A-and P-thujone

He, X. and Ortiz de Montellano, P.R. (2004) Radical rebound mechanism in cytochrome P-450 catalyzed hydroxylation of multifaceted radical clocks a-and p-thujone. The Journal of Biological Chemistry, 279, 39479-39484. 

The rate of the ring-opening reaction of 5, " and other substrates have been determined using an indirect method for the calibration of fast radical reactions, applicable for radicals with lifetimes as short as 1 ps/ This radical clock method is based on the use of Barton s use of pyridine-2-thione-Al-oxycarbonyl esters as radical precursors and radical trapping by the highly reactive thiophenol and benzeneselenol/ A number of radical clock substrates are known/ Other radical clock processes include racemization of radicals with chiral conformations, one-carbon ring expansion in cyclopentanones, norcarane and sprro[2,5]octane, a-and p-thujone radical rearrangements, and cyclopropylcarbinyl radicals or... 

Many other cases of free-radical migration of aryl groups have been found. Intramolecular radical rearrangements are known. The C-4 radicals of a- and p-thujone undergo two distinct rearrangement reactions, and it has been proposed that these could serve as simultaneous, but independent radical clocks. ... 

Karamenderes et al. [67] reported the composition and antimicrobial activity of the essential oils obtained from Achillea millefolium L. subsp. pannonica (Scheele) Hayek, Achillea millefolium subsp. millefolium, Achillea arithmifolia Waldst Kitt and Achillea kotschyi Boiss. subsp. kotschyi, four Achillea species from Turkey. 1,8-cineole, Fig. (2), artemisia alcohol and ascaridole were identified as major components. The essential oils showed antibacterial and antifungal effects even with low concentrations. The essential oil of the flowering tops of another Achillea species, Achillea fragantissimum (Forsk.) Sch. Bip growing in Sinai, was analyzed [68]. Santolina alcohol, a- and P-thujone, Fig. (5) and artemisia ketone account for approximately 80% of the oil. The oil showed marked antimicrobial activities against Escherichia coli. Bacillus subtilis and Staphylococcus aureus. 

Composition The European Pharmacopoeia lists linalyl acetate (56-78%), linalool (6.5-24%) and germacrene D (1.0-12%). a-Terpineol is limited to 5.0%, a- and P-thujone to 0.2%. Sclareol (0.4-2.6%) is found mainly in the concrete and is used for the synthesis of ambra fragrance materials. Further constituents are linalool oxide, geraniol, nerol, neryl and terpinyl acetate, citronellol, 1,8-cineole, benzaldehyde and n-nonanal. For further literature see [64, 65]. 

Composition 1,8-Cineole, terpinene-4-ol, bomeol, camphor, a- and p-thujone [163], Naef-Miiller et al. [164] report on unusual monoterpenes. 

Composition of the essential oil Mainly a- and P-thujone, thujyl alcohol and thujyl acetate respectively [301 ]. Some chemotypes contain cis- and trans-epoxyocimene, sabinyl and chrysanthenyl acetate, chrysanthenol as main components [302]. For latest literature see [303]. 

A list of 89 flavouring substances and 13 groups of substances without limitations is given (similar to the Japanese list). A restrictive list with 14 limited substances mentions e.g. P-asarone 0.1 ppm, coumarin in beverages 2 ppm, pulegone 100 ppm, quassine 5 ppm, quinine 85 ppm, safrole 1 ppm, a- and P-thujones 0.5 ppm etc. Propylene glycol and glycerol are mentioned as carrier solvents. 

Hold, K.M., N.S. Sirisoma, and J.E. Casida (2001). Detoxification of a- and P-thujones (the active ingredients of absinthe) Site specificity and species differences in cytochrome P450 oxidation in vitro and in vivo. Chem. Res. Toxicol. 14, 589-595. 

Wormwood contains a- and P-thujone, compounds that may cause convulsions and that bind to GABA receptors, resulting in excitation of the autonomic nervous system (H5ld et al. 2000). High amounts of thujone and thujone metabolites in the body may provoke convulsions and unconsciousness (Lee and Balick 2005 Olsen 2000). Nicotinic acid receptor, muscarinic cholinergic receptor, and 5-HT3 receptor activity has also been reported (Deiml et al. 2004 Lee and Balick 2005). 

The doses of intraperitoneally administered a- and P-thujone that produce convulsions have been reported as 590 mg/kg in mice (Wenzel and Ross 1957) and 100 mg/kg in rats (Sampson and Fernandez 1939). 

The LD50 of the compound thujone (mixture of a- and P thujone) is 500 mg/kg after oral administration to rats, 87.5 mg/kg after subcutaneous administration to mice, 240 mg/kg after intraperitoneal administration to rats, and 0.031 mg/kg after intravenous administration to rabbits (EMEA 1999 Naser et al. 2005). 

Fig. 4.8 a- and P-Thujone (P-thujone shown) function as dual radical clocks in which cyclopropyl ring opening serves as one clock and inversion of the methyl group stereochemistry as a second clock... 

Judzetiene and Budiene (2010) Lithuania 15 rratw-Sabinyl acetate (22% 51%), a- and P-Thujones (18% 72%)... 

This oil is often blended with a- and p thujones from cheaper sources like Thuja orientalis. Furthermore camphor or white camphor oil and camphene are used. GC-MS method is used to detect these adulterations. 

Gnitka R., 2010, Ef dent method of isolation of pnre (-)-a- and (+)-P-thujone from Thuja occidentcdis essential oil, Poster presented at the Symposium on Essential Oils, Wrodaw, Poland. 

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