Synthesis of Salvinorin A Analogues as Opioid Receptor Probes

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.