2,3-Dehydro-4-epi-N-acetylneuraminic acid; a neuraminidase inhibitor.
Treatment of N-acetylneuraminic acid methyl ester with sulfuric acid and acetic anhydride at 50 degrees followed by deacetylation gave 2,3-dehydro-2-deoxy-N-acetylneuraminic acid methyl ester and methyl 5-acetamido-2,6-anhydro-2,3,5-trideoxy-D-glycero-D-talo-non-2-enonate (2,3-dehydro-4-epi-NeuAc methyl ester) in equal yields (approximately 40% each). The structure of the latter was ascertained primarily from analysis of its mass spectrum and 1H- and 13C-nuclear magnetic resonance spectra. The relative proportions of these two glycals in the foregoing reaction was dependent on temperature, as at 0 degrees, the yield of 2,3-dehydro-4-epi-NeuAc was markedly diminished. A minor by-product of this acetylation reaction was 2-methyl-(methyl 7,8,9-tri-O-acetyl-2,6-anhydro-2,3,5-trideoxy-D-glycero-D-talo-non-2-enonate)-[ 4,5-d]-2-oxazoline. Based upon this finding and additional interconversion experiments, a mechanism involving the intermediacy of the latter oxazoline to account for the epimerization is proposed. These glycals and their methyl esters are competitive inhibitors of Arthrobacter sialophilus, neuraminidase, suggesting that the 4-hydroxyl group must be equatorially oriented for maximal enzyme inhibition.
D001173:Arthrobacter / Q000201:enzymology; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives*; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D012794:Sialic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D012794:Sialic Acids; C031870:2,3-dehydro-4-epi-N-acetylneuraminic acid; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid