Synthèse d'analogues de nucléosides à 4 et 6 chaînons et incorporation d'analogues cyclobutyliques dans un motif oligonucléotidique antisens - Approche vers la synthèse de composés galactosyl-pyrrolo-pyridinones.

摘要

This Ph.D thesis focused on the theme of nucleosides analogues. It was divided into three parts. First, the enantioselective synthesis of cyclobutyl nucleosides, and their incorporation into oligonucleotides chains, was performed. The preparation of new cyclohexenyl nucleosides derivatives was then accomplished. Finally, the approach toward the synthesis of galactosyl-pyrrolo pyridinones compounds was studied. In the first chapter we have highlighted the important role of nucleosides, nucleotides and nucleic acids (DNA and RNA) in physiological processes. Furthermore, different structural modifications that led to the development of new nucleosides analogues have been described. The interest of oligonucleotides in gene therapy was then highlighted before outlining the synthesis methods and the different structural modifications performed on these compounds. In the second chapter, the enantioselective synthesis of cyclobutyl nucleosides analogues, using a strategy initially developed in our team, was accomplished. These derivatives, after conversion to nucleotides, allowed the preparation of new and originals oligonucleotides chains. The developpement of new cyclohexenyl nucleosides analogues was described in chapter three. A strategy involving, among others, an asymmetric [4 +2] cycloaddition and the construction of heterocyclic bases, allowed us access to cyclohexenyl derivatives. The structure of those compounds prefigures access to new constrained cyclohexanyl nucleosies analogues. The last chapter, in continuation of our work on nucleoside analogues, outlines the approach toward the synthesis of galactosyl-pyrrolo pyridinones compounds. alpha-C-glycosyl acetylene derivatives were first prepared. Those key compounds in the synthesis should enable us to subsequently access to variously substituted pyrrolo-pyridinones via an inverse demand Diels Alder Reaction, the regression of pyridazine compounds and an intramolecular lactamization.