A new strategy in oligosaccharide synthesis using lipophilic protecting groups: synthesis of a tetracosasaccharide

The use of lipophilic, acyl-type protecting groups in the synthesis of higher-membered oligosaccharides is described by the example of oligosaccharides corresponding to the O-specific polysaccharide (O-SP) of Shigella dysenteriae type 1. Thus, O-stearoylated and O-lauroylated l-rhamnose and d-galactose precursors, respectively, were synthesized and were combined together with a 2-azido-2-deoxy-d-glucopyranosyl donor to form a fully protected lipidated repeating unit of the O-SP. This module was condensed with another tetrasaccharide containing conventional blocking groups. The resulting lipidated octasaccharide was isolated in a pure form by adsorption to a reverse phase adsorbent from which it could be selectively desorbed by alcoholic solvents. Subsequent chain elongation using the conventionally protected tetrasaccharide module as glycosyl donor afforded oligosaccharides up to and including a tetracosasaccharide. The proposed approach can substantially alleviate the difficulties associated with the conventional silica gel chromatographic purification of protected oligosaccharide intermediates and utilizes environmentally friendly solvents that are less expensive than the solvents used for silica gel chromatography. A new, highly efficient method is also proposed for the synthesis of carbohydrate acetals and cyclic orthoesters employing scandium trifluoromethanesulfonate as the catalyst.