- Silica-supported tantalum catalysts for asymmetric epoxidations of allyl alcohols
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Tantalum good, titanium bad: This appears to be the case for silica- supported catalysts for the asymmetric epoxidation of allyl alcohols. Complexes such as [SiO-Ta(OEt)4] were prepared from silica and [Ta(=CHCMe3)(CH2CMe3)3], and in the presence of a tartrate and an alkyl hydroperoxide, these surface tantalum compounds lead to efficient and convenient catalysts for the asymmetric epoxidation of 2-propen-1-ol (R = H) and trans-2-hexen-1-ol (R = nPr; see reaction).
- Meunier, Damien,Piechaczyk, Arnaud,De Mallmann, Aimery,Basset, Jean-Marie
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Read Online
- Enzymatic resolution of (±)-glycidyl butyrate in aqueous media. Strong modulation of the properties of the lipase from Rhizopus oryzae via immobilization techniques
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The enantioselectivity of the lipase from Rhizopus oryzae for the small yet highly interesting (±)-glycidyl butyrate have been greatly modulated by the use of different immobilization techniques. Thus, the enzyme immobilized by interfacial adsorption on an octyl-agarose support presented a very low enantioselectivity (E=2). This value could be improved up to an E=17 by covalently immobilizing the enzyme on the cyanogen bromide agarose. However, the best results were achieved by immobilizing the enzyme via ionic adsorption on supports coated with dextran sulfate, with an E value of 51 (ee99% at 55% conversion).
- Palomo, Jose M.,Segura, Rosa L.,Fernandez-Lorente, Gloria,Guisan, Jose M.,Fernandez-Lafuente, Roberto
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Read Online
- Synthesis of enantiomerically pure glycidol via a fully enantioselective lipase-catalyzed resolution
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The efficient enzymatic synthesis of enantiopure 2,3-epoxypropanol (glycidol) has been achieved. The racemic glycidyl butyrate was successfully resolved by enzymatic hydrolysis using a strategy that combines different immobilization protocols and different experimental reaction conditions. A new enzyme (25 kDa lipase)-which is a lipase-like enzyme purified from the pancreatic porcine lipase (PPL) extract-immobilized on DEAE-Sepharose was selected as the optimal biocatalyst. The optimal results were obtained at pH 7, 25°C and 10% dioxane using this biocatalyst and a very high enantioselectivity for the enzyme was displayed, obtaining both (R)-(-)-glycidyl butyrate and (R)-(+)-glycidol with enantiomeric excesses >99% (E >100). The hydrolysis of (R)-(-)-glycidyl butyrate produced pure (S)-(-)-glycidol.
- Palomo, Jose M.,Segura, Rosa L.,Mateo, Cesar,Terreni, Marco,Guisan, Jose M.,Fernandez-Lafuente, Roberto
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Read Online
- Novel applications of chloroperoxidase: Enantioselective oxidation of racemic epoxyalcohols
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The CPO-catalysed enantioselective oxidations of racemic glycidol and cis-2,3-epoxyhexanol to the corresponding aldehydes were studied using tert- butyl hydroperoxide in the 9:9:1 and 18:1 mixtures of hexane:ethyl acetate:buffer and hexane:buffer, respectively. Temperature and pH (100 mM citrate buffer, pH 4.0-7.0) effects on enantioselectivity in the terms of ee for the less reactive alcohol enantiomers with conversion were studied.
- Kiljunen, Eero,Kanerva, Liisa T.
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Read Online
- Continuous-Flow Synthesis of (R)-Propylene Carbonate: An Important Intermediate in the Synthesis of Tenofovir
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(R)-Propylene carbonate is an important intermediate in the synthesis of tenofovir pro-drugs such as tenofovir alafenamide fumarate (TAF) and tenofovir diisoproyl fumarate (TDF). Independent of the pro-drug type, tenofovir presents a chiral secondary hydroxy derivative, which can be obtained directly from (R)-propylene carbonate. Herein, we report our chemo-enzymatic continuous-flow strategy towards (R)-propylene carbonate starting from a very cheap and renewable raw material, glycerol. We were able to synthesize (R)-propylene carbonate in seven continuous-flow steps, starting from glycerol, in good-to-excellent yields (66–93 %) and excellent selectivity (E > 200).
