Tetrahedron letters
September 29, 2010
Zhongze Ma, Gang Deng, David Y W Lee
11 citations
Salvinorin A, a potent and selective kappa opioid receptor agonist, produces intense hallucinogenic effects when smoked. The smoke of salvinorin A contains at least eight neoclerodane diterpene derivatives, which were isolated and identified using spectroscopic methods. The major chemical transformations occurring during smoking include epimerizations, eliminations, and rearrangements, leading to these novel compounds.
Bioorganic & medicinal chemistry letters
October 1, 2010
David Y W Lee, Lu Yang, Wei Xu et al.
Salvinorin A, the main active ingredient of Salvia divinorum, is a potent and selective κ opioid receptor (KOPR) agonist. Researchers synthesized a series of C-2 halogenated analogs of salvinorin A as molecular probes to investigate the binding pocket at the C-2 position, particularly the effects of α versus β configuration. Binding and functional studies showed that β isomers generally bind better than α isomers, except for iodinated analogs. None of the C-2 halogenated analogs improved KOPR binding affinity compared to the parent compound. Functional assays characterized one analog, 6b, as a partial agonist with a maximum effect of 46% of the full agonist U50,488H at 250 nM. Affinity to the kappa receptor increased with atomic radius (I>Br>Cl>F), consistent with halogen bonding interactions.
Bioorganic & medicinal chemistry letters
March 1, 2009
Lu Yang, Wei Xu, Feng Chen et al.
Salvinorin A, the main active ingredient of Salvia divinorum, is a potent and selective kappa-opioid receptor agonist. A series of C-12 triazole analogs and an oxadiazole analog were synthesized and tested for binding affinity at kappa, mu, and delta opioid receptors. Surprisingly, all triazole analogs showed negligible binding affinity at opioid receptors, and the oxadiazole analog, previously reported as a mu and kappa opioid receptor antagonist, exhibited very low affinities and no antagonism in the binding assays. These results suggest that electronic factors affecting either the electron density of a hydrogen bond acceptor at C-12 or hydrophobic interactions between the C-12 moiety and the kappa-opioid receptor are critical for C-12 analog affinity.