- Chirality switching in the crystallization of 1-(4-chlorophenyl) ethylamine with binaphthoic acid by ketimine formation
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Axially chiral binaphthoic acid (BNA) was studied as a resolving agent for a stereoselective crystallization of 1-(4-chlorophenyl)ethylamine (CPEA). The diastereomeric pair of (R)-BNA/(S)-CPEA crystallizes in methylene chloride, on the other hand, the pair of (S)-BNA/(S)-CPEA crystallizes in acetone. The switch of the solubility of the diastereomeric pair is due to the imine formation with acetone. The very low solubility of the BNA/imine pair appears to be responsible for the fast and complete imine formation. The crystal structure of the BNA part in both crystals of the diastereomers maintains a same feature. Asymmetric chiral channels and pockets composed by intermolecular packing of BNA molecules appear in the crystal structures, and the robustness of them seem to contribute to the recognition of the chirality of CPEA with high selectivity.
- Jin, Ying-Ji,Choi, Yunseo,Chen, Qian,Shirbhate, Mukesh Eknath,Huang, Haofei,Kim, Youngmee,Kim, Sung-Jin,Jun, Moo-Jin,Koo, Eon Cheol,Kim, Kwan Mook
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Read Online
- Two-Step Protocol for Iodotrimethylsilane-Mediated Deoxy-Functionalization of Alcohols
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We have developed a two-step protocol for iodotrimethylsilane-mediated deoxy-functionalization of primary and secondary alcohols to afford products containing a C?N, C?S, or C?O bond. In the first step the alcohol undergoes iodination with iodotrimethylsilane, and in the second, the iodine atom is replaced by a N, S, or O nucleophile. Compared with traditional Mitsunobu reaction, non-acidic pre-nucleophiles can be used, and the reaction proceeds with retention of configuration. This operationally simple, highly efficient protocol can be used for some natural products and small-molecule drugs containing hydroxy-group.
- Chen, Yuming,He, Ru,Song, Hongjian,Yu, Guoqing,Li, Chenglin,Liu, Yuxiu,Wang, Qingmin
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supporting information
p. 1179 - 1183
(2021/02/01)
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- Enzymatic Primary Amination of Benzylic and Allylic C(sp3)-H Bonds
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Aliphatic primary amines are prevalent in natural products, pharmaceuticals, and functional materials. While a plethora of processes are reported for their synthesis, methods that directly install a free amine group into C(sp3)-H bonds remain unprecedented. Here, we report a set of new-to-nature enzymes that catalyze the direct primary amination of C(sp3)-H bonds with excellent chemo-, regio-, and enantioselectivity, using a readily available hydroxylamine derivative as the nitrogen source. Directed evolution of genetically encoded cytochrome P411 enzymes (P450s whose Cys axial ligand to the heme iron has been replaced with Ser) generated variants that selectively functionalize benzylic and allylic C-H bonds, affording a broad scope of enantioenriched primary amines. This biocatalytic process is efficient and selective (up to 3930 TTN and 96percent ee), and can be performed on preparative scale.
- Jia, Zhi-Jun,Gao, Shilong,Arnold, Frances H.
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supporting information
p. 10279 - 10283
(2020/07/27)
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- Enantioselective Bioamination of Aromatic Alkanes Using Ammonia: A Multienzymatic Cascade Approach
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Chiral amines are common drug building blocks and important active pharmaceutical ingredients. Preparing these functionalized compounds from simple materials, such as alkanes, is of great interest. We recently developed an artificial bioamination cascade for the C?H amination of cyclic alkanes by combining P450 monooxygenase, alcohol dehydrogenase, and amine dehydrogenase. Herein, this system has been extended to the synthesis of chiral aromatic amines. In the first hydroxylation step, process optimization increased the conversion to 77 %. Two stereoselectively complementary alcohol dehydrogenases and an amine dehydrogenase were selected for the bioconversion of aromatic hydrocarbons to amines. The amination reaction was optimized with respect to cofactor addition and enzyme dosage. Isopropanol was added to decrease ketone intermediate accumulation in the amination step, which further enhanced the overall conversion. This cascade system converted a panel of hydrocarbon substrates into the corresponding amines with excellent optical purity (>99 % ee) and moderate conversion ratios (13–53 %).
