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Nouvelles Réactions De Contraction De Cycle: Outils Pour La Construction D Nouvelles réactions de contraction de cycle : outils pour la construction d’édifices organisés Guilhem Chaubet To cite this version: Guilhem Chaubet. Nouvelles réactions de contraction de cycle : outils pour la construction d’édifices organisés. Génie chimique. Université Montpellier II - Sciences et Techniques du Languedoc, 2013. Français. NNT : 2013MON20119. tel-01066789 HAL Id: tel-01066789 https://tel.archives-ouvertes.fr/tel-01066789 Submitted on 22 Sep 2014 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Délivré par l’Université Montpellier 2 Préparée au sein de l’école doctorale Sciences Chimiques Balard Et de l’ Institut des Biomolécules Max Mousseron -UMR5247 Spécialité : Ingénierie Moléculaire Présentée par Guilhem CHAUBET Nouvelles réactions de contraction de cycle : outils pour la construction d'édifices organisés Soutenue le 04 décembre 2013 devant le jury composé de Dr Gilles Guichard, Directeur de Recherche, Rapporteur Université de Bordeaux 1 Dr Jean-Luc Parrain, Directeur de Recherche, Rapporteur Université d’Aix -Marseille Dr Jean Suffert, Directeur de Recherche, Président du jury Faculté de Pharmacie de Strasbourg Pr Pascal Dumy, Professeur, Examinateur ENSC Montpellier Pr Jean Martinez, Professeur, Directeur de thèse Université Montpellier 1 Dr Isabelle Parrot, Maître de Conférences, Examinateur Université Montpellier 2 (Co-encadrante) Délivré par l’Université Montpellier 2 Préparée au sein de l’école doctorale Sciences Chimiques Balard Et de l’ Institut des Biomolécules Max Mousseron -UMR5247 Spécialité : Ingénierie Moléculaire Présentée par Guilhem CHAUBET Nouvelles réactions de contraction de cycle : outils pour la construction d'édifices organisés Soutenue le 04 décembre 2013 devant le jury composé de Dr Gilles Guichard, Directeur de Recherche, Rapporteur Université de Bordeaux 1 Dr Jean-Luc Parrain, Directeur de Recherche, Rapporteur Université d’Aix -Marseille Dr Jean Suffert, Directeur de Recherche, Président du jury Faculté de Pharmacie de Strasbourg Pr Pascal Dumy, Professeur, Examinateur ENSC Montpellier Pr Jean Martinez, Professeur, Directeur de thèse Université Montpellier 1 Dr Isabelle Parrot, Maître de Conférences, Examinateur Université Montpellier 2 (Co-encadrante) Some men see things as they are and ask why. Others dream things that never were and ask why not. George Bernard Shaw Pour Anaïs, Sibylle & Alice REMERCIEMENTS Ce travail a été effectué à l’Institut des Biomolécules Max Mousseron (IBMM – UMR 5247, UM1 – UM2 – CNRS) au sein de la F aculté des Sciences de l’Université Montpellier 2, sous la direction du Professeur Jean Martinez et l’e ncadrement du Docteur Isabelle Parrot. Je souhaite tout d’abord remercier le Professeur Jean Martinez pour m’avoir accueilli dans son laboratoire. Il m’a fait l’honneur d’assurer le suivi et l’orientation de ma thèse. Qu’il trouve ici le témoignage de ma vive gratitude et de mon profond respect. Je souhaite également remercier très vivement le Docteur Isabelle Parrot qui a suivi l’avancement de ce projet jour après jour au laboratoire, pour m’avoir offert l’opportunité de pouvoir développer ces travaux de t hèse, bien qu’éloignés des thématiques initiales, pour m’avoir poussé à persévérer et à tenir bon dans les moments difficiles, et d’une manière générale pour sa confiance, son soutien et ses conseils avisés. Je tiens à lui exprimer ma profonde reconnaissance et ma respectueuse gratitude. Je remercie le Docteur Gilles Guichard de l’Université de Bordeaux 1, le Docteur Jean -Luc Parrain de l’Université d’Aix -Marseille, le Docteur Jean Suffert de la Faculté de Pharmacie de Strasbourg et le Professeur Pascal Dum y de l’École Nationale Supérieure de Chimie de Montpellier de l’honneur qu’ils me font en acceptant de juger ce travail. Qu’ils trouvent ici l’expression de ma considération respectueuse. Je souhaite remercier tout le personnel du laboratoire, et plus particulièrement le Professeur Georges Dewynter, pour son aide dans l’élucidation de certains mécanismes réactionnels, le Docteur Xavier Bantreil, le Docteur Thomas-Xavier Métro et le Docteur Xavier Salom-Roig avec qui j’ai pu avoir des discussions scientifiqu es toujours intéressantes, le Docteur Sonia Cantel pour l’aide précieuse qu’elle m’a apportée lors de mes trois années de monitorat ainsi que Monsieur Pierre Sanchez pour les analyses LC/MS. Je tiens aussi à exprimer ma plus profonde gratitude à l’ensemble du personnel du Laboratoire de Mesures Physiques de l’IBMM et plus particulièrement à