Synthetic studies of neoclerodane diterpenes from Salvia divinorum: role of the furan in affinity for opioid receptors

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 sugges...

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Bibliographic Details
Published in:Organic & biomolecular chemistry 2009-01, Vol.7 (18), p.3748-3756
Main Authors: Simpson, Denise S, Lovell, Kimberly M, Lozama, Anthony, Han, Nina, Day, Victor W, Dersch, Christina M, Rothman, Richard B, Prisinzano, Thomas E
Format: Article
Language:English
Subjects:
Crystallography, X-Ray
Diterpenes, Clerodane - chemical synthesis
Diterpenes, Clerodane - chemistry
Diterpenes, Clerodane - metabolism
Furans - metabolism
Humans
Protein Binding
Receptors, Opioid, kappa - metabolism
Salvia - chemistry
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Summary: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.
ISSN:1477-0520
1477-0539
DOI:10.1039/b905148a