新颖高效、低毒阿维菌素类大环内酯杀虫剂的设计合成及构效关系

Rice stem borer is one of the severe harmful insects in our country. Their main prevent and control insecticides are chlorantraniliprole and flubendiamide .They are ryanodine receptor activations, and their structures are protected by the abroad patents and the technical breakforth is very difficult. While the avermectins are non-protected by patent. The avermectins are applied to be rice stem insecticides in our country which have good insecticidal effect, but the resistance and toxicity problems are severe which have caused high attention of the adminitrative department.To overcome the problems of the above avermectin insecticides, some novel ultra effect, broad spectrum and low toxicity macrolides have been designed, their insecticidal activity to xylostella is 100 times more than that of avermectins and ivermectins while their rat acute oral toxicity is 10 times lower than that of them. Based on this, the following work is what mainly be studied in our programme: (1). study the activity and strucutre relationship of the obtained macrolides in order to design novel macrolides; (2). study the key infactors which influent the toxicity of this kind of chemicals; (3). study the infunction mode of the cadidate varieties, and study the crystall structures of the macrolide complexes by corperattion with others; (4). selecte one or two cadidate varieties to be studied in appliction. All in all, we aim to find a kind of rice stem moth insecticidal varieties which have ultra effect,broad spectrum and low toxicity based on the a series of systematic research.

螟虫是水稻田危害最严重的害虫之一。目前防治螟虫主流的品种是鱼泥丁类杀虫剂氯虫苯甲酰胺和氟虫双酰胺，而我们很难突破其结构的专利保护。我国推出了无专利保护的阿维菌素用于防治螟虫，取得很好效果，但抗性、尤其是毒性问题已经引起高度重视。我们针对阿维菌素类结构存在的问题，设计合成出一些新颖的超高效、广谱、低毒的大环内酯，其对小菜蛾活性的比阿维菌素和伊维菌素提高100倍，对螟虫的毒力是氯虫苯甲酰胺的2.5倍，而对大白鼠的急性经口毒性降低10倍以上，属低毒类化合物。本项目在此基础上开展如下研究工作：1）开展新颖大环内酯结构与活性关系，进一步设计合成新的大环内酯结构；2）探讨影响该类结构毒性的关键因素；3）开展已经发现的候选品种的作用方式研究；合作开展复合物晶体结构研究；4）选择1～2个候选化合物进行应用开发研究。希望通过以上系统性研究，力争开发出具有市场竞争性的高效、广谱、低毒的大环内酯结构杀螟虫品种

螟虫是水稻田危害最严重的害虫之一。目前防治螟虫主流的品种是鱼泥丁类杀虫剂氯虫苯甲酰胺和氟虫双酰胺，而我们很难突破其结构的专利保护，而且目前抗性问题也非常严重。我国推出了无专利保护的阿维菌素用于防治螟虫，取得很好效果，但抗性、尤其是毒性问题已经引起高度重视。本基金项目针对阿维菌素大环内酯类结构存在的问题，设计合成出一系列新颖的超高效、广谱、低毒的大环内酯衍生物，开展了生物活性研究和初步的毒性研究，发现一些化合物室内对小菜蛾活性的比阿维菌素和伊维菌素提高100倍，对螟虫的毒力是氯虫苯甲酰胺的2.5倍，而对大白鼠的急性经口毒性降低10倍以上，属低毒类化合物。并选择了一个候选化合物开展了应用开发研究：开发出一条成本较低的绿色合成工艺研究、并建立了中间体及产物分析方法；完成了目标候选化合物原药稳定性研究；初步开展了其制剂研究和制剂稳定性研究、室内生物活性研究及田间生物活性研究。研究发现目标候选化合物原药基本稳定，目前开发的制剂室内和田间生物活性存在较大差异，需继续开展研究，期望能开发成具有市场竞争性的高效、广谱、低毒的大环内酯结构杀螟虫品种。