Sialic acids methylation

Ci2H21N09 H20 Sialic acid, methyl ester, monohydrate N-ace-tylneuraminic acid, methyl ester, monohydrate methyl 5-acetamido-3,5-dideoxy-/3-i>g/ycero-D-gaiacto-nonulopyranosonate monohydrate19... 

Mass spectrometry has been used successfully to establish the structure of sialic acids, and the type of their bonds in the oligosaccharide chain. For this purpose, the fragmentation of various derivatives containing both the cyclic and the acyclic forms of sialic acid has been comprehensively studied. The methyl esters of sialic acid methyl ketosides, obtained as a... 

Methyl 5-acetamido-3,5-dideoxy-D-glycero- -D-galocto-nonulopyranosonate, monohydrate (N-acetylneuraminic acid, methyl ester, monohydrate sialic acid, methyl ester, monohydrate)... 

In structure analyses of sialic acids, the combination of g.l.c. and m.s. is almost indispensable. By careful studies of the mass spectra of the trimethylsilylated methyl esters of Neu5Ac and Neu5Gc and of some related derivatives, a general electron impact (e.i.) mass spectrometric micromethod has been developed for the identification of N,0-acylneuraminic acids isolated from biological material (Kamerling et al. 1974,1975 c, 1978). The method has also proved to be useful for the analysis of other isolated sialic acids, of (partially) O-methylated sialic acid methyl ester methyl glycosides as obtained in methylation analyses, and of synthetic sialic acid(s) (derivatives). 

IH-NMR spectroscopy is suitable for following the course of reactions either directly in the NMR-tube or by analysis of isolated reaction products. Simultaneous measurements of substrate and product concentrations allows under proper conditions the deduction of kinetic reaction parameters (Friebolin et al 1981c). Alternatively, the formed products can be isolated and analysed separately by NMR spectroscopy. For example in the saponification of sialic acid methyl esters under mild alkaline conditions both types of approaches are useful (Haverkamp et al 1982). The potency of NMR spectroscopy as a real-time analytical probe is in particular evident in the study of enzyme reactions. 

Sialidases require a negatively charged carboxyl function on the a-linked sialic acid-containing substrate for catalytic activity. V. cholerae sialidase did not cleave the sialic acid methyl esters of bovine submandibular gland mucus glycoproteins (Gottschalk 1962) or IPNeu5AcLac (Kuhn / al 1966). In colominic acid, esters... 

The carbohydrate has sites for ionic interaction (clusters of sialic acid or sulphate residues) and also hydrophobic interaction (clusters of hydrophobic methyl groups offered by fucose residues). Sedimentation velocity has been a valuable tool in the selection of appropriate mucoadhesives and in the characterisation of the complexes [ 138-143]. 

A-Acetyl-9-deoxy-9-fluoroneuraminic acid (591) was prepared by treatment of a protected 6-hydroxyl precursor with A, A-diethylaminosulfur trifluoride (DAST) or through condensation of 2-acetamido-2,6-dideoxy-6-fluoro-D-mannopyranose with potassium di(/ >r/-butyl) oxaloacetate. Compound 591 is a substrate for cytidine monophosphate (CMP)-sialic acid synthetase, giving rise to CMP-5-A-acetyl-9-deoxy-9-fluoroneuraminic acid, which is cytotoxic against tumor cells. 5-A-Acetyl-3-fluoroneuraminic acids 592-594 were prepared through fluorine (or acetyl hypofluorite) addition (in AcOH) to methyl 5-acetamido-4,7,8,9-tetra-0-acetyI-2,6-anhy-dro-2,3,5-trideoxy-D- /ycm>D- a/arto-non-2-enopyranosate. Compound 592 was found to be a potent neuraminidase inhibitor. 

In 1991, Li and Chan reported the use of indium to mediate Barbier-Grignard-type reactions in water (Eq. 8.49).108 When the allylation was mediated by indium in water, the reaction went smoothly at room temperature without any promoter, whereas the use of zinc and tin usually requires acid catalysis, heat, or sonication. The mildness of the reaction conditions makes it possible to use the indium method to allylate a methyl ketone in the presence of an acid-sensitive acetal functional group (Eq. 8.50). Furthermore, the coupling of ethyl 2-(bromomethyl)acrylate with carbonyl compounds proceeds equally well under the same reaction conditions, giving ready access to various hydroxyl acids including, for example, sialic acids. 

In about 1936, sialic acid was discovered by Blix, who found it to be a component of submaxillary-gland proteins, and who described many of its properties. However, little notice was taken of this work at the time it was published. In 1941, Klenk, who was working on glycolipids of the brain, described a compound, later shown to be a methyl glycoside of sialic acid, that had been obtained by treatment of a lipid fraction with 5% methanolic hydrogen chloride at 105°. In 1954, Klenk and Faillard reported the first isolation of pure N-acetyl-neuraminic acid from animal sources. 

Such studies, and others on an O-phosphonomannan155 and a tei-choic acid,168 relied on judicious comparisons (of shift) with signals of model compounds, and these are simpler than conventional, analytical procedures. For example, it is difficult to methylate alkali-labile O-phosphonomannans, and sialic acid and KDO-containing polymers would require difficultly available, O-methylated standards. In addition, periodate-oxidation analyses are restricted to polymers having fortuitously amenable, chemical structures. 

The linkage of sialic acid to Gal, GlcNAc, or GalNAc may be determined on the microscale by methylation analysis before and after treatment with... 

By carefully adjusting the distances between two sialoside residues in a number of divalent clusters. Click and Knowles [105] have obtained dimer 104 having the two sialic acid 5.7 nm apart. Compound 104 was 100-fold more potent than methyl a-sialoside (Neu5Aca2Me) in influenza virus inhibitions and 500-fold more potent in the case of polyomia virus. Alternatively, sialyl-a-(2,6)-/3-LacNAc dimers (105) branched at different positions of synthetic peptides, including compact glycine-rich and helical proline-rich peptides, afforded clusters which were only 8- and 4-fold more potent, respectively, than the corresponding monovalent trisaccharide [106]. 

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