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. The latter is characterized by an uninterrupted internal H-bond network and a syndiotactic arrangement of the asymmetric centers. It means that the presence of the optically pure residue acts as a conformational lock to select a single enantiomer through the cyclization by controlling the absolute configuration of all the nitrogen atoms. To our knowledge, this represents the first example of a dynamic enantioselection process involving several centers prone to pyramidal inversion. These results give a new impulsion to the control of nitrogen chirality, which remained limited to small cycles for 60 years.
Mocquet
Clémence
C
ICMV and CSM, UMR CNRS 6226, Université de Rennes I, 35042 Rennes Cedex, France.
Salaün
Arnaud
A
Claudon
Paul
P
Le Grel
Barbara
B
Potel
Michel
M
Guichard
Gilles
G
Jamart-Grégoire
Brigitte
B
Le Grel
Philippe
P
D000409:Alanine / Q000031:analogs & derivatives; D001372:Aza Compounds / Q000737:chemistry*; D008958:Models, Molecular; D009584:Nitrogen / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000737:chemistry*; D010649:Phenylalanine / Q000031:analogs & derivatives; D011487:Protein Conformation; D013237:Stereoisomerism
D001372:Aza Compounds; D010456:Peptides, Cyclic; D010649:Phenylalanine; D009584:Nitrogen; D000409:Alanine