7559-04-8

Usage

Uses

Used in Pharmaceutical Research:
D-ALPHA-TOCOPHERYLQUINONE is used as a research compound for studying the electron transport system in [application reason] to gain insights into cellular processes and potential therapeutic applications.
Used in Antioxidant Applications:
D-ALPHA-TOCOPHERYLQUINONE is used as an antioxidant agent for [application reason] to protect cells from oxidative damage and maintain overall cellular health.
Used in Biochemical Studies:
D-ALPHA-TOCOPHERYLQUINONE is used as a biochemical tool for [application reason] to investigate the role of NADH dehydrogenase and its impact on cellular metabolism and energy production.
Used in Chemical Synthesis:
D-ALPHA-TOCOPHERYLQUINONE is used as a starting material or intermediate in the synthesis of various compounds for [application reason] to develop new pharmaceuticals, nutraceuticals, or other chemical products with potential health benefits.

InChI:InChI=1/C29H50O3/c1-20(2)12-9-13-21(3)14-10-15-22(4)16-11-18-29(8,32)19-17-26-25(7)27(30)23(5)24(6)28(26)31/h20-22,32H,9-19H2,1-8H3/t21-,22-,29-/m1/s1

Upstream product

• 32466-45-8 (2R,4'R,8'R)-α-tocopheryl methyl ether 
• 58-95-7 RRR-α-tocopheryl acetate 
• 88083-17-4 2-Methyl-2-[2,5,7,8-tetramethyl-6-oxo-2-(4,8,12-trimethyl-tridecyl)-2,3,4,6-tetrahydro-chromen-8a-ylperoxy]-propionic acid butyl ester 
• 10191-41-0 (+/-)-α-tocopherol 
• 59-02-9 d-α-Tocopherol, E 
• 88056-74-0 2-Methyl-2-[2,5,7,8-tetramethyl-6-oxo-2-(4,8,12-trimethyl-tridecyl)-2,3,4,6-tetrahydro-chromen-8a-ylperoxy]-propionitrile 
• 197297-77-1 4-(2,5-dimethoxy-3,4,6-trimethylphenyl)butan-2-one 
• 131426-03-4 1-iodo-2,5-bis(methoxy)-3,4,6-trimethylbenzene 
• 16825-16-4 (6R,10R)-6,10,14-trimethylpentadecan-2-one 
• 150-86-7 phytol 
• 82299-54-5 2-(2,5-dimethoxy-3,4,6-trimethylphenyl)ethylmagnesium bromide 
• 4537-09-1 1,4-dimethoxy-2,3,5-trimethyl-benzene 
• 114341-71-8 (4R,8R)-1-Bromo-4,8,12-trimethyltridecane 
• 87247-35-6 (4R,8R)-4,8,12-trimethyltridecan-1-ol 

Downstream Products

• 59-02-9 Tocopherol 
• 916319-64-7 (R/S,R,R)-2,3,5-trimethyl-6-(3,7,11,15-tetramethyl-hexadecyl)-benzene-1,4-diol 
• 129658-44-2 3-((3R,7R,11R)-3-Hydroxy-3,7,11,15-tetramethyl-hexadecyl)-2,4,5,6-tetramethyl-phenol 
• 10191-41-0 (+/-)-α-tocopherol 
• 18920-63-3 vitamin E 
• 14745-36-9 2-((7R,11R)-3-Hydroxy-3,7,11,15-tetramethylhexadecyl)-3,5,6-trimethylbenzene-1,4-diol 
• 91418-95-0 (3R,7R,11R)-1-(2',5'-dimethoxy-3',4',6'-trimethylphenyl)-3,7,11,15-tetramethyl-hexadecan-3-ol 

Relevant academic research and scientific papers

Modulation of the mitochondrial cytochrome bc1 complex activity by chromanols and related compounds

Tocopherols (α-, β-, γ-, and δ-Toc) and tocopheryl quinones (α-, β-, γ-, and δ-TQ) were recently suggested to modulate mitochondrial electron transfer in mammals. Intriguingly, Tocs and stigmatellin, a potent inhibitor of the mitochondrial cytochrome (cyt) bc 1 complex, possess a common structural feature: the chroman core. Therefore, we studied the interference of Tocs as well as synthetic model compounds (low molecular weight TQ analogues and tetramethyl chromanones) at the mitochondrial cyt bc1 complex. Enzymatic experiments revealed that besides the inhibitor stigmatellin, among natural vitamin E-related derivatives, γ-TQ/δ-TQ and, among synthetic compounds, TMC2O (6-hydroxy-4,4,7,8-tetramethylchroman-2-one) were most effective in decreasing the cyt bc1 activities. Stopped-flow photometric and low-temperature electron paramagnetic resonance spectroscopic experiments showed for TMC2O an inhibition of electron transfer to cyt c1 and a modulation of the environment of the Rieske iron - sulfur protein (ISP). Docking experiments suggest a binding interaction of the 6-OH group and 1-O atom/2-C( = O) group of TMC2O with Glu-271 (cyt b) and His-161 (ISP) in the cyt bc1 complex, respectively. This binding pose is similar but not identical to the potent inhibitor stigmatellin. The data suggest that chroman-2-ones are possible templates for modulatory molecules for the cyt bc1 target.

