Total synthesis of (-)-pseudolaric acid B

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Medicinal Chemistry

Background:

• Pseudolaric acid B is a diterpene acid from Pseudolarix kaempferi bark.
• It exhibits antifungal, antifertility, and cytotoxic activities, particularly against multidrug-resistant cell lines.
• The complex polyhydroazulene core presents a synthetic challenge.

Purpose of the Study:

• To report the first enantioselective synthesis of pseudolaric acid B.
• To develop efficient synthetic strategies for constructing the natural product's core structure.
• To provide access to pseudolaric acid B for further biological evaluation.

Main Methods:

• Metal-catalyzed [5 + 2] vinylcyclopropane-alkyne intramolecular cycloaddition for polyhydroazulene core construction.
• Intramolecular alkoxycarbonyl radical cyclization to establish the quaternary center.
• Diastereoselective cerium acetylide addition for the introduction of the carboxylic acid side chain.

Main Results:

• Successful enantioselective synthesis of pseudolaric acid B (1a).
• Efficient construction of the tricyclic scaffold using key C-C bond-forming reactions.
• Establishment of the quaternary center and stereoselective installation of the acid side chain.

Conclusions:

• The developed synthetic route provides a viable method for accessing pseudolaric acid B.
• The employed methodologies are effective for constructing complex polycyclic natural products.
• This synthesis enables further investigation into the biological activities of pseudolaric acid B.