Sialyl synthesis

C. Unverzagt, S. Andre, J. Seifert, S. Kojima, C. Fink, G. Srikrishna, H. Freeze, K. Kayser, and H.-J. Gabius, Structure-activity profiles of complex biantermary glycans with core fucosyl-ation and with/without additional a2,3/a2,6 sialylation Synthesis of neoglycoproteins and their properties in lectin assays, cell binding, and organ uptake, J. Med Chem., 45 (2002) 478 91. 

In the second example, the synthesis of an I-active ganglioside analogue98 is covered. The sialyl I antigen is shown in Scheme 14. 

Flgure10.23 Sialyl Lewis -related selectin inhibitorandfluorogenicscreening compound for transketolase prepared using enzymatic aldolization, and multienzymatic oxidation-aldolization strategy for the synthesis of bicyclic higher carbon sugars. 

T. Furiuke, R. Sadamoto, K. Niikura, K. Monde, N. Sakairi, and S.-I. Nishimura, Chemical and enzymatic synthesis of glycocluster having seven sialyl lewis X arrays using /i-cyclodextrin as a key scaffold material, Tetrahedron, 61 (2005) 1737-1742. 

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. 

Wong and coworkers showed that 5-azido sialyl donors protected with O-acetyl ester are useful for a-selective glycosylations of primary hydroxyls (Scheme 4.6e) [169]. It was proposed that the linear and electron-withdrawing nature of the C-5 azido moiety stabilizes the reactive axial acetonitrile adduct to allow the incoming nucleophile to approach the a-face in an SN2-like fashion. In addition, a chemose-lective glycosylation method has been developed for the synthesis of NeuAca-(2 —> 9) NeuAc as thioglycoside donor for use in the subsequent glycosylations [169]. 

General Procedure for Synthesis of Sialyl Thioglycosides Using TMSSMe and TMSOTf [165]... 

Several other examples of successful application of sialyl xanthates for oligosaccharide synthesis have been reported [411,413-427]. 

Scheme 8.1 Synthesis of a sialyl-Lewis tetrasaccharide employing C-enriched protecting groups for the quantitative reaction monitoring using gated decoupling NMR spectroscopy.

Independently and at the same time the incorporation of a sialyl-TN-antigen building block in the synthesis of a fragment from the HIV gpl20 glycoprotein was described.41... 

Scheme 13.14 Synthesis of a sialyl Lewis A buiding block for solid-phase glycopeptide synthesis.

Scheme 13.15 Solid-phase synthesis of a sequence from PSGL-1 carrying sialyl-Lewis A.

A similar approach was used in the synthesis of the sialyl Lewis X mimetics of type 85 (Scheme 13.22).66 Protein crystallization,67 conformational studies of sLex in solution68 and in bound form to E- and P-selectin69 as well as the study of structure-function relationships70,71 gave information about the functional groups of the sLex-epitope essential for the binding to the selectins. Synthesized mimetics must contain the three essential hydroxyl functions of the fucose. Sialic acid, galactose, and... 

Scheme 8 Synthesis of PAMAM dendrons having aldehyde functionality at the focal point and sialylated dendrons using reductive amination...

Unverzagt, C., Chemoenzymatic synthesis of a sialylated undecasaccharide-asparagine... 

Scheme 10.1 Glycopeptide synthesis and a-chymotrypsin catalyzed release from the solid support, a) 25% TFA (CH2CI2) b) 0-(N-Boc-Phe)glycolic acid (7 eq), BOP, HOBt, DIEA b) 25% TFA (CH2CI2) c) Boc-Gly-OH (7 eq), BOP, HOBt, DIEA c) 25% TFA (CH2CI2) d) Boc-Asn(GlcNAcb)-OH (3 eq), BOP, DIEA e) galactosyl transferase, sialyl transferase f) CT, H2O, pH 7.0 g) ultrafiltration h) a-l,3-fuco-syltransferase, GDP-Fuc (2.5 eq), 0.1 M HEPES (pH 7.0), 95%.

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