P-N-Acetylneuraminic Acid

Besides the 0-glycosides mentioned so far, also attention has been paid to the synthesis of N- and S-analogues. The p-nitrophenyl N-glycoside of a-N-acetylneuraminic acid has been prepared by silver carbonate-promoted reaction of 4,7,8,9-tetra-0-acetyl-2-chloro-2-deoxy-p-N-acetylneuraminic acid methyl ester with p-nitroaniline and subsequent deprotection (Privalova and Khorlin 1969). Treatment of the same precursor with sodium azide, followed by de-esterification, led to the formation of 2-azido-2-deoxy-a-N-acetylneuraminic acid (Supp et al. 1980). The same authors reported also the preparation of the p-form. The azides can readily be converted into the 2-amino derivatives of N-acetylneuraminic acid. Subsequently, the amino function has been benzoylated. Data on the syntheses of the methyl and p-nitrophenyl S-glycosides of a-N-acetylneuraminic acid have been presented by Privalova and Khorlin (1969), whereas Ponpipom et al. (1980) have described a method for the synthesis of 5-acetamido-2-S-[6-(5-cholesten-3p-yloxy)hexyl]-3,5-dideoxy-2-thio-p-D-g/vccro-D-ga/acto-2-nonulopyranosonic acid. 

Privalova and Khorlin (1969) reported the synthesis of the p-nitrophenyl glycoside of a-N-acetylneuraminic acid. The substrate was obtained by glycosylation of p-nitrophenol with 4,7,8,9-tetra-0-acetyl-2-chloro-2-deoxy-p-N-acetylneuraminic acid methyl ester in chloroform in the presence of silver carbonate and Drierite, followed by 0-deacetylation and saponification. In enzymatic reactions, released p-nitrophenol can be determined spectrofoto-metrically. 

In studies on the chemical stability of CMP-Neu5Ac in dependence on the pH two interesting decomposition products were observed, viz. p-N-acetylneuraminic acid-2-phosphate (Neu5Ac2P) and 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (Neu5Ac2en) (Beau et al, unpublished results). Their iH-NMR spectra are given in Fig. 11 and 12, respectively. The presence of a phosphate group in Neu5Ac2P... 

Fig. 11. Resolution-enhanced 360 MHz IH-NMR spectrum of p-N-acetylneuraminic acid-2-phosphate (pNeu5Ac2P) dissolved in 2H2O, recorded at p H 7.5 and 25 °C. The relative-intensity scale of the 5Ac methyl proton signal differs from that of the other parts of the...

NeuAc, N-acetylneuraminic acid Cer, ceramide Gic, giucose Gai, gaiactose. -p, site of deficient enzyme reaction. 

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. 

The six-carbon chain of ManNAc 6-P can be extended by three carbon atoms using an aldol-type condensation with a three-carbon fragment from PEP (Eq. 20-7, step c) to give N-acetylneuraminic acid (sialic acid).48 Tire nine-carbon chain of this molecule can cyclize to form a pair of anomers with 6-membered rings as shown in Eq. 20-7. In a similar manner, arabi-nose 5-P is converted to the 8-carbon 3-deoxy-D-manno-octulosonic acid (KDO) (Fig. 4-15), a component of the lipopolysaccharide of gram-negative bacteria (Fig. 8-30), and D-Erythrose 4-P is converted to 3-deoxy-D-arafrmo-heptulosonate 7-P, the first metabolite in the shikimate pathway of aromatic synthesis (Fig. 25-1).48a The arabinose-P used for KDO synthesis is formed by isomerization of D-ribulose 5-P from the pentose phosphate pathway, and erythrose 4-P arises from the same pathway. 

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-... 

Figure 9.11 Structure of an oligosaccharide unit of human transferrin. The linkage between the oligosaccharide and polypeptide chains is of the N-asparaginyl type. Dotted arrows indicate positions in which one sometimes finds NeuNAc-Gal-GlcNAc units. Gal is galactose, GIcNAc is N-acetylglucosamine, NeuNAc is N-acetylneuraminic acid (sialic acid), and Man is mannose. (Reproduced with permission from Bezkorovainy A. Biochemistry of Nonheme Iron. New York Plenum Press, 1980, p. 175.)...

Koppert K, Brossmer R (1992) 5-C-Acetamidomethyl-5-deoxy-KDN, a branched homo-logue of N-acetylneuraminic acid, and additional KDN analogues modified at C-5. XVI International Carbohydrate Symposium (Paris) p 296 Wu W-Y, Kok GB, Jin B, von Itzstein M (unpublished work)... 

E. Schreiner, R. Christian, and E. Zribal, Synthesis of 9-deoxy-, 7,9-dideoxy-, and 4,7,9-trideoxy-N-acetylneuraminic acid and their behaviour towards CMP-sialate synthase, Liebigs Ann. Chem. p. 93 (1990). 

N-acetylglucosamine, = N-acetylneuramine acid. [Adapted, with permission, from N. Sharon and H. Lis, Special Report, Chem. Eng. News, p. 28 (March 30, 1981) 1981 by the American Chemical Society.]... 

In the late 1970s and early 1980s—the time when P. falciparum could be cultured continuously in the laboratory—there was mounting evidence that the receptor for P. falciparum differed from that of P. vivax and P. knozvlesi. Several laboratories reported that a receptor for P. falciparum merozoites was sialic acid (N-acetylneuraminic acid) since human erythrocytes treated with neuraminidase or trypsin resisted invasion by P. falciparum merozoites and this was unlike the situation with P. vivax and P. knozvlesi where stripping by chymotrypsin but not trypsin blocked invasion. Further, Tn erythrocytes, which lack a glycosyltransfer-ase that results in cells deficient in sialic acid, were also refractory to invasion, as were En (a-) cells and when and S-s-U (-) cells, which were... 

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