2-acetamido-2-deoxy-D-mannose

As 2-amino-2-deoxy-D-mannose is tumorstatic and 2-acetamido-2-deoxy-D-mannose 6-phosphate is an obligatory intermediate in the biosynthetic pathway to sialic acid, displacement of the essential OH-6 with a fluorine atom should be interesting from the biological viewpoint. 2-Acetamido-1,3,4-tri-0-acetyl-2,6-dideoxy-6-fluoro-D-mannopyranose (see Table 111 in Section 11,3) and its O- and A,0-deacetyl derivatives were prepared the first compound showed weak anticancer activity. 

The biosynthesis of Kdo and neuraminic acid is known to involve enol-pyruvate phosphate and D-arabinose or 2-acetamido-2-deoxy-D-mannose, respectively. Nothing is known about the biosynthesis of all the other glycu-losonic acids. One interesting problem is, for example, whether the two 5,7-diamino-3,5,7,9-tetradeoxynonulosonic acids are synthesized analogously to neuraminic acid, from a three- and a six-carbon fragment, by modification of neuraminic acid on the sugar nucleotide level, or by a third, less obvious route. 

Following the synthesis by Comforth and his associates18 of NeuAc from oxalacetate and 2-acetamido-2-deoxy-D-mannose, Ghalambor and Heath29,31 prepared KDO (isolated as the crystalline methyl 2,4,5,7,8-penta-0-acetyl-3-deoxy-D-manno-2-octulopyranosonate, 70) from D-arabinose and oxalacetate by an analogous reaction (see Scheme 20). 

Inversion of the acetamido group at C-2", with simultaneous hydrolysis of the glycosyl linkage, occurs when uridine 5 -(2-acetamido-2-deoxy-a-D-glucopyranosyl pyrophosphate) (34) is treated with a rat-liver enzyme.411,412 The products are uridine 5 -pyrophosphate (6) and 2-acetamido-2-deoxy-D-mannose (101), and they are also formed from uridine 5 -(2-acetamido-2-deoxy-a-D-mannopyranosyl pyrophos-... 

An anti-2-acetamido-2-deoxy-D-mannose immunoglobulin, MOPC 406, is an IgA that binds73 polysaccharides from Salmonella weslaco and Escherichia coli 031. These polysaccharides are known to contain 2-acetamido-2-deoxy-D-mannose,83 and it has been shown that the specificity of this protein is directed towards /3-D-linked 2-acetamido-2-deoxy-D-mannopyranosyl residues.84 Inhibition studies revealed that the apparent affinity of the methyl /3-D-glycoside for the combining region of MOPC 406 is high. 

Epimerization at C-2 of UDP-GlcNAc, leading to the UDP derivative of 2-acetamido-2-deoxy-D-mannose, was also observed115 118 the monosaccharide was identified as a constituent of several capsular polysaccharides from Streptococcus pneumonia119-122 and Neisseria meningitidis group A (Ref. 123), the teichuronic acid of Bacillus cereus,124 and the O-specific... 

Two of the most frequent monosaccharide components of bacterial polymers belonging to this group have been the subjects of articles in this Series. They are 3-deoxy-D-manno-2-octulosonic acid,247 a normal constituent of the core region of bacterial lipopolysaccharides that is also present in some other polymers, and N-acetylneuraminic acid,248 found in several capsular polysaccharides. Enolpyruvate phosphate serves as the precursor of the C-l-C-3 fragment of the monosaccharides, with D-arabinose 5-phosphate or 2-acetamido-2-deoxy-D-mannose 6-phosphate being an acceptor for transfer of the three-carbon unit. Characteristic, activated forms of these monosaccharides are the CMP derivatives. 

Other epimerases in this class are cellobiose 2-epimerase141a and, probably, UDP-2-acetamido-2-deoxy-D-glucose 2-epimerase (which gives141b 2-acetamido-2-deoxy-D-mannose and UDP), because both enzymes incorporate tritium from water-t onto C-2 of the products. 

Epimerization at C-2 of a sugar nucleotide has been described. An enzyme from Escherichia coli catalyzes the epimerization of UDP-2-acetamido-2-deoxy-D-glucose to UDP-2-acetamido-2-deoxy-D-mannose.59 Such an epimerization, together with the 3,5-epimerase reaction of a 4-ketose and stereospecific reduction at C-4, could lead to inversion at all of the chiral centers of, for instance, 2-amino-2-deoxy-D-glucose. 

