Nootkatone: Difference between revisions

| Verifiedfields = changed

| verifiedrevid = 408778015

| Name = Nootkatone

| ImageFile = Nootkatone recrystallized.jpg

| ImageSize =

| ImageName = Nootkatone crystals

| ImageFile1 = Nootkatone.svg

| ImageSize1 =

| ImageName1 =

| ImageFile2 = (+)-nootkatone-from-xtal-3D-bs-17.png

| IUPACName = 4α,5α-Eremophila-1(10),11-dien-2-one

| SystematicName = (4''R'',4a''S'',6''R'')-4,4a-Dimethyl-6-(prop-1-en-2-yl)-4,4a,5,6,7,8-hexahydronaphthalen-2(3''H'')-one

| OtherNames = (+)-nootkatone

|Section1={{Chembox Identifiers

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| KEGG_Ref = {{keggcite|correct|kegg}}

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 81377

| CASNo_Ref = {{cascite|correct|??}}

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = IZ2Y119N4J

| RTECS =

|Section2={{Chembox Properties

| C=15 | H=22 | O=1

| Appearance = Clear or white crystals, impure samples appear as a viscous yellow liquid

| Density = 0.968 g/mL

| Solubility = Insoluble in water, very soluble in ethanol, dichloromethane, ethyl acetate, soluble in hexanes

| MeltingPtC = 36

| BoilingPtC = 170

| pKa =

| pKb =

| Viscosity =

|Section3={{Chembox Structure

| MolShape =

| Coordination =

| CrystalStruct =

| Dipole =

|Section7={{Chembox Hazards

| ExternalSDS =

| MainHazards =

| FlashPt = ~

| FlashPtC = 100

| GHSPictograms = {{GHS07}}

| GHSSignalWord = warning

| HPhrases = {{HPhrases|H317}}

| PPhrases = {{PPhrases|P280}}

| GHS_ref = <ref>GHS: [https://www.sigmaaldrich.com/NL/en/product/ALDRICH/74437 Sigma-Aldrich 74437] (SDS)</ref>

|Section8={{Chembox Related

| OtherAnions =

| OtherCations =

| OtherCompounds =

| OtherFunction = [[Valencene]]

| OtherFunction_label = [[terpene]]s

'''Nootkatone''' is an [[organic compound]], a [[sesquiterpenoid]], which means that it is a C15 derivative that also contains an oxygen-containing [[functional group]] (a [[ketone]]). It is the most valuable [[aroma compound]] of [[grapefruit]].<ref>{{cite journal | last =Furusawa | first =Mai |author2=Toshihiro Hashimoto |author3=Yoshiaki Noma |author4=Yoshinori Asakawa | title =Highly Efficient Production of Nootkatone, the Grapefruit Aroma from Valencene, by Biotransformation | journal =Chem. Pharm. Bull. | volume =53 | issue =11 | pages =1513–1514 | date =November 2005 | doi =10.1248/cpb.53.1513 | pmid =16272746 | doi-access =free }}</ref> Nootkatone was originally isolated from the wood of the [[Cupressus nootkatensis|Alaskan yellow cedar]], ''Cupressus nootkatensis''. The species name, nootkatensis, is derived from the language of the [[Nuu-Chah-Nulth]] people of Canada (formerly referred to as the Nootka people).<ref>{{Cite web|url=https://conifersociety.org/conifers/cupressus-nootkatensis/|title = Cupressus nootkatensis / Nootka cypress &#124; Conifer Species}}</ref>

==Production ==

Nootkatone is produced commercially from valencene, another more abundant sesquiterpene.<ref>{{cite journal |doi=10.1038/nature17431 |title=Scalable and sustainable electrochemical allylic C–H oxidation |date=2016 |last1=Horn |first1=Evan J. |last2=Rosen |first2=Brandon R. |last3=Chen |first3=Yong |last4=Tang |first4=Jiaze |last5=Chen |first5=Ke |last6=Eastgate |first6=Martin D. |last7=Baran |first7=Phil S. |journal=Nature |volume=533 |issue=7601 |pages=77–81 |pmid=27096371 |pmc=4860034 |bibcode=2016Natur.533...77H }}</ref>

[[File:ValenceneToNootkatone.svg|thumb|center|322px|The conversion of valencene to nootkatone is an example of allylic oxidation.]]

Allylix (Now Lallemand of Montreal, PQ), developed a fermentation process to nootkatone.<ref name=AllylixSite>{{cite web|title=Cost effective fermentation replaces costly extraction |url=http://www.allylix.com/content/nootkatone|work=Allylix|accessdate=10 August 2012 |url-status=dead |archiveurl=https://web.archive.org/web/20120325001759/http://www.allylix.com/content/nootkatone |archivedate=2012-03-25}}</ref><ref name=xconomy2011>{{cite news|last=Bigelow|first=Bruce|title=Nootkatone, So A-peeling in Grapefruit, is Repellent to Mosquitoes and Ticks|url=http://www.xconomy.com/san-diego/2011/04/28/nootkatone-so-a-peeling-in-grapefruit-is-repellent-to-mosquitoes-and-ticks/|accessdate=10 August 2012|newspaper=xconomy.com|date=2011-04-28}}</ref>

