for DNA-encoded chemical libraries

Abstract

The DNA-encoded chemical library (DEL) 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 the thiol-Michael addition reaction, together with enzymatic ligation, were also successfully implemented to demonstrate the feasibility of this DNA-compatible synthesis in DEL construction.