- Thermodynamics of the Hydrolysis of N-Acetyl-L-phenylalanine Ethyl Ester in Water and in Organic Solvents
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Equilibrium measurements have been performed on the α-chymotrypsin-catalyzed hydrolysis reaction of N-acetyl-L-phenylalanine ethyl ester to (N-acetyl-L-phenylalanine + ethanol) with carbon tetrachloride, dichloromethane, toluene, and aqueous phosphate buffer as solvents for the reactants and products.Apparent equilibrium constants were measured as a function of temperature for this reaction in all four solvents.Calorimetric measurements were also performed for this reaction in aqueous phosphate buffer.The principal reaction occurring in the aqueous phosphate buffer at pH = 6-7 is N-acetyl-L-phenylalanine ethyl ester(aq) + H2O(aq) = N-acetyl-L-phenylalanine(-)(aq) + ethanol(aq) + H(+)(aq).Therefore, to compare the results for the reaction in water with those for the reaction in the organic solvents where it is assumed only neutral species are present, it was necessary to adjust the experimental results to the reaction involving neutral species: N-acetyl-L-phenylalanine ethyl ester(sln) + H2O(sln) = N-acetyl-L-phenylalanine(sln) + ethanol(sln), where sln denotes either aqueous media, carbon tetrachloride, dichloromethane, or toluene.The values of the equilibrium constant for this latter reaction, with the concentration of water included in the expression for the equilibrium constant, ranged from 0.057 to 0.20 at T = 298.15 K for the four solvents.This rather limited range of values for the equilibrium constants is significant.The very limited amount of information available from the literature is also suggestive of the rule that equilibrium constants for hydrolysis reactions in different solvents are comparable if the reaction refers to neutral species and the concentration of water is included in the formulation of the equilibrium constant.Also, the standard molar enthalpy of reaction was found to be a linear function (slope = 313 K) of the standard molar entropy of reaction.This is indicative of an enthalpy-entropy compensation effect.
- Tewari, Y. B.,Schantz, M. M.,Pandey, P. C.,Rekharsky, M. V.,Goldberg, R. N.
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- A facile microwave-mediated drying process of thermally unstable / labile products
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The drying behavior of (S)-N-acetylindoline-2-carboxylic acid, precipitated (1a, 17 wt %) and nonprecipitated (1b, 5 wt %), and N-acetyl-(S)-phenylalanine ((S)-2-acetamido-3-phenylpropanoic acid, 2), both pharmaceutical intermediates, and of cocarboxylase hydrochloride (thiamine pyrophosphate, 3), a coenzyme, a bioactive form of vitamin B1, being a thermolabile substance, has been determined in straightforward drying setups. The method of supplying energy to the system had a profound influence on the drying rate and on the internal temperature of the samples during drying. The drying time of (S)-N-acetylindoline-2-carboxylic acid (1b) with the low moisture content (5 wt %) could be reduced by a factor 4 using microwave irradiation instead of conventional heating, while keeping the sample temperature under 35 °C. N-Acetyl-(S)-phenylalanine (2) with a higher moisture content (22 wt %) demonstrated a decrease in drying time by a factor 2.5 to 4 depending on the applied microwave powers. A reduction in drying time of the precipitated (S)-N-acetylindoline-2-carboxylic acid (1a, 17 wt % moisture) by a factor 2 was demonstrated for drying at 150 W of microwave irradiation instead of using a water bath at 70 °C. A dramatically shorter drying time by a factor 10 was found for cocarboxylase hydrochloride (3, 15 wt % water) on lab-scale which could be reproduced on pilot-plant scale. To achieve with conventional heating similar drying times as under microwave irradiation for the four examples, extremely high energy inputs should be applied, necessitating extremely high temperature differences between the heating source and the sample. The results reveal that microwave irradiation is less energy-consuming and is particularly useful for effective drying of thermally unstable materials in short periods of time.
- Pinchukova,Voloshko,Shyshkin,Chebanov,Van De Kruijs,Arts,Dressen,Meuldijk,Vekemans,Hulshof
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- ASYMMETRIC HYDROGENATION BY CHIRAL AMINOPHOSPHINE-PHOSPHINITE RHODIUM COMPLEXES
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The ligands (S)-N-(diphenylphosphino)-2-diphenylphosphinomethylpyrrolidine, (S)-prolophos, and (S)-1-diphenylphosphinoxy-2-N-ethyl-N-diphenylphosphinoaminobutane,(S)-butaphos, have been prepared.The Rh(I) complexes of these phosphines act as an efficient homogenous hydrogenation catalysts at ambient temperature and pressure for α-N-acetaminoacrylic acid and itaconic acid.
- Cesarotti, E.,Chiesa, A.,D'Alfonso, G.
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- Chymotrypsin-catalyzed peptide synthesis in deep eutectic solvents
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Deep eutectic solvents (DESs) are formed by mixing quaternary ammonium salts (e.g., choline chloride) and hydrogen-bond donors (e.g., glycerol or urea), which leads to biodegradable and readily available ionic solvents at room temperature. Analogous to other ionic liquids, DESs represent a promising reaction media if hydrophobic and hydrophilic substrates need to be combined. This paper assesses DESs as reaction media for chymotrypsin-catalyzed peptide synthesis. After careful determination of the reaction conditions (e.g., water content, enzyme loading), α-chymotrypsin displayed high activity for peptide synthesis in choline chloride/glycerol mixtures to afford productivities of ca. 20 g L-1 h-1 and with complete selectivity for the peptide, which is in contrast to the detrimental hydrolysis pathway observed in aqueous media. The nonimmobilized suspended enzyme could be reused several times by simple filtration with excellent to moderate activities. Overall, the results reported suggest that choline chloride based DESs may become promising neoteric solvents for peptide synthesis through biocatalysis. Copyright
- Maugeri, Zaira,Leitner, Walter,Dominguez De Maria, Pablo
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- Asymmetric transfer hydrogenation of prochiral carboxylic acids catalyzed by a five-coordinate Ru(II)-binap complex
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Asymmetric transfer hydrogenation of representative prochiral carboxylic acids was performed, using [RuH((S)-binap2]PF6 or a related complex as a catalyst and 2-propanol or ethanol as a hydrogen source, to achieve good to excellent enantioselectivities.
- Saburi,Ohnuki,Ogasawara,Takahashi,Uchida
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- BIOCATALYTICAL TRANSFORMATIONS II. ENANTIOSELECTIVE HYDROLYSIS OF N-ACETYL-FLUORO-PHENYLALANINE-ETHYLESTERS BY LYOPHILISED YEAST
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The three nuclear substituted monofluoro D-N-acetylphenylalanine-ethylesters were obtained in excellent yield via enantioselective hydrolysis of their respective racemates by use of lyophilised yeast (Saccharomyces cerevisiae Hansen).
- Csuk, Rene,Glaenzer, Brigitte I.
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- Novel chiral dendritic diphosphine ligands for Rh(I)-catalyzed asymmetric hydrogenation: Remarkable structural effects on catalytic properties
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A series of dendritic ligands with a chiral diphosphine located at the focal point have been synthesized through coupling of pyrphos 2 with Frechet-type polyether dendron 3. The relationship between the primary structure of the dendrimer and its catalytic properties was established in the Rh-catalyzed asymmetric hydrogenation of α-acetamido cinnamic acid 4. A remarkable structural effect on catalytic activity was observed.
- Yi, Bing,Fan, Qing-Hua,Deng, Guo-Jun,Li, Yue-Ming,Qiu, Li-Qin,Chan, Albert S. C.
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- Novel phosphine-phosphite and phosphine-phosphinite ligands for highly enantioselective asymmetric hydrogenation
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Two novel phosphine-phosphite (S,R)-o-BINAPHOS and phosphine-phosphinite (S)-o-BIPNITE ligands based on ortho phenyl substituted (S)-BINOL have been synthesized. Extremely high enantioselectivity (over 99% ee in most cases) has been achieved for the Rh-catalyzed asymmetric hydrogenation of α-dehydroamino acid derivatives.
