C-Glycosides as Stable Pharmacophores

Glycosyltransferases assemble polysaccharides from their monomeric units by adding activated nucleotide sugars to the growing carbohydrate chain [19]. The chemistry of glycosyltransferases is well known [20-22] and is illustrated in the biosynthesis of sialyl Lewis [23], an essential contributor to the cell adhesion process. In fact, without both the siahc acid and fucose components, the sialyl Lewis remnant is incapable of binding to selectins and effecting cell adhesion necessary for leukocyte extravasation [24-29]. 

With the interest in glycosidase inhibitors, compounds lending insight to the structures and mechanisms of these enzymes have received much attention. Recently, Lehmann, et al.,27 prepared a series of diastereotopic C-glycosides designed to be substrates for p-D-galactosidase. The premise was that in order to confirm this enzyme s mechanism of action, proposed from an extrapolation of lysozyme activity,28 31 the structural analysis of products resulting from the enzyme s effect on its substrates would be helpful. Therefore, the structures 

Glycosyltransferases assemble polysaccharides from their monomeric units by adding, to the growing carbohydrate chain, activated nucleotide 

Since sialic acid and fucose are important in the binding interaction of sialyl Lewisx to the selectins,45-50 a reasonable conjecture is that removal of fucose from sialyl Lewisx will completely stop the binding of leukocytes to the endothelium. Furthermore, this may be accomplished by inhibiting the activity of a-l,3-fucosyltransferase thus preventing the formation of sialyl Lewisx. 

Lipopolysaccharides or endotoxins are present in the cell walls of Gramnegative bacteria and are immunostimulants responsible for many pathological effects.61-69 Lipid A is the lipophilic terminal of endotoxins and lipid X is the 

Pathogenic organisms are known to use carbohydrate receptors such as lectins to bind to cell surfaces.77 70 Type I pili, a type of proteinaceous appendage, are found on the surface of Escherichia coli30 and contain receptors capable of binding to a-linked mannosides.8183 In 1992, Bertozzi, ef a/.,84 Prepared new C-mannosides that bind to Escherichia coli receptors and are able 

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