Galactose-conjugates of the oseltamivir pharmacophore-new tools for the characterization of influenza virus neuraminidases
journal contribution
posted on 2023-06-07, 19:09authored byBenoit Carbain, Stephen R Martin, Patrick J Collins, Peter B Hitchcock, Hansjorg Streicher
We describe the synthesis of mimetics of the a23 and a26 sialogalactoside substrates of influenza neuraminidase which include the oseltamivir pharmacophore, and report the sub-nanomolar affinities for these novel neuraminidase inhibitors. The challenge of synthesizing a Phospha-Oseltamivir/Tamiphosphor monoester involving the secondary 3-hydroxy group of galactose required to mimic the a23 sialogalactoside has been overcome by palladium-promoted coupling of the oseltamivir-derived vinyl iodide with a protected galactose-3-phosphonate. The difference in binding of these two inhibitors to a given influenza neuraminidase should be a function of its a23/a26-selectivity, an important, but not yet fully understood factor in the adaptation of highly pathogenic avian influenza viruses to human hosts.