- Yan, Yongjun,Chi, Yongxiang,Zhang, Xumu
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- The effect of enzymatic reaction on dissolution rate: Theoretical analysis and experimental test
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The dissolution behavior of N-acetylphenylalanine ethyl ester (1) and N-benzoyltyrosine ethyl ester (2) from a rotating disk into aqueous solutions containing the enzyme α-chymotrypsin was investigated. The effect of the bulk enzymatic reaction on the dissolution rates is modeled using the continuity equation where the reaction term is considered a constant throughout the reaction zone. Dimensional analysis on the continuity equation defines the important parameter R* = K(cat)E0h2/(C(s)D) which is the ratio of the diffusion time to the reaction time. This parameter correctly predicted the fact that the enzymatic reaction had only a slight impact on the dissolution of the highly soluble 1 while the effect on the less soluble 2 was large. Also predicted by R* is the dissolution dependence on the catalytic rate constant. The variation of this rate constant with pH is consistent with the dependence on pH found for the dissolution rate of 2. It is further demonstrated that the decrease in dissolution rate with solubility can be significantly reduced when the dissolving compound is an enzyme substrate. For the two compounds used in this study the dissolution rate decreased with the square root of solubility, as predicted by the theoretical analysis in the presence of enzyme. Other experiments included the variation of the enzyme concentration and the rotational speed on the spinning disk. All experiments were designed to show how R* could correctly predict the relative importance of the convective, diffusive, and reactive processes.
- Johnson,Amidon
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- From batch to flow processing: Racemization of N-acetylamino acids under microwave heating
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The racemization of N-acetylindoline-2-carboxylic acid in P-xylene revealed beneficial rate enhancements due to microwave effects, by comparing conventional and microwave heating. The magnitude of this effect was governed by the degree of heterogeneity of the reaction system. The amount of catalyst, the temperature and the amount of cosolvent played a decisive role. The microwave effect completely vanished when a homogeneous solution was heated. During the microwave-assisted heterogeneous racemization of N-acetylphenylalanine in P-xylene a comparable microwave effect was observed. The microwave effects could be rationalized by adapting selective heating in the phase boundary region of solid and liquid. Additionally, a straightforward translation was achieved from batchwise operation in a stirred reactor to a batch-loop reactor. The (heterogeneous) racemization of N-acetylindoline-2-carboxylic acid retained its microwave effect in the loop reactor. Our results demonstrated that avoiding plugging of the tubular reactor is a severe challenge in scaling up.
- Dressen, Mark H. C. L.,Van De Kruijs, Bastiaan H. P.,Meuldijk, Jan,Vekemans, Jef A. J. M.,Hulshof, Lumbertus A.
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- From 2H-phospholes to BIPNOR, a new efficient biphosphine for asymmetric catalysis
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For many years now, we have studied the 1H-/2H-phosphole equilibrium and its synthetic applications. On reaction with alkynes, 2H-phospholes yield the corresponding 1-phosphanorbornadienes. As ligands of rhodium(I), these phosphines show some potential in catalytic hydrogenation and hydroformylation of alkenes. Starting from 3,3′,4,4′-tetramethyl-1,1′-biphospholyl and tolan, we have similarly obtained the corresponding 2,2′-bis-(1-phosphanorbornadienyl) (BIPNOR) with two chiral, non-racemisable, phosphorus atoms at the bridgeheads. The pure enantiomers of BIPNOR appear to be efficient ligands in asymmetric hydrogenation of C=C and C=O double bonds.
- Mathey, Francois,Mercier, Francois,Robin, Frederic,Ricard, Louis
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- A versatile synthesis of phosphine-aminophosphine ligands for asymmetric catalysis
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A new and versatile synthesis of phosphine-aminophosphine ligands allows the incorporation of a wide range of nitrogen and phosphorus substituents into these ligands, several of which exhibit improved properties for rhodium-catalyzed asymmetric hydrogenation reactions. This synthesis also allows the preparation of mixed phosphine-phosphoramidite species.
- Boaz, Neil W.,Ponasik Jr., James A.,Large, Shannon E.
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- Phosphonites based on the paracyclophane backbone: New ligands for highly selective rhodium-catalyzed asymmetric hydrogenation
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Figure presented The synthesis of new phosphonites with a chiral paracyclophane backbone is described. The rhodium complexes derived from the phosphonites bearing biphenoxy and binaphthoxy substituents are highly active and highly selective catalysts for the asymmetric hydrogenation of dehydroamino acids and esters.
- Zanotti-Gerosa, Antonio,Malan, Christophe,Herzberg, Daniela
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- Structure-activity relationship studies of dipeptide-based hepsin inhibitors with Arg bioisosteres
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Hepsin is a type II transmembrane serine protease (TTSP) associated with cell proliferation and overexpressed in several types of cancer including prostate cancer (PCa). Because of its significant role in cancer progression and metastasis, hepsin is an attractive protein as a potential therapeutic and diagnostic biomarker for PCa. Based on the reported Leu-Arg dipeptide-based hepsin inhibitors, we performed structural modification and determined in vitro hepsin- and matriptase-inhibitory activities. Comprehensive structure-activity relationship studies identified that the p-guanidinophenylalanine-based dipeptide analog 22a exhibited a strong hepsin-inhibitory activity (Ki = 50.5 nM) and 22-fold hepsin selectivity over matriptase. Compound 22a could be a prototype molecule for structural optimization of dipeptide-based hepsin inhibitors.
- Kwon, Hongmok,Ha, Hyunsoo,Jeon, Hayoung,Jang, Jaebong,Son, Sang-Hyun,Lee, Kiho,Park, Song-Kyu,Byun, Youngjoo
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supporting information
(2020/12/25)
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- Metal coordination compound, intermediate, preparation method and applications thereof
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The invention discloses a metal coordination compound, an intermediate, a preparation method and applications thereof. According to the invention, the metal coordination compound represented by a formula I can be used as a catalyst for an asymmetric catalytic hydrogenation reaction to efficiently and catalytically synthesize a series of chiral beta-aryl amides with high optical purity (ee value ofmore than 99%) particularly to asymmetrically and catalytically hydrogenate a tetra-substituted alkenyl amide compound to synthesize a chiral amide with high optical purity (ee value of more than 60%), wherein the ligand bearing capacity (s/c) can reach 100000.
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Paragraph 0378-0383
(2020/05/01)
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- P-chirogenic diphosphazanes with axially chiral substituents and their use in rh-catalyzed asymmetric hydrogenation
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A convenient synthesis of enantiopure P-chirogenic diphosphazanes incorporating bulky bisphenol and 1,1′-bi-2-naphtholderived substituents via the functionalization of a readily accessible enantiopure lithium phosphinoamide with chlorophosphoridites was developed. Since the product requires no subsequent deprotection, the protocol provides an easy, convenient synthesis of P-chirogenic ligands on the gram scale. The ligands were applied in the Rh-catalyzed asymmetric hydrogenation of benchmark substrates furnishing enantiomeric excess values up to 96%.
- Moritz, Jan-Ole,Chakrabortty, Soumyadeep,Bernd H. Mu.ller,Spannenberg, Anke,Kamer, Paul C. J.
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p. 14537 - 14544
(2020/12/29)
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- Oxidative damage of proline residues by nitrate radicals (NO3): A kinetic and product study
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Tertiary amides, such as in N-acylated proline or N-methyl glycine residues, react rapidly with nitrate radicals (NO3) with absolute rate coefficients in the range of 4-7 × 108 M-1 s-1 in acetonitrile. The major pathway proceeds through oxidative electron transfer (ET) at nitrogen, whereas hydrogen abstraction is only a minor contributor under these conditions. However, steric hindrance at the amide, for example by alkyl side chains at the α-carbon, lowers the rate coefficient by up to 75%, indicating that NO3-induced oxidation of amide bonds proceeds through initial formation of a charge transfer complex. Furthermore, the rate of oxidative damage of proline and N-methyl glycine is significantly influenced by its position in a peptide. Thus, neighbouring peptide bonds, particularly in the N-direction, reduce the electron density at the tertiary amide, which slows down the rate of ET by up to one order of magnitude. The results from these model studies suggest that the susceptibility of proline residues in peptides to radical-induced oxidative damage should be considerably reduced, compared with the single amino acid.
