Total Synthesis of Aplyronine A, a Potent Antitumor Substance of Marine Origin

Recently, we elucidated the gross structure of aplyronine A isolated as a minute constituent of the Japanese sea hare Aplysia kurodai. Further, the absolute stereochemistry has been fully determined. Although aplyronine A exhibits exceedingly potent antitumor activities, the scarcity from natural sources has prevented further evaluation of this compound as a potential therapeutic agent thus far. This fact and the novel polyfunctional 24-membered lactone structure prompted us to initiate the investigation toward the synthesis. Recently, the synthesis of the C21-C34 segment has been reported. We describe herein the total synthesis.