A Concise Synthesis of Pleurotin Enabled by a Nontraditional C-H Epimerization

Area of Science:

• Organic Chemistry
• Natural Product Synthesis

Background:

• Pleurotin and related benzoquinone natural products exhibit potent anticancer and antibiotic activities.
• The synthesis of these complex molecules is crucial for medicinal chemistry research.

Purpose of the Study:

• To describe an 8-step synthesis of a known pentacyclic intermediate towards the natural product pleurotin.
• To establish a synthetic route for accessing biologically active benzoquinone natural products.

Main Methods:

• Regio- and diastereoselective intermolecular photoenolization/Diels-Alder cycloaddition.
• Alkoxy-radical-induced hydrogen atom transfer-mediated C-H epimerization.
• Ring-forming benzylic C-H oxidation.

Main Results:

• An 8-step synthesis of a pentacyclic intermediate was achieved.
• The synthetic route successfully constructed the carbon framework of pleurotin with correct stereochemistry.
• Oxepane 19 was delivered as the final product.

Conclusions:

• The developed synthetic strategy is effective for constructing complex natural product skeletons.
• This synthesis provides a valuable pathway for accessing pleurotin and its analogs for further biological evaluation.