以α-亚甲基-γ-丁内酯为先导的化合物合成及抑菌构效关系研究

项目名称： 以α-亚甲基-γ-丁内酯为先导的化合物合成及抑菌构效关系研究

项目编号： No.31471800

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 农业科学

项目作者： 冯俊涛

作者单位： 西北农林科技大学

项目金额： 85万元

中文摘要： 从天然产物中发现农药活性先导化合物，对其进行人工合成和修饰合成以开发更高活性化合物，是近年来新农药创制的主要途径和研究热点。天名精内酯酮为菊科天名精属植物大花金挖耳的主要杀菌活性成分之一。申请者于2012年在国家自然科学基金的资助下，设计、合成了天名精内酯酮衍生物（类似物）180余个，抑菌构效关系分析表明α-亚甲基-γ-丁内酯是该类化合物的关键活性基团，具备作为农药活性先导化合物的潜质。本项目拟在此基础上，以α-亚甲基-γ-丁内酯为先导，利用药效团与骨架迁移的策略，设计、合成系列化合物200-300个；以黄瓜炭疽病菌和番茄灰霉病菌等为供试菌种测定抑菌活性，搭建合成化合物的结构－活性2D-和3D-QSAR模型，探讨其构效关系；在此基础上推测高抑菌活性化合物的理想结构，并建立具自主知识产权的新型农药分子模板；以此为基础合成2－3个具产业化开发前景的高活性化合物，为创制新型杀菌剂奠定基础。

中文关键词： α-亚甲基-γ-丁内酯；先导优化；抑菌活性；构效关系

英文摘要： Excavating leading compounds with pesticide activity from natural products, synthesizing and modifying their structures to explore compounds with more significant activities have become main methods and research highlights of new pesticide exploration recently. Carabrone is one of the antifungal compounds isolated from Carpesium macrocephalum, Asteraceae. Funded by NSFC in 2012, the applicant has designed and synthesized more than 180 derivatives and analogues of Carabrone. Based on the antifungal construct-activity analysis,α-Methylene-γ-butyrolactone is considered to be a key activity group of these compounds, with the potential to be a leading compound with pesticide activity. Based on the above, this project aims to design and synthesis 200-300 compounds utilizing the pharmacophore and skeleton migration strategy with α-Methylene-γ-butyrolactone as the leading compound, to determine of antibacterial activities with Colletotrichum lagenarium and Botrytis cinerea as tested strains, to construct the 2D- and 3D-QSAR model and explore its structure - activity relationship, to speculate that the ideal structure of the compounds with high antifungal activities and establish a new molecular template of pesticide with proprietary intellectual property right, to synthesis 2-3 high activity compounds with industrialization exploration potential, and to pave the foundation for the development of new agricultural disease control agents.

英文关键词： α-methylene-γ-butyrolactones;Lead optimization;antifungal activities;structure-activity relationship