Natural sialic acids (Schauer 1982 1991) are derivatives of 5-amino-3,5-dideoxy- D-glycero-D-galacto-nonu osonic acid 12.1. This awkward name has been replaced by neuraminic acid . The most common derivative is N-acetyl-neuraminic acid 12.2 whose configuration is easy to memorize because, in the Fischer representation, 12.3, it is presented as an aldolic condensation product of N-acetylmannosamine (2-acetamido-2-deoxy-D-mannose) and pyruvic acid. When the expression sialic acid is used without any other precision, it is in reference to derivative 12.2. It exists in the free state or glycosidated in the d-conformation, which allows an equatorial disposition of the three-carbon side chain. Structure 12.2 represents the stable /3-anomer of the free sugar with an axial anomeric hydroxyl group and all-equatorial non-anomeric substituents. An X-ray spectrum of this crystallized /3- anomer confirms this conformation and reveals, moreover, that the side chain has the zig-zag conformation with two... 

A-Acetyl-3-fluoroneuraminic acid (3-fluorosialic acid) has been synthesized in low yield by the condensation of fluoropyruvic acid with 2-acet-amido-2-deoxy-D-glucose or 2-acetamido-2-deoxy-D-mannose at pH 11. 

Both of the N-acylated neuraminic acids mentioned have been synthesized. Comforth, Daines, and Gottschalk192 made the first synthesis of N-acetylneuraminic acid. They condensed 2-acetamido-2-deoxy-D-glucose with oxalacetic acid at pH 11, and obtained a low yield (about 2%). Carroll and Comforth193 obtained a higher yield from 2-acetamido-2-deoxy-D-mannose and oxalacetic acid. 

Kuhn and Baschang194 used the same principle for the synthesis of N-acylated neuraminic acids by condensing the potassium salt of di-ferf-butyl oxalacetate (64) with 2-acetamido-2-deoxy-D-mannose (63) (or with 2-acetamido-4,6-0-benzylidene-2-deoxy-D-glucose), they obtained the corresponding lactone (65). This was hydrolyzed with water at 90-100° to give N-acetylneuraminic lactone (66) in a yield of 34%. 

The polysaccharide chain of the cell wall lipopolysaccharide of Escherichia coli 058 contains D-mannose, 2-acetamido-2-deoxy-D-mannose, 3-0-[(l R)-carboxyethyl)]-L-rhamnose (rhamnolytic acid), and 0-acetyl groups in the molar ratios of 2 1 1 . Structural investigations show that this polysaccharide, which contains a substituted trisaccharide repeating unit, has an identical structure (4) to that of Shigella dysenteriae type 5. 

Pneumococcal type 19 polysaccharide is composed of residues of D-glucose, L-rhamnose, 2-acetamido-2-deoxy-D-mannose, and phosphate. Strong acidic hydrolysis has been found to be accompanied by migration of the phosphate groups. 

Improved yields of 3-aminoheptoses were obtained from 2-acetamido-2-deoxy-hexoses by the nitromethane route when the aldehydo-sugar (10) was used instead of the free-sugar for the condensation with nitromethane. The same authors have developed a multi-step procedure for the sequential build-up to A-acetylneuraminic acid from 2-acetamido-2-deoxy-D-mannose which can be applied to the preparation of specifically labelled compounds and stereoisomers (Scheme 8). ... 

Chain extension. - Dondoni and co-workers have further exemplified the utility of thiazole chain-extension chemistry with the synthesis of 2-acetamido-2-deoxy-D-mannose (2) from the D-arabinose diacetonide 1 (Scheme 1), and the kanosamine derivative 4 from the D-eiythrose derivative 3 (Scheme 2), itself prepared fintxn 2,3-6>-is< )ropylidene-D-glyceraldehyde by a one carbon extension via diiazole anion addition. The methodology in Scheme 1, which features an improved thiazole to aldehyde deprotection sequence (step v), was also used to synthesize 2-amino-2-deoxy-D-mannose and, in adition, 2-amino-2-deoxy-D-erythrose from 2,3-0-isopropylidene-D-glyceraldehyde. 

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