Synthesizing Analogues Of Spiromesifen And Milbemycin And Their Bioactivity Evaluation

Owing to some special and excellent feature, spiral cycle compounds, especially spiral heterocyclic compounds, have been playing an important role in the new pharmaceutical and pesticides development. In recent years, there has little spiral cycle pesticides been developed in domestic and international market. Interestingly, Spiromesifen, developed by Bayer CropScience, is a new insecticide and miticide with class ketoenol structure and bioactive against white flies and spider mites. Because of its novel mode of action and excellent biological activities, Spiromesifen becomes an ideal lead compound in developing new insecticides and miticides.Recently, macrocyclic lactones play a great role in the pharmaceutical and pesticides such as spiramycin and erythromycin A. Normally, since macrocyclic lactones are both environmentally friendly and having efficient and wide biological activity features, they have been attracting great interests of scientists. For example, Milbemycins, as 16-membered macrocyclic lactones with miticidal, insecticidal and anthelmintic bioactivities, have been attracting great interests of scientists and a lot of interesting derivatives have been developed even commercially used.In this paper, spiromesifen and milbemycin were selected as lead compounds to develop new pesticides in this dissertation. According to traditional developing designation and typical preparing methods, 105 compounds derivatives, including 87 new compounds were synthesized. And their structures were confirmed by ¹H NMR and MS even by X-ray diffraction. At the same time, biological activities were also evaluated. The research work in this paper can be summarized as follows:1. An appropriate synthetic method of key intermediate 4-hydroxy-3-(2, 4, 6-trimethyl- phenyl)-1-oxa-spiro [4.4] non-3-en-2-one of spiromesifen was founded. At the same time, series of new compounds were also formed basing on this key intermediate. And compound 5-9 shows an excellent inhibition activity against aphid with LC₅₀ 1.09mg/L.2. 60 analogues of milbemycin were obtained from 5-O-TBDMS-ivermectin aglycones and ivermectin monosaccharide. And their bioactivities against spider mites, armyworm and aphid were also evaluated. Interestingly, compounds 4-13, 4′-9 and 4′-11 have shown an excellent inhibition activity against armyworm and aphid. Their LC₅₀ were 0.25mg/L and 0.15mg/L, 0.20mg/L and 0.07mg/L, 0.35mg/L and 0.12mg/L respectively. At the same time, we studied the relationship of the structure and biological activities.