- Nathanael, Joses G.,Nuske, Madison R.,Richter, Annika,White, Jonathan M.,Wille, Uta
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supporting information
p. 6949 - 6957
(2020/10/02)
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- The effect of imidazolium salts with amino acids as counterions on the reactivity of 4-nitrophenyl acetate: A kinetic study
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As a first approach to improve the “green character” of the surfactants based on imidazolium cations, three surfactants using 1-tetradecyl-3-methylimidazolium [C14mim]+ as cation and different amino acids (AA) as counterion, were syn
- Figueroa, Roberto,Orth, Elisa,Pavez, Paulina,Rojas, Mabel,Santos, José G.
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- Batch versus flow stereoselective hydrogenation of Α-acetamido-cinnamic acid catalyzed by an Au(I) complex
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A chiral gold (I) (2S,4S)-1-tert-butoxycarbonyl-4-diphenylphosphino-2-(diphenylphosphino- methyl) pyrrolidine (BPPM) complex has been prepared using [Au(SMe2)Cl] as precursor. The heterogenization of the Au-BPPM catalyst onto the CNT support followed two routes, ie (i) the non-covalent immobilization of the gold(I)complex by dry-impregnation, and (b) covalent immobilization of the gold(I)complex on a pre-functionalized CNT. These catalysts afford the stereoselective hydrogenation of α-acetamidocinnamic acid to the (R)-N-acetyl-phenylalanine enantiomer. The nature of the solvent affected both the enantioselectivity and TOFs. Among MeOH, EtOH, and TFE, methanol appeared to be the most efficient one (at 80 °C a TOF of 0.37 h?1 for a total enantioselectivity to the R-isomer). Transferring the reaction in the flow reactor, under similar conditions (methanol, room temperature) led to a 10 time increase of the TOF with no change in the stereoselectivity. The decrease of the TOF in time for both the reference Rh and the Au catalysts was assigned to their partial modification under the reaction conditions. The heterogenization of the Au-BPPM catalyst onto the CNT support, for the same content of Au-complex, led to a very important increase of the conversion with no change in the selectivity. However, the covalent bonding was more efficient affording a very high increase of the conversion even at room temperature (95% after 24 h), thus demonstrating that the anchoring a support increases the dispersion, and in consequence the efficiency. These CNT-Au-BPPM catalysts preserved the catalytic performances during recycling as also confirmed by the characterization results.
- Negoi, Alina,Cojocaru, Bogdan,Parvulescu, Vasile I.,Imlyhen, Nora,Gouygou, Maryse
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- Enhancement of water solubility of poorly water-soluble drugs by new biocompatible N-acetyl amino acid N-alkyl cholinium-based ionic liquids
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The major challenge of the pharmaceutical industry is to find potential solvents for poorly water-soluble drug molecules. Ionic liquids (ILs) have attracted this industry as (co-) solvents due to their unique physicochemical and biological properties. Herein, a straightforward approach for the enhancement of the water solubility of paracetamol and sodium diclofenac is presented, using new biocompatible N-acetyl amino acid N-alkyl cholinium-based ionic liquids as co-solvents (0.2–1 mol%). These new ionic liquids were able to increase the water solubility of these drugs up to four times that in pure water or in an inorganic salt solution. In the presence of these ILs, the drugs lipophilicity (log P was not significantly changed for paracetamol, but for sodium diclofenac it was possible to decrease significantly its lipophilicity. Concerning cytotoxicity in human dermal fibroblasts it was observed that ILs did not show a significant toxicity, and were able to improve cell viability compared with the respective precursors.
- Jesus, Ana R.,Soromenho, Mário R.C.,Raposo, Luís R.,Esperan?a, José M.S.S.,Baptista, Pedro V.,Fernandes, Alexandra R.,Reis, Patrícia M.
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p. 227 - 232
(2019/03/13)
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- GRANZYME B DIRECTED IMAGING AND THERAPY
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Provided herein are heterocyclic compounds useful for imaging Granzyme B. Methods of imaging Granzyme B, combination therapies, and kits comprising the Granzyme B imaging agents are also provided.
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Page/Page column 82; 98
(2019/09/04)
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- BABIPhos Family of Biaryl Dihydrobenzooxaphosphole Ligands for Asymmetric Hydrogenation
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Novel bidentate phosphine ligands BABIPhos featuring a biaryl bis-dihydrobenzooxaphosphole core are presented. Their synthesis was achieved via Pd-catalyzed reductive homocoupling of dihydrobenzooxaphosphole aryl triflates. An efficient route toward various analogues was also established, giving access to phosphines with different electronic and steric properties. The newly obtained ligands demonstrated high efficiency and selectivity in Rh-catalyzed asymmetric hydrogenation of di- and trisubstituted enamides. This new class of ligands is complementary to previously described bidentate benzooxaphosphole ligands BIBOP.
- Li, Guisheng,Zatolochnaya, Olga V.,Wang, Xiao-Jun,Rodríguez, Sonia,Qu, Bo,Desrosiers, Jean-Nicolas,Mangunuru, Hari P. R.,Biswas, Soumik,Rivalti, Daniel,Karyakarte, Shuklendu D.,Sieber, Joshua D.,Grinberg, Nelu,Wu, Ling,Lee, Heewon,Haddad, Nizar,Fandrick, Daniel R.,Yee, Nathan K.,Song, Jinhua J.,Senanayake, Chris H.
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p. 1725 - 1729
(2018/04/14)
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- Cinnamic acid derivative with aldose reductase inhibitory activity as well as preparation method and application thereof
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The invention discloses a cinnamic acid derivative with aldose reductase inhibitory activity, a preparation method thereof and an application of the cinnamic acid derivative in preparation of a medicine used for treating diabetic complications and diseases caused by oxidative stress. The structure of the compound is shown in a formula I. The preparation method comprises the following steps: firstly reacting substituted benzaldehyde with substituted acetic acid or acid anhydride thereof to obtain substituted cinnamic acid, then reacting with a diamine compound protected by N-tertiary butoxy acyl to obtain substituted cinnamoyl diamide protected by N-tertiary butoxy acyl; and carrying out tertiary butoxy acyl deprotection on the substituted cinnamoyl diamide protected by N-tertiary butoxy acyl, and then reacting with natural or non-natural N-acyl alpha-amino acid, so that the cinnamic acid derivative is obtained. The cinnamic acid derivative compound disclosed by the invention has excellent inhibitory activity on aldose reductase and excellent antioxidant activity and can be applied to preparation of a medicine used for treating the diabetic complications, especially diabetic retinopathy, senile dementia due to diabetes and nerve ending disturbance, as well as diseases caused by the oxidative stress.
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Paragraph 0087; 0091; 0115
(2017/09/01)
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- Modular solid-phase synthesis, catalytic application and efficient recycling of supported phosphine-phosphite ligand libraries
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In spite of decades of research in the field of homogeneous asymmetric catalysis the discovery of new high performance catalysts still relies heavily on trial-and-error. There is still a lack of efficient combinatorial methods which enable the synthesis and screening of vast ligand libraries, especially for bidentate phosphorus ligands. Here we present a highly modular solid-phase synthetic approach which provides facile access to libraries of phosphine-phosphite ligands in quantitative yield requiring only minimal work-up. The obtained library of supported phosphine-phosphites was successfully applied in rhodium catalyzed asymmetric hydrogenation obtaining high enantioselectivities up to 98%. Also, these polymer supported ligands could be successfully recycled under batch conditions exhibiting only a small decline of activity and no loss of selectivity.
