Total Synthesis of Tagetitoxin

Area of Science:

• Organic Chemistry
• Natural Product Synthesis

Background:

• Tagetitoxin (1) presents a structurally intricate and long-standing challenge in natural product synthesis.
• Previous structural assignments for tagetitoxin have undergone multiple revisions.

Purpose of the Study:

• To achieve the total synthesis of tagetitoxin (1).
• To confirm the structure of tagetitoxin through total synthesis.
• To assign the absolute configuration of tagetitoxin using bioassays.

Main Methods:

• Development of a 15-step synthetic route commencing from a renewable furan starting material.
• Utilization of unusual transformations including rearrangements, bromocyclization, and P(V)-based phosphate installation.
• Synthesis of both enantiomers of tagetitoxin to facilitate absolute configuration determination.

Main Results:

• Successful 15-step total synthesis of tagetitoxin (1).
• Confirmation of the intriguing and previously revised structure of tagetitoxin.
• Assignment of the natural product's absolute configuration via bioassays on both enantiomers.

Conclusions:

• The total synthesis validates the confirmed structure of tagetitoxin.
• The developed synthetic route provides access to both enantiomers, enabling absolute configuration assignment.
• This work addresses a significant challenge in natural product synthesis.