Pharmaceutical Sciences Faculty Publications

Title

Synthetic Studies of Neoclerodane Diterpenes from Salvia Divinorum: Role of the Furan in Affinity for Opioid Receptors

Document Type

Article

Publication Date

8-26-2009

Journal Title

Organic & Biomolecular Chemistry

Volume

7

Issue

18

First Page

3748

Last Page

3756

DOI

10.1039/b905148a

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.

Keywords

Neoclerodane diterpenes, salvia divinorum, furan, opioid receptors