- Suveges, Nicolas S.,Rodriguez, Anderson A.,Diederichs, Carla C.,de Souza, Stefania P.,Le?o, Raquel A. C.,Miranda, Leandro S. M.,Horta, Bruno A. C.,Pedraza, Sérgio F.,de Carvalho, Otavio V.,Pais, Karla C.,Terra, José H. C.,de Souza, Rodrigo O. M. A.
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supporting information
p. 2931 - 2938
(2018/06/27)
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- A high selective (S)-β-hydroxy-γ-butyrolactone simple method for preparing
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The invention relates to a simple and convenient preparation method of highly selective (S)-beta-hydroxy-gamma-butyrolactone. The simple and convenient preparation method comprises the following steps: with allyl alcohol as a starting material, preparing (R)-2, 3-epoxy propanol by virtue of asymmetric epoxidation, and carrying out cyanidation, cyan-hydrolysis and esterification on (R)-2, 3-epoxy propanol to prepare the (S)-beta-hydroxy-gamma-butyrolactone. The simple and convenient preparation method is short in reaction route, easily available in raw material, easy in reaction condition operation, high in reaction selectivity and suitable for industrial production.
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Paragraph 0048-0050; 0053-0056; 0065-0067; 0070-0072
(2019/02/04)
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- Engineering Homochiral Metal-Organic Frameworks by Spatially Separating 1D Chiral Metal-Peptide Ladders: Tuning the Pore Size for Enantioselective Adsorption
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The reaction of the chiral dipeptide glycyl-L(S)-glutamate with CoII ions produces chiral ladders that can be used as rigid 1D building units. Spatial separation of these building units with linkers of different lengths allows the engineering of homochiral porous MOFs with enhanced pore sizes, pore volumes, and surface areas. This strategy enables the synthesis of a family of isoreticular MOFs, in which the pore size dictates the enantioselective adsorption of chiral molecules (in terms of their size and enantiomeric excess).
- Stylianou, Kyriakos C.,G?mez, Laura,Imaz, Inhar,Verdugo-Escamilla, Crist?bal,Ribas, Xavi,Maspoch, Daniel
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supporting information
p. 9964 - 9969
(2015/07/07)
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- Synthesis and enzymatic resolution of racemic 2,3-epoxy propyl esters obtained from glycerol
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A method is described for the synthesis of (±)-2,3-epoxy propyl esters from glycerol, involving reaction of epichlorohydrin with sodium or potassium salts of carboxylic acids in the presence of TBAB as catalyst, with moderate to excellent yields. Kinetic resolution of glycidyl butyrate by lipase of Thermomyces lanuginosa has been achieved with remarkable enantiomeric excess (ee >99%) using 1,4-dioxane as a co-solvent in pure buffer solution (30 and 50 °C, pH = 7.0).
- Araujo, Yara Jaqueline Kerber,Avvari, Naga Prasad,Paiva, Derisvaldo Rosa,De Lima, Dênis Pires,Beatriz, Adilson
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supporting information
p. 1696 - 1698
(2015/03/14)
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- Substrate stereocontrol in bromine-induced intermolecular cyclization: Asymmetric synthesis of pitavastatin calcium
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A novel approach to synthesize pitavastatin calcium (1), an effective HMG-CoA reductase inhibitor, based on readily available and attractively functionalized (R)-3-chloro-1,2-propanediol is reported. This work highlights an intermolecular diastereoselective bromine-induced cyclization of homoallylic carbonate to meet stereochemical challenges in the synthesis of statins. An efficient route to a new triphenylphosphonium tetrafluoroborate salt of a quinoline core is also presented.
- Chen, Weiqi,Xiong, Fangjun,Liu, Qian,Xu, Lingjun,Wu, Yan,Chen, Fener
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p. 4730 - 4737
(2015/07/27)
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- Total Syntheses of Perenniporides
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The total syntheses of perenniporide A (1) and related compounds have been achieved. Starting from 1,3,5-trifluorobenzene (9), difluorodienone 6 was obtained by oxidative dearomatization, which served as a platform for the high-pressure cycloaddition and for the introduction of the C3-methoxy group. The synthesis allowed access to the natural congeners 2 and 3, enabling assignment of the absolute structures of these natural products.
