Studies On Sulfonation Reaction Of Flavonoid And Their Derivatives' Crystal Structures

As a classical type important natural organic compounds produced during plants metabolism, flavonoid is of great significance to cure, treat and prevent tumour, senescence and cardiovascular diseases. Flavonoid has been the potential source in the search of leading compounds and biologically active components and has also been the emphasis of the research, development and utilization at home and aboard in the recent 30 years.Firstly, the structure and classification, properties and applications of flavonoid are summarized. The regularity of sulfonation reaction of flavonoid is discussed by studying references at home and aboard. At the same time, the flavonoid sulfo-group and the metal ions self-assembled mainly by the action of hydrogen bonding and aromatic stacking is also introduced.Secondly, chrysin and apigenin, as the leading compounds, were modified. 5-hydroxy-7-methoxyflavone, 5-hydroxy-7-ethoxyflavone, 5,7-dihydroxy-4 '-methoxy-flavone, 5-hydroxy-7,4'-dimethoxyflavone and 5-hydroxy-7,4'-diethoxyflavone, sodium 5-hydroxy-7-methoxyflavone-4'-sulfonate and sodium 5-hydroxy-7,4'-dimethoxy-flavone-3'-sulfonate were synthesized and characterized by IR and ~1H NMR. Among of them, 5-hydroxy-7,4'-dimethoxyflavone and 5-hydroxy-7,4'-diethoxyflavone were determined by X-ray single-crystal diffraction analysis.Finally, four isoflavone sulfonate, sodium 7,4'-dihydroxyisoflavone-3'-sulfonate, sodium 4'-hydroxy-7-methoxyisoflavone-3'-sulfonate, sodium 7,4'-dimethoxy-isoflavone-3 '-sulfonate and sodium 7,4'-diethoxyisoflavone-3'-sulfonate were assembled with different metal ions or amine salt. Eight compounds were obtained, they are methylaminium 7,4'-dihydroxyisoflavone-3 '-sulfonate dihydrate (1), hexaaqua-copper(II) bis(7-methoxy-4'-hydroxyisoflavone-3'-sulfonate) decahydrate (2), ethylene-diamine bis(7-methoxy-4'-hydroxyisoflavone-3 '-sulfonate) dihydrate (3), hexaaquairon (II) bis(7,4'-dimethoxyisoflavone-3 '-sulfonate) octahydrate (4), hexaaquamagnesium(II) bis(7,4'-dimethoxyisoflavone-3'-sulfonate) octahydrate (5), methylaminium 7,4'-dimethoxyisoflavone-3'-sulfonate monohydrate (6), hexaaquairon(II) bis(7,4'-diethoxy-isoflavone-3'-sulfonate) tetrahydrate (7) and ammonium, diethylamine bis(7,4'-di-ethoxyisoflavone-3'-sulfonate) pentahydrate (8). Crystal structures of 1-8 were determined by X-ray single-crystal diffraction analysis. Many classical O—H—O> N— H-0 hydrogen bonding and C — H—O soft hydrogen bonding existed among sulfo-group, latticed water molecules, coordinated water molecules and hydroxyl groups, which formed a hydrophilic region. The n—n stacking or C—H'"tc interactions existed between the isoflavone skeletons, which formed a hydrophobic region. The sulfo-group was a vital bridge between the hydrophilic region and the hydrophobic region. The hydrogen bonding, aromatic stacking and the electrostatic interactions between the cations and the anions lead the sulfonated isoflavone into supermolecule with a three-dimensional structure.By modifying the chrysin, apigenin and studies on the crystal structures of sulfonated flavonoid not only enrich the properties and species of flavonoid, but also supply the theoretical foundations for further developing the new drug.