Epoxidation catalyst and process

DOEpatents

Linic, Suljo; Christopher, Phillip

2010-10-26

Disclosed herein is a catalytic method of converting alkenes to epoxides. This method generally includes reacting alkenes with oxygen in the presence of a specific silver catalyst under conditions suitable to produce a yield of the epoxides. The specific silver catalyst is a silver nanocrystal having a plurality of surface planes, a substantial portion of which is defined by Miller indices of (100). The reaction is performed by charging a suitable reactor with this silver catalyst and then feeding the reactants to the reactor under conditions to carry out the reaction. The reaction may be performed in batch, or as a continuous process that employs a recycle of any unreacted alkenes. The specific silver catalyst has unexpectedly high selectivity for epoxide products. Consequently, this general method (and its various embodiments) will result in extraordinarily high epoxide yields heretofore unattainable.

The first chiral diene-based metal-organic frameworks for highly enantioselective carbon-carbon bond formation reactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sawano, Takahiro; Ji, Pengfei; McIsaac, Alexandra R.

2016-02-01

We have designed the first chiral diene-based metal–organic framework (MOF), E₂-MOF, and postsynthetically metalated E₂-MOF with Rh(I) complexes to afford highly active and enantioselective single-site solid catalysts for C–C bond formation reactions. Treatment of E₂-MOF with [RhCl(C₂H₄)₂]₂ led to a highly enantioselective catalyst for 1,4-additions of arylboronic acids to α,β-unsaturated ketones, whereas treatment of E₂-MOF with Rh(acac)(C₂H₄)₂ afforded a highly efficient catalyst for the asymmetric 1,2-additions of arylboronic acids to aldimines. Interestingly, E₂-MOF·Rh(acac) showed higher activity and enantioselectivity than the homogeneous control catalyst, likely due to the formation of a true single-site catalyst in the MOF. E₂-MOF·Rh(acac) was also successfullymore » recycled and reused at least seven times without loss of yield and enantioselectivity.« less

Determinants of reactivity and selectivity in soluble epoxide hydrolase from quantum mechanics/molecular mechanics modeling.

PubMed

Lonsdale, Richard; Hoyle, Simon; Grey, Daniel T; Ridder, Lars; Mulholland, Adrian J

2012-02-28

Soluble epoxide hydrolase (sEH) is an enzyme involved in drug metabolism that catalyzes the hydrolysis of epoxides to form their corresponding diols. sEH has a broad substrate range and shows high regio- and enantioselectivity for nucleophilic ring opening by Asp333. Epoxide hydrolases therefore have potential synthetic applications. We have used combined quantum mechanics/molecular mechanics (QM/MM) umbrella sampling molecular dynamics (MD) simulations (at the AM1/CHARMM22 level) and high-level ab initio (SCS-MP2) QM/MM calculations to analyze the reactions, and determinants of selectivity, for two substrates: trans-stilbene oxide (t-SO) and trans-diphenylpropene oxide (t-DPPO). The calculated free energy barriers from the QM/MM (AM1/CHARMM22) umbrella sampling MD simulations show a lower barrier for phenyl attack in t-DPPO, compared with that for benzylic attack, in agreement with experiment. Activation barriers in agreement with experimental rate constants are obtained only with the highest level of QM theory (SCS-MP2) used. Our results show that the selectivity of the ring-opening reaction is influenced by several factors, including proximity to the nucleophile, electronic stabilization of the transition state, and hydrogen bonding to two active site tyrosine residues. The protonation state of His523 during nucleophilic attack has also been investigated, and our results show that the protonated form is most consistent with experimental findings. The work presented here illustrates how determinants of selectivity can be identified from QM/MM simulations. These insights may also provide useful information for the design of novel catalysts for use in the synthesis of enantiopure compounds.

Cooperative dual catalysis: application to the highly enantioselective conjugate cyanation of unsaturated imides.

PubMed

Sammis, Glenn M; Danjo, Hiroshi; Jacobsen, Eric N

2004-08-18

Cooperative heterobimetallic catalysis was used as a design principle to achieve a highly reactive system for the enantioselective conjugate addition of cyanide to alpha,beta-unsaturated imides. A dual-catalyst pathway involving chiral (salen)Al complex 1b and chiral (pybox)Er complex 4b provides measurable improvements in rates and enantioselectivities relative to single-catalyst systems. Mechanistic studies point to a cooperative bimetallic mechanism involving activation of the imide by the Al complex and activation of cyanide by the Er complex.

Assignment of the relative and absolute stereochemistry of two novel epoxides using NMR and DFT-GIAO calculations

NASA Astrophysics Data System (ADS)

Moraes, F. C.; Alvarenga, E. S.; Demuner, A. J.; Viana, V. M.

2018-07-01

Considering the potential biological application of isobenzofuranones, especially as agrochemical defensives, two novel epoxides, (1aR,2R,2aR,5S,5aS,6S,6aS)-5-(hydroxymethyl)hexahydro-2,6-methanooxireno[2,3-f]isobenzofuran-3(1aH)-one (9), and (1aS,2S,2aR,5S,5aS,6R,6aR)-5-(hydroxymethyl)hexahydro-2,6-methanooxireno[2,3-f]isobenzofuran-3(1aH)-one (10), were synthesized from the readily available D-mannitol in six steps. The multiplicities of the hydrogens located at the bridge of the bicycle are distinct for epoxides 9 and 10 due to W coupling, and this feature was employed to confirm the assignment of these nuclei. Besides analyses of the 2D NMR spectra, the assignments of the nuclei at the epoxide ring were also inferred from information obtained by theoretical calculations. The calculated 1H and 13C NMR chemical shifts for eight candidate structures were compared with the experimental chemical shifts of 9 and 10 by measuring the mean absolute errors (MAE) and by the DP4 statistical analysis. The structures and relative configurations of 9, and 10 were determined via NMR spectroscopy assisted with theoretical calculations. As consequence of the enantioselective syntheses starting from a natural polyol, the absolute configurations of the epoxides 9 and 10 were also defined.

Molecular Bases of Enantioselectivity of Haloalkane Dehalogenase DbjA

NASA Astrophysics Data System (ADS)

Sato, Yukari; Natsume, Ryo; Prokop, Zbynek; Brezovsky, Jan; Chaloupkova, Radka; Damborsky, Jiri; Nagata, Yuji; Senda, Toshiya

Enzymes are widely used for the synthesis of pharmaceuticals, agrochemicals, and food additives because they can catalyze high enantioselective transformations. In order to construct selective enzymes by protein engineering, it is important to understand the molecular basis of enzyme-substrate interactions that contribute to enantioselectivity. The haloalkane dehalogenase DbjA showed high enantioselectivity for two racemic mixtures: α-bromoesters and β-bromoalkanes. Thermodynamic analysis, protein crystallography, and computer simulations indicated that DbjA carries two bases for the enantiodiscrimination of each racemic mixture. This study helps us understand the molecular basis of the enantioselectivity and opens up new possibilities for constructing enantiospecific biocatalysts through protein engineering.

Mechanistic Basis for High Reactivity of (salen)Co–OTs in the Hydrolytic Kinetic Resolution of Terminal Epoxides

PubMed Central

Nielsen, Lars P. C.; Zuend, Stephan J.; Ford, David D.; Jacobsen, Eric N.

2012-01-01

The (salen)Co(III)-catalyzed hydrolytic kinetic resolution (HKR) of terminal epoxides is a bimetallic process with a rate controlled by partitioning between a nucleophilic (salen)Co–OH catalyst and a Lewis acidic (salen)Co–X catalyst. The commonly used (salen)Co–OAc and (salen)Co–Cl precatalysts undergo complete and irreversible counterion addition to epoxide during the course of the epoxide hydrolysis reaction, resulting in quantitative formation of weakly Lewis acidic (salen)Co–OH, and severely diminished reaction rates in the late stages of HKR reactions. In contrast, (salen)Co–OTs maintains high reactivity over the entire course of HKR reactions. We describe here an investigation of catalyst partitioning with different (salen)Co–X precatalysts, and demonstrate that counterion addition to epoxide is reversible in the case of the (salen)Co–OTs. This reversible counterion addition results in stable partitioning between nucleophilic and Lewis acidic catalyst species, allowing highly efficient catalysis throughout the course of the HKR reaction. PMID:22292515

Mechanistic basis for high reactivity of (salen)Co-OTs in the hydrolytic kinetic resolution of terminal epoxides.

PubMed

Nielsen, Lars P C; Zuend, Stephan J; Ford, David D; Jacobsen, Eric N

2012-03-02

The (salen)Co(III)-catalyzed hydrolytic kinetic resolution (HKR) of terminal epoxides is a bimetallic process with a rate controlled by partitioning between a nucleophilic (salen)Co-OH catalyst and a Lewis acidic (salen)Co-X catalyst. The commonly used (salen)Co-OAc and (salen)Co-Cl precatalysts undergo complete and irreversible counterion addition to epoxide during the course of the epoxide hydrolysis reaction, resulting in quantitative formation of weakly Lewis acidic (salen)Co-OH and severely diminished reaction rates in the late stages of HKR reactions. In contrast, (salen)Co-OTs maintains high reactivity over the entire course of HKR reactions. We describe here an investigation of catalyst partitioning with different (salen)Co-X precatalysts and demonstrate that counterion addition to epoxide is reversible in the case of the (salen)Co-OTs. This reversible counterion addition results in stable partitioning between nucleophilic and Lewis acidic catalyst species, allowing highly efficient catalysis throughout the course of the HKR reaction.

