Mild and Selective Trifluoromethylation of Peptides at Tryptophane Residues by a Water‐Soluble Copper Complex with Redox‐Active Ligands

2025/08/17 by Marie‐Julie Tilly, Loïc Groslambert, Nolwenn Le Breton +7 · 1 voice
Biochemistry, Genetics and Molecular Biology · Chemistry · Pharmacology, Toxicology and Pharmaceutics · #Chemical Synthesis and Analysis #Cyclopropane Reaction Mechanisms #Fluorine in Organic Chemistry

paper · pdf · doi:10.1002/chem.202501765

openalex publication_date 2025/08/17 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/27

Abstract

Selective chemical modifications of biomolecules are in high demand for the development and implementation of chemical biology strategies. Methods involving radicals have emerged as powerful options yet potentially generate side reactivities when involving harsh reaction conditions. We report the development of a mild catalytic method for the selective functionalization of tryptophane residues in peptides with a trifluoromethyl group using a water-soluble copper complex with redox-active ligands. This method displays both inter- and intramolecular selectivity for tryptophane residues and its synthetic relevance is demonstrated by the selective conversion of a 13-residue peptidic sequence and an endomorphine analogue in good yields.

Discussions

• Coincidence and fantastic collaborators made 3 papers in Chemistry in 3 weeks with Cu 1) mild and selective CF3 addition to peptides doi.org/10.1002/chem... 2) sensor for Cu(II) via 19F-NMR doi.org/1 [bsky, 1 points, 0 comments]

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