View source for Chemistry:Salvinorin B methoxymethyl ether

{{Short description|Chemical compound}}
{{Drugbox
| verifiedrevid      = 411541279
| 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
| image              = Salvinorin B methoxymethyl ether Structure.svg
| width              = <!--Clinical data-->
| tradename          = 
| legal_status       = Legal/Uncontrolled

<!--Identifiers-->| ATC_prefix         = none
| PubChem            = 44456192
| ChemSpiderID_Ref   = {{chemspidercite|correct|chemspider}}
| ChemSpiderID       = 23323947
| ChEMBL_Ref         = {{ebicite|correct|EBI}}
| PDB_ligand         = U99
| ChEMBL             = 258098

<!--Chemical data-->| C                  = 23
| H                  = 30
| O                  = 8
| molecular_weight   = 
| 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
| StdInChI_Ref       = {{stdinchicite|correct|chemspider}}
| StdInChI           = 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
| StdInChIKey_Ref    = {{stdinchicite|correct|chemspider}}
| StdInChIKey        = KFVUSZPWUZBAPF-AGQYDFLVSA-N
}}

'''Salvinorin B methoxymethyl ether''' ('''2-''O''-methoxymethylsalvinorin B''') is a semi-synthetic analogue of the natural product [[Chemistry:Salvinorin A|salvinorin A]] used in scientific research.<ref name="pmid18925386">{{cite journal | vauthors = Inan S, Lee DY, Liu-Chen LY, Cowan A | title = Comparison of the diuretic effects of chemically diverse kappa opioid agonists in rats: nalfurafine, U50,488H, and salvinorin A | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 379 | issue = 3 | pages = 263–270 | date = March 2009 | pmid = 18925386 | doi = 10.1007/s00210-008-0358-8 | s2cid = 8123431 }}</ref><ref name="pmid19014370">{{cite journal | vauthors = McLennan GP, Kiss A, Miyatake M, Belcheva MM, Chambers KT, Pozek JJ, Mohabbat Y, Moyer RA, Bohn LM, Coscia CJ | display-authors = 6 | title = Kappa opioids promote the proliferation of astrocytes via Gbetagamma and beta-arrestin 2-dependent MAPK-mediated pathways | journal = Journal of Neurochemistry | volume = 107 | issue = 6 | pages = 1753–1765 | date = December 2008 | pmid = 19014370 | pmc = 2606093 | doi = 10.1111/j.1471-4159.2008.05745.x }}</ref> It has a longer duration of action of around 2–3 hours, compared to less than 30 minutes for salvinorin A,<ref name="pmid18089845">{{cite journal | vauthors = Wang Y, Chen Y, Xu W, Lee DY, Ma Z, Rawls SM, Cowan A, Liu-Chen LY | display-authors = 6 | title = 2-Methoxymethyl-salvinorin B is a potent kappa opioid receptor agonist with longer lasting action in vivo than salvinorin A | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 324 | issue = 3 | pages = 1073–1083 | date = March 2008 | pmid = 18089845 | pmc = 2519046 | doi = 10.1124/jpet.107.132142 }}</ref> and has increased affinity and potency at the κ-opioid [[Biology:Receptor (biochemistry)|receptor]]. It is prepared from salvinorin B.<ref name="pmid15993589">{{cite journal | vauthors = Lee DY, Karnati VV, He M, Liu-Chen LY, Kondaveti L, Ma Z, Wang Y, Chen Y, Beguin C, Carlezon WA, Cohen B | display-authors = 6 | title = Synthesis and in vitro pharmacological studies of new C(2) modified salvinorin A analogues | journal = Bioorganic & Medicinal Chemistry Letters | volume = 15 | issue = 16 | pages = 3744–3747 | date = August 2005 | pmid = 15993589 | doi = 10.1016/j.bmcl.2005.05.048 }}</ref> The [[Chemistry:Crystal structure|crystal structure]] is almost superimposable with that of salvinorin A.<ref>{{cite journal |vauthors=Munro TA, Ho DM, Cohen BM |date=2012 |title=Salvinorin B methoxymethyl ether |journal=Acta Crystallographica Section E |volume=68 |issue=11 |pages=o3225–o3226 |doi=10.1107/s1600536812043449 |pmc=3515309 |pmid=23284529|bibcode=2012AcCrE..68O3225M }}</ref> Structures bound to the κ-opioid receptor have also been reported.<ref>{{cite journal | vauthors = Han J, Zhang J, Nazarova AL, Bernhard SM, Krumm BE, Zhao L, Lam JH, Rangari VA, Majumdar S, Nichols DE, Katritch V, Yuan P, Fay JF, Che T | display-authors = 6 | title = Ligand and G-protein selectivity in the κ-opioid receptor | journal = Nature | volume = 617 | issue = 7960 | pages = 417–425 | date = May 2023 | pmid = 37138078 | pmc = 10172140 | doi = 10.1038/s41586-023-06030-7 | bibcode = 2023Natur.617..417H }}</ref>

Salvinorin B methoxymethyl ether has a [[Chemistry:Dissociation constant#Protein-ligand binding|K<sub>i</sub>]] of 0.60 nM at the κ opioid receptor,<ref name="pmid17981041">{{cite journal | vauthors = Munro TA, Duncan KK, Xu W, Wang Y, Liu-Chen LY, Carlezon WA, Cohen BM, Béguin C | display-authors = 6 | title = Standard protecting groups create potent and selective kappa opioids: salvinorin B alkoxymethyl ethers | journal = Bioorganic & Medicinal Chemistry | volume = 16 | issue = 3 | pages = 1279–1286 | date = February 2008 | pmid = 17981041 | pmc = 2568987 | doi = 10.1016/j.bmc.2007.10.067 }}</ref> 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 [[Chemistry:Homologous series|homolog]], 'symmetry'.<ref name="pmid17981041" /><ref name="pmid19153716">{{cite journal | vauthors = Baker LE, Panos JJ, Killinger BA, Peet MM, Bell LM, Haliw LA, Walker SL | title = Comparison of the discriminative stimulus effects of salvinorin A and its derivatives to U69,593 and U50,488 in rats | journal = Psychopharmacology | volume = 203 | issue = 2 | pages = 203–211 | date = April 2009 | pmid = 19153716 | doi = 10.1007/s00213-008-1458-3 | doi-access = free }}</ref><ref>{{Cite journal | vauthors = Mercury D, Feelodd D |date=2008 |title=First look at a new psychoactive drug: symmetry (salvinorin B ethoxymethyl ether) |url=https://www.erowid.org/chemicals/salvinorin_b_ethoxymethyl_ether/salvinorin_b_ethoxymethyl_ether_article1.shtml |journal=Entheogen Review |volume=16 |issue=4 |pages=136–145 |issn=1066-1913 |via=}}</ref>

== See also ==
* [[Chemistry:RB-64|RB-64]]

== References ==
{{Reflist|2}}

{{Hallucinogens}}
{{Opioidergics}}

[[Category:Synthetic opioids]]
[[Category:3-Furyl compounds]]
[[Category:Lactones]]
[[Category:Ethers]]
[[Category:Ketones]]
[[Category:Kappa-opioid receptor agonists]]
[[Category:Methyl esters]]

{{Sourceattribution|Salvinorin B methoxymethyl ether}}