α- and β-Thujones (Herbal Medicines and Food Additives):  Synthesis and Analysis of Hydroxy and Dehydro Metabolites

• Published in: Journal of agricultural and food chemistry 2001-04, Vol.49 (4), p.1915-1921
• Main Authors: Sirisoma, Nilantha S, Höld, Karin M, Casida, John E
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Food Additives - analysis; Gas Chromatography-Mass Spectrometry - methods; General pharmacology; Medical sciences; Monoterpenes; Oxidation-Reduction; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Phytotherapy; Plant Extracts - analysis; Plant Extracts - metabolism; Terpenes - analysis; Terpenes - chemical synthesis; Terpenes - metabolism
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf001445+

Essential oils containing α- and β-thujones are important herbal medicines and food additives. The thujone diastereomers are rapidly metabolized convulsants acting as noncompetitive blockers of the γ-aminobutyric acid-gated chloride channel. Synthesis and analysis of the metabolites are essential steps in understanding their health effects. Oxidation of α- and β-thujones as their 2,3-enolates with oxodiperoxymolybdenum(pyridine)(hexamethylphosphoric triamide) gave the corresponding (2R)-2-hydroxythujones assigned by 1H and 13C NMR and X-ray crystallography. α-Thujone was converted to 4-hydroxy-α- and -β-thujones via the 3,4-enol acetate on oxidation with peracid and osmium tetroxide, respectively. Ozonation provided 7-hydroxy-α- and -β-thujones, and by dehydration provided the 7,8-dehydro compounds. 4,10-Dehydrothujone was prepared from sabinene via sabinol. The hydroxy and dehydro derivatives are readily identified and analyzed by GC/MS as the parent compounds and trimethylsilyl and methyloxime derivatives. A separate study established that all of these compounds are metabolites of α- and β-thujones. Keywords: α- and β-Thujones; oxidation reactions; metabolite synthesis; metabolite derivatization; GC/MS analysis