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

Abstract

This study describes an efficient one-pot strategy for the synthesis of a series of thirteen 8-oxoprotoberberine alkaloids through a cascade process involving carbonyl activation and regioselective cyclization. The synthesis demonstrates P₄O₁₀/TfOH-mediated annulation as a key step to obtain the tetracyclic scaffold from homophthalic acids and phenethylamines. The developed protocol provides a simplified and practical approach for accessing multisubstituted protoberberine scaffolds with excellent structural diversity. The synthetic utility of this methodology is demonstrated through the successful preparation of the natural product xylopinine via sequential reduction of an 8-oxoprotoberberine intermediate, thereby offering a concise and versatile route to biologically relevant protoberberine analogues.