基于pDOS策略的海洋甲壳源5-羟甲基糠醛衍生物的多样性合成及杀线活性评价

植物寄生线虫对作物危害严重，每年给我国农业生产带来巨大损失。化学防治是最有效的线虫病害防治方法。然而，目前有效的杀线剂严重缺乏，且多存在高毒、抗药性严重、稳定性较差等问题，使其应用受到很大限制。因此，开发安全、高效的杀线剂满足我国农业绿色发展的需求已势在必行。近期我们发现海洋甲壳源5-羟甲基糠醛（HMF）化合物具有高杀线活性。据此本项目以HMF为苗头化合物，基于优势结构的多样性导向合成（pDOS）理念为导向，通过仿生合成、活性亚结构拼接、成环反应等策略构建兼具结构多样性和类农药性的化合物库；然后搭建先导-活性-安全性相互关联制约的活性筛选平台，通过活性筛选和构效关系研究进行先导发现和优化，以期筛选到杀线剂候选物并初步明确其杀线机制，为新型杀线剂的创制奠定基础。这对于提升我国海洋生物资源的高值化利用水平，突破限制我国农业绿色发展的瓶颈问题，以及拓宽新农药的创制思路均有重要意义。

Plant-parasitic nematodes are responsible for serious crop damage and cause huge annual losses to China's agricultural production. Currently, chemical nematicides were considered to be the most efficient tools to control the diseases. However, there are only a few effective nematicides on the market. Moreover, most of the nematicides are considerably toxic or drug-resistant and unstable, which greatly restrict their applications. Therefore, it is imperative to develop safe and high-efficiency nematicides to meet the needs of China's agricultural green development. Recently, we discovered a highly nematicidal 5-hydroxymethylfurfural (HMF) compound derived from marine crustacean sources. Inspired by this fining, HMF will be firstly selected as the hit compound in this project, and based on the concept of privileged structure-based diversity-oriented synthesis (pDOS), the compound libraries with molecular structure diversity and pesticide-like properties will be quickly and efficiently constructed through the strategies including biomimetic synthesis, active substructure combination strategies, and cyclization reaction. Then, a lead-bioactivity-safety interaction screening platform will be built, and lead discovery and optimization will be conducted through activity screening and structure-activity relationship studies. It is expected that nematicide candidates can be screened and their nematicidal mechanism will be clarified initially to lay the foundation for the development of new nematicides. This project is of great significance for promoting the high-value utilization of China's marine biological resources, breaking through the bottleneck problem restricting China's agricultural green development, and broadening the idea of the development of new pesticides.