Isothiocyanate intermediates facilitate divergent synthesis of N-heterocycles for DNA-encoded libraries

Chem Commun (Camb). 2024 Jul 18;60(59):7638-7641. doi: 10.1039/d4cc02547d.

Abstract

The versatile reactivity of isothiocyanate intermediates enabled the diversity-oriented synthesis (DOS) of N-heterocycles in a DNA-compatible manner. We first reported a mild in situ conversion of DNA-conjugated amines to isothiocyanates. Subsequently, a set of diverse transformations was successfully developed to construct 2-thioxo-quinazolinones, 1,2,4-thiadiazoles, and 2-imino thiazolines. Finally, the feasibility of these approaches in constructing DELs was further demonstrated through enzymatic ligation and mock pool preparation. This study demonstrated the advantages of combining in situ conversion strategies with DOS, which effectively broadened the chemical and structural diversity of DELs.

MeSH terms

  • Amines / chemistry
  • DNA* / chemistry
  • Heterocyclic Compounds* / chemical synthesis
  • Heterocyclic Compounds* / chemistry
  • Isothiocyanates* / chemistry
  • Molecular Structure
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry

Substances

  • Isothiocyanates
  • DNA
  • Heterocyclic Compounds
  • isothiocyanic acid
  • Amines
  • Small Molecule Libraries