Synthesis of Thiohydantoin Scaffolds on DNA for Focused DNA-Encoded Library Construction

Thiohydantoin represents a significant class of biologically active privileged heterocyclic scaffolds. Herein, we present a convenient and robust DNA-compatible method for constructing a thiohydantoin-focused DNA-encoded library. This reaction can be applied to a wide variety of isothiocyanate partners, arylamine feedstocks, and diverse α-amine acid derivatives, exhibiting excellent conversions, high functional group tolerance, and preservation of DNA tag integrity. Our method allows for easy access to a valuable three-cycle thiohydantoin-focused DNA-encoded library.