LG2A

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

UMR 7378 CNRS

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  • Tutelle du CNRS
  • Tutelle UPJV

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Vincent CHAGNAULT

Maître de conférences

Mail :

Tel : 03 22 82 88 12

Fax : 03 22 82 75 60

orcid.org/0000-0002-7392-0866

Axe de recherche : Chimie pour le vivant

Description des travaux de recherche


Nos travaux portent sur la valorisation des substrats issus de la biomass et plus spécifiquement la valorisation des sucres et de leurs dérivés. Je m'intéresse particulièrement à la découverte de nouveaux outils, de nouvelles réactions, pour faciliter la transformation de ces molécules vers des produits à plus haute valeur ajoutée. Actuellement nous développons deux axes:

  • Etude de la réactivité des oses en milieux superacides : Exploration et modélisation (BDI)
  • Soft and selective oxidation of carbohydrates

Mots clés : N.C.

Sélection de publications


Using NMR to Dissect the Chemical Space and O-Sulfation Effects within the O- and S-Glycoside Analogues of Heparan Sulfate
Meneghetti, M. C. Z.; Naughton, L.; O’Shea, C.; Koffi Teki, D. S. E.; Chagnault, V.; Nader, H. B.; Rudd, T. R.; Yates, E. A.; Kovensky, J.; Miller, G. J.; Lima, M. A.
ACS Omega 2022.
Heparan sulfate (HS), a sulfated linear carbohydrate that decorates the cell surface and extracellular matrix, is ubiquitously distributed throughout the animal kingdom and represents a key regulator of biological processes and a largely untapped reservoir of potential therapeutic targets. The temporal and spatial variations in the HS structure underpin the concept of “heparanome” and a complex network of HS binding proteins. However, despite its widespread biological roles, the determination of direct structure-to-function correlations is impaired by HS chemical heterogeneity. Attempts to correlate substitution patterns (mostly at the level of sulfation) with a given biological activity have been made. Nonetheless, these do not generally consider higher-level conformational effects at the carbohydrate level. Here, the use of NMR chemical shift analysis, NOEs, and spin–spin coupling constants sheds new light on how different sulfation patterns affect the polysaccharide backbone geometry. Furthermore, the substitution of native O-glycosidic linkages to hydrolytically more stable S-glycosidic forms leads to observable conformational changes in model saccharides, suggesting that alternative chemical spaces can be accessed and explored using such mimetics. Employing a series of systematically modified heparin oligosaccharides (as a proxy for HS) and chemically synthesized O- and S-glycoside analogues, the chemical space occupied by such compounds is explored and described.
https://dx.doi.org/10.1021/acsomega.2c02070


Synthesis of novel S- and O-disaccharide analogs of heparan sulfate for heparanase inhibition
Koffi Teki, D. S. E.; Coulibaly, B.; Bil, A.; Vallin, A.; Lesur, D.; Fanté, B.; Chagnault, V.; Kovensky, J.
Org. Biomol. Chem. 2022.
Heparan sulfate (HS), a glycosaminoglycan related to heparin, is a linear polysaccharide, consisting of repeating disaccharide units. This compound is involved in multiple biological processes such as inflammation, coagulation, angiogenesis and viral infections. Our work focuses on the synthesis of simple HS analogs for the study of structure–activity relationships, with the aim of modulating these biological activities. Thioglycoside analogs, in which the interglycosidic oxygen is replaced by a sulfur atom, are very interesting compounds in terms of therapeutic applications. Indeed, the thioglycosidic bond leads to an improvement of their stability and can allow the inhibition of enzymes involved in physiological and pathological processes. In our previous work, we developed a synthetic sequence which led to a non-sulfated thiodisaccharide analog of HS. In this paper, we report our results of the development of a new synthetic method allowing access to the novel sulfated S-disaccharide, as well as to their oxygenated analogues (O-disaccharide and sulfated O-disaccharide). These 4 compounds were also tested for the inhibition of heparanase, an enzyme involved in biological processes like tumor growth and inflammation. The obtained IC50 values in the micromolar range showed the impact of the interglycosidic sulfur atom and the 6-sulfate group.
https://dx.doi.org/10.1039/d2ob00250g


Metal-free hydroxy and aminocyanation of furanos-3-uloses
Camara, T. E.; Koffi Teki, D. S.-E.; Chagnault, V.
Carbohydr. Res. 2021, 108486.
TSAO-T and ATSAO-T analogues are molecules of interest that are able to inhibit the reverse transcriptase (RT) of HIV-1 and HCV. We also recently highlighted their antiproliferative properties. In all cases, the spiro cycle was a required group for biological activities, which led chemists to produce many derivatives, especially on this ring. These structures can be accessed through the formation of glycoaminonitriles and glycocyanhydrins using methodologies not always adapted to the synthesis of large quantities. Moreover, these latter are poorly versatile (substrate-dependent), need expensive cyanogenic agents and implies the use of a metal in non-catalytic amounts. For this reason, we report here a new metal-free methodology for the synthesis of glycoaminonitriles and glycocyanhydrins using molecular iodine (I2).
https://dx.doi.org/10.1016/j.carres.2021.108486


