All-thioamidated homo-alpha-peptides: synthesis and conformation

Replacement of a peptide bond with its thioamide surrogate is a classical method for the generation of a peptidomimetic with altered spectroscopic, conformational, physicochemical, and biological properties. In this context, we synthesized short series of terminally protected homo-alpha-oligopeptides based on the alpha-amino acids Gly, Ala, and Nle, as well as their corresponding fully thioamidated analogues. For the first time, the preparation of the latter compounds was achieved in single-step fashion through direct thionation of their oxygenated precursors. Using X-ray diffraction analysis and NMR spectroscopy we were also able to confirm that the thioamidated alpha-amino acid residues can easily adopt either folded or fully extended conformations.