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

点击翻译按钮获取中文摘要

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.