Preliminary communication

Chemistry of the glycosidic linkage. An efficient synthesis of 1,2-trans-di-saccharides☆

In this chapter the historical background of chemical O-glycosylations, followed by a brief discussion of the stereochemical aspects of glycosidic bond formation is described. In the main part of the chapter, all the O-glycosylation methods found in the literature to date are listed, focusing on the recent developments but mentioning all published ones as well. The classification of the methods is based on the reaction mechanism. First, reactions were nucleophilic substitution takes place directly on the anomeric carbon atom of the donor are discussed, followed by reactions where the nucleophilic substitution takes place on the carbon atom at the site of glycosylation on the acceptor. Finally, reactions based on different mechanisms will be presented.

A small library of semisynthetic analogues of fuscol and eunicol have been prepared and evaluated for in vivo topical anti-inflammatory activity using the mouse-ear edema assay. The first glycosylation of fuscol and eunicol has been achieved using a modified Koenigs–Knorr glycosylation to synthesize new fuscosides and eunicosides, a novel structural class of diterpene glycosides. The availability of adequate glycosylation methods for this synthesis was limited owing to the instability of the glycosyl acceptors. Glycosyl donor protecting group type had a pronounced effect on overall glycosylation yields of a model glycosyl acceptor. This synthesis provided access to the unnatural β-glycosides allowing for an evaluation of the effect of differing anomeric stereochemistry on anti-inflammatory activity. The PEGylated derivatives of fuscol and eunicol were also synthesized by a convenient acid-promoted solvolysis of the natural product aglycones. This work highlights the importance of the glycan portion of fuscoside B, notably the stereochemical configuration of the glycosidic linkage, in the observed anti-inflammatory activity.

We develop herein the synthesis of a new class of monocatenary and bolaform surfactants from d-glucose, d-galactose and lactose. Two main pathways have been investigated: microwave-assisted glycosylation followed by olefin cross-metathesis, and the one-step click-chemistry methodology. Tensioactive properties of these new compounds have been studied in order to characterize the physicochemical behaviour of these new carbohydrate-based compounds in water.