==Mechanism of action==

As is true of other plant terpenoids, nootkatone activates α-adrenergic type 1 [[octopamine]] receptor (PaOA1) in susceptible [[arthropods]], causing fatal spasms.<ref>{{cite book|doi=10.1021/bk-2018-1289.ch012|chapter=Plant Terpenoids Modulate α-Adrenergic Type 1 Octopamine Receptor (PaOA1) Isolated from the American Cockroach (Periplaneta americana)|title=Advances in the Biorational Control of Medical and Veterinary Pests|series=ACS Symposium Series|year=2018|last1=Norris|first1=Edmund J.|last2=Gross|first2=Aaron D.|last3=Kimber|first3=Michael J.|last4=Bartholomay|first4=Lyric|last5=Coats|first5=Joel|volume=1289|pages=219–235|isbn=9780841233591}}</ref>

==Uses==

Nootkatone in spray form is an effective repellent or [[insecticide]] against [[Ixodes scapularis|deer ticks]]<ref name="USDA2011">{{Cite news |url=http://www.ars.usda.gov/is/AR/archive/jan11/ticks0111.htm |title=Lignin + Nootkatone = Dead Ticks |author=Jan Suszkiw |date=January 2011 |publisher=USDA}}</ref><ref name="Dolan2009"/><ref name="Jordan et al 2012">{{Cite journal

| last1 = Jordan | first1 = Robert A.

| last2 = Schulze | first2 = Terry L.

| last3 = Dolan | first3 = Marc C.

| title = Efficacy of Plant-Derived and Synthetic Compounds on Clothing as Repellents Against ''Ixodes scapularis'' and ''Amblyomma americanum'' (Acari: Ixodidae)

| doi = 10.1603/ME10241

| journal = Journal of Medical Entomology

| volume = 49

| pages = 101–106

| date=January 2012

| pmid = 22308777| pmc =

| issue = 1 | url = https://apps.dtic.mil/sti/pdfs/ADA557262.pdf| archive-url = https://web.archive.org/web/20170618123116/http://www.dtic.mil/get-tr-doc/pdf?AD=ADA557262| url-status = live| archive-date = June 18, 2017| doi-access = free}}</ref> and [[Amblyomma americanum|lone star ticks]].<ref name="Dolan2009">{{Cite journal | last1 = Dolan | first1 = MC. | last2 = Jordan | first2 = RA. | last3 = Schulze | first3 = TL. | last4 = Schulze | first4 = CJ. | last5 = Manning | first5 = MC. | last6 = Ruffolo | first6 = D. | last7 = Schmidt | first7 = JP. | last8 = Piesman | first8 = J. | last9 = Karchesy | first9 = JJ. | title = Ability of two natural products, nootkatone and carvacrol, to suppress ''Ixodes scapularis'' and ''Amblyomma americanum'' (Acari: Ixodidae) in a Lyme disease endemic area of New Jersey | journal = J Econ Entomol | volume = 102 | issue = 6 | pages = 2316–24 |date=Dec 2009 | doi = 10.1603/029.102.0638| pmid = 20069863 | s2cid = 2731012 }}</ref><ref name="Jordan et al 2012"/> It is also an effective repellent or insecticide against mosquitos, and may repel bed bugs, head lice, [[Formosan termite]]s,<ref name="pmid11441443">{{cite journal |vauthors=Zhu BC, Henderson G, Chen F, Maistrello L, Laine RA |title=Nootkatone is a repellent for Formosan subterranean termite (Coptotermes formosanus) |journal=J Chem Ecol |volume=27 |issue=3 |pages=523–31 |date=March 2001 |pmid=11441443 |doi=10.1023/a:1010301308649 |url=}}</ref> and other insects.<ref name="NPR2001">{{Cite news |url=https://www.npr.org/2011/04/18/135468567/repelling-bugs-with-the-essence-of-grapefruit |title=Repelling Bugs with the Essence of Grapefruit |author=Richard Knox |date=April 18, 2011 |work=[[NPR]]}}</ref> It is an environmentally friendly insecticide because it is a volatile essential oil that does not persist in the environment.<ref name="NPR2001"/> It was approved by the U.S. EPA for this use on August 10, 2020.<ref>{{Cite web|last=|first=|date=10 August 2020|title=EPS approves nootkatone|url=https://www.epa.gov/pesticides/nootkatone-now-registered-epa|access-date=|website=}}</ref> Its ability to repel ticks, mosquitoes, and other insects may last for hours, in contrast to other plant-based oil repellants like citronella, peppermint oil, and lemongrass oil.<ref>{{cite news|last=McNeil|first=Donald G. Jr.|title=Citrus Flavoring Is Weaponized Against Insect-Borne Diseases|url=https://www.nytimes.com/2020/08/10/health/tick-mosquito-repellant-nootkatone.html|accessdate=2021-07-05|newspaper=nytimes.com|date=2020-08-11}}</ref> It is nontoxic to humans, is an approved food additive,<ref name="NPR2001"/> and is commonly used in foods, cosmetics, and pharmaceuticals.<ref name="USDA2011"/> The [[Centers for Disease Control and Prevention|CDC]] has licensed patents to two companies to produce an insecticide and an insect repellant.<ref name=NPR2001 />

== See also ==

* [[Grapefruit mercaptan]]

== References ==

== External links ==

[[Category:Enones]]

[[Category:Decalins]]

[[Category:Alkene derivatives]]