Synthetic Studies of Neoclerodane Diterpenes from Salvia divinorum:  Preparation and Opioid Receptor Activity of Salvinicin Analogues

• Published in: Journal of medicinal chemistry Vol. 50; no. 15; pp. 3596 - 3603
• Main Authors: SIMPSON, Denise S., KATAVIC, Peter L., LOZAMA, Anthony, HARDING, Wayne W., PARRISH, Damon, DESCHAMPS, Jeffrey R., DERSCH, Christina M., PARTILLA, John S., ROTHMAN, Richard B., NAVARRO, Hernan, PRISINZANO, Thomas E.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 26-07-2007
• Subjects: Animals; Biological and medical sciences; CHO Cells; Cricetinae; Cricetulus; Crystallography, X-Ray; Diterpenes, Clerodane - chemical synthesis; Diterpenes, Clerodane - chemistry; Diterpenes, Clerodane - pharmacology; Furans - chemical synthesis; Furans - chemistry; Furans - pharmacology; General pharmacology; Humans; Medical sciences; Molecular Structure; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Radioligand Assay; Receptors, Opioid, delta - agonists; Receptors, Opioid, delta - antagonists & inhibitors; Receptors, Opioid, kappa - agonists; Receptors, Opioid, kappa - antagonists & inhibitors; Receptors, Opioid, mu - agonists; Receptors, Opioid, mu - antagonists & inhibitors; Salvia; Salvia - chemistry; Stereoisomerism; Structure-Activity Relationship; Central America; Mexico; America; Terpenoid; Pharmacognosy; Reaction product; Opioid receptor; Molecular interaction; Lactone; In vitro; Biological activity; Medicinal plant; Biological fixation; Folk medicine; Labiatae; Dicotyledones; Angiospermae; Plant origin; Diterpene; Oxadiazole derivatives; Isolation; Spermatophyta; Oxygenation; Salvia divinorum; Structural analysis
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm070393d

Further modification of salvinorin A (1a), the major active component of Salvia divinorum, has resulted in the synthesis of novel neoclerodane diterpenes with opioid receptor affinity and activity. We report in this study that oxadiazole 11a and salvidivin A (12a), a photooxygenation product of 1a, have been identified as the first neoclerodane diterpenes with kappa antagonist activity. This indicates that additional structural modifications of 1a may lead to analogues with higher potency and utility as drug abuse medications.