Synthesis of the Tetracyclic Cores of the Integrastatins, Epicoccolide A and Epicocconigrone A.

The integrastatins, epicoccolide A and epicoccongirone A, are natural products containing a unique [6.6.6.6]-tetracyclic core framework that exhibit a broad spectrum of biological activities. A synthesis of the common core of epicoccolide A and epicocconigrone A has been achieved using an umpolung alkylation-lactonization to assemble an isochromanone from which the bridged 1,3-dioxane was readily assembled. A different strategy was required to access the core on the integrastatins; an initial aryllithium addition to an aldehyde, followed by oxidation and treatment of the masked dihydroxyketone with acid gave the desired core structure.