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Synthesis 2007(13): 1899-1926  
DOI: 10.1055/s-2007-983723
REVIEW
© Georg Thieme Verlag Stuttgart · New York

Sialic Acid and Structural Analogues: Stereoselective Syntheses

Ivan Hemeon, Andrew J. Bennet*
Department of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada
Fax: +1(604)2915424; e-Mail: bennet@sfu.ca;
Further Information

Publication History

Received 23 February 2007
Publication Date:
18 June 2007 (online)

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Abstract

Sialic acid (N-acetylneuraminic acid) is a carbohydrate that is often found on the ends of oligosaccharide chains in biological systems. As such, it is important in several biological recognition/communication events mediated by sialic acid recognising proteins that play integral roles in these phenomena. It is therefore necessary to develop synthetic routes to sialic acid and its derivatives and analogues. Many of these routes have led to compounds used as enzyme inhibitors for treatment of disease states and also as probes of biologically relevant binding events and of the mechanisms of enzyme action. Every position on the nine-carbon backbone of sialic acid has been derivatised for such purposes, being synthesised both chemoenzymatically and chemically from precursors ranging from non-carbohydrate sources to sialic acid itself. This review describes various synthetic strategies developed for the synthesis of sialic acid and its variants at each position on the carbon skeleton.

  • 1 Introduction

  • 2 Naturally Occurring Variants

  • 3 Synthesis of Sialic Acid

  • 3.1 Enzymatic Syntheses

  • 3.2 Chemical Syntheses

  • 4 Substituted Sialic Acid Analogues

  • 4.1 Substitution at C1

  • 4.2 Variation at C3

  • 4.3 Modification at C4

  • 4.4 Amide Variation at C5

  • 4.5 Modification at C6

  • 4.5.1 Substitution of the Ring Oxygen

  • 4.5.2 Substitution of the Glycerol Side Chain

  • 4.6 Modifications at C7, C8, and C9

  • 5 Conclusions

Key words

carbohydrates - organometallic reagents - ozonolysis - stereoselectivity - sialic acids