- Chen, Fei-Fei,Wang, Hui,Xu, Jian-He,Yu, Hui-Lei,Zheng, Yu-Cong
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- The enzymatic resolution of 1-(4-chlorophenyl)ethylamine by Novozym 435 to prepare a novel triazolopyrimidine herbicide
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The kinetic resolution of (R,S)-1-(4-chlorophenyl)ethylamine was accomplished using a commercial lipase from Candida antarctica (Novozym 435). The performance of this lipase was investigated for the enantioselective amidation of (R,S)-1-(4-chlorophenyl)ethylamine, leaving the target product (S)-1-(4-chlorophenyl)ethylamine in its unreacted form. The effects of various types of solvents and an acyl donor, the molar ratio of the substrate to the acyl donor, and the reaction temperature were studied. The optimum reaction conditions were found to result in amidation with methyl 2-tetrahydrofuroate at 40°C in methyl tert-butyl ether, with a substrate/acyl donor molar ratio of 1:2.4. The conversion rate of (R,S)-1-(4-chlorophenyl)ethylamine was 52%, with an enantiomeric excess of 99% towards the unreacted substrate in a reaction time of 22?hours. Finally, using optically pure (S)-1-(4-chlorophenyl)ethylamine as the raw material, the chemical synthesis of (S)-N-(1-(4-chlorphenyl)ethyl)-2-(5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-ylthio)acetamide, a novel triazolopyrimidine herbicide, was achieved, and the total yield and purity were 83.5% and 95.3%, respectively.
- Zhang, Yinjun,Cheng, Feifei,Yan, Hongde,Zheng, Jianyong,Wang, Zhao
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p. 1225 - 1232
(2018/09/25)
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- Mapping the substrate scope of monoamine oxidase (MAO-N) as a synthetic tool for the enantioselective synthesis of chiral amines
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A library of 132 racemic chiral amines (α-substituted methylbenzylamines, benzhydrylamines, 1,2,3,4-tetrahydronaphthylamines (THNs), indanylamines, allylic and homoallylic amines, propargyl amines) was screened against the most versatile monoamine oxidase (MAO-N) variants D5, D9 and D11. MAO-N D9 exhibited the highest activity for most substrates and was applied to the deracemisation of a comprehensive set of selected primary amines. In all cases, excellent enantioselectivity was achieved (e.e. >99%) with moderate to good yields (55–80%). Conditions for the deracemisation of primary amines using a MAO-N/borane system were further optimised using THN as a template addressing substrate load, nature of the enzyme preparation, buffer systems, borane sources, and organic co-solvents.
- Herter, Susanne,Medina, Florian,Wagschal, Simon,Benha?m, Cyril,Leipold, Friedemann,Turner, Nicholas J.
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p. 1338 - 1346
(2017/10/06)
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- Asymmetric Synthesis of Chiral Primary Amines by Ruthenium-Catalyzed Direct Reductive Amination of Alkyl Aryl Ketones with Ammonium Salts and Molecular H2
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A ruthenium/C3-TunePhos catalytic system has been identified for highly efficient direct reductive amination of simple ketones. The strategy makes use of ammonium acetate as the amine source and H2 as the reductant and is a user-friendly and operatively simple access to industrially relevant primary amines. Excellent enantiocontrol (>90% ee for most cases) was achieved with a wide range of alkyl aryl ketones. The practicability of this methodology has been highlighted by scalable synthesis of key intermediates of three drug molecules. Moreover, an improved synthetic route to the optimal diphosphine ligand C3-TunePhos is also presented.
- Tan, Xuefeng,Gao, Shuang,Zeng, Weijun,Xin, Shan,Yin, Qin,Zhang, Xumu
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supporting information
p. 2024 - 2027
(2018/02/19)
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- Amine dehydrogenases: Efficient biocatalysts for the reductive amination of carbonyl compounds
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Amines constitute the major targets for the production of a plethora of chemical compounds that have applications in the pharmaceutical, agrochemical and bulk chemical industries. However, the asymmetric synthesis of α-chiral amines with elevated catalytic efficiency and atom economy is still a very challenging synthetic problem. Here, we investigated the biocatalytic reductive amination of carbonyl compounds employing a rising class of enzymes for amine synthesis: amine dehydrogenases (AmDHs). The three AmDHs from this study-operating in tandem with a formate dehydrogenase from Candida boidinii (Cb-FDH) for the recycling of the nicotinamide coenzyme-performed the efficient amination of a range of diverse aromatic and aliphatic ketones and aldehydes with up to quantitative conversion and elevated turnover numbers (TONs). Moreover, the reductive amination of prochiral ketones proceeded with perfect stereoselectivity, always affording the (R)-configured amines with more than 99% enantiomeric excess. The most suitable amine dehydrogenase, the optimised catalyst loading and the required reaction time were determined for each substrate. The biocatalytic reductive amination with this dual-enzyme system (AmDH-Cb-FDH) possesses elevated atom efficiency as it utilizes the ammonium formate buffer as the source of both nitrogen and reducing equivalents. Inorganic carbonate is the sole by-product.
- Knaus, Tanja,B?hmer, Wesley,Mutti, Francesco G.
