Bioactive Natural Product Assembly Using Precious Metal Catalysis: Total Synthesis of Phyllostictine A

利用贵金属催化组装生物活性天然产物：叶霉碱 A 的全合成

• 批准号: EP/K031783/1
• 负责人: Mike Shipman
• 金额: $ 52.93万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FK031783%2F1
• 关键词: Bioactive; Natural; Product; Assembly; Using

This project is focused on realizing the first total synthesis of phyllostictine A, the most potent member of a structurally unique class of natural product isolated from the fungus Phyllosticta cirsii. Phyllostictine A constitutes a formidable synthetic challenge, and its assembly will require us to develop a variety of new chemical reactions and processes. Emphasis will be placed on sustainable, catalytic transformations and on adhering to the principles of the 'ideal' synthesis (e.g. atom, step and redox economy). For example, the 4-, 5- and 11-membered rings will be made using palladium, gold, and ruthenium catalysis respectively. This natural product displays potent herbicidal activity against a variety of weeds, and most recently, anti-cancer activity. In parallel with the total synthesis, a selection of analogues and intermediates will be tested for bioactivity. This will help advance our understanding of the mode of action of phyllostictine A, and will pave the way for the development of simplified analogues of the natural product for use in medicine and agriculture.

该项目的重点是实现叶点霉素A的首次全合成，叶点霉素A是从真菌Phyllosticta cirsii中分离出的结构独特的一类天然产物中最有效的成员。叶枝菌素A是一个巨大的合成挑战，它的组装将需要我们开发各种新的化学反应和过程。重点将放在可持续的催化转化和坚持“理想”合成的原则（例如原子，步骤和氧化还原经济）。例如，4-、5-和11-元环将分别使用钯、金和钌催化剂制备。这种天然产物对多种杂草表现出有效的除草活性，最近还表现出抗癌活性。在全合成的同时，将检测选择的类似物和中间体的生物活性。这将有助于推进我们对叶枝蕈碱A作用模式的理解，并为开发用于医学和农业的天然产物的简化类似物铺平道路。