N-Acyl Transfer Reactions in Peptide Synthesis

We have developed a new method for peptide synthesis through the Ag(I)-promoted coupling of thioamides with carboxylic acids. This process generates an isoimide, which undergoes and N-acyl transfer to generate an imide. The peptide imide can be hydrolysed to generate a native amide bond, or can undergo subsequent acyl transfer reactions to generate a range of modified peptides. We are investigating applications in peptide ligation, peptide residue excision/insertion, and peptide thioester synthesis.

 

Recent Publications

C. A. Hutton, J. Shang and U. Wille, “Synthesis of Peptides by Silver-Promoted Coupling of Carboxylates and Thioamides: Mechanistic Insight from Computational Studies,” Chem. Eur. J. 2016, 22, 3163–3169.

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J. Shang, A. Pourvali, J. R. Cochrane and C. A. Hutton, “Steric and Electronic Effects in the Synthesis and Regioselective Hydrolysis of Unsymmetrical Imides,” Aust. J. Chem. 2015, 68, 1854–1858.

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A. Pourvali, J. R. Cochrane, C. A. Hutton, “A new method for peptide synthesis in the N–C direction: amide assembly through silver-promoted reaction of thioamides,” Chem. Commun., 2014, 50, 15963–15966.

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