Deoxy-2,3-dehydro-N-acylneuraminic Acids

2-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). 

2-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). 

The unsaturated sialic acid could also be obtained by prolonged heating (5 h, 90 °C) of 2,4,7,8,9-penta-O-acetyl-N-acetylneuraminic acid in dioxan, followed by O-deacetylation (Meindl and Tuppy 1969 a). 

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the synthesis of a 2-deoxy-2,3-dehydro-N-acetylneuraminic acid methyl ester, in which the primary hydroxyl group had been replaced by a Cl-atom.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). 

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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)...

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