Synthesis, Reaction And Properties Of Novel Flavonoids

Flavonoids are widely distributed diverse groups of plant secondary metabolites with widespread biological activities. Many of them have been used as medicine and pesticide. In order to search highly biological activities flavonoids, the reformation of the structure goes on in parallel with the separation of new flavonoids form plants. Since 1990s, pesticide has entered into a new period, heterocyclic compounds era. Heterocyclic compounds attracted significant interest of chemists due to its widespread and highly biological activities. For the low activities of flavonoids, we designed and synthesized six series of 233 novel heterocyclic flavonoids by introduction of thiazole, pyrazole and pyridazine in order to search new lead compounds with highly activities. At the same time, we explored the efficient methods for the preparation of flavonoids. It may be summarized as follows:(1) On the basis of the principle of combination of active groups, it is the first report about the application of liquid-phase combinatorial parallel synthesis under microwave irradiation to construct a library of 2-(4-oxo-4H-1-benzopyran-3-yl)-4-thiazolidinones with insecticidal activity by fusing a thiazolidinone to the flavonoid skeleton, using 3-formyl chromone, primary amine and mercaptoacetic acid as reactants. Compared with an identical library generated by conventional parallel synthesis, the microwave-assisted parallel synthesis approach dramatically decreased the reaction time, and substantially increased the product yields.The bioassay showed that they not exhibit obviously herbicidal activity and fungicidal activity but insecticidal activity. Five of them exhibited beyond 70% inhibition of Tetranychus cinnabarnus in 250 mg.L^-1. The best one was compound 2-9 c which exhibited 90.5 % inhibition of Tetranychus cinnabarnus. At the same time, the biological activities of N'-((4-oxo-4H- chromen-3-yl) methylene) acyl hydrazone derivatives were also studied. The results showed that they exhibited middling fungicidal activity and insecticidal activity.(2) On the basis of the principle of combination of active groups, it is the first report that a rapid library-generation via liquid-phase multiple-parallel synthesis of 2-(substituted)benzyl-1-benzopyrano [4,3-c] pyrazol-3-ones with insecticidal activity by fusing a pyrazol-3-one to the flavonoid skeleton under microwave irradiation was successfully performed using chromenone-3-carboxylic acids as starting materials. Compared with an identical library generated by conventional parallel synthesis, microwave-assisted parallel synthesis dramatically decreased reaction time from an average of 16 h to 13 min, and the yields of products and intermediates were improved in most cases. A bioassay indicated that the compounds of the library exhibited excellent insectidal activity aginst T cinnabarinus at the dosage of 250 mg.L^-1, and some compounds still exhibited insecticidal activity when the dosage was reduced to 50 mg.L^-1. This showed that 2-(substituted) benzyl-1-benzopyrano [4, 3-c] pyrazol-3-ones might be used as lead structures for further optimization. (3) Benzopyrano- [4,3-c] pyrazol-3-ones was identified as lead compounds for further studies. And four series of 115 novel heterocyclic flavonoids was designed and synthesized. But, the bioassay indicated only IV series compounds showed middling insecticidal activity. III and VI series compounds showed feeble insecticidal activity but middling fungicidal activity.(4) We developed a new efficient methods for the preparation of (3-hydroxybenzofuran-2-yl) (phenyl) methanone derivatives. (3-Hydroxybenzofuran-2-yl) (Phenyl) methanone derivatives were synthesized in a one step substitution cylization reaction of 2-bromo-1-phenylethanone and methyl 2-hydroxybenzoate in the presence of potassium carbonate. Compared with old methods, it reduces the steps and substantially increased the product yields.(5) We developed a new efficient methods for the preparation of methyl 4-oxo-4H-chromene-3-carboxylate derivatives. Methyl 4-oxo-4H-chromene-3- carboxylate derivatives were synthesized in excellent yields via a one step cylization reaction of ethyl 3-(2-hydroxyphenyl)-3- oxopropanoate and triethyl orthoformate.(6) On the base of a serier of crystal VI, the effects of substituents on molecule configuration and the structure of solid supermolecule crystals were studied. The properties of substituents have tremendous influence on the aromaticÏ€-Ï€stacking interactions. The aromaticÏ€-Ï€stacking interactions was weakened by introducing the electron drawing substituents. However, the aromaticÏ€-Ï€stacking interactions was strengthened by introducing the donating drawing substituents. At the same time, the molecular configurations also have tremendous influence on the structure of solid supermolecule crystals. When the donating drawing substituents shows trans configurations with furan ring, the molecules generates an dimer embosomed with each other by aromaticÏ€-Ï€stacking interactions. The phenomena shall be demonstrated later by a mass of experiments.(7) We presented the first report of a highly selective transformation of flavanones to 3-bromoflavones or flavones by using N-bromosuccinimide (NBS) as a brominating reagent in the presence of catalytic amount of 2, 2'-azobis (isobutyronitrile) (AIBN) under microwave irradiation. The combination of excellent yields, shorter reaction time (10 min), and high levels of functional group compatibility makes this an attractive synthetic approach to 3-bromoflavones and flavones.(8) We presented the first report of microwave-assisted intramolecular Stetter reaction using imidazolium-type room temperature ionic liquids (RTILs) as solvents, with thiazolium salts and Et₃N as catalysts. The features such as excellent yields, shorter reaction time (5 20 min), and recyclable and reusable ionic liquid and catalyst make this method an environmentally benign and highly efficient procedure for the preparation of chromanone derivatives.