Photocatalytic Tandem Radical Cyclization Enables Expeditious Total Synthesis of Epoxyhinokiol Analogues for Anticancer Activity Evaluation.

A photocatalytic radical cascade with an unusual endo -trig cyclization was developed, which enables the efficient assembly of divergent tricyclic diterpenoid frameworks. The first total synthesis of abietane 10- epi -epoxyhinoliol was thus achieved in six steps by a subsequent reductive coupling of i -PrBr under photoredox/nickel dual catalysis. Inhibitory tests of chiral 10- epi -epoxyhinoliol and its analogues in 4T1 cancer cells demonstrated the critical role of the C12 hydroxyl group, leading to a discovery of the simplified analogue with better activity.