Studies On Synthesis And Pharmacological Action Of Flavonoids Derivatives

As a classical type important natural organic compounds producedduring plants metabolism, flavonoid is of great significance to cure, treat and preventtumour, senescence and cardiovascular diseases. Flavonoid has been the potentialsource in the search of leading compounds and biologically active components and hasalso been the emphasis of the research, development and utilization at home and aboardin the recent 30 years. However, their biological utilization rates are low and the dosesare high for their poor solubilities, which limit their wide applications. Modifying theFlavonoid with chemical methods and enriching the species and properties of them arethe important tasks in today's research field. Structure modification, which can improvethe solubility of the Flavonoid, is an important way in exploring new drugs. In order tostudy the hydroxymethylation and their pharmacological action, 10 kinds of flavonehydroxymethylation derivatives and 2 kinds of single crystals were synthesized anddetermined, their interaction with DNA and the anti-anoxia experiment were studied.Firstly, the structure and classification, properties and applications of flavonoid, thephysiological activity and pharmacological action of chrysin, baicalein and daidzein andthe hydroxymethylation of phenol are summarized.Secondly, chrysin, baicalein and daidzein, as the leading compounds, weremodified. 5,7-dihydroxy-6,8-bis(hydroxymethyl)flavone(1), 5,7-dihydroxy-6,8-bis(methoxymethyl)flavone(2), 6,8-bis(ethoxymethyl)-5,7-dihydroxyflavone(3), 6,8-bis-(butoxymethyl)-5,7-dihydroxyflavone(4), 6,8-bis(pentyloxymethyl)flavone(5), 6,8-bis-(ethoxymethyl)-5-hydroxy-7-methoxyflavone(6), 5,5',6,6',7,7'-six-hydroxy-8,8'-methylene-bis-flavone(7), 8,3',5'-tris-(hydroxymethyl)isoflavone(8), 4',7-bis-(acetyl oxide)-8,3',5'-tris-(acetoxymethyl)isoflavone(9) and 4',7-bis-(hydroxyl)-3',5'-diisopropyl-8-hydroxymethylisoflavone(10) were synthesized and characterized by IR, ¹H NMR and¹³C NMR. Among of them, 6,8-bis-(ethoxymethyl)-5-hydroxy-7-methoxyflavone and4',7-bis-(acetyl oxide)-8,3',5'-tris-(acetoxymethyl)isoflavone were determined by X-raysingle-crystal diffraction analysis.Finally, the interaction of 5,7-dihydroxy-6,8-bis(hydroxymethyl)flavone,5,7-dihydroxy-6,8-bis(methoxymethyl)flavone, 6,8-bis(ethoxymethyl)-5,7-dihydroxy- flavone, and 6,8-bis-(butoxymethyl)-5,7-dihydroxyflavone with CT-DNA was studiedby Fluorescent spectroscopy. According to the Stern-Volmer equation their quenchingconstants were measured. The conclusion is that their unions with CT-DNA are allstronger than chrysin. Meanwhile carried on the anti-anoxia experiment to them, Theresult indicate that, the chrysin hydroxymethylation derivatives can significantlyprolong the gasp duration of decapitative mice, extend the survival time of mice whichhave been poisoned by erinitrit and the cardiac-specific hypoxia mouse survival time, inwhich 5,7-dihydroxy-6,8-bis(hydroxymethyl)flavone have good effect.Studies on synthesis and pharmacological action of chrysin, baicalein and daidzeinderivatives not only enrich the properties and species of flavonoid, but also supply thetheoretical foundations for further developing the new drug.