Sialosides

Straightforward solutions to this problem have been addressed in the following publications describing the synthesis of sialoside dendrimers 554, where the glycans are interspaced by TRIS residues used as dummy functionalities (Fig. 68).335... 

R. Roy, D. Zanini, S. J. Meunier, and A. Romanowska, Solid phase synthesis of dendritic sialoside inhibitors of influenza A virus haemagglutinin, J. Chem. Soc. Chem. Commun. (1993) 1869-1872. 

S. A. Kalovidouris, O. Blixt, A. Nelson, S. Vidal, W. B. Turnbull, J. C. Paulson, and J. F. Stoddart, Chemically defined sialoside scaffolds for investigation of multivalent interactions with sialic acid binding proteins, /. Org. Chem., 68 (2003) 8485-8493. 

D. Zanini and R. Roy, Novel dendritic x-sialosides Synthesis of glycodendrimers based on a 3,3 -iminobis(propylamine) core, /. Org. Chem., 61 (1996) 7348-7354. 

The siglecs constitute a novel subfamily of immunoglobulin-like molecules that bind to sialosides 113... 

The siglecs constitute a novel subfamily of immunoglobulin-like molecules that bind to sialosides. These molecules, previously termed sialoadhesins, share considerable sequence similarity among the first four amino-terminal Ig domains [8,9]. More importantly, all members... 

Special topics (synthesis of P-mannosides, furanosides, sialosides, glycosides of aminosugars and deoxysugars, if applicable)... 

BF3-OEt2 Unnatural P-sialoside derivatives are produced preferentially by using O-acetylated glycosyl fluoride donor and BF3-OEt2 as the promoter. When P-sialyl fluoride derivative 28 was reacted with acceptor 22 in the presence of BF3-OEt2 in dichloromethane, the P-sialoside 28 was obtained in a mixture of anomers (a/p 17/83) (Scheme 2.11) [44],... 

Takahashi and coworkers described an effective sialylation method utilizing the N-Fmoc, N-Troc and N-trichloroacetyl-P-thiophenyl sialosides (Scheme 4.6d) [167]. It was found that the N-Troc derivative of N-acetylneuraminic acid performed better than the corresponding N-Fmoc derivative. An N-Troc P-thiosialoside was applied for the synthesis of glycosyl amino acids by one-pot glycosylation [167]. Importantly, it was found that the N-Troc protecting group could be converted into an acetamido moiety without causing racemization of the peptide. 

In brief, the use of acetonitrile as solvent and the selection of an appropriate C-5 amino protecting group and reactive promoter system are critical for achieving high a-selectivities and yields in the synthesis of sialosides. 

Novel sialosyl donors, S-benzoxazolyl and S-thiazolyl sialosides, have been synthesized [170], Both SBox and STaz sialosides proved to be excellent glycosyl donors... 

Fig. 3 Zanamivir , an antiviral drug which inhibits viral sialidases and below the mechanism of hydrolysis of sialosides with the transition state 4 mimed by Zanamivir .

The initial step in the sequence of events leading to influenza virus infections in mammalian hosts is mediated by the multiple attachment of virus particles to host sialoside receptors in the nasopharynx [41]. These receptors consist largely of cell surface sialylated glycoproteins and gangliosides. The subsequent steps involve receptor-mediated endocytosis with ensuing release of the viral nucleo-plasmid. The first event responsible for the receptor-virus interaction is therefore an attractive target for both antiviral and related microbial intervention. 

Influenza virus particles are spheroidal and approximately 100 nm in diameter. The outer-membrane envelope contains 500 copies of hemagglutinin (HA) trimers and 100 copies of neuraminidase tetramers. The hemagglutinin constitutes the receptor sites for a-sialoside ligands. X-ray analyses show that the three sialic acid binding pockets reside 46 A apart, each trimer being separated on the virion surface by about 65-110 A [42],... 

Figure 15.2 Hyperbranched sialosides and related glycopolymers can inhibit microbial attachment to host tissues by blocking their receptor sites...

Scheme 1 Sialoside precursors having varied functionalities for direct attachment to hyperbranched or dendritic scaffolds...

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