Studies On The Addition Reaction Of Isoflavonoids With Methanol Promoted By Bromine

Isoflavonoids are important natural second metabolizability products.Thediversity of biological species results in the diversity of chemical structure andbiological activity of isoflavonoids, such as antioxidant, anti-inflammatory, anticancer,anti-hyperkinesias. Halogenated flavonoids are considered potential benzodiazepinereceptor ligands, possessing anxiolytic activity and low sedative or myorelaxant effects.Reports on the synthesis and biological activity of halogenated flavonoids are rare,which limits their wide application. Modifying isoflavones with chemical methods toafford more halogenated isoflavonoids for biologically active studies is not only theimportant task in today's research field but also the source to find new promising leadingcompound and biologically active components.Firstly, the structure, biological activity, applications, addition reaction ofisoflavonoids, and the biological activity of halogenated flavonoids were reviewed.Secondly, the addition reaction of 7 kinds of isoflavonoids with methanol promoted bybromine and the crystal structure of the corresponding addition products were studied. 9kinds of isoflavone addition products were synthesized and they are5',6,8-tribromo-2,3,4'-trimethoxyl-7-hydroxyisoflavanone (1), 3',5',6,8-tetrabromo-2,3-dimethoxyl-4',7-dihydroxyisoflavanone(2), 5',6,8-tribromo-2,3-dimethoxyl-4',7-diethoxyisoflavanone (3), 3',5',6-tribromo-2,3,7-trimethoxyl-4'-hydroxyisoflavanone (4),3',5',6,8-tetrabromo-2,3,7-trimethoxyl-4',5-dihydroxyisoflavanone(5), 5',6-dibromo-2,3,4',7-tetramethoxylisoflavanone(6), 5',6,8-tribromo-2,3,4',7-tetramethoxylisoflavanone(7),3',5',6,8-tetrabromo-2,3,4',7-tetramethoxylisoflavanone (8), 3,6,8-tribromo-2-methoxyl-7-isopropoxyisoflavanone (9), respectively. (1)～(9) are all new compounds, and theywere characterized by IR, ¹H NMR, ¹³C NMR, MS and elementary analysis. The crystalstructure of (1), (2), (4), (6) and (7) were determined by X-ray single-crystal diffractionanalysis, and the interaction of (2) with CT-DNA has been studied by the method of UVand fluorescence, the results show that there is strong interaction between (2) and DNA.The reaction of adding two methoxy groups to the double bond C₂=C₃ was first reportedand the reactive mechanism was discussed.Thirdly, in the addition reaction course of genistein with methanol, we found that the intermediate product: 3,3',5',6,8-pentabromo-2-methoxyl-4',5,7-trihydroxyisoflavanone did not convert to target addition product: 3',5',6,8-tetrabromo-2,3-dimethoxyl-4',5,7-trihydroxyisoflavanone, but gave benzfuran derivative [3,4-dihydrogen-3-(3',5'-dibromo-4'-hydroxyphenyl)-3-dimethoxylmethyl-5,7-dihydroxy-6, 8-dibromobenzfuran-4-ketone] (10) through a series of mucleophilic substitution reactionin acidic condition, (10) is a new compound, and the reactive mechanism was discussed.Last, in the course of proceeding hydrolysis and ammonolysis on the bromobenzylstructure of 3,6-dibromo-2-methoxy-7-isopropoxyisoflavanone, 3,8-dibromo-2-methoxy-7-isopropoxyisoflavanone or 3,6,8-thibromo-2-methoxy-7-isopropoxy-isoflavanone, we found that the stuff subjected to weak base, such as ammonia liquor,Na₂CO₃ or NaHCO₃, in the solution of ethanol-water could eliminate one methoxylgroup and one bromine anion to give products: 6-bromo-7-isopropoxyisoflavone (11),8-bromo-7-isopropoxyisoflavone (12) and 6,8-dibromo-7-isopropoxyisoflavone (13),respectively. The elimination products can further react in the ethanol-water solution ofstrong base to afford split-ring products.The properties and species of isoflavones were enriched by structural modificationof a series of isoflavones. Studies on the crystal structures of isoflavone derivativesprovided the theoretical foundations for developing and selecting high-technical newdugs.