A new synthesis of N‐acetylneuraminic acid

A new synthesis of N-acetylneuraminic acid (Neu5Ac; 28) via aldehyde 10 is described. The aldehyde 10 was obtained from N, acetyl-D-glucosamine (11; 5 steps, overall yield ca. 6%) or from D-glucono-1,5-lactone (17; 6 steps, overll yield ca 57%). Thus, on the one hand, N-acetyl-D-mannosamine (12), obtained from 11, was transformed into the known dithioacetal 14 and hence into the (ethylthio)dihydrooxazole 16, which was cleaved under weakly acidic conditions to the aldehyde 10. On the other hand, the known ester 18, obtained from 17, was sulfonylated and further transformed via the azide 20 into the N-acetyl-D-mannonate 22. Reduction of 22 to 23 and oxidation of 23 with ‘periodinane’ again gave 10. The aldehyde 10 was treated with the organozinc reagent 8 obtained from tert-butyl 2-(bromomethyl)acrylate (2) to yield predominantly 24, which was transformed (two steps) into the 2-methylidene-D-glycero-nononic acid 27 and hence into Neu5Ac (28).

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