- Novel PEGylated derivatives of α-tocopherol for nanocarrier formulations; synthesis, characterization and in vitro cytotoxicity against MCF-7 breast cancer cells
-
Despite numerous beneficial therapeutic effects namely antioxidant and anti-inflammatory activity, Vitamin E has limited clinical applications due to its low water solubility. Throughout the present work, α-tocopherol's new PEGylated derivatives alongside with polyethylene glycol 300 (α-TPGT300), 400 (α-TPGT400), and 1000 (α-TPGT1000) were synthesized. A 1,2,3-triazole ring was utilized as a linker for the attachment of alpha tocopherol to the PEGs through a click reaction. The purified derivatives were characterized by the means of 1H NMR, 13C NMR, mass spectroscopy, UV–vis and FT-IR methods. Synthesized derivatives’ capacity to produce self-assembly nanoparticles was evaluated employing the critical micelle concentration (CMC) values. The stability of the micelles was studied by size analysis. In vitro cytotoxicity of the products was investigated using MTT assay against MCF-7 breast cancer cells. The IC50 value for TPGT1000 after 24 h treatment was 15.0 ± 1.8 μM, whereas no significant cytotoxicity effect was observed following the treatment of MCF-7 cells by TPGT300, 400. The present study showed that polymeric micelle TPGT1000 possessed better physicochemical and biological properties including relatively lower CMC value, higher stability in FBS environment in addition to higher cytotoxicity against MCF-7 breast cancer cells compared to the lower molecular weight PEGylated derivatives. These results confirmed that increasing PEG chain length left a positive effect on the polymeric micelle properties and also improved the cytotoxicity effect of new PEGylated vitamin E derivatives.
- Esmaeelzadeh, Maryam,Mazarei, Zeinab,Rafati, Hasan,Salehi, Peyman,Savadkouhi, Niloofar
-
supporting information
(2021/03/17)
-
- FORMATION OF ALPHA TOCOPHEROL FROM 2,3,6-TRIMETHYLPHENOL
-
The present invention relates to the formation of α-tocopherol from 2,3,6- tri?methyl?phenol comprising the steps a) the oxidation of 2,3,6-trimethylphenol to 2,3,5-trimethylquinone. b) the reduction of 2,3,5-trimethylquinone to 2,3,5-trimethylhydroquinone c) the condensation of 2,3,5-trimethylhydroquinone and isophytol or a phytol derivative in such a manner that all reaction steps a), b) and c) are performed in cyclic alkylene carbonate solvent.
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Page/Page column 15-16
(2021/06/26)
-
- A mild and practical method for deprotection of aryl methyl/benzyl/allyl ethers with HPPh2andtBuOK
-
A general method for the demethylation, debenzylation, and deallylation of aryl ethers using HPPh2andtBuOK is reported. The reaction features mild and metal-free reaction conditions, broad substrate scope, good functional group compatibility, and high chemical selectivity towards aryl ethers over aliphatic structures. Notably, this approach is competent to selectively deprotect the allyl or benzyl group, making it a general and practical method in organic synthesis.
- Pan, Wenjing,Li, Chenchen,Zhu, Haoyin,Li, Fangfang,Li, Tao,Zhao, Wanxiang
-
p. 7633 - 7640
(2021/09/22)
-
- SYNTHESIS OF CHROMANOL AND 2-METHYL-1,4-NAPHTHOQUINONE DERIVATIVES
-
The present invention relates to a process for the production of chromanol and 2-methyl-1,4-naphthoquinone derivatives, more specifically to a process for preparing a compound of the general formula (I) or (II) wherein the variables are as defined in the claims and the description.
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Page/Page column 49-71
(2020/03/05)
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- Imidazole ionic liquid, preparation method thereof, and application thereof in synthesis of vitamin E acetate
-
The invention discloses an imidazole ionic liquid, a preparation method thereof, and an application thereof in the synthesis of vitamin E acetate. The structure of the imidazole ionic liquid is represented by formula (I) shown in the description, and Y in the formula (I) is ZnCl2Br or ZnBr. The catalyst has the advantages of cheapness, easiness in obtaining, and stable performances, and has the advantages of good catalytic activity, simple reaction process, mild reaction conditions, high conversion rate and selectivity and no pollution when used in catalytically synthesizing the reaction of vitamin E.
