546-80-5

Basic information

• Product Name: ALPHA-(-)-THUJONE
• Synonyms: (1s,4r,5r)-(-)-3-thujanon;3-Thujanone, (-)-;3-Thujanone, (1S,4R,5R)-(-)-;4-methyl-1-(1-methylethyl)-,[1S-(1.alpha.,4.alpha.,5.alpha.)]-Bicyclo[3.1.0]hexan-3-one;4-Methyl-1-(1-methylethyl)bicyclo[3.1.0]hexan-3-one;6-Ketosabinane;bicyclo(3.1.0)hexan-3-one,4-methyl-1-(1-methylethyl)-,(1s-1-alpha,4-alpha,5;Bicyclo[3.1.0]hexan-3-one, 4-methyl-1-(1-methylethyl)-, [1S-(1alpha,4alpha,5alpha)]-
• CAS NO: 546-80-5
• Molecular Formula: C₁₀H₁₆O
• Molecular Weight: 152.23
• EINECS: 208-912-2
• Product Categories: Organics
• Mol File: 546-80-5.mol
• Article Data: 5

Chemical Properties

• Melting Point: 181℃
• Boiling Point: 84-86 °C17 mm Hg(lit.)
• Flash Point: 148 °F
• Appearance: Colorless or almost colorless liquid with a menthol- like odor (Albert-Puleo, 1978; Budavari, 1996)
• Density: 0.914 g/mL at 20 °C(lit.)
• Refractive Index: n20/D 1.450
• Storage Temp.: 2-8°C
• BRN: 4660369
• CAS DataBase Reference: ALPHA-(-)-THUJONE(CAS DataBase Reference)
• NIST Chemistry Reference: ALPHA-(-)-THUJONE(546-80-5)
• EPA Substance Registry System: ALPHA-(-)-THUJONE(546-80-5)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Safety Statements: 23-26-36/37/39-45
• RIDADR: UN 2810 6.1/PG 3
• WGK Germany: 3
• RTECS: XO9625000
• F: 23
• Hazardous Substances Data: 546-80-5(Hazardous Substances Data)

Usage

Uses

α-Thujone is a GABA modulator and a genotoxic compound found in plants used in traditional medicines in developing countries.

Chemical Properties

Colorless liquid. Insoluble in water; soluble in alcohol. Combustible.

Definition

ChEBI: The (1S,4R,5R)-stereoisomer of alpha-thujone.

General Description

(-)-α-Thujone, a monoterpene ketone found in the essential oil of Thuja occidentalis, shows potent antitumorigenic effect.

Hazard

Toxic by ingestion.

Biochem/physiol Actions

GABAA receptor antagonist.

Safety Profile

Poison by intravenous, intraperitoneal, and subcutaneous routes. Moderately toxic by ingestion. Serious physiological consequences from abuse of absinthe (mainly in France) led to its abolition in 1915. Wormwood is still used in concentrations of less than 10 ppm in flavored wines. Thujone at 30 mg/kg causes convulsions associated with lesions of the cerebral cortex. Little is known of thujone metabolism. Both forms occur in wormwood oil, oak moss. The a form is major constituent of cedar leaf oil or oil of thuja, sage. The p form occurs in tansy, yarrow. When heated to decomposition it emits acrid smoke and irritating fumes.

InChI:InChI=1/C10H16O/c1-6(2)10-4-8(10)7(3)9(11)5-10/h6-8H,4-5H2,1-3H3

Upstream product

• 21653-18-9 (-)-neothujol 
• 1125-12-8 thujone 
• 7712-81-4 sabinol 
• 471-15-8 (+)-isothujone 
• 2175-91-9 6,6'-dimethyl fulvene 
• 74-88-4 methyl iodide 
• 542-92-7 cyclopenta-1,3-diene 
• 191861-60-6 (1S,4R,5R)-3-Benzenesulfonyl-1-isopropyl-4-methyl-bicyclo[3.1.0]hexane 
• 21653-20-3 (-)-3-thujol 
• 85-44-9 phthalic anhydride 
• 4584-08-1 (1S,4R)-thujan-3-one semicarbazone 
• 7647-01-0 hydrogenchloride 
• 7732-18-5 water 
• 191861-57-1 Carbonic acid (R)-5,5-bis-benzenesulfonyl-6-methyl-oct-7-en-2-ynyl ester methyl ester 

Downstream Products

• 21653-20-3 (-)-3-thujol 
• 21653-18-9 (-)-neothujol 
• 7712-79-0 isothujol 
• 21653-19-0 1-isopropyl-4-methylbicyclo[3.1.0]hexan-3-ol 
• 18791-12-3 (-)-thujone p-tosylhydrazone 
• 1416449-87-0 C₂₇H₃₁NO₅ 
• 1416449-89-2 C₂₇H₃₁NO₅ 
• 1416449-84-7 C₂₇H₃₁NO₅ 
• 1416449-86-9 C₂₇H₃₁NO₅ 
• 7788-93-4 (-)-Isothujanol-p-toluolsulfonat 
• 7788-93-4 (-)-Thujyl-p-toluolsulfonat 
• 5033-79-4 (-)-Thujylamin 
• 40267-59-2 (+)-isothujone oxime 
• 2553-61-9 (1S,4S)-thujan-3-one-(2,4-dinitro-phenylhydrazone); (+)-isothujone-(2,4-dinitro-phenylhydrazone) 

Relevant articles and documents

A six-step total synthesis of α-thujone and: D 6-α-thujone, enabling facile access to isotopically labelled metabolites

The short synthesis of α-thujone relies on the functionalization of the readily available dimethylfulvene. Furthermore, the three main metabolites of the natural product were also synthesized. Since d6-acetone can be used as a starting material, the route developed allows for the facile incorporation of isotopic labels which are required for detecting and quantifying trace amounts via GC/MS analysis.

Palladium-Catalysed Intramolecular Cyclisation of Olefinic Propargylic Carbonates and Application to the Diastereoselective Synthesis of Enantiomerically pure (-)-α-Thujone

Intramolecular [Pd2(dba)3]/tri(2-furyl)phosphine-catalysed (dba = dibenzylideneacetone, PhCH= CHCOCH=CHPh) cyclisations of olefinic propargylic carbonates I provided alk-1-enyl-(3-aza)bicyclo[3.1.0]-hexanes VIII in good yields. A palladium cascade sequence I → II → III → IV → VII → VIII is proposed. Furthermore, chiral propargylic carbonates such as 23, 24 and 25 allowed diastereoselective formation of bicyclo[3.1.0]hexanes 29, 30 and 31, respectively. The first diastereoselective synthesis of the monoterpene, (-)-α-thujone 40 illustrates the potential of the method.

(-) 3 Isothujone, a small nonnitrogenous molecule with antinociceptive activity in mice

(-) 3 isothujone and (+) 3 thujone were examined for antinociceptive activity using the hot plate and Nilsen tests. In the hot plate test (-) 3 isothujone (ED50 = 6.5 mg/kg) was found to be codeine like and equipotent with (-) Δ9 tetrahydrocannabinol while the racemic material was essentially half as potent as the levorotatory isomer. (+) 3 Thyjone was inactive in both antinociceptive tests as were several structural analogues of the 3 thujones. As with the THC's less antinociceptive activity was observed in the Nilsen test than in the hot plate assay. Acute toxicities for the 3 thujones were determined and vastly improved synthetic procedures have been developed for two long known but difficultly accessible 3 thujanols.