Z/E isomerism in Nα-Nα-disubstituted hydrazides and the amidoxy bond: application to the conformational analysis of pseudopeptides built of hydrazinoacids and α-aminoxyacids.

We have investigated the Z/E isomerism of the hydrazide link (CO-NH-N) and amidoxy link (CO-NH-O). The study was first focused on small molecular models using NMR and X-ray diffraction. It allowed determination of simple NMR criterions to differentiate easily the Z and E forms, which were then applied to investigate the behavior of these links inside the corresponding oligomers.

Aza-beta3-cyclopeptides: a new way of controlling nitrogen chirality.

Sixteen and 24 membered aza-beta(3)-peptidic macrocycles containing a alpha-hydrazinoacid or a beta(3)-aminoacid were synthesized. The conformation of these pseudopeptides was determined by using NH chemical shift analysis, NH extinction, VT-NMR experiments, and X-ray diffraction. The study shows that a stable conformation is retained between 223 and 413 K.

Aza-beta3-cyclotetrapeptides.

The cyclization of aza-beta(3)-tetrapeptides gives access to new CTP (cyclotetrapeptide) analogues. These stereocontrolled templates are assembled without any asymmetric synthesis. X-ray crystallographic structure and NMR analysis show that the macrocyclic scaffold is characterized by a fully cooperative intramolecular H-bond network, in sharp contrast with the nanotubular assemblies observed for beta(3)-cyclotetrapeptides.

Postsynthetic modification of C3-symmetric aza-beta3-cyclohexapeptides.

We have synthesized a series of C3-symmetric aza-beta3-cyclohexapeptides with functionally diverse side chains carrying a good functional diversity. The very simple chemical sequence that we used (debenzylation/acylation) makes it certain that the series synthesized could be easily expanded, leading to a wide family of C3-symmetric cyclohexapeptides analogues. The macrocyclic backbone of the aza-beta3-cyclohexapeptides shows a highly ordered conformation that is sustained by a dense intramolecular H-bond network where all endocyclic NHs are hydrogen bonded, the side chains being projected in equatorial position around the macrocycle.