- Stereoselective total synthesis method of (2R, 4 'R, 8' R)-alpha-tocopherol
-
The invention discloses a stereoselective total synthesis method of (2R, 4 'R, 8' R)-alpha-tocopherol. The method comprises the following steps: performing iodination on trimethylhydroquinone serving as a raw material to generate aromatic halide, and performing Heck reaction and Pd/C hydrogenation on the aromatic halide and diester containing a terminal olefinic bond to form saturated aromatic diester; then diester is selectively hydrolyzed to generate monoester with high optical activity, and a chiral three-dimensional center is constructed; then carrying out methylsulfonyl chlorination and lithium aluminum hydride reduction to form a methyl-containing chiral compound; carrying out oxidation ring closing and hydrogenation reduction to construct a chiral chroman mother nucleus; then carrying out benzyl protection and Wittig reaction, and realizing carbon-carbon bond connection with C15 * fat long-chain phosphine salt; finally, double bonds are reduced to obtain (2R, 4 'R, 8' R)-alpha-tocopherol I. The method has the advantages that the raw materials are easy to obtain, the reaction condition is mild, the operation is simple and convenient, the used lipase has good stability, the catalytic form is green and environment-friendly, and the industrial application value is realized.
- -
-
-
- CHINONE-, HYDROCHINOME- AND NAPHTHOCHINONE-ANALOGUES OF VATIQUIONE FOR TREATMENT OF MITOCHONDRIAL DISORDER DISEASES
-
The disclosure provides therapeutic compositions (i.e., therapeutic agents) and methods of preventing or treating Friedreich's ataxia in a mammalian subject, reducing risk factors, signs and/or symptoms associated with Friedreich's ataxia (e.g. Complex I deficiency), and/or reducing the likelihood or severity of Friedreich's ataxia. The disclosure further provides novel intermediates for the production of said therapeutic compositions and related reduced versions of said therapeutic compositions, which reduce forms may also be used as therapeutic agents (or prodrugs of the therapeutic agent(s)).
- -
-
-
- Enantioselective Halo-oxy- and Halo-azacyclizations Induced by Chiral Amidophosphate Catalysts and Halo-Lewis Acids
-
Catalytic enantioselective halocyclization of 2-alkenylphenols and enamides have been achieved through the use of chiral amidophosphate catalysts and halo-Lewis acids. Density functional theory calculations suggested that the Lewis basicity of the catalyst played an important role in the reactivity and enantioselectivity. The resulting chiral halogenated chromans can be transformed to α-Tocopherol, α-Tocotrienol, Daedalin A and Englitazone in short steps. Furthermore, a halogenated product with an unsaturated side chain may provide polycyclic adducts under radical cyclization conditions.
- Lu, Yanhui,Nakatsuji, Hidefumi,Okumura, Yukimasa,Yao, Lu,Ishihara, Kazuaki
-
p. 6039 - 6043
(2018/05/14)
-
- DEUTERATED EPI-743
-
This invention relates to novel α-tocotrienol quinones of Formula I: (I), and pharmaceutically acceptable salts thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treat
- -
-
Paragraph 190
(2017/06/12)
-
- 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.
- Noguchi, Taro,Oishi, Shinya,Honda, Kaori,Kondoh, Yasumitsu,Saito, Tamio,Ohno, Hiroaki,Osada, Hiroyuki,Fujii, Nobutaka
-
p. 7653 - 7656
(2016/07/06)
-
- 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.
-
p. 850 - 855
(2015/11/03)
-
- Synthesis and screening of novel vitamin e derivatives for anticancer functions
-
α-TEA, RRR-α-tocopherol ether linked acetic acid, exhibits potent anticancer actions in vitro and in vivo; whereas, the parent molecule has no anticancer activity. In this study, we incorporated fluorine at the chroman head and/or ether linkage between the chroman head and phytyl tail of α-TEA as well as RRR-α-tocopherol to synthesize 6 vitamin E derivatives, and evaluated the anticancer actions in vitro for ability to induce cell death by apoptosis of human MCF-7 and MDA-MB-231 breast cancer cell lines and mouse mammary cancer cell line 66cl-4GFP. All derivatives, with the exception of compound 12, exhibited anticancer properties. The modified α-TEA ether-type phytyl group exhibited the highest pro-apoptotic activity in comparison with α-TEA as well as other vitamin E derivatives.
- Chen, Wenbin,Park, Sook Kyung,Yu, Weiping,Xiong, Ailian,Sanders, Bob G.,Kline, Kimberly
-
-
- New possibilities in a synthesis of (2R,4'R,8'R)-α-tocopherol (natural vitamin E)
-
New methods for the synthesis of homochiral C14 and C 15-terpenoids desired as building blocks for phytilic side chain of natural α-tocopherol have been developed. A natural phytone resulted from the proposed effective method of chlo
- Spivak, Anna Yu,Shafikov, Ruslan V.,Odinokov, Victor N.
