- Syntheses of chiral 1,8-cineole metabolites and determination of their enantiomeric composition in human urine after ingestion of 1,8-cineole- containing capsules
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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.
- Schaffarczyk, Monika,Balaban, Teodor Silviu,Rychlik, Michael,Buettner, Andrea
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- Regiospecific Functionalization of the Monoterpene Ether 1,3,3-Trimethyl-2-oxabicyclooctane (1,8-Cineole). Synthesis of the Useful Bridged γ-Lactone 1,3-Dimethyl-2-oxabicyclooctan-3-->5-olide
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The regiospecific functionalization at C-5 and difuctionalization at C-5/C-8 and C-5/C-10 of the monoterpene 1,3,3-trimethyl-2-oxabicyclooctane (1) is described.Chromyl acetate oxidation of 1 afforded 1,3,3-trimethyl-2-oxabicyclooctan-5-one (6) in 60percent yield along with 28percent of unreacted 1 and minor amounts of exo-1,3,3-trimethyl-2-oxabicyclooctan-5-ol acetate (9), 1,3,3-trimethyl-2-oxabicyclooctane-5,8-dione (13), exo-8-acetoxy-1,3,3-trimethyl-2-oxabicyclooctan-5-one (16), 1,3,3-trimethyl-2-oxabicyclooctane-5,7-dione (14), and orcinol (15).On digestion with oxalic or phthalic acid, ketone 6 was converted into a mixture of piperitenone (20), 3-methyl-2-cyclohexenone (22), acetone, and traces of isopiperitenone (21), while 60percent sulfuric acid at room temperature yielded 20 as the sole reaction product.Oxidation of 6 with chromyl acetate yielded diketone 13, which decomposed into orcinol (15) on digestion with either boiling water or a 2.5percent sodium bicarbonate solution.Sodium borohydride or lithium aluminum hydride reduction of 6 gave stereospecifically exo-1,3,3-trimethyl-2-oxabicyclooctan-5-ol (7) while reduction with sodium-ethanol or aluminum isopropoxide in isopropyl alcohol (equilibrium conditions) yielded a 3:2 mixture of the alcohols 7 and 8, respectively.Treatment of 7 with phosphoryl chloride produced 1,3,3-trimethyl-2-oxatricyclo5,8>octane (25) together with minor amounts of the chlorocineoles 10 and 11.Pyrolysis of the methyl xanthate of 7 yielded 1,3,3-trimethyl-2-oxabicyclooct-5-ene (2).Photolysis of 7 in the presence of mercuric oxide and iodine or iodosylbenzene diacetate and iodine gave the tricyclic diether 29, which was quantitatively converted into the bridged γ-lactone 30 by oxidation with ruthenium tetraoxide.Oxidation of 29 with chromyl acetate yielded a 1:1 mixture of 30 and the formate lactone 31.Lithium aluminum hydride reduction of 30 produced diol 37, which was converted into menthofuran (44) in five steps.
- Boggiatto, Margarita V. de,Heluani, Carola S. de,Fenik, Ines J. S.,Catalan, Cesar A. N.
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p. 1505 - 1511
(2007/10/02)
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- FORMATION OF REACTIVE TRICYCLIC INTERMEDIATES VIA THE INTRAMOLECULAR CYCLOPROPANATION OF DIHYDROPYRANS. SYNTHESIS OF EUCALYPTOL
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Tricyclic compound 3 was synthesized via a cyclopropanation reaction promoted by 2.This highly srained compound was found to undergo selective chemical transformations to give oxa-bicyclic ketones.This methodology was applied in a total synthesis of the monoterpene, eucalyptol.
- Adams, Julian,Belley, Michel
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p. 2075 - 2078
(2007/10/02)
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- Process for the preparation of 1,3,3-trimethyl-2-oxabicyclo[2,2,2]octan-6-ones
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1,3,3-Trimethyl-2-oxabicyclo[2,2,2]octan-6-ones are prepared by first epoxidizing α-terpineol with a peracid and thereafter oxidizing the resulting product with an appropriate oxidizing agent.
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