Facile Anomer-oriented Syntheses of 4-Methylumbelliferyl Sialic Acid Glycosides

Abstract

<p>As part of a program to find new sialidases and determine their enzymatic specificity and catalytic activity, a library of 4-methylumbelliferyl sialic acid glycosides derivatised at the C-5 position were prepared from <i>N</i>-acetylneuraminic acid. Both α- and β-4-methylumbelliferyl sialic acid glycosides were prepared in high yields and excellent stereoselectivity. Alpha anomers were accessed via reagent control by utilising additive CH<sub>3</sub>CN and TBAI, whereas the beta anomers were synthesised through a diastereoselective addition reaction of iodine and the aglycone to the corresponding glycal followed by reduction of the resulting 3-iodo compounds. Both anomer-oriented synthetic pathways allow for gram-scale stereoselective syntheses of the desired C-5 modified neuraminic acid derivatives for use as tools to quantify the enzymatic activity and substrate specificity of known<b> </b>sialidases, and potential detection and investigation of<b> </b>novel sialidases.</p>