Salvinorin B meth-oxy-methyl ether.
Thomas A Munro, Douglas M Ho, Bruce M Cohen
Acta crystallographica. Section E, Structure reports online November 1, 2012 DOI: 10.1107/s1600536812043449 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Crystallographic structure analysis Peer reviewed |
|---|---|
| Topics | Salvia divinorum |
| Key points | The authors report that the MOM ether of MOM-SalB adopts a 'classic anomeric' conformation, causing its terminal C and O atoms to overlap with corresponding atoms in salvinorin A despite an additional bond. This overlap is absent in a less potent tetrahydropyranyl ether, and the authors propose that the anomeric conformation may contribute to the derivative's enhanced potency, selectivity, and duration of action. |
Abstract
The title compound [MOM-SalB; systematic name: methyl (2S,4aR,6aR,7R,9S,10aS,10bR)-2-(3-fur-yl)-9-meth-oxy-meth-oxy-6a,10b-dimethyl-4,10-dioxo-2,4a,5,6,7,8,9,10a-octa-hydro-1H-benzo[f]isochromene-7-carboxyl-ate], C(23)H(30)O(8), is a deriv-ative of the κ-opioid salvinorin A with enhanced potency, selectivity, and duration of action. Superimposition of their crystal structures reveals, surprisingly, that the terminal C and O atoms of the MOM group overlap with the corresponding atoms in salvinorin A, which are separated by an additional bond. This counter-intuitive isosterism is possible because the MOM ether adopts the 'classic anomeric' conformation (gauche-gauche), tracing a helix around the planar acetate of salvinorin A. This overlap is not seen in the recently reported structure of the tetra-hydro-pyranyl ether, which is less potent. The classic anomeric conformation is strongly favoured in alk-oxy-methyl ethers, but not in substituted acetals, which may contribute to their reduced potency. This structure may prove useful in evaluating models of the activated κ-opioid receptor.
Citations in the library
Cites 6
- Neuropharmacology of the naturally occurring kappa-opioid hallucinogen salvinorin A. Pharmacological Reviews June 1, 2011
- Salvinorin B derivatives, EOM-Sal B and MOM-Sal B, produce stimulus generalization in male Sprague-Dawley rats trained to discriminate salvinorin A. Behavioural Pharmacology September 1, 2011
- Differential signaling properties at the kappa opioid receptor of 12-epi-salvinorin A and its analogues. Bioorganic & Medicinal Chemistry Letters January 15, 2012
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- 2-Methoxymethyl-salvinorin B is a potent kappa opioid receptor agonist with longer lasting action in vivo than salvinorin A. Journal of Pharmacology and Experimental Therapeutics March 2008
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