Sialylation is biologically important modification referring to the covalent addition of sialic acid units, which are monosaccharides, to glycoproteins and glycolipid, mediated by various sialyltransferases.  In mammalian systems, this sialylation is involved in various biological functions, influencing a variety of physiologically and pathologically important processes, such as viral infection and replication.  Recently it was also suggested that this process may be implicated in the infection of SARS-CoV-2.  Therefore, inhibitors of sialyltransferase are anticipated to serve as useful probes for studying the mechanisms of these sialyltransferase-dependent biological processes, even potentially serving as medicines for the treatment of COVID-19.<br/> <br/>Herein we report a synthetic pathway for sialyl donor analogues as potential sialyltranferase inhibitors, utilizing half-esters that are prepared by the selective monohydrolysis reactions we reported earlier.  As was previously established in our group, these reactions selectively monohydrolyze only one of the two equivalent ester groups in symmetric diesters, producing half-esters having an ester group and a carboxyl group within the same molecule.  Furthermore, as water is utilized as the main solvent, these reactions are environmentally friendly and cost-effective.  It has also been found that regio- and stereospecific rearrangement reactions can take place in high yields by dissolving certain half-esters in a weakly basic buffer solution.  Using the product of this rearrangement as a starting material, we conducted synthetic studies of a library of compounds that mimics the transition state of the catalysis of sialyltransferases.  Such libraries are expected to serve as inhibitors of the activities of sialyltransferases.

Synthetic studies of sialyl donor analogues via a novel buffer-mediated rearrangement for finding sialyltransferase inhibitors

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