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supporting information
p. 453 - 463
(2017/08/14)
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- Whole-Cell Biocatalysts for Stereoselective C-H Amination Reactions
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Enantiomerically pure chiral amines are ubiquitous chemical building blocks in bioactive pharmaceutical products and their synthesis from simple starting materials is of great interest. One of the most attractive strategies is the stereoselective installation of a chiral amine through C-H amination, which is a challenging chemical transformation. Herein we report the application of a multienzyme cascade, generated in a single bacterial whole-cell system, which is able to catalyze stereoselective benzylic aminations with ee values of 97.5 %. The cascade uses four heterologously expressed recombinant enzymes with cofactors provided by the host cell and isopropyl amine added as the amine donor. The cascade presents the first example of the successful de novo design of a single whole-cell biocatalyst for formal stereoselective C-H amination.
- Both, Peter,Busch, Hanna,Kelly, Paul P.,Mutti, Francesco G.,Turner, Nicholas J.,Flitsch, Sabine L.
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p. 1511 - 1513
(2016/02/14)
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- Monoamine oxidase-ω-transaminase cascade for the deracemisation and dealkylation of amines
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Herein we report a one-pot protocol for the deracemisation of chiral benzylic amines employing a novel monoamine oxidase-ω-transaminase cascade, allowing access to enantiopure compounds in >99 % ee. We also demonstrate that the same enzymatic cascade can be employed for the dealkylation of secondary amines with >99 % conversion. Cascade ball: A monoamine oxidase- ω-transaminase cascade has been developed for the deracemisation of chiral benzylic amines, allowing access to the enantiopure compounds in >99 % ee. The same system was also employed for the efficient dealkylation of secondary amines.
- O'Reilly, Elaine,Iglesias, Cesar,Turner, Nicholas J.
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p. 992 - 995
(2014/05/06)
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- A highly fluorescent metallosalalen-based chiral cage for enantioselective recognition and sensing
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A highly fluorescent coordination cage [Zn8L4I 8] has been constructed by treating enantiopure pyridyl- functionalized metallosalalen units (L) with zinc(II) iodide and characterized by a variety of techniques including microanalysis, thermogravimetric analysis (TGA), circular dichroism (CD) spectroscopy, and single-crystal and powder X-ray diffraction. Strong intermolecular π-π, CH-π, and CH-I interactions direct packing of the cage molecules to generate a 3D polycage network interconnected by pentahedral cages formed by adjacent pentamers. The cage has an amphiphilic helical cavity decorated with chiral NH functionalities capable of interactions with guest species such as saccharides. The fluorescence of the cage was greatly enhanced by five enantiomeric saccharides in solution, with enantioselectivity factors of 2.480-4.943, and by five enantiomeric amines in the solid state, with enantioselective fluorescence enhancement ratios of 1.30-3.60. This remarkable chiral sensing of both saccharides and amines with impressive enantioselectivity may result from the steric confinement of the cavity as well as its conformational rigidity. It holds great promise for the development of novel chiral cage materials for sensing applications. Cage-based chiral sensor: A highly fluorescent coordination cage [Zn8L 4I8] can be prepared from enantiopure pyridyl- functionalized metallosalalen units (L). The cage has an amphiphilic helical cavity decorated with chiral NH functionalities and supramolecular interactions generate a 3D polycage network interconnected by pentahedral cages formed by adjacent pentamers (see graphic). The fluorescence of the cage is greatly enhanced either in solution or in the solid state in the presence of enantiomeric saccharides or amines, respectively, with significant enantioselectivity factors.
- Dong, Jinqiao,Zhou, Yanfang,Zhang, Fangwei,Cui, Yong
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supporting information
p. 6455 - 6461
(2014/06/09)
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- Enantioselective synthesis of (R)-2-arylpropanenitriles catalysed by ene-reductases in aqueous media and in biphasic ionic liquid-water systems
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The enantioselective reduction of α-methylene nitrile derivatives catalysed by ene-reductases affords the corresponding (R)-2-arylpropanenitriles with high conversion values. The reaction is investigated either in aqueous medium (with an organic cosolvent or by loading the substrate onto hydrophobic resins) or in a biphasic ionic liquid-water system. The use of ionic liquids, herein with isolated ene-reductases, is found to improve the work-up and the substrate recovery method. The synthetic manipulation of the final chiral nitrile derivatives indicates how this biocatalysed method can be exploited for the preparation of a wide range of chiral compounds.
- Brenna, Elisabetta,Crotti, Michele,Gatti, Francesco G.,Manfredi, Alessia,Monti, Daniela,Parmeggiani, Fabio,Santangelo, Sara,Zampieri, Davila
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p. 2425 - 2431
(2014/08/18)
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- Transaminases applied to the synthesis of high added-value enantiopure amines
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Critical parameters affecting the stereoselective amination of (hetero)aromatic ketones using transaminases have been studied, such as temperature, pH, substrate concentration, cosolvent, and source and percentage of amino donor, to further optimize the production of enantiopure amines using both (S)- and (R)-selective biocatalysts from commercial suppliers. Interesting enantiopure amino building blocks have been obtained, overcoming some limitations of traditional chemical synthetic methods. Representative processes were scaled up, affording halogenated and heteroaromatic amines in enantiomerically pure form and good isolated yields.
