Enhancement of the water solubility of flavone glycosides by disruption of molecular planarity of the aglycone moiety.

Enhancement of the water solubility by disruption of molecular planarity has recently been reviewed as a feasible approach in small-molecule drug discovery programs. We applied this strategy to some natural flavone glycosides, especially diosmin, a highly insoluble citroflavonoid prescribed as an oral phlebotropic drug. Disruption of planarity at the aglycone moiety by 3-bromination or chlorination afforded 3-bromo- and 3-chlorodiosmin, displaying a dramatic solubility increase compared with the parent compound.