Synthetic studies of neoclerodane diterpenoids from Salvia splendens and evaluation of opioid receptor affinity

Salvinorin A (1), a neoclerodane diterpene from the hallucinogenic mint Salvia divinorum, is the only known non-nitrogenous and specific k-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 m, d, and k opioid receptors. None of these compounds showed high affinity binding to these receptors. However, 10 showed modest affinity for k receptors suggesting that other natural neoclerodanes from different Salvia species may possess opioid affinity.