- Morita, Masao,Ohmori, Ken,Suzuki, Keisuke
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supporting information
p. 5634 - 5637
(2015/12/01)
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- Catalytic olefin epoxidation over cobalt(ii)-containing mesoporous silica by molecular oxygen in dimethylformamide medium
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A cobalt(ii) Schiff base complex has been immobilized onto the surface of Si-MCM-41 to prepare a new catalyst. The amine group-containing organic moiety 3-aminopropyl-triethoxysilane had first been anchored on the surface of Si-MCM-41 via a silicon alkoxide route. Upon condensation with salicylaldehyde, the amine group affords a bidentate Schiff-base moiety in the mesoporous matrix, which is subsequently used for anchoring of cobalt(ii) centers. The prepared catalyst has been characterized by UV-vis, infrared (IR), EPR spectroscopic and small angle X-ray diffraction (XRD) analyses, and N2 sorption studies. The catalytic activity was tested in epoxidation reactions of olefinic compounds, including styrene and allyl alcohol, with molecular oxygen at atmospheric pressure in dimethylformamide medium in the absence of additional sacrificial reductant. The reactions seemed to proceed through a radical formation mechanism. The immobilized catalyst showed good activity and epoxide selectivity in the alkene epoxidation. Notably, the catalyst can be recovered and reused without any loss of activity. This journal is the Partner Organisations 2014.
- Bhunia, Susmita,Jana, Sreyashi,Saha, Debraj,Dutta, Buddhadeb,Koner, Subratanath
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p. 1820 - 1828
(2014/06/09)
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- Lipophilic oligopeptides for chemo- and enantioselective acyl transfer reactions onto alcohols
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Inspired by the extraordinary selectivities of acylases, we envisioned the use of lipophilic oligopeptidic organocatalysts for the acylative kinetic resolution/desymmetrization of rac- and meso-cycloalkane-1,2-diols. Here we describe in a full account the discovery and development process from the theoretical concept to the final catalyst, including scope and limitations. Competition experiments with various alcohols and electrophiles show the full potential of the employed oligopeptides. Additionally, we utilized NMR and IR-spectroscopic methods as well as computations to shed light on the factors responsible for the selectivity. The catalyst system can be readily modified to a multicatalyst by adding other catalytically active amino acids to the peptide backbone, enabling the stereoselective one-pot synthesis of complex molecules from simple starting materials.
- Mueller, Christian E.,Zell, Daniela,Hrdina, Radim,Wende, Raffael C.,Wanka, Lukas,Schuler, Soeren M. M.,Schreiner, Peter R.
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p. 8465 - 8484
(2013/09/24)
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- Synthesis of optically active 2-hydroxy monoesters via-kinetic resolution and asymmetric cyclization catalyzed by heterometallic chiral (salen) Co complex
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The binuclear chiral (salen) Co complexes bearing Lewis acids of Al and Ga catalyze regio- and enantioselective ring opening of terminal epoxides with carboxylic acids. The ring opened product of epichlorohydrin with carboxylic acids followed by cyclization step in the presence of catalyst and base represent straightforward, efficient methods for the synthesis of enatiomerically enriched (>99% ee) valuable terminal epoxides. Strong synergistic effects of different Lewis acid of Co-Al and Co-Ga were exhibited in the catalytic process.
- Li, Wenji,Thakur, Santosh Singh,Chen, Shu-Wei,Shin, Chang-Kyo,Kawthekar, Rahul B.,Kim, Geon-Joong
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p. 3453 - 3457
(2007/10/03)
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- A new dinuclear chiral salen complexes for asymmetric ring opening and closing reactions: Synthesis of valuable chiral intermediates
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A new dinuclear chiral Co(salen) complexes bearing group 13 metals have been synthesized and characterized. The easily prepared complexes exhibited very high catalytic reactivity and enantioselectivity for the asymmetric ring opening of epoxides with H2O, chloride ions and carboxylic acids and consequently provide enantiomerically enriched terminal epoxides (>99% ee). It also catalyzes the asymmetric cyclization of ring opened product, to prepare optically pure terminal epoxides in one step. The homogeneous dinuclear chiral Co(salen) have been covalently immobilized on MCM-41. The potential benefits of heterogenization include facilitation of catalyst separation and recyclability requiring very simple techniques. The system described is very efficient.