- Heutz, Frank J. L.,Kamer, Paul C. J.
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supporting information
p. 2116 - 2123
(2016/02/09)
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- A kind of ionic liquid covalent load of the chiral phosphine ligand and use thereof
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The invention discloses an ionic liquid covalent-loaded chiral phosphine ligand and application thereof. The ionic liquid covalent-loaded chiral phosphine ligand is formed by connecting functionalized ionic liquid and a corresponding micro-molecule chiral phosphine ligand by an amide group through a condensation reaction. The ionic liquid covalent-loaded chiral phosphine ligand has the characteristics of few synthesis steps of a target molecule and simple separation-purification process. The invention further discloses application of the ionic liquid covalent-loaded chiral phosphine ligand in an asymmetrical catalytic hydrogenation reaction. The catalyst including the load type chiral phosphine ligand and metal rhodium (Rh) can be conveniently separated from reaction products in the asymmetrical hydrogenation reaction, so that the catalyst is recycled and re-utilized.
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Paragraph 0041; 0046; 0047
(2017/03/25)
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- Preparation method for amprenavir intermediate
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The invention relates to a synthesis method for an amprenavir intermediate, an anti-AIDS drug, in particular to a synthesis method for (2R,3S)-1,2-epoxy-3-(tert-butoxycarbonylamino)-4-phenylbutane. The synthesis method comprises the following steps: reacting L-phenylalanine, as a raw material, with acetic anhydride to generate N-acetyl-L-phenylalanine, and then carrying out a Mannich reaction, an Appel reaction and olefin epoxidation to obtain an intermediate. The method for preparing the (2R,3S)-1,2-epoxy-3-(tert-butoxycarbonylamino)-4-phenylbutane is reasonable in route, high in operability and high in yield, and facilitates industrial production.
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Paragraph 0042; 0043
(2016/10/08)
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- Pyrazole-based potent inhibitors of GGT1: Synthesis, biological evaluation, and molecular docking studies
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In this study, a series of pyrazole-based structural analogues of GGTI-DU40 (1) have been synthesized and biologically evaluated for geranylgeranyltransferase 1 (GGT1) and farnesyltransferase (FT) inhibition. The screening results revealed that 2 (IC50?=?2.4?μM) and 5 (IC50?=?3.1?μM) are potent GGT1 inhibitors (GGTIs), possessing higher inhibitory activity compared to the control compound 1 (IC50?=?3.3?μM). The anti-proliferative efficacy of these compounds was further assayed against MDA-MB-231?cells which indicated a significantly higher activity of 2 (IC50?=?7.6?μM) compared to 1 (IC50?=?23.0?μM). To examine the capacity of the synthesized compounds to inhibit GGT1 in an intact cell, western blot analysis was performed on the MDA-MB-231?cell line, which revealed very high inhibitory cellular activity of 2 and 5 and demonstrated their capacity to inhibit prenylation of endogenous proteins. Molecular docking studies of 2 against the crystal structure of GGT1 complexed with a geranylgeranyl pyrophosphate (GGPP) Analog and a CaaX (C?=?cysteine, aa?=?aliphatic amino acids, and X?=?any amino acid) portion of the KKKSKTKCVIL peptide substrate revealed several hydrogen bonding interactions and π-π contacts between 2 and the binding pocket of GGT1. Together these data suggest that compound 2 could proceed to in?vivo investigation to further assess its efficacy and cytotoxicity.
- Mansha, Muhammad,Kumari, Udayappan Udhaya,Cournia, Zoe,Ullah, Nisar
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p. 666 - 676
(2016/09/14)
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- Energetic contribution to both acidity and conformational stability in peptide models
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The acidity of N-acyl amino acids is dependent upon the rotameric state of the amide bond. In this work we systematically investigated the acidity difference of the rotamers (ΔpKa) in the frames of various acetylated amino acids. Our results indicated a mutual interaction of two carbonyl groups of an attractive type. We observed conservative ΔpKas for acyclic amino acids (2.2-3.0 kJ mol-1), whereas in the case of alicyclic amino acids, the experimental values revealed a strong dependency on the structural context (1.5-4.4 kJ mol-1). In homologous amino acids (α-, β-, γ-, etc.), the strength of the attraction decays in an exponential fashion. Furthermore, the interaction can accumulate through a chain of amide bonds in a cascade fashion, as demonstrated by an Ac-Pro-Pro dipeptide. As a result, we demonstrate that ΔpKa is an experimental parameter to estimate increments in the carbonyl-carbonyl alignment, as determined by the amino acid or peptidyl context. This parameter is also important in understanding the roles of amino acids in both protein folding and translation in biological systems as well as their evolutionary appearance in the genetic code.
- Kubyshkin, Vladimir,Durkin, Patrick,Budisa, Nediljko
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supporting information
p. 5209 - 5220
(2016/07/06)
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- Reversible, short α-peptide assembly for controlled capture and selective release of enantiomers
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Although significant progress has been achieved with short peptide nanostructures, the construction of switchable membrane assemblies remains a great challenge. Here we report short α-peptide assemblies that undergo thermo-reversible switching between assembly and disassembly states, triggered by the conformational change of laterally grafted short peptides from a folded α-helix to a random coil conformation. The α-helical peptide based on two oligoether dendron side groups forms flat disks, while the peptide helix based on three dendron side groups forms hollow vesicles. The vesicular membrane can spontaneously capture a racemic mixture through the self-formation of vesicular containers upon heating and enantioselectively release the chiral guest molecule through preferential diffusion across the vesicular walls.
- Chen, Xi,He, Ying,Kim, Yongju,Lee, Myongsoo
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p. 5773 - 5776
(2016/06/09)
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- Aqueous MW eco-friendly protocol for amino group protection
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In this paper a new catalyst-free and on-water method for protection of amines and amino acids with di-tert-butyl dicarbonate, 9-fluorenylmethoxycarbonyl chloride, acetyl chloride and tosyl chloride is presented. The protection can be realized in a few minutes under microwave-assistance. The reaction proved to be chemoselective in presence of ambident nucleophiles and water solution of di-tert-butyl carboxylic acid or chloride acid are the only wastes produced.
- Nardi,Cano, N. Herrera,Costanzo,Oliverio,Sindona,Procopio
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p. 18751 - 18760
(2015/06/15)
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- MgI2-Mediated Chemoselective Cleavage of Protecting Groups: An Alternative to Conventional Deprotection Methodologies
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The scope of MgI2 as a valuable tool for quantitative and mild chemoselective cleavage of protecting groups is described here. This novel synthetic approach expands the use of protecting groups, widens the concept of orthogonality in synthetic processes, and offers a facile opportunity to release compounds from solid supports. Amazing MgI2: Protecting groups have had a tremendous positive impact on the art of biomolecule synthesis. In a context in which the use of attractive protecting groups is often limited by harsh deprotection conditions and low chemoselective flexibility, MgI2 offers, by the execution of a very simple protocol, a fresh vision with extensive perspectives.
- Berthet, Mathéo,Davanier, Florian,Dujardin, Gilles,Martinez, Jean,Parrot, Isabelle
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supporting information
p. 11014 - 11016
(2015/11/10)
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- Synthesis of phospholane-phosphoramidite ligands and their application in asymmetric catalysis
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A set of phospholane-phosphoramidite ligands, which possess four elements of chirality, has been synthesized through a modular diastereoselective process. The ligands were applied in the Rh-catalyzed asymmetric C =C hydrogenation of several functionalized olefins with enantioselectivities of up to 99 % ee and a turnover frequency of up to 12 000 h-1, in the Rh-catalyzed hydroformylation of vinyl arenes with enantioselectivities of up to 79 % ee, and in the Ir-catalyzed asymmetric C =N hydrogenation of different aryl imines with enantioselectivities of up to 79 % ee. New P,P′ hybrid ligands: A set of phospholane-phosphoramidites (quinaphoslane) with four elements of chirality are synthesized through a modular diastereoselective process and applied in the Rh-catalyzed hydrogenation of functionalized olefins with up to 99 % ee and a turnover frequency (TOF) of up to 12 000 h-1, in the Rh-catalyzed hydroformylation of vinyl arenes with regioselectivities of up to 99 % and up to 79 % ee, and in the Ir-catalyzed hydrogenation of imines with up to 79 % ee.