- -
-
Paragraph 0032-0051
(2019/05/02)
-
- COSMETIC COMPOSTION COMRPISING ACTIVE INGREDIENT PRECURSOR AND ENZYME FOR MAINTAIN CONSTANTLY CONCENTRATION OF SKIN ACTIVE SUBSTANCE
-
PURPOSE: A cosmetic composition containing enzyme and precursor with an activity at low temperature is provided to promoter skin cell activation and to improve anti-wrinkling and elasticity. CONSTITUTION: A cosmetic composition contains an enzyme with an activity at 0°C-15°C and at least one precursor which produces an active ingredient by reaction with the enzyme. The enzyme is hydrolase such as lipase, choline esterase, phosphatase, dioxyribonuclease, carboxypeptidase, pepsin, trypsin, or chemotrypsin. The precursor is retinyl palmitate, tocopheryl acetate, or piceid. The cosmetic composition is used for anti-aging, skin moisturizing, or skin whitening. The active ingredient is retinol, tocopherol, or resveratrol.
- -
-
Paragraph 0045-0047
(2018/05/24)
-
- Preparation method for high-purity tocopherol succinate salt
-
The invention relates to the field of organic synthesis, specifically to a preparation method for tocopherol succinate salt. The preparation method for the tocopherol succinate salt provided by the invention comprises the following steps: hydrogenating dl-alpha-tocopherol in the presence of a precious metal catalyst, subjecting a hydrogenated product and succinic anhydride to an esterification reaction in the presence of alkali so as to prepare a tocopherol succinate intermediate; and subjecting the tocopherol succinate intermediate to salt-forming. The preparation method for the tocopherol succinate salt provided by the invention can effectively improve the purity of a target product, can effectively reduce the content of a single impurity, and can prepare a calcium salt product with a purity capable of reaching 99.9% or above.
- -
-
Paragraph 0054; 0055; 0056
(2018/09/11)
-
- Synthesis of 2,2-dialkyl chromanes by intramolecular Ullmann C–O coupling reactions toward the total synthesis of D-α-tocopherol
-
The complete synthesis of D-α-tocopherol was achieved using our developed-Ullmann C–O coupling reaction as a key reaction. The synthesis of the core structure of D-α-tocopherol, which is a chiral chromane, has never been reported using intramolecular Ullmann C–O coupling reactions owing to the low reactivity of electron-rich iodoarenes with tertiary alcohols. Because the developed intramolecular C–O coupling reactions prefer electron-rich iodoarenes with tertiary alcohols, we successfully synthesized the chiral chromane core and achieved the total synthesis of D-α-tocopherol.
- Tsubogo, Tetsu,Aoyama, Saki,Takeda, Rika,Uchiro, Hiromi
-
p. 843 - 846
(2018/09/10)
-
- 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.
- Bieszczad, Bartosz,Gilheany, Declan G.
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p. 6483 - 6492
(2017/08/16)
-
- Highly Acidic BINOL-Derived Phosphoramidimidates and their Application in the Bronsted Acid Catalyzed Synthesis of α-Tocopherol
-
The design and synthesis of highly acidic BINOL-derived N,N′-bistriflylphosphoramidimidate and N,N′-bisarylsulfonylphosphoramidimidate Bronsted acid catalysts are reported.
- Kaib, Philip S. J.,List, Benjamin
-
p. 156 - 158
(2015/12/26)
-
- Fast multigram scale microwave-assisted synthesis of Vitamin E and C10-, C15-analogues under vacuum
-
A novel protocol for the microwave-assisted synthesis of (all-rac)-α-tocopherol, including its C10- and C15-analogues, is reported. A rotating microwave reactor working under vacuum favoured the rapid evaporation of condensation water and solvent at the end of the process. The main advantages of this fast procedure are its good yield, selectivity, versatility, lower solvents and energy consumption, easier workup and-scalability.
- Rotolo,Calcio Gaudino,Carnaroglio,Barge,Tagliapietra,Cravotto
-
p. 63515 - 63518
(2016/07/19)
-
- 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.
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Page/Page column 30; 31; 32; 36; 37
(2016/12/22)
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- Photostability of alpha-tocopherol ester derivatives in solutions and liposomes. Spectroscopic and LC-MS studies
-
α-Tocopherol (Toc) is known to degrade to the tocopheroxyl radicals (Toc?) by exposure to UV light irradiation. In the present study, the stability of Toc ester derivatives exposed to UV light was investigated and compared with Toc in organic solution and in phospholipid vesicles. To follow the depletion of Toc and its esters the absorbance and fluorescence methods were applied whereas degradation products were detected using LC-MS method. The irradiation with UVB light of air-equilibrated solutions of di-α-Tocopheryl malonate (DTMO), α-Tocopheryl malonate (TMO) and α-Tocopheryl succinate (TS) strongly modifies their absorption and fluorescence spectra. Upon UVB irradiation, absorption band at 279/285 nm becomes less pronounced indicating the photodegradation of esters. During irradiation, the fluorescence maximum of esters at 305 nm shifts to 326 nm, a maximum characteristic for Toc. Photorecovery of Toc from its esters derivatives was finally confirmed by LC-MS method. Among studied esters, only α-tocopheryl nicotinate (TN) did not undergo depletion and appeared resistant to UVB radiation. Kinetic studies indicated that photoinduced transformation occurs through the first order consecutive reaction chain mechanism. The photodissociation of Toc esters in the liposomes occurred with one order of magnitude slower than in organic solvents. Using MS/MS method it was found that final stable product of irradiation was α-tocopheryl quinone (TQ), an animal and plant metabolite of Toc.
