Functionalization of the 6,14-bridge of the orvinols. Part 3: Preparation and pharmacological evaluation of 18- and 19-hydroxyl substituted orvinols

The orvinols are a class of potent opioids which have been extensively studied, yet little is known about the effects of introducing substituents into the 18- and 19-positions. The etheno bridge of thevinone was hydroxylated to give both the 18- and 19-hydroxyl substituted thevinols. After 3-O-demethylation to the corresponding orvinols, binding and GTPγS functional assays indicated that hydroxyl substitution at the 18- and 19-positions differentially affects the μ opioid efficacy of orvinols.