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

The enantioselective synthesis of 1-(R)-hydroxypolygodial and its epimer at C-9 is described. a-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.