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

(-)-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.