抗菌成分胶黏毒素衍生物合成与构效关系研究

Microbial natural products have been a continuous source of new lead compounds, and chemical entities in the agrochemical and pharmaceutical industries. Chemists have been engaged in the discovery of novel bioactives from microbial metabolites. Despite a focused interest on synthetic products, bioactive natural products retain an immense impact on modern medicine and agriculture..1. In the previous study, we first demonstrated that gliotoxin, an epipolythiodioxopiperazine metabolite isolated from Chaetomium globosum, an endophytic fungus isolated from Ginkgo biloba, possessed remarkable antifungal activity against some phytopathogens. Structural modification of this compound will be performed by chemical methods to ynthesize a series of its derivatives. .2.The epipolythiodioxopiperazine derivatives containing a disulphide bridge as the core structure moiety will be prepared. All synthetic compounds are identified and characterized by means of spectroscopic data..3. Evaluation of the antifungal activity of the synthezied compounds will be conducted against several phytopathogens by using mycelial growth rate assay..3. The structure−antifungal activity relationships will be studied to elucidate their active requirements for antifungal effects and to find some strong active compounds..The present study is focusing on elucidating structure-activity relationships (SARs)of this class of epipolythiodioxopiperazins to lay a foundation for development of new pesticides with higher efficacy, lower toxicity and lower residue.

从微生物次生代谢产物中发现先导化合物，通过对其进行结构改造或修饰，得到全新的生物源农药活性物质，是当今新型高效安全农药创制研究的有效途径之一。银杏内生菌球毛壳霉中胶黏毒素具有显著抑制植物病原真菌活性，拟以此活性成分为模板，制备表二硫代二酮哌嗪衍生物，借助波谱技术等手段对合成的化合物结构进行鉴定。采用生长速率法，测定胶黏毒素类化合物对几种植物病原真菌的抑菌活性，分析探讨不同衍生物的分子结构对抑菌活性的影响；以期获得高活性化合物。本研究将为创制一类高效、低毒、低残留的创新农药提供可能的理论依据。

本研究以银杏内生菌球毛壳霉产生的胶黏毒素为原料，制备了13个新衍生物； 基于二硫桥为关键结构因子，制备了11个新简化的胶黏毒素类似物（二硫代二酮哌嗪化合物），采用核磁共振、高分辨质谱等波谱手段对合成的化合物进行了结构表征。. 采用生长速率法，测定这些化合物对5种植物病原真菌的抑菌活性，初步探讨了不同衍生物的分子结构对抑菌活性的影响。本工作为进一步研究高活性的候选化合物提供了重要的依据。本项目发表1篇SCI收录论文，申请1项国家发明专利。