Synthèse d'alcaloïdes de Vinca et nouvelle approche de la synthèse de la (D)-méquitazine

Abstract : The work carried out during this thesis has focused on two independent parts.The first two sections have dealt with the “Vinca alkaloids” part, natural products with anticancer properties. Firstly, the work has focused on the synthesis of oxygenated analogs of the 20,20-difluorocatharanthine as precursors of original dimeric Vinca alkaloid. Although explored synthesis pathways have not led to the desired oxygenated derivatives, different results has enabled to show that the presence of the gem-difluoro groupment on catharanthine skeleton dramatically changed the reactivity of the substrate in an unpredictable manner. The second part of this work was dedicated to the elucidation of the mechanism of fluorination of alkaloids dimers of Vinca in superacid medium. Isotopic labelling with deuterium has allowed to discriminate two mechanistic hypotheses and to validate the mechanism of fluoridation via a 1,2-hydride migration whose minimum contribution is 20 %.Finally, the third part of this work has been devoted to the asymmetric synthesis of (R)- mequitazine. The synthesis is based on the chirality already "printed" into the skeleton of cinchona alkaloids. Synthesis of (R)-mequitazine with greater than 99% final enantiomeric excess was reached in 8 steps from quinine, confirming full control of the asymmetrical centre during the synthesis.
Document type :
Theses
Other. Université Paris Sud - Paris XI, 2011. French. <NNT : 2011PA112113>


https://tel.archives-ouvertes.fr/tel-00605094
Contributor : ABES STAR <>
Submitted on : Thursday, June 30, 2011 - 3:26:24 PM
Last modification on : Wednesday, March 11, 2015 - 6:56:21 PM

File

VA2_LEROUX_SEBASTIEN_13012011....
fileSource_public_star

Identifiers

  • HAL Id : tel-00605094, version 1

Collections

STAR | CEA

Citation

Sébastien Leroux. Synthèse d'alcaloïdes de Vinca et nouvelle approche de la synthèse de la (D)-méquitazine. Other. Université Paris Sud - Paris XI, 2011. French. <NNT : 2011PA112113>. <tel-00605094>

Export

Share

Metrics

Consultation de
la notice

330

Téléchargement du document

518