ABSTRACT
Several neoclerodanes, such as salvinorin A (1) and herkinorin (3), have recently been shown to possess opioid receptor activity in vitro and in vivo. To explore the structure-affinity relationships of this interesting class of compounds, we have synthesized a series of analogues from 1 isolated from Salvia divinorum. Here, we report the semisynthesis of neoclerodane diterpenes and their structure-affinity relationships at opioid receptors. This work will allow the further development of novel opioid receptor ligands.
Subject(s)
Diterpenes , Plants, Medicinal/chemistry , Receptors, Opioid/agonists , Salvia/chemistry , Crystallography, X-Ray , Diterpenes/chemical synthesis , Diterpenes/chemistry , Diterpenes/pharmacology , Diterpenes, Clerodane , Molecular Conformation , Molecular Structure , Structure-Activity RelationshipABSTRACT
Structural modification of salvinorin A, the active component of Salvia divinorum, has resulted in the synthesis of novel neoclerodane diterpenes with opioid receptor affinity and activity. We report in this study a nonnitrogenous neoclerodane diterpene with mu opioid receptor affinity (13) that is an agonist at mu opioid receptors. This represents the identification of a novel structural class of mu opioid receptor agonists.