- Thakur, Santosh Singh,Chen, Shu-Wei,Li, Wenji,Shin, Chang-Kyo,Kim, Seong-Jin,Koo, Yoon-Mo,Kim, Geon-Joong
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p. 1862 - 1872
(2007/10/03)
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- Synthesis of optically pure terminal epoxide and 1,2-diol via hydrolytic kinetic resolution catalyzed by new heterometallic salen complexes
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The inactive chiral (salen)Co complex is easily activated by InCl 3 and TlCl3 Lewis acids by forming heterometallic salen complexes. These complexes show very high catalytic activity for the synthesis of enantiomerically enriched terminal epoxides (>99% ee) and 1,2-diols simultaneously via hydrolytic kinetic resolution. Strong synergistic effects of different Lewis acids, Co-In and Co-Tl, were exhibited in the catalytic process. The system described is very simple and efficient. Copyright Taylor & Francis Group, LLC.
- Thakur, Santosh Singh,Chen, Shu-Wei,Li, Wenji,Shin, Chang-Kyo,Koo, Yoon-Mo,Kim, Geon-Joong
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p. 2371 - 2383
(2007/10/03)
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- PROCESS FOR THE PREPARATION OF GLYCIDYL DERIVATIVES
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There is provided a process for preparing a glycidyl derivative from 3-chloro-1,2-propanediol, comprising i) adding a phosphate salt to a solution into which 3-chloro-1,2-propanediol is dissolved into a solvent to produce glycidol, and ii) adding to the solution of step i) a base capable of releasing a glycidyl group from the glycidol and a substrate susceptible to nucleophilic attack to produce the desired glycidyl derivative by nucleophilic attack of the glycidyl group to the substrate.
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Page/Page column 7-9
(2008/06/13)
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- Highly reactive and enantioselective kinetic resolution of terminal epoxides with H2O and HCl catalyzed by new chiral (salen)Co complex linked with Al
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The asymmetric hydrolytic kinetic resolution (HKR) of racemic terminal epoxides by new easily synthesized dimeric chiral (salen)Co bearing Al, provides a practical and straightforward method for the synthesis of enantiomerically enriched terminal epoxides (>99% ee) and diols. An inorganic acid, HCl is applied first time for the asymmetric ring opening reaction of terminal epoxides. Reactions are conveniently carried out at room temperature under an air atmosphere.
- Thakur, Santosh Singh,Li, Wenji,Kim, Seong-Jin,Kim, Geon-Joong
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p. 2263 - 2266
(2007/10/03)
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- Organocatalytic kinetic resolution of racemic primary alcohols using a chiral 1,2-diamine derived from (S)-proline
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A highly efficient and good enantioselective organocatalytic asymmetric acylation of racemic primary alcohols with acyl chlorides has been achieved catalyzed by a chiral 1,2-diamine derived from (S)-proline.
- Terakado, Dai,Koutaka, Hitomi,Oriyama, Takeshi
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p. 1157 - 1165
(2007/10/03)
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- PROCESS FOR THE PREPARATION OF PROTECTED 3-AMINO-1,2-DIHYDROXYPROPANE ACETAL AND DERIVATIVES THEREOF
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A process for producing protected 3-amino-1,2-dihydroxypropane acetal, particularly in chiral forms, for use as an intermediate in the preparation of various 3-carbon compounds which are chiral. In particular, the present invention relates to the process for preparation of 3-amino-1,2-dihydroxypropane isopropylidene acetal. The protected 3-amino-1,2-dihydroxypropane acetal is a key intermediate to the preparation of chiral 3-carbon compounds which in turn are intermediates to various pharmaceuticals.
