Synthèse d'analogues du 8(S)-HETE et étude de leur interaction avec les PPARs en vue d'applications thérapeutiques, notamment antidiabétiques

Les PPARs ont été découverts il y a une dizaine d'années. Il existe 3 isotypes de PPARs : a, b et g. PPAR a est impliqué dans l’activation de gènes liés au catabolisme des lipides. Quant à PPAR g, il a un rôle dans le stockage des lipides. Le 8HETE a été retenu comme structure de base, de par son activité de très bon ligand du PPAR a. L'objectif de ce travail a été de synthétiser en particulier, des molécules remplaçant le diène E, Z par un noyau aromatique en joignant les carbones 9 et 14. Le carbone sp2 en position 15 sera substitué par un oxygène. Pour l'aromatique nous avons envisagé la synthèse de 4 familles. La 1ére d'entre elles aura un benzène pour noyau aromatique et les 3 suivantes auront un naphtalène, une pyridine et une quinoléine. De plus, les produits avec diverses saturations ont été synthétisés. Ces molécules testées sur les PPARs puis comparées aux antidiabétiques connus. Les résultats sont très encourageant in vitro mais doivent être améliorés pour les tests in vivo.RENNES1-BU Sciences Philo (352382102) / SudocSudocFranceF

New library of aminosulfonyl-tagged Hoveyda-Grubbs type complexes: Synthesis, kinetic studies and activity in olefin metathesis transformations.

International audienceSeven novel Hoveyda-Grubbs precatalysts bearing an aminosulfonyl function are reported. Kinetic studies indicate an activity enhancement compared to Hoveyda's precatalyst. A selection of these catalysts was investigated with various substrates in ring-closing metathesis of dienes or enynes and cross metathesis. The results demonstrate that these catalysts show a good tolerance to various chemical functions

Terpenic Compounds as Renewable Sources of Raw Materials for Cross-Metathesis

International audienceDihydromyrcenol is used as a hydrated masked form of citronellene in olefin cross-metathesis reactions in order to solve the selectivity problem that results from the presence of two double bonds in many terpenes. Several ruthenium catalysts are evaluated, with the best, M71-SIPr, utilized in the cross-metathesis of dihydromyrcenol with various olefins affording the expected products in good yields. It is shown that the masked double bond can be regenerated via an acid-catalyzed elimination reaction and the product is then subjected to a further cross-metathesis reaction with a second olefin

Sustainable oxidative cleavage of catechols for the synthesis of muconic acid and muconolactones including lignin upgrading

International audienceMuconic acid and muconolactones are attracting high interest as platform molecules for the synthesis of a variety of compounds, especially in the domain of materials. Although several technologies have been described for their synthesis, there is still a lack of performance, especially regarding green chemistry principles. In this study, we describe the development of an optimized catechol oxidative cleavage to muconic acid using performic acid in an intriguingly safe fashion. Common iron salts were used as catalysts to a level as low as 0.005 mol%, for a maximum turnover number of 13 200. Maximum muconic acid yield reached 84% after isolation by simple filtration. This procedure optimized on catechol was also efficient over a wide range of substituted catechols, providing access to muconolactones in a domino reaction. Noticeably, biobased catechols produced by a proven technology of lignin depolymerization were cleaved into muconolactones of high functional value. Applying this supplementary cleavage step to catechols obtained by lignin depolymerization was thus an ultimate way to maximize the economical value created from lignin. In contrast to other studies, lignin was not only depolymerized, but also depolymerization products were further transformed to take as much value from biomass as possible

Screening of a selection of commercially available homogeneous Ru-catalysts in valuable olefin metathesis transformations.

International audienceA library of thirteen different commercially available Ru-based catalysts was evaluated in valuable metathesis reactions for the production of fragrance and bioactive molecule precursors. Rigorous library screening clearly illustrated the different catalytic behaviour of the catalyst selection and highlighted its significant advantage to provide efficiency in specific metathesis applications. Interestingly, this strategy offered substantial improvement over the state of the art, with the efficient synthesis of the macrocyclic Exaltolide 2 at low catalyst loading and dilution conditions

Catalytic Activity Studies of Aminocarbonyl Group Containing Hoveyda-Grubbs-Type Complexes for the Syntheses of Herbarumin I and Stagonolide A

International audienceThe catalytic activity of four aminocarbonyl group containing 'boomerang'-type ring-closing metathesis catalysts have been studied for ten-membered lactone and compared well with the Grubbs I and II as well as the Hoveyda-Grubbs catalysts. The activity was found to be superior to the above three ring-closing metathesis catalysts and suggesting novel stereoselective total syntheses of herbarumin I and stagonolide A

Enantioselective synthesis of methyl-5(R)-fluorohept-6-ynoate

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Double Catalytic Kinetic Resolution (DoCKR) of Acyclic anti-1,3-Diols: The Additive Horeau Amplification

International audienceThe concept of a synergistic double catalytic kinetic resolution (DoCKR) as described in this article was successfully applied to racemic acyclic anti-1,3-diols, a common motif in natural products. This process takes advantage of an additive Horeau amplification involving two successive enantioselective organocatalytic acylation reactions, and leads to diesters and recovered diols with high enantiopurities. It was first developed with C 2-symmetrical diols and then further extended to non-C 2-symmetrical anti diols to prepare useful chiral building blocks. The protocol is highly practical as it only requires 1 mol % of a commercially available organocatalyst and leads to easily separable products. This procedure was applied to the shortest reported total synthesis of (+ +)-cryptocaryalactone, a natural product with anti-germinative activity

Continuous flow homogeneous alkene metathesis with built-in catalyst separation

International audienceContinuous flow homogeneous alkene metathesis using a supported ionic liquid phase (SILP) catalyst with CO2 as a transport vector allows the self-metathesis of methyl oleate with only a slight loss of activity for at least 10 h; cross-metathesis of dimethyl maleate with methyl oleate ceases after 3 h, but the catalyst remains active for methyl oleate metathesis. The reasons for this unusual behaviour are explored and a practical system for the cross-metathesis of methyl oleate with dimethyl maleate, under batch conditions, is described