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Structural Variations of N ‐Acetylneuraminic Acid, 11, Synthesis of the 4‐Methylumbelliferyl 2α‐Glycosides of 7‐Epi‐, 8‐Epi‐, and 7,8‐Bis(epi)‐ N ‐acetylneuraminic Acids, as well as of 7‐Deoxy‐, 8‐Deoxy‐, 9‐Deoxy‐, and 4,7‐Dideoxy‐ N ‐acetylneuraminic Acids and Their Behaviour Towards Sialidase from Vibrio cholerae
Author(s) -
Zbiral Erich,
Schreiner Erwin,
Salunkhe Mamikrao M.,
Schulz Gerhard,
Kleineidam Reinhard G.,
Schauer Roland
Publication year - 1989
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.198919890192
Subject(s) - chemistry , anomer , sialidase , glycoside , stereochemistry , hydrolysis , n acetylneuraminic acid , sialic acid , enzyme , organic chemistry , neuraminidase , biochemistry
The methyl esters of 7‐epi‐Neu5Ac ( 1a ), 8‐epi‐Neu5Ac ( 2a ), 7,8‐bis(epi)‐Neu5Ac ( 3a ), 7‐deoxy‐Neu5Ac ( 4a ), 8‐deoxy‐Neu5Ac ( 5a ), 9‐deoxy‐Neu5Ac ( 6a ), and 4,7‐dideoxy‐Neu5Ac ( 7a ) were transformed into their peracetylated mixtures of the α‐anomers 1b–7b and β‐anomers 1c–7c . In the next step the 2‐Cl derivatives were prepared with acetyl chloride/HCl which yielded in the following Königs‐Knorr reaction with 4‐methylumbelliferone (MU) the corresponding methylumbelliferyl 2α‐glycosides 7‐epi‐Neu4,5,7,8,9Ac 5 1Me‐αMU ( 1d ), 8‐epi‐Neu4,5,7,8,9Ac 5 1Me‐αMU ( 2d ), 7,8‐bis(epi)‐Neu4,5,7,8,9Ac 5 1Me‐αMU ( 3d ), 7‐deoxy‐Neu‐4,5,8,9Ac 4 1Me‐αMU ( 4d ), 8‐deoxy‐Neu4,5,7,9Ac 4 1Me‐αMU ( 5d ), 9‐deoxy‐Neu4,5,7,8A 4 1Me‐αMU ( 6d ), and 4,7‐dideoxy‐Neu‐5,8,9Ac 3 1Me‐αMU ( 7d ). In the last case also the β‐anomer of 4,7‐dideoxy‐Neu5,8,9Ac 3 1Me‐βMU ( 7d′ ) was formed. Zemplen saponification followed by hydrolysis of the ester group with sodium hydroxide, resulted in the sodium salts of the sialic acid MU 2α‐glycosides 7‐epi‐, 8‐epi‐, 7,8‐bis(epi)‐, 8‐deoxy‐, 9‐deoxy‐ and 4,7‐dideoxy‐Neu5Ac‐MU 1e–7e . The enzymatic hydrolysis of these compounds with sialidase from Vibrio cholerae showed only for 3e and 7e significantly reduced rates of cleavage, which is in agreement with the inhibitor constants K i of the related 2,3‐didehydro sialic acids 7,8‐bis(epi)‐Neu5Ac2en and 4,7‐dideoxy‐Neu5Ac2en 1,15) .