Monsieur Guillaume Cazals et Monsieur Aurélien Lebrun sans qui les travaux ici présentés n’auraient jamais été possibles. Je remercie également mes camarades de paillass e ainsi que tous les stagiaires qui ont permis l’avancement de ce projet (Jérémy, Marie, Marjorie, Stéphanie, Alexis, Maxime, Hong-ling, Coline et Alice). Enfin, je tiens à remercier toutes les personnes qui ont collaborées à cette thèse : le Docteur Morgane Pasco qui a travaillé au sein de notre groupe sur les thématiques ici présentées lors d’un contrat ATER, le Docteur Yves Collette, le Docteur Xavier Morelli et le Docteur Stéphane Betzi (Centre de Recherche en Cancérologie de Marseille) pour les études de modélisation moléculaire et de RMN, le Docteur Loïc Toupet pour la diffraction des rayons X (Université de Rennes), le Docteur Yannick Guari (Institut Charles Gerhardt de Montpellier) pour la microscopie électronique, et le Docteur Arnaud Martel (Unité de Chimie Organique Moléculaire et Macromoléculaire du Mans, UCO2M) pour les études de chimie numérique. 5 SOMMAIRE REMERCIEMENTS .............................................................................................................................. 5 SOMMAIRE .......................................................................................................................................... 7 LISTE DES ABRÉVIATIONS .......................................................................................................... 11 INTRODUCTION GÉNÉRALE ........................................................................................................ 15 CHAPITRE I. ÉTAT DE L’ART DES R ÉACTIONS DE CONTRACTI ON D’H ÉTÉROCYCLES DEPUIS 2007 .................................................................................................................................... 19 I.1. GENERALITES SUR LES REACTIONS DE CONTRACTION DE CYCLE .............................................. 21 I.1.1. Définition ..................................................................................................................................... 21 I.1.2. Occurrence naturelle des réactions de contraction de cycle .................................... 21 I.1.3. Contractions de cycle en chimie médicinale ................................................................... 22 I.2. CONTRACTIONS D ’HETEROCYCLES ............................................................................................ 24 I.2.1. Contra ction d’hétérocycles en milieu acide .................................................................... 24 1.2.1.1. Utilisation d’acides de Br ønsted......................................................................................................... 24 1.2.1.1.1. Obtention d’hétérocycles azotés saturé s ......................................................................................... 25 1.2.1.1.2. Obtention d’hétérocycles azotés insaturés ..................................................................................... 27 1.2.1.1.3. Obtention d’hétérocycles oxygénés saturés ................................................................................... 30 1.2.1.1.4. Obtention d’hétérocycles oxygénés insaturés ............................................................................... 32 1.2.1.1.5. Obtention d’autres types d’hétérocycles et de carbocycles ..................................................... 33 1.2.1.2. Utilisation d’acides de Lewis ................................................................................................................ 34 1.2.1.2.1. Obtention d’hétérocycles ........................................................................................................................ 35 1.2.1.2.2. Obtention de carbocycles ........................................................................................................................ 37 I.2.2. Contraction d’hétérocycles en milieu basique ............................................................... 39 1.2.2.1. Utilisation de bases faibles ................................................................................................................... 39 1.2.2.1.1. Obtention d’hétérocycles azotés saturés ......................................................................................... 39 1.2.2.1.2. Obtention d’hétérocycles azotés insaturés ..................................................................................... 42 1.2.2.1.3. Obtention d’hétérocycles oxygénés ...................................................................................................
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