3-Deoxy-2-ulosonic acid structure

Such an important biological and immunological role of 3-deoxy ulosonic acids, as well as their unique chemical structure has emerged as an important area of many research fronts. Much attention has been also focused on enzymatic, chemoenzymatic, and stereocontrolled chemical syntheses of all of these compounds and their analogues. 

Fig. 6. Structures of the LPS-derived oligosaccharides and OPS containing legionaminic acid (Leg). [D-a-D-Hep and L-a-D-Hep, D-glycero- and L-glycero-a-D-manno-heptose Kdo, 3-deoxy-D-manno-oct-2-ulosonic acid Fuc4NR3Hb, 4-[(R)-3-hydroxybutanamido]-4,6-dideoxygalactose Ala, L-alanyl Cm, carbamoyl PEtn, ethanolamine phosphate R is acetyl in some repeating units and (S)-3-hydroxybutanoyl in the others.]...

Fig. 10.2 Structures of the minor hexa-acyl lipid A molecular species found in H. pylori smooth-form LPS (left) and the tetra-acyl lipid A species found in H. pylori rough- and predominating in smooth-form LPS (right) (Moran et al., 1997). One 3-deoxy-D-man ooct-2-ulosonic acid residue, as occurs in the H. pylori core OS, is shown attached to the 6 -position of lipid A. The numbers in circles refer to the number of carbon atoms in the acyl chains. Compared to the hexa-acyl minor species, the tetra-acyl molecular species lacks 4 -phosphate and is substituted at position-1 by phosphoethanolamine...

Fig. 1. Chemical structures for simple sialic acids in different views, (a) S-amino-S.S-dideoxy-D-gfycero-D-ga/acro-non-2-ulosonic acid (Neu, open chain, Fischer projection formula) (b) 5-acetaraido-3,5-dideoxy-D-g/> cero-a-D-gfl/acto-non-2-ulopyranosonic acid (a-Neu5Ac, Fischer projection formula, note that C7 is the anomeric reference atom) (c) a-Neu5Ac (Haworth projection formula) (d) a-Neu5Ac ( 5 chair conformation) (e) 3-deoxy-D-g/ycero-3-D-gfl/acto-non-2-ulopyranosonic acid (P-Kdn, 5 chair conformation). Note that the D-notation is part of the trivial name.

ABSTRACT This article describes recent developments in the chemistry of an important family of complex monosaccharides which have diverse structures and participate in a wide range of biological processes. For example 3-deoxy-D-/n nno-2-octulosonic acid (KDO) is a key component of the lipopolysaccharides (LPS) of Grammnegative bacteria, 3-deoxy-D-araftmo-2-heptulosonic acid (DAH) is a key intermediate in the biosynthesis of aromatic amino acids in bacteria and plants. A number of their syntheses that were achieved by homologation reactions of the natural carbohydrate units using enzymatic or chemical methods, as well as by total synthetic approaches are here included. Special emphasis is placed on new methodologies and their correlation with the biosynthetic pathway of the corresponding ulosonic acids. 

The aldolases which have been investigated for their synthetic utility can be classified on the basis of the donor substrate accepted by the enzyme. For the synthesis of 3-deoxy-2-ulosonic acids pyruvate- and phosphoenolpyruvate dependent aldolases are the most desirable enzymes as they are involved in the metabolism of sialic acids (or structurally related ones) in vivo. They use pyruvate or phosphoenolpyruvate as a donor to form 3-deoxy-2-keto acids (Table 1). Both of them add a three-carbons ketone fragment onto a carbonyl group of an aldehyde. The pyruvate dependent aldolases have a catabolic function in vivo, whereas the phosphoenolpyruvate dependent aldolases are involved in the biosynthesis of the keto acids. For synthetic purpose the equilibrium of the pyruvate dependent aldolases is shifted toward the condensation products through the use of an excess of pyruvate. 

All previously described approaches to 3-deoxy-2-ulosonic acids started from advanced carbohydrate precursors, and thus they are not easily applicable to the synthesis of structurally diverse analogues. This concerns chemical syntheses relying on sugar-derived stereocenters and enzymatic ones, providing only very limited access to some naturally occurring compounds. In contrast, de novo syntheses starting from simple, achiral compounds offer much more flexible alternative approaches to synthesis of unnatural ulosonic acid analogues. 

The transfer of the pyruvate unit as phosphoenolpyruvate (PEP) to aldoses results in 4-hydroxy-2-oxocarboxylic acid structures and constitutes an important natural C-C bond forming reaction for the biosynthesis of ulosonic [36] and sialic acids [37,38]. Important compounds such as N-acetylneuraminic acid, 3-de-oxy-D-manno-octulosonic acid (KDO), and 3-deoxy-D-araZ mo-2-heptulosonic acid 7-phosphate (DAHP), the precursor of shikimic acid, are formed in this way. 

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