N-acetylneuraminic acid derivative

The N-acetylneuraminic acid derivative 44 is widely distributed. It was isolated from a strain182 of Escherichia coli, and has been obtained from cytidine 5 -triphosphate and N-acetylneuraminic acid by the action of enzyme preparations from Neisseria meningitidis183 and from animal tissues.184-186 The latter enzyme can also make use of N-glycolylneuraminic acid as a substrate, to give the respective cytidine 5 -phosphate derivative. 

N-Acetylneuraminic acid (derived from CMP-NANA) often forms g branches from the main chain. 

Besides the ceramide trisaccharide and its N-acetylneuraminic acid derivative, small fragments, namely, ceramide lactoside and monosialoceramide lactoside (Hematoside), were found.416... 

The detritylated intermediate product (30) was oxidized at the 9-position to the corresponding 9-aldehyde derivative (31) and then converted to the 9-deoxy-9-difluoro-N-acetylneuraminic acid derivative (32). The spectrum of 9-deoxy-9-fluoro-MANA... 

Both diastereomeric N-acetylneuraminic acid-derived nononic acids 12a and... 

Acetolysis followed by acetylation of the epoxide (17) afforded the acetate (18) and its 7-epimer in the ratio 3 1, and various derivatives of the N-acetylneuraminic acid derivative (19) have been reported. 

The N -acetylneuraminic acid derivative (63) was converted via the iV-nitroso-derivatives (64) into the diazo-intermediate (65) which was then captured with nucleophilic reagents to give the azide (66) or the KDN (3-deoxy-D-gfycero-D-ga/flcro-nonulosonic acid) derivative (67), the stereoselectivity implying the operation of neighbouring group participation during the addition process (Scheme 10). °... 

Kiefel, M. J., Wilson, J. C., Bennett, S., Gredley, M., and von Itzstein, M., Synthesis and evaluation of C-9 modified N-acetylneuraminic acid derivatives as substrates for N-acetylneuraminic acid aldolase. Bioorg. Med. Chem. 2000,8 (3), 657-664. 

The c.d. spectra of a number of other derivatives have been measured as models for the linkages found in oligomers. Spectra of the methyl a-and )8-D-ketopyranosides of N-acetylneuraminic acid are given in Fig. 29. They do not differ substantially from the c.d. spectra for the fundamental sugars, except that the a-ketopyranoside has a positive c.d. band of low intensity at 250 nm. These types of bands occur from time to time for still obscure reasons, as discussed for carboxyl derivatives. 

The c.d. spectra are also available for a few oligosaccharides that contain N-acetylneuraminic acid. " These spectra depend on the intersaccharide linkages and the state of ionization of the carboxyl group, but no systematic scheme has yet been set up to derive configurational information from the c.d. spectra. Of particular interest is the c.d. spectrum of beef ganglioside, which fully differentiates the amide mr, amide tttt, and carboxylate nir c.d. bands. 

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. 

It has been observed that the neuraminic acid linkages can also be conveniently analyzed by the methylation technique.33,34 Some important fragments, the origins of which were confirmed by deuteriumlabelling experiments,33 are shown for two common, N-acetylneura-minic acid derivatives, namely, the terminal sugar derivative 10 and the 8-O-substituted N-acetylneuraminic acid (11). 

Fig. 3.—Mass Fragmentography of Methylated Neuraminic Acids. [Detection at m/e 274 A, disialosyl-lactosylceramide B, the disialosyl ganglioside isolated C, B after treatment with neuraminidase D, the fraction containing the trisialosyl ganglioside. Detection at m/e 330 E, the disialosyl ganglioside F, the trisialosyl fraction. The peaks identified are (1) the permethylated (terminal) N-acetylneuraminic acid, and (2) the 8-O-acetyl (8-O-substituted) derivative of the methylated N-acetylneuraminic acid. Conditions 1% of SE-30, at 240°. Reproduced, by permission, from Ref. 80.]...

The structure shown was confirmed by the identification of cytidine 5 -phosphate and N-acetylneuraminic acid after mild acidic hydrolysis, and by the stability of the derivative on treatment with sodium borohydride. Comparison of the optical rotation of the starting derivative182 (44), the products of its hydrolysis,182 and the anomeric... 

Two of the most frequent monosaccharide components of bacterial polymers belonging to this group have been the subjects of articles in this Series. They are 3-deoxy-D-manno-2-octulosonic acid,247 a normal constituent of the core region of bacterial lipopolysaccharides that is also present in some other polymers, and N-acetylneuraminic acid,248 found in several capsular polysaccharides. Enolpyruvate phosphate serves as the precursor of the C-l-C-3 fragment of the monosaccharides, with D-arabinose 5-phosphate or 2-acetamido-2-deoxy-D-mannose 6-phosphate being an acceptor for transfer of the three-carbon unit. Characteristic, activated forms of these monosaccharides are the CMP derivatives. 

In the trisialoglycolipid from D. nipon hepatopancreas, some of the N-acetylneuraminic acid residues are in the form of the 8-O-methyl derivative, whose structure was proved by mass spectrometry.192... 

The N-acetylneuraminic acid residue situated closer to the nonreducing end of the chain is present in the form of its 8-O-methyl derivative. 

In order to try to overcome some of the problems associated with chemical synthesis of oligosaccharides containing N-acetylneuraminic acid, Sabesan and Paulson [277] have used a combination of chemical and enzymatic methods using purified sialyl-transferases in the presence of CMP-iV-acetylneuraminic acid and synthetic acceptor molecules to give sialyl derivatives of oligosaccharides which were characterised by NMR. Thus, methyl P-D-galactopyranoside, methyl P-D-lactoside and iV-acetyl-... 

The reagent reacts selectively with the allylic hydroxyl group of 6-deoxyglycals 95 % of 3-0-(/ert-butyldimethylsilyl)-L-rhamnal were isolated after 2 h reaction at room temperature, in addition to 3 % of the 4-silyl and 2 % of 3,4-disilyl ethers [424]. Reinvestigation of this reaction by Thiem and coworkers revealed that temperatures below —20 °C are necessary in order to achieve such a high regioselectivity. At room temperature, a complicated mixture of products was obtained [127a]. Derivatives of N-acetylneuraminic acid such as 59 were also partially silylated with efficiency... 

L.M. von Itzstein, W.Y. Wu, V. Phan Tho, B. Danylec, and B. Jin, Preparation of Derivatives and Analogs of 2-Deoxy-2,3-Didehydro-N-Acetylneuraminic Acid as Antiviral Agents, Biota Scientific Management Pty. Ltd., Australia, 1991, WO 9116320. 

Neutral sugars and hexosamines were estimated after Dowex-50 (H+)-catalyzed hydrolysis by gas liquid chromatography of glycitol acetate derivatives (26,27). N-Acetylneuraminic acid was measured by a periodate-resorcTrToT"procedure (28). 

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