Sur le rôle de la partie glucidique ou de la partie lipidique dans l auto-organisation des neoglycolipides (Synthèse de deux nouvelles familles de glycoamphiphiles et étude de leur comportement liquide cristallin)

Cette thèse est une contribution à l étude des relations structure propriétés dans le domaine de la glycoamphiphilie. Trois nouvelles familles de neoglycolipides ont été synthétisées, deux familles principalement destinées à apporter des éléments sur l état liquide cristallin des glycolipides, et une troisième famille permettant d aborder l étude de nouvelles glycosondes fluorescentes. Plus de 50 produits finaux ont été préparés (et donc leurs très nombreux précurseurs) et caractérisés structuralement par spectroscopie RMN, de masse, et par analyse élémentaire. Les propriétés liquides cristallines de ces nouveaux produits ont été ensuite étudiées par microscopie optique et DSC. L étude des propriétés liquides cristallines de la famille d éthers montrent que la localisation de la chaine sur le squelette sucre modifie la répartition entre liaisons hydrogène inter- ou intra moléculaires entre têtes polaires sucres. L analyse du comportement thermotrope des glucostéroïdes, notamment ceux qui sont disubstitués, montre que les interactions lipide-lipide sont également très importantes. Il a été observé que ces systèmes complexes pouvaient adopter deux types d architectures au niveau supramoléculaire en fonction de la flexibilité du système, laissant plus ou moins aux trois motifs présents dans la molécule la liberté de choisir leur préférence d autoassociation. Les glycostéroïdes étant largement rencontrés dans la Nature, on peut considérer que ces observations nouvelles qui ont été apportées signalent que le comportement supramoléculaire de telles molécules est potentiellement multiple. Enfin, une brève exploration d une nouvelle famille de glycosondes fluorescentes a été abordée.In this study, we have synthesized two families of new carbohydrate-based amphiphilic derivatives: a series of alkyl glucoside ethers varying in terms of chain length and position on the sugar, and a series of glucosteroids varying in terms of alkyl spacer and, for the disutibstuted systems, in terms of alkyl side chain length. By the means of analytical methods, such as NMR spectroscopy, mass spectroscopy and elementary analysis, the structure of all the compounds was carefully established, as well as their purity. Their liquid crystalline behaviors were studied by the means of transmission light microscopy and differential scanning calorimetry. The two families of compounds which have been studied illustrate how much the behavior can be essentially related to polar interactions (H-bonding), therefore to the sugar moiety, for the ether series, or to hydrophobic interactions (lipid-lipid) in the glucosteroid series. In this latter series, preference for either steroid-stroid or steroid alkyl packing appears as an insight in understanding the behavior of complex lipids, showing potentially more than one conformational structure with important consequences on the supramolecular level, therefore to their potential biological role. This could be regarded as lipid denaturation by analogy to the protein denaturation. Also, when we see that compounds like the glycosteroids having an long chain ester -CAG, BbGL-I, are found to exist in Nature, and how much glycolipid-cholesterol interactions were recently shown to be critical in some biological processes, it is hoped that our observations can provide a new vision angle for the study of complex lipids and glycolipids. As a start to develop new probes targeting the lipid raft microdomain in membranes, we also explored a sequence towards carbohydrate laurdan hybrids. Further development of this strategy and evaluation of the biological properties is programmed within new collaborative projects.VILLEURBANNE-DOC'INSA-Bib. elec. (692669901) / SudocSudocFranceF

Carboxymethyl Tri‐O‐acetyl‐α‐D‐glucopyranoside 2‐O‐Lactone — A Synthon for the Preparation of Neoglucoconjugates

International audienceCarboxymethyl triO -acetyl-α-D-glucopyranoside 2-O-lactone (CMGL), the bicyclic lactone obtained in two steps from isomaltulose by an oxidation-acetylation sequence, is a convenient synthon for connecting a glucosyl moiety with other constructs. Its synthesis and its reactivity with regards to various nucleophilic species are described and the different types of glucoconjugates which have been prepared by this method, as well as other sources of carboxymethyl glycosides, are reviewed

Synthesis of sugars embodying conjugated carbonyl systems and related triazole derivatives from carboxymethyl glycoside lactones. Evaluation of their antimicrobial activity and toxicity.

International audienceThe synthesis of a series of pyranoid derivatives comprising a conjugated carbonyl function and related triazole derivatives, structurally suitable for bioactivity evaluation, was achieved in few steps starting from readily available carboxymethyl glycoside lactones (CMGL). 3-Enopyranosid-2-uloses were generated by oxidation/elimination of tri-O-acylated 2-hydroxy pyranosides. Subsequent Wittig olefination provided stereoselectively 2-C-branched-chain conjugated dienepyranosides with (E)-configuration around the exocyclic double bond. A heterogeneous CuI/Amberlyst-catalyzed 'click' chemistry protocol was used to convert glycosides bearing a propargyl moiety into the corresponding 1,2,3-triazoles. These new molecules were screened for their in vitro antibacterial and antifungal activities and those containing conjugated carbonyl systems demonstrated the best efficacy. (N-Dodecylcarbamoyl)methyl enone glycerosides were the most active ones among the enones tested. The α-anomer displayed very strong activities against Bacillus cereus and Bacillus subtilis and strong activity toward Enterococcus faecalis and the fungal pathogen Penicillium aurantiogriseum. The corresponding β-anomer presented a very strong inhibitory effect against two fungal species (Aspergillus niger and P. aurantiogriseum). (N-Dodecyl-/N-propargyl/or N-benzylcarbamoyl)methyl dienepyranosides exhibited selectively a strong activity toward E. faecalis. Further acute toxicity evaluation indicated low toxic effect of the (N-dodecylcarbamoyl)methyl enone glyceroside α-anomer and of the carbamoylmethyl dienepyranosides N-protected with propargyl or benzyl groups

Sporopollenin exine capsules (SpECs) derived from Lycopodium clavatum provide practical antioxidant properties by retarding rancidification of an ω-3 oil

In recent years the use of natural antioxidants in foodstuffs and personal care products has become increasingly important for consumers and therefore manufacturers. In this work, sporopollenin exine capsules (SpECs), extracted from spores of the common club moss Lycopodium clavatum L, have been shown to protect an ω-3 oil from oxidation caused by natural light or accelerated oxidation with UV irradiation. The mechanism of action has been shown to be principally by free radical quenching as opposed to light shielding, supported by evidence of similarity in levels of protection when the ratio of SpECs to oil was 0.2 % w/v compared with 50 % w/w. The antioxidant effect is not materially altered by the extraction process from the raw material and is clearly an inherent property of the sporopollenin contained in the spores of L. clavatum due to the accessible phenolic groups on the surface on the SpECs. These results provide promising evidence that SpECs could be useful as a bio-sourced antioxidant for protecting ω-3 oils and related oxidation-prone molecules

Franco-Chinese chemicals bonds - Avant-propos

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