Sialosides synthesis

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. 

V,2. This is not the case with cytidine monophosphate JV-acetylneuraminic acid (49) (see Scheme 18), the activated form of JV-acetylneuraminic acid for sialoside synthesis, as no sialylation cycle has so far been achieved, and thus this precursor must be added to the system in stoichiometric quantity. Thus, the availability of 49 is still the limiting factor in the large-scale synthesis of sialosides. 

Since other thiophilic activation systems (DMTST [48], NIS-TfOH [60,61], PhSeOTf [62], NBS-Bu4NOTf or Ph2lOTf [63], MeSBr-AgOTf [64]) are also compatible with the acetonitrile assistance, the combined use of a thioglycoside donor and acetonitrile (or other nitrile solvents) became a powerful option for a-sialoside synthesis, being parallel with C3-appended donors. 

In sialoside synthesis, the use of enzymes can dramatically reduce the multiple protection-deprotection steps and provide great stereo- and regio-selectivity. Many enzymes accept uimatural substrates. Genetic engineering can further alter their stability, broaden their substrate specificity, and increase their specific activity [73]. Therefore, chemoenzymatic approaches using enzymes in combination with classical carbohydrate chemistry opened up a new venue, avoiding many of the problems encountered in traditional chemical synthesis. 

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. 

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

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. 

Liakatos, A. Kiefel, M. J. yon Itzsteirr, M., Synthesis of lactose-based S-linked sialylmimetics of alpha(2,3)-sialosides. Org. Lett. 2003,5,4365-4368. 

The latter approach has been followed in our laboratory. For instance, in studies related to the synthesis of potent multivalent sialoside inhibitors of influenza virus hemagglutinin [34], it became of interest to evaluate the immunogenicity of neoglycoproteins containing sialosides as sole immunodominant hapten. To this end, acetochloroneuraminic acid (1) was transformed into allyl glycoside 2 (Scheme 1) which upon reductive ozonolysis afforded aldehyde 3 in excellent overall yields [35], Reductive amination of 3 to bovine serum albumin (BSA) and tetanus toxoid provided immunogenic vaccines from which specific rabbit IgG anti-sialic acid antibodies were obtained [36]. In order... 

R. Roy, F. O. Andersson and M. Leteilier, Active and latent thioglycosyl donors in oligosaccharide synthesis. Application to the synthesis of a-sialosides. Tetrahedron Lett. 33 6053 (1992). 

S. Sabesan, S. Neira, F. Davidson, J. Duus, and K. Bock, Synthesis and enzymatic and NMR-studies of novel sialoside probes Unprecedented, selective neuraminidase hydrolysis of and inhibition by C-6-(methyl)-Gal sialosides, J. Am. Chem. Soc. 776 1616 (1994). 

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