- Neunert, Grazyna,Szwengiel, Artur,Walejko, Piotr,Witkowski, Stanislaw,Polewski, Krzysztof
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p. 121 - 127
(2016/04/26)
-
- Tunneling effect in Vitamin E recycling by green tea
-
Recycling reactions of natural vitamin E (α-tocopherol) by catechins contained in green tea were studied with a double-mixing stopped-flow spectrophotometer. The second-order reaction rate constants of the catechins and deuterated analogues were determined by using a simulation, the activation energies were obtained from the temperature dependences, and the deuterium kinetic-isotope effects were examined. From these results, a tunneling effect was found to play an important role in the vitamin E recycling reactions by the catechins, and the structure-activity relationship was clarified. Furthermore, conditions under which the tunneling effect manifests itself in various vitamin E recycling reactions in biological systems and foods were suggested. A new α-tocopherol-recycling capacity assay-method was also proposed, and named an ATREC assay-method after the acronym.
- Nagaoka, Shin-Ichi,Nitta, Akiko,Suemitsu, Ai,Mukai, Kazuo
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p. 47325 - 47336
(2016/06/09)
-
- FORMATION OF CHIRAL 4-CHROMANONES USING CHIRAL PYRROLIDINES IN THE PRESENCE OF ACIDS
-
The present invention relates to a synthesis of chromanones or chromanes in a stereospecific matter in view of the 2-position in the chromanone or chromane ring. It has been found that this synthesis is particularly possible in the presence of a chiral compound of a specific type and of at least one Bransted acid or in the presence a specific chiral compound having a Bransted acid functional group in the molecule.
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Page/Page column 32; 33
(2015/01/16)
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- 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.
- Lankhorst, Peter P.,Netscher, Thomas,Duchateau, Alexander L. L.
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p. 850 - 855
(2015/11/03)
-
- Synthesis of triphenylphosphonium Vitamin E derivatives as mitochondria-targeted antioxidants
-
A series of mitochondria-targeted antioxidants comprising a lipophilic triphenylphosphonium cation attached to the antioxidant chroman moiety of vitamin E by an alkyl linker have been prepared. The synthesis of a series of mitochondria-targeted vitamin E derivatives with a range of alkyl linkers gave compounds of different hydrophobicities. This work will enable the dependence of antioxidant defence on hydrophobicity to be determined in vivo.
- Jameson, Victoria J.A.,Cochemé, Helena M.,Logan, Angela,Hanton, Lyall R.,Smith, Robin A.J.,Murphy, Michael P.
-
supporting information
p. 8444 - 8453
(2015/10/12)
-
- 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.
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-
- 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.
- 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
-
scheme or table
p. 391 - 395
(2012/03/11)
-
- 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.
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Page/Page column 14
(2012/12/13)
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- Silver(I)-Catalyzed deprotection of p -methoxybenzyl ethers: A mild and chemoselective method
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The p-methoxybenzyl protecting group (PMB) on various alcohols and an acid was efficiently and selectively cleaved by the action of a catalytic amount of silver(I) hexafluoroantimonate combined with 0.5 equiv of 1,3,5- trimethoxybenzene in dichloromethane at 40 °C.
- Kern, Nicolas,Dombray, Thomas,Blanc, Aurelien,Weibel, Jean-Marc,Pale, Patrick
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p. 9227 - 9235,9
(2012/12/12)
-
- Mesoporous and hexagonally ordered CuAl-SBA-15-catalyzed tandem C-C and C-O bond formation between phenols and allylic alcohols
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A novel mesoporous catalyst, CuAl-SBA-15, with a hexagonally ordered porous structure prepared via a soft-templating approach in a highly acidic medium is used for tandem C-C and C-O bond formation between phenols and allylic alcohols to afford a variety of dihydrobenzopyrans in good yields. The catalyst is also found to be highly active for the synthesis of vitamin E and can be recycled several times without significant loss of its activity.
