Designing Peptide-Based Nucleophilic Catalysts Possessing Multiple Identical Active Sites for Late-Stage Chlorination of Peptides and Drugs

In the quest for developing catalysts with multiple active sites, we designed a series of methionine-based peptide catalysts prepared by classical peptide coupling. Given the widespread presence of aromatic chloro-substituents and their significant pharmacokinetic properties, the performance of these catalysts were evaluated for the late-stage chlorination of tyrosine residue on peptides up to octamer as well as aromatic drug molecules. The operationally simple reaction conditions, excellent catalyst loading up to 0.25 mol %, and gram-scale reactions are major highlights of this method.