Total Synthesis of Sculponin U through a Photoinduced Radical Cascade Cyclization

Abstract

AbstractWe have accomplished the total synthesis of sculponin U, a polycyclic C‐20‐oxygenated kaurane diterpenoid featuring a 7,20‐lactone‐hemiketal bridge, through a radical cascade cyclization triggered by photoinduced electron transfer (PET) of a silyl enolate to form the cyclohexanone‐fused bicyclo[3.2.1]octane skeleton. Other key points in our synthetic strategy encompass a Diels–Alder reaction to construct the middle six‐membered ring of sculponin U, and an intramolecular radical cyclization induced by iron‐catalyzed hydrogen atom transfer to close the western cyclohexane ring. Successful preparation of the enantiopure silyl enolate as the PET precursor enables the asymmetric total synthesis of sculponin U, opening a new avenue for divergent syntheses of structurally related C‐20‐oxygenated kaurane congeners and pharmaceutical derivatives thereof.