A synthesis of N-acetylneuraminic acid and [6-2H]-N-acetylneuraminic acid from N-acetyl-D-glucosamine.
N-Acetylneuraminic acid (Neu5Ac) and [6-2H]-Neu5Ac were prepared from 2-acetamido-2-deoxy-D-glucose (N-acetyl-D-glucosamine). Then Henry reaction of a 1-deoxy-1-nitro derivative of GlcNAc (protected 1-C-nitroanhydro-D-glucitol) with cyclohexylidene-D-glyceraldehyde, followed by successive acetylation and reductive denitration with Bu3SnH, gave an anhydrononitol intermediate (6) diastereo-selectively in high yields. Debenzylidenation of 6 freed its distal primary carbinol group, which was subjected to catalytic oxidation followed by hydrolysis, esterification (diazomethane), and acetylation to give a protected methyl nononate. This ester was transformed into the known methyl N-acetyl-4,7,8,9-tetra-O-acetyl-2,3-dehydroneuraminate (15), which was identical with a sample prepared from Neu5Ac. Neu5Ac was obtained from 15 by bromoetherification (NBS, methanol) followed by reductive debromination with Bu3SnH and hydrolysis. Similarly, the [6-2H]-derivative of 15 was transformed into [6-2H]-Neu5Ac.
D000117:Acetylglucosamine; D003903:Deuterium; D005944:Glucosamine / Q000031:analogs & derivatives; D007202:Indicators and Reagents; D007553:Isotope Labeling / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D019158:N-Acetylneuraminic Acid; D009904:Optical Rotation; D012794:Sialic Acids / Q000138:chemical synthesis*; D013053:Spectrophotometry
D007202:Indicators and Reagents; D012794:Sialic Acids; D003903:Deuterium; D019158:N-Acetylneuraminic Acid; D005944:Glucosamine; D000117:Acetylglucosamine