Total Synthesis of Epicolactone

The biologically active and structurally complex secondary metabolite epicolactone is a member of the natural product pool found in cash crop endophytes of the genus Epicoccum. By exploiting inherent reactivity, a total synthesis of this highly oxygenated and polycyclic molecule met chemo- and regioselectivity challenges. The key buildup of complexity was accomplished via an intramolecular [2+2] photocycloaddition between a quinone and an electron-deficient diene followed by a cyclobutane ring expansion. The use of a dioxene as an acyl anion equivalent and an intramolecular carbonyl methenylation furnished the natural product.