- Paul, Caroline E.,Rodriguez-Mata, Maria,Busto, Eduardo,Lavandera, Ivan,Gotor-Fernandez, Vicente,Gotor, Vicente,Garcia-Cerrada, Susana,Mendiola, Javier,De Frutos, Oscar,Collado, Ivan
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supporting information
p. 788 - 792
(2014/07/08)
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- Microwave-Enhanced Asymmetric Transfer Hydrogenation of N-(tert-Butylsulfinyl)imines
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Microwave irradiation has considerably enhanced the efficiency of the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)imines in isopropyl alcohol catalyzed by a ruthenium complex bearing the achiral ligand 2-amino-2-methylpropan-1-ol. In addition to shortening reaction times for the transfer hydrogenation processes to only 30 min, the amounts of ruthenium catalyst and isopropyl alcohol can be considerably reduced in comparison with our previous procedure assisted by conventional heating, which diminishes the environmental impact of this new protocol. This methodology can be applied to aromatic, heteroaromatic and aliphatic N-(tert-butylsulfinyl)ketimines, leading, after desulfinylation, to the expected primary amines in excellent yields and with enantiomeric excesses of up to 96 %. Microwave irradiation promotes the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)imines in 2-propanol catalysed by a ruthenium complex bearing an achiral β-amino alcohol as ligand. After desulfinylation, α-branched primary amines containing aromatic, heteroaromatic and aliphatic substituents are obtained in excellent yields and with enantiomeric excesses of up to 96 %.
- Pablo, Oscar,Guijarro, David,Yus, Miguel
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p. 7034 - 7038
(2016/02/19)
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- Asymmetric synthesis of nonracemic primary amines via spiroborate-catalyzed reduction of pure (E)- and (Z)-O-benzyloximes: Applications toward the synthesis of calcimimetic agents
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Highly enantiopure (1-aryl)- and (1-naphthyl)-1-ethylamines were synthesized by the borane-mediated reduction of single-isomeric (E)- and (Z)-O-benzyloxime ethers using the stable spiroborate ester derived from (S)-diphenyl valinol and ethylene glycol as the chiral catalyst. Primary (R)-arylethylamines were prepared by the reduction of pure (Z)-ethanone oxime ethers in up to 99% ee using 15% of catalyst. Two convenient and facile approaches to the synthesis of new and known calcimimetic analogues employing enantiopure (1-naphthalen-1-yl)ethylamine as chiral precursor are described.
- Ou, Wenhua,Espinosa, Sandraliz,Meléndez, Héctor J.,Farré, Silvia M.,Alvarez, Jaime L.,Torres, Valerie,Martínez, Ileanne,Santiago, Kiara M.,Ortiz-Marciales, Margarita
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p. 5314 - 5327
(2013/07/25)
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- Nickel nanoparticles as racemization catalysts for primary amines
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By combining bases that are known to racemize benzylic amines with a nickel(II) salt, active nickel nanoparticles were obtained that can be used as catalysts in the racemization of both aliphatic and benzylic primary amines. The nanoparticles are stable in the ionic liquid tetrabutylammonium bromide and can complete most racemizations within a few hours with excellent selectivity. The problem of the incompatibility of the strongly reducing racemization catalyst and the enzymatic amine resolution catalyst was overcome by using a two-pot system with a biphasic racemization step. Consecutive contact of a nonane layer that contained the amine with the acylating enzyme and with the racemizing Ni nanoparticles in the ionic liquid allowed the 50 % amide yield limit of a kinetic resolution to be successfully surpassed. Copyright
- Geukens, Inge,Plessers, Eva,Seo, Jin Won,De Vos, Dirk E.
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p. 2623 - 2628
(2013/07/11)
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- Organocatalytic asymmetric biomimetic transamination of aromatic ketone to optically active amine
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An asymmetric biomimetic transamination of aromatic ketones to optically active amines with o-HOPhCH2NH2 as amine source catalyzed by hydroquinine-derived chiral base is described. Up to 85% ee was obtained.
- Xie, Ying,Pan, Hongjie,Xiao, Xiao,Li, Songlei,Shi, Yian
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supporting information
p. 8960 - 8962,3
(2012/12/12)
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- Organocatalytic asymmetric biomimetic transamination of aromatic ketone to optically active amine
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An asymmetric biomimetic transamination of aromatic ketones to optically active amines with o-HOPhCH2NH2 as amine source catalyzed by hydroquinine-derived chiral base is described. Up to 85% ee was obtained.
