Postsynthetic modification of C3-symmetric aza-beta3-cyclohexapeptides

The Journal of Organic Chemistry
Philippe Le GrelMichel Potel

Abstract

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.

References

Jun 26, 2003·Journal of the American Chemical Society·Sijbren Otto, Stefan Kubik
Mar 18, 2004·Journal of the American Chemical Society·Katri Rosenthal-AizmanAnders Undén
Dec 24, 2005·Nature Chemical Biology·Sarah G Hymowitz, Avi Ashkenazi
Dec 24, 2005·Nature Chemical Biology·Sylvie FournelGilles Guichard
Aug 24, 2006·Journal of the American Chemical Society·Zaida Rodriguez-DocampoSijbren Otto

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Citations

May 10, 2013·Chirality·Philippe Le GrelAlexandre Hocquet
Jul 20, 2011·Chemical Society Reviews·Tamás A Martinek, Ferenc Fülöp
Oct 10, 2008·The Journal of Organic Chemistry·Arnaud SalaünPhilippe Le Grel
Aug 14, 2009·The Journal of Organic Chemistry·Sri Kamesh NarasimhanYan-Yeung Luk

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