Salvinorin B methoxymethyl ether

Salvinorin B methoxymethyl ether
Clinical data
ATC code	none;
Legal status
Legal status	Legal/Uncontrolled;
Identifiers
	IUPAC name 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;
CAS Number	864378-87-0;
PubChem CID	44456192;
ChemSpider	23323947 ;
ChEMBL	ChEMBL258098 ;
PDB ligand	U99 (PDBe, RCSB PDB);
CompTox Dashboard (EPA)	DTXSID201028497 ;
Chemical and physical data
Formula	C23H30O8
Molar mass	434.485 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES 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 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 ; Key:KFVUSZPWUZBAPF-AGQYDFLVSA-N ;
	(verify)

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 has a K_i 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]

References

^ 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.
^ 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.
^ 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.
^ 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.
^ Munro TA, Ho DM, Cohen BM (2012). "Salvinorin B methoxymethyl ether". Acta Crystallographica Section E. 68 (11): o3225–o3226. Bibcode:2012AcCrE..68o3225M. doi:10.1107/s1600536812043449. PMC 3515309. PMID 23284529.
^ 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.
^ ^a ^b 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.
^ 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.
^ 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.

[pmid18925386-1] 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.

[pmid19014370-2] 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.

[pmid18089845-3] 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.

[pmid15993589-4] 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. Bibcode:2012AcCrE..68o3225M. 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.

[pmid17981041-7] 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.

[pmid19153716-8] 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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See also

References