0000000000237085
AUTHOR
Christina M. Dersch
Synthetic studies of neoclerodane diterpenoids from Salvia splendens and evaluation of opioid receptor affinity
Abstract Salvinorin A ( 1 ), a neoclerodane diterpene from the hallucinogenic mint Salvia divinorum , is the only known non-nitrogenous and specific κ-opioid agonist. Several structural congeners of 1 isolated from Salvia splendens ( 2 – 8 ) together with a series of semisynthetic derivatives ( 9 – 24 ), some of which possess a pyrazoline structural moiety ( 9 , 19 – 22 ), have been tested for affinity at human μ, δ, and κ opioid receptors. None of these compounds showed high affinity binding to these receptors. However, 10 showed modest affinity for κ receptors suggesting that other natural neoclerodanes from different Salvia species may possess opioid affinity.
Synthetic studies on neoclerodane diterpenes from Salvia splendens: oxidative modifications of ring A.
Salvinorin A (1), a neoclerodane diterpene from the hallucinogenic mint Salvia divinorum, is the only known naturally occurring non-nitrogenous and specific κ-opioid agonist. Some oxidative modifications of the A ring in the congeners of 1 isolated from Salvia splendens salviarin, splenolide B, splendidin and in the non-natural 8-epi-salviarin gave new derivatives, some of which were tested as agonists at opioid receptors. However, none of these compounds were active. The presence of the C-18, C-19 lactone could be at the origin of the observed lack of binding affinity.