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 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.
Simpson
Denise S
DS
Department of Medicinal Chemistry, The University of Kansas, Lawrence, KS 66045-7582, USA.
Lovell
Kimberly M
KM
Lozama
Anthony
A
Han
Nina
N
Day
Victor W
VW
Dersch
Christina M
CM
Rothman
Richard B
RB
Prisinzano
Thomas E
TE
D018360:Crystallography, X-Ray; D045785:Diterpenes, Clerodane / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D005663:Furans / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D027544:Salvia / Q000737:chemistry*
D045785:Diterpenes, Clerodane; D005663:Furans; D017473:Receptors, Opioid, kappa; C090499:salvinorin A; C039281:furan
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