Synthesis Of Cholesterol Ester Derivatives Containing Isoxazoline/Isoxazole Fragments And Their Insecticidal Activities

Due to the“3R”problems raised by unreasonable application of synthetic pesticides,the development of new pesticide candidates from natural bioactive products has received extensive attention.In this paper,terminal double/triple bonds were firstly introduced at the C-3 position of cholesterol,and then a series of novel cholesterol ester derivatives containing isoxazoline/isoxazole fragments were constructed by 1,3-dipolar cycloaddition reaction.Their agricultural activities were evaluated against Mythimna separata,Plutella xylostella and Aphis citricola.The main results were as follows:（1）40 novel cholesterol ester derivatives containing isoxazoline/isoxazole fragments（Ia-It and IIa-IIt）were constructed from cholesterol（1）as a lead compound.Their structures were confirmed by ¹H NMR,IR and HRMS.（2）Compound Ii exhibited the most pronounced insecticidal activity with the final corrected mortality rate of 67.8%against M.separata at 1 mg/m L,which was significantly higher than that of toosendanin（42.8%）and displayed 3.2-fold activity of cholesterol（21.4%）.The 48 h corrected mortality rates of Ie,IIe,IIf and IIr were 50.0%-54.5%against P.xyllostella at 1 mg/m L,and compound IIe(LC₅₀:0.794 mg/m L)had the best activity,which was 3.2-fold oral toxicity than that of cholesterol(LC₅₀:2.566 mg/m L);The 48 h corrected mortality rate of IIf was 49.4%against A.citricola at 0.04μg/nymph and showed better aphicidal activity than cholesterol（13.8%）.Its LD₅₀value was 0.039μg/nymph,which was 5.8-fold activity of that of cholesterol(LD₅₀:0.228μg/nymph).（3）For some isoxazoline derivatives containing aromatic substituents,when the halogen atom（F,Cl,or Br）at the ortho position of phenyl showed that a strong electron-withdrawing effect（-F>-Cl>-Br）with the insecticidal activity against M.separata:for example,the final corrected mortality rates of compounds Ih（R=2-FPh）,Ic（R=2-Cl Ph）and Il（R=2-Br Ph）were 42.8%,39.2%,and 28.5%,respectively.However,derivatives with the halogen atom at the para position of phenyl showed a strong electron-withdrawing effect with the aphicidal activity against A.citricola:for example,the48 h corrected mortality rates of If（R=4-FPh）,Ia（R=4-Cl Ph）and Id（R=4-Br Ph）were45.9%,40.2%and 29.9%,respectively.The introduction of the Br atom at the meta position of phenyl can significantly improve the insecticidal activity against M.separata and P.xyllostella（Lepidopteran）,when compared with the aphicidal activity against A.citricola（Homopteran）.For example,the 48 h corrected mortality rates of Ie（R=3-Br Ph）and IIe（R=3-Br Ph）were all 60.7%against M.separata;the 48 h corrected mortality rates of Ie and IIe were 52.2%and 54.5%against P.xyllostella;however,the 48 h corrected mortality rates of Ie and IIe was only 34.5%and 27.6%against A.citricola.Introduction of a strong electron-withdrawing group-CF₃and a F atom on the phenyl was beneficial to the insecticidal activities against M.separata and A.citricola.The 48 h corrected mortality rates of It and IIt（R as naphthalene ring）was 47.7%and 40.9%against P.xyllostella.They showed 2.0 and 2.3 folds insecticidal activity of precursor cholesterol（20.4%）.