Zeaxanthin epoxidation - an in vitro approach.

PubMed

Kuczyńska, Paulina; Latowski, Dariusz; Niczyporuk, Sylvia; Olchawa-Pajor, Monika; Jahns, Peter; Gruszecki, Wiesław I; Strzałka, Kazimierz

2012-01-01

Zeaxanthin epoxidase (ZE) is an enzyme operating in the violaxanthin cycle, which is involved in photoprotective mechanisms. In this work model systems to study zeaxanthin (Zx) epoxidation were developed. Two assay systems are presented in which epoxidation of Zx was observed. In these assays two mutants of Arabidopsis thaliana which have active only one of the two xanthophyll cycle enzymes were used. The npq1 mutant possesses an active ZE and is thus able to convert Zx to violaxanthin (Vx) but the violaxanthin de-epoxidase (VDE) is inactive, so that Vx cannot be converted to Zx. The other mutant, npq2, possesses an active VDE and can convert exogenous Vx to Zx under strong light conditions but reverse reaction is not possible. The first assay containing thylakoids from npq1 and npq2 mutants of A. thaliana gave positive results and high efficiency of epoxidation reaction was observed. The amount of Zx was reduced by 25%. To optimize high efficiency of epoxidation reaction additional factors facilitating both fusion of the two types of thylakoids and incorporation of Zx to their membranes were also studied. The second kind of assay contained npq1 mutant thylakoids of A. thaliana supplemented with exogenous Zx and monogalactosyldiacylglycerol (MGDG). Experiments with different proportions of Zx and MGDG showed that their optimal ratio is 1:60. In such system, due to epoxidation, the amount of Zx was reduced by 38% of its initial level. The in vitro systems of Zx epoxidation described in this paper enable analysis some properties of the ZE without necessity of its isolation.

An enantioselective enzymatic desymmetrization route to hexahydro-4H-furopyranol, a high-affinity ligand for HIV-1 protease inhibitors.

PubMed

Ghosh, Arun K; Sarkar, Anindya

2017-08-16

An enantioselective synthesis of ( 3 a S , 4S , 7 a R )-hexahydro-4 H -furo[2,3- b ]pyran-4-ol, a high-affinity nonpeptide ligand for a variety of potent HIV-1 protease inhibitors is described. The key steps involved a highly enantioselective enzymatic desymmetrization of meso -diacetate, an efficient transacetalization, and a highly diastereoselective reduction of a ketone. This route is amenable to large-scale synthesis using readily available starting materials.

Enzyme-catalyzed cationic epoxide rearrangements in quinolone alkaloid biosynthesis.

PubMed

Zou, Yi; Garcia-Borràs, Marc; Tang, Mancheng C; Hirayama, Yuichiro; Li, Dehai H; Li, Li; Watanabe, Kenji; Houk, K N; Tang, Yi

2017-03-01

Epoxides are highly useful synthons and biosynthons for the construction of complex natural products during total synthesis and biosynthesis, respectively. Among enzyme-catalyzed epoxide transformations, a reaction that is notably missing, in regard to the synthetic toolbox, is cationic rearrangement that takes place under strong acid. This is a challenging transformation for enzyme catalysis, as stabilization of the carbocation intermediate upon epoxide cleavage is required. Here, we discovered two Brønsted acid enzymes that can catalyze two unprecedented epoxide transformations in biology. PenF from the penigequinolone pathway catalyzes a cationic epoxide rearrangement under physiological conditions to generate a quaternary carbon center, while AsqO from the aspoquinolone pathway catalyzes a 3-exo-tet cyclization to forge a cyclopropane-tetrahydrofuran ring system. The discovery of these new epoxide-modifying enzymes further highlights the versatility of epoxides in complexity generation during natural product biosynthesis.

General Catalytic Enantioselective Access to Monohalomethyl and Trifluoromethyl Cyclopropanes.

PubMed

Huang, Wei-Sheng; Schlinquer, Claire; Poisson, Thomas; Pannecoucke, Xavier; Charette, André B; Jubault, Philippe

2018-05-29

An efficient catalytic enantioselective access to chiral functionalized trifluoromethyl cyclopropanes from two classes of diazo compounds and alpha-trifluoromethyl styrenes using Rh2((S)-BTPCP)4 as a catalyst is described. This method provides an efficient and practical strategy for the synthesis of highly functionalized CF3-cyclopropanes with excellent diastereoselectivities (up to 20:1) and enantioselectivities (up to 99% ee). The depicted methodology represents up to date the most efficient catalytic enantioselective method to access highly decorated chiral CF3-cyclopropanes. Extension to chiral monohalomethyl cyclopropanes in high ee is also reported. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development of Catalysts and Ligands for Enantioselective Gold Catalysis

PubMed Central

Wang, Yi-Ming; Lackner, Aaron D.; Toste, F. Dean

2014-01-01

CONSPECTUS The use of Au(I) complexes for the catalytic activation of C-C π-bonds has been the subject of intense investigation in the last decade or so. The facile formation of carbon-carbon and carbon-heteroatom bonds facilitated by gold naturally led to efforts to render these transformations enantioselective. Early examples of enantioselective gold-catalyzed transformations have focused on bis(phosphinegold) complexes derived from axially chiral scaffolds. Although these complexes were highly successful in some reactions like cyclopropanation, careful choice of the weakly coordinating ligand (or counterion) was needed to obtain high levels of enantioselectivity for the case of allene hydroamination. These counterion effects led us to use the anion itself as a source of chirality, which was successful in the case of allene hydroalkoxylation. In order to expand the scope of reactions amenable to enantioselective gold catalysis to cycloadditions and other carbocyclization processes, a new class of mononuclear phosphite and phosphoramidite ligands was developed to supplement the previously widely utilized phosphines. Finally carbene ligands, in particular, the acyclic diaminocarbenes, have also been successfully applied to enantioselective transformations. PMID:24228794

Highly enantioselective organocatalytic oxidative kinetic resolution of secondary alcohols using chiral alkoxyamines as precatalysts: catalyst structure, active species, and substrate scope.

PubMed

Murakami, Keiichi; Sasano, Yusuke; Tomizawa, Masaki; Shibuya, Masatoshi; Kwon, Eunsang; Iwabuchi, Yoshiharu

2014-12-17

The development and characterization of enantioselective organocatalytic oxidative kinetic resolution (OKR) of racemic secondary alcohols using chiral alkoxyamines as precatalysts are described. A number of chiral alkoxyamines have been synthesized, and their structure-enantioselectivity correlation study in OKR has led us to identify a promising precatalyst, namely, 7-benzyl-3-n-butyl-4-oxa-5-azahomoadamantane, which affords various chiral aliphatic secondary alcohols (ee up to >99%, k(rel) up to 296). In a mechanistic study, chlorine-containing oxoammonium species were identified as the active species generated in situ from the alkoxyamine precatalyst, and it was revealed that the chlorine atom is crucial for high reactivity and enantioselectivity. The present OKR is the first successful example applicable to various unactivated aliphatic secondary alcohols, including heterocyclic alcohols with high enantioselectivity, the synthetic application of which is demonstrated by the synthesis of a bioactive compound.

Rhodium(II)-catalyzed enantioselective synthesis of troponoids.

PubMed

Murarka, Sandip; Jia, Zhi-Jun; Merten, Christian; Daniliuc, Constantin-G; Antonchick, Andrey P; Waldmann, Herbert

2015-06-22

We report a rhodium(II)-catalyzed highly enantioselective 1,3-dipolar cycloaddition reaction between the carbonyl moiety of tropone and carbonyl ylides to afford troponoids in good to high yields with excellent enantioselectivity. We demonstrate that α-diazoketone-derived carbonyl ylides, in contrast to carbonyl ylides derived from diazodiketoesters, undergo [6+3] cycloaddition reactions with tropone to yield the corresponding bridged heterocycles with excellent stereoselectivity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective Organocatalytic α-Fluorination of Cyclic Ketones

PubMed Central

Kwiatkowski, Piotr; Beeson, Teresa D.; Conrad, Jay C.

2011-01-01

The first highly enantioselective α-fluorination of ketones using organocatalysis has been accomplished. The long-standing problem of enantioselective ketone α-fluorination via enamine activation has been overcome via high-throughput evaluation of a new library of amine catalysts. The optimal system, a primary amine functionalized Cinchona alkaloid, allows the direct and asymmetric α-fluorination of a variety of carbo- and heterocyclic substrates. Furthermore, this protocol also provides diastereo-, regio- and chemoselective catalyst control in fluorinations involving complex carbonyl systems. PMID:21247133

Enantioselective Synthesis of α-Oxy Amides via Umpolung Amide Synthesis

PubMed Central

Leighty, Matthew W.; Shen, Bo

2012-01-01

α-Oxy amides are prepared through enantioselective synthesis using a sequence beginning with a Henry addition of bromonitromethane to aldehydes, and finishing with Umpolung Amide Synthesis (UmAS). Key to high enantioselection is the finding that ortho-iodo benzoic acid salts of the chiral copper(II) bis(oxazoline) catalyst deliver both diastereomers of the Henry adduct with high enantiomeric excess, homochiral at the oxygen-bearing carbon. Overall, this approach to α-oxy amides provides an innovative complement to alternatives that focus almost entirely on the enantioselective synthesis of α-oxy carboxylic acids. PMID:22967461

Enantioselective synthesis of α-oxy amides via Umpolung amide synthesis.

