Syntheses de l'acide 3-desoxy-D-erythro-2-hexulosonique et de derives O-methyles. Etude de leurs proprietes inductrices de la biosynthese des enzymes chez Erwinia chrysanthemi

SIGLEINIST T 74802 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Synthèse d une nouvelle série de thiosucres et sulfoniums insaturés à partir de dithioacétals de cétène dérivés de sucres

REIMS-BU Sciences (514542101) / SudocSudocFranceF

Nouveaux ligands uronamides dérivés de l'acide D-galacturonique: synthèse, propriétés physico-chimiques et études de complexation avec les ions cuivre (II)

Le travail de thèse réalisé décrit la synthèse de ligands amphiphiles de type uronamides, les propriétés physicochimiques ainsi qu une étude de complexation avec les ions Cu (II). La synthèse de ces nouvelles molécules amphiphiles et complexantes a été réalisée à partir de l acide D-galacturonique, en élaborant une séquence réactionnelle directe, écocompatible et peu coûteuse, avec une étude détaillée des conditions expérimentales accompagnant chaque transformation mise en jeu afin d optimiser le processus. Cette nouvelle famille de molécules a pour objectif final de complexer les ions Cu (II) et de les transporter à travers l épiderme afin d activer certaines enzymes responsables du déclenchement du cycle de la mélanogénèse, en l occurrence la tyrosinase et la catéchol oxydase. Les propriétés physicochimiques et complexantes des ligands préparés ont été étudiées au cours de ce travail. L étude physico-chimique de cette famille de composés de type n-octyl D-galacturonamides a montré qu ils possédaient de très bonnes qualités tensioactives par comparaison aux n-octyl glycosides. D autre part, des études de complexation ont été réalisées en présence des ions Cu (II) en fonction du pH, afin de définir les différentes espèces présentes dans chaque gamme de pH, ainsi que leurs constantes de stabilité. Des complexes métalliques ont été synthétisés à l état solide, puis utilisés pour tester leur potentiel catalytique dans la réaction d oxydation modèle du 3,5-di-tert-butyl catéchol en 3,5-di-tert-butyl quinone. Cette réaction réalisable dans le méthanol ainsi qu en milieu aqueux micro-hétérogène, a montré que ces complexes cuivriques possédaient la faculté de catalyser cette réaction avec une activité équivalente dans les deux milieux. Enfin, une dernière partie a été consacrée à l élaboration d une voie d accès originale vers des macrocycles à base d acide D-galacturonique pour la conception d une nouvelle gamme de glycocryptands permettant la complexation sélective des cationsThis PhD work describes the synthesis of amphiphilic D-galacturonamide ligands, their physico-chimical properties and their complexation with copper (II) ions. These original ligands were synthesized from D-galacturonic acid, the major component of pectins from sugar beet pulp, the co-product of sugar industry. The final aim of these amphiphilic glycoligands was their use as copper ions carriers through the skin for the activation of enzymes responsible for the release of the melanogenesis cycle such as tyrosinase and catechol oxidase. The synthesis of the glycoligands used a direct, cheap and eco-compatible two step reaction sequence from D-galacturonic acid: O-glycosylation esterification and aminolysis of ester function. A detailed study of the experimental conditions (temperature, time, acid catalyst, amount of alcohol, thermal or microwave activation) for each step was developed in order to optimize the synthetic process. The physico-chemical properties were studied and the prepared ligands showed interesting tensioactive properties compared to the known n-octyl glycosides. Studies of complexation with copper (II) ions were achieved, as function of the pH, to define the various species present in every range of pH as well as their stability constants. Metallic complexes were synthesized in the solid state and used to assess their catalytic activities in the model oxidation reaction of 3,5-di-tert-butyl catechol to 3,5-di-tert-butyl quinone. These complexes can catalyze this oxidation reaction in methanol and also, interestingly, in a micro-heterogeneous aqueous medium with the same activity in both media. Free ligands as well as the corresponding copper complexes proved to be weak inhibitors for the tyrosinase activity. Finally, a last part of this work was devoted to the elaboration of synthetic routes towards macrocycles ligands from D-galacturonic acid and to the conception of a new range of glycocryptands for selective cations complexationREIMS-BU Sciences (514542101) / SudocSudocFranceF

Le D-xylose et le L-arabinose (Matière première pour la préparation de synthons polyfonctionnels énantiomériquement purs)

