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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
Author(s) -
Schreiner Erwin,
Zbiral Erich,
Kleineidam Reinhard G.,
Schauer Roland
Publication year - 1991
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.199119910124
Subject(s) - chemistry , trifluoroacetic acid , saponification , sialidase , oxazoline , derivative (finance) , hydrolysis , vibrio cholerae , cyclopropanation , epimer , stereochemistry , organic chemistry , enzyme , neuraminidase , catalysis , biology , bacteria , financial economics , economics , genetics
The peracetylated methyl ester 1 of N‐acetylneuraminic acid was transformed into the oxazoline derivative 2 , which was hydrogenated with Pd/C/H 2 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)/HN 3 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 K i values were determined.