| Glycobiology has gained a lot of interest in the scientific community in the past few years. It is now well established that the oligosaccharides on cell surfaces are involved in key recognition processes. However, the determination of oligosaccharide sequence on a specific glycoconjugate and their chemical synthesis are still far from routine. Herein, we report a new strategy in chemical glycobiology making use of olefin metathesis reaction as a powerful chemical tool towards the synthesis of oligosaccharide mimics. This strategy allows the synthesis of multivalent molecules that could help to understand and control events mediated by oligosaccharides. A glycomimetic approach to the branched trimannoside 3,6-di-O-(α-D-mannopyranosyl)-α-D-mannopyranoside will also be described.; The synthesis of carbohydrate homodimers was accomplished by self metathesis of O- and C-alkenyl glycosides using 10 mol% of Grubbs' catalyst bis (tricyclohexylphosphine) benzylidene ruthenium (IV) dichloride, [(PCy3)2RuCl2 = CHPh]. The reaction is high yielding, compatible with different protecting groups and the length of the linker can be easily changed. A mixture of stereoisomers was obtained in which the E isomer was major. Once deprotected, these homodimers can be viewed as chemical inducers of dimerization therefore the hypothesis that they can induce signal transduction was suggested.; Extension of O- and C-alkenyl glycosides was also achieved by cross-metathesis reaction using Grubbs' catalyst. Extended alkenyl glycosides with reactive functional groups were obtained in high yield and good stereoselectivity. The utilization of 2–4 equiv. of alkenes and 20 mol % of catalyst were sufficient to favor the formation of the cross-metathesis products. A novel C-linked (1-6)-pseudodisaccharide could be synthesized using this procedure.; A sequence of olefin metathesis and Sharpless asymmetric dihydroxylation reactions were used to create a novel class of glycoclusters having varied structural and stereochemical environments. Well-defined tri- and tetra-valent mannoside-based glycoclusters were thus prepared.; Another application of olefin metathesis reaction was found in the synthesis of a trimannoside ligand toward human Mannose-binding protein which plays an important role in the innate immunity. To further understand its role, the design of high affinity ligands was attempted. Preliminary biological results showed improved inhibitory potentials.; Finally, two generation of glycomimetics of 3,6-di-O-(α-D-mannopyranosyl)-α-D-mannopyranoside, the natural ligand recognized by legume lectin, concanavalin A were synthesized. Thus, highly substituted C-aryl mannoside, as well as O, N, C-linked 1,2,3-triazole mannosides were prepared. |
