基于植物系统获得抗病性的新型噻二唑和异噻唑衍生物的合成与生物活性研究

Novel pesticide development is the request of the sustainable development of agriculture and plant protection, on the basis of systemic acquired resistance, 1,2-isothiazole and 1,2,3-thiadiazole active substructures, aimed at the key insect and disease damage especially virus causing disease, novel pro-elicitor derivatives with insecticidal and fungicidal activity were designed and synthesized by combination of theories of organic chemistry, pesticide molecular designation, pro-pesticides and principles of plant protection, as a pro-elicitor, the highly active target compounds will keep their original fungicide activity or insecticide activity, their metabolites will play a role of the elicitor. The chemical diversity with bioactive substructure of heterocyclic compounds libraries were also designed by introducing highly active substructures by chemistry principle and reactions. The biological activities of all the novel target compounds including fungicide activity, insecticide activity and systemic acquired resistance will be screened for structure activity relationship studies too. For the highly active compounds, the biological activity, the mode of action and metabolism in the plants will be studied on the basis of the mechanism of fungicide mode, insecticide mode, antivirus mode or systemic acquired resistance mode. Because of the target molecule itself possesses original biological activity, its metabolite with sustainable systemic acquired resistance against the succeeding pathogen attack, this will greatly improve the efficiency and application of pesticide molecule. The results of this proposal will provide integrated new measure for key insect, disease especially virus control in our country and make great contribution to the novel systemic acquired resistance based pesticide development and plant protection in theory and practice.

新农药创制是农业和植物保护可持续发展的需要，本项目结合有机化学、农药分子设计、农药前药及植物保护的原理，针对我国重大病虫害和病毒病害，基于植物系统获得抗病性和1,2-异噻唑或1,2,3-噻二唑活性亚结构单元，设计合成具有杀菌(虫)活性的前植物激活剂先导结构的衍生物，保持分子原有的生物活性，代谢产物发挥诱导抗病的活性。利用有机化学反应构筑结构多样的杂环化合物库，在分子中引入具有高活性的亚结构单元，对新的目标分子进行系统的生物活性筛选和构效关系的研究，对高活性分子进行代谢降解和杀菌、杀虫、抗病毒及诱导抗病作用机制的研究。高活性目标分子本身将保持杀菌(虫)活性，其代谢产物的诱导抗病活性能提高植物对病害和病毒病害的防御能力，极大提高了农药分子的有效利用率。研究结果对我国重大病虫害尤其是病毒病害的综合防治提供了新的手段，对基于植物系统获得抗病性的新农药创制和植物保护具有重要的理论意义和实践价值。

本项目利用农药分子设计和有机化学的原理设计合成含1,2-异噻唑和1,2,3-噻二唑及其他杂环的新化合物400多个，发现高活性化合物5个，其中3个化合物有望进入产业化开发阶段；本课题开展了前农药的分子设计合成和生物活性及构效关系的研究，还利用分子生物学和转录组学及农药环境毒理学的手段开展了高活性候选前农药作用机制和代谢降解的研究。本项目的研究成果发表了SCI学术论文12篇，其中，在国际期刊上发表较高水平学术论文6篇，申请了中国国家发明专利15件，申请了PCT国际发明专利4件，获得了中国国家发明专利授权10件；培养毕业了硕士研究生6名。项目的研究成果拓展了与俄罗斯专家俄罗斯联邦乌拉尔叶利钦大学Bakulev教授和美国专家俄亥俄州立大学余建华教授以及加州大学滨河分校Thomas Eulgem教授的高层次国际合作研究，并获得了国家国际科技合作专项中俄国际合作项目(No. 2014DFR41030)以及国家重点研发计划(No. 2017YFD0200903)的后续资助。项目执行期间，3件授权中国国家发明专利实现了成果转化，应邀在2014年8月10-14在美国加州旧金山举办的第13届IUPAC国际农药大会(第248届美国化学会)上做1个分会报告和1个候选优秀Poster分会报告。本项目课题组创制的我国第一个具有自主知识产权的植物激活剂甲噻诱胺于2016年获得我国农业部颁发的新农药登记证。甲噻诱胺等农药系列新品种、绿色生态农药分子设计和系统优化重大共性关键技术2016年被工信部列为产业技术创新能力发展规划(2016-2020年)中石化和化学工业的重点发展方向。