- Xie, Ying,Pan, Hongjie,Xiao, Xiao,Li, Songlei,Shi, Yian
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supporting information
p. 8960 - 8962
(2013/01/15)
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- Cyclohexylamine oxidase as a useful biocatalyst for the kinetic resolution and dereacemization of amines
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The biocatalytic performance of a cloned cyclohexylamine oxidase derived from Brevibacterium oxydans IH-35A towards structurally different amines was investigated. Cycloalkyl primary amines, alkyl aryl amines, and α-carbon-substituted aliphatic amines were identified as suitable substrates for the biocatalyst based on an activity assay. Kinetic resolutions of several amines by either recombinant whole cells or crude enzyme extracts prepared therefrom gave enantiomerically pure (R)-amines besides the corresponding ketones. When cyclohexylamine oxidase in combination with a borane-ammonia complex as reducing agent was applied to the deracemization of several substrates, excellent enantiomeric ratios (>99:1) and good isolated yields (62%-75%) of the corresponding (R)-amines were obtained.
- Leisch, Hannes,Grosse, Stephan,Iwaki, Hiroaki,Hasegawa, Yoshie,Lau, Peter C.K.
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experimental part
p. 39 - 45
(2012/03/07)
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- Enantioselective reduction of ketoxime ethers with borane-oxazaborolidines and synthesis of the key intermediate leading to (S)-rivastigmine
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The reduction of representative alkyl aryl (E)-ketoxime O-benzyl ethers with borane catalyzed by terpene oxazaborolidines, derived from (1R)-nopinone and (1R)-camphor, gave the corresponding amines with 82-99% ee. Oxazaborolidines derived from (1S)-2-carene and (1S)-3-carene were less selective. (S)-1-(3-Methoxyphenyl)ethanamine (94% ee) the key intermediate in the synthesis of (S)-rivastigmine, was obtained by the reduction of (E)-1-(3-methoxyphenyl) ethanone O-benzyl oxime with borane/oxazaborolidine generated from (S)-valinol.
- Pakulski, Marcin M.,Mahato, Sanjit K.,Bosiak, Mariusz J.,Krzeminski, Marek P.,Zaidlewicz, Marek
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p. 716 - 721
(2012/09/21)
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- A versatile Ru catalyst for the asymmetric transfer hydrogenation of both aromatic and aliphatic sulfinylimines
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A highly efficient Ru catalyst based on an achiral, very simple, and inexpensive amino alcohol ligand (2-amino-2-methylpropan-1-ol) has been developed for the asymmetric transfer hydrogenation (ATH) of chiral N-(tert-butylsulfinyl)imines. This complex is able to catalyze the ATH of both aromatic and the most challenging aliphatic sulfinylimines by using isopropyl alcohol as the hydrogen source. The diastereoselective reduction of aromatic, heteroaromatic, and aliphatic sulfinylketimines, including sterically congested cases, over short reaction times (1-4 h), followed by desulfinylation of the nitrogen atom, affords the corresponding highly enantiomerically enriched (ee up to >99%) α-branched primary amines in excellent yields. The same ligand was equally effective for the synthesis of both (R)- and (S)-amines by using the appropriate absolute configuration in the iminic substrate. DFT mechanistic studies show that the hydrogen-transfer process is stepwise. Moreover, the origin of the diastereoselectivity has been rationalized.
- Pablo, Oscar,Guijarro, David,Kovacs, Gabor,Lledos, Agusti,Ujaque, Gregori,Yus, Miguel
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p. 1969 - 1983
(2012/03/26)
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- A fast and sensitive assay for measuring the activity and enantioselectivity of transaminases
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A fast and sensitive method for screening transaminase activity and enantioselectivity, using d- and l-amino acid oxidases, allows new amine substrates to be rapidly identified. The Royal Society of Chemistry 2011.
- Hopwood, Jennifer,Truppo, Matthew D.,Turner, Nicholas J.,Lloyd, Richard C.
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supporting information; experimental part
p. 773 - 775
(2011/04/15)
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- Achiral β-amino alcohols as efficient ligands for the ruthenium-catalysed asymmetric transfer hydrogenation of sulfinylimines
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Some achiral β-amino alcohols have been shown as efficient ligands for the ruthenium-catalysed asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)imines in isopropanol. The ruthenium complex prepared from [RuCl2(p-cymene)]2 (2.5 mol %) and 2-amino-2-methyl-1- propanol (5 mol %) leads to α-branched chiral primary amines with very high optical purities (up to 98% ee) by the diastereoselective reduction of the imines followed by removal of the sulfinyl group under mild acidic conditions. Short reaction times (2-3 h) were needed to complete the reduction reactions when they were performed at 50 °C.
- Guijarro, David,Pablo, óscar,Yus, Miguel
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experimental part
p. 789 - 791
(2011/03/20)
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- COMPOSITIONS AND METHODS FOR CYCLOFRUCTANS AS SEPARATION AGENTS
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The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.
