4‐Methylumbelliferyl 5‐Acetamido‐3,4,5‐trideoxy‐α‐<scp>D</scp>‐<i>manno</i>‐2‐nonulopyranosidonic Acid: Synthesis and Resistance to Bacterial Sialidases

Abstract

Abstract The synthesis of 4‐methylumbelliferyl α‐ D ‐glycoside 13 of N ‐acetyl‐4‐deoxyneuraminic acid and its behaviour towards bacterial sialidases is described. N ‐Acetyl‐4‐deoxyneuraminic acid ( 1 ) was transformed into its methyl ester 2 and then acetylated to give the anomeric pentaacetates 3 and 4 of methyl 4‐deoxyneuraminate and the enolacetate 5 ( Scheme ). A mixture 3/4 was treated with HCl/AcCl to give the glycosyl chloride, which was directly converted into the 4‐methylumbelliferyl α‐ D ‐glycoside 9 of methyl 7‐ O ,8‐ O ,9‐ O , N ‐tetraacetylneuraminate and into the 2,3‐dehydrosialic acid 11 . The ketoside 9 was de‐ O ‐acetylated to 12 with NaOMe in MeOH. Saponification (NaOH) of the methyl ester 12 followed by acidification gave the free 13 , which was also converted into the sodium salt 14 by passage through Dowex 50 (Na + ). The 4‐deoxy α‐ D ‐glycoside 13 is not hydrolyzed at significant rates by Vibrio cholerae and Arthrobacter ureafaciens sialidase. Neither the free N ‐acetyl‐4‐deoxyneuraminic acid ( 1 ), nor the α‐ D ‐glycoside 13 inhibit the activity of these sialidases.