Structural Variations on N-acetylneuraminic acid, 20. Synthesis of some 2,3-didehydro-2-deoxysialic Acids structurally varied at C-4 and their behavior towards Sialidase from Vibrio cholerae

Autor: Roland Schauer, Reinhard G. Kleineidam, Erwin Schreiner, Erich Zbiral
Rok vydání: 1991
Předmět:
Zdroj: Liebigs Annalen der Chemie. 1991:129-134
ISSN: 1099-0690
0170-2041
DOI: 10.1002/jlac.199119910124
Popis: The peracetylated methyl ester 1 of N-acetylneuraminic acid was transformed into the oxazoline derivative 2, which was hydrogenated with Pd/C/H2 to give the 4-deoxy-Neu5Ac2en derivative 3. Acid cleavage of the oxazoline 2 by trifluoroacetic acid (THF) gave the 4-epi-Neu5Ac2en derivative 4a, which was saponified to the known 4-epi-Neu5Ac2en 4b. Treatment of 4a with triphenylphosphane/diethylazodicarboxylate (DEAD)/HN3 in toluene gave the 4-azido-4-deoxy-Neu5Ac2en derivative 5a as well as the 4-epi-azido-4-deoxy-Neu5Ac2en derivative 6a. Both epimers could be saponified yielding the free dehydrosialic acid derivatives 5b and 6b. Furthermore, 4-formamido-4-deoxy-Neu5Ac2en 7b was prepared via the derivative 7a, which was formed from 5a by reaction with triphenylphosphane/formyl acetate. In addition, the free dehydrosialic acid derivatives 5b and 6b were transformed into the stable PN ylides 8 and 10, but only 8 could be hydrolyzed to the triethylammonium salt of 4-amino-4-deoxy-Neu5Ac2en 9a, which was converted into the zwitter ionic compound 9b. Finally 4-acetamido-4-deoxy-Neu5Ac2en 11e was prepared from 4-acetamido-4-deoxy-N-acetylneuraminic acid 10 via the derivatives 11a and 11b by well-known methods. The compounds 4b, 5b, 6b, 7b, 9b, and 11c were investigated as inhibitors of Vibrio cholerae sialidase, and their Ki values were determined.
Databáze: OpenAIRE
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