Oral Presentation 10th Australian Peptide Conference 2013

New methods for amide bond formation (#80)

James R Cochrane 1 , Aysa Pourvali 1 , Craig A Hutton 1
  1. University of Melbourne, Parkville, VIC, Australia

In recent years a range of novel amide ligation strategies have been developed, many incorporating thioacids or thioesters as carboxylic acid surrogates.1  Most of these methods also require either a thiol-functionalised amine coupling partner, or an amine surrogate. We will present investigations into the scope and limitations of the reaction of amino acid thioamides with carboxylic acids in the presence of silver(I) to generate imide and amide adducts, based on the work of Palacios.2  This transformation represents an umpolung approach to amide bond formation that does not require pre-activation of the carboxylic acid, and as such epimerisation levels are very low.

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The application of this methodology to the solution-phase, N→C direction synthesis of the pentapeptide thymopentin (Arg-Lys-Asp-Val-Tyr) will be described.

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  1. Pattabiraman, V. R.; Bode, J. W. Nature 2011, 480, 471–479.
  2. Avalos, M.; Babiano, R.; Duran, C. J.; Jiminez, J.; Palacios, J. C. Tetrahedron Letters 1994, 35, 477–480. Avalos, M.; Babiano, R.; Cintas, P.; Durán, C. J.; Higes, F. J.; Jimenez, J. L.; Lopez, I.; Palacios, J. C. Tetrahedron 1997, 53, 14463–14480.