- Hammerer, Tim,Leitner, Walter,Franciò, Giancarlo
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p. 1583 - 1592
(2015/05/27)
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- Solid-phase synthesis of recyclable diphosphine ligands
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An efficient solid-phase synthetic approach towards diphosphine ligands is demonstrated. This modular method offers facile access to this important class of ligands, in quantitative yield, providing huge potential for ligand fine-tuning. These supported ligands can be efficiently applied in asymmetric catalysis. Moreover, the immobilized catalysts can successfully be recycled multiple times addressing several synthetic and work-up challenges in the field of catalytic chemistry.
- Heutz, Frank J.L.,Samuels, Michiel C.,Kamer, Paul C.J.
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p. 3296 - 3301
(2015/06/08)
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- Highly Enantioselective Pd-Catalyzed Synthesis of P-Stereogenic Supramolecular Phosphines, Self-Assembly, and Implication
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Metal-catalyzed asymmetric addition of a secondary phosphine to an aryl halide is one of the most efficient and reliable approaches for the construction of enantiopure carbon-phosphorus bonds. An isolated Pd(II) complex (5) catalyzes the carbon-phosphorus coupling reaction between tolylphenylphosphine (1a) and 3-iodophenylurea (2b), which proceeds with an unprecedented enantiomeric excess (ee) of 97%. The generality of the strategy has been demonstrated by preparing a small library of a new class of P-stereogenic phosphines with an in-built hydrogen bonding motif for the first time. The P-stereogenic phosphines self-assemble on a metal template via deliberately installed hydrogen-bonding motifs and mimic the bidentate ligand coordination. Interestingly, when it was employed in asymmetric hydrogenation, the supramolecular phosphine {1-(3-(phenyl(o-tolyl)phosphanyl)phenyl)urea} (6b) produced the corresponding hydrogenated product with the highest enantiomeric excess of 99% along with excellent conversion, demonstrating the potential of these enantioenriched P-chirogenic supramolecular phosphines in asymmetric catalysis.
- Koshti, Vijay S.,Mote, Nilesh R.,Gonnade, Rajesh G.,Chikkali, Samir H.
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supporting information
p. 4802 - 4805
(2015/11/09)
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- RHODIUM CATALYST AND METHOD FOR MANUFACTURING OPTICALLY ACTIVE COMPOUND USING THE SAME
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PROBLEM TO BE SOLVED: To provide a new rhodium complex stable in the air, easy in handling and using an inexpensive optically active H-phosphinate HP(O)R(OR') as a ligand, and a method for asymmetrically hydrogenating olefins efficiently using the same. SOLUTION: The rhodium complex compound has a structure represented by the following general formula (I). (Where in the formula (I), R1 and R2 are carbon substituents which may be the same or different, and two olefins coordinated in Rh may combine with each other as shown by a dotted line to form a ring structure.) COPYRIGHT: (C)2015,JPOandINPIT
- -
-
Paragraph 0024; 0025; 0026
(2017/01/05)
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- Synthesis of tertiary and quaternary amine derivatives from wood resin as chiral NMR solvating agents
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Chiral tertiary and quaternary amine solvating agents for NMR spectroscopy were synthesized from the wood resin derivative (+)-dehydroabietylamine (2). The resolution of enantiomers of model compounds [Mosher's acid (3) and its n-Bu4N salt (4)] (guests) by (+)-dehydroabietyl-N,N-dimethylmethanamine (5) and its ten different ammonium salts (hosts) was studied. The best results with 3 were obtained using 5 while with 4 the best enantiomeric resolution was obtained using (+)-dehydroabietyl-N,N-dimethylmethanaminium bis(trifluoromethane-sulfonimide) (6). The compounds 5 and 6 showed a 1:1 complexation behaviour between the host and guest. The capability of 5 and 6 to recognize the enantiomers of various α-substituted carboxylic acids and their n-Bu4N salts in enantiomeric excess (ee) determinations was demonstrated. A modification of the RES-TOCSY NMR pulse sequence is described, allowing the enhancement of enantiomeric discrimination when the resolution of multiplets is insufficient.
- Laaksonen, Tiina,Heikkinen, Sami,W?h?l?, Kristiina
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supporting information
p. 20873 - 20886
(2015/12/23)
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- Peptide Tyrosinase Activators
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Peptides that increase melanin synthesis are provided. These peptides include pentapeptides YSSWY, YRSRK, and their variants. The peptides may activate the enzymatic activity of tyrosinase to increase melanin synthesis. The pharmaceutical, cosmetic, and other compositions including the peptides are also provided. The methods of increasing melanin production in epidermis of a subject are provided where the methods include administering compositions comprising an amount of one or more peptides effective to increase the melanin production. The methods also include treating vitiligo or other hypopigmentation disorders with compositions including one or more peptides.
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- Efficient asymmetric hydrogenation of α-acetamidocinnamates through a simple, readily available monodentate chiral H-phosphinate
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An air-stable, simple (RP)-mentylbenzylphosphinate, readily available in large quantities, can efficiently induce the rhodium-catalyzed asymmetric hydrogenation of α-acetamidocinnamates with high enantioselectivity (up to 99.6 % ee). Intramolecular hydrogen bonding plays an important role in this asymmetric induction.
- Wang, Xiang-Bo,Goto, Midori,Han, Li-Biao
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supporting information
p. 3631 - 3635
(2014/04/03)
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- Synthesis and Reactivity of Chiral, Wide-Bite-Angle, Hybrid Diphosphorus Ligands
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Effective and modular synthetic approaches toward phosphine-phosphite ligands and phosphine-phosphonite ligands featuring a diphenyl ether backbone have been developed. The phosphine-phosphite ligands are obtained by a two-step protocol from 2-bromo-2′-methoxydiphenyl ether. The phosphine-phosphonite ligands are prepared in a four-step synthetic protocol that involves a novel, unsymmetrical diphenyl ether derived phosphine-phosphorusdiamide as key building block. Structural studies on PtII complexes with either phosphine-phosphite or phosphine-phosphonite ligands indicate strict cis coordination for these ligand systems. High-pressure NMR spectroscopy studies of Rh complexes under syngas indicate the presence of two ea isomers for Rh(H)(CO)2(PP). The existence of this mixture is further supported by high-pressure IR spectroscopy studies. In order to benchmark the activity and selectivity of these novel, wide-bite-angle, mixed-donor ligands, they were screened in Pd-catalyzed asymmetric allylic alkylation as well as Rh-catalyzed hydrogenation and hydroformylation reactions. The ligands give 100-% conversion and low-to-moderate enantioselectivity in the allylic alkylation of 1,3-diphenyl-2-propenyl acetate and cyclohexyl-2-enyl acetate with dimethyl malonate. In the hydroformylation of styrene, good conversion and regioselectivities are achieved but only moderate enantioselectivity. The ligands give good conversions in asymmetric hydrogenation of typical substrates, with good-to-excellent enantioselectivities of up to 97-% depending on the substrate. Copyright
- Czauderna, Christine Fee,Cordes, David B.,Slawin, Alexandra M. Z.,Müller, Christian,Van Der Vlugt, Jarl Ivar,Vogt, Dieter,Kamer, Paul C. J.
