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Synthèse et application de composés gem-bisphosphonates, de puissants complexants de métaux

Abstract : This thesis was devoted to the development of new ways to prepare gem-bisphosphonates compounds (BPs), and was carried out under the Program of Nuclear and Environmental Toxicology (ToxNuc-E). Two applications of these compounds have been investigated, the preparation of potent ligands of the uranyl ion for a target of decorporation, and the preparation of new anticancer compounds. The first of these applications was the consequence of work done in the laboratory, that have shown

the strong uranium-binding properties of bisphosphonics ligands. The in vivo tests performed on these compounds have shown the tendency of these ligands to cause liver accumulation of uranium, we wanted to address this problem by modifying the method of anchoring of the bisphosphonates functions. To this end we have developed a new way to access to these compounds using a metal-carbenoid mediated poly-ols and poly-amines insertion, the metal-carbenoid species bearing the bisphosphonate function. Regarding the preparation of BPs as anticancer agents, we have developed a new synthetic pathway using a phosphine catalyzed á-P addition of phosphorated pronucleophiles to alkynylphosphonates as a key step. This enabled us to prepare thirty compound whose activity was evaluated on two cell lines (A431 and HuH7). Five of these compounds possess an activity equivalent to that of the compound described as the most active, the Zolédronate ®.
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  • HAL Id : tel-00359912, version 1



Delphine Lecercle. Synthèse et application de composés gem-bisphosphonates, de puissants complexants de métaux. Chimie. Université Paris Sud - Paris XI, 2007. Français. ⟨tel-00359912⟩



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