- C3-Symmetric Tricyclo[2.2.1.02,6]heptane-3,5,7-triol
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A straightforward access to a hitherto unknown C3-symmetric tricyclic triol both in racemic and enantiopure forms has been developed. Treatment of 7-tert-butoxynorbornadiene with peroxycarboxylic acids provided mixtures of C1- and C3-symmetric 3,5,7-triacyloxynortricyclenes via transannular π-cyclization and replacement of the tert-butoxy group. By refluxing in formic acid, the C1-symmetric esters were converted to the C3-symmetric formate. Hydrolysis gave diastereoisomeric triols, which were separated by recrystallization. Enantiomer resolution via diastereoisomeric tri(O-methylmandelates) delivered the target triols on a gram scale. The pure enantiomers are useful as core units of dopants for liquid crystals.
- Kozel, Volodymyr,Daniliuc, Constantin-Gabriel,Kirsch, Peer,Haufe, Günter
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supporting information
p. 15456 - 15460
(2017/11/13)
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- (R)- N - [5 - (2 - methoxy - 2 - phenyl-acetyl) - 1, 4, 5, 6 - tetrahydro-pyrrolo [3, 4 - c] pyrazole - 3 - yl] - 4 - (4 - methyl piperazine - 1 - yl) benzamide synthesis method
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The invention belongs to the technical field of medicine and relates to a preparation method for PHA739358(Danusertib), i.e., (R)-N-[5-(2-methoxy-2-phenylacetyl)-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole-3-yl]-4-(4-methyl piperazine-1-yl)benzamide. According to the invention, altogether four reaction routes are designed, simple and easily available glycine is used as a raw material, reactions like addition, esterification, amino protection and cyclization are carried out so as to prepare (R)-N-[5-(2-methoxy-2-phenylacetyl)-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole-3-yl]-4-(4-methyl piperazine-1-yl)benzamide, yield of the route 1, 2 and 4 is more than 25%, respectively, and yield of the route 3 is more than 20%. The preparation method has the advantages of a few reaction steps, simple and convenient post-treatment operation, little time consumption, high yield and low total cost. Thus, a novel method is provided for preparation of the antitumor drug PHA739358.
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Paragraph 0056; 0068
(2017/02/17)
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- Effect of the concentration of organic modifier in an aqueous-ethanol mobile phase on the chromatographic retention and thermodynamic characteristics of the adsorption of enantiomers of α-phenylcarboxylic acids on silica gel with immobilized eremomycin antibiotic
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Regularities of the chromatographic retention and thermodynamics of the adsorption of enantiomers of α-phenylcarboxylic acids on a chiral stationary phase with immobilized macrocyclic antibiotic eremomycin under conditions of reversed-phase liquid chromatography with aqueous-ethanol mobile phases are studied. Relationships between the retention characteristics of the acids, the enantioselectivity of their separation, and the concentration of organic modifier in the mobile phase are found. It is shown that the sterical structure of substituents on the chiral atoms of the acids affect the mechanism of retention. The compensation effect in the studied systems is considered.
- Blinov,Reshetova
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p. 1778 - 1784
(2014/11/08)
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- Enantioseparation of typical pesticides using cellulose carbamate stationary phases by capillary liquid chromatography
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Cellulose-tris(3,5-dimethylphenylcarbamate) was initially synthesized as the chiral selector, then stable coated and bonded chiral stationary phases were prepared, respectively, using aminopropyl-functionalized silica gel as the support media. The prepared stationary phases were used for micro-column chiral separation by self-installed capillary high performance liquid chromatography system. Eighteen kind of chiral compounds including some typical pesticides were tested on both prepared chiral stationary phases and different chromatographic parameters such as resolution and retention time were comparatively investigated.
