Aza-beta3-cyclohexapeptides: pseudopeptidic macrocycles with interesting conformational and configurational properties slow pyramidal nitrogen inversion in 24-membered rings!
Among pseudopeptidic foldamers, aza-beta3-peptides have the unique property to possess nitrogen stereocenters instead of carbon stereocenters. As the result of pyramidal inversion at N(alpha)-atoms along the backbone, they behave as a set of C8-based secondary structures in equilibrium. This structural modulation is exploited here to prepare 24-membered macrocycles with great efficiency. Both crystal structures and spectroscopic data establish that aza-beta3-cyclohexapeptides adopt a highly organized conformation where the relative configuration of chiral nitrogen atoms is alternated. This makes them an interesting scaffold as the stereocontrol occurs spontaneously through the cyclization. These compounds reveal an unprecedented slow pyramidal nitrogen inversion in macrocycles. Pyramidal ground state stabilization, hindered rotation, steric crowding, and H-bond cooperativity are proposed to participate in this striking phenomenon. The equilibrium between invertomers of aza-beta3-cyclohexapeptides is reminiscent of the interchange between the two chair forms of cyclohexane.
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
Potel
Michel
M
Le Grel
Barbara
B
Lassagne
Fredéric
F
D001372:Aza Compounds / Q000737:chemistry*; D003461:Crystallography; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D047028:Macrocyclic Compounds / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry*; D011487:Protein Conformation
D001372:Aza Compounds; D047028:Macrocyclic Compounds; D009842:Oligopeptides; D010456:Peptides, Cyclic; D009584:Nitrogen