Total Synthesis of (–)‐Penostatins G, B and C Featuring an Intramolecular oxa‐Diels–Alder Reaction of a Cyclic Tricarbonyl Precursor

ABSTRACT (−)‐Penostatin G, isolated from the marine green alga Enteromorpha intestinalis , has an interesting tetracyclic structure and potent anticancer activity. Herein, the total synthesis of (−)‐penostatin G and its conversion to (–)‐penostatins B and C are achieved for the first time. Our strategy for construction of the distinctive tetracyclic skeleton of penostatin G features a chiral exocyclic enone‐induced exo Diels–Alder reaction, an MMPP‐mediated chemo‐ and regioselective Baeyer–Villiger oxidation, and an intramolecular oxa‐Diels–Alder reaction of the cyclic vicinal tricarbonyl precursor with high stereoselectivity. By the protection‐free approach, penostatin G was synthesized from the commercial substituted cyclopentanone in 12 longest linear steps.