- Varghese, Shaji,Anand, Chokkalinkam,Dhawale, Dattatray,Mano, Ajayan,Balasubramanian, Veerappan V.,Raj, George Allen Gnana,Nagarajan, Samuthira,Wahab, Mohammad A.,Vinu, Ajayan
-
p. 5656 - 5659
(2012/10/29)
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- Simultaneous synthesis of both rings of chromenes via a benzannulation/ o -quinone methide formation/electrocyclization cascade
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A new route to the chromene ring system has been developed which involves the reaction of an α,β-unsaturated Fischer carbene complex of chromium with a propargyl ether bearing an alkenyl group on the propargylic carbon. This transformation involves a cascade of reactions that begins with a benzannulation reaction and is followed by the formation of an o-quinone methide, and finally results in the emergence of a chromene upon an electrocyclization. This reaction was extended to provide access by employing an aryl carbene complex. This constitutes the first synthesis of chromenes in which both rings of the chromene system are generated in a single step and is highlighted in the synthesis of lapachenole and vitamin E.
- Majumdar, Nilanjana,Korthals, Keith A.,Wulff, William D.
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p. 1357 - 1362
(2012/03/11)
-
- Kinetic study of the α-tocopherol-regeneration reaction of ubiquinol-10 in methanol and acetonitrile solutions: Notable effect of the alkali and alkaline earth metal salts on the reaction rates
-
A kinetic study of regeneration reaction of α-tocopherol (α-TocH) by ubiquinol-10 has been performed in the presence of four kinds of alkali and alkaline earth metal salts (LiClO4, NaClO4, NaI, and Mg(ClO4)2) in methanol and acetonitrile solutions, using double-mixing stopped-flow spectrophotometry. The second-order rate constants (kr's) for the reaction of α-tocopheroxyl (α-Toc?) radical with ubiquinol-10 increased and decreased notably with increasing concentrations of metal salts in methanol and acetonitrile, respectively. The kr values increased in the order of no metal salt 4 ～ NaI 4 4)2 at the same concentration of metal salts in methanol. On the other hand, in acetonitrile, the kr values decreased in the order of no metal salt > NaClO4 ～ NaI > LiClO4 > Mg(ClO4)2 at the same concentration of metal salts. The metal salts having a smaller ionic radius of cation and a larger charge of cation gave a larger kr value in methanol, and a smaller k r value in acetonitrile. The effect of anion was almost negligible in both the solvents. Notable effects of metal cations on the UV-vis absorption spectrum of α-Toc? radical were observed in aprotic acetonitrile solution, suggesting complex formation between α-Toc? and metal cations. On the other hand, effects of metal cations were negligible in protic methanol, suggesting that the complex formation between α-Toc? and metal cations is hindered by the hydrogen bond between α-Toc? and methanol molecules. The difference between the reaction mechanisms in methanol and acetonitrile solutions was discussed on the basis of the results obtained. High concentrations of alkali and alkaline earth metal salts coexist with α-TocH and ubiquinol-10 in plasma, blood, and many tissues, suggesting the contribution of the metal salts to the above regeneration reaction in biological systems.
- Mukai, Kazuo,Oi, Masanori,Ouchi, Aya,Nagaoka, Shin-Ichi
-
experimental part
p. 2615 - 2621
(2012/05/20)
-
- HYALURONIC ACID COMPOSITIONS FOR DERMATOLOGICAL USE
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The disclosure provides hyaluronic acid (HA) gel formulations and methods for treating the appearance of the skin. The formulations hyaluronic acid and at least one additional constituent selected from the group consisting of vitamin B, C and vitamin E, wherein the formulation exhibits greater stability than an HA gel formulation without the additional constituent. Methods for treating lines, wrinkles, fibroblast depletions, and scars with the disclosed composition are provided as well.
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- 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.
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Page/Page column 23-25
(2011/10/05)
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- Iridium-catalyzed asymmetric hydrogenation of unfunctionalized, trialkyl-substituted olefins
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Chiral iridium complexes with bicyclic pyridine-based N,P ligands have emerged as efficient catalysts for the enantioselective hydrogenation of unfunctionalized trialkyl-substituted olefins. Optimization of the reaction conditions by variation of the solvent, pressure, and temperature led to enantiomeric excesses of up to 99%. Three pure alkenes, (E)-2-cyclohexyl-2- butene and (E)- and (Z)-3,4-dimethyl-2-pentene were converted into the corresponding chiral alkanes with 97%, 94%, and 93% ee, respectively. Hydrogenation of the three C=C bonds of both α- and γ-tocotrienyl acetate led to α- and γ-tocopheryl acetate with very high diastereoselectivity. The same catalysts were successfully applied in the hydrogenation of trisubstituted alkenes with a carboxylic ester or a keto group in the γ position. This reaction was used as a key step in a highly enantioselective synthesis of the pheromone of the caddisfly Hesperophylax occidentalis. The hydrogenation of a structurally analogous allylic alcohol also gave high enantioselectivities. Unfunctionalized trialkyl-substituted olefins are hydrogenated with high efficiency and excellent enantioselectivity using iridium complexes derived from chiral N,P ligands. In this way, pharmaceutically interesting and industrially relevant compounds with chiral alkyl fragments are easily accessible with high diastereo- and enantioselectivities. Copyright
- Wang, Aie,Fraga, Rui P. A.,Hoermann, Esther,Pfaltz, Andreas
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experimental part
p. 599 - 606
(2011/10/12)
-
- 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.
