Synthetic studies of neoclerodane diterpenes from Salvia divinorum: exploration of the 1-position.
Kenneth G Holden, Kevin Tidgewell, Alfred Marquam, Richard B Rothman, Hernan Navarro, Thomas E Prisinzano
Bioorganic & Medicinal Chemistry Letters November 15, 2007 DOI: 10.1016/j.bmcl.2007.09.050 (opens in new tab) via PubMed
Summary
AI-generated from the abstractRemoving the C-1 ketone from salvinorin A and its analogue herkinorin changes their activity at opioid receptors. A derivative called 1-deoxo-1,10-dehydrosalvinorin A acts as a moderately potent antagonist at all three opioid receptor subtypes. Herkinorin, a mu opioid agonist, becomes a weak antagonist when its C-1 ketone is removed. These results indicate the C-1 ketone is a key structural feature for mu agonist activity.
Study at a glance
| Characteristics | Peer reviewed |
|---|---|
| Key finding | The C-1 ketone of herkinorin is essential for mu agonist activity; removing it converts the compound to a weak antagonist. |
Abstract
Modification of the C-1 ketone of salvinorin A (2a) produces analogues with opioid antagonist properties. Of particular significance is the finding that 1-deoxo-1,10-dehydrosalvinorin A (11a) is a moderately potent antagonist at all three opioid receptor subtypes, and that herkinorin (2b), a mu agonist, is converted to a weak antagonist by removal of the C-1 ketone (3b and 11b). These observations suggest that the ketone of 2b is a key structural feature responsible for mu agonist activity.