Selective (a)-L-Rhamnosylation and Neuroprotective Activity Exploration of Cardiotonic Steroids

This work describes the studies on the direct C3-glycosylation of the C19-hydroxylated cardiotonic steroids strophanthidol, anhydro-ouabagenin and ouabagenin using a strategy based on in situ protection of the C5 and C19 hydroxyl groups with boronic acids. While this strategy resulted in a successful one-pot C3-selective glycosylation of strophanthidol and anhydro-ouabegenin, it failed to provide ouabain from ouabagenin. The neuroprotective activity of the synthetic and natural glyco-sides against LPS-induced neuroinflammation was explored in neonatal mice primary glia cells. Co-administration of natural and synthetic C3-glycosides at 200 nM concentrations resulted in the significant reduction of the LPS-induced neuroinflam-matory markers IL-6, IL-1, TNFα, and IKBKE, with the anhydro-ouabagenin-3-(a)-L-rhamnoside (anhydro-ouabain) show-ing the most significant effect. At the same time, unglycosylated anhydro-ouabagenin enhanced rather than suppressed LPS-induced neuroinflammation.