{{Chembox | ImageFile = Tremetone_chemical_structure.svg | ImageSize = 200px | PIN = 1-[(2''R'')-2-(Prop-1-en-2-yl)-2,3-dihydro-1-benzofuran-5-yl]propan-1-one | OtherNames = |Section1={{Chembox Identifiers | CASNo = 4976-25-4 | CASNo_Ref = {{cascite|correct|CAS}} | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 451MA27V7H | PubChem = 78673 | ChemSpiderID = 71024 | SMILES = O=C(C1=CC=C(O[C@@H](C(C)=C)C2)C2=C1)C | InChI = 1S/C13H14O2/c1-8(2)13-7-11-6-10(9(3)14)4-5-12(11)15-13/h4-6,13H,1,7H2,2-3H3/t13-/m1/s1 | InChIKey = UVYUUQGGBNKRFU-CYBMUJFWSA-N | StdInChI = | StdInChIKey = }} |Section2={{Chembox Properties | C=13 | H=14 | O=2 | Appearance = | Density = | MeltingPt = | BoilingPt = | Solubility = }} |Section3={{Chembox Hazards | MainHazards = | FlashPt = | AutoignitionPt = }} }}

'''Tremetone''' is a constituent of the toxic compound '''tremetol''', found in snakeroot (''Ageratina altissima''), that contributes<ref>[Davis, T. Zane, et al. "Toxicity of white snakeroot (Ageratina altissima) and chemical extracts of white snakeroot in goats." Journal of agricultural and food chemistry 63.7 (2015): 2092-2097. https://scholar.google.com/scholar?hl=en&as_sdt=0%2C26&q=Identification+of+the+toxic+components+in+white+snakeroot+%28Ageratina+altissima%29+&btnG=]</ref> to cause milk sickness in humans and trembles in livestock.<ref name=Bonner_1962>{{cite journal |last1=Bonner |first1=W. A. |title=Ketones from "white snakeroot" ''Eupatorium urticaefolium'' |journal=Tetrahedron |date=1962 |volume=18 |issue=11 |pages=1295–1309 |doi=10.1016/0040-4020(62)80010-6 }}</ref><ref name=Bowen_1963>{{cite journal |doi=10.1021/jm00339a023 |pmid=14185993 |title=The Synthesis and Pharmacological Action of Tremetone |journal=Journal of Medicinal Chemistry |volume=6 |issue=3 |pages=315–9 |year=1963 |last1=Bowen |first1=Douglas M. |last2=Degraw |first2=Joseph I. |last3=Shah |first3=Vinod R. |last4=Bonner |first4=William A. }}</ref><ref name=Bonner_1964>{{cite journal |last1=Bonner |first1=W. A. |title=The absolute configurations of tremetone and toxol |journal=Tetrahedron |date=1964 |volume=20 |issue=6 |pages=1419–25 |doi=10.1016/S0040-4020(01)99135-5 }}</ref><ref name=Lee_2010>{{cite journal |doi=10.1021/jf1012456 |pmid=20681643 |title=Tremetone and Structurally Related Compounds in White Snakeroot (''Ageratina altissima''): A Plant Associated with Trembles and Milk Sickness |journal=Journal of Agricultural and Food Chemistry |volume=58 |issue=15 |pages=8560–5 |year=2010 |last1=Lee |first1=Stephen T. |last2=Davis |first2=T. Zane |last3=Gardner |first3=Dale R. |last4=Colegate |first4=Steven M. |last5=Cook |first5=Daniel |last6=Green |first6=Benedict T. |last7=Meyerholtz |first7=Kimberly A. |last8=Wilson |first8=Christina R. |last9=Stegelmeier |first9=Bryan L. |last10=Evans |first10=Tim J. |bibcode=2010JAFC...58.8560L }}</ref> Tremetone is the main constituent of at least 11 chemically related substances in tremetol.<ref name=Lee_2010 /> Tremetone is toxic to fish, but not to chicken, and is therefore not the major toxic compound in tremetol.<ref name=Bowen_1963 /> Tremetol can be found in a number of different species of the family Asteraceae, including snakeroot and rayless goldenrod (''Isocoma pluriflora'').<ref>{{cite web|title=Metabolite Information: Tremetone|url=http://kanaya.naist.jp/knapsack_jsp/information.jsp?word=C00002412}}</ref>

==Synthesis== Tremetol, an oil with a straw-colored tinge, was first isolated from white snakeroot by J.F. Couch in 1929. Column chromatography of tremetol yielded a hydrocarbon, two steroids, and three ketones. Further isolation experiments revealed that tremetone is the major ketone constituent of the compound tremetol. Hence, tremetone was hypothesized to be responsible for the “trembles” that characterize the milk sickness disease. Tremetone was first synthesized in July 1963 by DeGraw, Bowen, and Bonner.<ref>{{cite journal |doi=10.1016/0040-4020(63)80002-2 |title=The synthesis of racemic tremetone |journal=Tetrahedron |volume=19 |issue=1 |pages=19–24 |year=1963 |last1=Degraw |first1=J.I. |last2=Bowen |first2=D.M. |last3=Bonner |first3=W.A. }}</ref> This synthesis is illustrated below. The final dehydration step was accomplished by treatment with phosphoryl chloride/pyridine at 75 °C.

600px|thumb|center|4-step synthesis of racemic tremetone

This synthesis had a 75% yield, but the final product was a racemate that would not suitably undergo chiral resolution. This prevented isolation of the natural levorotary enantiomer of tremetone; thus limiting the ability to further analyze its biological mechanisms. However, in November 1963, the enantiomers of tremetone were isolated by Bowen, et al. via the synthesis illustrated below.<ref name="Bowen_1963"/> Resolution of enantiomers occurred by co-crystallization of the acid following Na/Hg reduction.

600px|thumb|center|Synthesis (Enantiomeric)

== See also ==

* Milk sickness * Snakeroot (''Ageratina altissima'') * Toxol, a structurally related substance (3-hydroxy-tremetone)

== References ==

<references />

Category:Piceol ethers Category:Plant toxins Category:Benzofurans Category:Alkene derivatives Category:Aromatic ketones