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Catalysis of Thiol–Thioester Exchange by Water-Soluble Alkyldiselenols Applied to the Synthesis of Peptide Thioesters and SEA-Mediated Ligation

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journal contribution
posted on 19.09.2018, 00:00 by Marine Cargoët, Vincent Diemer, Benoît Snella, Rémi Desmet, Annick Blanpain, Hervé Drobecq, Vangelis Agouridas, Oleg Melnyk
N-Alkyl bis­(2-selanylethyl)­amines catalyze the synthesis of peptide thioesters or peptide ligation from bis­(2-sulfanylethyl)­amido (SEA) peptides. These catalysts are generated in situ by reduction of the corresponding cyclic diselenides by tris­(2-carboxyethyl)­phosphine. They are particularly efficient at pH 4.0 by accelerating the thiol–thioester exchange processes, which are otherwise rate-limiting at this pH. By promoting SEA-mediated reactions at mildly acidic pH, they facilitate the synthesis of complex peptides such as cyclic O-acyl isopeptides that are otherwise hardly accessible.