- Bai, Lian-Yang,Zhang, Yu-Ping,Deng, Pu-Hong,Zhang, Yi-Jun,Chen, Jun
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experimental part
p. 4917 - 4922
(2012/10/08)
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- Kinetic resolution of (R,S)-pyrazolides containing substituents in the leaving pyrazole for increased lipase enantioselectivity
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With hydrolysis of (R,S)-azolides in water-saturated methyl tert-butyl ether (MTBE) via Candida antarctica lipase B (CALB) as the model system, (R,S)-pyrazolides containing a leaving 3-, 4- or 3,4-substituted-pyrazole moiety are selected as the best substrates for preparing various optically pure carboxylic acids containing an α-chiral center. Great improvements of enzyme activity for the (R)-enantiomers with excellent enantioselectivity (VR/VS > 100) are obtainable, if (R,S)-pyrazolides containing a leaving 3- or 3,4-substituted-pyrazole moiety are employed for the hydrolysis or alcoholysis by methanol in anhydrous MTBE. A detailed kinetic analysis for (R,S)-N-2-phenylpropionylpyrazoles indicates that a bulky 3-substituent such as 3-(3-bromophenyl) or 3-(2-pyridyl) in the leaving pyrazole moiety has profound effects on decreasing the nucleophilic attack and proton transfer of catalytic serine for the slow-reacting enantiomer in anhydrous MTBE, as well as that and substrate affinity for both enantiomers in water-saturated MTBE. The resolution platform is also successfully applied to the hydrolysis of (R,S)-pyrazolides in water-saturated cyclohexane via Candida rugosa lipase (Lipase MY) having opposite enantioselectivity to CALB.
- Wang, Pei-Yun,Wu, Chia-Hui,Ciou, Jyun-Fen,Wu, An-Chi,Tsai, Shau-Wei
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experimental part
p. 113 - 119
(2011/02/21)
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- High-performance liquid chromatography separation of enantiomers of mandelic acid and its analogs on a chiral stationary phase
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The enantiomers of mandelic acid and its analogs have been chromatographically separated on a chiral stationary phase (CSP) derived from 4-(3,5-dinitrobenzamido) tetrahydrophenanthrene. The rationale of separations of these compounds is discussed with respect to the method development for determining enantiomeric purity and possibility of obtaining enantiomerically pure materials by high-pressure liquid chromatography. The relationship of analyte structure to the extent of enantiomeric separation has been examined and separation factors (a) are presented for various groups of structurally related compounds. Chiral recognition models have been suggested to account for the observed separations. These models provide mechanistic insights into the chiral recognition process.
- Aneja, Ritu,Luthra, Pratibha Mehta,Ahuja, Satinder
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experimental part
p. 479 - 485
(2010/08/20)
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- Homobenzotetramisole-catalyzed kinetic resolution of α-Aryl-, α-Aryloxy-, and α-Arylthioalkanoic acids
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Effective kinetic resolutions of α-aryl-, αaryloxy-, and α-arylthioalkanoic acids have been achieved via in situ generation of their symmetrical anhydrides and enantioselective alcoholysis in the presence of homobenzotetramisole (HBTM) 3.
- Yang, Xing,Birman, Vladimir B.
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supporting information; experimental part
p. 2301 - 2304
(2010/01/19)
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- Enantiomerically pure α-methoxyaryl acetaldehydes as versatile precursors: a facile chemo-enzymatic methodology for their preparation
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A facile and efficient synthesis of optically active α-methoxyaryl acetic acids (up to 95% ee), α-methoxyaryl ethanols (up to 93% ee) and α-methoxyaryl acetonitriles (up to 93% ee) was achieved via Arthrobacter sp. lipase-catalyzed kinetic resolution of masked aldehydes as the key synthons, that is, α-hydroxyaryl acetaldehyde acetals.
- Singh, Buddh,Gupta, Pankaj,Chaubey, Asha,Parshad, Rajinder,Sharma, Shiromani,Taneja, Subhash C.
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experimental part
p. 2579 - 2588
(2009/04/05)
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- Parallel kinetic resolution of 2-methoxy and 2-phenoxy-substituted carboxylic acids using a combination of quasi-enantiomeric oxazolidinones
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2-Methoxy-2-phenyl acetic acid and 2-phenoxy-2-phenylpropionic acid were resolved by the parallel kinetic resolution of their corresponding pentafluorophenyl active ester using a quasi-enantiomeric combination of lithiated oxazolidinones.
