Synthetic studies of neoclerodane diterpenes from Salvia divinorum: role of the furan in affinity for opioid receptors.
Denise S Simpson, Kimberly M Lovell, Anthony Lozama, Nina Han, Victor W Day, Christina M Dersch, Richard B Rothman, Thomas E Prisinzano
Organic & biomolecular chemistry September 21, 2009 DOI: 10.1039/b905148a via PubMed
Summary
AI-generated from the abstractModifying the furan ring of salvinorin A, the active component of Salvia divinorum, produced new compounds with activity at opioid receptors. A computational study predicted salvinorin A to be a reproductive toxicant in mammals, suggesting its use may have adverse effects. Two new compounds, piperidine 21 and thiomorpholine 23, were identified as selective partial agonists at kappa opioid receptors. This suggests further structural changes could yield ligands with good opioid receptor selectivity but lower toxicity.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Key finding | Piperidine 21 and thiomorpholine 23 are selective partial agonists at kappa opioid receptors. |
Abstract
Further synthetic modification of the furan ring of salvinorin A (1), the major active component of Salvia divinorum, has resulted in novel neoclerodane diterpenes with opioid receptor affinity and activity. A computational study has predicted 1 to be a reproductive toxicant in mammals and is suggestive that use of 1 may be associated with adverse effects. We report in this study that piperidine 21 and thiomorpholine 23 have been identified as selective partial agonists at kappa opioid receptors. This indicates that additional structural modifications of 1 may provide ligands with good selectivity for opioid receptors but with reduced potential for toxicity.