All N-linked glycoproteins, a fundamental class of glycoconjugates responsible for many recognition phenomena and susceptible to modify the conformations and activities of proteins in many disease states, consists of a common core pentasaccharide to which are attached usually two, sometimes three, antennary saccharides which modify activity and confer post-translational specificity. At the branch point of the common core pentasaccahride is a beta-mannopyranoside residue, one of the more difficult types of glycosidic linkage to synthesize. Beta- Mannospyranoside linkages are also found in numerous other natural oligosaccharides such as in a series of glycolipids from Hyriopsis schlegelli, in components of the phosphomannan-protein complex of Candida albicans, and in a novel phospholipase C inhibitor known as caloporoside. The closely related beta-rhamnopyranosides (6-deoxy- betamannopyranosides) occur very frequently as constituents of the repeating units of capsular polysaccharides, especially those from Streptococcus pneumoniae, and Escherichia hermanni. The isolation of pure glycoconjugates from nature is extremely tedious and hampers any thorough investigation of their properties and potential medical use. Chemical synthesis is therefore a very attractive entry into these molecules.
The aims of this project are: i)to develop technology for the efficient, highly stereoslective synthesis of the 1,2-cis-equatorial class of pyranosides, as found in the beta-mannosides and beta- rhamnosides, ii)to illustrate this technology through its application to the synthesis of biologically relevant target molecules; and iii)to adapt the chemistry to the solid and fluorous phases.
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