- Boyd, Ewan,Chavda, Sameer,Eames, Jason,Yohannes, Yonas
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p. 476 - 482
(2007/10/03)
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- Process for producing optically active compound
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A process for producing an optically active compound based on the hydrolysis of an alkenyl ester compound or the cleavage of an alkenyl ether compound. The process uses neither an acidic compound nor a basic compound, and rectants can be reacted in a high concentration. It does not necessitate a buffer, nutrient, etc. unlike enzymatic reactions or reactions using a microorganism. It is a simple process which attains a satisfactory production efficiency. The process, which is for producing an optically active carboxylic acid or optically active alcohol represented by the general formula (VI): (wherein R1, R2, and R3 are different groups; and A represents methylene, carbonyl, or a single bound), is characterized by causing water to act on an alkenyl ester or alkenyl ether represented by the general formula (I): (wherein R4, R5, and R6 each represents hydrogen, alkyl, etc.) in the presence of a specific transition metal complex having an optically active ligand.
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Page/Page column 6
(2008/06/13)
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- Asymmetric synthesis of α-methoxyarylacetic acid derivatives
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Stereoselective synthesis of a series of 2-aryl-2-methoxyethanols was achieved from inexpensive chiral pool tartaric acid employing a diastereoselective reduction of a symmetrical 1,4-diaryldiketone as the key step. 2-Aryl-2-methoxyethanols were enantioselectively prepared in 80-90% yield
- Prasad, Kavirayani R.,Chandrakumar, Appayee
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p. 1897 - 1900
(2007/10/03)
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- An efficient procedure for the resolution of α-cyano-α-fluoro- p-tolylacetic acid (CFTA) via the diastereomeric N-carbobenzyloxy-cis-1-amino-2- indanol esters
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Development of a new, efficient resolution method of α-cyano-α- fluoro-p-tolylacetic acid (CFTA) 2a has been successfully achieved, which has been troublesome to obtain by conventional methods, in spite of its outstanding ability as an NMR chiral derivatizing agent. Fractional recrystallization of a mixture of the diastereomeric CFTA esters prepared from racemic CFTA chloride and (1R,2S)-N-carbobenzyloxy-cis-1-amino-2-indanol (-)-B afforded the less-soluble diastereomer, which was hydrolyzed to give (S)-2a. It has also been demonstrated that optically active N-acetyl-cis-1-amino-2-indanol is effective for the chromatographic resolution of α-arylacetic acids including ibuprofen and naproxen.
- Fujiwara, Tomoya,Sasaki, Masaki,Omata, Kenji,Kabuto, Chizuko,Kabuto, Kuninobu,Takeuchi, Yoshio
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p. 555 - 563
(2007/10/03)
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- Crosslinked three-dimensional polymer network, method for preparing same, support material comprising same and uses thereof
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The invention concerns a crosslinked optically active three-dimensional polymer network, consisting of homochiral units of a first selector and of homochiral units of at least a second selector of different structure from the first selector, the homochiral units of the first selector comprising at least three polymerisable or crosslinkable functional groups and the homochiral units of the second selector comprising at least two polymerisable or crosslinkable functional groups, the homochiral groups being chemically mutually bound. The invention also concerns a method for making such a polymer network and its uses.
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Page/Page column 7-8
(2010/02/09)
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- Enantioselective synthesis of arylmethoxyacetic acid derivatives
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The preparation of several arylmethoxyacetic acids by a sequence of asymmetric dihydroxylation and further oxidation of the resulting glycol with TEMPO/NaClO/NaClO2 is described. The scope and limitations of the reaction are discussed.
- Moreno-Dorado, F. Javier,Guerra, Francisco M.,Ortega, Maria J.,Zubia, Eva,Massanet, Guillermo M.
