Synthesis of 12 Stereochemically and Structurally Diverse C-Trisaccharides

Article abstract of DOI:10.1021/jo9621534

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 for the cell surface proteins of the bacterium Helicobactor pylori. The strategy used has resulted in the generation of C-trisaccharides structures that are represented by the formula Fuc-α(1-2)-hexose-(1-3)-GlcNAc where each of the 12 compounds possesses a central sugar that has been systematically replaced with stereochemically diverse structures, including D and L sugars, through de novo synthesis. This aroach relies upon an organometallic coupling of terminal monosaccharides 19 and 20 to prepare a "disaccharide" in a convergent manner. This intermediate is then divergently derivatized to form a variety of structural analogs about the central hexose. For the separable compounds, the assignment of stereochemistry was done using standard NMR techniques. In cases where inseparable diastereomeric mixtures were generated, we have described a novel recursive stereochemical deconvolution strategy. This recursive strategy is demonstrated in the diastereoselective synthesis of trisaccharides 14, subsequent to its initial rapid synthesis as a component of a diastereomeric mixture. Biological assays of these compounds should provide an insight into the binding requirements of carbohydrate receptors.