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p. 1797 - 1810
(2014/04/17)
-
- Synthesis and reactivity of chiral, wide-bite-angle, hybrid diphosphorus ligands
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Effective and modular synthetic approaches toward phosphine-phosphite ligands and phosphine-phosphonite ligands featuring a diphenyl ether backbone have been developed. The phosphine-phosphite ligands are obtained by a two-step protocol from 2-bromo-2′-methoxydiphenyl ether. The phosphine-phosphonite ligands are prepared in a four-step synthetic protocol that involves a novel, unsymmetrical diphenyl ether derived phosphine-phosphorusdiamide as key building block. Structural studies on PtII complexes with either phosphine-phosphite or phosphine-phosphonite ligands indicate strict cis coordination for these ligand systems. High-pressure NMR spectroscopy studies of Rh complexes under syngas indicate the presence of two ea isomers for Rh(H)(CO)2(PP). The existence of this mixture is further supported by high-pressure IR spectroscopy studies. In order to benchmark the activity and selectivity of these novel, wide-bite-angle, mixed-donor ligands, they were screened in Pd-catalyzed asymmetric allylic alkylation as well as Rh-catalyzed hydrogenation and hydroformylation reactions. The ligands give 100-% conversion and low-to-moderate enantioselectivity in the allylic alkylation of 1,3-diphenyl-2-propenyl acetate and cyclohexyl-2-enyl acetate with dimethyl malonate. In the hydroformylation of styrene, good conversion and regioselectivities are achieved but only moderate enantioselectivity. The ligands give good conversions in asymmetric hydrogenation of typical substrates, with good-to-excellent enantioselectivities of up to 97-% depending on the substrate. The design of two subclasses of chiral, mixed-donor diphosphorus ligands with a diphenylether backbone is described. Both phosphine-phosphonite and phosphine-phosphite derivatives are accessible. Coordination to PtII and RhI is described, and high-pressure spectroscopy under syngas provides information on coordination geometry. The chiral ligand systems are benchmarked in Pd-catalyzed allylic alkylation and Rh-catalyzed hydrogenation and hydroformylation.
- Czauderna, Christine Fee,Cordes, David B.,Slawin, Alexandra M. Z.,Müller, Christian,Van Der Vlugt, Jarl Ivar,Vogt, Dieter,Kamer, Paul C. J.
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p. 1797 - 1810
(2015/04/27)
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- Oxidative damage of aromatic dipeptides by the environmental oxidants NO2 and O3
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Irreversible oxidative damage at both aromatic side chains and dipeptide linkage occurs in the aromatic N- and C-protected dipeptides 7-11 upon exposure to the environmental pollutants NO2 and O3. The reaction proceeds through initial oxidation of the aromatic ring by in situ generated NO3, or by NO2, respectively, which leads to formation of nitroaromatic products. The indole ring in Phe-Trp undergoes oxidative cyclization to a pyrroloindoline. An important reaction pathway for dipeptides with less oxidisable aromatic side chains proceeds through fragmentation of the peptide bond with concomitant acyl migration. This process is likely initiated by an ionic reaction of the amide nitrogen with the NO2 dimer, N2O4. This journal is
- Gamon,White,Wille
-
supporting information
p. 8280 - 8287
(2015/01/08)
-
- An eco-benign and highly efficient procedure for N-acylation catalyzed by heteropolyanion-based ionic liquids using carboxylic acid under solvent-free conditions
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An eco-benign and highly efficient route for N-acylation of amines has been developed by treating amines with corresponding carboxylic acids in the presence of 2 mol % of heteropolyanion-based ionic liquids as catalysts under solvent-free conditions. This practical reaction could tolerate a wide range of substrates. Thus, various N-acylation products including N-acyl α-amino acid derivatives were obtained in moderate to excellent yields at 70 C to 120 C. Moreover, recycling studies revealed that heteropolyanion-based ionic liquids were easily reusable for this N-acylation. This method provides a green and much improved protocol over the existing methods.
- Chen, Zhikai,Fu, Renzhong,Chai, Wen,Zheng, Hao,Sun, Lin,Lu, Qiang,Yuan, Rongxin
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p. 2237 - 2245
(2014/03/21)
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- Asymmetric synthesis of unnatural amino acids and tamsulosin chiral intermediate
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An efficient and enantioselective hydrogenation of N-acetylamino phenyl acrylic acids was successfully developed by using ruthenium catalyst. This methodology is important in the field of pharmaceuticals and provides a new process for the preparation of unnatural amino acids and tamsulosin chiral intermediate.
- Arava, Veera Reddy,Amasa, Srinivasulu Reddy,Goud Bhatthula, Bharat Kumar,Kompella, Laxmi Srinivas,Matta, Venkata Prasad,Subha
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p. 2892 - 2897
(2013/09/02)
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- Pyridinylquinazolines selectively inhibit human methionine aminopeptidase-1 in cells
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Methionine aminopeptidases (MetAPs), which remove the initiator methionine from nascent peptides, are essential in all organisms. While MetAP2 has been demonstrated to be a therapeutic target for inhibiting angiogenesis in mammals, MetAP1 seems to be vital for cell proliferation. Our earlier efforts identified two structural classes of human MetAP1 (HsMetAP1)-selective inhibitors (1-4), but all of them failed to inhibit cellular HsMetAP1. Using Mn(II) or Zn(II) to activate HsMetAP1, we found that 1-4 could only effectively inhibit purified HsMetAP1 in the presence of physiologically unachievable concentrations of Co(II). In an effort to seek Co(II)-independent inhibitors, a novel structural class containing a 2-(pyridin-2-yl)quinazoline core has been discovered. Many compounds in this class potently and selectively inhibited HsMetAP1 without Co(II). Subsequently, we demonstrated that 11j, an auxiliary metal-dependent inhibitor, effectively inhibited HsMetAP1 in primary cells. This is the first report that an HsMetAP1-selective inhibitor is effective against its target in cells.
- Zhang, Feiran,Bhat, Shridhar,Gabelli, Sandra B.,Chen, Xiaochun,Miller, Michelle S.,Nacev, Benjamin A.,Cheng, Yim Ling,Meyers, David J.,Tenney, Karen,Shim, Joong Sup,Crews, Phillip,Amzel, L. Mario,Ma, Dawei,Liu, Jun O.
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p. 3996 - 4016
(2013/07/19)
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- Pd and Ru complexes bearing axially chiral ligands for the asymmetric hydrogenation of C=C and C=O double bonds
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Complexes composed of either Pd or Ru as central metal and ligands with axial chirality in all cases were used as hydrogenation catalysts. The ligands were (R)- and (S)-6,6′-dimethyl-2,2′-diaminobiphenyl, (R)-(+)-1-1′-Bi(2-naphtylamine), (R)-2,2′-Bis(diphenylphosphino)-1, 1′-binaphthalene and (R)-2,2′-Bis(di-p-tolylphosphino)-1,1′- binaphthyl. The Pd(II) complexes had one diamine ligand and the Ru(II) complexes had one bisphosphine and one diamine ligand, forming seven member chelate rings with the metal center. The pro-chiral substrates used were itaconic acid, α-acetamidocinnamic acid and acetophenone. The Pd complexes showed 100% chemoselectivity toward the CC bond, and toward the CO bond in the case of Ru. The yield and enantiomeric excess versus time behavior was studied using a large substrate/catalyst ratio. The addition of an organic base to the reaction with Pd complexes enhanced yield and enantiomeric excess. Use of the (S)-diamine ligand in the complex favored the (R)-products. The best results with itaconic acid were 61% yield and 56% enantiomeric excess and 55% yield and 52% enantiomeric excess with α-acetamidocinnamic acid, both catalyzed by Pd(OCOCF3)2 ((S)-6,6′-dimethyl-2,2′- diaminobiphenyl) in 2,2,2-trifluoroethanol. In the case of the Ru catalysts, (S)-1-phenylethanol formed preferentially during hydrogenation of acetophenone. Potassium tert-butoxide stabilized the enantiomeric excess. The best result was 87% yield and 41% enantiomeric excess catalyzed by ((R)-2,2′-Bis(di-p- tolylphosphino)-1,1′-binaphthyl)-RuCl2-((R)-(+)-1-1′- Bi(2-naphtylamine)).