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p. 503 - 510
(2007/10/03)
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- The crystallographic structure of a Lewis acid-assisted chiral Bronsted acid as an enantioselective protonation reagent for silyl enol ethers
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It is difficult to control the enantioselectivity in the protonation of silyl enol ethers with simple chiral Bronsted acids, mainly due to bond flexibility between the proton and its chiral counterion, the orientational flexibility of the proton, and the fact that the proton sources available are limited to acidic compounds such as chiral carboxylic acids. To overcome these difficulties, we have developed a Lewis acid-assisted chiral Bronsted acid (LBA) system. The coordination of Lewis acids with Bronsted acids restricts the orientation of protons and increases their acidity. Optically active binaphthol (BINOL) derivative·SnCl4 complexes are very effective as enantioselective protonation reagents for silyl enol ethers. However, their exact structures have not yet been determined. We describe here optically active 1,2-diarylethane-1,2-diol derivative·SnCl4 as a new type of LBA for the enantioselective protonation as well as its crystallographic structure. A variety of optically active 1,2-diarylethane-1,2-diols could be readily prepared by asymmetric syn-dihydroxylation. This is a great advantage over BINOL for the flexible design of a new LBA. The most significant finding is that we were able to specify the conformational direction of the H-O bond of LBA, which has some asymmetric inductivity, by X-ray diffraction analysis. The stereochemical course in the enantioselective protonation of silyl enol ethers using LBA would be controlled by a linear OH/π interaction with an initial step. The absolute stereopreference in enantioselective reactions using BINOL·SnCl4 can also be explained in terms of this uniformly mechanistic interpretation. Copyright
- Ishihara, Kazuaki,Nakashima, Daisuke,Hiraiwa, Yukihiro,Yamamoto, Hisashi
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- Covalent modification of subtilisin Bacillus lentus Cysteine mutants with enantiomerically pure chiral auxiliaries causes remarkable changes in activity
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Methanethiosulfonate reagents may be used to introduce virtually unlimited structural modifications in enzymes via reaction with the thiol group of cysteine. The covalent coupling of enantiomerically pure (R) and (S) chiral auxiliary methanethiosulfonate ligands to cysteine mutants of subtilisin Bacillus lentus induces spectacular changes in catalytic activity between diastereomeric enzymes. Amidase and esterase kinetic assays using a low substrate approximation were used to establish k(cat)/K(M) values for the chemically modified mutants, and up to 3-fold differences in activity were found between diastereomeric enzymes. Changing the length of the carbon chain linking the phenyl or benzyl oxazolidinone ligand to the mutant N62C by a methylene unit reverses which diastereomeric enzyme is more active. Similarly, changing from a phenyl to benzyl oxazolidinone ligand at S166C reverses which diastereomeric enzyme is more active. Chiral modifications at S166C and L217C give CMMs having both high esterase k(cat)/K(M)'s and high esterase to amidase ratios with large differences between diastereomeric enzymes. Copyright (C) 2000 Elsevier Science Ltd.
- Dickman, Michael,Jones, J. Bryan
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p. 1957 - 1968
(2007/10/03)
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- Enantioselective protonation of silyl enol ethers and ketene disilyl acetals with Lewis acid-assisted chiral Bronsted acids: Reaction scope and mechanistic insights
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Enantioselective protonation is a potent and efficient way to construct chiral carbons. Here we report details of the reaction using Lewis acid-assisted chiral Bronsted acids (chiral LBAs). The 1:1 coordinate complex of tin tetrachloride and optically active binaphthol ((R)- or (S)-BINOL) can directly protonate various silyl enol ethers and ketene disilyl acetals to give the corresponding α-aryl ketones and α-arylcarboxylic acids, respectively, with high enantiomeric excesses (up to 98% ee). A catalytic version of enantioselective protonation has also been achieved using stoichiometric amounts of 2,6-dimethylphenol and catalytic amounts of monomethyl ether of optically active BINOL in the presence of tin tetrachloride. This protonation is also effective for producing α-halocarbonyl compounds (up to 91% ee). DFT calculations on the B3LYP/LANL2DZ level show that the conformational structure of the chiral LBA and the orientation of activated proton on (R)-BINOLs are important for understanding the absolute stereochemistry of the products.
