:Elemicin
{{Short description|Chemical compound}}
{{Drugbox
| Watchedfields = changed
| verifiedrevid = 410138806
| IUPAC_name = 1,2,3-Trimethoxy-5-(prop-2-en-1-yl)benzene
| image = ElemicinSVG.svg
| alt = Skeletal formula of elemicin
| image2 = Elemicin-3D-balls.png
| alt2 = Ball-and-stick model of the elemicin molecule
| tradename =
| pregnancy_category =
| legal_status = Uncontrolled
| dependency_liability = None
| addiction_liability = Low / None
| routes_of_administration = Oral
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life =
| excretion =
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 487-11-6
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = HSZ191AKAN
| ATC_prefix =
| ATC_suffix =
| PubChem = 10248
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank =
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 9830
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C10451
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 458690
| C = 12
| H = 16
| O = 3
| smiles = C=CCC1=CC(OC)=C(OC)C(OC)=C1
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C12H16O3/c1-5-6-9-7-10(13-2)12(15-4)11(8-9)14-3/h5,7-8H,1,6H2,2-4H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = BPLQKQKXWHCZSS-UHFFFAOYSA-N
}}
Elemicin is a phenylpropene, a natural organic compound, and is a constituent of several plant species' essential oils.
Natural occurrence
Elemicin is a constituent of the oleoresin and the essential oil of Canarium luzonicum (also referred to as elemi). Elemicin is named after this tree. One study found it to compose 2.4% of the fresh essential oil.
{{cite journal | vauthors = Villanueva MA, Torres RC, Baser KH, Özek T, Kürkçüoglu M | title = The Composition of Manila Elemi Oil | journal = Flavour and Fragrance Journal | year = 1993 | volume = 8 | pages = 35–37 | doi = 10.1002/ffj.2730080107 }} Elemicin is also present in the oils of the spices nutmeg and mace, with it composing 2.4% and 10.5% of those oils respectively.{{cite book| vauthors = Leela N |title=Chemistry of Spices|year=2008|publisher=Biddles Ltd. |location=Calicut, Kerala, India |isbn=9781845934057|pages=165–188 [170] |url=https://books.google.com/books?id=5WY08iuJyawC&q=Chemistry+of+Spices}} Structurally, elemicin is similar to myristicin, differing only by myristicin's methyl group that joins the two oxygen atoms that make up its dioxymethy moiety, with both constituents being found in nutmeg and mace.
Isolation
Elemicin was first isolated from elemi oil using vacuum distillation. Specifically, the substance was collected between 162-165 °C at a reduced pressure of 10 torr.{{cite journal |title=Constituents of Essential Oils. Elemicin, a High-boiling Constituent of Elemi Oil, and the Displacement of Alkyloxygroups in the Benzene Nucleus by Hydrogen|journal=Journal of the Chemical Society, Abstracts|year=1908|volume=94|issue=A493|pages=557–558|url=https://books.google.com/books?id=JGJFAQAAIAAJ&q=Constituents+of+Essential+Oils.+Elemicin%2C+a+High-boiling+Constituent+of+Elemi+Oil%2C+and+the+Displacement+of+Alkyloxygroups+in+the+Benzene+Nucleus+by+Hydrogen&pg=PA557|doi=10.1039/CA9089400493|url-access=subscription}}{{cite journal| vauthors = Semmler F |title=Zur Kenntnis der Bestandteile der ätherischen Öle. (Über das Elemicin, einen hochsiedenden Bestandteil des Elemiöls, und über Ersetzung von Alkyloxy-gruppen am Benzolkern durch Wasserstoff.)|journal=Berichte der Deutschen Chemischen Gesellschaft|date=1908|volume=41|issue=2|pages=1768–1775 |doi=10.1002/cber.19080410240 |url=https://zenodo.org/record/1426299}}
Preparation
