P₄O₁₀/TfOH-assisted one-pot access to 8-oxoprotoberberines

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Protoberberine alkaloids are a significant class of natural products with diverse biological activities.
• Efficient synthetic routes to complex protoberberine scaffolds are crucial for drug discovery and development.

Purpose of the Study:

• To develop an efficient one-pot synthetic strategy for 8-oxoprotoberberine alkaloids.
• To demonstrate the versatility of the method for accessing structurally diverse protoberberine analogues and natural products.

Main Methods:

• A cascade process involving carbonyl activation and regioselective cyclization.
• P4O10/TfOH-mediated annulation of homophthalic acids and phenethylamines to form the tetracyclic scaffold.
• Sequential reduction of an 8-oxoprotoberberine intermediate to synthesize xylopinine.

Main Results:

• Successful synthesis of thirteen 8-oxoprotoberberine alkaloids in a one-pot procedure.
• Demonstrated regioselective cyclization and efficient tetracyclic scaffold formation.
• Concise and versatile synthesis of the natural product xylopinine.

Conclusions:

• The developed protocol offers a simplified and practical approach to multisubstituted protoberberine scaffolds.
• This methodology provides a versatile route to biologically relevant protoberberine analogues.
• The study highlights the utility of P4O10/TfOH-mediated annulation in alkaloid synthesis.