Imidazolidinone-Tethered α-Hydrazidopeptides – Synthesis and Conformational Investigation

N-alpha-acylated beta(2,3)-3-azapeptides, or alpha-hydrazidopeptides, of different lengths were synthesized starting from a conformationally restricted imidazolidinone-tethered monomer. The preferential conformations of the oligomers were investigated by NMR and CD spectroscopy, supported by computational analysis. The experimental data clearly confirmed the tendency of these alpha-hydrazidopeptides to fold into a zig-zag (Z8) 8-helix conformation, whose stability is length-dependent, stabilized by the C=O(i)center dot center dot center dot H-N(i + 2) and N(i)center dot center dot center dot H-N(i + 1) intramolecular H-bonding pattern, as well as by non-standard C=O center dot center dot center dot H-C hydrogen bonds.