18920-63-3

Upstream product

• 14745-36-9 2-((7R,11R)-3-Hydroxy-3,7,11,15-tetramethylhexadecyl)-3,5,6-trimethylbenzene-1,4-diol 
• 79434-77-8 (S)-6-Benzyloxy-2,5,7,8-tetramethyl-2-((4R,8R)-4,8,12-trimethyl-tridecyl)-chroman 
• 59-02-9 Tocopherol 
• 79434-97-2 (S,R,R)-α-tocopheryl methyl ether 
• 918876-45-6 benzyl (R)-6-(benzyloxy)-3,4-dihydro-2,5,7,8-tetramethyl-2H-1-benzopyran-2-carboxylate 
• 118100-81-5 (R)-6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromene-2-carbaldehyde 
• 474255-79-3 (3R,7S)-3,7,11-trimethyl-10-dodecenal 
• 188416-16-2 (R)-(+)-6-benzyloxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-1-benzopyran-2-ylmethanol 
• 59-02-9 vitamin E 
• 87247-35-6 (4R,8R)-4,8,12-trimethyltridecan-1-ol 
• 114341-71-8 (4R,8R)-1-Bromo-4,8,12-trimethyltridecane 
• 4537-09-1 1,4-dimethoxy-2,3,5-trimethyl-benzene 
• 82299-54-5 2-(2,5-dimethoxy-3,4,6-trimethylphenyl)ethylmagnesium bromide 
• 150-86-7 phytol 

Downstream Products

• 87291-70-1 DL-α-Tocopheryl phosphate dianilide 
• 1406-70-8 (all-rac)-α-tocopheryl acetate 
• 16676-75-8 DL-α-tocopherol nicotinate 
• 54165-54-7 2S,4'R,8'R-α-tocopheryl acetate 

Relevant academic research and scientific papers

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.

Screening of a virtual mirror-image library of natural products

We established a facile access to an unexplored mirror-image library of chiral natural product derivatives using d-protein technology. In this process, two chemical syntheses of mirror-image substances including a target protein and hit compound(s) allow the lead discovery from a virtual mirror-image library without the synthesis of numerous mirror-image compounds.

SEPARATION OF CHIRAL ISOMERS BY SFC

The present invention relates to the field of separating chiral isomers from each other. Particularly, it relates to the field of separating of chiral isomers of chromane or chromene compounds, particularly tocopherols, 3,4-dehydro-tocopherols and tocotrienols, as well as the protected forms thereof. It has been found that the use of supercritical carbon dioxide as mobile phase combined with the very specific chiral phase as stationary phase leads to a very efficient separation of the individual chiral isomers. As the method is very efficient and fast combined with advantageous in view of ecology it is of big industrial interest.

A Simple 13C NMR Method for the Discrimination of Complex Mixtures of Stereoisomers: All Eight Stereoisomers of α-Tocopherol Resolved

A simple one-dimensional 13C NMR method is presented to discriminate between stereoisomers of organic compounds with more than one chiral center. By means of this method it is possible to discriminate between all eight stereoisomers of α-tocopherol. To achieve this the chiral solvating agent (S)-(+)-1-(9-anthryl)-2,2,2-trifluoroethanol and the compound of interest were dissolved in high concentrations in chloroform-d, and the nuclear magnetic resonance (NMR) spectrum was recorded at a low temperature. The individual stereoisomers of α-tocopherol were assigned by spikes of the reference compounds. The method was also applied to six other representative examples.

Process of separating chiral isomers of chroman compounds and their derivatives and precursors

The present invention relates to a process of separating chiral isomers of chroman compounds, particularly tocopherols and tocotrienols as well as the esters and intermediates thereof. It has been found that this process allows a separation of the desired isomer with a higher yield and enables the use of the non-desired isomers in a very efficient way. Said process is particularly useful when implemented in an industrial process. Furthermore, it has been found that this process allows using isomer mixtures as they result from traditional industrial synthesis.