- Rivera, Victor M.,Ruelas-Leyva, J. Pablo,Fuentes, Gustavo A.
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p. 109 - 114
(2013/08/23)
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- A NOVEL PROCESS FOR THE PREPARATION OF SITAGLIPTIN
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The present invention is directed to a process for the preparation of enantiomerically enriched β-amino acid derivatives which are important chiral building blocks and intermediates in pharmaceuticals. More specifically, the invention pertains to a novel process for practically convenient and economically producing enantiomerically enriched β-amino acid derivatives which are useful for the synthesis of amide inhibitors of dipeptidyl peptidase IV like Sitagliptin, which have been used to treat type 2 diabetes.
- -
-
Page/Page column 30
(2013/08/15)
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- Bortezomib congeners induce apoptosis of hepatocellular carcinoma via CIP2A inhibition
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CIP2A is an oncoprotein that upregulates p-Akt and promotes cancer cell proliferation and survival. The proteasome inhibitor bortezomib has been shown to reduce CIP2A and lead to cell apoptosis. Here; we modified the functional group of bortezomib to generate a series of novel compounds and conducted a structure-activity relationship (SAR) study. The results showed that compound 1 was able to repress CIP2A expression and cell apoptosis in the same manner as bortezomib, but with less potency in inhibition of proteasome activity. This finding provides a new direction for the design of CIP2A inhibitors.
- Hou, Duen-Ren,Huang, Ann-Chi,Shiau, Chung-Wai,Wang, Chun-Yi,Yu, Hui-Chuan,Chen, Kuen-Feng
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p. 15398 - 15411
(2014/01/17)
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- Thioacids mediated selective and mild N-acylation of amines
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N-Acylated amines are ubiquitous in nature. Selective N-acylation at neutral conditions remains a key area of interest. Here we are reporting the copper sulfate-mediated highly selective, mild, and rapid N-acylation of various aliphatic and aromatic amines using thioacids in methanol at neutral conditions. All N-acylated products of primary and secondary amines were isolated in good to excellent yields. This method is found to be highly selective for the amines and not sensitive to other functional groups such as phenols, alcohols, and thiols. The simple workup, high yields, and high selectivity of this reaction can be an attractive alternative to those of the existing acyl halide- and acid anhydride-mediated N-acylation reactions.
- Mali, Sachitanand M.,Bhaisare, Rupal D.,Gopi, Hosahudya N.
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p. 5550 - 5555
(2013/07/25)
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- Asymmetric hydrogenation of C=C double bonds using Rh-complex under homogeneous, heterogeneous and continuous mode conditions
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A green process for enantioselective hydrogenation of dehydroamino acid derivatives and dimethyl itaconate with a rhodium catalyst modified by a new phosphine-phosphoramidite has been developed providing 97.7-99.8% enantioselectivity in green solvents such as ethylene carbonate and propylene carbonate. The l-DOPA precursor was obtained by simple filtration in 71% yield with 99.5% ee. Dimethyl itaconate was hydrogenated under solvent-free condition at 50 °C with 98.7% ee. The new rhodium complex was heterogenized on a mesoporous Al2O3 support using phosphotungstic acid (PTA) as an anchoring agent and tested in heterogeneous batch and flow reaction modes. The supported catalyst was reused eight times in the batch mode with over 97% ee and used over 12 hours in the flow reaction mode with an average of 97% ee in the asymmetric hydrogenation reaction of (Z)-α-acetamidocinnamic acid methyl ester.
- Balogh, Szabolcs,Farkas, Gergely,Madarasz, Jozsef,Szoellsy, Aron,Kovacs, Jozsef,Darvas, Ferenc,Uerge, Laszlo,Bakos, Jozsef
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supporting information; experimental part
p. 1146 - 1151
(2012/06/18)
-
- Self-assembly and nonlinear optical properties of a synthetic dipeptide
-
The self-assembly propensities and nonlinear optical properties of synthetic dipeptides are illustrated. The single crystal X-ray diffraction study of dipeptide 1 containing a p-nitrophenylalanine moiety reveals that the peptide adopts a supramolecular antiparallel β-sheet structure using hydrogen bonding, as well as π-π stacking interactions, in the solid state and the peptide exhibits nonlocal thermal nonlinear refraction due to the thermal lensing effect. The heat dissipation in the dipeptide 1 was a slow process with a millisecond to microsecond time scale. However the peptide 2 containing a p-nitrophenylacetic acid moiety adopts a parallel β-sheet structure and has no thermal lensing effect.
- Maity, Suman Kumar,Kumar, Ravi,Ambast, Deepak K. S.,Pal, Bipul,Haldar, Debasish
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supporting information
p. 22198 - 22203
(2013/01/15)
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- Chemoenzymatic synthesis of a mixed phosphine-phosphine oxide catalyst and its application to asymmetric allylation of aldehydes and hydrogenation of alkenes
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The chemoenzymatic synthesis of a Lewis basic phosphine-phosphine oxide organocatalyst from a cis-dihydrodiol metabolite of bromobenzene proceeds via a palladium-catalysed carbon-phosphorus bond coupling and a novel room temperature Arbuzov [2,3]-sigmatropic rearrangement of an allylic diphenylphosphinite. Allylation of aromatic aldehydes were catalysed by the Lewis basic organocatalyst giving homoallylic alcohols in up to 57% ee. This compound also functioned as a ligand for rhodium-catalysed asymmetric hydrogenation of acetamidoacrylate giving reduction products with ee values of up to 84%.
- Boyd, Derek R.,Bell, Mark,Dunne, Katherine S.,Kelly, Brian,Stevenson, Paul J.,Malone, John F.,Allen, Christopher C. R.
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experimental part
p. 1388 - 1395
(2012/03/27)
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- Synthesis of Binol-based diphosphinites bearing chiral phospholane units and their application in asymmetric catalysis
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New diphosphinite ligands based on atropoisomeric diol backbones and (R,R)-2,5-dimethylphospholane moieties have been prepared and fully characterised. For each ligand structure, both diastereomers have been synthesised. These ligands are available through a straightforward procedure in good yields. The solid state structures of two diastereomeric ligands are reported. These ligands have been applied to Rh-catalysed asymmetric hydrogenations and hydroformylations of CC bonds as well as in Ir-catalysed asymmetric hydrogenations of CN bonds. Turnover frequencies in the range of 10,000 h-1 and enantioselectivities of up to 98% ee have been achieved. The different chirality elements within the ligands led to marked cooperative effect in catalysis. Interestingly, there is no general privileged diastereomeric structure but rather a matched diastereomer for each application.
- Hammerer, Tim,Weisgerber, Laurent,Schenk, Stefan,Stelzer, Othmar,Englert, Ulli,Leitner, Walter,Franci, Giancarlo
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experimental part
p. 53 - 59
(2012/05/20)
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- Synthesis of novel chiral monophosphine ligands derived from isomannide and isosorbide. Application to enantioselective hydrogenation of olefins
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A new class of monophosphine ligands has been prepared from natural chirality renewable source, 1,4:3,6-dianhydrohexitol compounds, via a nucleophilic substitution process, or a hydrophosphination reaction involving microwave activation. These ligands have been evaluated for the rhodium-catalyzed enantioselective hydrogenation of olefins giving good conversion and enantioselectivity up to 95% and 96% ee, respectively.
