ORGN 627 |
| Mridula Kadalbajoo, Fehmi Damkaci, Michael J. Patterson, and Philip DeShong. Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742 |
| Glycoproteins play an important role in biological processes including intercellular communication, cell-cell recognition, and cell growth regulation. The crucial step of any synthesis of a glycopeptide is the introduction of the carbohydrate residue to the amino acid or peptide in a stereoselective manner under conditions which are compatible with glycosidic linkages and common protecting groups for peptide synthesis. A novel synthesis of glycopyranosyl isoxazolines has been developed employing readily available 2-acetoxy-glycosyl azides and triphenylphosphine. The synthesis of the isoxazolines proceeded via epimerization of a b-phosphorimine to the a-phosphorimine followed by cyclization to provide the isoxazoline. This methodology has been employed to synthesize glucopyranosyl, galactopyranosyl, and mannopyranosyl isoxazoline derivatives. The methodology has also been extended with di- and trisaccharide azides. The stereoselective synthesis of the glycosylamide linkage has been developed utilizing in situ generated glycosyl isoxazolines. Results of the coupling studies demonstrated that the optimum conditions for the synthesis of glycosylamides involved the coupling of the isoxazoline with a 2-pyridyl thioester in the presence of copper(II) chloride. The stereoselective syntheses of a-glucosylamide and b-mannosyl amide have been accomplished in high yields. Isoxazoline couplings were applied to the synthesis of a-glucosyl amino acid derivatives also. It was shown that the coupling conditions are compatible with different protection strategies used in peptide couplings. Treatment of 2-NAc- or 2-NPhth-2-deoxyglucopyranosyl azides gave phosphorimine intermediates which coupled efficiently with thiopyridyl esters to provide the glycosyl-b-amide linkage. The yields in these couplings were superior to the yields from the traditional Staudinger reactions utilizing carboxylic acids. Coupling of these phosphorimines with the thiopyridyl ester of asparagine derivatives has proven to be a superior method for the synthesis of N-linked glycopeptide derivatives. |
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New Reactions, Methodology, Heterocycles, Aromatics
8:00 PM-10:00 PM, Wednesday, August 25, 2004 Pennsylvania Convention Center -- Hall D, Poster
Division of Organic Chemistry |