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).