Ring-Opening of Cyclodextrins: An Efficient Route to Pure Maltohexa-, Hepta-, and Octaoses
Pélingre, M.; Koffi Teki, D. S.-E.; El-Abid, J.; Chagnault, V.; Kovensky, J.; Bonnet, V.
Organics 2021, 2, 287-305.
Many preparations of maltooligosaccharides have been described in literature, essentially using enzymatic or biotechnological processes. These compounds, derived from starch, are well-known as prebiotic agents. The use of maltohexa-, hepta-, and octaoses as synthons in organic synthesis was also well documented in literature. They can indeed be obtained as single compounds by the cyclodextrins’ ring-opening. This reaction has been studied for many years, varying the protecting and functional groups and the reaction conditions, leading to functionalized oligomaltoses. These compounds are of wide interest in various fields. They have a strong potential as scaffolds for multivalence in chemobiology, as building blocks for the production of biomimetic pseudo-glycopeptides, as well as monomers for the preparation of materials. In view of the importance of these oligomaltoses, this review focuses on the different methodologies allowing access to them via chemical and enzymatic ring-opening of cyclodextrins.
https://dx.doi.org/10.3390/org2030015


Design, Synthesis and Antibacterial Activity Evaluation of 4,5-Diphenyl-1H-Imidazoles Derivatives
Bamoro, C.; Bamba, F.; Steve-Evanes, K. T. D.; Aurélie, V.; Vincent, C.
Open Journal of Medicinal Chemistry 2021, 11, 17-26.
Due to the continuous emergence and rapid spread of drug-resistant strains of bacteria, there is an urgent need for the development of novel antimicrobials. Along this line, the synthesis and antibacterial activity of 4,5-diphenylimidazol-2-thiol derivatives 2a-g and 6a-e are reported. The structures of the synthesized compounds were confirmed by Nuclear Magnetic Resonance (NMR) and High Resolution Mass Spectrometry (HRMS). All compounds were screened in vitro for their antibacterial activity against Pseudomonas aeruginosa and Escherichia coli (Gram-negative bacteria) and also against Staphyloccocus aureus and Enterococcus faecalis (Gram-positive bacteria). The results showed most of the synthesized compounds have no antibacterial activity. However compound 6d was two-fold potent than ciprofloxacin against Staphylococcus aureus with Minimum Inhibitory Concentration (MIC) of 4 μg/mL and 6c showed moderate biological activity against Staphylococcus aureus (16 μg/mL) and Enterococcus faecalis (16 μg/mL).
https://dx.doi.org/10.4236/ojmc.2021.112002


Effects of CoCl2 on the regioselective tosylation of oligosaccharides
El-Abid, J.; Moreau, V.; Kovensky, J.; Chagnault, V.
J. Mol. Struct. 2021, 130609.
The tosyl functional group is commonly used in carbohydrate chemistry as a nucleofuge. Tosylation of the primary hydroxyls of carbohydrates are generally performed after orthogonal protection/deprotection reactions. However, it can be done regioselectively from unprotected sugars. Several examples have been described in the literature starting from free monosaccharides. Yields are generally good but may vary according to the nature of the sugar. Starting from free oligosaccharides, the regioselectivity and the yields generally drop significantly. The use of catalysts, such as DMAP or NEt3, improves the conversion but to the detriment of the regioselectivity. In our current work, we developed a tosylation reaction of the primary positions of several oligosaccharides with improved regioselectivity, using cobalt II chloride in catalytic amounts. Adaptability of this methodology has been tested on cellobiose, maltose, lactose, sucrose and maltotriose.
https://dx.doi.org/10.1016/j.molstruc.2021.130609


Synthesis and interfacial properties of new 6-sulfate sugar-based anionic surfactants
Abdellahi, B.; Bois, R.; Golonu, S.; Pourceau, G.; Lesur, D.; Chagnault, V.; Drelich, A.; Pezron, I.; Nesterenko, A.; Wadouachi, A.
Tetrahedron Lett. 2021, 153113.
Three families of anionic sugar-based surfactants bearing a sulfate functional group on the primary position of a monosaccharide were synthesized and their physicochemical properties were compared. The first family corresponds to 6-sulfate derivatives of commercially available octa- and dodecyl β-D-gluco- and galactopyranosides. The second and the third families contain an amide linker between the sulfated monosaccharide (galactose, glucose or xylose) and the hydrophobic alkyl chain. Twelve of the as-synthesized anionic glycolipids, including nine novel sulfated compounds, were investigated for their surface activity at the air/liquid interface and for their self-assembling properties. These sugar-based surfactants show surface properties similar to those of commercial anionic surfactants (SDS and SLES) with good ability to reduce surface tension. The obtained results confirm the interest in these new bio-based molecules for potential substitution of anionic surfactants in various formulations.
https://dx.doi.org/10.1016/j.tetlet.2021.153113


