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Synthèse de Produits Naturels à Activité Biologique Importante : Iridal, Acide Galbanique, Marneral et analogues.

Abstract : The research area of my Ph.D. thesis is the methodological development of useful reactions, that permit developing the total syntheses of various natural products. A central role is played by a "domino" reaction that employs lead tetraacetate to produce highly functionalized cyclohexane moieties possessing multiple functions and asymmetric centers. The mild reaction conditions, together with the ease of the experimental and the absence of any detectable side products, constitute the most outstanding feature of this methodology; it has provided a convenient route to multigram quantities of molecules possessing functionality and absolute configuration that are appropriate for elaboration of a variety of natural products. A careful examination of the chiral centers and functionalities showed that our intermediates could also be used as precursors for Iridal, but also Galbanic acid , Pathylactone A, Anthecularine and other terpenoid natural products. One of the early o! bjectives was the optimization of this reaction, in order to implement it in the synthetic schemes of Iridal and Galbanic Acid. By introducing the microwaves, this "domino" reaction was accelerated greatly, the usual procedure being reduced to only 5 min. at 90 °C, instead of 12 hours reaction time at room temperature. The main objective was the approach of the Galbanic Acid, and the Iridal family of natural products, both A-seco terpenes, as they posses a central 6-member ring that can come from the previous "domino" methodology. In order to synthesize the Galbanic acid and to prove its structure, we used the chiral pool, choosing the (R)–pulegone as the starting material for the synthesis. The pulegone was functionalized, and the lateral chain was installed by a Claisen rearrangement. The last step was the ether bond formation by a SN2 substitution. Iridal, the parent molecule of an entire family of derived natural compounds, that were isolated from the Iris plant, presents IC50 values that compare with Taxol and Doxorubicin, and it is toxic against MDR cancer lines. In order to synthesize this complex target, we used the "domino" strategy to obtain the central B-ring. The methodology of the laboratory was employed in the synthesis of highly substituted cyclohexanes and was the key step in the synthesis of the Iridal parent molecule, as well as in the construction of the galbanic acid analogs. The galbanic acid's structure was confirmed by total synthesis, using a readily available natural product, pulegone.
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Submitted on : Wednesday, July 21, 2010 - 11:31:24 AM
Last modification on : Monday, June 22, 2020 - 12:08:07 PM
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Andrei Corbu. Synthèse de Produits Naturels à Activité Biologique Importante : Iridal, Acide Galbanique, Marneral et analogues.. Chimie. Ecole Polytechnique X, 2008. Français. ⟨pastel-00004528⟩

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