PubMed

Leighty, Matthew W; Shen, Bo; Johnston, Jeffrey N

2012-09-19

α-Oxy amides are prepared through enantioselective synthesis using a sequence beginning with a Henry addition of bromonitromethane to aldehydes and finishing with Umpolung Amide Synthesis (UmAS). Key to high enantioselection is the finding that ortho-iodo benzoic acid salts of the chiral copper(II) bis(oxazoline) catalyst deliver both diastereomers of the Henry adduct with high enantiomeric excess, homochiral at the oxygen-bearing carbon. Overall, this approach to α-oxy amides provides an innovative complement to alternatives that focus almost entirely on the enantioselective synthesis of α-oxy carboxylic acids.

Enantioselective cyclizations and cyclization cascades of samarium ketyl radicals

NASA Astrophysics Data System (ADS)

Kern, Nicolas; Plesniak, Mateusz P.; McDouall, Joseph J. W.; Procter, David J.

2017-12-01

The rapid generation of molecular complexity from simple starting materials is a key challenge in synthesis. Enantioselective radical cyclization cascades have the potential to deliver complex, densely packed, polycyclic architectures, with control of three-dimensional shape, in one step. Unfortunately, carrying out reactions with radicals in an enantiocontrolled fashion remains challenging due to their high reactivity. This is particularly the case for reactions of radicals generated using the classical reagent, SmI2. Here, we demonstrate that enantioselective SmI2-mediated radical cyclizations and cascades that exploit a simple, recyclable chiral ligand can convert symmetrical ketoesters to complex carbocyclic products bearing multiple stereocentres with high enantio- and diastereocontrol. A computational study has been used to probe the origin of the enantioselectivity. Our studies suggest that many processes that rely on SmI2 can be rendered enantioselective by the design of suitable ligands.

Transition-metal-free catalysts for the sustainable epoxidation of alkenes: from discovery to optimisation by means of high throughput experimentation.

PubMed

Lueangchaichaweng, Warunee; Geukens, Inge; Peeters, Annelies; Jarry, Benjamin; Launay, Franck; Bonardet, Jean-Luc; Jacobs, Pierre A; Pescarmona, Paolo P

2012-02-01

Transition-metal-free oxides were studied as heterogeneous catalysts for the sustainable epoxidation of alkenes with aqueous H₂O₂ by means of high throughput experimentation (HTE) techniques. A full-factorial HTE approach was applied in the various stages of the development of the catalysts: the synthesis of the materials, their screening as heterogeneous catalysts in liquid-phase epoxidation and the optimisation of the reaction conditions. Initially, the chemical composition of transition-metal-free oxides was screened, leading to the discovery of gallium oxide as a novel, active and selective epoxidation catalyst. On the basis of these results, the research line was continued with the study of structured porous aluminosilicates, gallosilicates and silica-gallia composites. In general, the gallium-based materials showed the best catalytic performances. This family of materials represents a promising class of heterogeneous catalysts for the sustainable epoxidation of alkenes and offers a valid alternative to the transition-metal heterogeneous catalysts commonly used in epoxidation. High throughput experimentation played an important role in promoting the development of these catalytic systems.

Enantioselective Protonation

PubMed Central

Mohr, Justin T.; Hong, Allen Y.; Stoltz, Brian M.

2010-01-01

Enantioselective protonation is a common process in biosynthetic sequences. The decarboxylase and esterase enzymes that effect this valuable transformation are able to control both the steric environment around the proton acceptor (typically an enolate) and the proton donor (typically a thiol). Recently, several chemical methods to achieve enantioselective protonation have been developed by exploiting various means of enantiocontrol in different mechanisms. These laboratory transformations have proven useful for the preparation of a number of valuable organic compounds. PMID:20428461

Enantioselective ultra-high and high performance liquid chromatography: a comparative study of columns based on the Whelk-O1 selector.

PubMed

Kotoni, Dorina; Ciogli, Alessia; D'Acquarica, Ilaria; Kocergin, Jelena; Szczerba, Ted; Ritchie, Harald; Villani, Claudio; Gasparrini, Francesco

2012-12-21

This paper reports on the thermodynamic and kinetic evaluation of a new ultra-high performance liquid chromatography broad-spectrum Pirkle-type chiral stationary phase (CSP) for enantioselective applications (eUHPLC). The well-known Whelk-O1 selector was covalently immobilized onto 1.7-μm high-surface-area, porous spherical silica particles to produce a totally synthetic, covalently bonded CSP that was packed into 150 mm, 100mm, 75 mm and 50mm columns, either 4.6 or 3.0mm ID. A 100 mm × 4.6 mm ID column was fully characterized from a kinetic and thermodynamic point of view, using as reference a conventional HPLC Whelk-O1 column, 250 mm×4.6mm ID, based on 5-μm porous silica particles. On the eUHPLC column, van Deemter plots generated H(min) values of 3.53 μm for 1,3-dinitrobenzene, at an interstitial mobile phase linear velocity (μ(inter)) of 5.07 mm/s, and H(min) of 4.26 and 4.17 μm for the two enantiomers of acenaphthenol, at μ(inter) of 4.85 mm/s and 4.24 mm/s, respectively. Resolution of 21 enantiomeric pairs including alcohols, epoxides, sulfoxides, phosphine oxides, benzodiazepines and 2-aryloxyproprionic esters used as herbicides, were obtained with significant advantages in terms of efficiency and analysis time. Speed gain factors were calculated for the different column geometries (150 mm, 100mm, 75 mm and 50mm, either 4.6 or 3.0mm ID), with respect to the standard HPLC column (250 mm ×4.6 mm ID), and were as high as 13, in the case of the 50-mm-long column, affording sub-minute separations of enantiomers with excellent resolution factors. In particular, trans-stilbene oxide was resolved in only 10s, while a 50 mm×3.0 mm ID column was used as a compromise between reduced mobile phase consumption (less than 1 mL per analysis) and smaller extra-column band-broadening effect. Given the relatively low viscosity in NP mode, and the excellent permeability of these eUHPLC columns, with backpressure values under 600 bar for a wide range of flow rates, the

Highly versatile enantioselective conjugate addition of Grignard reagents to alpha,beta-unsaturated thioesters.

PubMed

Ruiz, Beatriz Maciá; Geurts, Koen; Fernández-Ibáñez, M Angeles; ter Horst, Bjorn; Minnaard, Adriaan J; Feringa, Ben L

2007-11-22

Herein, we report efficient catalysts for the asymmetric copper-catalyzed conjugate addition of Grignard reagents to alpha,beta-unsaturated thioesters. MeMgBr adds to aromatic alpha,beta-unsaturated thioesters with excellent enantioselectivities and moderate to good yields using Josiphos/CuBr and Tol-BINAP/CuI complexes. The use of bulky Grignard reagents leads to unprecedented enantioselectivities in the 1,4-addition to a broad range of aromatic and aliphatic alpha,beta-unsaturated thioesters using Tol-BINAP/CuI. The highest enantioselectivities reported so far for the addition of Grignard reagents to crowded beta-substituted aliphatic substrates are achieved with Tol-BINAP/CuI.

Enantioselective decarboxylative chlorination of β-ketocarboxylic acids

PubMed Central

Shibatomi, Kazutaka; Kitahara, Kazumasa; Sasaki, Nozomi; Kawasaki, Yohei; Fujisawa, Ikuhide; Iwasa, Seiji

2017-01-01

Stereoselective halogenation is a highly useful organic transformation for multistep syntheses because the resulting chiral organohalides can serve as precursors for various medicinally relevant derivatives. Even though decarboxylative halogenation of aliphatic carboxylic acids is a useful and fundamental synthetic method for the preparation of a variety of organohalides, an enantioselective version of this reaction has not been reported. Here we report a highly enantioselective decarboxylative chlorination of β-ketocarboxylic acids to obtain α-chloroketones under mild organocatalytic conditions. The present method is also applicable for the enantioselective synthesis of tertiary α-chloroketones. The conversions of the resulting α-chloroketones into α-aminoketones and α-thio-substituted ketones via SN2 reactions at the tertiary carbon centres are also demonstrated. These results constitute an efficient approach for the synthesis of chiral organohalides and are expected to enhance the availability of enantiomerically enriched chiral compounds with heteroatom-substituted chiral stereogenic centres. PMID:28580951

Enantioselective decarboxylative chlorination of β-ketocarboxylic acids

NASA Astrophysics Data System (ADS)

Shibatomi, Kazutaka; Kitahara, Kazumasa; Sasaki, Nozomi; Kawasaki, Yohei; Fujisawa, Ikuhide; Iwasa, Seiji

2017-06-01

Stereoselective halogenation is a highly useful organic transformation for multistep syntheses because the resulting chiral organohalides can serve as precursors for various medicinally relevant derivatives. Even though decarboxylative halogenation of aliphatic carboxylic acids is a useful and fundamental synthetic method for the preparation of a variety of organohalides, an enantioselective version of this reaction has not been reported. Here we report a highly enantioselective decarboxylative chlorination of β-ketocarboxylic acids to obtain α-chloroketones under mild organocatalytic conditions. The present method is also applicable for the enantioselective synthesis of tertiary α-chloroketones. The conversions of the resulting α-chloroketones into α-aminoketones and α-thio-substituted ketones via SN2 reactions at the tertiary carbon centres are also demonstrated. These results constitute an efficient approach for the synthesis of chiral organohalides and are expected to enhance the availability of enantiomerically enriched chiral compounds with heteroatom-substituted chiral stereogenic centres.