- Ibrahim, Houssein,Bournaud, Chloée,Guillot, Régis,Toffano, Martial,Vo-Thanh, Giang
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scheme or table
p. 4900 - 4902
(2012/09/21)
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- Facile synthesis of chiral diphosphine-containing multiple dendrimeric catalysts for enantioselective hydrogenation
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A new kind of chiral diphosphine PyrPhos-functionalized codendrimers have been synthesized via a liquid-phase strategy in high yields. The resulting dendrimeric PyrPhos ligands were purified by a simple solvent precipitation without the need for chromatographic separation, and well characterized by 1H, 13C and 31P NMR, MALDI-TOF mass spectroscopy as well as elemental analysis. Their rhodium complexes were applied to the asymmetric hydrogenation of α-acetamido cinnamic acids. Excellent enantioselectivities were achieved, which are comparable to those with the corresponding small molecular catalysts. In addition, these codendrimeric catalysts showed better catalytic performance than the dendrimeric catalysts with Rh(PyrPhos) sites located in the focal point of poly(aryl ether) dendrons or in the periphery of poly(propyleneimine) dendrimers.
- Zhao, Liwen,Liu, Ji,Feng, Yu,He, Yanmei,Fan, Qinghua
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p. 2009 - 2015,7
(2020/09/09)
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- Protease activation in glycerol-based deep eutectic solvents
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Deep eutectic solvents (DESs) consisting of mixtures of a choline salt (chloride or acetate form) and glycerol are prepared as easily accessible, biodegradable, and inexpensive alternatives to conventional aprotic cation-anion paired ionic liquids. These DES systems display excellent fluidity coupled with thermal stability to nearly 200 °C. In this work, the transesterification activities of cross-linked proteases (subtilisin and α-chymotrypsin), immobilized on chitosan, were individually examined in these novel DESs. In the 1:2 molar ratio mixture of choline chloride/glycerol containing 3% (v/v) water, cross-linked subtilisin exhibited an excellent activity (2.9 μmol min -1 g-1) in conjunction with a selectivity of 98% in the transesterification reaction of N-acetyl-l-phenylalanine ethyl ester with 1-propanol. These highly encouraging results advocate more extensive exploration of DESs in protease-mediated biotransformations of additional polar substrates and use of DESs in biocatalysis more generally.
- Zhao, Hua,Baker, Gary A.,Holmes, Shaletha
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experimental part
p. 163 - 167
(2012/07/01)
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- Ferrocenyl-aryl based trans-chelating diphosphine ligands: Synthesis, molecular structure and application in enantioselective hydrogenation
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Potentially trans-chelating diphosphine ligands based on a ferrocenyl-aryl backbone were synthesised in a four-step sequence and the molecular structures in the solid state of two representatives were determined by X-ray diffraction. High throughput screening of these ligands in rhodium-, ruthenium- and iridium-mediated hydrogenations of a variety of alkenes and ketones revealed that these ligands can deliver high enantioselectivity for alkenes (up to 98% ee) but are less selective when ketones are used as the substrates. The coordination behaviour of one ligand in its square planar palladium and platinum dichloride complexes was studied by 31P NMR and only trans-chelated complexes, together with oligomeric by-products, were observed. Reaction with the (p-cymene)ruthenium dichloride dimer, [RuCl2(pcymene)] 2, resulted in a mixture of diastereomeric complexes.
- Schuecker, Raffael,Mereiter, Kurt,Spindler, Felix,Weissensteiner, Walter
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scheme or table
p. 1063 - 1074
(2010/06/17)
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- Soluble, folded and active subtilisin in a protic ionic liquid
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The activity of proteases chymotrypsin and subtilisin dissolved in a range of protic hydroxylalkylammonium ionic liquids was tested against the model substrate APEE (N-acetyl-l-phenylalanine ethyl ester); activity was only observed for subtilisin in diethanolammonium chloride (DEA Cl), while chymotrypsin was not active in any PIL tested.
- Falcioni, Francesco,Housden, Hazel R.,Ling, Zhenlian,Shimizu, Seishi,Walker, Adam J.,Bruce, Neil C.
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supporting information; experimental part
p. 749 - 751
(2010/06/12)
-
- Resolution of N-protected amino acid esters using whole cells of Candida parapsilosis ATCC 7330
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Whole cells of Candida parapsilosis ATCC 7330 were used for the resolution of N-acetyl amino acid esters. Excellent enantioselectivities (E = 40 to >500) were achieved for the resolution of N-protected protein and non-protein amino acid esters giving good yields (28-50%) and high enantiomeric excesses (up to >99%) for both enantiomers.
- Stella, Selvaraj,Chadha, Anju
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experimental part
p. 457 - 460
(2010/06/21)
-
- Novel and efficient chiral bisphosphorus ligands for rhodium-catalyzed asymmetric hydrogenation
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(Figure Presented) A series of structurally novel, operationally convenient, and efficient chiral 2-phosphino-2,3-dihydrobenzo[d][1,3] oxaphosphole ligands was developed. Applications of ligands 3a and 3b in rhodium-catalyzed asymmetric hydrogenation of α-(acylamlno)acrylates andβ-(acylamino)acrylates provided excellent enantioselectivities (up to >99% ee) and reactivities (up to 10 000 TON).
- Tang, Wenjun,Capacci, Andrew G.,White, Andre,Ma, Shengli,Rodriguez, Sonia,Qu, Bo,Savoie, Jolaine,Patel, Nitinchandra D.,Wei, Xudong,Haddad, Nizar,Grinberg, Nelu,Yee, Nathan K.,Krishnamurthy, Dhileepkumar,Senanayake, Chris H.
-
supporting information; experimental part
p. 1104 - 1107
(2010/06/13)
-
- Quinaphos and dihydro-quinaphos phosphine-phosphoramidite ligands for asymmetric hydrogenation
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New derivatives of the Quinaphos ligands and the related Dihydro-Quinaphos ligands based on the more flexible 1,2,3,4-tetrahydroquinoline backbone have been prepared and fully characterised. A general and straightforward separation protocol was devised, which allowed for the gram-scale isolation of the R a,Sc and Sa,Rc diastereomers. These new phos-phine-phosphoramidite ligands have been applied in the Rh-catalysed asymmetric hydrogenation of functionalised olefins with the achievement of excel-lent enantioselectivities (≥99%) in most cases and turnover frequency (TOF) values of up to ≥ 20000 h-1. These results substantiate the practical utility of readily accessible Quinaphostype ligands, which belong to the most active and selective category of ligands for Rh-catalysed hydrogenation known to date.
- Pullmann, Thomas,Engendahl, Barthel,Zhang, Ziyun,Hoelscher, Markus,Zanotti-Gerosa, Antonio,Dyke, Alan,Francio, Giancarlo,Leitner, Walter
-
experimental part
p. 7517 - 7526
(2010/10/04)
-
- Synthesis and application of peripherally alkyl-functionalized dendritic pyrphos ligands: Homogeneous-supported catalysts for enantioselective hydrogenation
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A new series of dendritic ligands with a chiral diphosphine located at the focal point have been synthesized through coupling of (R,R)-3,4-bis(biphenylphosphino)pyrrolidine (pyrphos) with peripherally alkyl-functionalized benzoic acid dendrons. These ligands were employed in the Rh-catalyzed asymmetric hydrogenation of prochiral dehydroamino acids, exhibiting excellent catalytic activities and enantioselectivities. The second-generation dendritic catalyst could be recovered by simple liquid-liquid biphasic separation and reused four times without serious loss of its activity and selectivity.
- Yi, Bing,He, Hua-Ping,Fan, Qing-Hua
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experimental part
p. 82 - 85
(2010/04/25)
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- Electron-donating and rigid p-stereogenic bisphospholane ligands for highly enantioselective rhodium-catalyzed asymmetric hydrogenations
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More electron donating, more rigid: A new highly electron-donating P-stereogenic bisphospholane ligand (ZhangPhos) was synthesized in a practical and highly enantioselective manner from a commercially available chiral source. Better or comparable enantioselectivities and reactivities than TangPhos were achieved in rhodium-catalyzed hydrogenation of various functionalized olefins (see scheme; nbd=3,5-norbornadiene). Copyright
- Zhang, Xiaowei,Huang, Kexuan,Hou, Guohua,Cao, Bonan,Zhang, Xumu
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supporting information; experimental part
p. 6421 - 6424
(2010/12/19)
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