Chemical synthesis of oligosaccharide mimetics

A variety of C-disaccharides have been selectively and expeditiously synthesized through the so-called tether approach. Jntroduction . 'Oligosacch&ides are involved in a increasing number of biological processes. This has stimulated the development of selective methods for the synthesis of such complex molecules. Among others, the imidate. procedure that we have discovered (ref. l), and which has been remarkably modified as the ttichloroacetimidate version (ref. 2), is of classical use in the field of glycosylation. A host of synthetic complex oligosaccharides are thus easily available for the benefit of glycobiology. Knowledge of their geometrical and motional properties in aqueous solution is important for understanding the structureactivity relationship and for an appreciation of the ease of taking-up of the active conformation the one matching the corresponding receptor and inducing an optimal biological response-. A potential way to subtly alter such a conformation is to replace the interglycosidic oxygen atom by a methylene group. In doing so, the exo anomeric effect is removed. A comparison of recent studies (ref. 3) has shown that the effect of such a replacement on geomeuical and motional properties of di or oligosaccharide is a matter of discussion. It should also be noted that such disaccharide close mimetics are not degraded by glycosidases, a feature which could be of practical interest if one's try to develop an oligosaccharide based drug. The purpose of this invited lecture is to report on recent advances on the development of a synthetic entry to C-disaccharides, based on a 8 or 9 e n d o t r i g radical cyclisation reaction from two monosaccharide temporarily connected through a tether. Silicon tethered reactions have gained increasing general importance for the successful synthesis of a variety of complex molecules (ref. 4). The practical use of the temporary silicon connector in the carbohydrate field has been materialized by Stork within the context of C-glycoside synthesis (ref. 5) . tive svof a Galactose and galactosamine are monosaccharides which are frequently found in natural oligosaccharides of biological importance. As previously shown by us (ref. 6), we can modulate the alp selectivity of the C-galactosylation through the position of tethering (Scheme 1).