Swelling behaviour in n-pentane and mechanical properties of epoxidized natural rubber with different epoxide content

NASA Astrophysics Data System (ADS)

Kinasih, N. A.; Fathurrohman, M. I.; Winarto, D. A.

2017-07-01

Epoxidized natural rubber (ENR) with different level of epoxidation (i.e. 10, 20, 30, 40 and 50 mol% indicated as ENR ENR10, ENR20, ENR30, ENR40 and ENR50, respectively) were prepared. They were then vulcanized by using efficient system vulcanization. The effect of epoxide content on curing characteristic, swelling and mechanical properties in N-pentane was investigated. The Attenuated Resonance Fourier Transform Infrared (ATR-FTIR) and H-Nuclear Magnetic Resonance (H-NMR) were used to determine the epoxidation level. Glass transition (Tg) of ENR samples was determined by using Direct Scanning Calorimetry (DSC). The result revealed that the resistance of ENR in N-pentane increased with increasing epoxidation level, which indicated by decreasing equilibrium mol uptake and diffusion coefficient. The compression set of ENR and aging resistance increased with increasing epoxide content, except ENR50 was due to ENR 50 have two Tg value. However, the value of hardness and tensile strength were not effected by epoxidation level.

Nickel-catalyzed regio- and enantioselective aminolysis of 3,4-epoxy alcohols.

PubMed

Wang, Chuan; Yamamoto, Hisashi

2015-04-08

The first catalytic regio- and enantioselective aminolysis of 3,4-epoxy alcohols has been accomplished. Under the catalysis of Ni(ClO4)2·6H2O, the C4 selective ring opening of various 3,4-epoxy alcohols proceeded in a stereospecific manner with high regioselectivities. Furthermore, with the Ni-BINAM catalytic system the enantioselective ring opening of 3,4-epoxy alcohols furnished various γ-hydroxy-δ-amino alcohols as products with complete regiocontrol and high enantioselectivities (up to 94% ee).

Infrared-thermographic screening of the activity and enantioselectivity of enzymes.

PubMed

Reetz, M T; Hermes, M; Becker, M H

2001-05-01

The infrared radiation caused by the heat of reaction of an enantioselective enzyme-catalyzed transformation can be detected by modern photovoltaic infrared (IR)-thermographic cameras equipped with focal-plane array detectors. Specifically, in the lipase-catalyzed enantioselective acylation of racemic 1-phenylethanol, the (R)- and (S)-substrates are allowed to react separately in the wells of microtiter plates, the (R)-alcohol showing hot spots in the IR-thermographic images. Thus, highly enantioselective enzymes can be identified at kinetic resolution.

Enantioselective syntheses of aeruginosin 298-A and its analogues using a catalytic asymmetric phase-transfer reaction and epoxidation.

PubMed

Ohshima, Takashi; Gnanadesikan, Vijay; Shibuguchi, Tomoyuki; Fukuta, Yuhei; Nemoto, Tetsuhiro; Shibasaki, Masakatsu

2003-09-17

We developed a versatile synthetic process for aeruginosin 298-A as well as several attractive analogues, in which all stereocenters were controlled by a catalytic asymmetric phase-transfer reaction and epoxidation. Furthermore, drastic counteranion effects in phase-transfer catalysis were observed for the first time, making it possible to three-dimensionally fine-tune the catalyst (ketal part, aromatic part, and counteranion).

Lipase-catalyzed highly enantioselective kinetic resolution of boron-containing chiral alcohols.

PubMed

Andrade, Leandro H; Barcellos, Thiago

2009-07-16

The first application of enzymes as catalysts to obtain optically pure boron compounds is described. The kinetic resolution of boron-containing chiral alcohols via enantioselective transesterification catalyzed by lipases was studied. Aromatic, allylic, and aliphatic secondary alcohols containing a boronate ester or boronic acid group were resolved by lipase from Candida antartica (CALB), and excellent E values (E > 200) and high enantiomeric excesses (up to >99%) of both remaining substrates and acetylated product were obtained.

Highly Enantioselective Three-Component Direct Mannich Reactions of Unfunctionalized Ketones Catalyzed by Bifunctional Organocatalysts

PubMed Central

Guo, Qunsheng; Zhao, John Cong-Gui

2013-01-01

A highly stereoselective three-component direct Mannich reaction between aromatic aldehydes, p-toluenesulfonamide, and unfunctionalized ketones was achieved through an enolate mechanism for the first time with a bifunctional quinidine thiourea catalyst. The corresponding N-tosylated β-aminoketones were obtained in high yields and excellent diastereo- and enantioselectivities (up to >99:1 dr and >99% ee). PMID:23343472

Highly enantioselective alpha-aminoxylation of aldehydes and ketones with a polymer-supported organocatalyst.

PubMed

Font, Daniel; Bastero, Amaia; Sayalero, Sonia; Jimeno, Ciril; Pericàs, Miquel A

2007-05-10

The first catalytic enantioselective alpha-aminoxylation of aldehydes and ketones using an insoluble, polymer-supported organocatalyst (1) derived from trans-4-hydroxyproline is reported (ee: 96-99%). Reaction rates in the aminoxylation of cyclic ketones with 1 are higher than those reported with l-proline. The insoluble nature of 1 simplifies workup conditions and allows catalyst recycling without an apparent decrease in enantioselectivity or yield.

Organocatalytic asymmetric anti-selective Michael reactions of aldehydes and the sequential reduction/lactonization/Pauson-Khand reaction for the enantioselective synthesis of highly functionalized hydropentalenes.

PubMed

Hong, Bor-Cherng; Dange, Nitin S; Yen, Po-Jen; Lee, Gene-Hsiang; Liao, Ju-Hsiou

2012-10-19

A new method has been developed for the enantioselective synthesis of highly functionalized hydropentalenes bearing up to four stereogenic centers with high stereoselectivity (up to 99% ee). This process combines an enantioselective organocatalytic anti-selective Michael addition with a highly efficient one-pot reduction/lactonization/Pauson-Khand reaction sequence. The structures and absolute configurations of the products were confirmed by X-ray analysis.

Epoxide Hydrolase Conformational Heterogeneity for the Resolution of Bulky Pharmacologically Relevant Epoxide Substrates.

PubMed

Serrano-Hervás, Eila; Casadevall, Guillem; Garcia-Borràs, Marc; Feixas, Ferran; Osuna, Sílvia

2018-04-06

The conformational landscape of Bacillus megaterium epoxide hydrolase (BmEH) and how it is altered by mutations that confer the enzyme the ability to accept bulky epoxide substrates has been investigated. Extensive molecular dynamics (MD) simulations coupled to active site volume calculations have unveiled relevant features of the enzyme conformational dynamics and function. Our long-timescale MD simulations identify key conformational states not previously observed by means of X-ray crystallography and short MD simulations that present the loop containing one of the catalytic residues, Asp239, in a wide-open conformation, which is likely involved in the binding of the epoxide substrate. Introduction of mutations M145S and F128A dramatically alters the conformational landscape of the enzyme. These singly mutated variants can accept bulky epoxide substrates due to the disorder induced by mutation in the α-helix containing the catalytic Tyr144 and some parts of the lid domain. These changes impact the enzyme active site, which is substantially wider and more complementary to the bulky pharmacologically relevant epoxide substrates. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Catalytic asymmetric trifluoromethylthiolation via enantioselective [2,3]-sigmatropic rearrangement of sulfonium ylides

NASA Astrophysics Data System (ADS)

Zhang, Zhikun; Sheng, Zhe; Yu, Weizhi; Wu, Guojiao; Zhang, Rui; Chu, Wen-Dao; Zhang, Yan; Wang, Jianbo

2017-10-01

The trifluoromethylthio (SCF3) functional group has been of increasing importance in drug design and development as a consequence of its unique electronic properties and high stability coupled with its high lipophilicity. As a result, methods to introduce this highly electronegative functional group have attracted considerable attention in recent years. Although significant progress has been made in the introduction of SCF3 functionality into a variety of molecules, there remain significant challenges regarding the enantioselective synthesis of SCF3-containing compounds. Here, an asymmetric trifluoromethylthiolation that proceeds through the enantioselective [2,3]-sigmatropic rearrangement of a sulfonium ylide generated from a metal carbene and sulfide (Doyle-Kirmse reaction) has been developed using chiral Rh(II) and Cu(I) catalysts. This transformation features mild reaction conditions and excellent enantioselectivities (up to 98% yield and 98% e.e.), thus providing a unique, highly efficient and enantioselective method for the construction of C(sp3)-SCF3 bonds bearing chiral centres.

Catalytic asymmetric epoxidation of alpha,beta-unsaturated amides: efficient synthesis of beta-aryl alpha-hydroxy amides using a one-pot tandem catalytic asymmetric epoxidation-Pd-catalyzed epoxide opening process.

PubMed

Nemoto, Tetsuhiro; Kakei, Hiroyuki; Gnanadesikan, Vijay; Tosaki, Shin-Ya; Ohshima, Takashi; Shibasaki, Masakatsu

2002-12-11

The catalytic asymmetric epoxidation of alpha,beta-unsaturated amides using Sm-BINOL-Ph3As=O complex was succeeded. Using 5-10 mol % of the asymmetric catalyst, a variety of amides were epoxidized efficiently, yielding the corresponding alpha,beta-epoxy amides in up to 99% yield and in more than 99% ee. Moreover, the novel one-pot tandem process, one-pot tandem catalytic asymmetric epoxidation-Pd-catalyzed epoxide opening process, was developed. This method was successfully utilized for the efficient synthesis of beta-aryl alpha-hydroxy amides, including beta-aryllactyl-leucine methyl esters. Interestingly, it was found that beneficial modifications on the Pd catalyst were achieved by the constituents of the first epoxidation, producing a more suitable catalyst for the Pd-catalyzed epoxide opening reaction in terms of chemoselectivity.