QUINONES AND PROCESS OF OBTAINING SAME

Disclosed is a process for the oxidation of at least one chroman (C1) in a solvent mixture comprising at least two solvents or in a C-bearing solvent, with a gaseous compound comprising, essentially consisting of, or consisting of oxygen in the presence of a copper catalyst, said copper catalyst exhibiting the oxidation state (+1) or (+2). A further part of the disclosure is a composition comprising at least one chroman (C1) and/or at least one quinone (C30), a solvent mixture comprising at least two solvents or a C-bearing solvent, a copper catalyst, said copper catalyst exhibiting the oxidation state (+1) or (+2) and a gaseous compound comprising, essentially consisting or consisting of oxygen. A quinone preparation and a process of making same is also part of the invention.

Vitamin E hydroquinone is an endogenous regulator of ferroptosis via redox control of 15-lipoxygenase

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

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.

Effect of α-tocopherol on the hemin-catalyzed decomposition of 1-palmitoyl-2-linoleoyl-3-sn-phosphatodylcholine 13-hydroperoxide in micelles and liposomes

The secondary process of lipid peroxidation produces some toxic aldehydes. Since this process takes place via free radical reaction in lipophilic circumstances, α-tocopherol would suppress the formation of such aldehydes by trapping free-radical intermedi

Towards a modern definition of vitamin e - Evidence for a quinone hypothesis

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.

Bromination of tocopherols: Oxidative halogenations and rearrangements

The bromination behaviour of all four tocopherols and the corresponding model compounds in acidic and basic aqueous media was studied. Acidic conditions resulted in quinones and brominated quinones, with the bromination of the tocopherol preceeding the oxidation to the quinone. Buffer type and concentration did not influence the reaction results, whereas pH and the ratio of buffer and ethanol used as a co-solvent strongly affected the reaction rates. In alkaline media, two or three major products and a multitude of minor byproducts were obtained, because the combination of oxidizing hypobromite and alkaline conditions allowed for more complex reaction pathways (oxidation, substitution, condensation, elimination than the acidic conditions did. The para-quinones were major reaction products observed for all four tocopherols. Interestingly, if the quinone was substituted at C-5, it rearranged in a Michael-type addition process followed by substitution with a bromonium ion. The absence of a substituent at C-5, the presence of a bromine atom at C-7, or the absence of bromine in the reaction medium were all able to prevent this reaction. The rearrangement products could react further by substitution of the newly acquired bromine group for a hydroxy group. In the cases of γ- and δ-tocopherol, further rearrangement led to the formation of trioxo compounds. Bromination of all four tocopherols under alkaline conditions was compared, and the products were characterized to provide standard compounds for study of the interplay of tocopherols with halogenativeenzymes. Brominated para-quinones and rearrangement products were the major products. A "reactivity pairing" between α- and β-tocopherol on one hand and γ- and δ-tocopherol on the other was observed.

SYNTHESIS OF ALPHA-TOCOPHEROLQUINONE DERIVATIVES, AND METHODS OF USING THE SAME

The present invention is directed to a method of synthesizing a compound of Formula I: the method comprising oxidizing alpha-tocopherol with a metal salt oxidizing agent to form the compound of Formula I, wherein the stoichiometric ratio (mol/mol) of metal salt oxidizing agent/alpha-tocopherol is 1.6 to 4. The invention is also directed to a method of synthesizing a compound of Formula I, the method comprising (a) hydrolyzing alpha-tocopheryl acetate in the presence of a base; (b) neutralizing the hydrolyzing of (a), thereby forming alpha-tocopherol; and (c) oxidizing the alpha-tocopherol of I (b) with a metal salt oxidizing agent to form the compound of Formula I, wherein the stoichiometric ratio (mol/mol) of metal salt oxidizing agent/aipha-tocopherol is 1.6 to 4.

Tocotrienamines and tocopheramines: Reactions with radicals and metal ions

The antioxidant activity of vitamin E (VE) homologs a, c and d-tocotrienamines (4b-6b), never studied before, and a, c and d-tocopheramines (4a-7a) was investigated by means of different total antioxidant capacity (TAC) tests. In all the test model systems, compounds 4a-7a and 4b-6b showed similar or higher TAC values than the parental vitamin E forms and their physiological metabolites. α-Homologs of VE amines showed markedly higher activity than the VE congeners in the TEAC test, which is tailored for liposoluble antioxidants, while c-homologs of the amine analogs showed higher activity in the FRAP tests. Kinetics analysis of the reaction with DPPH showed higher second order rate k for 4a than for α-tocopherol (1a). α-Tocopherolquinone 1f was the common main oxidation product for both 1a and α-tocopheramine (4a) exposed to ferric ions or DPPH, and the implied oxidative deamination of 4a was accompanied by a nitration reaction of phenolic substrates that were added to the reaction medium. Possible mechanisms of these reactions were studied.

REDUCTION OF ALPHA-TOCOPHEROL QUINONE

α-tocopherol quinone is chemically reduced by combination with a reducing agent, such as tin (II) ion in the form of stannous chloride (SnCl2-2H20), or by chromium (III) ion, such as chromium (III) in the form of chromium chloride (CrCl3- 6H20). Purified α-tocopherol is obtained from α-tocopherol formed by reduction of an oxidized α-tocopherol, such as α-tocopherol quinone, by tin (II) ion or chromium (III) ion. Purified a-tocopherol of the invention can be administered to patients in need thereof, α-tocopherol is preserved by combination with a reducing agent.