57721-81-0Relevant articles and documents
Reaction of α-(n-alkylcarbonyloxy)alkyl (ACOA) halides with 4-hydroxyacetanilide and 2,2,5,7,8-pentamethyl-6-chromanol: The effect of steric hindrance on reaction path
Thomas, Joshua D.,Sloan, Kenneth B.
, p. 272 - 278 (2008/12/22)
A convenient synthesis of α-(n-alkylcarbonyloxy)alkyl (ACOA) iodides has been developed and a homologous series of n-alkylcarbonyloxymethyl (ACOM) iodides have been used to alkylate 4-hydroxyacetanilide (acetaminophen, APAP), a sterically unhindered phenol, and a sterically hindered phenol (2,2,5,7,8-pentamethyl-6-chromanol). Steric hindrance was not a significant factor in the ratio of acylated (Path b) to alkylated (Path a) for these reactions. Given the reported toxicity associated with sterically hindered ACOM prodrugs, n-alkyl ACOM and ACOA promoieties present themselves as viable alternatives to the more commonly used pivalate-based derivatives. Georg Thieme Verlag Stuttgart.
Novel tocopheryl compounds XXV: synthesis and comparison of the para-quinones of all four homologous tocopherol model compounds and their 3,4-dehydro derivatives
Patel, Anjan,Netscher, Thomas,Gille, Lars,Mereiter, Kurt,Rosenau, Thomas
, p. 5312 - 5318 (2008/02/01)
Four tocopherol model compounds, the chroman-6-ols (1-4) having the typical substitution pattern of α-, β-, γ-, and δ-tocopherol (vitamin E), were oxidized to the corresponding para-quinones (5-8), and dehydrogenated to the 2H-chromen-6-ols (17-20) involving initial acetyl protection of the phenolic OH and deprotection as the last step. The chromenols were also converted into the para-quinones (21-24), which existed in the bicyclic hemiketal form, in contrast to the chromanol-derived, monocyclic quinones 5-8, the ketalization behavior agreeing well with computations on the DFT level.
Chroman derivatives as lipoxygenase inhibitors
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Page/Page column 21-22, (2008/06/13)
The present invention is concerned with certain novel derivatives of Formula I: wherein X and R1 to R10 are as described in the specification, and where either R5 is OH, —NRdORa or —NRd—NRbRc, or R7 is —NRdORa or —NRd—NRbRc, or C=R7R8 is C=NORa or C=N—NRbRc, which may be useful in the manufacture of pharmaceutical compositions for treating disorders mediated by lipoxygenases. They may also be useful in the manufacture of skin care and/or pharmaceutical compositions for the treatment of lipoxygenase mediated disorders.
3-Tocopherylisoxazolines by [2+3] cycloaddition
Rosenau, Thomas,Adelwoehrer, Christian,Hofinger, Andreas,Mereiter, Kurt,Kosma, Paul
, p. 1323 - 1329 (2007/10/03)
New isoxazoline derivatives of α-tocopherol (1), the main component of vitamin E, were synthesized in a facile, two-step sequence consisting of nitration followed by 1,3-dipolar cycloaddition. 5-Nitromethyl-γ- tocopheryl acetate (3), obtained from the cheap α-tocopheryl acetate (2) by direct nitration in one step, acted as the nitrile oxide precursor in the reaction with various alkenes. The facile conversion proceeded in the presence of equimolar amounts of PhNCO and catalytic amounts of triethylamine. The NMR spectra of the product isoxazolines 5-13, showing strongly temperature-dependent resonances of the 4″-CH, 4-CH2 and the acetyl group, are discussed, and the crystal structures of model compounds containing a methyl group instead of the isoprenoid side chain are presented. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
Active oxygen chemistry within the liposomal bilayer: Part III: Locating Vitamin E, ubiquinol and ubiquinone and their derivatives in the lipid bilayer
Afri, Michal,Ehrenberg, Benjamin,Talmon, Yeshayahu,Schmidt, Judith,Cohen, Yael,Frimer, Aryeh A.
, p. 107 - 121 (2007/10/03)
We have previously shown that the location and orientation of compounds intercalated within the lipid bilayer can be qualitatively determined using an NMR chemical shift-polarity correlation. We describe herein the results of our application of this method to analogs of Vitamin E, ubiquinol and ubiquinone. The results indicate that tocopherol - and presumably the corresponding tocopheroxyl radical - reside adjacent to the interface, and can, therefore, abstract a hydrogen atom from ascorbic acid. On the other hand, the decaprenyl substituted ubiquinol and ubiquinone lie substantially deeper within the lipid membrane. Yet, contrary to the prevailing literature, their location is far from being the same. Ubiquinone-10 is situated above the long-chain fatty acid slab . Ubiquinol-10 dwells well within the lipid slab, presumably out of striking range of Vitamin C. Nevertheless, ubiquinol can act as an antioxidant by reducing C- or O-centered lipid radicals or by recycling the lipid-resident tocopheroxyl radical.
Autoxidation of Biological Molecules. 4. Maximizing the Antioxidant Activity of Phenols
Burton, G. W.,Doba, T.,Gabe, E. J.,Hughes, L.,Lee, F. L.,et al.
, p. 7053 - 7065 (2007/10/02)
Rate constants, k1, for H-atom abstraction by peroxyl radicals from α-tocopherol and 35 structurally related phenols have been measured at 30 deg C by the inhibited autoxidation of styrene (IAS) method.An independent laser-flash kinetic EPR method was used with ten of these phenols which gave k1 values at 24 deg C that were in satisfactory agreement with the values found by the IAS method.The structures of several phenols were determined by X-ray analysis.The EPR spectral parameters for the phenoxyl radicals derived from many of these phenols were also measured.The relative magnitudes of k1 values for phenols that are structurally closely related and have an oxy substituent para to the hydroxyl group can be correlated with the degree of stabilization of the phenoxyl radical.Stabilization depends on two factors: (i) the extent of orbital overlap between the 2p type lone pair on the para oxygen atom and the aromatic ? electron system and (ii) the electron-donating or withdrawing character of the group bonded to the para oxygen atom.Orbital overlap depends on the dihedral angle, θ, between the direction of the 2p orbital on the para oxygen and a line perpendicular to the aromatic plane.It can be estimated from the X-ray structures.Along the series 4-methoxytetramethylphenol (VIc), 6-hydroxy-2,2,5,7,8-pentamethylchromene, 6-hydroxy-2,2,5,7,8-pentamethylchroman, and 2,3-dihydro-5-hydroxy-2,2,4,6,7-pentamethylbenzofuran (IIIb), k1 increases from 3.9x105, 2.5x106, 3.8x106, to 5.7x106 M-1s-1, as θ decreases from 89, 38, 17, to 6 deg.Compound IIIb is the most active antioxidant being 1.8 times more active than α-tocopherol.For 2-substituted 6-hydroxy-2,5,7,8-tetramethylchromans log(k1/M-1s-1) can be correlated with the ?1 constant of the 2-substituent, ρ1=-1.25.For these compounds and for some 2,6-dimethylphenols log(k1/M-1s-1) can also be correlated with the extent of stabilization of corresponding phenoxyl radicals as measured by the unpaired spin density at the two ortho methyl groups.Some additional kinetic and spectroscopic data are presented.It is also shown that the perpendicular methoxy group in VIc is not deactivating relative to a hydrogen atom but is, instead, about as activating as a methyl group.
