Décanolides hydroxylés : nouvelles approches synthétiques et glycosylation par de nouveaux réactifs à base d'iode hypervalent

During this co-direction Ph.D. thesis we were interested both in:(i) New synthetic approaches towards hydroxylated 10-membered macrolactones, involving two key-steps: formation of a bicyclic heteroadduct and its oxidative fragmentation.(ii) Glycosylation of natural 9-decanolides using a methodology based on tagged hypervalent iodine reagents. The multi-step synthesis part of this work required a study for the inverse electronic demand heterocycloaddition reaction. Therefore, we synthesized new heterodienes, aiming to favour endo configured bicyclic adducts, which showed unique reactivity, and may lead to structural diversity. In this process, we developed a new cyclohexanone-derived chiral dienophile bearing oxazolidinone moiety, which was subjected to Eu(fod)3-catalyzed heterocycloaddition with methyl arylidenepyruvates to afford the desired adduct in good yields. The reaction proceeds with high facial and endo double stereocontrol. These results were then applied to access natural 10-membered macrolactones (such as decarestrictines or herbarumins). In the second part of this work, we have synthesized novel hypervalent iodine reagents tagged with iso-butyl sulfonate group. This particular group allows the scavenging of the hypervalent iodine species and especially their by-products. Nucleophilic substitution occuring at the sulfonate group by an azide ion exchange resin allows indeed this scavenging. Four sulfonate-tagged iodanes were prepared and applied to several reactions, including oxidative fragmentation of bicycles and O-glycosylation of polyfunctional alcohols. Using this reaction, hybrid molecules bearing both decarestrictine and sugar moiety were quickly obtained with limited purification step based on the scavenging methodology.Lors de ces travaux de thèse effectués en co-tutelle, nous nous sommes intéressés à la fois : (i) à de nouvelles approches synthétiques de macrolactones hydroxylées à 10 chaînons via deux étapes clés de formation d'un hétéroadduit bicyclique et d'ouverture oxydante de ce bicycle.(ii) à la glycosidation de 9-décanolides naturels par une méthodologie utilisant un réactif à iode hypervalent sous une forme immobilisable.Le travail de synthèse multi-étapes a nécessité une étude de la réactivité, en hétérocycloaddition [4+2] à demande électronique inverse, de nouveaux hétérodiènes visant à favoriser une configuration endo des adduits bicycliques obtenus. Ceux-ci ont alors montré des réactivités particulières pouvant conduire à une certaine diversité structurale. Nous avons également développé un nouveau diénophile chiral issu de la cyclohexanone porteur d'une copule oxazolidinone. L'hétérocycloaddition catalysée par l'Eu(fod)3 de ce diénophile avec des arylidènepyruvates de méthyle, s'opère avec un double stéréocontrôle endo et facial excellent et de très bons rendements. Ces résultats ont ensuite pu être mis en application lors de l'accès à des cibles macrolactoniques à 10 chaînons d'origine naturelle (décarestrictines et herbarumines). Dans une seconde partie, nous avons mis au point la synthèse de nouveaux réactifs à base d'iode hypervalent fonctionnalisés par un groupement sulfonate d'iso-butyle. Nous avons montré que ce groupement permettait l'immobilisation des réactifs iodés hypervalents et surtout de leurs produits d'évolution. L'utilisation d'une résine échangeuse d'ion fonctionnalisée par un azoture permet en effet cette immobilisation via une substitution nucléophile du groupement sulfonate. Nous avons ainsi préparé quatre iodanes (III) à ancre sulfonate originaux et avons testé ces réactifs dans diverses réactions parmi lesquelles l'ouverture oxydante de bicycles, et la O-glycosidation d'alcools polyfonctionnels. Cette dernière nous a permis d'obtenir des structures hybrides décarestrictine-sucre de façon rapide et en limitant les étapes de purification en utilisant la méthodologie précédemment mise au point

Glycosidations of 2-deoxy glycosyl dithiophosphates using a tagged iodine(III)-promoter for simple purification

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Organocatalysis applied to carbohydrates: from roots to current developments

International audienceThis review is devoted to the broad application of organocatalysis in the synthesis of (un)natural carbohydrates as well as organocatalyzed glycosylation and the aldol reaction for the synthesis of C -glycosides

Towards a [4+2] Route to (+/-)-decarestrictines J and H: Synthesis of a Bicyclic Key-intermediate

International audienceTowards a [4+2] Route to ()-decarestrictines J and Towards a [4+2] Route to ()-decarestrictines J and Towards a [4+2] Route to ()-decarestrictines J and Towards a [4+2] Route to ()-decarestrictines J and Towards a [4+2] Route to ()-decarestrictines J and Sopa Chewchanwuttiwong [a], Arnaud Martel [b], Duang Buddhasukh [a], Eric Brown [b], Sopa Chewchanwuttiwong [a], Arnaud Martel [b], Duang Buddhasukh [a], Eric Brown [b], Sopa Chewchanwuttiwong [a], Arnaud Martel [b], Duang Buddhasukh [a], Eric Brown [b], Sopa Chewchanwuttiwong [a], Arnaud Martel [b], Duang Buddhasukh [a], Eric Brown [b], Sopa Chewchanwuttiwong [a], Arnaud We describe here the development of an approach to the synthesis of 3-oxo-7-hydroxy-9-decanolides of biological interest. This strategy involves two key steps : the inverse electron demand Hetero-Diels-Alder reaction of an original dienophile (1,5-dimethoxy-cyclohexa-1,4-diene), which will ensure the construction of an advanced structure in a very short number of steps, and the ring opening of a functionalized bicyclic lactol, leading to the requisite decanolide. The diastereocontrolled synthesis of such a lactol will be detailed in this communication

Copper(II) SBA-15: A reusable catalyst for azide–alkyne cycloaddition

International audienceThe azide-alkyne cycloaddition reaction was investigated under catalytic conditions involving a copper (II) loaded silica based mesoporous material. Cu(II) SBA-15 demonstrated a high catalytic effect in 1,4-triazoles synthesis in organic. No additives such as a base or a reductant are required. Quantitative yields were obtained and a mere filtration of the mesoporous material which retains copper (II) allows the recovery of the catalyst. In addition, up to 5 times recycling of the catalyst was achieved without loss of the activity affording 1,4-triazoles in a yield up to 98%

Partially perfluorinated derivatives as powerful tool for the restoration of blanching easel paintings

Perfluorinated oligoamides/amines were prepared and characterized. They were evaluated then for easel painting restoration by filling pores resulting of the blanching. They were used on prepared mock-ups analysed by FEG-SEM for morphological changes and by spectro-colorimetry analysis for the restoration. Compared to DG6G900 , the new partially perfluorinated products DSTF and DSF are recommended as restoration products for blanching easel paintings

Direct Synthesis of Mesoporous Organosilica and Proof-of-Concept Applications in Lysozyme Adsorption and Supported Catalysis

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Anti-HCV and Zika activities of ribavirin C-nucleosides analogues

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Synthesis, antiviral and antitumor activities investigations of a series of Ribavirin C-nucleoside analogue prodrugs

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