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Page/Page column 11
(2011/11/30)
-
- Friedel-Crafts alkylations on nanoscopic inorganic fluorides
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The catalytic potential of nanoscopic MFx (M = Mg, Al; x = 2, 3) has been investigated using batch Friedel-Crafts alkylation of aromatic compounds, including benzene, ethylbenzene, trimethylhydroquinone (TMHQ), and menadiol (MDL), with isophytol and benzyl alcohol. The conversion of isophytol was 100% in the reactions with trimethylhydroquinone (TMHQ), menadiol (MDL) and benzene while the highest selectivity in alkylated compounds was achieved with TMHQ (>99%). The different reaction rates of the alkylation reactions are due to the different nucleophylicities of the substrates, and therefore, due to their ability to delocalize the positive charge in the Wheland intermediate by inductive and resonance effects. The conversions of benzyl alcohol varied between 10 and 84% as a function of the catalyst nature and reaction conditions while the highest selectivity to monobenzyl derived compounds (25%) was achieved with ethylbenzene. The formation of high amounts of dibenzyl ether was also observed, indicating the presence of high amounts of Br?nsted acid sites in this type of catalysts.
- Candu,Wuttke,Kemnitz,Coman,Parvulescu
-
experimental part
p. 169 - 174
(2011/10/05)
-
- Zinc catalyst recycling in the preparation of (all-rac)-α-tocopherol from trimethylhydroquinone and isophytol
-
Recycling of ZnCl2 as a catalyst in the cyclocondensation of trimethylhydroquinone and isophytol to all-rac-a-tocopherol was studied. ZnCl2 was recycled at over 98 % efficiency in required purity by repeated extraction of the reaction streams with water, followed by switching of solvent to butyl acetate and then back to water. Recycled ZnCl2 had no negative effect on the yield of all-rac-a- tocopherol (maintaining over 90 %) at nearly total conversion of isophytol and only a 3 % molar excess of trimethylhydroquinone.
- Goemoery, Juraj,Kralik, Milan,Kaszonyi, Alexander
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experimental part
p. 427 - 436
(2012/07/13)
-
- Ionic liquids - Advanced reaction media for organic synthesis
-
The advantages in the application of ionic liquids as reaction media in organic synthesis, i.e., in the preparation of chromane derivatives, substituted pyrazines, 4-aminofuran-2(5H)-ones, or in bromination of Levulinic acid or dehydration of alcohols, saccharides, and polysaccharides, have been demonstrated on several examples. Ionic liquids with Bronsted acidity have been shown to possess catalytic activity and provide access to convenient technologies for the preparation of various useful compounds. Copyright Merck KGaA.
- Ignat'ev, Nikolai V.,Schulte, Michael,Koppe, Karsten,Barthen, Peter,Zlotin, Sergei G.,Makhova, Nina N.,Sheremetev, Aleksei B.,Valente, Anabela A.
-
scheme or table
p. 1205 - 1216
(2011/09/16)
-
- Directing zeolite structures into hierarchically nanoporous architectures
-
Crystalline mesoporous molecular sieves have long been sought as solid acid catalysts for organic reactions involving large molecules. We synthesized a series of mesoporous molecular sieves that possess crystalline microporous walls with zeolitelike frameworks, extending the application of zeolites to the mesoporous range of 2 to 50 nanometers. Hexagonally ordered or disordered mesopores are generated by surfactant aggregates, whereas multiple cationic moieties in the surfactant head groups direct the crystallization of microporous aluminosilicate frameworks. The wall thicknesses, framework topologies, and mesopore sizes can be controlled with different surfactants. The molecular sieves are highly active as catalysts for various acid-catalyzed reactions of bulky molecular substrates, compared with conventional zeolites and ordered mesoporous amorphous materials.
