14745-36-9Relevant articles and documents
The reduction of α-tocopherolquinone by human NAD(P)H: Quinone oxidoreductase: The role of α-tocopherolhydroquinone as a cellular antioxidant
Siegel, David,Bolton, Emiko M.,Burr, Jeanne A.,Liebler, Daniel C.,Ross, David
, p. 300 - 305 (1997)
α-Tocopherolquinone (TQ), a product of α-tocopherol oxidation, can function as an antioxidant after reduction to α-tocopherolhydroquinone (TQH2). We examined the ability of human NAD(P)H:quinone oxidoreductase (NQO1) to catalyze the reduction o
Towards a modern definition of vitamin e - Evidence for a quinone hypothesis
Shrader, William D.,Amagata, Akiko,Barnes, Adam,Hinman, Andrew,Jankowski, Orion,Lee, Edgar,Kheifets, Viktoria,Komatsuzaki, Ryo,Mollard, Paul,Murase, Katsuyuki,Rioux, Patrice,Wesson, Kieron,Miller, Guy
, p. 391 - 395 (2012)
We report on the synthesis, biological and pharmacological activity of the tocoquinone natural product, α-tocopherol quinone (ATQ); an oxidative metabolite of α-tocopherol. ATQ is a potent cellular protectant against oxidative stress, whose biological activity is dependent upon its ability to undergo reversible two-electron redox cycling. ATQ is orally bioavailable, with a favorable pharmacokinetic profile and has demonstrated a beneficial clinical response in patients with Friedreich's ataxia. ATQ is a member of a broader class of vitamin E derived quinone metabolites which may be ascribable in whole or in part to the activity of vitamin E.
Vitamin E hydroquinone is an endogenous regulator of ferroptosis via redox control of 15-lipoxygenase
Hinman, Andrew,Holst, Charles R.,Latham, Joey C.,Bruegger, Joel J.,Ulas, G?zde,McCusker, Kevin P.,Amagata, Akiko,Davis, Dana,Hoff, Kevin G.,Kahn-Kirby, Amanda H.,Kim, Virna,Kosaka, Yuko,Lee, Edgar,Malone, Stephanie A.,Mei, Janet J.,Richards, Steve James,Rivera, Veronica,Miller, Guy,Trimmer, Jeffrey K.,Shrader, William D.
, (2018/09/27)
Ferroptosis is a form of programmed cell death associated with inflammation, neurodegeneration, and ischemia. Vitamin E (alpha-tocopherol) has been reported to prevent ferroptosis, but the mechanism by which this occurs is controversial. To elucidate the biochemical mechanism of vitamin E activity, we systematically investigated the effects of its major vitamers and metabolites on lipid oxidation and ferroptosis in a striatal cell model. We found that a specific endogenous metabolite of vitamin E, alpha-tocopherol hydroquinone, was a dramatically more potent inhibitor of ferroptosis than its parent compound, and inhibits 15-lipoxygenase via reduction of the enzyme's non-heme iron from its active Fe3+ state to an inactive Fe2+ state. Furthermore, a non-metabolizable isosteric analog of vitamin E which retains antioxidant activity neither inhibited 15-lipoxygenase nor prevented ferroptosis. These results call into question the prevailing model that vitamin E acts predominantly as a non-specific lipophilic antioxidant. We propose that, similar to the other lipophilic vitamins A, D and K, vitamin E is instead a pro-vitamin, with its quinone/hydroquinone metabolites responsible for its anti-ferroptotic cytoprotective activity.
Highly stereoselective construction of the C2 stereocentre of α-tocopherol (Vitamin E) by asymmetric addition of Grignard reagents to ketones
Bieszczad, Bartosz,Gilheany, Declan G.
, p. 6483 - 6492 (2017/08/16)
Tertiary alcohol precursors of both C2 diastereoisomers of α-tocopherol were prepared in three ways by our recently reported asymmetric Grignard synthesis. The versatility of Grignard chemistry inherent in its three-way disconnection was exploited to allow the synthesis of three product grades: 77:23 dr (5 steps), 81:19 dr (5 steps) and 96:4 dr (7 steps, one gram scale) from readily available and abundant starting materials. The products were converted to their respective α-tocopherols in 3 steps, which allowed a definitive re-assignment of their absolute configurations.
Improved General Method of Ortho Alkylation of Phenols Using Alkyl Isopropyl Sulfide, Sulfuryl Chloride and Triethylamine. An Expedient Synthesis of Representative Oxygen Heterocycles and (2R,4'R,8'R)-α-Tocopherol
Inoue, Seiichi,Ikeda, Hiroshi,Sato, Shuichi,Horie, Kiyohiro,Ota, Tomomi,et al.
, p. 5495 - 5497 (2007/10/02)
Functionalized alkyl groups have been introduced regioselectively into the ortho position of phenols via sigmatropic rearrangement of isopropylphenoxysulfonium alkylide, providing a quite efficient synthesis of precursors for chromans, chromens, coumarins, and d-α-tocopherol.