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- Solid oxidation catalysts, in particular for epoxidation of prochiral compounds
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The invention concerns recyclable solid oxidation catalysts comprising a metal compound of a pentavalent or hexavalent metal M and selected among the group consisting of tantalum, vanadium, niobium, chromium, molybdenum, tungsten, grafted at the surface of a solid oxide with at least one, preferably one, covalent bond between an oxygen atom of the solid oxide and the metal M atom, the grafted metal compound having at least two alkoxy groups bound to the metal by the oxygen atom. Preferably, at least 2 alkoxy groups bound to the metal M belong to a polyol unit, preferably diol. The invention also concerns oxidation methods, in particular epoxidation methods using same.
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Page/Page column 10-11
(2008/06/13)
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- Stereoselective ring opening reactions
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The present invention relates to a process for stereoselective or regioselective chemical synthesis which generally comprises reacting a nucleophile and a chiral or prochiral cyclic substrate in the presence of a non-racemic, chiral catalyst to produce a stereoisomerically- and/or regioisomerically-enriched product. The present invention also relates to hydrolytic kinetic resolutions of racemic and diastereomeric mixtures of epoxides.
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- Enantiopure poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate): A new material for supported catalytic asymmetric hydrogen transfer reduction
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A novel copolymer containing chiral epoxy residues was prepared. Free radical initiated suspension copolymerization of (R)- or (S)-glycidyl methacrylate with ethylene glycol dimethacrylate afforded crosslinked copolymer 1 in high yield. Optically active polymers containing amino alcohol functionalities were then formed from 1 through epoxide ring opening with a number of achiral and homochiral amines. It was shown that ruthenium complexes based on these new polymeric amino alcohol ligands were effective catalysts for the asymmetric hydrogen transfer reduction of acetophenone.
- Rolland, Alice,Herault, Damien,Touchard, Francois,Saluzzo, Christine,Duval, Raphael,Lemaire, Marc
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p. 811 - 815
(2007/10/03)
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- Mapping the substrate selectivity of new hydrolases using colorimetric screening: Lipases from Bacillus thermocatenulatus and Ophiostoma piliferum, esterases from Pseudomonas fluorescens and Streptomyces diastatochromogenes
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Recent advances in biochemistry and molecular biology have simplified the discovery and preparation of new hydrolases. Although these hydrolases might solve problems in organic synthesis, measuring their selectivity, especially enantioselectivity, remains tedious and time consuming. Recently, we developed a colorimetric screening method to measure the enantioselectivity of hydrolases. Here we apply this rapid screening method to map the substrate selectivity of four new hydrolases: lipases from the thermophilic Bacillus thermocatenulatus (DSM 730, BTL2) and a filamentous fungus Ophiostoma piliferum (NRRL 18917, OPL) and esterases from two bacteria, Pseudomonas fluorescens (SIK-W1, esterase I, PFE) and Streptomyces diastatochromogenes (Tue 20, SDE). We screened a general library of 29 substrates and a chiral library of 23 pairs of enantiomers. All four hydrolases catalysed the hydrolysis of unnatural substrates, but the two lipases accepted a broader range of substrates than the two esterases. As expected, the two lipases favoured more hydrophobic substrates, while the two esterases showed a preference for smaller substrates. Several moderately enantioselective reactions were identified for the solketal esters: BTL2, butyrate, E = 7.9 (R); octanoate, E = 4.9 (R) and 3-bromo-2-methyl propionate methyl esters, PFE, E = 12 (S); SDE, E = 5.6 (S). OPL showed low enantioselectivity toward all substrates tested. The current colorimetric screen could not measure the selectivity for several slow-reacting substrates. Traditional screening identified high enantioselectivity of BTL2 and PFE toward one of these slow substrates, 1-phenylethyl acetate (E>50).
- Liu, Andrew Man Fai,Somers, Neil A.,Kazlauskas, Romas J.,Brush, Terry S.,Zocher, Frank,Enzelberger, Markus M.,Bornscheuer, Uwe T.,Horsman, Geoff P.,Mezzetti, Alessandra,Schmidt-Dannert, Claudia,Schmid, Rolf D.
