Structure Modification And Bioactivity Of Natural Active Compound Daphneolone

The structural modification of bioactive nature products from plants is a very efficient way in new pesticide discovery. Stellera chamaejasma L., which is a kind of traditional plant in China, drawed many chemists' attentions for its wide pharmaceutical and agricultural bioactivities. In order to explore novel Daphneolone analogues with high activities, using Daphneolone A- (E)-1,5-diphenyl-2-penten-l-one from Stellera chamaejasma L. as the lead compound, four series with 131 compounds were designed and synthesized according to introducing the chomone fragments and bioisosteres. The structures of all compounds were confirmed by 1H NMR(13C NMR), IR, HRMS or elemental analysis.In this thesis the main achievements are summarized as follows:(1) Taking the natural product Daphneolone A as the lead compound, 2-(2-phenylethtyl) chromone analogues (series ?) were prepared by insertion of chromone fragment through O-bridge bond. On study of fungicidal activity in vitro, series ? showed enhanced activity caused by the insertion of chromone.Especially, compound ?-09, with EC50 of 16.5 mg/L and 25.4 mg/L against Rhizoctonia solani and Botrytis cinerea,is valuable for further study. The preliminary SAR analysis showed that the insertion of chromone could improve fungicidal activities comparing with Daphneolone A. When R1 was H, R2,which was smaller alkyl group or halogen, especially fluorine, could improve fungicidal activities.(2) Taking the natural product Daphneolone A as the lead compound, Pyridino-pyranone analogues(series ?) was designed by insertion of chromone containing pyridine through O-bridge bond. And the crystal structure of the typical compound ?-28 was identified by X-Ray. The preliminary bioassay results indicated that some compounds showed moderate to good fungicidal activity against Botrytis cinerea at 100 mg/L. Inspiringly, EC50 of compound ?-01 equaled 8.0 mg/L. The preliminary SAR analysis showed that the insertion of pyridine-chromone could improve fungicidal activity against Botrytis cinerea. When R1 was H or OCH3, X, which was heterocycle, could improve fungicidal activities.(3) With natural product Daphneolone A as lead compound,(4-oxo-4H-chromen -3-yl) methyl cinnamate analogues (series ?) were designed by using ester bond to keep the chain length of C6-C5-C6 and replacing phenyl with the chromone fragments. The preliminary bioassay results indicated that most compounds showed low fungicidal activities in vitro at 100 mg/L but compound?-13 exhibited better activity than the lead A. The preliminary SAR analysis showed the insertion of chromone by ester bond could not improve the fungicidal activity obviously, but the insertion of thiophene ring can improve the fungicidal activity.(4) According to bioisosterism, quinazolin-4(3H)-ylidenes (series ?-A) and benzo[a]carbazoles(series IV-B) were designed and synthesized by copper-catalyst. The synthesis method of series IV was very important in organic methodology. Firstly, a new "one pot" copper-catalyzed method for synthesis of quinazolin-4(3H)-ylidene derivatives was developed. The reaction condition was very simple and effic ient at room temperature without ligand loadings. Secondly,a novel simple and efficient copper-catalyzed method for the synthesis of benzo[a]carbazole analogues was developed under mild conditions. And it was the first report that copper-catalyzed a-C-arylation of ketones and two C-C bond formations with "one pot" in the synthesis of benzo[a]carbazoles. The preliminary bioassay results indicated that series ?-A showed better fungicidal activity than Daphneolone A against Colletotrichum lagenarium at 100 mg/L. The results were valuable for further structural modification.