Access to N‑Fluorinated Azapeptides and Azapeptoids as Peptidomimetic Scaffolds

In this study, a diverse range of short azapeptides and azapeptoids incorporating -CH₂CF₃ or -CH₂CF₂H groups was synthesized. The key strategy involved coupling fluorinated hydrazines with amino acids using acyl chloride derivatives or triphosgene activation. Structural and conformational analyses were conducted by using NMR spectroscopy and X-ray diffraction, revealing the impact of these fluorinated moieties on the overall molecular architecture. Crystallographic studies highlighted a preferential type II β-turn conformation with influences from short hydrogen bonding and fluorine-hydrogen interactions.