Synthesis of ent-Cleistanthane Diterpenoid Spruceanol: Construction of an Aromatic C Ring via Lewis Acid-Controlled Regioselective Diels–Alder Cycloaddition

The first synthesis of ent-cleistanthane-type diterpenoid spruceanol with significant anticancer activity is described. A chiral pool approach was employed with a linear sequence of 13 steps beginning from readily available and inexpensive andrographolide. The approach features the construction of an aromatic ring with hydroxyl and methyl groups at C-12 and C-13 of the target compound, respectively, via Lewis acid-controlled regioselective Diels–Alder cycloaddition and the regioselective removal of the primary hydroxyl group of the Diels–Alder adduct.