STEPWISE SYNTHESIS OF N-ACETYLNEURAMINIC ACID AND N-ACETYL[1-C-13]NEURAMINIC ACID

N-Acetylneuraminic acid (NANA) has been synthesized from 2-acetamido-2-deoxy-D-mannose by the stepwise extension of the carbon chain. Addition of nitromethane to 2-acetamido-2-deoxy-D-mannose gave 3-acetamido-1, 3-dideoxy-1-nitro-D-galycero-D-galacto-heptitol, which underwent a modified Nef reaction to yield 3-acetamido-3-deoxy-D-giycero-D-galacto-heptose. The heptose was converted to 3-acetamido-3-deoxy-4, 5:6, 7-di-O-isopropyli-dene-aldehydo-D-glycero-D-galacto-heptose via its isopropylidenated dimethyl dithioacetal derivative. The aldehydo-heptose was converted via a second nitromethane addition, and subsequent standard reactions, to 4-acetamido-l, 2, 4-trideoxy-l-nitro-D-glycero-D-galacto-octitol, which underwent a modified Nef reaction to yield 4-acetamido-2,4-dideoxy-D-glycero-D-galacto-octose. Treatment of the octose with aqueous sodium cyanide gave the expected nononic acid derivatives 5-acetamido-3, 5-dideoxy-D-erythoro-L-manno-nononic acid and 5-acet-amido-3, 5-dideoxy-D-erythro-L-gluco-nononic acid, which were selectively oxidized at C-2 to give 5-acetamido-3, 5-dideoxy-D-glycero-D-galacto-2-nonulosonic acid (NANA). Using Na13CN in the synthesis gave [1-13C]-NANA. © 1978, American Chemical Society. All rights reserved.