New neoclerodane diterpenoids isolated from the leaves of Salvia divinorum and their binding affinities for human κ opioid receptors

Three new neoclerodane diterpenoids—divinatorin D, divinatorin E, and salvinorin G, along with 10 known terpenoids, were isolated from the leaves of Salvia divinorum. All these compounds were evaluated for their binding affinities to the human κ opioid receptors. Bioactivity-guided fractionation of the leaves of Salvia divinorum has resulted in the isolation of three new neoclerodane diterpenoids: divinatorin D ( 1), divinatorin E ( 2), and salvinorin G ( 3), together with 10 known terpenoids, divinatorin C ( 4), hardwickiic acid ( 5), salvinorin-A ( 6), -B ( 7), -C ( 8), -D ( 9), -E ( 10), and -F ( 11), presqualene alcohol ( 12), and ( E)-phytol ( 13). The structures of these three new compounds were characterized by spectroscopic methods. All these compounds were evaluated for their binding affinities to the human κ opioid receptors. In comparison with divinatorin D ( 1), divinatorin E ( 2), and salvinorin G ( 3), salvinorin A ( 6) is still the most potent κ agonist.