Elemicin has been synthesized from syringol and allyl bromide using Williamson ether synthesis and Claisen rearrangement.{{cite journal| vauthors = Mauthner F |title=Die Synthese des Elemicins und Isoelemicins|journal=Justus Liebigs Annalen der Chemie|year=1918|volume=414|issue=2|pages=250–255|doi=10.1002/jlac.19184140213|url=https://zenodo.org/record/1427645}}{{cite journal |title=Synthesis of Elemicin and of isoElemicin|journal=Journal of the Chemical Society, Abstracts|year=1918|volume=114|pages=i428|doi=10.1039/CA9181400421}} The electrophilic aromatic substitution entering the para-position was made possible by secondary Cope rearrangement.{{cite book| vauthors = Thomas L |title=Named Organic Reactions, 2nd Edition|year=2005|publisher=John Wiley & Sons, Ltd.|location=Wolfsburg, Germany|isbn=978-0470010402|pages=58–60 [59]|url=https://books.google.com/books?id=-BEdbO-08WMC&q=Named+Organic+Reactions,+2nd+Edition+2005}} This is due to syringol's allyl aromatic ether being blocked by ethers in both ortho-positions. When blocked the allyl group migrates to the para-position, in this case with yields above 85%.{{cite book| vauthors = Adams R |title=Organic Reactions| volume = II |year=1944|publisher=John Wiley & Sons, Inc.|location=New York|pages=2–44 [44]|doi=10.1002/0471264180.or002.01 |chapter=The Claisen Rearrangement |isbn=978-0471264187 }}
Uses
Elemicin has been used to synthesize the proto-alkaloid mescaline.{{cite journal| vauthors = Hahn G, Wassmuth H |title=Über β-[Oxyphenyl]-äthylamine und ihre Umwandlungen, I. Mitteil.: Synthese des Mezcalins |journal=Berichte der Deutschen Chemischen Gesellschaft (A and B Series) |year=1934 |volume=67 |issue=4 |pages=696–708 |doi= 10.1002/cber.19340670430}}
Pharmacology
Raw nutmeg causes anticholinergic-like effects, which are attributed to elemicin and myristicin.
{{cite journal | vauthors = McKenna A, Nordt SP, Ryan J | title = Acute nutmeg poisoning | journal = European Journal of Emergency Medicine | volume = 11 | issue = 4 | pages = 240–241 | date = August 2004 | pmid = 15249817 | doi = 10.1097/01.mej.0000127649.69328.a5 | s2cid = 21133983 }}{{cite journal | vauthors = Shulgin AT, Sargent T, Naranjo C | title = The chemistry and psychopharmacology of nutmeg and of several related phenylisopropylamines | journal = Psychopharmacology Bulletin | volume = 4 | issue = 3 | pages = 13 | date = December 1967 | pmid = 5615546 | url = http://bitnest.ca/external.php?id=%250E%253D9%250F%2524G%252F%2518B%255B%255B4%2522.FXQ%255CO%2500TK | access-date = 2015-09-02 | url-status = dead | format = pdf | archive-url = https://web.archive.org/web/20140420142511/http://bitnest.ca/external.php?id=%250E%253D9%250F%2524G%252F%2518B%255B%255B4%2522.FXQ%255CO%2500TK | archive-date = 2014-04-20 }} Elemicin inhibits Stearoyl-CoA Desaturase 1 (SCD1) by metabolic activation. Elemicin is one of the main components in aromatic food and has antimicrobial, antioxidant, and antiviral activities. Elemicin possesses genotoxicity and carcinogenicity. Excess consumption of raw nutmeg results in delirium and disorientation.{{Citation |title=elemicin |url=https://medical-dictionary.thefreedictionary.com/elemicin |work=The Free Dictionary |access-date=2022-10-28}}
Elemicin's psychoactivity is still a point of research, however some research suggests it may act like an agonist of the 5-HT2A receptors, similar to many psychedelics.[http://herbpedia.wdfiles.com/local--files/attachments/Elemicin_2014_Journal.pdf Evaluation of 5-HT2A Receptor Agonistic Property of Elemicin] However, this is controversial as the psychoactive effects of elemicin and plants it is found in, such as nutmeg, seem to cause more deliriant-like effects than psychedelic ones.{{cite journal | vauthors = Kelly BD, Gavin BE, Clarke M, Lane A, Larkin C | title = Nutmeg and psychosis | journal = Schizophrenia Research | volume = 60 | issue = 1 | pages = 95–96 | date = March 2003 | pmid = 12505144 | doi = 10.1016/s0920-9964(02)00204-9 | s2cid = 7540364 }}