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Syntheses of Chiral 1,8-Cineole Metabolites and Determination of Their Enantiomeric Composition in Human Urine After Ingestion of 1,8-Cineole-Containing Capsules

Authors

  • Monika Schaffarczyk,

    1. Fraunhofer Institute for Process Engineering and Packaging (IVV), 85354 Freising (Germany), Fax: (+49) 9131-8522587
    2. BIOANALYTIK Weihenstephan, Z I E L Research Center for Nutrition and Food Sciences, Technical University Munich, 85350 Freising (Germany)
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  • Prof. Teodor Silviu Balaban,

    1. Aix Marseille Université, iSm2, CNRS, UMR 7313, 13397 Marseille (France)
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  • Prof. Michael Rychlik,

    1. BIOANALYTIK Weihenstephan, Z I E L Research Center for Nutrition and Food Sciences, Technical University Munich, 85350 Freising (Germany)
    2. Chair of Analytical Food Chemistry, Technical University of Munich, 85350 Freising (Germany)
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  • Prof. Andrea Buettner

    Corresponding author
    1. Fraunhofer Institute for Process Engineering and Packaging (IVV), 85354 Freising (Germany), Fax: (+49) 9131-8522587
    2. Department of Chemistry and Pharmacy, Food Chemistry, Emil Fischer, Center, University of Erlangen-Nuremberg, 91052 Erlangen (Germany)
    • Fraunhofer Institute for Process Engineering and Packaging (IVV), 85354 Freising (Germany), Fax: (+49) 9131-8522587
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Abstract

The chiral metabolites in human urine were investigated after ingestion of a 1,8-cineole (eucalyptol)-containing entero-coated capsule (Soledum). For identification of the various enantiomers the enantiomerically pure (−/+)-α2-hydroxy-1,8-cineole, (−/+)-β2-hydroxy-1,8-cineole, (−/+)-9-hydroxy-1,8-cineole, and (−/+)-2-oxo-1,8-cineole were prepared. To achieve this aim, after acetylation of the synthesized racemic 2- and 9-hydroxy-1,8-cineoles, pig liver esterase- or yeast-mediated hydrolysis provided the (−)-alcohols with their antipodal (+)-acetates with enantiomeric excess of 33–100 %. Dess–Martin periodinane oxidation of the alcohol (+)-α2-hydroxy-1,8-cineole, obtained by hydrolysis of the resolved acetate, provided the corresponding (+)-2-oxo-1,8-cineole, meanwhile the oxidation of (−)-α2-hydroxy-1,8-cineole gave (−)-2-oxo-1,8-cineole. Using these standards seven metabolites (+/−)-α2-hydroxy-1,8-cineole, (+/−)-β2-hydroxy-1,8-cineole, (+/−)-α3-hydroxycineole, (+/−)-3-oxo-1,8-cineole, 4-hydroxy-1,8-cineole, 7-hydroxy-1,8-cineole, and (+/−)-9-hydroxy-1,8-cineole, all liberated from their glucuronides, were identified in urine by GC-MS on a chiral stationary phase after consumption of 100 mg of 1,8-cineole. Metabolite screening using 2H3-1,8-cineol as the internal standard revealed (+/−)-α2-hydroxy-1,8-cineole as the predominant metabolite followed by (+/−)-9-hydroxy-1,8-cineole. Furthermore, the results showed that one enantiomer is always formed preferentially.

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