The Chan–Lam-type synthesis of thioimidazolium salts for thiol–(hetero)arene conjugation

Abstract

The design of stable and variable aryl linkers for conjugating drug moieties to the metabolism-related thiols is of importance in drug discovery. We disclosed that thioimidazolium groups are unique scaffolds for the thiol–(hetero)arene conjugation under mild conditions. The drug bound thioimidazolium salts, which are easily accessible via a copper-mediated Chan–Lam process in gram-scale, could be successfully applied to the late-stage coupling of bioactive thiols to construct a broad array of drug-like molecules.