2,9-Dihydroxy- and 2,10-Dihydroxy-1,8-cineole. Two New Possum Urinary Metabolites

Carman, RM; Garner, A. Christopher; Klika, KD

doi:10.1071/ch9941509

Cited by 18 publications

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“…1) along with 7-hydroxy-1,8-cineole and the secondary alcohols 2-hydroxy-1,8-cineole (both a-and b-isomers) and 3-hydroxyl-1,8-cineole (both a-and b-isomers). Besides these, the dihydroxylated derivatives, cineolic acids and hydroxycineolic acids have been identified as cineole metabolites [6,7]. Due to eucalyptus leaves being their main diet, possums and koalas are adopted to high intake of 1,8-cineole.…”

Section: Qualitative Analysis Of 18-cineole Metabolites In Humansmentioning

confidence: 99%

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

Horst

Rychlik

2010

Molecular Nutrition Food Res

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The metabolism of 1,8-cineole after ingestion of sage tea was studied. After application of the tea, the metabolites 2-hydroxy-1,8-cineole, 3-hydroxy-1,8-cineole, 9-hydroxy-1,8-cineole and, for the first time in humans, 7-hydroxy-1,8-cineole were identified in plasma and urine of one volunteer. For quantitation of these metabolites and the parent compound, stable isotope dilution assays were developed after synthesis of [(2)H(3)]-1,8-cineole, [9/10-(2)H(3)]-2-hydroxy-1,8-cineole and [(13)C,(2)H(2)]-9-hydroxy-1,8-cineole as internal standards. Using these standards, we quantified 1,8-cineole by solid phase microextraction GC-MS and the hydroxyl-1,8-cineoles by LC-MS/MS after deconjugation in blood and urine of the volunteer. After consumption of 1.02 mg 1,8-cineole (19 μg/kg bw), the hydroxycineoles along with their parent compound were detectable in the blood plasma of the volunteer under study after liberation from their glucuronides with 2-hydroxycineole being the predominant metabolite at a maximum plasma concentration of 86 nmol/L followed by the 9-hydroxy isomer at a maximum plasma concentration of 33 nmol/L. The parent compound 1,8-cineole showed a low maximum plasma concentration of 19 nmol/L. In urine, 2-hydroxycineole also showed highest contents followed by its 9-isomer. Summing up the urinary excretion over 10 h, 2-hydroxycineole, the 9-isomer, the 3-isomer and the 7-isomer accounted for 20.9, 17.2, 10.6 and 3.8% of the cineole dose, respectively.

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Section: Qualitative Analysis Of 18-cineole Metabolites In Humansmentioning

confidence: 99%

“…Fig. 1) and the respective diols, cineolic acids and hydroxyl cineolic acids as phase I metabolites in urine and blood plasma [6][7][8]. Regarding toxicity of 1,8-cineole, the oral acute LD 50 in rats is reported to be 2480 mg/kg bw [9].…”

Section: Introductionmentioning

confidence: 97%

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

Horst

Rychlik

2010

Molecular Nutrition Food Res

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“…Consequently, there are a large number of possible regio-and stereo-isomers of cineole metabolites. For example, 9-hydroxy-, 9-carboxy-, 2-hydroxy-, 3-hydroxy-and 3-hydroxycineole are excreted in possum urine as partial racemates (Carman and Klika 1992;Carman et al 1994). Although and represent a trivial stereochemical nomenclature, the structures of metabolites are shown in the cited references.…”

Section: Introductionmentioning

confidence: 98%

“…The metabolism of cineole in the possum is known in general terms although the detailed structures have only been described for some metabolites (Carman et al 1994 Figure 1. Cineole and its metabolites.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of 1,8-cineole, a dietary toxin, in the brushtail possum (Trichosurus vulpecula): Significance for feeding

McLean¹,

Boyle²,

Brandon³

et al. 2007

Xenobiotica

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1,8-Cineole (cineole) is a Eucalyptus leaf toxin that defends against predation by herbivores such as the brushtail possum (Trichosurus vulpecula). The aim of the current study was to characterize the pharmacokinetics of cineole in the possum to improve understanding about how possums can avoid cineole toxicity when eating a Eucalyptus diet. Nine male possums were trapped in the wild and acclimated to captivity; a subcutaneous port was then implanted for venous blood sampling. Cineole was administered intravenously (10 and 15 mg kg(-1)) via a lateral tail vein and orally (30, 100 and 300 mg kg(-1)) by gavage, and blood concentrations of cineole and its metabolites were determined by gas chromatography. Cineole had a large terminal volume of distribution (V(z) = 27 l kg(-1)) and a high clearance (43 ml min(-1) kg(-1)), equal to hepatic blood flow. The terminal half-life was approximately 7 h. Oral bioavailability was low (F = 0.05) after low doses, but increased tenfold with dose, probably due to saturable first-pass metabolism. These findings indicate that when possums feed on a cineole diet, they eat until the cineole consumed is sufficient to saturate pre-systemic metabolism, leading to a rapid rise in bioavailability and cineole blood levels, and a cessation of the feeding bout. This is the first report on the pharmacokinetics of a dietary toxin in a wild herbivore, and provides insights into the interactions between the blood concentration of a plant secondary metabolite and the browsing behaviour of a herbivore.

