Synthesis And Insecticidal Activity Of Novel Isoxazolines And Oxime Sulfonates Of Podophyllotoxin With E-ring Halogenation

In recent years,people have put forward higher requirements for the development of new pesticides due to the negative impact of chemical pesticides.The development of high efficient,low residue,and environmentally friendly pesticides has been one of the research topics.Podophyllotoxin,a natural plant product,exhibits a variety of biological activities.In order to further clarify the relationship between the structure and insecticidal activity of podophyllotoxin derivatives,we designed and synthesized a series of 2?(2?,6?)-(di)halogeno-isoxazolopodophyllic acids-based esters,and oxime sulfonates of 2?(2?,6?)-(di)halogenopodophyllones.Some results were obtained as follows:1.Twenty-seven podophyllotoxin derivatives,2?(2?,6?)-(di)halogeno-isoxazolopodophyllic acids-based esters and oxime sulfonates of 2?(2?,6?)-(di)halogenopodophyllones,and nine intermediates were prepared.Their structures were all characterized by 1H NMR,HRMS,mp,IR,and optical rotation.The steric structures of Ie,IIe and IIIb were well determined by single-crystal X-ray diffraction analysis.Thirty-one derivatives were new compounds.2.Their insecticidal activity was evaluated at 1 mg/mL against the pre-third-instar larvae of Mythimna separata(oriental armyworm).The results showed that compounds 9,?a,?b,?c,?f,?c,?e and ?b,?c,?c,?c showed higher insecticidal activity than the positive control toosendanin.3.During the bioassay,the symptoms of the treated M.separata were observed: many larvae of the treated groups died slowly during the larval stage;some malformed pupae of the treated groups also appeared and died during the pupation stage;some malformed moths with imperfect wings also appeared in the treated groups.4.The structure-activity analysis showed that introduction of the chlorine or bromine atom at the C-2' or C-2',6' position on the E ring of picropodophyllotoxins could improve the insecticidal activity;among 2?(2?,6?)-(di)halogeno-isoxazolopodophyllic acids-based esters,derivatives containing the n-butyl displayed the best insecticidal activity;among oxime sulfonates of 2?(2?,6?)-(di)halogenopodophyllones,introduction of a bromine atom on the phenyl can greatly improve the insecticidal activity.In conclusion,some prepared podophyllotoxin derivatives have a great advantage on insecticidal activity,and the final mortality rate of compound ?c was 65.2%.Moreover,some interesting results of structure-insecticidal activity relationships of 2?(2?,6?)-(di)halogeno-isoxazolopodophyllic acids-based esters,and oxime sulfonates of 2?(2?,6?)-(di)halogenopodophyllones were observed.This will pave the way for further design and structural modifications of podophyllotoxin derivatives as insecticidal agents.