Glycosides of sialic acids

Miscellaneous Sialic Acids and Sialic Acid Derivatives 

Sialic acids as such, sialic acid derivatives, analogues, glycosides and sialo-oligosaccharides have been subject of many synthetic investigations. These studies were aimed at a further exploration of the properties of sialic acids, the preparation of substrates and inhibitors for sialidases, sialyltransferases or for sialic acid converting enzymes, and to make compounds accessable for analytical purposes or for studies related to metabolism or biological functions of sialic acids. 

In comparison to the synthesis of analogous compounds from simple aldoses or ketoses, the situation for sialic acid is more complicated, due to the occurrence of several different functional groups. Synthetic studies on sialo-compounds have been reviewed by Box and Jeanloz (1969), Tuppy and Gottschalk (1972), Holmquist (1975), and Van der Vleugel (1981). 

For the synthesis of alkyl and aryl a-glycosides of sialic acids often Koenigs-Knorr-like procedures have been applied. A large number of these glycosides have been obtained by silver carbonate-promoted condensation of 5-acylamino-4,7,8,9- 

Brossmer and Nebelin 1969 Kuhn et al. 1966( ), Meindl and Tupfy 1965a, 1966b, Van der Vleugel et al. 1982a, Yuand Ledeen 1969, Beau and SCHAUER 1979 

---

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. 

K, Okamoto and T. Goto, Glycosidation of sialic acid, Tetrahedron 46 5835 (1990). 

For detailed information with respect to the synthesis of C-glycosides of sialic acids, see refs. [559-563]. As an example, the synthesis of a multivalent material that consists of the C-glycoside of Neu5Ac, which is resistant to viral sialidase hydrolysis, should be mentioned [562]. 

D., Hidari, K.I.-P.J., Wong, C.-H., and Suzuki, Y. (2002) An 0-glycoside of sialic acid derivative that inhibits both hemagglutinin and sialidase activities of influenza viruses. Glycobiology, 12, 183-190. 

Three reviews have covered issues related to the synthesis of glycosides of sialic acids. a-Unked glycosides, including di- and tri-saccharides, have been prepared by use of the chloride (22) together with alcohols and silver zeolite. The a-glycoside (23),... 

The initial demonstration of the a-anomeric specificity was made with IPNeu5AcLac (Kuhn and Brossmer 1958) with influenza and mumps virus sialidases. The preparation of synthetic p-glycosides of sialic acid allowed this specificity to be tested and verified for several viral and bacterial sialidases (Meindl and Tuppy 1965, Faillard et al 1966, Kuhn et al 1966). A further analysis was carried out on synthetic a-N- and a-S-glycosides of Neu5Ac, which proved not to be substrates for viral and bacterial sialidases (Khorlin et al 1970). Subsequent studies with V. cholerae sialidase and 4-nitrophenyl-a-Neu5Ac, however, showed low but significant release by the enzyme (Eschenfelder 1979). 

---