First total synthesis and structural reassignment of (-)-aplysiallene

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Natural Product Synthesis

Background:

• (-)-Aplysiallene is a marine natural product with a unique bis-tetrahydrofuran (THF) structure.
• Previous synthetic routes have not been reported.
• The stereochemical assignment of (-)-aplysiallene required clarification.

Purpose of the Study:

• To achieve the first total synthesis of (-)-aplysiallene.
• To develop an efficient synthetic strategy employing a key cyclization reaction.
• To revise and confirm the stereochemical assignment of the natural product.

Main Methods:

• A 16-step synthetic sequence was designed and executed.
• A sequential Mukaiyama aerobic oxidative cyclization was employed as a key step.
• Spectroscopic methods were used to confirm the structure and stereochemistry.

Main Results:

• The first total synthesis of (-)-aplysiallene was successfully completed.
• The fused bis-THF core was efficiently prepared using the Mukaiyama cyclization.
• The original stereochemical assignment was revised based on synthetic and analytical data.

Conclusions:

• The total synthesis demonstrates a viable route to (-)-aplysiallene.
• The Mukaiyama aerobic oxidative cyclization is a powerful tool for constructing fused THF systems.
• The revised stereochemistry provides a more accurate understanding of this marine natural product.