Bioinspired Total Synthesis of Bussealin E.

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Medicinal Chemistry

Background:

• Bussealin E is a complex natural product possessing a distinctive cycloheptadibenzofuran scaffold.
• The intricate structure of bussealin E presents a significant challenge for synthetic chemists.
• Understanding its synthesis can provide insights into potential biological activities.

Purpose of the Study:

• To achieve the first total synthesis of bussealin E.
• To develop a synthetic strategy inspired by proposed biosynthetic pathways.
• To establish a robust method for constructing the unique tetracyclic core.

Main Methods:

• Employing a strategy based on a proposed biosynthetic route.
• Utilizing an oxidative phenolic coupling to form the tetracyclic ring system.
• Executing a key sp2-sp3 Hiyama coupling for diphenylpropane synthesis.

Main Results:

• The first total synthesis of bussealin E was successfully accomplished.
• A novel diphenylpropane derivative was synthesized via sp2-sp3 Hiyama coupling.
• The tetracyclic cycloheptadibenzofuran core was efficiently constructed through oxidative phenolic coupling.

Conclusions:

• The reported synthesis provides access to bussealin E and its analogs.
• The employed strategy validates the proposed biosynthetic pathway.
• This work expands the toolkit for synthesizing complex natural products with similar scaffolds.