Synthetic studies of neoclerodane diterpenes from Salvia divinorum: exploration of the 1-position.
Bioorganic & medicinal chemistry letters November 15, 2007 Kenneth G Holden, Kevin Tidgewell, Alfred Marquam et al.
Removing the C-1 ketone from salvinorin A and its analogue herkinorin changes their activity at opioid receptors. A derivative called 1-deoxo-1,10-dehydrosalvinorin A acts as a moderately potent antagonist at all three opioid receptor subtypes. Herkinorin, a mu opioid agonist, becomes a weak antagonist when its C-1 ketone is removed. These results indicate the C-1 ketone is a key structural feature for mu agonist activity.