Cette thèse s'inscrit dans un programme de recherche multidisciplinaire dédié à la valorisation de co-produits agricoles de la région Champagne-Ardenne (blé et raisin) : GLYCOVAL. La structure des D-xylose et L-arabinose, pentoses issus de l'hydrolyse des hémicelluloses (co-produit de l'industrie céréalière), ne diffère que par la configuration du carbone 4. Le concept de base de notre projet est de mettre au point une transformation supprimant l'asymétrie de cet atome pour aboutir, quel que soit le pentose utilisé, à un intermédiaire unique : un énal comportant deux carbones asymétriques. Ensuite des transformations effectuées sur ce synthon commun permettront d'obtenir des composés à haute valeur ajoutée. Nous avons d'abord déterminé un système de protection adaptable aux deux sucres permettant d'obtenir des 5-iodopentofuranosides épimères possédant un groupement isopropylidène en position 1,2. Ces deux épimères traités par le zinc (réaction de Vasella) ont montré une différence de réactivité. Une étude approfondie a été entreprise tant sur le plan expérimental que sur le plan théorique pour expliquer cette différence. La formation de méthylosides à partir de ces iodosucres a permis de contourner ce problème de réactivité et synthétiser différents aldéhydes transformés ensuite en diènes ou oxime. Le traitement des iodosucres par des organométalliques a permis de réaliser une réaction en cascade :échange halogène-métal/ouverture/addition nucléophile conduisant à la formation de divers diols. Cette réaction domino généralisée à l'emploi de lithiens a-silylés a conduit à la synthèse de composés bis-insaturés, par une réaction " one pot " impliquant une oléofination de Pete.This PhD is part of a multi-partnership research program devoted to the valorization of Champagne-Ardenne's agricultural resources (grapes and wheat) : GLYCOVAL. Structure of D-xylose and L-arabinose obtained from hydrolysis of hemicelluloses of wheat straw and bran only differ by the absolute configuration of carbon 4. Our project's main purpose involves the transformation of these two pentoses into a unique multifunctional, optically pure, five-carbon synthon and its transformation into higher value compounds. First of all, we have investigated convenient protection of hydroxyl groups for both sugars in order to get two epimeric iodopentofuranosides with an isopropylidene on 1,2- position. The treatment of these two epimers with zinc (Vasella's reaction) shows a difference of reactivity. A thorough study was undertaken on experimental and theoretical level to rationalize this observation. We worked around this lack of reactivity using formation of methylosides from these iodosugars. This work led us to the synthesis of several unsaturated aldehydes later transformed into dienes and oximes. Reaction of these iodosugars with organometallic reagents resulted in a domino reaction of halogeno-metal exchange/ring-opening/nucleophilic addition leading to the formation of various diols. Then, this domino reaction was extended to the use of a-silylated organolithium reagents allowing the synthesis of various bis (unsaturated) compounds by a one-pot reaction involving a Peterson oleofination.REIMS-BU Sciences (514542101) / SudocSudocFranceF

Synthesis and glycosidase inhibition potency of all- trans substituted 1- C -perfluoroalkyl iminosugars

International audienceSynthetic analogues of the naturally occurring iminosugar homoDMDP, which feature a perfluoroalkyl group at the pseudo-anomeric position, have been synthesized from the corresponding sugar-derived cyclic aldonitrone. The new fluorinated iminosugars as well as homoDMDP and its 6-deoxy counterpart were evaluated for their inhibitory activity against a panel of glycosidases. While the replacement of the (1′,2′)-dihydroxyethyl substituent of homoDMDP with –C4F9 proved detrimental for enzyme binding, introduction of a –C3F7 moiety tuned the inhibitory activity spectrum selectively towards α-fucosidase and α-glucosidase from yeast

Trifluoromethide as a Strong Base: [CF₃^–] Mediates Dichloromethylation of Nitrones by Proton Abstraction from the Solvent

An unprecedented reactivity of CF₃-TMS has been revealed, which exploits the basic character of the generated [CF₃^–] capable of delivering dichloromethide from dichloromethane with subsequent transfer to nitrones under smooth conditions. The proton-abstraction pathway was demonstrated through isotopic labeling experiments in CD₂Cl₂. The same reaction was achieved in acetonitrile with the introduction of a cyanomethyl group onto the nitrones

Synthesis of pentose-containing disaccharides using a thermostable α-l-arabinofuranosidase

International audienceTo date, the enzymatically-catalysed synthesis of pentose-containing compounds has been limited to the production of oligo-beta-(1-->3) and oligo-beta-(1-->4)-linked xylopyranosides. To our knowledge, no such syntheses have involved arabinofuranose or, indeed, any other sugars in the furanose configuration. In this report, we describe the use of a thermostable alpha-L-arabinofuranosidase for the synthesis of p-nitrophenyl alpha-L-arabinofuranosyl-(1-->2)-alpha-L-arabinofuranoside, p-nitrophenyl beta-D-xylopyranosyl-(1-->2)-beta-D-xylopyranoside, p-nitrophenyl beta-D-xylopyranosyl-(1-->3)-beta-D-xylopyranoside and benzyl alpha-D-xylopyranosyl-(1-->2)-alpha-L-arabinofuranoside. Importantly, this latter compound is synthesised in a highly regiospecific reaction, which leads to the production of a single disaccharide

Synthesis of D- and L-erythro 1,5-dithiopent-1-enopyranoside sulfonium salts and their evaluation as glycosidase inhibitors

A series of sulfonium salts derived from 1,5-dithiopent-1-enopyranosides was prepared in a three-step sequence from protected D- and L-erythrofuranoses. The key step is the nucleophilic displacement of a leaving group by a sulfur atom of carbohydrate-derived ketene dithioacetals. Such compounds were assayed for their properties as glycosidase inhibitors. (C) 2009 Elsevier Ltd. All rights reserved

D-Xylose and L-arabinose laurate esters: Enzymatic synthesis, characterization and physico-chemical properties

Efficient enzymatic synthesis of D-xylose and L-arabinose lauryl mono- and diesters has been achieved by transesterification reactions catalysed by immobilized Candida antarctica lipase B as biocatalyst, in organic medium in the presence of D-xylose or L-arabinose and vinyllaurate at 50°C. In case of L-arabinose, one monoester and one diester were obtained in a 57% overall yield. A more complex mixture was produced for Dxylose as two monoesters and two diesters were synthesized in a 74.9% global yield. The structures of all these pentose laurate esters was solved. Results demonstrated that the esterification first occurred regioselectively onto the primary hydroxyl groups. Pentose laurate esters exhibited interesting features such as low critical aggregation concentrations values all inferior to 25μM. Our study demonstrates that the enzymatic production of L-arabinose and D-xylose-based esters represents an interesting approach for the production of green surfactants from lignocellulosic biomass-derived pentoses