Divergent Total Syntheses of 7,20‐Epoxy, 3,20‐Epoxy, and 6,7‐<i>seco‐ent</i>‐Kaurane Diterpenoids

The genus Isodon is a well‐known traditional medicinal herb that serves as a rich source of cytotoxic ent ‐kaurane diterpenoids, which bear the same tetracyclic core of ent ‐kaurane with different oxygenation, bond‐cleavage, and rearrangement patterns. The 7,20‐epoxy‐ ent ‐kaurane diterpenoids are the most studied subclasses, which show promising anticancer activities. Moreover, they also have the potential for transforming to other subclasses of ent ‐kaurane diterpenoids. Herein, the details of this study on developing a highly diastereoselective synthetic strategy for the 7,20‐epoxy‐ ent ‐kaurane diterpenoid (5 natural products) and its conversion to the 3,20‐epoxy (2 natural products) and 6,7‐ seco derivatives (2 natural products) are reported. The synthetic strategy features a thermal Diels–Alder cycloaddition for the construction of the AB ring system, an intramolecular Mukaiyama Michael/carbocyclization cascade reaction for establishing the CD ring system, a site‐stereoselective oxidation/reduction strategy for completion of the total syntheses of several representative 7,20‐epoxy‐ ent ‐kaurane diterpenoids, and the divergent syntheses of Isodon diterpenoids in the 3,20‐epoxy and 6,7‐ seco subclasses via bioinspired strategies.