Enantioselective synthesis of 1-(R)-hydroxypolygodial and its 9α epimer, 1-(R)-hydroxyisotadeonal

The enantioselective synthesis of 1-(R)-hydroxypolygodial and its epimer at C-9 is described. α-Ionone was the starting material. Key steps of these syntheses included a Corey–Bakshi–Shibata oxazaborolidine-mediated reduction and a stereoselective Diels–Alder reaction. No vanilloid activity was detected for both compounds in assays on VR1 vanilloid receptor in HEK cells transfected with the human VR1.