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. The resulting internal secondary structure relies on the cooperative alternation of two slightly different C8-bifidic pseudocycles, which differ mainly by the hybridization of the Nalpha nitrogen atom (N-Nsp3-turn and N-Nsp2-turn). In both cases, the nitrogen lone pair participates to stabilize the pseudocycle. This has been established by NMR experiments and X-ray diffraction analysis. As in the precursors, the nitrogen stereocenters are characterized by a strikingly slow rate of pyramidal inversion, considering the size of the macrocycle.
Le Grel
Philippe
P
ICMV, UMR CNRS 6226, Université de Rennes I, 263 avenue du Général Leclerc, 35042 Rennes Cedex, France. philippe.legrel@univ-rennes1.fr
Salaün
Arnaud
A
Mocquet
Clémence
C
Le Grel
Barbara
B
Roisnel
Thierry
T
Potel
Michel
M
D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D011487:Protein Conformation
D009842:Oligopeptides; D010456:Peptides, Cyclic