Total synthesis of cynaropicrin

Area of Science:

• Natural Product Chemistry
• Organic Synthesis
• Medicinal Chemistry

Background:

• Cynaropicrin, a sesquiterpene lactone found in artichoke (Cynara scolymus), imparts a bitter taste.
• This natural product exhibits significant biological activities, including inhibition of NF-κB activation, anti-hepatitis C, and antitrypanosomal effects.
• The complex structure of cynaropicrin, featuring a 5-7-5 tricyclic skeleton, six chiral centers, and four exo-olefins, presents a synthetic challenge.

Purpose of the Study:

• To achieve the first total synthesis of the natural product cynaropicrin.
• To explore novel synthetic strategies for complex sesquiterpene lactones.
• To provide a scalable route for obtaining cynaropicrin for further biological evaluation.

Main Methods:

• The total synthesis commenced from (S)-α-pinene, a readily available chiral starting material.
• Key synthetic steps included a stereoselective Favorskii rearrangement.
• An indium-promoted diastereoselective Barbier reaction was employed to construct the molecular framework.

Main Results:

• The first successful total synthesis of cynaropicrin was accomplished.
• The synthetic route demonstrated high stereoselectivity and diastereoselectivity.
• The study provides a validated pathway for the preparation of cynaropicrin.

Conclusions:

• The total synthesis of cynaropicrin has been successfully realized.
• The developed synthetic methodology offers a valuable approach for accessing complex sesquiterpene lactones.
• This synthesis enables further investigation into the medicinal potential of cynaropicrin.