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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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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cited_by cdi_FETCH-LOGICAL-c436t-90c5b98960b25fd712682fcaa28c3985a7256637fe6e28446059b3f0f6677ac43
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container_end_page 3756
container_issue 18
container_start_page 3748
container_title Organic & biomolecular chemistry
container_volume 7
creator Simpson, Denise S
Lovell, Kimberly M
Lozama, Anthony
Han, Nina
Day, Victor W
Dersch, Christina M
Rothman, Richard B
Prisinzano, Thomas E
description 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.
doi_str_mv 10.1039/b905148a
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source Royal Society of Chemistry:Jisc Collections:Royal Society of Chemistry Read and Publish 2022-2024 (reading list)
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
title Synthetic studies of neoclerodane diterpenes from Salvia divinorum: role of the furan in affinity for opioid receptors
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