Concise Total Synthesis of (-)-Bipolarolide D.

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Medicinal Chemistry

Background:

• Ophiobolin-derived sesterterpenes are complex natural products with potential biological activities.
• Bipolarolide D is a specific sesterterpene within this class that has not been previously synthesized.
• Developing efficient synthetic routes to complex natural products is crucial for further biological investigation.

Purpose of the Study:

• To report the first total synthesis of bipolarolide D.
• To establish a modular and enantioselective synthetic strategy.
• To demonstrate the utility of pentafulvene derivatives in complex molecule construction.

Main Methods:

• Enantioselective pentafulvene-involved [6+2] cycloaddition reaction.
• Regioselective and diastereoselective pentafulvene-involved Heck cyclization.
• Late-stage selective allylic addition for side chain installation.

Main Results:

• Successful and concise total synthesis of bipolarolide D achieved.
• Demonstrated the effectiveness of pentafulvene-based cycloaddition and Heck cyclization strategies.
• Established an enantioselective and modular synthetic route.

Conclusions:

• The developed synthetic strategy provides the first enantioselective total synthesis of bipolarolide D.
• Pentafulvenes are versatile synthons for constructing complex natural products.
• This synthesis facilitates future studies on the biological activities of bipolarolide D and related compounds.