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Conformation of Nα-Substituted Hydrazino Acetamides in CDCl3, the Precious Help of the Analysis of Δδ between Amidic Hydrogens, and Correlation to the Conformation of Aza-β3-peptides

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posted on 06.01.2006, 00:00 by Arnaud Salaün, Annaïck Favre, Barbara Le Grel, Michel Potel, Philippe Le Grel
We studied the conformation of a series of primary amides in a solution of chloroform. Classical NMR tools such as dilution experiments, influence of DMSO, and 2D-NOESY, together with X-ray diffraction, were combined with an analysis of the difference of the chemical shift Δδ between the geminal amidic protons. This study was addressed in order to understand the conformation adopted by hydrazino acetamides 1a and 1b as model compounds for aza-β3-peptides. In this manner, it was possible to show that the amidic group of these compounds acts as a H-bond donor and interacts with two different H-bond acceptors. We concluded that the hydrazinoturn, a specific bifurcated H-bond system observed in the solid state, is also the preferred conformation of hydrazino acetamides 1a and 1b in solution. Our results show that the short-range interaction with the Nα-nitrogen lone pair not only stabilizes the C8 pseudocycle but could also contribute to the folding process of aza-β3-peptides. In light of this, it could explain why aza-β3-peptides develop a different H-bond network in comparison to their isosteric β3-peptides analogues. Our work is in keeping with the recent interest of hydrazino peptides as an extension of the β-peptide concept.