Enantioselective synthesis of spirooxoindoles via chiral auxiliary (bicyclic lactam) controlled SNAr reactions.

PubMed

Sen, Subhabrata; Potti, Venkata R; Surakanti, Ramu; Murthy, Y L N; Pallepogu, Raghavaiah

2011-01-21

A highly efficient enantioselective S(N)Ar reaction of chiral acyl bicyclic lactam with substituted-2,4-dinitrobenzenes was developed, affording products containing quarternary stereogenic centers. They are further utilized towards an enantioselective synthesis of spirooxoindoles.

Enantioselective degradation of Myclobutanil and Famoxadone in grape.

PubMed

Lin, Chunmian; Zhang, Lijun; Zhang, Hu; Wang, Qiang; Zhu, Jiahong; Wang, Jianmei; Qian, Mingrong

2018-01-01

The enantioselective degradation of myclobutanil and famoxadone enantiomers in grape under open field was investigated in this study. The absolute configuration of myclobutanil and famoxadone enantiomers was determined by the combination of experimental electronic circular dichroism (ECD) and calculated ECD spectra. The enantiomers residues of myclobutanil and famoxadone in grape were measured by sensitive high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS). The linearity, precision, accuracy, matrix effect, and stability were assessed. And the limit of quantification (LOQ) for each enantiomer of myclobutanil and famoxadone in grape was evaluated to be 1.5 and 2 μg kg -1 . The myclobutanil and famoxadone showed the enantioselective degradation in grape, and the enantioselectivity of degradation for myclobutanil was more pronounced than that for famoxadone. The half-lives were 13.1 days and 25.7 days for S-(+)-myclobutanil and R-(-)-myclobutanil in grape, separately. The half-life of S-(+)-famoxadone was 31.5 days slightly shorter than that of R-(-)-famoxadone with half-life being 38.5 days in grape. The probable reasons for the enantioselective degradation behavior of these two fungicides were also discussed. The results in the article might provide a reference to better assess the risks of myclobutanil and famoxadone enantiomers in grapes to human and environment. Graphical abstract The enantioselective analysis of myclobutanil and famoxadone in grape.

Enantioselective environmental toxicology of chiral pesticides.

PubMed

Ye, Jing; Zhao, Meirong; Niu, Lili; Liu, Weiping

2015-03-16

The enantioselective environmental toxic effect of chiral pesticides is becoming more important. As the industry develops, increasing numbers of chiral insecticides and herbicides will be introduced into use, potentially posing toxic effects on nontarget living beings. Chiral pesticides, including herbicides such as acylanilides, phenoxypropanoic acids, and imidazolinones, and insecticides such as synthetic pyrethroids, organophosphates, and DDT often behave enantioselectively during agricultural use. These compounds also pose unpredictable enantioselective ecological threats to nontarget living beings and/or humans, affecting the food chain and entire ecosystems. Thus, to investigate the enantioselective toxic effects of chiral insecticides and herbicides is necessary during environmental protection. The environmental toxicology of chiral pesticides, especially the findings obtained from studies conducted in our laboratory during the past 10 years, is reviewed.

Enantioselective ultra high performance liquid and supercritical fluid chromatography: The race to the shortest chromatogram.

PubMed

Ciogli, Alessia; Ismail, Omar H; Mazzoccanti, Giulia; Villani, Claudio; Gasparrini, Francesco

2018-03-01

The ever-increasing need for enantiomerically pure chiral compounds has greatly expanded the number of enantioselective separation methods available for the precise and accurate measurements of the enantiomeric purity. The introduction of chiral stationary phases for liquid chromatography in the last decades has revolutionized the routine methods to determine enantiomeric purity of chiral drugs, agrochemicals, fragrances, and in general of organic and organometallic compounds. In recent years, additional efforts have been placed on faster, enantioselective analytical methods capable to fulfill the high throughput requirements of modern screening procedures. Efforts in this field, capitalizing on improved chromatographic particle technology and dedicated instrumentation, have led to highly efficient separations that are routinely completed on the seconds time scale. An overview of the recent achievements in the field of ultra-high-resolution chromatography on column packed with chiral stationary phases, both based on sub-2 μm fully porous and sub-3 μm superficially porous particles, will be given, with an emphasis on very recent studies on ultrafast chiral separations. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective Hydroformylation of Aniline Derivatives

PubMed Central

Joe, Candice L.; Tan, Kian L.

2011-01-01

We have developed a ligand that reversibly binds to aniline substrates allowing for the control of regioselectivity and enantioselectivity in hydroformylation. In this paper we address how the electronics of the aniline ring affect both binding of the substrate to the ligand and the enantioselectivity in this reaction. PMID:21842847

Enantioselective Copper-Catalyzed Oxy-Alkynylation of Diazo Compounds.

PubMed

Hari, Durga Prasad; Waser, Jerome

2017-06-28

Enantioselective catalytic methods allowing the addition of both a nucleophile and an electrophile onto diazo compounds give a fast access into important building blocks. Herein, we report the highly enantioselective oxyalkynylation of diazo compounds using ethynylbenziodoxol-(on)e reagents and a simple copper bisoxazoline catalyst. The obtained α-benzoyloxy propargylic esters are useful building blocks, which are difficult to synthesize in enantiopure form using other methods. The obtained products could be efficiently transformed into vicinal diols and α-hydroxy propargylic esters without loss in enantiopurity.

Epoxide hydrolases: structure, function, mechanism, and assay.

PubMed

Arand, Michael; Cronin, Annette; Adamska, Magdalena; Oesch, Franz

2005-01-01

Epoxide hydrolases are a class of enzymes important in the detoxification of genotoxic compounds, as well as in the control of physiological signaling molecules. This chapter gives an overview on the function, structure, and enzymatic mechanism of structurally characterized epoxide hydrolases and describes selected assays for the quantification of epoxide hydrolase activity.

Enantioselective aldol reactions with masked fluoroacetates

NASA Astrophysics Data System (ADS)

Saadi, Jakub; Wennemers, Helma

2016-03-01

Despite the growing importance of organofluorines as pharmaceuticals and agrochemicals, the stereoselective introduction of fluorine into many prominent classes of natural products and chemotherapeutic agents is difficult. One long-standing unsolved challenge is the enantioselective aldol reaction of fluoroacetate to enable access to fluorinated analogues of medicinally relevant acetate-derived compounds, such as polyketides and statins. Herein we present fluoromalonic acid halfthioesters as biomimetic surrogates of fluoroacetate and demonstrate their use in highly stereoselective aldol reactions that proceed under mild organocatalytic conditions. We also show that the methodology can be extended to formal aldol reactions with fluoroacetaldehyde and consecutive aldol reactions. The synthetic utility of the fluorinated aldol products is illustrated by the synthesis of a fluorinated derivative of the top-selling drug atorvastatin. The results show the prospects of the method for the enantioselective introduction of fluoroacetate to access a wide variety of highly functionalized fluorinated compounds.

Exciton characteristics in graphene epoxide.

PubMed

Zhu, Xi; Su, Haibin

2014-02-25

Exciton characteristics in graphene epoxide (GE) are investigated by density functional theory with quasi-particle corrections and many-body interactions. The nature of the exciton is influenced by epoxide content and detailed geometric configurations. Two kinds of excitons are identified in GE: Frenkel-like exciton originated from the sp(2) carbon cluster and charge-transfer exciton formed by localized states involving both oxygen and carbon atoms. The unusual blue shift associated with the Frenkel-like exciton leaking is highlighted. One scaling relationship is proposed to address the power-law dependence of Frenkel-like exciton binding strength on its size. The charge-transfer exciton appears in GE samples with the high oxygen coverage. Particularly, the exciton in GE structures exhibits long lifetime by analyzing both radiative and nonradiative decay processes. This study sheds light on the potential applications of GE-based structures with attractive high quantum yield in light emission and optoelectronic technology.

Learning epistatic interactions from sequence-activity data to predict enantioselectivity

NASA Astrophysics Data System (ADS)

Zaugg, Julian; Gumulya, Yosephine; Malde, Alpeshkumar K.; Bodén, Mikael

2017-12-01

Enzymes with a high selectivity are desirable for improving economics of chemical synthesis of enantiopure compounds. To improve enzyme selectivity mutations are often introduced near the catalytic active site. In this compact environment epistatic interactions between residues, where contributions to selectivity are non-additive, play a significant role in determining the degree of selectivity. Using support vector machine regression models we map mutations to the experimentally characterised enantioselectivities for a set of 136 variants of the epoxide hydrolase from the fungus Aspergillus niger (AnEH). We investigate whether the influence a mutation has on enzyme selectivity can be accurately predicted through linear models, and whether prediction accuracy can be improved using higher-order counterparts. Comparing linear and polynomial degree = 2 models, mean Pearson coefficients (r) from 50 {× } 5 -fold cross-validation increase from 0.84 to 0.91 respectively. Equivalent models tested on interaction-minimised sequences achieve values of r=0.90 and r=0.93 . As expected, testing on a simulated control data set with no interactions results in no significant improvements from higher-order models. Additional experimentally derived AnEH mutants are tested with linear and polynomial degree = 2 models, with values increasing from r=0.51 to r=0.87 respectively. The study demonstrates that linear models perform well, however the representation of epistatic interactions in predictive models improves identification of selectivity-enhancing mutations. The improvement is attributed to higher-order kernel functions that represent epistatic interactions between residues.

