Highly Alpha-Selective Sialyl Phosphate Donors for Efficient Preparation of Natural Sialosides

摘要

N-Acetyl neuraminic acid (Neu5Ac) is most frequently found at the terminal end of glycoconjugates on the cell surface. This terminally exposed position allows Neu5Ac-containing conjugates to be exploited as receptors for viruses and bacteria, in addition to governing a wide variety of biological processes, such as tumor metastasis, cell differentiation, and cell–cell interactions.[1] In naturally occurring sialosides, Neu5Ac is found linked to galactosides through the a- ACHTUNGTRENUNG(2!3) or aACHTUNGTRENUNG(2!6) linkage in N- and O-linked glycoproteins, and also to N-acetylgalactosamine through the aACHTUNGTRENUNG(2!6) linkage in O-linked glycoproteins. In addition, polysialosides formed by the aACHTUNGTRENUNG(2!8) or aACHTUNGTRENUNG(2!9) linkages are constituents of glycoproteins and glycolipids.[2] The biological significance of sialoside receptors has driven research for their efficient synthesis. This has included significant efforts directed toward the development of sialic acid donors for efficient a-sialylation,[3] including the use of anomeric leaving groups, such as halides,[4] phosphites,[5] sulfides,[6] xanthates,[7] and phenyltrifluoroacetimidates,[8] the introduction of an auxiliary group at C-1[9] and C-3,[10] the modification of the Nacetyl functional group at C-5,[11] or the optimized combinations of the leaving group with positional modification.[12] However, high yielding a-selective sialylation is still problematic owing to the presence of the C-1 electron-withdrawing carboxyl group at the tertiary anomeric center and the lack of a participating group at C-3 to direct the stereochemical outcome of glycosylation.