Deoxy-nitrosugars 15th communication Synthesis of N-acetylneuraminic acid and N-acetyl-4-epineuraminic Acid

✍ Scribed by Franz Baumberger; Andrea Vasella

• Publisher: John Wiley and Sons
• Year: 1986
• Tongue: German
• Weight: 800 KB
• Volume: 69
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19860690528

✦ Synopsis

A synthesis of N-acetylneuraminic acid (1) and of N-acetyl-4-epineuraminic acid (2, R = H) from 2-acetamido-4,6-O-benzylidene-l,2-dideoxy-1 -nitro-D-mannopyranose (3) and 2-acetamido-l,2-dideoxy-4,6-0-isopropylidene-l -nitro-D-mannopyranose (4), respectively, is described. Michael addition of 3 and 4 to tert -butyl 2-(bromomethyl)prop-2-enoate (5) and subsequent hydrolytic removal of the NO, group gave the 4-nonulosonate tautomers 6/7 and 8/9, respectively (Scheme). Stereoselective reduction of 6/7 and S/9 with NaBH,/AcOH in dioxane/H20 yielded 12/13 (94:6) and 14/15 (92 :8), respectively. Reduction of 6/7 and 8/9 in the absence of AcOH orinEtOHgave 12/13(15:85)and 14/15(15:85),respectively. Ozonolysisof l2and 13followed by hydrolysisgave tert-butyl neuraminate 22 and tert-butyl4-epineuraminate 24, respectively. Ozonolysis of 14/15, separation of the products 20 and 21, and hydrolytic removal of the isopropylidene groups gave 22 and 24, respectively. The tert-butyl ester 22 was saponified to give 1, which was further characterized as the methyl ester 23. Saponification of 24 gave the crude 4-epimer of 1, which was converted into the stable Na salt 2 and also into the methyl ester 25.