-
-
- Enantioselective transesterification of (±)-6-benzyloxy-2,5,7,8- tetramethyl-3,4-dihydro-2H-1-benzopyran-2-ylmethanol catalyzed by the Amano PS lipase in the ionic liquid [bmim]PF6
-
(S)-(-)-6-Benzyloxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-1-benzopyran-2- ylmethanol, a synthon for the design of natural α-tocopherol, was obtained by kinetically selective acetylation of the corresponding racemic alcohol in the presence of the Amano PS lipase from Burkholderia cepacia in the ionic liquid 1-butyl-3-methylimidazolinium hexafluorophosphate ([bmim]PF6).
- Shafikov,Spivak, A. Yu.,Odinokov
-
experimental part
p. 2129 - 2132
(2011/07/30)
-
- Reagent directing group controlled organic synthesis: Total synthesis of (R,R,R,)-α-tocopherol
-
(Chemical Equation Presented) The direct approach: The efficient use of substrate control has served as the basis for the enantioselective total synthesis of (R,R,R)-α-tocopherol. A single reagent directing group (ortho-diphenylphosphanyl benzoate, o-DPPB) served to control the stereoselectivity of a rhodium-catalyzed hydroformylation reaction and the directed allylic substitution as the fragment-coupling step (see picture).
- Rein, Christian,Demel, Peter,Outten, Robert A.,Netscher, Thomas,Breit, Bernhard
-
p. 8670 - 8673
(2008/09/18)
-
- Chemoenzymatic synthesis of both enantiomers of α-tocotrienol
-
The stereoselective acylation of the achiral chromanedimethanol derivative 1 by vinyl acetate in the presence of Candida antarctica lipase B gave the (S)-monoester 2 in high enantiomeric purity (ee ≥ 98%). Enzymatic hydrolysis of diesters of compound 1 failed to give (R)-monoester 2 in good yield and high ee. Thus, both enantiomers of α-tocotrienol were synthesized from the (S)-monoester 2.
- Chenevert, Robert,Courchesne, Gabriel,Pelchat, Nicholas
-
p. 5389 - 5396
(2007/10/03)
-
- Enantioselective synthesis of (2R,4'R,8'R)-α-tocopherol (Vitamin E) based on enzymatic function
-
Syntheses of (S)-chroman-2-carboxaldehyde congener 1 and (S)-chiral isoprene unit 3 were achieved based on the enzymatic acetylation of (±)- chroman-2-methanol 6 and (±)-(2,3)-anti-2-methyl-3-(p-methoxyphenyl)-1,3- propane diol 12, respectively. Synthesis of the side-chain part corresponding to (3R,7R)-3,7,11-trimethyldodecan-1-ol 27 was achieved by the coupling reaction of (S)-3 and (R)-3,7-dimethyloctyl iodide 4. The Wittig reaction of (3R,7R)-phosphonium salt 2 derived from (3R,7R)-27 and (S)-1 gave the olefin 28 which was subjected to catalytic hydrogenation to afford (2R,4'R,8'R)-α- tocopherol.
- Nozawa, Masako,Takahashi, Keiko,Kato, Keisuke,Akita, Hiroyuki
-
p. 272 - 277
(2007/10/03)
-
- Enantioselective Functionalization of Prochiral Diols via Chiral Spiroketals: Preparation of Optically Pure 2-Substituted 1,3-Propanediol Derivatives and Asymmetric Synthesis of Chroman Ring and Side Chain of α-Tocopherol
-
The enantioselective functionalization of a prochiral hydroxyl group in 2-substituted 1,3-propanediols (HOCH2CR1R2CH2OH) is presented.The reaction of the bis(trimethylsilyl) derivative of the diol with l-menthone in the presence of trimethylsilyl trifluoromethanesulfonate selectively gave one of the diastereomers of the spiroketal in which the larger substituent (R1) occupies an equatorial position.The equatorial spiroketal was treated with acetophenone enol trimethylsilyl ether in the presence of titanium tetrachloride to give the ring-cleavage product which was produced by the selective cleavage of the equatorial C-O bond.After a proper functionalization of the hydroxyl group, the chiral auxiliary was removed under basic conditions to give the optically pure (>95percent ee) derivatives 5. The stereoselective preparation of the axial spiroketal (R1 = H, R2 = Me) and its ring-cleavage are also described.The potentiality of the present method is demonstrated in an asymmetric synthesis of (2R,6R)-2,6,10-trimethylundecanol and (S)-6-benzyloxy-3,4-dihydro-2,5,7,8-tetramethyl-2H-benzopyran-2-methanol which are key intermediates in the total synthesis of naturally occuring (2R,4'R,8'R)-α-tocopherol.
- Harada, Toshiro,Hayashiya, Toshio,Wada, Isao,Iwa-ake, Naoko,Oku, Akira
-
p. 527 - 532
(2007/10/02)
-
- Synthesis of optically active vitamin E
-
Synthesis of optically active vitamin E from 2-methyl-5-oxotetrahydro-2-furoic acid including intermediates in this synthesis.
- -
-
-