Transformations Of Three Natural Furan-based Compounds And Their Insecticidal Activity

Furan ring as an important pharmacophore is present in a variety of natural products.Transformations that chem-and regio-selectively modify the furan ring might be useful in the synthesis of biological probes from active natural products.Fraxinellone,obacunon and limonin are the furan ring compounds extracted from Meliaceae and Rutaceae plants,and they exhibit insecticidal,antibacterial,anti-inflammatory activities.In this study,the furan rings of these three types of natural products were synthesized by bromination,Pd-catalyzed coupling,and three-membered cyclization.All derivatives were systematically evaluated for insecticidal activity against the third-instar armyworm,expecting to obtain new pesticides with high insecticidal activity.The key findings are as follows:（1）For brominating conditions of fraxinellone furan ring,it was found that increasing the temperature up to 40^oC can effectively avoid the by-products;the yield of monobrominated product 5 can reach 62%at 40 ^oC;while 1.4 equivalent of 1,3-dibromo-5,5-dimethylhydantoin（DBDMH）was used as a brominating reagent,the mixture was stirred at 40^oC in the dark,and the reaction selectively produced a dibrominated product with a yield of 91%.This reaction condition was applied to the bromonation of limonin and obacunon,and the target product was obtained in 99%and 60%yield,respectively,indicating the brominating condition might be universal to furan ring compounds.（2）A series of aliphatic and aromatic rings were introduced into the furan ring by Pd-catalyzed Suzuki and Sonogashira coupling reactions,and the yields of the derivatives 3a and 4a of the fraxinellone reached 95%and 98%,respectively.In addition,three furan ring C-4’and C-5’double bonds were successfully three-membered cyclized by the reaction ofα-carbonyl diazonium with fraxinellone.,The ¹H NMR,¹³C NMR and HRESIMS techniques were used to characterize 46 derivatives,of which 43 were new compounds.of which 43 were new compounds.The structure of the three derivatives was analyzed by X-ray diffraction.（3）The insecticidal activity of all derivatives against the pre-third-instar larvae of M.separata in vivo was evaluated by the leaf-dipping method.The results showed that all of the derivatives exhibited the delayed insecticidal activity against M.separata,of which the fraxinellone derivatives 2,3b,3g,5a,5d,5h,10c and the obacunon derivatives 3e,3f,3g exhibited higher insecticidal activity than their precursors and the positive control toosendanin.The antifeedant rate（48 h）of reduced derivative 2 reached 96.8%,which was better than83.4%of toosendanin and 71.6%of fraxinellone.The inhibitory rate of compound 2 and 5d on growth and development of armyworm was also significantly higher than that of toosendanin.By observing the morphology of the armyworm we also found that many compounds exhibited potential teratogenic activity.In summary,this study focused on transformation the furan ring of three natural products through Pd catalytic conversion and cyclopropanation reaction and their insecticidal activity.Furan-site bromination conditions were optimized,and 43 new analogues were synthesized.All derivatives were systematically investigated for insecticidal activity against the third-instar armyworm,and a number of candidate molecules with good development potential were found.These results provided basis for the structural modification of based-furan natural products and the research and development of new insecticides.