Learning epistatic interactions from sequence-activity data to predict enantioselectivity

NASA Astrophysics Data System (ADS)

Zaugg, Julian; Gumulya, Yosephine; Malde, Alpeshkumar K.; Bodén, Mikael

2017-12-01

Enzymes with a high selectivity are desirable for improving economics of chemical synthesis of enantiopure compounds. To improve enzyme selectivity mutations are often introduced near the catalytic active site. In this compact environment epistatic interactions between residues, where contributions to selectivity are non-additive, play a significant role in determining the degree of selectivity. Using support vector machine regression models we map mutations to the experimentally characterised enantioselectivities for a set of 136 variants of the epoxide hydrolase from the fungus Aspergillus niger ( AnEH). We investigate whether the influence a mutation has on enzyme selectivity can be accurately predicted through linear models, and whether prediction accuracy can be improved using higher-order counterparts. Comparing linear and polynomial degree = 2 models, mean Pearson coefficients ( r) from 50 {× } 5-fold cross-validation increase from 0.84 to 0.91 respectively. Equivalent models tested on interaction-minimised sequences achieve values of r=0.90 and r=0.93. As expected, testing on a simulated control data set with no interactions results in no significant improvements from higher-order models. Additional experimentally derived AnEH mutants are tested with linear and polynomial degree = 2 models, with values increasing from r=0.51 to r=0.87 respectively. The study demonstrates that linear models perform well, however the representation of epistatic interactions in predictive models improves identification of selectivity-enhancing mutations. The improvement is attributed to higher-order kernel functions that represent epistatic interactions between residues.

Learning epistatic interactions from sequence-activity data to predict enantioselectivity.

PubMed

Zaugg, Julian; Gumulya, Yosephine; Malde, Alpeshkumar K; Bodén, Mikael

2017-12-01

Enzymes with a high selectivity are desirable for improving economics of chemical synthesis of enantiopure compounds. To improve enzyme selectivity mutations are often introduced near the catalytic active site. In this compact environment epistatic interactions between residues, where contributions to selectivity are non-additive, play a significant role in determining the degree of selectivity. Using support vector machine regression models we map mutations to the experimentally characterised enantioselectivities for a set of 136 variants of the epoxide hydrolase from the fungus Aspergillus niger (AnEH). We investigate whether the influence a mutation has on enzyme selectivity can be accurately predicted through linear models, and whether prediction accuracy can be improved using higher-order counterparts. Comparing linear and polynomial degree = 2 models, mean Pearson coefficients (r) from [Formula: see text]-fold cross-validation increase from 0.84 to 0.91 respectively. Equivalent models tested on interaction-minimised sequences achieve values of [Formula: see text] and [Formula: see text]. As expected, testing on a simulated control data set with no interactions results in no significant improvements from higher-order models. Additional experimentally derived AnEH mutants are tested with linear and polynomial degree = 2 models, with values increasing from [Formula: see text] to [Formula: see text] respectively. The study demonstrates that linear models perform well, however the representation of epistatic interactions in predictive models improves identification of selectivity-enhancing mutations. The improvement is attributed to higher-order kernel functions that represent epistatic interactions between residues.

Regioconvergent and Enantioselective Rhodium-Catalyzed Hydroamination of Internal and Terminal Alkynes: A Highly Flexible Access to Chiral Pyrazoles.

PubMed

Haydl, Alexander M; Hilpert, Lukas J; Breit, Bernhard

2016-05-04

The rhodium-catalyzed asymmetric N-selective coupling of pyrazole derivatives with internal and terminal alkynes features an utmost chemo-, regio-, and enantioselective access to enantiopure allylic pyrazoles, readily available for incorporation in small-molecule pharmaceuticals. This methodology is distinguished by a broad substrate scope, resulting in a remarkable compatability with a variety of different functional groups. It furthermore exhibits an intriguing case of regio-, position-, and enantioselectivity in just one step, underscoring the sole synthesis of just one out of up to six possible products in a highly flexible approach to allylated pyrazoles by emanating from various internal and terminal alkynes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Succinic anhydrides from epoxides

DOEpatents

Coates, Geoffrey W.; Rowley, John M.

2013-07-09

Catalysts and methods for the double carbonylation of epoxides are disclosed. Each epoxide molecule reacts with two molecules of carbon monoxide to produce a succinic anhydride. The reaction is facilitated by catalysts combining a Lewis acidic species with a transition metal carbonyl complex. The double carbonylation is achieved in single process by using reaction conditions under which both carbonylation reactions occur without the necessity of isolating or purifying the product of the first carbonylation.

Succinic anhydrides from epoxides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coates, Geoffrey W.; Rowley, John M.

2016-06-28

Catalysts and methods for the double carbonylation of epoxides are disclosed. Each epoxide molecule reacts with two molecules of carbon monoxide to produce a succinic anhydride. The reaction is facilitated by catalysts combining a Lewis acidic species with a transition metal carbonyl complex. The double carbonylation is achieved in single process by using reaction conditions under which both carbonylation reactions occur without the necessity of isolating or purifying the product of the first carbonylation.

Catalytic Enantioselective Aza-Benzoin Reactions of Aldehydes with 2H-Azirines.

PubMed

Peng, Qiupeng; Guo, Donghui; Bie, Jianbo; Wang, Jian

2018-03-26

The unprecedented enantioselective aza-benzoin reaction of aldehydes with 2H-azirines was developed by utilizing a chiral N-heterocyclic carbene as the catalyst. A wide range of corresponding aziridines can be obtained in good yields with high enantioselectivities. The obtained optically active aziridines should be useful in the synthesis of other valuable molecules. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

40 CFR 721.2675 - Perfluoroalkyl epoxide (generic name).

Code of Federal Regulations, 2010 CFR

2010-07-01

... Substances § 721.2675 Perfluoroalkyl epoxide (generic name). (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified generically as perfluoroalkyl epoxide (PMN P... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Perfluoroalkyl epoxide (generic name...

40 CFR 721.2675 - Perfluoroalkyl epoxide (generic name).

Code of Federal Regulations, 2011 CFR

2011-07-01

... Substances § 721.2675 Perfluoroalkyl epoxide (generic name). (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified generically as perfluoroalkyl epoxide (PMN P... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Perfluoroalkyl epoxide (generic name...

40 CFR 721.2675 - Perfluoroalkyl epoxide (generic name).

Code of Federal Regulations, 2013 CFR

2013-07-01

... Substances § 721.2675 Perfluoroalkyl epoxide (generic name). (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified generically as perfluoroalkyl epoxide (PMN P... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Perfluoroalkyl epoxide (generic name...

40 CFR 721.2675 - Perfluoroalkyl epoxide (generic name).

Code of Federal Regulations, 2012 CFR

2012-07-01

... Substances § 721.2675 Perfluoroalkyl epoxide (generic name). (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified generically as perfluoroalkyl epoxide (PMN P... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Perfluoroalkyl epoxide (generic name...

40 CFR 721.2675 - Perfluoroalkyl epoxide (generic name).

Code of Federal Regulations, 2014 CFR

2014-07-01

... Substances § 721.2675 Perfluoroalkyl epoxide (generic name). (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified generically as perfluoroalkyl epoxide (PMN P... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Perfluoroalkyl epoxide (generic name...

Prediction of metabolites of epoxidation reaction in MetaTox.

PubMed

Rudik, A V; Dmitriev, A V; Bezhentsev, V M; Lagunin, A A; Filimonov, D A; Poroikov, V V

2017-10-01

Biotransformation is a process of the chemical modifications which may lead to the reactive metabolites, in particular the epoxides. Epoxide reactive metabolites may cause the toxic effects. The prediction of such metabolites is important for drug development and ecotoxicology studies. Epoxides are formed by some oxidation reactions, usually catalysed by cytochromes P450, and represent a large class of three-membered cyclic ethers. Identification of molecules, which may be epoxidized, and indication of the specific location of epoxide functional group (which is called SOE - site of epoxidation) are important for prediction of epoxide metabolites. Datasets from 355 molecules and 615 reactions were created for training and validation. The prediction of SOE is based on a combination of LMNA (Labelled Multilevel Neighbourhood of Atom) descriptors and Bayesian-like algorithm implemented in PASS software and MetaTox web-service. The average invariant accuracy of prediction (AUC) calculated in leave-one-out and 20-fold cross-validation procedures is 0.9. Prediction of epoxide formation based on the created SAR model is included as the component of MetaTox web-service ( http://www.way2drug.com/mg ).

Bifunctional ferrocene-based squaramide-phosphine as an organocatalyst for highly enantioselective intramolecular Morita-Baylis-Hillman reaction.

PubMed

Zhang, Xiaorui; Ma, Pengfei; Zhang, Dongxu; Lei, Yang; Zhang, Shengyong; Jiang, Ru; Chen, Weiping

2014-04-21

This work demonstrates that, in accord with metal catalysis, ferrocene could be an excellent scaffold for organocatalysts. The simple and easily accessible bifunctional ferrocene-based squaramide-phosphine shows high enantioselectivity in the intramolecular Morita-Baylis-Hillman reaction of 7-aryl-7-oxo-5-heptenals, giving a variety of 2-aroyl-2-cyclohexenols in up to 96% ee.