Physicochemical, foaming and biological properties of lowly irritant anionic sugar-based surfactants
Bois, R.; Abdellahi, B.; Mika, B.; Golonu, S.; Vigneron, P.; Chagnault, V.; Drelich, A.; Pourceau, G.; Wadouachi, A.; Vayssade, M.; Pezron, I.; Nesterenko, A.
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2020, 607, 125525.
Surface-active compounds derived from biomass, especially sugar-based amphiphiles, have received wide attention regarding their biodegradability, low toxicity and ecological acceptability. Compared to nonionic sugar-based surfactants, the anionic ones show significantly better solubility, higher surface activity and foaming performance. Thus they are largely used in personal care formulations and many technological applications. However, anionic surfactants are well known to induce skin and eye irritation. In this study, three sugar-based anionic surfactants, bearing a lipidic chain grafted to the anomeric position of a monosaccharide (glucose or xylose) and a sulfate group on the primary hydroxyl, were synthesized: 6-O-sulfo-N-(β-d-glucopyranosyl) dodecanamide (GlcNC12S), N-dodecyl-6-O-sulfo-d-gluconamide (GlcCC12S) and N-dodecyl-6-O-sulfo-d-xylonamide (XylCC12S). These molecules were investigated in details for their self-assembling behavior, foaming properties and biological effects. All their properties were compared to those of two commercially available anionic surfactants, sodium laureth sulfate (SLES) and sodium dodecylsulfate (SDS). Results revealed that the three anionic glycolipids show surface properties and foaming behavior comparable to those of SDS. Furthermore, their cytotoxic and irritation potentials are significantly lower compared to commercial molecules, which make these renewable molecules potential candidates for replacement of petroleum-based compounds.
https://doi.org/10.1016/j.colsurfa.2020.125525


Synthesis of multivalent S-glycosides analogs of a heparan sulfate sequence
Koffi Teki, D. S.-E.; Bil, A.; Moreau, V.; Chagnault, V.; Fanté, B.; adjou, a.; Kovensky, J.
Organic Chemistry Frontiers 2019.
Glycosaminoglycans (GAGs) are involved in the regulation of a large number of biological processes such as inflammation, cell signalling, angiogenesis, viral infection and coagulation. Unlike molecules isolated from tissues, pure molecules, derived from organic synthesis, can prevent side effects and are very useful tools for understanding the structure-activity relationships of many biological and pharmacological activities. In our research group, we focus particularly on the synthesis of multivalent thioglycoside analogs. In this article, we report the synthesis of new glycoclusters with thiodisaccharide units, S-analogs of heparan sulfate. The thiodisaccharide analog was obtained by nucleophilic displacement of a 4-triflate galactoside derivative, by an anomeric thiol of a glucuronic acid precursor. After modifying the aglycone part to introduce an azide, the thiodisaccharide was coupled to maltotriose scaffolds carrying one, two or three propargyl groups by CuAAC.
https://dx.doi.org/10.1039/C9QO00581A


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)]
https://patents.google.com/patent/WO2018109416A1/en?oq=WO2018109416A1


Metal-free oxidative esterification of benzylated monosaccharides
Camara, T.; Bil, A.; Chagnault, V.
Carbohydr. Res. 2018.
Methyl glyconates have been attracting considerable attention as intermediates for the preparation of aryl C-glycosides, polyphenolic products, aliphatic polyesters, SGLT2 inhibitors, antibiotics etc … In view of the interest in those compounds, we report herein our work on the synthesis of methyl glyconates using an oxidative esterification carried out by molecular iodine. This reaction is catalyzed by non-toxic K4Fe(CN)6 that releases a small amount of cyanide ion into the reaction mixture. Four benzylated carbohydrates which contain a hemiacetalic functional group have been tested successfully.
http://dx.doi.org/10.1016/j.carres.2018.04.003


Water-mediated synthesis of disubstituted 5-aminopyrimidines from vinyl azides under microwave irradiation
Dehbi, O.; Ishak, E. A.; Bakht, M. A.; Geesi, M. H.; Alshammari, M. B.; Chagnault, V.; Kaiba, A.; Lazar, S.; Riadi, Y.
Green Chemistry Letters and Reviews 2018, 11, 62-66.
An efficient and ecofriendly method for the synthesis of disubstituted 5-aminopyrimidines from vinyl azides and urea or thiourea was developed. This reaction proceeds under microwave irradiation conditions in the presence of water as a solvent. The remarkable features of this new protocol are high conversion, short reaction times, cleaner reaction profiles and straightforward procedure.
http://dx.doi.org/10.1080/17518253.2018.1437225


