Synthesis And Insecticidal/Acaricidal Activities Of(E-Ring Halogenation) Podophyllotoxin-succinic Acid-amines Conjugates

Podophyllotoxin,a naturally lignan,is isolated from the plants of Sinopodophyllum.It shows antitumor,antiviral,anti-inflammatory,and insecticidal activities.In our previous papers,many podophyllotoxin derivatives were synthesized,and some compounds exhibited potent insecticidal activity.Herein,a series of(E-ring halogenation)podophyllotoxin-succinic acid-amines hybrids were prepared.Their insecticidal/acaricidal activities were tested against Mythimna separata and Tetranychus cinnabarinus.Some results were obtained as follows:1.Thirty derivatives(23 new compounds)were synthesized,including 7 intermediates and 23 target compounds,and characterized by ~1H NMR,HRMS,IR,and optical rotation.2.The antifeedant and insecticidal activities were tested against pre-third-instar larvae of M.separata at 1 mg/m L by the leaf-dipping method.Compounds Ia and Ie showed high antifeedant activity with 48 h antifeedant rates of 47.8%and 42.5%,respectively,which were higher than that of podophyllotoxin(34.8%).Compounds IIIc and IIId exhibited potent insecticidal activity with the final mortality rates of 65.5%and 69.0%,which were higher than those of podophyllotoxin(31.0%)and toosendanin(44.8%).3.The acaricidal activity was tested against female adults of T.cinnabarinus at 0.5mg/m L.Compounds 5,IIIa and IIIb showed high activity with 72 h mortality rates of 36.1%,31.3%and 29.6%,respectively.They were higher than that of podophyllotoxin(9.2%).The preliminary analysis of structure-activity relationship showed that the insecticidal and acaricidal activities of 2′,6′-dichloropodophyllotoxin derivatives were more poent than those of 2′-chloro/bromopodophyllotoxin,and introduction of n-butylamine or benzylamine at C-4 position of podophyllotoxins could improve the acaricidal activity.This will pave the way for further structural modifications of podophyllotoxins as insecticidal and acaricidal agents.