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

本项目的重点是实现第一次全合成phyllostictine A，这是从真菌Phyllosticta cirsii中分离出来的结构独特的天然产物中最有效的成员。Phyllostictine A是一个巨大的合成挑战，它的组装将要求我们开发各种新的化学反应和工艺。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元、5元和11元环将分别使用钯、金和钌催化制成。这种天然产物对多种杂草具有强大的除草活性，最近还具有抗癌活性。在进行全合成的同时，将对一些类似物和中间体进行生物活性测试。这将有助于促进我们对毛状胶A的作用方式的理解，并将为开发用于医学和农业的天然产品的简化类似物铺平道路。

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.