- Na, Kyungsu,Jo, Changbum,Kim, Jeongnam,Cho, Kanghee,Jung, Jinhwan,Seo, Yongbeom,Messinger, Robert J.,Chmelka, Bradley F.,Ryoo, Ryong
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scheme or table
p. 328 - 332
(2012/06/18)
-
- Polyglutamic Acids Functionalised by Histidine Derivatives and Hydrophobic Groups and the Uses Thereof, in Particular for Therapeutic Purposes
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The invention relates to novel biodegradable materials based on modified polyamino acids and suitable, in particular, for vectoring active substance(s) (AS). Said invention also relates to novel pharmaceutical, cosmetic, dietary or plant protective compositions which are based on said polyamino acids. The aim of said invention is to provide a novel polymer raw material usable for vectoring the AS and capable to optimally meet all specification in this area: biocompatibility, biodegradability, ability to become easily associated with many active substances or to solubilise them and to release said active substances in vivo. The aim is attained to 30 carbon atoms. Said polyglutamates modified by histidine derivatives are soluble with pH lower than 5 and are easily and economically convertible into active substance vectorization particles which are able to form stable aqueous colloidal suspensions. On the contrary, said modified polyglutamates are insoluble in water with a physiological pH (7.4), and thereby have to be precipitated on an injection site in the case of a subcutaneous injection.
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- Polyamino acids functionalized by hydrophobic grafts bearing an anionic charge and applications thereof, such as therapeutic applications
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The present invention relates to novel materials based on biodegradable polyamino acids that are useful especially for the vectorization of active principle(s) (AP). The invention further relates to novel pharmaceutical, cosmetic, dietetic or phytosanitary compositions based on these polyamino acids. The object of the invention is to provide a novel polymer starting material that is capable of being used for the vectorization of AP and makes it possible on the one hand to achieve high polymer/AP ratios, and on the other hand optimally to satisfy all the specifications required in the case in point: biocompatibility, biodegradability, ability to associate easily with numerous active principles or to solubilize them, and ability to release these active principles in vivo. This object is achieved by the present invention, which relates first and foremost to linear polyamino acids comprising aspartic units or glutamic units and having hydrophobic grafts comprising hydrophobic groups containing from 8 to 30 carbon atoms, at least one of these hydrophobic grafts having at least one anionic charge and/or one or more mutually identical or different ionizable groups each capable of giving rise to at least one anionic charge. These polymers are amphiphilic and anionic and are capable of being converted easily and economically to particles for the vectorization of active principles, these particles themselves being capable of forming stable aqueous colloidal suspensions.
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- SCAFFOLDS FOR FOLLICLE TRANSPLANTATION
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The present invention provides for a device comprising a scaffold composition, a bioactive composition and a bio-in-hibiting composition, wherein said bioactive and bio-inhibiting compositions are incorporated into or coated onto said scaffold composition, wherein said scaffold composition temporally supports survival and growth of resident follicles, migration and multiplication of stroma cells and spreading and organization of endothelial cells and new vessels wherein said bioactive composition regulates development of a resident follicle, formation of new blood vessels and chemoattraction and proliferation of stroma cells and wherein the bio-inhibiting composition regulates inhibition of the development of a second resident follicle. The presence of the bio-inhibiting composition within the scaffold is involved in the quiescence of the follicles in the primordial stage, which is important to restore fertility.
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- Sol-gel prepared nanoscopic metal fluorides - A new class of tunable acid-base catalysts
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In this article, the high potential of the fluorolytic sol-gel process to synthesise nanoscopic metal fluorides with different acid-base properties is shown. These nanoscopic materials exhibit high potential to be used as heterogeneous catalysts due to their high surface areas and their tunable surface properties. Thus, for each specific reaction the required surface properties of the catalysts can be "adjusted" to achieve a high yield and selectivity of the desired product. As a consequence, a greener method of chemical production can be accomplished. Moreover the cheap and easy synthesis of the catalysts using basic chemicals not only makes them interesting for fundamental research but also provides an easy transformation to industrial applications.
- Wuttke,Coman,Kr?hnert,Jentoft,Kemnitz
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experimental part
p. 2 - 10
(2010/10/04)
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- Asymmetric synthesis of α-Tocopherol
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α-Tocopherol was synthesized from a chiral intermediate α-hydroxy ester by means of two ring-closing methods to yield the chromanol in 94 % diastereomeric excess.
- Hengartner, Urs,Chougnet, Antoinette,Liu, Kegang,Woggon, Wolf-D.
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scheme or table
p. 1306 - 1311
(2010/06/12)
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- Tunneling effect in regeneration reaction of vitamin e by ubiquinol
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A kinetic study of the regeneration reaction of vitamin E by ubiquinol was carried out by means of double-mixing stopped-flow spectroscopy. A substantial deuterium kinetic-isotope effect was observed on the second-order rate constant and the activation energy. In the regeneration reaction of α-tocopherol, deuteration of ubiquinol increased and decreased the activation energy and the second-order rate constant by 6.1 kJ/mol and a factor of 18.3, respectively. From this result, it is considered that proton tunneling plays an important role in the regeneration reaction of vitamin E by ubiquinol. The conditions under which the tunneling effect becomes an important factor were discussed in conjunction of our experimental results.
