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

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‐Neu4,5,7,8,9Ac51Me‐αMU (1d), 8‐epi‐Neu4,5,7,8,9Ac51Me‐αMU (2d), 7,8‐bis(epi)‐Neu4,5,7,8,9Ac51Me‐αMU (3d), 7‐deoxy‐Neu‐4,5,8,9Ac41Me‐αMU (4d), 8‐deoxy‐Neu4,5,7,9Ac41Me‐αMU (5d), 9‐deoxy‐Neu4,5,7,8A41Me‐αMU (6d), and 4,7‐dideoxy‐Neu‐5,8,9Ac31Me‐αMU (7d). In the last case also the β‐anomer of 4,7‐dideoxy‐Neu5,8,9Ac31Me‐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 Ki of the related 2,3‐didehydro sialic acids 7,8‐bis(epi)‐Neu5Ac2en and 4,7‐dideoxy‐Neu5Ac2en1,15). Strukturelle Abwandlungen an N‐Acetylneuraminsäure, 111). ‐ Synthese der 4‐Methylumbelliferyl‐2α‐glycoside von 7‐Epi‐, 8‐Epi‐und 7,8‐Bis(epi)‐N‐acetylneuraminsäuren, sowie von 7‐Desoxy‐, 8‐Desoxy‐, 9‐Desoxy‐ und 4,7‐Didesoxy‐N‐acetylneuraminsäure und ihr Verhalten gegenüber Vibrio‐cholerae‐Sialidase Die Methylester von 7‐Epi‐Neu5Ac (1a), 8‐Epi‐Neu5Ac (2a), 7,8‐Bis(epi)‐Neu5Ac (3a), 7‐Desoxy‐Neu5Ac (4a), 8‐Desoxy‐Neu5Ac (5a), 9‐Desoxy‐Neu5Ac (6a) und 4,7‐Didesoxy‐Neu5Ac (7a) wurden in die peracetylierten Gemische der α‐ und β‐Anomeren 1b–7b und 1c–7c umgewandelt. Aus den mit Acetylchlorid/HCl hergestellten 2‐Chlorderivaten wurden in der folgenden Königs‐Knorr‐Reaktion mit 4‐Methylumbelliferon (MU) die entsprechenden Methylumbelliferyl‐2α‐glycoside 7‐Epi‐Neu‐4,5,7,8,9Ac51Me‐αMU (1d), 8‐Epi‐Neu4,5,7,8,9Ac51Me‐αMU (2d), 7,8‐Bis(epi)‐Neu4,5,7,8,9Ac51Me‐αMU (3d), 7‐Desoxy‐Neu‐4,5,8,9Ac41Me‐αMU (4d), 8‐Desoxy‐Neu4,5,7,9Ac41Me‐αMU (5d), 9‐Desoxy‐Neu4,5,7,8Ac41Me‐αMU (6d) und 4,7‐Didesoxy‐Neu5,8,9Ac31Me‐αMU (7d) hergestellt. Im letztgenannten Fall entstand auch das β‐Anomere von 4,7‐Didesoxy‐Neu5,8,9‐Ac31Me‐βMU (7d′)‐ Zemplen‐V