KDO 3-deoxy-D-manno-2-octulosonic

The key component of the cell wall lipopolysaccharide of Gram-negative bacteria, KDO (3-deoxy-D-manno-2-octulosonic acid), was synthesized by S.D. Burke and co-workers. One of the key transformations in the synthetic sequence was a doubie SAD of a 6-vinyldihydropyran-2-carboxylate template. This 1,4-diene was cleanly converted to a mixture of two C7 epimeric tetraols in a 20 1 ratio. The endocyclic olefin had an intrinsic preference for dihydroxyiation from the 3-face and not from the desired a-face. This stereofacial bias was impossible to override with any ligand normally used in the SAD, so later in the synthesis these two stereocenters had to be inverted in order to give the required stereochemistry at C4 and C5. 

Figure 2 Schematic representation of the LOS structure of N. meningitidis and N. gonor-rhoeae. Variations in the largest a chain are responsible for most of the immunogenic properties of the LOS. Abbreviations KDO, 3-deoxy-D-manno-2-octulosonic acid Hep, l -glycero-D-wanno-heptose Glc, glucose GlcNAc, A-acetylglucosamine PEA, phosphoethanolamine. Note Cii indicates an additional 11 carbon atoms, not the total chain length.

Upon treatment with n-BruiNF, product 97 is converted to 98, which is a key intermediate for the synthesis of the monosaccharide 3-deoxy-D-manno-2-octulosonic acid (KDO)—an essential constituent of the outer membrane lip-op oly s accharide (LPS) of gram-negative bacteria.40... 

THE CHEMISTRY AND BIOLOGICAL SIGNIFICANCE OF 3-DEOXY-D-manno-2-OCTULOSONIC ACID (KDO) ... 

Deoxy-D-manno-2-octulosonic acid109 ( KDO ) is homomorphous with 3-deoxy-D-gaiacfo(and falo)-heptulose a preponderance of the a-pyranose form (15), accompanied by substantial proportions of the two furanose forms, would therefore be expected. Actually, there is, again, a small proportion of the / -pyranose form present. The composition found110 in a 0.72 M solution of the ammonium salt at 28° is 64 6 20 10 and, in a 0.18 M solution, 60 11 20 9. 

R. Ramage, A. M. MacLeod, and G. W. Rose, Dioxolanes as synthetic intermediates. Part 6. Synthesis of 3-deoxy-D-manno-2-octulosonic acid (KDO), 3-deoxy-D-araMiio-2-heptulosonic acid (DAH) and 2-keto-3-deoxy-D-gluconic acid (KDG), Tetrahedron 47 5625 (1991). 

A. Dondoni and P. Merino, Chemistry of the enolates of 2-acetylthiazole Aldol reactions with chiral aldehydes to give 3-deoxy aldos-2-uloses and 3-deoxy-2-ulosonic acids. A short total synthesis of 3-deoxy-D-manno-2-octulosonic acid (KDO), J. Org. Chem. 56 5294 (1991). 

Unger, F. M. The Chemistry and Biological Significance of 3-Deoxy-D-manno-2-octulosonic Acid (KDO), Tipson, R. S7 Horton, D., eds. ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY, Vol. 

Synthesis and Use of 3-Deoxy-D -manno-2-octulosonate (KDO) in Escherichia coli... 

Neszmelyi, A., Jann, K., Messner, P. and Unger, F.M. (1982) Constitutional and configurational assignements by JC NMR spectroscopy of Escherichia coli capsular polysaccharides containing ribose and 3-deoxy-D-manno-2-octulosonic acid (KDO). J. Chem. Soc. Chem. Commun. 1017-1019... 

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