All-thioamidated homo-α-peptides: Synthesis and conformation

摘要

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-α-oligopeptides based on the α-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 α-amino acid residues can easily adopt either folded or fully extended conformations. Short series of terminally protected, fully thioamidated, homo-α-peptides were synthesized. For the first time, their preparation was achieved in single-step fashion through direct thionation of their oxygenated precursors. Conformation analysis confirms that the thioamidated α-amino acid residues can easily adopt either folded or fully extended conformations.