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“…Thus, for the depiction of all four stereoisomeric diepoxides of (+)-(4R)-limonene, structure 1e nicely fulfills the demands for clarity and consistency with chemical restraints. Overall, the terminology in use for processes, behavio ocesses, take for example the m Similarly, for 2α,9-dihydroxy-1,8-cineole [13], to depict both enantiomers of this compound unambiguously, structure 2a depicted in Figure 2 fulfills the demands in contrast to 2b which, due to the undefined stereo bonds at C 1 -C 2 and C 1 -C 6 , implies the presence of one or other or both of the C-8 inverse epimers [7] {viz. (1S,2S,4R,8R) -2α,9-dihydroxy-1,8-cineole and (1R,2R,4S,8R)-2α,10-dihydroxy-1,8-cineole}, whilst 2c with undefined stereo bonds at C 8 -C 9 and C 8 -C 10 , implies the presence of one or other or both of the C-8 epimers {viz.…”

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confidence: 99%

Suggested New Terms for Describing Chiral States and the State-Dependent Behavior of Chiral Systems

Klika¹

2012

IJOC

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Deficiencies in the terminology used to describe chiral systems exist for behaviors under various processes and thus a more general, robust terminology is considered. For example, the descriptions for characterizing melting point, solubility, and recrystallization behaviors were adopted well before it was realized that perturbation of the enantiomeric composition (ec) due to self-disproportionation could be effected by processes other than recrystallization such as sublimation, chromatography over achiral substrates, and even distillation. Thus, an endeavor has been made to address the question of universally describing behaviors under processes that effect, or are dependent on, the ec. The main terms that have been defined with respect to behavior are homomate (analogous to a conglomerate), heteromate, bimate (analogous to a racemic compound), and unimate (analogous to a solid solution) and they apply to melting point, solubility, recrystallization, sublimation, distillation, and chromatographic processes. Additionally, suggestions for improving the terminology for describing the states of chiral systems are also considered and the defined terms are: holemate (hol, ec = 100%), scalemate (scl, 50% < ec < 100%), and equimate (eqm, ec = 50%).Keywords: Stereochemistry; Terminology; Chirality; State-Dependent Behavior; Conglomerate; Racemate A clear consensus for describing chiral systems, both for processes, behaviors, and for the general state of systems, does not seem to be in effect despite the enormous amount of study devoted to chiral systems and their associated behaviors ever since the seminal experiments of Pasteur into the relationships between the crystalline state and chemical composition and their relation to optical rotation (OR) [1,2]-thus consequently the very embodiment of chirality and the subsequent inferences for homochirality, not to mention of course, the very report of the spontaneous resolution of a conglomerate itself [3]. Invariably, whatever particular description is adopted encounters objection from one quarter or another and hence the obvious question, though rhetorical in nature, is, what is the origin of the confusion and ambiguity that exists? In part, confusion and ambiguity arise because authors may be, for example, be referring to a single molecule or type of molecule or, on the other hand, an aggregation of molecules or a real sample analysis without taking due care to be precise in their meaning and simply assuming that the context of the discussion is sufficient to effect a distinction. Another source of confusion is the fact that as new frontiers were explored or developed, the terminology failed to keep pace and terms were simply borrowed out of convenience. There is no better example of this than the term homochiral 1 [4][5][6]. Thus it is the intention of this report to help alleviate some of the deficiencies that have developed in the terminology in use with respect to chiral systems, especially since the systems that give rise to varying chiral behaviors have risen...

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2,9-Dihydroxy- and 2,10-Dihydroxy-1,8-cineole. Two New Possum Urinary Metabolites

Abstract: 2,9-Dihydroxy-1,8-cineole (7a) and the corresponding 2,10-dihydroxy compound (8a) are present in the urine of brushtail possums fed a diet enhanced with 1,8-cineole (1). Chemical syntheses of these two novel metabolites are described.

Cited by 18 publications

References 0 publications

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

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

Pharmacokinetics of 1,8-cineole, a dietary toxin, in the brushtail possum (Trichosurus vulpecula): Significance for feeding

Suggested New Terms for Describing Chiral States and the State-Dependent Behavior of Chiral Systems

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