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Synthèse de Molécules et de Macromoléculespour le Vivant et l’Environnement |
The discovery of atom-economical, catalytic one-pot multi-step processes for the chemo- and regioselective transformations of carbohydrates and polyols ("one catalyst in a single reaction vessel"). These transformations, avoiding time-consuming protection/deprotection steps and the isolation of intermediates, are catalyzed by copper(II) triflate or the environmentally friendly and inexpensive iron(III) chloride hexahydrate. This last catalyst was very efficient on disaccharides and one trisaccharide. Catalysis by triflic acid associated with powdered molecular sieves is a better option with the important the NHCO-containing functionalities on carbohydrates (e.g. derivatives of D-glucosamine). In addition, we demonstrated that chitin, source of the α-pentaacetate of N-acetyl glucosamine (GlcNAc) in one step, is the "bio-precursor" of simple GlcNAc α-glycosides by direct activation with catalytic amounts of copper(II) triflate in a heated sealed-vessel reactor. This methodological work also includes new developments in radical chemistry, such as the first evidence of a 1,7-hydride shift in a regioselective deprotection reaction on polyfunctional substrates.
C-Glycosides
The development of a novel direct and chemoselective umpolung process on the carbohydrate glycals without relying on the preparation of intermediary pi-allyl transition metal complexes, with samarium diiodide as a simple reducing system. This proceeds with a high stereochemical outcome in the carbon-carbon bond forming step. It provided a new approach to the α-C-glycosides of the N-acetyl neuraminic acid. This single electron reductive metallation procedure was applied to the discovery of new selective hemagglutinin (HA) ligands and neuraminidase (NA) inhibitors targeting the binding or the catalytic site, respectively. Both glycoproteins are crucial for the viral infection by Influenza of type A virus (flu virus).
Plant growth
The deconstruction of chitin, one of the most abundant renewable biopolymers, and reconstruction from fragments to highly bioactive glycoconjugates and glycoprobes. It has been used in the total synthesis of the Nodulation and Mycorrhizal Factors and some mimetic structures for open-field tests (in collaboration with Bayer CropScience). The elaboration of photoactivatable glycolipid probes has also been very useful for the first identification of the long-elusive nodulation factor receptor.
Synthesis of complex glycolipids
The catalytic one-pot multi-step processes using the iron catalyst was extended to the trehalose disaccharide for the synthesis of novel highly antigenic sulfoglycolipids. Increasing the length of the chiral 1,3-methyl branch fatty acid of mycobacterial diacylated sulfoglycolipid analogues induces a dramatic improvement in their antigenic properties, giving products more potent than the natural antigens. These constructs should make excellent candidates as components of sub-unit vaccines. This project also involves the preparation of imaging probes based on trehalose and mycolic acids for the study of the mycomembrane biogenesis in mycobacterium and related organisms.