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Page/Page column 45-49; 62
(2010/12/31)
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- Halogen-bonding interaction stabilizing cluster-type diastereomeric salt crystals
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O-Ethyl 4-chlorophenylphosphonothioic acid (1) was newly synthesized and applied as a chiral selector for the enantioseparation of racemic l-(4-halophenyl)ethylamines (halo = F, Cl, Br, I; 2a-d) through diastereomeric salt formation. The phosphonothioic acid 1 showed an excellent chirality-recognition ability for the fluorinated and iodinated amines 2a and 2d with the dramatic switch of the absolute configuration of the enantio-enriched isomers in the deposited salts from R for the amine 2a to S for the amine 2d. The X-ray crystallographic analyses of the four pairs of diastereomeric salts revealed that halogen-bonding interaction in the salt crystals plays a very important role for the switch.
- Kobayashi, Yuka,Maeda, Jin,Ando, Tetsuo,Saigo, Kazuhiko
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experimental part
p. 685 - 690
(2011/10/09)
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- Asymmetric synthesis of chiral primary amines by transfer hydrogenation of N -(tert -Butanesulfinyl)ketimines
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(Figure presented) The diastereoselective reduction of (R)-N-(tert- butanesulfinyl)ketimines by a ruthenium-catalyzed asymmetric transfer hydrogenation process in isopropyl alcohol, followed by desulfinylation of the nitrogen atom, is an excellent method to prepare highly enantiomerically enriched α-branched primary amines (up to >99% ee) in short reaction times (1-4 h). (1S,2R)-1-Amino-2-indanol has been shown to be a very efficient ligand to perform this transformation. Ketimines bearing either an aryl or a heteroaryl group and an alkyl group as substituents of the iminic carbon atom are very good substrates for this process. The reduction of a dialkyl ketimine could also be achieved, affording the expected amine with moderate optical purity (69% ee). Some amines which are precursors of very interesting biologically and pharmacologically active compounds have been prepared in excellent yields and enantiomeric excesses.
- Guijarro, David,Pablo, Oscar,Yus, Miguel
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supporting information; experimental part
p. 5265 - 5270
(2010/10/21)
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- Efficient kinetic resolution of racemic amines using a transaminase in combination with an amino acid oxidase
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A range of enantiomerically pure (R)- and (S)-configured chiral amines has been prepared in excellent e.e. (99%) by combining a transaminase enzyme with an amino acid oxidase and catalytic quantities of pyruvate.
- Truppo, Matthew D.,Turner, Nicholas J.,Rozzell, J. David
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supporting information; experimental part
p. 2127 - 2129
(2009/09/06)
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- New P,N-ferrocenyl ligands for the asymmetric Ir-catalyzed hydrogenation of imines
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The Ir-catalyzed enantioselective hydrogenation of various N-3,5-dimethyl-4-methoxy)phenylimines was performed under mild conditions in the presence of new P,N-ferrocenyl iridium complexes leading to (R)-N-(3,5-dimethyl-4-methoxy)phenylamines in high yields and enantioselectivities (up to 99%). These chiral aryl amines can be readily deprotected using Ce(NH4)2(NO3)6.
- Cheemala, Murthy N.,Knochel, Paul
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p. 3089 - 3092
(2008/02/09)
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- Resolution of 1-arylalkylamines with 3-O-hydrogen phthalate glucofuranose derivatives: Role of steric bulk in a family of resolving agents
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The development of three new acidic resolving agents which are hydrogen phthalates of 1,2:5,6-di-O-isopropylidene-α-d-glucofuranose 1, 1,2:5,6-di-O-cyclohexylidene-α-d-glucofuranose 2 and 1,2-O- cyclohexylidene-5,6-O-diphenylmethylidene-α-d-glucofuranose 3 is shown for the resolution of 1-arylalkylamines 7a-k. The salts between 1, 2 and (RS)-1-arylalkylamines 7a-k selectively crystallize 1?(S) 7a-j and 2?(S) 7a-h salts, allowing us to recover the corresponding bases (S) 7a-j and (S) 7a-h, respectively, in good yield and enantiomeric excess (73-95% ee). Whereas, the salts between 3 and (RS)-1-arylalkylamines 7a-c,g-i,k selectively crystallize 3?(S)-7a-c,g-i salts to recover the corresponding bases (S)-7a-c,g-i in poor enantiomeric excess (4-35% ee). The difference between the resolving ability of 1 and 2 for 1-arylalkylamines 7a-h is very slight, but there is considerable difference compared to ortho-substituted 1-arylalkylamines 7i and 7j. The role of substituents on a family of resolving agents 1, 2 and 3 is also discussed to interpret their resolving ability.
- Mereyala, Hari Babu,Koduru, Sreenivasulu Reddy,Cheemalapati, Venkata Narasimhaji
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p. 259 - 267
(2007/10/03)
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- Optical resolution reagent and manufacturing method of optically active amines that uses it
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PROBLEM TO BE SOLVEDTo provide an effective reagent for optical resolution which produce an optically active amines by resolving the (+/-)-amines and the method for producing the optically active amines characterized by using the same reagent. SOLUTION The O-alkylthiophosphoric acid represented as the following formula (1) is effective for the optical resolution of various amines.