PROCESS OF SEPARATING CHIRAL ISOMERS OF CHROMAN COMPOUNDS AND THEIR DERIVATIVES AND PRECURSORS

The present invention relates to a process of separating chiral isomers of chroman compounds, particularly tocopherols and tocotrienols as well as the esters and intermediates thereof. It has been found that this process allows a separation of the desired isomer with a higher yield and enables the use of the non-desired isomers in a very efficient way. Said process is particularly useful when implemented in an industrial process. Furthermore, it has been found that this process allows using isomer mixtures as they result from traditional industrial synthesis.

Biomimetic chromanol cyclisation: A common route to a-tocotrienol and α-tocopherol

A common synthetic route to a-tocotrienol and a-tocopherol has been accomplished by a biomimetic cyclisation that yields the chromanol ring. The chirality at C2 of the chro- manol was induced by a covalently attached chiral dipeptide. Its terminal Asp participates in the enantioface-selective pro-tonation of the double bond of the a-tocotrienol precursor. a-Tocotrienol was diastereoselectively hydrogenated to a-tocopherol.

A short route to α-tocopherol

(Chemical Equation Presented) Short and sweet: A simple and practical route to α-tocopherol is described (see scheme; TES=triethylsilyl). The key step is a remarkably diastereoselective domino aldol/oxa-Michael reaction, which is promoted by proline derivative 1.

'Vitamin CE,' a novel prodrug form of vitamin E

Reaction of 5a-bromo-α-tocopherol with ascorbic acid produces 5a- tocopheryl ascorbate which is designated 'vitamin CE.' This novel tocopherol derivative represents an interesting prodrug form of α-tocopherol (vitamin E) that is stable under acidic conditions, but regenerates finely dispersed vitamin E in basic media. The reaction mechanism of the base-induced decomposition of vitamin CE involves elimination of ascorbate and production of an ortho-quinone methide intermediate that oxidizes ascorbate, and is reduced to vitamin E. Kinetic experiments showed the reaction to proceed in the pH range of 8 to 11 under physiological conditions. Tissue culture measurements demonstrated that vitamin E generated from the novel derivative is absorbed at much higher rates than conventional preparations and can even be absorbed under simulated conditions of malabsorption where there is no uptake of conventional vitamin E medications.

Electron-transfer reactions of alkyl peroxy radicals

One-electron-transfer reactions of alkyl peroxy radicals were studied by pulse radiolysis of aqueous solutions. At pH 13, the methyl peroxy radical was found to rapidly, k = 1 × 105-4.9 × 107 s-1, and quantitatively oxidize various organic substrates with E13 = 0.13-0.76 V vs NHE. On the other hand, this radical was unreactive with compounds with E13 ≥ 0.85 V. Consequently, E13 of the methyl peroxy radical is higher than 0.76 V and lower than 0.85 V, which means that E7 is in the range 1.02-1.11 V. At pH 8, the rate constants of the oxidation of four ferrocene derivatives by the alkyl peroxy radicals ranged from 7.1 × 104 M-1 s-1 for ferrocenedicarboxylate (E8 = 0.66 V) to 2.3 × 106 M-1 s-1 for (hydroxymethyl)ferrocene (E8 = 0.42 V). These rate constants were used to evaluate the reduction potential and self-exchange rate of alkyl peroxy radicals in neutral media from the Marcus equation. The calculated E7 = 1.05 V is in excellent agreement with the estimated E7 = 1.02-1.11 V and with one of the perviously published values E7 = 1.0 V, but the value is in excellent agreement higher than the other E7 ～ 0.6 V. It is suggested that the high reorganization energy, λ = 72 kcal mol-1 redox couple originates from the requirement for solvent reorganization due to the solvation of hydroperoxide anion in the transition state. In support of this are the activation parameters of the reaction of the methyl peroxy radical with uric acid. The activation entropy is 9 eu lower at pH 7.3 than it is at pH 13.2, whereas the activation enthalpies are unchanged. The importance of entropy control was verified in the reactions of cyclohexyl peroxy radicals with α- and δ-tocopherol in aerated cyclohexane (ΔH+ ≈ 0 kcal/mol, and ΔS+ = -25 and -26 eu). The implications of these findings on the inactivation of alkyl peroxy radicals in general are discussed.