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, 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 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 anhydro-ouabagenin-3-(α)-l-rhamnoside (anhydro-ouabain) showing the most significant effect. At the same time, unglycosylated anhydro-ouabagenin enhanced rather than suppressed LPS-induced neuroinflammation.

Development of Recyclable Polystyrene-Supported Phosphonic Acid Resins for Carbohydrate Immobilization and Glycosylation.

This article describes the development of a recyclable polystyrene-based phosphonic acid resin and its use for the synthesis of immobilized glycosyl phosphonate donors and subsequent glycosylation reaction. This solid support was generated on a decagram scale from the commercially available Merrifield resin and subsequently functionalized via two different methods into eight different glycosylphosphonates. The resultant glycosylphosphonate-containing resins were obtained in 59-96% yields and were found to be bench-stable at room temperature. These donors could be activated using trifluoroborane etherate at 80 °C to react with various alcohol- and thiol-based acceptors to provide 17 different glycosides in good-to-excellent yields (53-98%). In addition, it was demonstrated that glycosylated resin could be recovered and recycled multiple times to regenerate immobilized glycosylphosphonate donors and could be subjected to on-resin glycan elongation.

Recent Progress in Steroid Synthesis Triggered by the Emergence of New Catalytic Methods.

The rich biology associated with steroids dictates a growing demand for the new synthetic strategies that would improve the access to natural and unnatural representatives of this family. The recent advances in the field of catalysis have greatly impacted the field of natural product synthesis including the synthesis of steroids. This article provides a short overview of the recent progress in the synthesis of steroids that was enabled by the advances in catalysis.