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p. 545 - 556
(2007/10/03)
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- Process for the preparation of protected 3-amino-1,2-dihydroxypropane acetal and derivatives thereof
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A process for producing protected 3-amino-1,2-dihydroxypropane acetal, particularly in chiral forms, for use as an intermediate in the preparation of various 3-carbon compounds which are chiral. In particular, the present invention relates to the process for preparation of 3-amino-1,2-dihydroxypropane isopropylidene acetal. The protected 3-amino-1,2-dihydroxypropane acetal is a key intermediate to the preparation of chiral 3-carbon compounds which in turn are intermediates to various pharmaceuticals.
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- Macrocyclic bisindolylmaleimides: Synthesis by inter- and intramolecular alkylation
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Macrocyclic bisindolylmaleimides 1-4 have been identified as competitive reversible inhibitors of PKC β1 and β2 and are being advanced to the clinic for evaluation as a treatment of retinopathy associated with diabetic complications. Highly convergent and stereoselective syntheses of 1-4 have been developed. The key synthetic step involves intermolecular alkylation of symmetrical bisindolylmaleimide 9 with chiral bisalkylating agent 8c and is amenable to the preparation of multikilogram quantities of these compounds. The synthetic sequence to 1, the most active the compound, proceeds in 11 steps and 26% overall yield (> 98% ee) from (R)-1-chloro-2,3-propanediol. No chromatographic purifications are required throughout the process and the final product is isolated in >97% purity after crystallization from DMF/MeOH. Synthesis of 1-4 by intramolecular alkylation proved less efficient, requiring 17 steps and affording 1-4 in lower overall yields of 6.0-8.5%.
- Faul, Margaret M.,Winneroski, Leonard L.,Krumrich, Christine A.,Sullivan, Kevin A.,Gillig, James R.,Neel, David A.,Rito, Christopher J.,Jirousek, Michael R.
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p. 1961 - 1973
(2007/10/03)
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- A direct HPLC method for the determination of enantiomeric excess of some highly enantiomerically enriched derivatives of chiral glycidols
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A newly developed HPLC method which requires no derivatization is used to determine accurately the enantiomeric purity of some glycidol-based derivatives that have been enantiomerically enriched by recrystallization or lipase-catalyzed kinetic resolution after the Sharpless Asymmetric Epoxidation.
- Chen, Jian
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p. 7663 - 7666
(2007/10/02)
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- A convenient gas chromatographic method for the optical purity determination of chiral epoxy alcohols
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Short-chain aliphatic epoxy alcohols can be readily resolved without derivatization on a capillary gc column coated with permethylated hydroxypropyl derivative of α-cyclodextrin.
- Dougherty,Liotta,Mondimore,Shum
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p. 4389 - 4390
(2007/10/02)
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- SUBSTRATE SPECIFICITY AND ENANTIOSELECTIVITY OF PENICILLINACYLASE CATALYZED HYDROLYSIS OF PHENACETYL ESTERS OF SYNTHETICALLY USEFUL CARBINOLS
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Penicillinacylase from E. coli, immobilized on Eupergit C beads catalyzes the hydrolysis in water/CH3CN 10:1, at pH 7.5 and 23 deg C, of a set of O-phenylacetate esters of primary carbinols.The highest enantioselectivity is observed in the case of the 2,2-dimethyl-1,3-dioxolane-4-methanols structurally related to the penicillin (1) framework.Minor modifications of this basic structure are not altering the acceptability by the enzyme, but significantly decrease the enantioselectivity of the hydrolysis, as does the use of benzene as solvent and Sepharose-bound enzyme.