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Page/Page column 19-20
(2008/06/13)
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- Synthesis of enantiopure 6-methoxy-2-naphthylglycolic acid and its application as a resolving agent
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6-Methoxy-2-naphthylglycolic acid (6-MNGA) was designed as a novel acidic resolving agent, on the model of 2-naphthylglycolic acid (2-NGA). Enantiopure 6-MNGA was easily obtained from commercially available 2-bromo-6- methoxynaphthalene through four steps and was found to show a better chiral recognition ability for racemic 1-arylethylamines than the prototype 2-NGA did. The X-ray crystallographic analyses of less-soluble diastereomeric salts revealed that the introduction of a methoxy group at the 6-position of the 2-NGA skeleton made CH/π interaction(s) effective between 6-MNGA molecules and also between the 6-MNGA molecule and the target amine molecule. The methoxy group was also found to contribute to the realization of effective van der Waals interaction. These interactions played important roles for the stabilization of the less-soluble diastereomeric salts to improve the chiral recognition ability of 6-MNGA, compared to that of 2-NGA.
- Shimada, Takayoshi,Kobayashi, Yuka,Saigo, Kazuhiko
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p. 3807 - 3813
(2007/10/03)
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- Resolution of 1-arylalkylamines with 6-(1,2:3,4-di-O-isopropylidene- α-D-galactopyranosyl)hydrogen phthalate
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The resolving ability of a new acidic resolving agent, the hydrogen phthalate of 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose 1, against various 1-arylalkylamines 2a-k is described. Treatment of 1 with amines 2a-f to obtain diastereomeric salts 1·(S)2a-f in 2-propanol allowing the corresponding (S)-amines 2a-f to be recovered in good yield and 61-89% ee. Recrystallization in dichloromethane/hexane, and regeneration gave the amines in enhanced enantiomeric purity (>98% ee). 1 resolved 1-phenylpropylamine 2f in high enantiomeric purity (99% ee) than 1-phenylethylamine 2g (11% ee) and o- and m-methoxy 2h-i, o-chloro-2j and p-fluoro-2k substituted 1-arylamines (11-19% ee). A possible chiral recognition mechanism based on the ability of 1 to exist in two conformations is described.
- Mereyala, Hari Babu,Fatima, Liyakat,Pola, Pallavi
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p. 585 - 587
(2007/10/03)
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- A new hydrogen-bonding motif for chiral recognition in the diastereomeric salts of racemic 1-phenylethylamine derivatives with enantiopure O-ethyl phenylphosphonothioic acid
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(Chemical Equation Presented) An enantiopure phosphonothioic acid showed a unique and superior chiral recognition ability, arising from its P-stereogenicity, for racemic 1-phenylethylamine derivatives through diastereomeric crystallization. Spherical molecular clusters, associated by hydrogen bonds and CH/π interactions, aggregated with high symmetry in the less-soluble diastereomeric salts.
- Kobayashi, Yuka,Morisawa, Fumi,Saigo, Kazuhiko
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p. 4227 - 4230
(2007/10/03)
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- Highly Enantioselective Hydrogen-Transfer Reductive Amination: Catalytic Asymmetric Synthesis of Primary Amines
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Ammonium formate is the hydrogen source in the catalytic asymmetric reductive amination of ketones presented here (Leuckart-Wallach-type reaction). The reaction proceeds smoothly in methanol in the presence of Ir, Rh, and Ru catalysts. Primary amines were obtained as products in good yields with high enantioselectivities after hydrolytic workup when [((R)-tol-binap) RuCl 2] was used as the catalyst (see scheme). R1, R 2=alkyl, aryl.
- Kadyrov, Renat,Riermeier, Thomas H.
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p. 5472 - 5474
(2007/10/03)
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- Resolution of 1-arylethylamines with 5-(1,2-O-isopropylidene-3,6-anhydro- α-D-glucofuranosyl) hydrogen phthalate
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The potential of the hydrogen phthalate of 1,2-O-isopropylidene-3,6- anhydro-α-D-glucofuranose 1 obtainable by the reaction of phthalic anhydride with 1,2-O-isopropylidene-3,6-anhydro-α-D-glucofuranose 8 as a new resolving agent is shown. The salts between 1 and (RS)-1-arylethylamines 2-6 and (RS)-1-arylpropylamine 7 selectively crystallize 1·(R)-salts allowing the recovery of the corresponding (R)-amines 2-7. The more soluble 1·(S)-salts were analogously processed to obtain (S)-amines, respectively. In all of the cases (R)- and (S)-amines 2-7 were obtained in high chemical yield and enantiomeric excess >98%. Resolving agent 1 has been recovered in a quantitative yield and high purity.
