Laboratoire de Glycochimie, des Antimicrobiens
et des Agroressources UMR 7378 CNRS


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Axe de recherche : Chimie pour le Vivant

Description des travaux de recherche

Les axes majeurs de recherche concernent la synthèse et l'utilisation de glyco-α-aminonitriles pour l'élaboration de composés d'intérêt biologique (glycoamino acides ; dérivés polyhétérocycliques ; pseudo-oligosaccharides) ainsi que la synthèse asymétrique de nucléosides modifiés, analogues azotés de TSAO (inhibiteurs non-compétitifs de la transcriptase inverse du VIH-1).
Nous avons également entrepris récemment l'exploration de nouvelles voies d'accès aux alkylidènes carbènes dérivés de glucides. Ces composés sont des intermédiaires de choix pour l'obtention de cycles, principalement de type cyclopropane mais également par réaction d'insertion (C-C, C-H, O-H, O-Si) de type [1,6] ou [1,5]. L'utilisation d'intermédiaires glycocarbénoïques peut permettre un accès efficace à des composés polycycliques d'intérêt thérapeutique tels les nucléosides à conformation restreinte.

Mots clés : N.C.

Sélection de publications

Cyanohydrins and Aminocyanides as Key Intermediates to Various Spiroheterocyclic Sugars
Josse, S.; Postel, D.
Carbohydrate-spiro-heterocycles 2019, 137-169.
Derivatives with a double functionalization attract great interest in organic synthesis. The association on the same carbon atom of a nitrile group and a hydroxyl or amine function allows access to promising heterocyclic compounds of particular interest resulting from reactions taking advantage of the electrophilic character of the cyano group and the nucleophilic character of hydroxyl and amino groups. Thus, α-hydroxynitriles (cyanohydrins) or α-aminonitriles represent important classes of organic intermediates. The development of these families in glycochemistry has allowed syntheses of compounds with chain elongations (Kiliani-Fischer synthesis, Strecker synthesis) or even the preparation of chiral building blocks versatile in asymmetric syntheses of biologically active compounds or their intermediates. In this chapter, we summarize the synthesis of quaternized glycoderivatives such as cyanohydrins or glycoaminonitriles and their uses as intermediates to access spiro-heterocycles. Beyond the great structural diversity, stereochemical aspects will also be identified.

Preparation of nucleoside derivative carrying an isothiazole or oxathiole cycle with an antiproliferative activity
Postel, D.; Marolleau, J.-P.; Josse, S.; Nguyen Van Nhien, A.; Chagnault, V.; Marcq, I.; Bouhlal, H.
Patent 2018, WO2018109416A1.
Nucleoside deriv. carrying an isothiazole or oxathiole cycle I, wherein A is dioxo-isothiazole or dioxo-oxathiole spiro-furan derivs; R is oxygen; R1 is alkyl, alkenyl, alkynyl, hetero-aryl; R2 is H, halogen, alkyl, alkenyl, alkynyl, aryl, hetero-aryl, aryl, were prepd. as antitumor agents with antiproliferative activity. Thus, nucleoside II was prepd. and tested in vitro as antitumor agent (EC50 = 15 μM). [on SciFinder(R)]

Synthesis of phosphorus analogs of TSAO-T
Moura, M.; Josse, S.; Postel, D.
Tetrahedron 2018, 74, 4721-4727.
Phosphorus Analogs of TSAO bearing an oxaphospholene ring instead of an oxathiole dioxide ring at C-3′ position were prepared. Strategy developed previously on saccharidic moiety was used with introduction of an electron withdrawing α group neighboring the phosphorus atom. Biological evaluation on both HIV-1 and HCV showed that these compounds have no activity.

Measurement of cytotoxicity and irritancy potential of sugar-based surfactants on skin-related 3D models
Lu, B.; Miao, Y.; Vigneron, P.; Chagnault, V.; Grand, E.; Wadouachi, A.; Postel, D.; Pezron, I.; Egles, C.; Vayssade, M.
Toxicol. in Vitro 2017, 40, 305-312.
Sugar-based surfactants present surface-active properties and relatively low cytotoxicity. They are often considered as safe alternatives to currently used surfactants in cosmetic industries. In this study, four sugar-based surfactants, each with an eight carbon alkyl chain bound to a glucose or a maltose headgroup through an amide linkage, were synthesized and compared to two standard surfactants. The cytotoxic and irritant effects of surfactants were evaluated using two biologically relevant models: 3D dermal model (mouse fibroblasts embedded in collagen gel) and reconstituted human epidermis (RHE, multi-layered human keratinocytes). Results show that three synthesized surfactants possess lower cytotoxicity compared to standard surfactants as demonstrated in the 3D dermal model. Moreover, the IC50s of surfactants against the 3D dermal model are higher than IC50s obtained with the 2D dermal model (monolayer mouse fibroblasts). Both synthesized and standard surfactants show no irritant effects after 48h of topical application on RHE. Throughout the study, we demonstrate the difficulty to link the physico-chemical properties of surfactants and their cytotoxicity in complex models. More importantly, our data suggest that, prior to in vivo tests, a complete understanding of surfactant cytotoxicity or irritancy potential requires a combination of cellular and tissue models.

