Design,Synthesis,and Biological Evaluation Of Novel Sarisan Analogues Containing 1,3,4-oxadiazole/N-phenylpyrazole

Using of natural products as lead compounds is one of major approaches to develop novel drugs or pesticides.Sarisan clould be isolated from many species of plants and has a variety of biological activities in the field of medicine and agriculture.Two series of 41 novel sarisan analogues containing 1,3,4-oxadiazole/ N-phenylpyrazole were designed and synthesized through iodine-catalyzed oxidative cyclisation.For the sarisan analogues containing 1,3,4-oxadiazole,we evaluated for their insecticidal activities against the pre-third Mythimna separata Walker at 1 mg/mL and inhibitory activities against five phytopathogenic fungi at 50 ?g/mL.The results showed that compound 8r,8t,8k and 8q exhibited potent insecticidal activities with final mortality rates(FMRs)of >60%,when compared with sarisan and toosendanin(a commercial insecticide),Among them,compound 8r exhibited the best insecticidal activity with final mortality rate(FMR)of 69.0%;Compound 8e,8p,8r showed more promising antifungal activities against phytopathogenic fungi.Among them,the inhibition rates of compound 8p,8r against Valsa mali Miyabe et Yamada reached 70.9% and 69.7%.The structure-activity relationships indicated that introduction of fluorophenyl or 4-cyanophenyl unit on the 1,3,4-oxadiazole ring at the C-3 position of sarisan could afford more potent compounds.Moreover,introduction of heteroaromatic fragments on the 1,3,4-oxadiazole ring at the C-3 position of sarisan was very crucial for the insecticidal and antifungal activities.For the sarisan analogues containing N-phenylpyrazole,we evaluated for their insecticidal activities against the pre-third Mythimna separata Walker at 1 mg/mL and inhibitory activities against six Gram-positive/ negative bacterial strains.The results showed that compounds 8l-r exhibited more promising insecticidal activity with the final mortalityrates(FMRs)>62.1%,when compared with the positive control toosendanin.Especially,compound 8r with 2-fluoro-4-bromophenyl showed the most potent insecticidal activity,the FMR of which was 79.3%.Futhermore,only compound 11 o,11p showed moderate antibacterial activity against Enterococcus faecalis with MIC50 value of 64 ?g/mL.The other compounds exhibited poor antibacterial activity with MIC50 values ? 128 ?g/mL.Moreover,the structure-activity relationships suggested that introduction of N-(fluorophenyl)pyrazole and polyhalogenated phenylpyrazole at the C-3 position of sarisan could lead to more potent compounds with better insecticidal activity.