Sclerotiorin类天然产物的结构优化及其杀菌活性和作用机制研究

项目名称： Sclerotiorin类天然产物的结构优化及其杀菌活性和作用机制研究

项目编号： No.21272091

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 吴琼友

作者单位： 华中师范大学

项目金额： 80万元

中文摘要： 先导结构的选择和发现是创制新农药的关键要素，而天然产物则是发现具有新型骨架农药先导结构的宝库，对天然先导结构的优化是农药的重要创新之路。Sclerotiorin衍生物具有广谱生物活性，针对该天然产物的合成及从不同途径分离该天然产物的类似物引起了科学家的广泛兴趣。但是，以该类天然产物为先导进行结构优化来开发农用药物分子还没有文献报道，我们的前期研究表明，通过对该天然产物结构中3-位进行改变（用苯环取代共轭侧链）可显著提高其杀菌活性。本项目拟在前期工作的基础上进一步对该化合物结构进行改造，优化策略包括：保持其基本母核结构，优化不同侧位取代基以及通过并环、缩环等策略设计对其母核结构作有限改变，合成结构信息丰富的化合物库，筛选其杀菌活性，探索其作用机制。希望经过设计-合成-生测-构效关系的循环，找到具有新型骨架、优良生物活性的绿色杀菌剂先导结构。

中文关键词： 天然产物；杀菌剂；先导；结构优化；构效关系

英文摘要： The selection and discovery of the lead structure play an important role during the development of novel pesticide. It is well known that natural products are the abundant source for the discovery of pesticide lead with an absolutely novel structure. The structure optimization of natural lead is an efficient approach to the innovation of pesticides. Sclerotiorin and its analogues are a representative class of natural products, structurally featured with a highly oxigenated backbone. Because of their broad spectrum biological properties, the total synthesis and isolation from different fungal species of this kind of natural products have received considerable attention of chemists. To the best of our knowledge, there is no publication describe the structure optimization of Sclerotiorin with an aim for the development of novel fungicide. In our previous research, we found that the antifungal activity was highly improved by replacement of the conjugated side chain of Sclerotiorin with a phenyl substituent. We envisioned that Sclerotiorin might be a good lead for the discovery of novel agricultural fungicides. In this project, we would like to get further insight into the structure-activity relationship of Sclerotiorin. We will focus on the structure optimization by changing the substituents pattern of the Sclerotio

英文关键词： natural product；fungicide；lead；structure optimization；structure-activity relationship