- Stereoselective total synthesis method of (2R, 4 'R, 8' R)-alpha-tocopherol
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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.
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- Screening of a virtual mirror-image library of natural products
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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
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supporting information
p. 7653 - 7656
(2016/07/06)
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- Gold-catalyzed asymmetric allylic substitution of free alcohols: An enantioselective approach to chiral chromans with quaternary stereocenters for the synthesis of Vitamin E and analogues
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The enantioselective synthesis of α- and γ-tocopherol (the most biologically active members of vitamin E family) and analogues has been accomplished employing a new enantioselective gold catalyzed intramolecular allylic alkylation reaction followed by an olefin cross-metathesis as key steps. The methodology proved to be applicable to different olefins highlighting its potential for the synthesis of diverse libraries. The enantioselective synthesis of α- and γ-tocopherol (the most biologically active members of vitamin E family) and analogues has been accomplished employing an enantioselective gold-catalyzed intramolecular allylic alkylation reaction followed by an olefin cross-metathesis as key steps (see scheme).
- Uria, Uxue,Vila, Carlos,Lin, Ming-Yuan,Rueping, Magnus
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supporting information
p. 13913 - 13917
(2016/02/18)
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- New possibilities in a synthesis of (2R,4'R,8'R)-α-tocopherol (natural vitamin E)
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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.
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experimental part
p. 67 - 75
(2011/06/21)
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- 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
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(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
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experimental part
p. 2129 - 2132
(2011/07/30)
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- Reagent directing group controlled organic synthesis: Total synthesis of (R,R,R,)-α-tocopherol
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(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
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p. 8670 - 8673
(2008/09/18)
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- Improved synthesis of tocopherol fatty alcohols and analogs: microglial activation modulators
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The synthesis of tocopherol fatty alcohols (TFAs), potent microglial activation modulators, was achieved via C-alkylation of trimethylhydroquinone. Several analogs, in particular water-soluble prodrugs, have been synthesized using a Wittig reaction and th
- Muller, Thierry,Coowar, Djalil,Hanbali, Mazen,Heuschling, Paul,Luu, Bang
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p. 12025 - 12040
(2007/10/03)
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- Tocopherol, tocotrienol, other chromane, and their side chain deriv. and method for using the same
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The present invention provides an antiproliferative compound having the structural formula wherein X is oxygen, nitrogen or sulfur; Y is selected from the group consisting of oxygen, nitrogen and sulfur wherein when Y is oxygen or nitrogen, n is 1 and when Y is sulfur, n is 0. Also provided is a method for inducing apoptosis in a cell comprising administering a composition comprising a compound having said structural formula.
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Page/Page column 26
(2008/06/13)
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- Tocopherols, tocotrienols, other chroman and side chain derivatives and uses thereof
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The present invention provides an antiproliferative compound having a structural formula where X and Y independently are oxygen, nitrogen o r sulfur; R1 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, carboxylic acid, carboxylate, carboxamide, ester, thioamide, thiolacid, thiolester, saccharide, alkoxy-linked saccharide, amine, sulfonate, sulfate, phosphate, alcohol, ethers or nitriles; R2 and R3 are hydrogen or R4; R4 is methyl, benzyl carboxylic acid, benzyl carboxylate, benzyl carboxamide, benzylester, saccharide or amine; and R5 is alkenyl; where when Y is nitrogen, said nitrogen is substituted with R6, wherein R6 is hydrogen or methyl. Also provided are methods for treating a cell proliferative disease and for inducing apoptosis in a cell comprising administering this compound is also provided.
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Page column 22-23
(2008/06/13)
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- A new synthetic route to (S)-chroman aldehyde, a key chiral precursor of vitamin E
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A highly stereocontrolled synthetic route to (S)-chroman aldehyde has been developed which starts with trimethyl-p-hydroquinone and (R)-glycerladehyde acetonide and employs as key steps the Michael addition of the aromatic copper species onto the (R)-4-acryloyl-1,3-dioxolane followed by the highly diastereoselective methylation of the resulting ketone adduct.
- Mikoshiba,Mikami,Nakai
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p. 989 - 990
(2007/10/03)
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- Enantioselective synthesis of (2R,4'R,8'R)-α-tocopherol (Vitamin E) based on enzymatic function
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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
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p. 272 - 277
(2007/10/03)
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- Enantioselective synthesis of chromans for the preparation of enantiopure vitamin E and analogues
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Coupling of the differently protected (hydroxymethyl)enynes 11 a-e and 12a-c with the iodoarene 7 in the presence of catalytic amounts of Pd(PPh3)4 afforded the arylenynes 5a-e and 6a-c which were transformed into the monoprotected chiral trihydroxy compounds 13 a-d and 14a,b by Sharpless bishydroxylation with >95% ee for 13 a-d, 91% ee for 14b, and 64% ee for 14a. A 5-step transformation of 13a led to the desired chroman derivative 3a which was cleaved to give the aldehyde 2 a known precursor for the enantioselective synthesis of vitamin E.
- Tietze, Lutz F.,G?rlitzer, Jochen
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p. 877 - 885
(2007/10/03)
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- 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
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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
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p. 527 - 532
(2007/10/02)
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- Synthesis of optically active vitamin E
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Synthesis of optically active vitamin E from 2-methyl-5-oxotetrahydro-2-furoic acid including intermediates in this synthesis.
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