SYNTHESIS OF 12 STEREOCHEMICALLY AND STRUCTURALLY DIVERSE C-TRISACCHARIDES

Cell surface carbohydrates and their analogs may be used to study the cellular interactions responsible for adhesion to pathogenic bacteria, viruses, and other cells and may represent leads for drug discovery. We have generated 12 C-trisaccharides (7-18) as potential inhibitors f or the cell surface proteins of the bacterium Helicobactor pylori. The strategy used has resulted in the generation of C-trisaccharides stru ctures that are represented by the formula Fuc-alpha(1-2)-hexose-(1-3) -GlcNAc where each of the 12 compounds possesses a central sugar that has been systematically replaced with stereochemically diverse structu res, including D and L sugars, through de novo synthesis. This approac h relies upon an organometallic coupling of terminal monosaccharides 1 9 and 20 to prepare a ''disaccharide'' in a convergent manner. This in termediate is then divergently derivatized to form a variety of struct ural analogs about the central hexose. For the separable compounds, th e assignment of stereochemistry was done using standard NMR techniques . In cases where inseparable diastereomeric mixtures were generated, w e have described a novel recursive stereochemical deconvolution strate gy. This recursive strategy is demonstrated in the diastereoselective synthesis of trisaccharides 14, subsequent to its initial rapid synthe sis as a component of a diastereomeric mixture. Biological assays of t hese compounds should provide an insight into the binding requirements of carbohydrate receptors.