Synthesis And Insecticidal Activity Of6,7-O,O-disubstituted-4-acyloxypodophyllotoxin

Discovery of new medicinal compounds by using natural plant products as thelead-compounds for structural modification has recently been one of the important proceduresfor research and development of new drugs. It is well-known that podophyllotoxin derivativesdisplayed good antitumor and antiviral activities, and some drugs such as VP-16and VM-26have been used on the clinic in the treatment of solid tumor. Meanwhile, podophyllotoxinderivatives showed the interesting insecticidal activities. In order to investigate therelationship between the insecticidal activities and chemical structures of podophyllotoxinderivatives, we designed and synthesized4series of31podophyllotoxin derivatives, in which27compounds have not been reported. The structures of these compounds were wellcharacterized by1H NMR, IR, optical rotation and m.p., and the purity of these compoundswas above95%determined by HPLC.When6and carboxylic acid reacted in the presence of N, N-dicyclohexylcarbodiimide(DIC) and dimethylaminopyridine (DMAP), only C-4α-substituted esters were obtained;whereas when6and carboxylic acid reacted in the presence of BF3Et2O, the isomer mixtures,i.e., C-4α/β-substituted esters, were produced.The insecticidal activity of all31compounds against the pre-third-instar larvae ofMythimna separata Walker was evaluated by leaf-dipping method at the concentration of1mg/mL, and the toosendanin was used as a positive control. Most of compounds showed poorantifeedant activities compared with toosendanin.6compounds (8e，8g，8j，9d，9f，and11g)showed more potent or comparable insecticidal activity to toosendanin.It revealed the proper length of the side chain to alkylacyloxy series was essential fortheir insecticidal activity, the6,7-dihydroxy of5should not be free, and the C-4position ofpodophyllotoxin was the important modification location.