Study On Sialylation Using N-phenyltrifluoroacetimidate And Ortho-alkynylbenzoate As Donors

N-Acetylneuraminic acid (Neu5Ac), the most abundant sialic acid congener in nature, is found at the termini of glycoproteins and glycolipids on mammalian cell surfaces. In humans, Neu5Ac occurs frequently via aα(2→3) glycosidic linkage to galactose orα(2→6) linkages to galactose and N-acetylgalactosamine. Since Neu5Ac on the cell surfaces plays diverse and important roles in cell-cell interaction processes, such as pathogen-host recognition, tumor metastasis, toxin-receptor interaction, malignant alteration, cell differentiation and proliferation, much effort has been devoted to the efficient and stereoselective synthesis ofα(2→3) andα(2→6)-Neu5Ac-Gal units in order to further investigate their biological functions.1. Efficient Synthesis of a Sialic Acidα(2→3) Galactose Building Block using N-phenyltrifluoroacetimidate as leaving group and Its Application to the Synthesis of Ganglioside GM3.Glycosylation of various galactose derivatives with O-acetylated sialic acid N-phenyltrifluoroacetimidate as the donor was investigated. Efficientα(2→3) sialylation of galactose, with up to 73% yield and 8.4:1 stereoselectivity, was realized when 2,3,4-unprotected galactose derivatives and TBSOTf were used as acceptors and promoter, respectively. Sialylation of 2-(trimethylsilyl)ethyl 6-O-tert -butyldiphenylsilyl-β-D-galactopyranoside gave the best result, and the resultant Neu5Acα(2→3) Gal disaccharide was successfully used to synthesize ganglioside GM3. 2. Study on sialylation using ortho-alkynylbenzoate as donorsA novel sialylation method was investigated, which using ortho-alkynylbenzoates as the donor, Au(I) as promoter and THF as the solvent, showed favorability compared with previous protocols for direct sialylation. The donors are readily available and stable; the glycosidic coupling yields are generally excellent; the promotion system is catalytic, neutral, and orthogonal to the known glycosylation conditions.