Asymmetric Total Synthesis of (+)-Ineleganolide.

Polycyclic cembrane diterpenoids and norditerpenoids have garnered sustained interest from the synthetic community due to their unique polycyclic frameworks and promising biological activities. Herein, we report a 13-step total synthesis of (+)-ineleganolide, a highly oxidized cembrane norditerpenoid possessing a synthetically challenging [6,7,5,5,5] cage-type pentacyclic scaffold. This synthesis is highlighted by a novel strategy relying on an intramolecular Diels-Alder reaction that stereoselectively constructs the pivotal [6,6,5,5,5] pentacyclic framework as a single diastereoisomer, addressing stereochemical control challenges. In the late-stage elaboration, a tandem epoxidation/Meinwald rearrangement efficiently forges the sterically congested central seven-membered ring. This synthetic strategy provides a new blueprint for accessing other members of the cembrane norditerpenoid family.