Synthesis And Acaricidal Activity Of (E)-Ethyl Cinnamate Derivatives

Cinnamic acids and their derivatives(mainly cinnamtates), which are widely distributed in natural world, are phenylpropanoids. Their excellent bioactivities like antimicrobial, insectcidal, antitumor and antioxidant have been shown in large quantities of research papers. However, there is no systematic research on their acaricidal activity against Psoroptes cuniculi, a parasite which does harm to breeding industry. There are many developed synthetic methods of cinnamaic acids and cinnamates, but the problems of synthetic and aftertreatment method still exist. Based on present work, a series of(E)-ethyl cinnamte derivatives were synthesized. Besides, the reaction condition and aftertreatment were also improved. Finally, acarcidal activity against Psoroptes cuniculi of synthesized compounds was assayed and the preliminary structure-activity relationship was discussed.The details and the most important results of the thesis are listed below.1. Wittig reaction was used as the main method to synthesize 18 kinds of(E)-ethyl cinnamates with substituted benzaldehydes and ylide called Carbethoxymethylene triphenylphosphorane were used as reactants. Besides, 4 target compounds were synthesized by methylation or acetoxylation of compounds with hydroxy. Afterwards, the structure of all 22 compounds was characterised by 1H NMR, 13 C NMR and ESI-MS, respectively.2. The condition and aftertreatment method of Wittig reaction were improved. Ethanol absolute or toluene was selected as reaction solvent. For the most part, the reaction time was short and reuqired 0.5 to 1 h only under the reaction temperature was 90℃ or 120℃. Besides, the conversion ratio of product was high. The primary product(E)-ethyl cinnamate derivatives and byproduct triphenylphosphine oxide could be seperated completely through short silicagel column chromotography.3. Acaricidal activity in vitro against Psoroptes cuniculi of(Z)-ethyl cinnamate,(E)-ethyl cinnamate and its derivatives, and ethyl 3-phenylpropionate was assayed by dipping mite method. The the preliminary screening result of acaricidal assay showed that EC-09, EC-20, EC-21, EC and EP possessed obvious activity. At 0.25 mg/mL, their Psorotpes cuniculi death rates were 73.3%~100.0% and significantly higher than that of ivermectin(45.0%), a commercial drug. Besides, The median lethal concentration(LC50) values of five compounds described above were 29.68~118.96 μg/mL, which were lower than the value of ivermectin(247.40 μg/mL). Their median lethal time(LT50) values were 7.94~11.00 h, and they were smaller or similar with that of ivermectin(8.90 h) at 4.5 μmol/mL.4. The preliminary structure-activity relationship of ethyl cinnamate and its derivatives on their acaricidal activity was discussed. The presence of o-NO2 or m-NO2 on the benzene ring led to significant improvement of the activity. In contrast, electro donating group(hydroxy, methoxy, acetoxy, methylenedioxy), chloro or bromo reduced activity. The acricidal activity of(E)-isomer was stronger than its corresponding(Z)-isomer. Nevertheless, the trans-carbon–carbon double bond was not a necessary group to improve the activity.5. EC-20 was selected for preparation with 6 mg/mL and acarcicidal activity in vivo against psoroptes cuniculi for sicked rabbit was assayed. Subcutaneous injection test showed the compound had no toxicity and treatment on rabbit, while impregnating method could effectively eliminante psoroptes cuniculi from rabbit’s ear.