- Nakamura, Shingo,Kaneeda, Masanobu,Ishihara, Kazuaki,Yamamoto, Hisashi
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p. 8120 - 8130
(2007/10/03)
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- Resolution of (±)-mandelic- and (±)-2-(chiorophenoxy)propionic-acid derivatives by crystallization of their diastereomeric amides with (R)- or (S)-α-arylethylamines
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An alternative and cost effective route for the resolution in high ees (95-99%) of (±)-mandelic-and (±)-2-(chlorophenoxy)propionic- acid derivatives is reported. The key step involves the covalent derivatization and separation of their diastereomeric amides with (R)- or (S)-α- arylethylamines.
- Jourdain, Franck,Hirokawa, Takahiko,Kogane, Tamizo
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p. 2509 - 2512
(2007/10/03)
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- Enantioselective carboxylation of α-methoxybenzyllithium generated via asymmetric lithiation with a t-BuLi/chiral bis(oxazoline) complex
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Treatment of benzyl methyl ether with a t-BuLi/chiral bis(oxazoline) complex followed by carboxylation is shown to afford α-methoxy phenylacetic acid in high % ee (up to 95%). The asymmetric induction was proved to occur at the post-lithiation step.
- Komine, Nobuyuki,Wang, Lan-Fang,Tomooka, Katsuhiko,Nakai, Takeshi
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p. 6809 - 6812
(2007/10/03)
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- Resolution of (±)-mandelic- and (±)-2-(chlorophenoxy)propionic-acid derivatives by crystallization of their diastereomeric amides with (R)- or (S)-α-arylethylamines
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An alternative and cost effective route for the resolution in high ees (95-99%) of (±)-mandelic-and (±)-2-(chlorophenoxy)propionic- acid derivatives is reported. The key step involves the covalent derivatization and separation of their diastereomeric amides with (R)- or (S)-α- arylethylamines.
- Jourdain, Franck,Hirokawa, Takahiko,Kogane, Tamizo
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p. 2307 - 2310
(2007/10/03)
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- Lewis acid-promoted carbonyl addition of lithium (α- carbalkoxyvinyl)cuprates to aldehydes provides a novel asymmetric synthesis of β,β-disubstituted α-(hydroxyalkyl)acrylates
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A new anionic addition process has been developed for the asymmetric synthesis of unusual Baylis-Hillman adducts, β,β-disubstituted α- (hydroxyalkyl)acrylates. The new process involves conjugate addition of R2CuLi to β-substituted α,β-acetylenic ester to give lithium (α- carbalkoxyvinyl)cuprate which was then subjected to the carbonyl addition to aldehyde promoted by Et2AlCl. Modest to good diastereoselectivity (50.0- 87.7%de) has been obtained by using (1R,2S,5R)-(-)-menthol as the chiral auxiliary (59.0-94.0% yield). The absolute configuration was unambiguously assigned by transforming the product to methyl (R)-α-methoxyphenylacetate.
- Wei, Han-Xun,Willis, Steven,Li, Guigen
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p. 8203 - 8206
(2007/10/03)
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Treatment of the readily available (S)-(+) and (R)-(-) enantiomers of 2-aminobutan-1-ol 1 with sodium hydride followed by benzyl chloride, or a substituted benzyl halide, afforded the corresponding O-benzyl bases 4-7 in good yields. These new bases are recommended for the large scale resolution of racemic acids. For instance, they proved efficient for the practical resolutions of α-methylsuccinic acid (±)-9, N-acetylphenylglycine (±)-11, N-acetyl-(4-hydroxyphenyl) glycine (±)-14 and N-chloroacetyl-(4-hydroxyphenyl) glycine (±)-15.
