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Elucidation des Mécanismes de O- et C-glycosylation par des Moyens Chimiques et Spectroscopiques

Abstract : Kinetic isotopic effects (KIEs) are powerful tools to obtain insight into the mechanism of a great range of reactions. We demonstrated differing primary 13C kinetic isotope effect (KIE) measurements for the formation of α-, β-mannopyranosides and α-, β-glucopyranosides from the 4,6-O-benzylidene protected mannosyl and glucosyl sulfoxides by NMR (13C at 200 MHz and 1H at 800 MHz). We have also calculated the KIEs in collaboration with the Pratt group at the University of Ottawa for these reactions. Experimental and calculated (B3LYP/ 6-31G (d,p) values with a polarizable continuum model) were in good agreement, except for the -mannopyranoside. Three of (-mannpyanoside and the -, -glupyranosides) four cases showed a SN2-like character. The formation of the -mannopyranoside on the other hand suggests a strongly dissociative mechanism (SN1). Such a difference in mechanism necessarily demands authentication by kinetic measurements. We turned then our attention to the development of an intramolecular clock reaction with which to probe the relative kinetics of glycosylation reactions and to the formation of the tricyclic products that provides strong evidence for the existence of a mannosyl oxocarbenium ion as a transient intermediate. Competition reactions with isopropanol and trimethylmethallylsilane are interpreted as indicating β-O-mannosylation to proceed via an associative SN2-like mechanism, whereas α-O-mannosylation and β-C-mannosylation are dissociative and SN1-like. This is in full agreement with our experimental KIE results. This approach to the determination of relative kinetics of glycosylation reactions, is straightforward and is potentially applicable to a broad range of glycosyl donors.
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Min Huang. Elucidation des Mécanismes de O- et C-glycosylation par des Moyens Chimiques et Spectroscopiques. Autre. Université Paris Sud - Paris XI, 2012. Français. ⟨NNT : 2012PA112272⟩. ⟨tel-00923152⟩

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