Chemistry of sialic acids

X. Chen and A. Varki, Advances in the biology and chemistry of sialic acids, ACS Chem. Biol., 5 (2010) 163-176. 

The interesting chemistry of sialic acid has been discussed in several reviews [213,214,215]. Sialic acid is an important component of complex oligosaccharides, when it is placed in the terminal position, and often masks the penultimate saccharide sequences. In this position, it interacts with numerous receptors including the influenza virus neuraminidase, and receptors mediating intercellular interactions such as the selectins (members of the C-t) e animal lectin family) and siglecs (or sialoadhesins, members of the immunoglobulin superfamily). The structure of influenza B neuraminidase in complex with sialic acid has been solved by X-ray crystallography at 2.2 A resolution (O Fig. 17) [216]. 

This review summarizes the latest developments in the chemistry of sialic acid which involve modifications of the natural 5-acetamido function (NHAc) into a) N-acetylacetamido (NAca), b) azido (N3), c) N-trifiuoroacetamido (NHTFA) and d) N-trichloroethoxycarbonyl (NHTroc). Last section is dedicated to protecting groups that have been introduced at the N-position but fiieir potential as sialosyl donors has not emerged yet, e.g. tert-Butoxycarbonyl (Boc), Benzyloxycarbonyl (Z or CBz) and 9-Fluorenylmethoxycarbonyl (Fmoc). 

The chemistry of sialic acid was pioneered in the late 1960s and focussed on the preferential formation of the a-ketosidic linkage. This is a particularly difficult chemical problem since the anomeric centre sterically and electronically disfavours formation of the oxocarbenium ion intermediate in the course of glycosidation. 

In this chapter, the chemistry of sialic acid is briefly reviewed and some advantages and problems of strategies described for the construction of the a-ketosidic linkage of sialic acid and complicated sialosides are presented. Experimental details are also provided to allow practical preparation of the chosen targets. 

Corfleld AP, Schauer R (1982) Metabolism of sialic acids. In Schauer R (ed) Sialic acids - Chemistry, metabolism and function. Springer, Wien, pp 195-261 Corfleld AP, Higa H, Paulson JC, Schauer R (1983) The specificity of viral and bacterial sial-idases for alpha(2-3)- and alpha(2-6)-linked sialic acids in glycoproteins. Biochim Biophys Acta 744 121-126... 

CHEMISTRY, METABOLISM, AND BIOLOGICAL FUNCTIONS OF SIALIC ACIDS... 

A. Gottschalk, The Chemistry and Biology of Sialic Acids and Related Substances, University Press, Cambridge, 1960. 

I should like to thank my coworkers at the Universities of Bochum and Kiel who have contributed to the progress in the chemistry and biology of sialic acid over the past 14 years, and also the many colleagues, all over the world, who have given me advice, and participated in fruitful collaboration. Thanks are also due A. P. Corfield, G. Reuter (University of Kiel), and H. Rahmann (University of Stuttgart-Hohenheim) for assistance and criticism during the preparation of the manuscript. 

IR and synthesis Cornforth et al. BJ 68 57 1958 Zillikin and O Brien Biochemical Preparations 7 1 1960 13C NMR and 1-13C synthesis Nguyen, Perry JOC 43 551 1978 Danishevski, DeNinno JOC 51 2615 1986 Gottschalk, The Chemistry and Biology of Sialic Acids and Related Substances, Cambridge University Press, London, I960]. 

R. Schauer, Chemistry, metabolism and biological functions of sialic acids, Adv. Carbohydr. Chem. Biochem. 40 131 (1982). 

W. Reutier, E. Kottgen, C. Bauer, and W. Gerok, Biological significance of sialic acid, in Sialic Acids. Chemistry, Metabolism, and Function, R. Schauer, ed., Springer-Verlag, Vienna, 1982, p. 263. 

The use of enzymes in carbohydrate chemistry is covered in two chapters on izymatic synthesis of sialic acid, KDO, and related deoxyulosonic acids, and oligosac-aarides. 

Vliegenthart JFG, Kamerling JP (1982) Synthesis of sialic acids and sialic acid derivatives, in Schauer R (ed) Sialic acids, chemistry, metabolism and function Springer-Verlag, New York, p 59... 

Gottschalk, A. Chemistry and biology of sialic acids, Cambridge University Press. New York, p. 65 (1960). 

A number of carbohydrates have therapeutic applications [285, 286], and there are now reports of several potential therapeutic applications for sialic acid-containing compounds [189,287-289]. The field of sialic acid chemistry is ever-expanding, and most of those working in this challenging area of chemistry are now closely allied with glycobiologists. The future for this field is bright, and much is yet to be discovered. 

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