A-Methyl ketoside

A. Schrell and G. M. Whitesides, Synthesis of the a-methyl ketoside of 5-amino neuraminic acid methyl ester and its corresponding 5-myristoyl and 5-cyclopropanoyl derivative, Liebigs Ann. Chem. p. 1111 (1990). 

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... 

FIGURE 14. Gas-liquid chromatograms of sialic acid liberated by mild methanolysis from purified ovine adrenal medulla and converted to trimethylsilyl ether derivatives. Left, 3% OV-1, 225°C right, 3% OV-225, 225°C. Peak identification A, methoxyneuraminic acid methyl ester (de-N-acylated product) B, methyl a-ketoside methyl ester of NANA C, methyl ketoside methyl ester of NANA D, phenyl N-acetyl-a-D-glucosaminide (internal standard) E, methyl a-ketoside methyl ester of NONA F, methyl /8-ketoside methyl ester of NONA. (Price and Yu, 1976). 

Neuberger, A., and Ratcliffe, W. A., 1973, Kinetic studies on the acid hydrolysis of the methyl ketoside of unsubstituted and O-acetylated N-acetylneuraminic acid, Biochem. J. 133 623. 

Bhattachaijee and coworkers101 reported the first synthesis of the methyl a- and /3-ketoside carboxylates, 63 and 66, to be used as model compounds for the n.m.r.-spectroscopic analysis of the Neisseria meningitidis exopolysaccharide. The method used was that employed by Kuhn and coworkers109 for the synthesis of the analogous methyl /3-and a-ketosides of NeuAc (compounds 67 and 68 compare Section IV,5). 

Thus, ketose 361 was first methylated and then subjected to a three step transformation including desilylation followed by iodination and hydride-promoted HI elimination. This furnished vinyl ketoside 362 whose treatment with excess of TIBAL ensured smooth Claisen rearrangement to afford cyclooctenic carbocycle 363 in excellent yield. 

Theander reported that acidic degradation of methyl D-arabino-hexopyranosiduloae and of methyl /3-D-ri )o-hexopyranosid-3-ulose (the 2-and 3-keto derivatives from methyl d-o-glucopyranoside) yield a complex mixture. The proportions of ketosides decrease slightly faster than the parent compounds under the same conditions, but the author doubted that hydrolysis of the glycosidic bond is the primary reaction. 

Considering that the acid-catalysed hydrolysis ( inversion ) of sucrose has been studied perfunctorily for the last century and a half, surprisingly little is known about the hydrolysis of ketosides. The positive entropies of activation of methyl -D-fructofuranoside (-1-13 eu) and sucrose (-f8 eu) argue in favour of an A-1 mechanism [1] involving a fructofuranosyl cation. 

Brief oxidation with 0.025 M-sodium metaperiodate at pH 7, followed by estimation with the resorcinol or thiobarbituric acid reagent, has been used in the simultaneous assay of free and ketosidically bonded sialic acids, respectively." Treatment of 2-acetamido-2-deoxy-3,4 5,6-di-O-isopropylidene-aW liydo-D-glucose (192) or the analogous D-mannose derivative with alkali gave 2-acetamido-2,3-dideoxy-5,6-0-isopropylidene-a-D-eryt/iro-hex-2-enofuranose (193), which afforded the methyl 2-enofuranosides (194) with acidified methanol-acetone (194)... 

Glycoproteins containing sialic acid may be detected by staining with a cationic carbocyanine dye before and after digestion with neuraminidase a change in the colour of the stain from blue to red-purple indicates the presence of sialic acid. The n.m.r. spectra of iV-acetylneuraminic acid and its methyl ester in DMSO and in water have indicated that the acid exists predominantly in the /S-form in solution. The finding supports the assumption that 7V-acetyl-neuraminic acid, produced by the enzymic cleavage of its a-ketosides, leaves the catalytic site of Vibrio cholerae neuraminidase as the j3-anomer. 

Aminoethylaminocarbonyl-methyl a-ketoside of 5-acet-amido-3,5-dideoxy-D- /ycero-D-ga/acto-2-nonulosonic acid ... 

KETOSIDE. Any glycoside which, on hydrolysis, yields a ketose, e.g.-, methyl-fructoside. 

TABLE II. /8-Ketosides of Neuraminic Acid and A-Acylneuraminic Acids and Their Methyl Esters... 

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