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.
• It exhibits antifungal, antifertility, and tubulin polymerization inhibitory activities.
• Its structure presents significant synthetic challenges.

Purpose of the Study:

• To achieve the total synthesis of pseudolaric acid B.
• To explore novel synthetic methodologies for complex diterpene acids.
• To investigate the structure-activity relationship for potential therapeutic applications.

Main Methods:

• Ru- or Rh-catalyzed [5 + 2] intramolecular cycloaddition for polyhydroazulene core construction.
• Radical cyclization strategy for quaternary center formation.
• Cerium organometallic reagents for late-stage ketone addition.

Main Results:

• Successful construction of the polyhydroazulene core.
• Development of a novel strategy for introducing the quaternary center via radical cyclization.
• Demonstration of cerium organometallic reagent utility in complex settings.
• Identification of challenges in late-stage synthesis due to oxo-bridged derivative formation.

Conclusions:

• The total synthesis of pseudolaric acid B was accomplished.
• Novel synthetic methods were developed and validated.
• The study highlights the complex reactivity of pseudolaric acid derivatives and informs future synthetic efforts.