- Mereyala, Hari Babu,Pola, Pallavi
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p. 2683 - 2685
(2007/10/03)
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- Ruthenium-catalysed asymmetric hydrosilylation of ketoximes using chiral oxazolinylferrocenylphosphines
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Chiral ruthenium(II) complexes, RuCl2(PPh3)(oxazolinylferrocenylphosphine), have been found to be effective catalysts for asymmetric hydrosilylation of ketoximes to give the corresponding primary amines in good yields with high enant
- Takei,Nishibayashi,Ishii,Mizobe,Uemura,Hidai
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p. 2360 - 2361
(2007/10/03)
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- A high-performance, tailor-made resolving agent: Remarkable enhancement of resolution ability by introducing a naphthyl group into the fundamental skeleton1
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A novel resolving agent, 2-naphthylglycolic acid (2-NGA), was designed for p-substituted 1-arylethylamines on the basis of the consideration that a rigid and large naphthyl group would be favorable for the close packing of supramolecular hydrogen-bond sheets formed between the carboxy groups of 2-NGA and the amino groups of p-substituted 1-arylethylamines. Racemic 2-NGA was readily available from commercially available raw materials, and both enantiopure forms could be obtained by simple diastereomeric resolution with enantiopure 1-phenyl-ethylamine. Thus-prepared enantiopure 2-NGA was found to have an excellent resolution ability not only for p-substituted 1-arylethylamines, but also for a wide variety of chiral primary amines. X-Ray crystallographic analyses of the less- and more-soluble diastereomeric salts revealed that this excellent resolution ability of 2-NGA arose from the formation of a supramolecular hydrogen-bond sheet with the primary amine, as we had expected, and also from the possible achievement of an infinite chain of CH... π interaction between its naphthyl group and the aromatic group of the amine, which was formed in the hydrophobic region of the supramolecular hydrogen-bond sheet.
- Kinbara, Kazushi,Harada, Yoshiko,Saigo, Kazuhiko
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p. 1339 - 1347
(2007/10/03)
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- Method for producing optically active 1-phenylethylamines
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PCT No. PCT/EP97/02988 Sec. 371 Date Dec. 17, 1998 Sec. 102(e) Date Dec. 17, 1998 PCT Filed Jun. 9, 1997 PCT Pub. No. WO97/49665 PCT Pub. Date Dec. 31, 1997The invention concerns a new method for producing optically active 1-phenylethylamines, wherein (a) racemic 1-phenylethylamines are reacted with (S)-(-)-N-phenylcarbamate lactic acid in the presence of an aliphatic or aromatic hydrocarbon and in the presence of a lower aliphatic alcohol, wherein the reaction components are measured so that for every mole of racemic amine, between 0.25 and 0.5 mole of (S)-(-)-N-phenylcarbamate lactic acid are present, the reaction mixture is then concentrated at a liquid-phase temperature of up to 40 DEG C., the resulting solid product is separated, treated with diluted, aqueous alkaline lye in the presence of a hydrocarbon, and the respective (R)-amine is isolated by distillation from the organic phase, and if necessary, (b) the mother liquor remaining after the separation of the solid product is reacted in the presence of a lower aliphatic alcohol with (S)-(-)-N-phenylcarbamate lactic acid, wherein the reaction components are measured so that the molar quantity of (S)-(-)-N-phenylcarbamate lactic acid is twice as great as the quantity of (R)-amine still remaining in the mother liquor, the reaction mixture is then concentrated at a liquid-phase temperature of up to 40 DEG C., the resulting solid product is separated and the (S)-amine is isolated by distillation from the mother liquor.
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- Process for preparing optically active amines
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In accordance with a novel process, (R)-amines of the formula STR1 in which R1, R2 and n have the meanings given in the description, can be prepared by reacting reating N-acyl-amines of the formula STR2 in which R1, R2, R3 and n have the meanings given in the description, with lipases which are suitable for cleaving the (R)-enantiomers of N-acyl-amines of the formula (II), in the presence of water and optionally in the presence of an organic diluent, at a pH of between 3.0 and 10.0 and at temperatures of between 0° C. and 80° C.
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- OPTICALLY ACTIVE F-2-ISOPROPOXYPROPIONIC ACID: A NOVEL DERIVATIZING AGENT FOR GAS CHROMATOGRAPHIC ANALYSIS
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F-2-Isopropoxypropionic acid (PIPA) was resolved into enantiomers via its diastereomeric (+)-1-phenylethylamide. (+)-F-2-Isopropoxypropionyl derivatives of several chiral 1-arylalkylamines and α-amino acids were effectively resolved by gas chromatography at low temperature.
- Kawa, Hajimu,Yamaguchi, Fumihiko,Ishikawa, Nobuo
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p. 745 - 748
(2007/10/02)
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