Study On The Synthesis Of GM3-Saccharide Analogs

Sialic acids constitute family of naturally occurring 2-keto-3-deoxy-nononic acids that play important roles in a wide range of biological processes. N-Acetylneuramic acid (Neu5Ac), the most abundant sialic acid congener in nature, is found at the termini of glycoproteins and glycolipids on mammalian cell surfaces, usually linkedα(2→3) andα(2→6) sialoglycoside linkages. Since Neu5Ac on the cell surfaces plays diverse and important roles in cell-cell interaction processes, such as pathogen/host recognition, tumor metastasis, and cell differentiation/proliferation. In this thesis a series ofα(2→3) andα(2→6)-Neu5Ac-Gal units were synthesized in order to further investigate their biological functions.Part 1: Efficient sialylation with phenyltrifluoroacetimidates as leaving groupsSialylation to make equatorial 2-α-ketosidic linkages is one of the most challenging tasks. The early attempts often afforded the 2,3-dehydro product and gave only a fewα-sialyl, and/orβ-glycoside products. Fortunately, N-phenyltrifluoroacetimidates were disclosed as excellent leaving groups for direct sialylation, which compares favorably with the previous protocols with respect to the coupling yields,α-selectivity , ease of operations and employment of a nontoxic catalytic amount of the promoter.Part 2: Study on the synthesis of Neu5Acα(2→3)Galβ(1→4) GM3-Saccharide analogsGanglioside GM3 is a ubiquitous metabolite with a variety of cellular activities that have been reviewed and include differentiation, the modulation of several receptors and other enzymes, immunosupression, and tumorassociation. Using Neu5Ac, D-Glucose and D-Galactose as starting materials, we had synthesized the protected GM3-Saccharide...