Enantioselective Total Synthesis of Daedaleanol B from (+)-Sclareolide

Daedaleanol B is a drimane-derived merosesquiterpenoid isolated from the brown-rot fungus <i>Daedalea incana</i>. Herein, we report its first enantioselective total synthesis from commercially available (+)-sclareolide. A one-pot transformation afforded 11-acetoxy drimane-8α-ol, which was saponificated and selectively esterified with enantiopure L-pyroglutamic acid to give crystalline hydroxy-daedaleanol. Single-crystal X-ray diffraction of this intermediate, together with the known configuration of the chiral starting materials, enabled assignment of the absolute configuration of the daedaleanol B framework. Final elimination provided daedaleanol B, whose NMR data matched those reported for the natural product. Both hydroxy-daedaleanol and daedaleanol B exhibited time- and concentration-dependent antiproliferative effects in HT-29 colorectal cancer cells, with higher activity observed for daedaleanol B.