alpha- and beta-Thujones (herbal medicines and food additives): synthesis and analysis of hydroxy and dehydro metabolites.
Essential oils containing alpha- and beta-thujones are important herbal medicines and food additives. The thujone diastereomers are rapidly metabolized convulsants acting as noncompetitive blockers of the gamma-aminobutyric acid-gated chloride channel. Synthesis and analysis of the metabolites are essential steps in understanding their health effects. Oxidation of alpha- and beta-thujones as their 2,3-enolates with oxodiperoxymolybdenum(pyridine)(hexamethylphosphoric triamide) gave the corresponding (2R)-2-hydroxythujones assigned by (1)H and (13)C NMR and X-ray crystallography. alpha-Thujone was converted to 4-hydroxy-alpha- and -beta-thujones via the 3,4-enol acetate on oxidation with peracid and osmium tetroxide, respectively. Ozonation provided 7-hydroxy-alpha- and -beta-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 alpha- and beta-thujones.
Sirisoma
N S
NS
Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, 115 Wellman Hall, University of California, Berkeley, California 94720-3112, USA.
Höld
K M
KM
Casida
J E
JE
D000081008:Bicyclic Monoterpenes; D005503:Food Additives / Q000032:analysis; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D039821:Monoterpenes; D010084:Oxidation-Reduction; D008517:Phytotherapy; D010936:Plant Extracts / Q000032:analysis* / Q000378:metabolism; D013729:Terpenes / Q000032:analysis* / Q000138:chemical synthesis / Q000378:metabolism*
D000081008:Bicyclic Monoterpenes; D005503:Food Additives; D039821:Monoterpenes; D010936:Plant Extracts; D013729:Terpenes; C005790:beta-thujone