- Ouchi, Aya,Nagaoka, Shin-Ichi,Mukai, Kazuo
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experimental part
p. 6601 - 6607
(2011/01/03)
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- Biomimetic chromanol cyclisation: A common route to a-tocotrienol and α-tocopherol
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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.
- Chapelat, Julien,Chougnet, Antoinette,Woggon, Wolf-D.
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experimental part
p. 2069 - 2076
(2009/09/08)
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- Self-precipitating pharmaceutical formulations for the moified release of an active principle
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The present invention relates to novel pharmaceutical formulations for the release of an active principle (AP) over a sustained period of time of several days, or even several weeks. The invention relates, in a first aspect, to a liquid formulation comprising at least one active principle (AP) and an aqueous suspension based on collo?dal particles of a polymer (PO), wherein said formulation satisfies the following four conditions: (a) the polymer (PO) is a polyamino acid comprising glutamic residues, wherein some glutamic residues each carry a pendant cationic group (CG), said cationic groups being identical or different from one another, andother glutamic residues each carry a pendent hydrophobic group (GH), said hydrophobic groups (GH) being identical or different from one another, (b) the pHf value of the pH of said formulation is between 3.0 and 6.5; (c) at the pHf value, the polymer (PO) forms a collo?dal solution which associates spontaneously and noncovalently with the active principle (AP); (d) 1 ml of said formulation precipitates during mixing with a volume of 1 ml of a test buffer solution Tp. The invention also relates to a process for the preparation of such formulations and to a process for the preparation of medicaments including such formulations.
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- Formation and decay dynamics of vitamin e radical in the antioxidant reaction of vitamin E
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In order to understand the dynamics of antioxidant actions of vitamin E (α-, β-, γ-, and δ-tocopherols, TocH) in biological systems, kinetic study of the formation and decay reactions of vitamin E radicals (α-, β-, γ-, and γ- tocopheroxyls, Toc ?) has been performed in organic solvents, using stopped-flow spectrophotometry. By mixing α-, β-, γ-, and δ-TocH with aryloxyl radical (ArO ?) in ethanol, the peaks of the UV-vis absorption due to α-, β-, γ-, and δ-Toe? radical appeared rapidly at ca. 430-340 nm, showed maxima, and then decayed gradually. The second-order rate constants (κa and 2κd) for the formation and decay (that is, bimolecular disproportionation) reactions of a-Toe were determined by comparing the observed curves with the simulation ones obtained by the numerical calculation of differential equations related to the above reactions. From the results, the wavelengths of absorption maxima (λmax i) and molar extinction coefficients (ε) (i = 1-4) of the optical spectra were determined for α-Toc? radical. Notable solvent effects have been observed for the reaction rates (κf and 2κd) and absorption spectra (λmax i and εi) of α-Toc? radical. The scheme of the formation and decay reactions of α-, β-, γ-, and δ-Toc? radicals has been discussed based on the results obtained.
- Mukai, Kazuo,Ouehi, Aya,Mitarai, Akiko,Ohara, Keishi,Matsuoka, Chihiro
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experimental part
p. 494 - 503
(2009/08/07)
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- Method for the synthesis of dl.(alpha)-tocopherol and means therefore
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The present invention is related to a method for synthesizing dl-alpha-tocopherol comprising the steps of - providing 2,3,5-trimethylhydroquinone; - providing isophytol; - providing a solid fluoride catalyst; and - reacting the 2,3,5-trimethylhydroquinone with the isophytol in the presence of the catalyst.
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Page/Page column 8; 10
(2009/05/29)
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- Synthesis of chromans via [3 + 3] cyclocoupling of phenols with allylic alcohols using a Mo/o-chloranil catalyst system
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(Chemical Equation Presented) The combination of a molybdenum complex (CpMoCl(CO)3 or [CpMo(CO)3]2) and o-chloranil was used as a catalyst in the [3 + 3] cyclocoupling of phenols and allylic alcohols under microwave heating conditions. Substituted chromans were selectively obtained in moderate to good isolated yields.
- Yamamoto, Yoshihiko,Itonaga, Kouhei
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scheme or table
p. 717 - 720
(2009/08/19)
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- Polyphenolic Bioprecursors
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Cosmetic and therapeutic, in particular dermatological bioprecursors have the formula [A]n—PP—[B]m wherein PP is a polyphenol radical in which each hydroxyl function is protected by a group A or a group B, A is a saturated or unsaturated, substituted or unsubstituted alkyl radical having 1 to 20 carbon atoms which is bonded to the polyphenol, n is an integer not less than 1, and B is a precursor of a biologically active molecule, which is also bonded to the polyphenol, and m is an integer also not less than 1.
