Synthesis and biological evaluation of non-hydrolyzable 1,2,3-triazole-linked sialic acid derivatives as neuraminidase inhibitors

Article abstract of DOI:10.1002/ejoc.200900117

αa-Sialic acid, azide 1 has been used as a substrate for the efficient preparation of 1,2,3-triazole derivatives of sialic acid using the copper-catalyzed azide-alkyne Huisgen cycloaddition ("click chemistry"). Our approach is to generate nonnatural N-glycosides of sialic acid, that are resistant to neuraminidase-catalyzed hydrolysis as opposed, to the natural Oglycosides. These N-glycosides would act as neuraminidase inhibitors to prevent the release of new virions. As a preliminary study, a small library of 1,2,3-triazole-linked sialic acid, derivatives has been synthesized in 71-89% yield. A. disaccharide mimic of sialic acid, has also been prepared using the α-sialic acid azide 1 and a C-8 propargyl sialic acid acceptor in 68 % yield. A model sialic acid coated dendrimer was also synthesized from a perpropargylated pentaerythritol acceptor. These novel sialic acid derivatives were then evaluated, as potential neuraminidase inhibitors using a 96-well plate fluorescence assay; micromolar IC50 values were observed, comparable to the known sialidase inhibitor Neu5Ac2en.