Postsynthetic Modification of C3-Symmetric Aza-3-Cyclohexapeptides

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• 作者：Philippe Le Grel ; Arnaud Sala&uuml ; n ; Clé ; mence Mocquet ; Barbara Le Grel ; Thierry Roisnel ; Michel Potel
• 刊名：Journal of Organic Chemistry
• 出版年：2008
• 出版时间：February 15, 2008
• 年：2008
• 卷：73
• 期：4
• 页码：1306 - 1310
• 全文大小：274K
• 年卷期：v.73,no.4(February 15, 2008)
• ISSN：1520-6904

文摘

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We have synthesized a series of C₃-symmetric aza-ges/gifchars/beta2.gif" BORDER=0 ALIGN="middle">³-cyclohexapeptides with functionally diverse sidechains 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, leadingto a wide family of C₃-symmetric cyclohexapeptides analogues. The macrocyclic backbone of the aza-ges/gifchars/beta2.gif" BORDER=0 ALIGN="middle">³-cyclohexapeptides shows a highly ordered conformation that is sustained by a dense intramolecularH-bond network where all endocyclic NHs are hydrogen bonded, the side chains being projected inequatorial position around the macrocycle. The resulting internal secondary structure relies on thecooperative alternation of two slightly different C₈-bifidic pseudocycles, which differ mainly by thehybridization of the N^{ges/gifchars/alpha.gif" BORDER=0>} nitrogen atom (N-N_sp³-turn and N-N_sp²-turn). In both cases, the nitrogen lonepair participates to stabilize the pseudocycle. This has been established by NMR experiments and X-raydiffraction analysis. As in the precursors, the nitrogen stereocenters are characterized by a strikinglyslow rate of pyramidal inversion, considering the size of the macrocycle.