Enantioselectivity in Candida antarctica lipase B: A molecular dynamics study

PubMed Central

Raza, Sami; Fransson, Linda; Hult, Karl

2001-01-01

A major problem in predicting the enantioselectivity of an enzyme toward substrate molecules is that even high selectivity toward one substrate enantiomer over the other corresponds to a very small difference in free energy. However, total free energies in enzyme-substrate systems are very large and fluctuate significantly because of general protein motion. Candida antarctica lipase B (CALB), a serine hydrolase, displays enantioselectivity toward secondary alcohols. Here, we present a modeling study where the aim has been to develop a molecular dynamics-based methodology for the prediction of enantioselectivity in CALB. The substrates modeled (seven in total) were 3-methyl-2-butanol with various aliphatic carboxylic acids and also 2-butanol, as well as 3,3-dimethyl-2-butanol with octanoic acid. The tetrahedral reaction intermediate was used as a model of the transition state. Investigative analyses were performed on ensembles of nonminimized structures and focused on the potential energies of a number of subsets within the modeled systems to determine which specific regions are important for the prediction of enantioselectivity. One category of subset was based on atoms that make up the core structural elements of the transition state. We considered that a more favorable energetic conformation of such a subset should relate to a greater likelihood for catalysis to occur, thus reflecting higher selectivity. The results of this study conveyed that the use of this type of subset was viable for the analysis of structural ensembles and yielded good predictions of enantioselectivity. PMID:11266619

Highly enantioselective asymmetric direct aldol reaction promoted by aziridine amides constructed on chiral terpene scaffold.

PubMed

Wujkowska, Zuzanna; Strojewska, Aleksandra; Pieczonka, Adam M; Leśniak, Stanisław; Rachwalski, Michał

2017-05-01

Optically pure, diastereomeric aziridine amides built on the chiral skeletons of camphor, fenchone, and menthone have proven to be highly efficient ligands for enantioselective asymmetric direct aldol reaction in the presence of water and zinc triflate. Desired products were formed in moderate to high chemical yields (up to 95%) and with enantiomeric excess up to 99%. The influence of the stereogenic centers located at the aziridine subunit on the stereochemical course of the reaction is discussed. © 2017 Wiley Periodicals, Inc.

Rhodium/chiral diene-catalyzed asymmetric 1,4-addition of arylboronic acids to chromones: a highly enantioselective pathway for accessing chiral flavanones.

PubMed

He, Qijie; So, Chau Ming; Bian, Zhaoxiang; Hayashi, Tamio; Wang, Jun

2015-03-01

Chromone has been noted to be one of the most challenging substrates in the asymmetric 1,4-addition of α,β-unsaturated carbonyl compounds. By employing the rhodium complex associated with a chiral diene ligand, (R,R)-Ph-bod*, the 1,4-addition of a variety of arylboronic acids was realized to give high yields of the corresponding flavanones with excellent enantioselectivities (≥97% ee, 99% ee for most substrates). Ring-opening side products, which would lead to erosion of product enantioselectivity, were not observed under the stated reaction conditions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The effects of metyrapone, chalcone epoxide, benzil, clotrimazole and related compounds on the activity of microsomal epoxide hydrolase in situ, in purified form and in reconstituted systems towards different substrates.

PubMed

Seidegård, J; DePierre, J W; Guenthner, T M; Oesch, F

1986-09-01

found with different effectors. Activation of epoxide hydrolase activity towards styrene oxide by clotrimazole was found to be uncompetitive with the substrate and highly structure specific. On the other hand, inhibition of epoxide hydrolase activity towards androstene oxide by clotrimazole was found to be competitive in microsomes. It is concluded that the marked effects of these four modulators on microsomal epoxide hydrolase activity are due to an interaction with the enzyme protein itself, but that the presence of total microsomal phospholipids allows the maximal expression leading to similar degrees of modulation as those observed in intact microsomes.(ABSTRACT TRUNCATED AT 400 WORDS)

Heptachlor epoxide

Integrated Risk Information System (IRIS)

Heptachlor epoxide ; CASRN 1024 - 57 - 3 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogen

Copper-Catalyzed Enantioselective Henry Reaction of β,γ-Unsaturated α-Ketoesters with Nitromethane in Water.

PubMed

Li, Yanan; Huang, Yekai; Gui, Yang; Sun, Jianan; Li, Jindong; Zha, Zhenggen; Wang, Zhiyong

2017-12-01

A highly enantioselective Henry reaction of β,γ-unsaturated α-ketoesters with nitromethane in water by virtue of chiral copper complexes has been developed. A series of unsaturated β-nitro-α-hydroxy esters bearing tetrasubstituted carbon stereocenters were obtained exclusively with high yields and excellent enantioselectivities. This method could avoid tedious anaerobic anhydrous manipulation and reduce the environmental pollution caused by organic solvents.

Regiospecific Epoxidation of Carvone: A Discovery-Oriented Experiment for Understanding the Selectivity and Mechanism of Epoxidation Reactions

ERIC Educational Resources Information Center

Mak, Kendrew K. W.; Lai, Y. M.; Siu, Yuk-Hong

2006-01-01

This article describes a discovery-oriented experiment for demonstrating the selectivity of two epoxidation reactions. Peroxy acids and alkaline H[subscript 2]O[subscript 2] are two commonly used reagents for alkene epoxidation. The former react preferentially with electron-rich alkenes while the latter works better with alpha,beta-unsaturated…

Di-epoxides of the three isomeric dicyclopenta-fused pyrenes: ultimate mutagenic active agents.

PubMed

Otero-Lobato, María José; Kaats-Richters, Veronica E M; Havenith, Remco W A; Jenneskens, Leonardus W; Seinen, Willem

2004-11-14

To rationalize the high bacterial mutagenic response recently found for the (di-) cyclopenta-fused pyrene congeners, viz. cyclopenta[cd]-(1), dicyclopenta[cd,mn]-(2), dicyclopenta[cd,fg]-(3) and dicyclopenta[cd,jk]pyrene (4), in the presence of a metabolic activation mixture (S9-mix), their (di-)epoxides at the externally fused unsaturated five-membered rings were previously proposed as the ultimate mutagenic active forms. In this study, cyclopenta[cd]pyrene-3,4-epoxide (5) and the novel dicyclopenta[cd,mn]pyrene-1,2,4,5-di-epoxide (6), dicyclopenta[cd,fg]pyrene-5,6,7,8-di-epoxide (7) and dicyclopenta[cd,jk]pyrene-1,2,6,7-di-epoxide (8) were synthesised from 1 to 4, respectively, and subsequently assayed for bacterial mutagenicity in the standard microsomal/histidine reverse mutation assay (Ames-assay with Salmonella typhimurium strain TA98). The di-epoxides 6-8 are present as a mixture of their cis- and trans-stereo-isomers in a close to 1:1 ratio ((1)H NMR spectroscopy and ab initio IGLO/III//RHF/6-31G** calculations). The direct-acting mutagenic activity and the strong cytotoxicity exerted by 5-8 both in the absence or presence of an exogenous metabolic activation system (+/-S9-mix) demonstrate that the ultimate mutagenic active forms are the proposed (di-)epoxides of 1-4.

Direct Epoxidation of Propylene over Stabilized Cu + Surface Sites on Ti Modified Cu 2O

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, X.; Kattel, S.; Xiong, K.

2015-07-17

Direct propylene epoxidation by O 2 is a challenging reaction because of the strong tendency for complete combustion. Results from the current study demonstrate the feasibility to tune the epoxidation selectivity by generating highly dispersed and stabilized Cu + active sites in a TiCuO x mixed oxide. The TiCuO x surface anchors the key surface intermediate, oxametallacycle, leading to higher selectivity for epoxidation of propylene.

Occurrence of neoxanthin and lutein epoxide cycle in parasitic Cuscuta species.

PubMed

Kruk, Jerzy; Szymańska, Renata

2008-01-01

In the present study, xanthophyll composition of eight parasitic Cuscuta species under different light conditions was investigated. Neoxanthin was not detected in four of the eight species examined, while in others it occurred at the level of several percent of total xanthophylls. In C. gronovii and C. lupuliformis it was additionally found that the neoxanthin content was considerably stimulated by strong light. In dark-adapted plants, lutein epoxide level amounted to 10-22% of total xanthophylls in only three species, the highest being for C. lupuliformis, while in others it was below 3%, indicating that the lutein epoxide cycle is limited to only certain Cuscuta species. The obtained data also indicate that the presence of the lutein epoxide cycle and of neoxanthin is independent and variable among the Cuscuta species. The xanthophyll cycle carotenoids violaxanthin, antheraxanthin and zeaxanthin were identified in all the examined species and occurred at the level found in other higher plants. The xanthophyll and lutein epoxide cycle pigments showed typical response to high light stress. The obtained results also suggest that the ability of higher plants to synthesize lutein epoxide probably does not depend on the substrate specificity of zeaxanthin epoxidase but on the availability of lutein for the enzyme.

Synthesis of water-soluble multidentate aminoalcohol β-cyclodextrin derivatives via epoxide opening.