- Touet, Joel,Faveriel, Laurent,Brown, Eric
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p. 1709 - 1720
(2007/10/02)
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- The enantioselective influence on the hydrolysis of nitroarylesters of 2-methoxy-2-phenylacetic acids by cyclodextrins
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2-Nitrophenyl-, 4-nitrophenyl- and 2,4-dinitrophenylesters of the (P)-,(S)- and (R/S)-2-methoxy-2-phenylacetic acid (MPE) are produced to study the catalytic influence of cyclodextrins (CD) on the hydrolysis of chiral esters. γ-CD demonstrates a higher effect than α-CD, which does not decrease by increasing the pH value. The stability constants of the complexes are not very different. The cleavage of the (S)-enantiomers by α-, hydroxypropyl (HP)-β- and γ-CD is lower than that of the (R)-enantiomers whereby the extent of difference depends on the kind of the substrate. Most distinctly one can recognize the reaction of MPE-4-nitrophenylester to HP-β-CD. Obviously the interaction of the D-glucose unit of the CD with the (S)-substrate leads to a diastereomer which is energetically discriminated against the (R)-substrate resulting in an inhibition of hydrolysis. Because the same especially appears with HP-β-CD it is demonstrated that the enantioselectivity of CD demands an optimum of adaptability of the substrate existing in small limits only.
- Beyrich,Friedrich,Schreck
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- Synthesis, Configuration, and Calcium Modulatory Properties of Enantiomerically Pure 5-Oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylates
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Enantiomerically pure hexahydroquinolinones of the structural type 9 were prepared by a variation of the Hantzsch synthesis in which an optically active acetoacetate served as a chiral auxiliary reagent.Determination of the de and ee values are described.The absolute configurations of the optically pure products were characterized by single-crystal X-ray analysis.The antipodes 9a and 9b exhibited calcium antagonistic activities on smooth musculature; the (S)-(-)-enantiomer 9b was the more potent compound with regard to the EC50 values which differed by a factor of 100; the intrinsic axctivity of 9b was 1.2, compared with a value of 0.54 for 9a.On the other hand, R-(+)-9a exerted positive inotropic effects on electrically stimulated atria.The cause of these effects is discussed.
- Rose, Ulrich,Draeger, Martin
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p. 2238 - 2243
(2007/10/02)
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- Synthesis of chiral epoxy alcohols by use of baker's yeast
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Synthesis of optically active 3,4-epoxy-4-phenyl-2-butanols, which are expected to be useful intermediates for the synthesis of biologically active compounds such as β-blocker, was achieved by asymmetric reduction of 3,4-epoxy-4-phenyl-2-butanone with baker's yeast.
- Takeshita,Akutsu
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p. 1381 - 1384
(2007/10/02)
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- A Practical Synthesis of (R)-Methoxy(phenyl)acetic Acid
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(R)-Methoxy(phenyl)acetic acid is efficiently prepared from (2S,3S)-3-phenylglycidol in two steps.
- Takano, Seiichi,Yanase, Masashi,Ogasawara, Kunio
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- Direct Optical Resolution of Carboxylic Acids by Chyral HPLC on Tris(3,5-dimethylphenylcarbamate)s of Cellulose and Amylose
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A variety of racemic carboxylic acids have been for the first time directly resolved by normal-phase, high-performance liquid chromatography using a hexane-2-propanol eluting system containing a small amount (ca. 1percent) of a strong carboxylic acid, like formic acid, trichloroacetic acid, and trifluoroacetic acid.
- Okamoto, Yoshio,Aburatani, Ryo,Kaida, Yuriko,Hatada, Koichi
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p. 1125 - 1128
(2007/10/02)
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- REACTIVITY AND STEREOSELECTIVITY IN THE CLEAVAGE OF COMPLEXES OF ACTIVATED ENANTIOMERIC SUBSTRATES WITH CYCLODEXTRINS.
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Remarkable rate accelerations and enantioselectivities in the cleavage of the enantiomers of carbonate 1 and of ester 2 in the presence of α- and β-cyclodextrins are reported.
- Fornasier, Roberto,Scrimin, Paolo,Tonellato, Umberto
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p. 5541 - 5542
(2007/10/02)
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