Oral Presentation 14th Australian Peptide Conference 2022

Exploiting Thioamide Reactivity in Peptide Synthesis (#3)

Craig Hutton 1 , Varsha J Thombare 1 , Sadegh Shambani 1 , Jing Shang 1
  1. University of Melbourne, Parkville, VIC, Australia

In recent years a range of novel amide ligation strategies have been developed, many incorporating sulfur-containing reagents as thioesters and other carboxylic acid surrogates. We recently reported a novel method for peptide synthesis based on the reaction of thioamides with carboxylic acids in the presence of Ag(I).1,2 These reactions proceed via Ag(I)-promoted activation of the thioamide leading to formation of an isoimide intermediate, which can undergo acyl transfer processes to generate a variety of adducts. Recent progress in this area will be highlighted, including novel strategies for macrocyclization and ligation of peptide thioamides.3,4

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  1. Pourvali, A.; Cochrane, J. R.; Hutton, C. A. Chem. Commun., 2014, 50, 15963–15966
  2. Hutton, C. A.; Shang J.; U. Wille, Chem. Eur. J. 2016, 22, 3163–3169
  3. Thombare, V. J.; Hutton, C. A. Angew. Chem. Int. Ed., 2019, 58, 4998–5002
  4. Shabani, S; Hutton, C. A. Chem. Commun. 2021, 57, 2081–2084.