Biomimetic Design,Synthesis And Acaricidal Activity Of 1-phenyl-?,?-unsaturated Ketone Compounds

Natural products with 1-phenyl-?,?-unsaturated ketone such as Chalcone,flavones,and 1,5-diphenyl-2-penten-1-one(which is isolated from Stellera chamaejasme L.)are widely distributed in nature.Their excellent bioactivities like anti-bacteria,anti-tumor,anti-parasitic and antioxidant are reported in various research papers.However,there is no research on their acaricidal activity against Psoroptes cuniculi,a parasite which does harm to breeding industry.Acaricidal activity against Psoroptidae cuniculi of all synthesized compounds was assayed and the preliminary structure activity relationship was discussed.The details and the most important result of the thesis are listed as follows.1.23 compounds of the structure of 1-phenyl-?,?-unsaturated ketone were synthesized.Wittig reaction was used as the main method to synthesize 13(E)-compounds and 4(Z)-compounds.Besides,the carbonyl and double bond of ?,?-unsaturated ketone were reduced respectively to obtain 6 target compounds.The structures of all target molecules were characterized by 1H NMR,13 C NMR and MS,respectively.2.Through referring Horner-Wadsworth-Emmons reaction,a new method to obtain sufficient amount(Z)-compounds was found.In contrast with Wittig reaction,the ratio of(Z)-compounds was significantly increased.3.Acaricidal activity in vitro against Psoroptes cuniculi of target compounds was assayed by dipping mite method.At the concentration of 200 ?g/mL,compounds of 2,3,4,5,6,18,and 19 revealed good activity with death rate between 70.0%–100.0% and significantly higher than that of Ivermectin(50.0%).The lethal concentration of 50%(LC50)and lethal time of 50%(LT50)of these compounds was obtained through toxic evaluation.LC50 was 43.75 –111.94 ?g/mL,which was lower than that of Ivermectin(247.40 ?g/m L).LT50 of compound 4 and 5 were 48.5 min,and 20–30 min respectively which were smaller than that of Ivermectin(137.6 min)at the concentration of 2.0 mM.4.The preliminary structure-activity relationship of acaricidal activity was discussed.With the increase of the carbon chain's length,acaricidal activity of compound increased at first and then decreased generally.The activity of straight-chain compounds is significantly higher than that of branched compounds.The acricidal activity of(E)-isomer was stronger than its corresponding(Z)-isomer.The ?,?-unsaturated ketone was a necessary group to improve the activity.Changing the position of carbonyl and double bond reduced acaricidal activity.In summary,this study found a series of compounds with high acaricidal activity.We can increase the substituent on the phernyl ring to establish entire structure-activity relationship for further research.We also can do some experiment of acarcicidal activity in vivo against psoroptes cuniculi.