2-deoxy-, 2,3-dehydro

Bossart-Whitaker P, Carson M, Babu YS, Smith CD, Laver WG, Air GM (1993) Three-dimensional structure of influenza A N9 neuraminidase and its complex with the inhibitor 2-deoxy 2,3-dehydro-V-acetyl neuraminic acid. J Mol Biol 232 1069-1083 Burmeister WP, Ruigrok RW, Cusack S (1992) The 2.2 A resolution crystal structure of influenza... 

Viral replication, packaging and release. Drug Disc Today 1 388-397 Meindl P, Tuppy H (1969) 2-Deoxy-2,3-dehydrosialic acids. II. Competitive inhibition of Vibrio cholerae neuraminidase by 2-deoxy-2,3-dehydro-V-acyIneuraminic acids. Hoppe-Seyler s Z Physiol Chem 350 1088-1092... 

Nohle U, Beau JM, Schauer R (1982) Uptake, metabolism and excretion of orally and intravenously administered, double-labeled A-glycoloylneuraminic acid and single-labeled 2-deoxy-2,3-dehydro-A-acetylneuraminic acid in mouse and rat, Eur J Biochem 126 543-548 Oxford J (2005) Oseltamivir in the management of influenza. Expert Opin Pharmacother 6 2493-2500... 

Palese P, Compans RW (1976) Inhibition of influenza vims replication in tissue culture by 2-deoxy-2,3-dehydro-A-trifluoroacetylneuraminic acid (EANA) mechanism of action, J Gen Virol 33 159-163... 

Usuki, S., Hoops, P., and Sweeley, C. C. (1988). Growth control of human foreskin fibroblasts and inhibition of extracellular sialidase activity by 2-deoxy-2,3-dehydro-N-acetylneura-minic acid. /. Biol. Chem. 263, 10595-10599. 

The structures of TV-acetyl neuraminic acid (sialic acid Neu5Ac) and the 2-deoxy-2,3-dehydro-/V-acetyl neuraminic acid (Neu5Ac2en) inhibitor complexed with N2 neuraminidase [66] revealed the nature of the interactions of the... 

T. Kondo, H. Abe, and T. Goto, Efficient synthesis of 2a-glycoside of W-acetylneuraminic acid via phenylsulfenyl chloride adduct of 2-deoxy-2,3-dehydro-lV-acetylneuraminic acid methyl esier tetra-O-acetate, Chem. Lett., p. 1657 (1988). 

P. Meindl, G. Bodo, P. Palese, J. Schulman, and H. Tuppy, Inhibition of neuraminidase activity by derivatives of 2-deoxy-2,3-dehydro-jV-acetylneuraminic acid, Virology, 58 (1974) 457 463. 

Fig. 43.4. Sialic acid derivatives 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (DANA), zanamir, and oseltamivir phosphate, which act as inhibitors of neuraminidase. ...

Meindl, P. and Tuppy, H. (1969) 2-Deoxy-2,3-dehydrosialic acids. I. Synthesis and properties of 2-deoxy-2,3-dehydro-A/-acylneuraminic acids and their methyl esters. Monatshefte fiir Chemie, 100,... 

Inhibition of neuraminidase activity by derivatives of 2-deoxy-2,3-dehydro-Af-acetylneuraminic acid. Virology, 58, 457-463. 

Competitive inhibition of Vibrio cholerae neuraminidase by 2-deoxy-2,3-dehydro-A/-acyl-neuraminic acids. Hoppe-Seylers Zeitschrift Fur Physiologische Chemie,... 

Deoxy-2,3-dehydro-N-acylneuraminic acids have been applied in several competitive inhibition studies with neuraminidases from different sources (see for instance Meindl and Tuppy 1969b, Meindl et al. 1971, 1974, Palese and CoMPANS 1976, Veh and Schauer 1978, Kumar et al. 1981). 

Deoxy-2,3-dehydro-N-acetylneuraminic acid has been synthesized by treatment of 4,7,8,9-tetra-0-acetyl-2-chloro-2-deoxy-[5-N-acetylneuraminic acid (Meindl and Tuppy 1965 a) with triethylamine (10 min, 20 °C) or silver carbonate (60-90 min, 80 90°C) in dioxan or acetone, and subsequent alkaline O-deacetylation (Meindl and Tuppy 1969 a). This compound has also been detected frequently as a by-product in the synthesis of a-glycosides (Meindl and Tuppy 1965 a) and of a-linked sialodisaccharides (Van der Vleugel / al. 1982 b, 1982 c). 

Table 3. Survey of N-acyl groups of 2-deoxy-2,3-dehydro-N-acylneuraminic acid(s) (methyl esters) (Meindl and Tuppy 1969 a, 1973)...

Another approach for the synthesis of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid has been reported by Beau and Schauer (1979). 4,7,8,9-Tetra-0-/7-nitrobenzoyl-2-bromo-2-deoxy-N-acetylneuraminic acid methyl ester could be converted quantitatively into the unsaturated analogue using triethylamine or molecular sieves 4A in dichloromethane. After deprotection of the latter derivative the free unsaturated N-acetylneuraminic acid was obtained. These authors also mentioned the synthesis of a 2-deoxy-2,3-dehydro-N-acetylneuraminic acid methyl ester, in which the primary hydroxyl group had been replaced by a Cl-atom. 

When N-acetylneuraminic acid methyl ester was treated with sulfuric acid and acetic anhydride, after O-deacetylation a mixture of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid methyl ester and 2-deoxy-2,3-dehydro-4-epi-N-acetylneuraminic acid methyl ester was obtained. The ratio of the two compounds was influenced by the reaction temperature. A minor by-product of the acetylation reaction showed to be 2-methyl-(methyl 7,8,9-tri-0-acetyl-2,6-anhydro-2,3,5-trideoxy-D-g/> cer o-D- a/o-non-2-enonate)-[4,5-tfl-2-oxazoline (Kumar et al 1981). 

The periodate oxidation/reduction approach has also been used to differentiate between the methyl a- and p-glycosides of N-acetylneuraminic acid. Only the C7-analogue of the p-anomer could be lactonized (Yu and Ledeen 1969). The preparation of the C7-analogue of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid using periodate oxidation/borohydride reduction was reported by Meindl and Tuppy (1970). 

In studies on the chemical stability of CMP-Neu5Ac in dependence on the pH two interesting decomposition products were observed, viz. p-N-acetylneuraminic acid-2-phosphate (Neu5Ac2P) and 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (Neu5Ac2en) (Beau et al, unpublished results). Their iH-NMR spectra are given in Fig. 11 and 12, respectively. The presence of a phosphate group in Neu5Ac2P... 

Fig. 12. Resolution-enhanced 360 MHz IH-NMR spectrum of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (Neu5Ac2en) dissolved in 2H2O, recorded at p H 6 and 25 C. The relative-intensity scale of the 5Ac methyl proton signal differs from that of the other parts...

---