Formal Total Synthesis of (±)-Isoalantolactone

Abstract

Herein, we report a concise formal synthesis of (±)-isoalantolactone through a six-step route to the advanced intermediate of Tada. The 5/6/6-fused eudesmanolide core is assembled through a SmI2-mediated reductive lactonization, while a late-stage acid-promoted sequence combines global deprotection, intramolecular aldol condensation, and thermodynamic stereochemical convergence to establish the required relative stereochemistry. Computational analysis supports thermodynamically controlled formation of the observed diastereomer and validates the overall synthetic design.