Salvinorin B methoxymethyl ether

Salvinorin B methoxymethyl ether (2-O-methoxymethylsalvinorin B) is a semi-synthetic analogue of the natural product salvinorin A used in scientific research.[1][2] It has a longer duration of action of around 2–3 hours, compared to less than 30 minutes for salvinorin A,[3] and has increased affinity and potency at the κ-opioid receptor. It is prepared from salvinorin B.[4] The crystal structure is almost superimposable with that of salvinorin A.[5] Structures bound to the κ-opioid receptor have also been reported.[6]

Salvinorin B methoxymethyl ether
Clinical data
ATC code
  • none
Legal status
Legal status
  • Legal/Uncontrolled
Identifiers
  • methyl (2S,4aR,6aR,7R,9S,10aS,10bR)-2-(furan-3-yl)-9-(methoxymethoxy)-6a,10b-dimethyl-4,10-dioxo-2,4a,5,6,7,8,9,10a-octahydro-1H-benzo[f]isochromene-7-carboxylate
PubChem CID
ChemSpider
ChEMBL
PDB ligand
Chemical and physical data
FormulaC23H30O8
Molar mass434.485 g·mol−1
3D model (JSmol)
  • C[C@@]12CC[C@H]3C(=O)O[C@@H](C[C@@]3([C@H]1C(=O)[C@H](C[C@H]2C(=O)OC)OCOC)C)C4=COC=C4
  • InChI=1S/C23H30O8/c1-22-7-5-14-21(26)31-17(13-6-8-29-11-13)10-23(14,2)19(22)18(24)16(30-12-27-3)9-15(22)20(25)28-4/h6,8,11,14-17,19H,5,7,9-10,12H2,1-4H3/t14-,15-,16-,17-,19-,22-,23-/m0/s1 checkY
  • Key:KFVUSZPWUZBAPF-AGQYDFLVSA-N checkY
  (verify)

Salvinorin B methoxymethyl ether has a Ki of 0.60 nM at the κ opioid receptor,[7] and is around five times more potent than salvinorin A in animal studies, although it is still only half as potent as its ethoxymethyl ether homolog, 'symmetry'.[7][8][9]

See also

References
  1. Inan S, Lee DY, Liu-Chen LY, Cowan A (March 2009). "Comparison of the diuretic effects of chemically diverse kappa opioid agonists in rats: nalfurafine, U50,488H, and salvinorin A". Naunyn-Schmiedeberg's Archives of Pharmacology. 379 (3): 263–270. doi:10.1007/s00210-008-0358-8. PMID 18925386. S2CID 8123431.
  2. McLennan GP, Kiss A, Miyatake M, Belcheva MM, Chambers KT, Pozek JJ, et al. (December 2008). "Kappa opioids promote the proliferation of astrocytes via Gbetagamma and beta-arrestin 2-dependent MAPK-mediated pathways". Journal of Neurochemistry. 107 (6): 1753–1765. doi:10.1111/j.1471-4159.2008.05745.x. PMC 2606093. PMID 19014370.
  3. Wang Y, Chen Y, Xu W, Lee DY, Ma Z, Rawls SM, et al. (March 2008). "2-Methoxymethyl-salvinorin B is a potent kappa opioid receptor agonist with longer lasting action in vivo than salvinorin A". The Journal of Pharmacology and Experimental Therapeutics. 324 (3): 1073–1083. doi:10.1124/jpet.107.132142. PMC 2519046. PMID 18089845.
  4. Lee DY, Karnati VV, He M, Liu-Chen LY, Kondaveti L, Ma Z, et al. (August 2005). "Synthesis and in vitro pharmacological studies of new C(2) modified salvinorin A analogues". Bioorganic & Medicinal Chemistry Letters. 15 (16): 3744–3747. doi:10.1016/j.bmcl.2005.05.048. PMID 15993589.
  5. Munro TA, Ho DM, Cohen BM (2012). "Salvinorin B methoxymethyl ether". Acta Crystallographica Section E. 68 (11): o3225–o3226. doi:10.1107/s1600536812043449. PMC 3515309. PMID 23284529.
  6. Han J, Zhang J, Nazarova AL, Bernhard SM, Krumm BE, Zhao L, et al. (May 2023). "Ligand and G-protein selectivity in the κ-opioid receptor". Nature. 617 (7960): 417–425. Bibcode:2023Natur.617..417H. doi:10.1038/s41586-023-06030-7. PMC 10172140. PMID 37138078.
  7. Munro TA, Duncan KK, Xu W, Wang Y, Liu-Chen LY, Carlezon WA, et al. (February 2008). "Standard protecting groups create potent and selective kappa opioids: salvinorin B alkoxymethyl ethers". Bioorganic & Medicinal Chemistry. 16 (3): 1279–1286. doi:10.1016/j.bmc.2007.10.067. PMC 2568987. PMID 17981041.
  8. Baker LE, Panos JJ, Killinger BA, Peet MM, Bell LM, Haliw LA, Walker SL (April 2009). "Comparison of the discriminative stimulus effects of salvinorin A and its derivatives to U69,593 and U50,488 in rats". Psychopharmacology. 203 (2): 203–211. doi:10.1007/s00213-008-1458-3. PMID 19153716.
  9. Mercury D, Feelodd D (2008). "First look at a new psychoactive drug: symmetry (salvinorin B ethoxymethyl ether)". Entheogen Review. 16 (4): 136–145. ISSN 1066-1913.
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