Physico-chemical properties and cytotoxic effects of sugar-based surfactants: Impact of structural variations
Lu, B.; Vayssade, M.; Miao, Y.; Chagnault, V.; Grand, E.; Wadouachi, A.; Postel, D.; Drelich, A.; Egles, C.; Pezron, I.
Colloids Surf B Biointerfaces 2016, 145, 79-86.
Surfactants derived from the biorefinery process can present interesting surface-active properties, low cytotoxicity, high biocompatibility and biodegradability. They are therefore considered as potential sustainable substitutes to currently used petroleum-based surfactants. To better understand and anticipate their performances, structure-property relationships need to be carefully investigated. For this reason, we applied a multidisciplinary approach to systematically explore the effect of subtle structural variations on both physico-chemical properties and biological effects. Four sugar-based surfactants, each with an eight carbon alkyl chain bound to a glucose or maltose head group by an amide linkage, were synthesized and evaluated together along with two commercially available standard surfactants. Physico-chemical properties including solubility, Krafft point, surface-tension lowering and critical micellar concentration (CMC) in water and biological medium were explored. Cytotoxicity evaluation by measuring proliferation index and metabolic activity against dermal fibroblasts showed that all surfactants studied may induce cell death at low concentrations (below their CMC). Results revealed significant differences in both physico-chemical properties and cytotoxic effects depending on molecule structural features, such as the position of the linkage on the sugar head-group, or the orientation of the amide linkage. Furthermore, the cytotoxic response increased with the reduction of surfactant CMC. This study underscores the relevance of a methodical and multidisciplinary approach that enables the consideration of surfactant solution properties when applied to biological materials. Overall, our results will contribute to a better understanding of the concomitant impact of surfactant structure at physico-chemical and biological levels.

Reactivity of D-fructose and D-xylose in acidic media in homogeneous phases
Fusaro, M. B.; Chagnault, V.; Postel, D.
Carbohydr. Res. 2015, 409, 9-19.
Chemistry development of renewable resources is a real challenge. Carbohydrates from biomass are complex and their use as substitutes for fossil materials remains difficult (European involvement on the incorporation of 20% raw material of plant origin in 2020). Most of the time, the transformation of these polyhydroxylated structures are carried out in acidic conditions. Recent reviews on this subject describe homogeneous catalytic transformations of pentoses, specifically toward furfural, and also the transformation of biomass-derived sugars in heterogeneous conditions. To complete these informations, the objective of this review is to give an overview of the structural variety described during the treatment of two monosaccharides (D-Fructose and D-xylose) in acidic conditions in homogeneous phases. The reaction mechanisms being not always determined with certainty, we will also provide a brief state of the art regarding this.

Metal-Free Oxidative Lactonization of Carbohydrates Using Molecular Iodine
Fusaro, M.; Chagnault, V.; Josse, S.; Drillaud, N.; Anquetin, G.; Postel, D.
Carbohydrate Chemistry 2015, 33-38.

Metal-Free, Diamine-Mediated, Oxidative Monoamidation of Benzylated Carbohydrates
Fusaro, M.; Chagnault, V.; Dussouy, C.; Postel, D.
Carbohydrate Chemistry 2015, 27-32.
Presents reliable and tested protocols for preparation of intermediates for carbohydrate synthesis Offers a unique resource in carbohydrate chemistry, compiling useful information in one reference Explores carbohydrate chemistry from both the academic and industrial points of view Features contributions from world-renowned experts and is overseen by a highly respected series editor

SiO2/Ionic Liquid Hybrid Nanoparticles for Solid-State Lithium Ion Conduction
Delacroix, S.; Sauvage, F.; Reynaud, M.; Deschamps, M.; Bruyère, S.; Becuwe, M.; Postel, D.; Tarascon, J.-M.; Van Nhien, A. N.
Chem. Mater. 2015, 27, 7926-7933.
We report the physical and electrical characterization of a series of substituted imidazolium-based ionic liquids grafted on Stöber-type SiO2. This hybrid architecture affords an increase of the lithium transference to 0.56 by hindering TFSI? (bis(trifluoromethane)sulfonimide) mobility to the total ionic conductivity. When doped with 16 wt % wt LiTFSI, the resulting hybrid organic/inorganic solid material exhibits a lithium diffusion coefficient of 2 ? 10?12 m2/s at 87 °C and a conductivity of ca. 10?6 S/cm at room temperature and 10?4 S/cm at 65 °C with an activation energy barrier of 0.89 eV.