- Synthesis, properties, and identification of epimeric hepoxilins (-)-(10R)-B3 and (+)-(10S)-B3
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To characterize the individual epimers of hepoxilin B3, a new total synthesis procedure was developed consisting of subsequent condensations of enentiomerically pure (2R,3S)-epoxy-5-undecynal with LiC≡CCH2Cl and HC≡C(CH2)3COOMe, followed by Lindlar hydrogenation, and finally epimer separation. Derivatives of hepoxilin syn-(10R,11R,12S)-B3 (free acid, methyl ester and acetate of methyl ester) are more polar on silica gel, have negative optical rotations [α]25D -60.6°, -62.6°, -25.2°, respectively, and in 1H NMR spectra have the larger splitting of carbinolic H-10 signal (J10,11 5.0-6.1 Hz). Corresponding values for less polar hepoxilin anti-(10S, 11R,12S)-B3 derivatives are: [α]25D +73.5°, +61.9°, and -2.0°; J10-11 2.95-3.3 Hz. These data suggest that an epimer of hepoxilin B3 recently isolated by W.H.Gerwick et al. from red algae is syn-(10R,11R,12S)-B3.
- Vasiljeva, Ludmila L.,Manukina, Tatjana A.,Demin, Peter M.,Lapitskaja, Margarita A.,Pivnitsky, Kasimir K.
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- LC-MS/MS analysis of epoxyalcohols and epoxides of arachidonic acid and their oxygenation by recombinant CYP4F8 and CYP4F22
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CYP4F22 and CYP4F8 are expressed in epidermis, and mutations of CYP4F22 are associated with lamellar ichthyosis. Epoxyalcohols (HEETs) and epoxides (EETs) of 20:4n-6 appear to be important for the water permeability barrier of skin. Our aim was to study the MS/MS spectra and fragmentation of these compounds and to determine whether they were oxidized by CYP4F22 or CYP4F8 expressed in yeast. HEETs were prepared from 15-hydroperoxyeicosatetraenoic acid (15-HPETE), 12-HPETE, and their [2H8]labeled isotopomers, and separated by normal phase-HPLC with MS/MS analysis. CYP4F22 oxygenated 20:4n-6 at C-18, whereas metabolites of HEETs could not be identified. CYP4F8 formed ω3 hydroxy metabolites of HEETs derived from 12R-HPETE with 11,12-epoxy-10-hydroxy configuration, but not HEETs derived from 15S-HPETE. 8,9-EET and 11,12-EET were also subject to ω3 hydroxylation by CYP4F8. We conclude that CYP4F8 and CYP4F22 oxidize 20:4n-6 and that CYP4F8 selectively oxidizes 8,9-EET, 11,12-EET, and 10,11R,12R-HEET at the ω3 position.
- Nilsson,Ivanov,Oliw
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experimental part
p. 64 - 71
(2011/02/21)
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- Hepoxilins B3: Synthesis of all four stereoisomers and a glutathione adduct
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Utilizing (-)-quinic acid as a differentiated bis-aldehyde chiron, both pairs of hepoxilin B3 enantiomers and a glutathione adduct were synthesized by regiospecific functionalization of an acyclic vic-diol.
- Belosludtsev,Belosludtsev, Yuri Y.,Kollah,Omindine Kollah,Falck,Capdevila,Capdevila, Jorge H.
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p. 5327 - 5330
(2007/10/02)
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