Bioorganic & Medicinal Chemistry Letters
October 15, 2015
David Y W Lee, Gang Deng, Zhongze Ma et al.
The synthesis of a new series of C-2-alkyl-2-methoxymethyl-salvinorin ethers and their binding affinities at κ-, μ-, and δ-opioid receptors are presented. We have developed a synthesis that enables installation of alkyl-substituents at C-2 while maintaining the integrity of the C-2 methoxymethyl ether and retaining κ-opioid receptor binding activity. Among these new compounds,...
Tetrahedron Letters
September 29, 2010
Zhongze Ma, Gang Deng, David Y W Lee
11 citations
Salvinorin A is a naturally-occurring potent and selective kappa opioid receptor agonist, and smoking salvinorin A produces the most intense hallucinogenic effects in human. Eight neoclerodane diterpene derivatives were isolated from the smoke of salvinorin A, and their structures were identified by spectroscopic methods. The major structural changes include epimerizations, eliminations, and...
Bioorganic & Medicinal Chemistry Letters
March 1, 2009
Lu Yang, Wei Xu, Feng Chen et al.
Salvinorin A (1), the main active ingredient of Salvia divinorum, is a potent and selective kappa-opioid receptor (KOPR) agonist. A series of C-12 triazole analogs and the oxadiazole (4) analog of 1 are synthesized and screened for binding affinity at kappa, mu (MOPR), or delta (DOPR). Surprisingly, all triazole analogs have shown negligible binding affinity at opioid receptors and the...
Tetrahedron Letters
March 10, 2008
Zhongze Ma, David Y W Lee
To unambiguously confirm the actual product in autoxidation of salvinorin A under basic conditions, deacetyl-1,10-didehydrosalvinorin G was synthesized from salvinorin C via intermediate salvinorin H. Furthermore, oxidation of salvinorin D with manganese dioxide gave salvinorin G in good yield.
Journal of Pharmacology and Experimental Therapeutics
March 2008
Yulin Wang, Yong Chen, Wei Xu et al.
Salvinorin (Sal) A is a naturally occurring, selective kappa opioid receptor (KOPR) agonist with a short duration of action in vivo. Pharmacological properties of a C(2) derivative, 2-methoxymethyl (MOM)-Sal B, were characterized. MOM-Sal B bound to KOPR with high selectivity and displayed approximately 3-fold higher affinity than U50,488H...
Tetrahedron Letters
July 30, 2007
Zhongze Ma, David Y W Lee
In comparison with the NMR data of salvinorin A and its 8-epimer, the published structure of deacetyl-1,10-didehydrosalvinorin G was revised to its 8-epimer. The stereochemistry of 8-epi-deacetyl-1,10-didehydrosalvinorin G was further confirmed by NOESY and chemical synthesis.
Bioorganic & Medicinal Chemistry Letters
November 1, 2006
David Y W Lee, Minsheng He, Lee-Yuan Liu-Chen et al.
Salvinorin A, a compound isolated from the plant Salvia divinorum, is a potent and highly selective agonist for the kappa opioid receptor. For exploration of its structure and activity relationships, further modifications, such as reduction at the C(4) position, have been studied and a series of salvinorin A derivatives were prepared. These C(4)-modified salvinorin A analogues were screened for...
Journal of Pharmacology and Experimental Therapeutics
January 2006
William A Carlezon, Cécile Béguin, Jennifer A DiNieri et al.
Endogenous opioids seem to play a critical role in the regulation of mood states. For example, there is accumulating evidence that stimulation of kappa-opioid receptors, upon which the endogenous opioid dynorphin acts, can produce depressive-like behaviors in laboratory animals. Here we examined whether systemic administration of salvinorin A (SalvA), a potent and highly selective kappa-opioid...
Bioorganic & Medicinal Chemistry
October 1, 2005
David Y W Lee, Zhongze Ma, Lee-Yuan Liu-Chen et al.
Bioactivity-guided fractionation of the leaves of Salvia divinorum has resulted in the isolation of three new neoclerodane diterpenoids: divinatorin D (1), divinatorin E (2), and salvinorin G (3), together with 10 known terpenoids, divinatorin C (4), hardwickiic acid (5), salvinorin-A (6), -B (7), -C (8), -D (9), -E (10), and -F (11), presqualene alcohol (12), and (E)-phytol (13). The...
Bioorganic & Medicinal Chemistry Letters
October 1, 2005
David Y W Lee, Minsheng He, Leelakrishna Kondaveti et al.
Salvinorin A is the most potent naturally occurring opioid agonist with a high selectivity and affinity for kappa-opioid receptor. To explore its structure-activity relationships, modifications at the C(4) position have been studied and a series of salvinorin A derivatives were prepared. These C(4)-modified salvinorin A analogues were screened for binding and functional activities at the human...