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.
http://dx.doi.org/10.1016/j.tiv.2017.02.002


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.
http://dx.doi.org/10.1016/j.colsurfb.2016.04.044


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.
http://dx.doi.org/10.1016/j.carres.2015.03.012


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.
http://dx.doi.org/10.1201/b18400-7


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
http://dx.doi.org/10.1201/b18400-6


Synthesis of glycosylamines and glyconamides using molecular iodine
Fusaro, M. B.; Chagnault, V.; Postel, D.
Tetrahedron 2013, 69, 542-550.
We describe herein the synthesis of glyconamides and glycosylamines using mol. iodine on benzylated carbohydrates. During the improvement and the optimization of the direct oxidative amidation reaction, we also discovered the possibility to form glycosylamines with excellent yields and short reaction times in comparison with the previously reported procedures. Advantages of these methods are the operational simplicity, elimination of use of complicated reagents and procedures, and generality of the reactions. Our methodol. is an excellent access to precursors of N-alkyliminosugars and imino-C-glycosides.
http://dx.doi.org/10.1016/j.tet.2012.11.027


Metal-free oxidative lactonization of carbohydrates using molecular iodine
Fusaro, M. B.; Chagnault, V.; Josse, S.; Postel, D.
Tetrahedron 2013, 69, 5880-5883.
We describe herein the oxidative lactonization of fully or partially protected carbohydrates using mol. iodine. Oxidn. of aldose hemiacetals is generally carried out by classical procedures, which are rarely chemo or regioselective. We recently reported an optimized methodol. for the oxidative amidation of aldose with functionalized amines and we found mol. iodine as a good selective oxidant. This property has been already obsd. by other research groups but the scope of this reactivity has never been studied for carbohydrates. The main advantage of this approach relies on the operational simplicity, elimination of use of complicated reagents and procedures.
http://dx.doi.org/10.1016/j.tet.2013.05.021


Synthesis of 1,5-di-C-alkyl 1,5-iminoxylitols related to 1-deoxynojirimycin
Chagnault, V.; Compain, P.; Martin, O. R.; Behr, J.-B.
Carbohydr. Chem.: Proven Synth. Methods 2012, 1, 259-267.
Iminosugars form a class of carbohydrate mimics of increasing importance. In this context, the development of rapid and general access to original iminosugars is highly needed. A double benzotriazolyl/carbon nucleophile exchange was first investigated with alkyl, allyl- or vinylmagnesium bromide with little success. With or without additives, such as ZnBr2 or MgBr2, the expected 2,6-dialkyl piperidines were obtained in poor and unreproducible yields. The best results were finally obtained with 5 equiv of allyl zinc bromide, generated by treatment of allyl bromide with activated Zn dust according to Knochel's procedure. Following these conditions, 2,6-diallyl piperidines were obtained as a mixt. of stereoisomers in 57% yield after protection of the hydroxyl groups. Subsequent acetylation of the crude product was necessary for the next step of the synthesis and for the sepn. of the desired products from benzotriazole. The chemoselective removal of the TV-benzyl group using CAN and the sepn. of the stereoisomers were performed in the same step, thus providing the two meso 2,6-cis piperidines ratio of about 4:3 (2,3-trans:2,3-cis), the racemic 2,6-trans diallylated piperidine in a ratio of 4:1 with respect to the cis isomers (2,6-cis:2,6-trans), and an overall yield of 57%. The 2,6-cis stereoisomers have been used as substrates for a ring-closing metathesis, thus affording the skeleton of calystegin analogs.


Biological study of a somatostatin mimetic based on the 1-deoxynojrimycin scaffold
Zhao, Y.; Liu, M.; Chagnault, V.; Wang, J.; Zhang, X.; Murphy, P. V.
Bioorg. Med. Chem. Lett. 2011, 21, 824-828.
Previously the synthesis of novel somatostatin mimetic from 1-deoxynojrimycin (DNJ) led to identification of a compd. with affinity for human somatostatin receptor subtypes 4 and 5 (hSSTR4 and hSSTR5). Here we examd. the properties of this peptidomimetic in a human umbilical vein endothelial cell (HUVEC) based assays. The peptidomimetic prevented capillary tube formation based on HUVECs. It also inhibited HUVEC proliferation by inducing G1 phase cell cycle arrest and apoptosis. Stress fiber assembly and cell migration in HUVECs was markedly suppressed by the somatostatin receptor ligand.
http://dx.doi.org/10.1016/j.bmcl.2010.11.088