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Page/Page column 9-10
(2009/09/07)
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- Novel sol-gel synthesis of acidic MgF2-x(OH)x materials
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Novel magnesium fluorides have been prepared by a new fluorolytic sol-gel synthesis for fluoride materials based on aqueous HF. By changing the amount of water at constant stoichiometric amount of HF, it is possible to tune the surface acidity of the resulting partly hydroxylated magnesium fluorides. These materials possess medium-strength Lewis acid sites and, by increasing the amount of water, Br?nsted acid sites as well. Magnesium hydroxyl groups normally have a basic nature and only with this new synthetic route is it possible to create Br?nsted acidic magnesium hydroxyl groups. XRD, MAS NMR, TEM, thermal analysis, and elemental analysis have been applied to study the structure, composition, and thermal behaviour of the bulk materials. XPS measurements, FTIR with probe molecules, and the determination of N 2/Ar adsorption-de-sorption isotherms have been carried out to investigate the surface properties. Furthermore, activity data have indicated that the tuning of the acidic properties makes these materials versatile catalysts for different classes of reactions, such as the synthesis of (all-rac)-[α]-tocopherol through the condensation of 2,3,6- trimethylhydroquinone (TMHQ) with isophytol (IP).
- Wuttke, Stefan,Coman, Simona M.,Scholz, Gudrun,Kirmse, Holm,Vimont, Alexandré,Daturi, Maro,Schroeder, Sven L. M.,Kemnitz, Erhard
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experimental part
p. 11488 - 11499
(2009/12/03)
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- Diastereoselective synthesis of α-tocopherol: A new concept for the formation of chromanols
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(Chemical Equation Presented) A diastereoselective synthesis of α-tocopherol 1 (93% de) was achieved via two key steps, (i) a highly diastereoselective Shi epoxidation of a trisubstituted alkene and (ii) an acid supported, "anti-Baldwin" epoxide ring opening under inversion of configuration leading to the 6-membered chromanol ring.
- Chapelat, Julien,Buss, Axel,Chougnet, Antoinette,Woggon, Wolf-D.
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scheme or table
p. 5123 - 5126
(2009/05/30)
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- A short route to α-tocopherol
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(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.
- Liu, Kegang,Chougnet, Antoinette,Woggon, Wolf-D.
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supporting information; experimental part
p. 5827 - 5829
(2009/03/11)
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- Determination of the stereoisomers of racemic α-tocopherol in pharmaceutical preparations by high-performance liquid chromatography and gas chromatography
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In the present study we used chiral high performance liquid chromatography and gas chromatography to determine the stereoisomers of racemic α-tocopherol. The Chiralcel OD-H and Silar-100 AT columns were used. Statistical evaluation of the results established the precision of these methods.
- Klaczkow, Gabriela,Anuszewska, Elzbieta L.
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experimental part
p. 715 - 721
(2009/07/25)
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- Catalytic performance of nanoscopic, aluminium trifluoride-based catalysts in the synthesis of (all-rac)-α-tocopherol
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A novel nanoscopic, partly hydroxylated aluminium fluoride was prepared in a sol-gel fluorination synthesis and characterised by IR probe molecules. It was shown that this material has, in contrast to high surface area aluminium fluoride (HSAlF3) which is one of the strongest Lewis acids, a low amount of strong Lewis acid sites combined with weak and medium strength Br?nsted sites. Both materials were tested in the synthesis of (all-rac)-α-tocopherol through the condensation of 2,3,6- trimethylhydroquinone (TMHQ) with isophytol (IP). The activity data indicate the partly hydroxylated aluminium fluoride to be a very efficient and highly selective catalyst for (all-rac)-α-tocopherol (>99.9%, for an IP conversion of 100%) whereas high surface area aluminium fluoride is a poor catalyst for this reaction.
- Coman,Wuttke,Vimont,Daturi,Kemnitz
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experimental part
p. 2517 - 2524
(2009/08/14)
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- Tocopherols by hydride reduction of dialkylamino derivatives
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Aminomethylation with Mannich reagents derived from secondary amines and paraformaldehyde under improved conditions has been used to convert non-α-tocopherol homologues into α-tocopherol, the biologically most important vitamin E compound. Mono- and bis(aminomethylated) β-, γ-and δ-tocopherol were then subsequently transformed into the corresponding tocopherols (α- and β-tocopherol) by reductive deamination. As an alternative to classical catalytic hydrogenation in the last step, efficient laboratory protocols using complex hydrides have been derived and applied to the preparation of labelled vitamin E compounds. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Netscher, Thomas,Mazzini, Francesco,Jestin, Roselyne
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p. 1176 - 1183
(2008/02/08)
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