Synthèse d'Analogues Bis-azotés de la Proline et Applications

Abstract : The peptidic bond in a peptide or a protein is usually flat and in trans conformation for the majority of amino acids. The situation is a little bit different upstream the proline: the thermodynamic barrier which opposes the rotation of the amide bond is weaker and the tendency of the bond to remain flat is lesser. So, this AA-Pro bond can adopt a cis conformation, leading to the formation of a turn in the peptidic chain. This work describes the synthesis and the chemical reactivity of new bis-nitrogen analogous of proline in solution to facilitate the cis conformation of a AA-PPro bond. The conformational impact that these residues may generate in pseudopeptides is also exposed.Initially, a new access road to the orthogonally protected and enantiomerically pure azaproline has been developed by exploiting previous work on the synthesis of hydrazinoesters and N-aminodipeptides. The study of the reactivity of this pseudoproline helped define the best conditions for forming pseudotripeptides of formula P1-AA1--azaPro-AA3-P3. It also guided the work, in a second step, towards the synthesis of pseudopeptide incorporating a pyrazole acid motif. Finally, the structure of the prepared compounds was analyzed by NMR, IR and molecular modeling. Examination of the P1-AA1-azaPro(Boc)-AA3-P3 revealed the formation of a pseudocycle C7 by a Hydrogen bond, favoring the trans conformation of the AA1-azaPro bond, while the absence of Boc function seems to favor the cis conformation of this bond.
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Emelyne Voss. Synthèse d'Analogues Bis-azotés de la Proline et Applications. Autre. Institut National Polytechnique de Lorraine, 2011. Français. ⟨NNT : 2011INPL059N⟩. ⟨tel-01749538⟩

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