546-80-5

Usage

Uses

Used in Traditional Medicine:
ALPHA-(-)-THUJONE is used as a traditional medicine ingredient for its potential therapeutic effects. It has been incorporated into various remedies in developing countries, where it is believed to possess healing properties.
Used in Pharmaceutical Research:
As a GABA modulator, ALPHA-(-)-THUJONE is used in pharmaceutical research to explore its potential as a treatment for neurological disorders and conditions related to the central nervous system. Its ability to interact with the GABA receptor suggests that it may have applications in managing anxiety, epilepsy, and other related conditions.
Used in Toxicological Studies:
Due to its genotoxic nature, ALPHA-(-)-THUJONE is utilized in toxicological studies to better understand the mechanisms of genotoxicity and to develop methods for assessing the safety of natural compounds. This research can contribute to the development of guidelines and regulations for the use of plant-based medicines and other products containing ALPHA-(-)-THUJONE.
Used in Flavor and Fragrance Industry:
ALPHA-(-)-THUJONE is used as a flavoring agent and in the fragrance industry for its distinct scent and taste. Its unique aroma profile makes it a valuable component in the creation of various perfumes, colognes, and flavorings.

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

• 85-44-9 phthalic anhydride 
• 4584-08-1 (1S,4R)-thujan-3-one semicarbazone 
• 21653-18-9 (-)-neothujol 
• 1125-12-8 thujone 
• 7712-81-4 sabinol 
• 7647-01-0 hydrogenchloride 
• 7732-18-5 water 
• 2175-91-9 6,6'-dimethyl fulvene 
• 74-88-4 methyl iodide 
• 542-92-7 cyclopenta-1,3-diene 
• 191861-57-1 Carbonic acid (R)-5,5-bis-benzenesulfonyl-6-methyl-oct-7-en-2-ynyl ester methyl ester 
• 191861-58-2 (1R,4R,5R)-3,3-Bis-benzenesulfonyl-1-isopropenyl-4-methyl-bicyclo[3.1.0]hexane 
• 191861-59-3 (1S,4R,5R)-3,3-Bis-benzenesulfonyl-1-isopropyl-4-methyl-bicyclo[3.1.0]hexane 
• 471-15-8 (+)-isothujone 

Downstream Products

• 69460-05-5 ((1S)-2c-acetyl-1-isopropyl-cycloprop-r-yl)-acetic acid 
• 74418-34-1 4β-(Hydroxymethyl)-thujan-3-one 
• 21653-20-3 (-)-3-thujol 
• 1125-12-8 thujone 
• 499-75-2 carvacrol 
• 40267-59-2 thujone oxime 
• 40267-59-2 (-)-thujone oxime 
• 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 
• 2553-61-9 (1S,4S)-thujan-3-one-(2,4-dinitro-phenylhydrazone); (+)-isothujone-(2,4-dinitro-phenylhydrazone) 
• 40267-59-2 (+)-isothujone oxime 
• 1416449-87-0 C₂₇H₃₁NO₅ 

Relevant academic research and scientific papers

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.

Kinetics of thermal rearrangements in the Δ2-thujene system: A full quadrisection of a perturbed bicyclo[3.1.0]hex-2-ene

Further insight into the behavior of suppositional diradicals in a caldera is sought in the thermal rearrangements among the four "Δ 2-thujenes", two 1-isopropyl-4-methylbicyclo[3.1.0]hex-2-enes [(-)-cis-1 and (+)-trans-2] and two isomers, exo- and endo-3-isopropyl-6- methylbicyclo[3.1.0]hex-2-ene [(+)-exo-3 and (-)-endo-4]. Optically pure trans-3-isopropyl-5-vinylcyclopentene (5) is the final, strongly thermochemically favored product, the result of an intramolecular homodienyl shift of a methyl hydrogen atom in (-)-endo-4. The set of twelve specific rate constants, four sets of three each, that define the interrelations among the four isomers has been extracted from data acquired starting from each isomer. An attractive mechanistic hypothesis involving an, intermediate diradical of iso conformation, common, for example, to both (-)-cis-1 and (+)-exo-3 (as educts), that proceeds to an anticonformer common to both (+)-trans-2 and (-)-endo-4 does not lead to a satisfactory rationalization of the product distribution. Addition of a second mechanistic conceptual scheme, that of a diradical-in-transit behaving as if there were a measure of continuous bonding (for example, (+)-trans-2 proceeding directly to (-)-cis-1), improves agreement with experiment. Over a 30 °C range of temperature, there is no credible change in product distribution.

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.

THE OCTANT RULE. XVI. CONFORMATION AND CIRCULAR DICHROISM OF SYN AND ANTI 2-METHYLBICYCLOHEXAN-3-ONES, THUJONE AND ISOTHUJONE

(1S,5S)-exo-2(R)-Methylbicyclohexan-3-one (1) and (1S,5S)-endo-2(S)-methylbicyclohexan-3-one (2) were synthesized and their circular dichroism (CD) spectra run.Conformational analysis based on molecular mechanics calculations and Karplus equation analyses of vicinal H/H NMR coupling constants indicate boat-like sofa conformations for both 1 and 2, with very little ring distortion from the symmetry of the parent bicyclohexan-3-one.The lone dissymmetric ψ-axial and ψ-equatorial methyl groups of 1 and 2, respectively, are both octant consignate.The natural product analogs of 1 and 2, (-)-3-isothujone (3) and (+)-3-thujone (4) were prepared and examined similarly.Their α-methyl perturbers dominate the CD n-?* Cotton effects.

(-) 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.