Study On Synthesis And Fungicidal Activity Of Isoxazole(lin) Containing Dihydrobenzofuran

Isoxazole and isoxazoline compounds have attracted more and more researchers’attention because of their excellent antibacterial activity.In this paper,two series of isoxazole and isoxazoline compounds were synthesized by[3+2]cycloaddition reaction with chalcone and hydroxylamine hydrochloride as raw materials.In order to find the isoxazoline compounds with good bactericidal activity,the isoxazole and isoxazoline compounds were synthesized from 2,3-dihydro-2,2-dimethyl-7-benzofuranol through four-step reaction,including methylation,acetylation,aldol condensation and1,3-dipolar cycloaddition.In the first step,the phenolic hydroxyl group of the benzofuranol was methylated by methyl iodide;In the second step,the methylation product 7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran（A）was acetylated by acetyl chloride to generate the1-（7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl）ethan-1-one（B）;In the third step,compound B and substituted benzaldehyde generate 1-（7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl）-3-substituted phenylprop-2-en-1-one（C）;In the end,chalcone（C）and hydroxylamine hydrochloride undergo[3+2]cycloaddition reaction to synthesize isoxazoles（D）and isoxazolines（E）respectively.The structures of the 22 synthesized compounds were characterized by ¹H NMR,¹³C NMR and HRMS,respectively,and their antibacterial activities were determined.Firstly,the antibacterial activities against Escherichia coli,Aeromonas salmonella were studied with microdilution method,and the results showed that the target compounds had weak antibacterial activity.Lately,we conducted the plant diseases antifungal experimental study on 22 compounds,taking the plant pathogenic fungi of Bacillus anthraci,Puccinia sorghi Schw and Pseudoperonospora cubensis as research objects.The final screening test results showed that the target compound had no activity against Bacillus anthraci and Puccinia sorghi Schw,but had good activity against Pseudoperonospora cubensis.When the substituent on the benzene ring of isoxazole and isoxazoline was 3-Br,the activity was the best,at 80%and 95%,respectively,almost equivalent to that of the positive control drug.Finally,The cytotoxic activity of the compounds was tested and the target compounds tested were found to have low cytotoxicity to cells.Molecular docking was performed on the synthesized target compound E2,and it was found that the target for inhibiting Pseudoperonospora cubensis might be succinic dehydrogenase.