Complex Bacterial Carbohydrate Surface Antigen Structures: Syntheses of Kdo- and Heptose-containing Lipopolysaccharide Core Structures and Anomerically Phosphodiester-Linked Oligosaccharide Structures

Microbial carbohydrate structures show a considerable complexity due to the presence of an immense variety in the integral substituents and monosaccharide residues, both regarding structure and position. This severely complicates both the analyses and syntheses of these compounds. This article discusses the synthetic preparation of structures containing some of these intricate structural features. The inner core region of lipopolysaccharides (LPS) of Gram-negative bacteria contains a number of unusual sugars, which are not found elsewhere, the two most abundant are the higher carbon sugars, 3-deoxy-D-manno-2-octulosonic acid (Kdo) and L-glycero-D-manno-heptose (Hep). To prepare core structures, these residues must first be synthesised in a stereospecific manner and then converted to suitable donors and acceptors. Furthermore, must their assembly into oligosaccharide structures be mastered, which is especially difficult with Kdo donors. Recent achievements in the synthesis of core structures are presented including the preparation of Kdo and heptose intermediates, and the construction of complex heptose- and Kdo-containing oligosaccharides, corresponding to structures from Salmonella, Chlamydia, Haemophilus, Neisseria and Moraxella LPSs. Bacterial capsular polysaccharides are frequently built up by phosphodiester linked repeating units. Most often one of the ester bonds is an anomeric linkage. This makes their synthetic formation especially complicated, since not only must the right stereochemistry be introduced but also the lability of anomeric phosphodiester linkages must be considered. Consequently have earlier synthesis of these structures not been possible. In the second part of this article is presented a review of modern achievements in this field, both considering methods and their applications to oligosaccharide synthesis. Synthesised structures from Staphylococcus lactis, Hansenula capsulata, Escherichia coli, Streptococcus pneumonia, Haemophilus influenzae, Neisseria meningitidis, and Leishmania are discussed.