Detection of a “Nonaromatic” NIH Shift during In Vivo Metabolism of the Monoterpene Carvone in Humans

Abstract

High-resolution gas chromatography in combination with mass spectrometry and high-resolution mass spectrometry was used to determine the positions and extent of labeling in the metabolites of carvone, namely in alpha,4-dimethyl-5-oxo-3-cyclohexene-1-acetic acid (dihydrocarvonic acid), alpha-methylene-4-methyl-5-oxo-3-cyclohexene-1-acetic acid (carvonic acid), and 5-(1,2-dihydroxy-1-methylethyl)-2-methyl-2-cyclohexen-1-one (uroterpenolone), after human ingestion of 9,9-dideutero- and 9-(13)C-carvone. Carvonic acid was formed by oxidation at the methyl carbon of the isopropenyl group of carvone, whereas dihydrocarvonic acid was formed by oxidation at the methylene position, most probably via carvone epoxide. A "nonaromatic" NIH shift must occur during the subsequent reactions yielding dihydrocarvonic acid. Additionally, dehydrogenation of dihydrocarvonic acid and hydrogenation of carvonic acid were observed, resulting in minor amounts of both acids owning a carboxy group of opposite origin. Uroterpenolone was found to be exclusively formed by oxidation at the methylene carbon of the isopropenyl group of carvone, and thus, most probably by hydrolysis of carvone epoxide.

Quantification of 1,8‐cineole and of its metabolites in humans using stable isotope dilution assays

“…unchen (1996/07). For wash out, the volunteer (female, 26 years old, body mass index 19.2) used toothpaste devoid from terpenes according to Engel [20] and avoided spices, herbs and fruits and other foods and cosmetics containing 1,8-cineole during 3 days prior to the study. Dried sage (6.4 g) was weighed into a tea filter and was brewed with 600 mL of boiling water.…”

Sensory and molecular characterisation of human milk odour profiles after maternal fish oil supplementation during pregnancy and breastfeeding

“…On the other hand, one must bear in mind that food aromas can originate from a diversity of substance classes with a broad range of chemical reactivity (Grosch, 2001;Nijssen et al, 1996), being often heavily metabolised in vivo (Buettner, 2002a(Buettner, , 2002bBuettner, 2010;Engel, 2001Engel, , 2002Zeller, Horst, & Rychlik, 2009).…”

Liquid-phase noncatalytic oxidation of monoterpenoids with nitrous oxide

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