Selective (α)-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, -ouabagenin, and ouabagenin using a strategy based on 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 -ouabegenin, it failed to provide ouabain from ouabagenin. The neuroprotective activity of the synthetic and natural glycosides against LPS-induced neuroinflammation was explored in neonatal mouse primary glia cells. Co-administration of natural and synthetic C3-glycosides at 200 nM concentrations resulted in the significant reduction of the LPS-induced neuroinflammatory markers IL-6, IL-1, TNFα, and IKBKE, with the -ouabagenin-3-(α)-l-rhamnoside (-ouabain) showing the most significant effect. At the same time, unglycosylated -ouabagenin enhanced rather than suppressed LPS-induced neuroinflammation.