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Doubles couplages de Suzuki-Miyaura sélectifs sur des dérivés dihalogénés symétriques – Application à la synthèse de la ningaline B et de ses analogues

Abstract : New therapeutic targets inversigation is one of the most serious challenges for the scientific community. Nowadays, 60% of clinically used drugs are natural products or their analogs. Thus, the development of new efficient synthetic tools to easily access such library of compounds is crucial. Marin natural products are an important source of inspiration for original drug design. Here we focused on development of an easy and efficient synthesis of ningalin B and its analogs. Indeed, while the literature reports the potential of the hexamethyl ether form to reverse multidrug resistance inhibing P-glycoprotein, only few studies have been done on analogs.Thereby, here we suggest a synthesis based on double Suzuki-Miyaura couplings on symmetrical dihaloarenes as a key step. This is a step to deal with studies in depth and two approaches have been envisaged. The first one relies on a previous simultaneous work in the laboratory. Thus, like a multicomponent reaction, all the starting materials are introduced in the mixture at the beginning of the reaction. This method show promising results when opposed electronic aryl boron derivatives are employ. Nevertheless, using electronic similar boron derivatives, a statistical mixture of dicoupling products is obtained. Since the preparation of our targets only needs the introduction of electron rich aryl moieties, a sequential approach has been envisaged. Preliminary optimizations afford optimal monocoupling conditions on symmetrical dihaloarenes. The scope of the reaction has then been studied including pyrrol nucleuses that are required for the synthesis of ningalins.This work led to desired molecules and analogs can be easily access in a few steps to fulfil a library of compounds.
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https://tel.archives-ouvertes.fr/tel-00919884
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Submitted on : Tuesday, December 17, 2013 - 2:27:11 PM
Last modification on : Monday, June 22, 2020 - 12:08:07 PM
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  • HAL Id : tel-00919884, version 1

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Corinne Minard. Doubles couplages de Suzuki-Miyaura sélectifs sur des dérivés dihalogénés symétriques – Application à la synthèse de la ningaline B et de ses analogues. Autre. Université Paris Sud - Paris XI, 2013. Français. ⟨NNT : 2013PA112239⟩. ⟨tel-00919884⟩

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