54164-88-4Relevant articles and documents
Syntheses of chiral 1,8-cineole metabolites and determination of their enantiomeric composition in human urine after ingestion of 1,8-cineole- containing capsules
Schaffarczyk, Monika,Balaban, Teodor Silviu,Rychlik, Michael,Buettner, Andrea
, p. 77 - 85 (2013/06/27)
The chiral metabolites in human urine were investigated after ingestion of a 1,8-cineole (eucalyptol)-containing enterocoated 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 achievethis 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 GCMS on a chiral stationary phase after consumption of 10 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.
Cineole biodegradation: Molecular cloning, expression and characterisation of (1R)-6β-hydroxycineole dehydrogenase from Citrobacter braakii
Slessor, Kate E.,Stok, Jeanette E.,Cavaignac, Sonia M.,Hawkes, David B.,Ghasemi, Younes,De Voss, James J.
experimental part, p. 81 - 86 (2010/05/17)
The first steps in the biodegradation of 1,8-cineole involve the introduction of an alcohol and its subsequent oxidation to a ketone. In Citrobacter braakii, cytochrome P450cin has previously been demonstrated to perform the first oxidation to produce (1R)-6β-hydroxycineole. In this study, we have cloned cinD from C. braakii and expressed the gene product, which displays significant homology to a number of short-chain alcohol dehydrogenases. It was demonstrated that the gene product of cinD exhibits (1R)-6β-hydroxycineole dehydrogenase activity, the second step in the degradation of 1,8-cineole. All four isomers of 6-hydroxycineole were examined but only (1R)-6β-hydroxycineole was converted to (1R)-6-ketocineole. The (1R)-6β-hydroxycineole dehydrogenase exhibited a strict requirement for NAD(H), with no reaction observed in the presence of NADP(H). The enzyme also catalyses the reverse reaction, reducing (1R)-6-ketocineole to (1R)-6β-hydroxycineole. During this study the N-terminal His-tag used to assist protein purification was found to interfere with NAD(H) binding and lower enzyme activity. This could be recovered by the addition of Ni2+ ions or proteolytic removal of the His-tag.
Chiral 2α,4-dihydroxy-1,8-cineole as a possum urinary metabolite
Carman, Raymond M.,Rayner, Anthony C.
, p. 1 - 6 (2007/10/03)
Both enantiomers of 2α,4-dihydroxy-1,8-cineole (2) have been synthesized. The enantiomer present in possum urine is the (-)-(1R,2R,4R)-isomer (2′). This diol is biosynthesized in the possum from (1R,2R,4S)-2α-hydroxy-1,8-cineole (18).