- Fuganti, Claudio,Grasselli, Piero,Servi, Stefano,Lazzarini, Ameriga,Casati, Paolo
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p. 2575 - 2582
(2007/10/02)
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- Process for the preparation of optically-active carbazole derivatives, new R- and S-carbazole derivatives and pharmaceutical compositions containing these compounds
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A process for the preparation of S- or R-carbazole derivatives of the general formula: STR1 in which R is an unsubstituted or substituted amino radical and pharmacologically acceptable salts, by either reacting R-(-)-epichlorohydrin (for the S-carbazole derivative); or reacting an S-epoxide derivative of the general formula: STR2 in which R1 is the residue of a substituted sulphonic acid derivative (for the R-carbazole derivative); with 4-hydroxycarbazole and then with ammonia or a substituted amine of the general formula RH, and recovering the compound or converting it to a pharmacologically acceptable salt. The new R-(+)- and S(-)-carbazole derivatives provided by the inventive process have unexpected beta blocking and vasodilatory properties and are useful in pharmaceutical compositions. R-(+)-carbazole derivatives are also useful for the treatment of glaucoma.
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- Optical isomers, processes for production thereof and pharmaceutical composition thereof
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An optical isomer selected from the group consisting of (2'R),(3R)-3,4-dihydro-8-(2'-hydroxy-3'-isopropylamino)propoxy-3-nitroxy-2H-1-benzopyran, (2'S),(3R)-3,4-dihydro-8-(2'-hydroxy-3'-isopropylamino)propoxy-3-nitroxy-2H-1-benzopyran and acid addition salts of these isomers, process for producing these isomers and a pharmaceutical composition thereof useful for the treatment of cardiovascular diseases.
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- Catalytic Asymmetric Epoxidation and Kinetic Resolution: Modified Procedures Including in Situ Derivatization
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The use of 3A or 4A molecular sieves ( zeoiltes ) substantially increases the scope of the titanium(IV)-catalyzed asymmetric epoxidation of primary allylic alcohols.Whereas without molecular sieves epoxidations employing only 5 to 10 mol percent Ti(O-i-Pr)4 generally led to low conversion or low enantioselectivity, in the presence of molecular sieves such reactions generally led to high conversion (>95percent) and high enantioselectivity (90-95percent ee).The epoxidations of 20 primary allylic alcohols are described.Especially noteworthy are the epoxidations of cinnamyl alcohol, 2-tetradecyl-2-propen-1-ol, allyl alcohol, and crotyl alcohol-compounds which heretofore had been considered difficult substrates for asymmetric epoxidation.In the case of allylic alcohol, the use of cumene hydroperoxide substantially increases both the reaction rate and the conversion, even in the absence of molecular sieves.In general, enantioselectivities are slightly depressed (by 1-5percent ee) relative to reactions employing 50-100 mol percent Ti(O-i-Pr)4.The epoxidation of low molecular weight allylic alcohols is especially facilitated and, in conjuction with in situ derivatization, provides for the synthesis of many epoxy alcohol synthons which were previously difficult to obtain.The kinetic resolution of four secondary allylic alcohols with 10 mol percent Ti(O-i-Pr)4 is also described.The role of molecular sieves in the reaction and the effects of variation in reaction stoichiometry, oxidant, and tartrate are discussed.
- Gao, Yun,Hanson, Robert M.,Klunder, Janice M.,Ko, Soo Y.,Masamune, Hiroko,Sharpless, K. Barry
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p. 5765 - 5780
(2007/10/02)
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- Process for preparing optically active [S]-2-acetyl-7-(2-hydroxy-3-isopropylaminopropoxy)benzofuran and salts thereof
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[S]-(+)-2-acetyl-7-(2,3-epoxypropoxy)benzofuran (SEBF) is prepared by subjecting 2-acetyl-7-hydroxybenzofuran and [R]-glycidol to dehydration condensation in an inert organic solvent in the presence of triphenylphosphine and a dialkyl azodicarboxylate. The [S]-(+)-2-acetyl-7-(2,3-epoxypropoxy)benzofuran can be easily converted into [S]-2-acetyl-7-(2-hydroxy-3-isopropylaminopropoxy)benzofuran ([S]-befunolol) or salts thereof which are useful as a β-adrenergic blocking agent, by reacting it with isopropylamine.
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- Preparation of epihalohydrin enantiomers
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Processes for preparing (S) or (R) epihalohydrin and an (S) substituted glycerol intermediate are disclosed.
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- Preparation of epihalohydrin enantiomers
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Processes for preparing (S) or (R) epihalohydrin and an (S) substituted glycerol intermediate are disclosed.
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