PubMed

Martina, K; Caporaso, M; Tagliapietra, S; Heropoulos, G; Rosati, O; Cravotto, G

2011-12-13

New highly soluble β-aminoalcohol β-cyclodextrin (β-CD) derivatives have been synthesized via nucleophilic epoxide opening reactions with mono-6-amino mono-6-deoxy-permethyl-β-CD and mono-6-amino mono-6-deoxy-β-CD. The binding properties of the β-CD were enhanced by linking aminoalcohol subunits which caused its solubility to improve markedly. The reaction conditions were optimised using microwave irradiation giving moderate-to-good yields with a series of epoxides. A regioselective epoxide opening reaction was observed in the reaction with styrene oxide while the stereoselectivity was strictly dependent on substrate structure. Copyright © 2011 Elsevier Ltd. All rights reserved.

Enantiomerization and enantioselective bioaccumulation of metalaxyl in Tenebrio molitor larvae.

PubMed

Gao, Yongxin; Wang, Huili; Qin, Fang; Xu, Peng; Lv, Xiaotian; Li, Jianzhong; Guo, Baoyuan

2014-02-01

The enantiomerization and enantioselective bioaccumulation of metalaxyl by a single dose of exposure to Tenebrio molitor larvae under laboratory condition were studied by high-performance liquid chromatography tandem mass spectroscopy (HPLC-MS/MS) based on a ChiralcelOD-3R [cellulosetris-tris-(3, 5-dichlorophenyl-carbamate)] column. Exposure of enantiopure R-metalaxyl and S-metalaxyl in Tenebrio molitor larvae exhibited significant enantiomerization, with formation of the R enantiomers from the S enantiomers, and vice versa, which might be attributed to the chiral pesticide catalyzed by a certain enzyme in Tenebrio molitor larvae. Enantiomerization was not observed in wheat bran during the period of 21 d. In addition, bioaccumulation of rac-metalaxyl in Tenebrio molitor larvae was enantioselective with a preferential accumulation of S-metalaxyl. These results showed that enantioselectivity was caused not only by actual degradation and metabolism but also by enantiomerization, which was an important process in the environmental fate and behavior of metalaxyl enantiomers. Copyright © 2013 Wiley Periodicals, Inc.

Enantioselective Total Syntheses of FR901464 and Spliceostatin A and Evaluation of Splicing Activity of Key Derivatives

PubMed Central

2015-01-01

FR901464 (1) and spliceostatin A (2) are potent inhibitors of spliceosomes. These compounds have shown remarkable anticancer activity against multiple human cancer cell lines. Herein, we describe efficient, enantioselective syntheses of FR901464, spliceostatin A, six corresponding diastereomers and an evaluation of their splicing activity. Syntheses of spliceostatin A and FR901464 were carried out in the longest linear sequence of 9 and 10 steps, respectively. To construct the highly functionalized tetrahydropyran A-ring, we utilized CBS reduction, Achmatowicz rearrangement, Michael addition, and reductive amination as key steps. The remarkable diastereoselectivity of the Michael addition was specifically demonstrated with different substrates under various reaction conditions. The side chain B was prepared from an optically active alcohol, followed by acetylation and hydrogenation over Lindlar’s catalyst. The other densely functionalized tetrahydropyran C-ring was derived from readily available (R)-isopropylidene glyceraldehyde through a route featuring 1,2-addition, cyclic ketalization, and regioselective epoxidation. These fragments were coupled together at a late stage through amidation and cross-metathesis in a convergent manner. Six key diastereomers were then synthesized to probe the importance of specific stereochemical features of FR901464 and spliceostatin A, with respect to their in vitro splicing activity. PMID:24873648

Enantioselective functionalization of allylic C-H bonds following a strategy of functionalization and diversification.

PubMed

Sharma, Ankit; Hartwig, John F

2013-11-27

We report the enantioselective functionalization of allylic C-H bonds in terminal alkenes by a strategy involving the installation of a temporary functional group at the terminal carbon atom by C-H bond functionalization, followed by the catalytic diversification of this intermediate with a broad scope of reagents. The method consists of a one-pot sequence of palladium-catalyzed allylic C-H bond oxidation under neutral conditions to form linear allyl benzoates, followed by iridium-catalyzed allylic substitution. This overall transformation forms a variety of chiral products containing a new C-N, C-O, C-S, or C-C bond at the allylic position in good yield with a high branched-to-linear selectivity and excellent enantioselectivity (ee ≤97%). The broad scope of the overall process results from separating the oxidation and functionalization steps; by doing so, the scope of nucleophile encompasses those sensitive to direct oxidative functionalization. The high enantioselectivity of the overall process is achieved by developing an allylic oxidation that occurs without acid to form the linear isomer with high selectivity. These allylic functionalization processes are amenable to an iterative sequence leading to (1,n)-functionalized products with catalyst-controlled diastereo- and enantioselectivity. The utility of the method in the synthesis of biologically active molecules has been demonstrated.

Enantioselective pharmacokinetics of sibutramine in rat.

PubMed

Noh, Keumhan; Bae, Kyoungjin; Min, Bokyoung; Kim, Eunyoung; Kwon, Kwang-il; Jeong, Taecheon; Kang, Wonku

2010-02-01

Racemic sibutramine is widely used to treat obesity owing to its inhibition of serotonin and noradrenaline reuptake in synapses. Although the enantioselective effects of sibutramine and its two active desmethyl-metabolites, monodesmethylsibutramine (MDS) and didesmethylsibutramine (DDS), on anorexia and energy expenditure have been elucidated, the enantioselective pharmacokinetics of sibutramine are still unclear. Therefore, we aimed to characterize the enantioselective pharmacokinetics of sibutramine and its metabolites in plasma and urine following an intravenous and a single oral administration of sibutramine in rats. The absolute bioavailability of sibutramine was only about 7%. The pharmacologically less effective S-isomer of DDS was predominant in the plasma: the C ( max ) and the AUC ( inf ) were 28 and 30 times higher than those of the R-isomer, respectively (p<0.001). In the urine, the concentrations of the R-isomers of hydroxylated DDS and hydroxylated and carbamoylglucuronized MDS and DDS appeared to be 11.3-, 5.1-, and 5.3-times the concentrations of the respective S-isomers. Thus, regardless of increased potency than the S-enantiomers, the R-enantiomers of the sibutramine metabolites MDS and DDS were present at lower concentrations, owing to their rapid biotransformation to hydroxylated and/or carbamoylglucuronized forms and their faster excretion in the urine. The present study is the first to elucidate the enantioselective pharmacokinetics of sibutramine in rats.

Iminium and enamine catalysis in enantioselective photochemical reactions.

PubMed

Zou, You-Quan; Hörmann, Fabian M; Bach, Thorsten

2018-01-22

Although enantioselective catalysis under thermal conditions has been well established over the last few decades, the enantioselective catalysis of photochemical reactions is still a challenging task resulting from the complex enantiotopic face differentiation in the photoexcited state. Recently, remarkable achievements have been reported by a synergistic combination of organocatalysis and photocatalysis, which have led to the expedient construction of a diverse range of enantioenriched molecules which are generally not easily accessible under thermal conditions. In this tutorial review, we summarize and highlight the most significant advances in iminium and enamine catalysis of enantioselective photochemical reactions, with an emphasis on catalytic modes and reaction types.

Iminium and enamine catalysis in enantioselective photochemical reactions

PubMed Central

Hörmann, Fabian M.

2018-01-01

Although enantioselective catalysis under thermal conditions has been well established over the last few decades, the enantioselective catalysis of photochemical reactions is still a challenging task resulting from the complex enantiotopic face differentiation in the photoexcited state. Recently, remarkable achievements have been reported by a synergistic combination of organocatalysis and photocatalysis, which have led to the expedient construction of a diverse range of enantioenriched molecules which are generally not easily accessible under thermal conditions. In this tutorial review, we summarize and highlight the most significant advances in iminium and enamine catalysis of enantioselective photochemical reactions, with an emphasis on catalytic modes and reaction types. PMID:29155908

Enantioselective Biotransformation of Chiral Persistent Organic Pollutants.

PubMed

Zhang, Ying; Ye, Jing; Liu, Min

2017-01-01

Enantiomers of chiral compounds commonly undergo enantioselective transformation in most biologically mediated processes. As chiral persistent organic pollutants (POPs) are extensively distributed in the environment, differences between enantiomers in biotransformation should be carefully considered to obtain exact enrichment and specific health risks. This review provides an overview of in vivo biotransformation of chiral POPs currently indicated in the Stockholm Convention and their chiral metabolites. Peer-reviewed journal articles focused on the research question were thoroughly searched. A set of inclusion and exclusion criteria were developed to identify relevant studies. We mainly compared the results from different animal models under controlled laboratory conditions to show the difference between enantiomers in terms of distinct transformation potential. Interactions with enzymes involved in enantioselective biotransformation, especially cytochrome P450 (CYP), were discussed. Further research areas regarding this issue were proposed. Limited evidence for a few POPs has been found in 30 studies. Enantioselective biotransformation of α-hexachlorocyclohexane (α-HCH), chlordane, dichlorodiphenyltrichloroethane (DDT), heptachlor, hexabromocyclododecane (HBCD), polychlorinated biphenyls (PCBs), and toxaphene, has been investigated using laboratory mammal, fish, bird, and worm models. Tissue and excreta distributions, as well as bioaccumulation and elimination kinetics after administration of racemate and pure enantiomers, have been analyzed in these studies. Changes in enantiomeric fractions have been considered as an indicator of enantioselective biotransformation of chiral POPs in most studies. Results of different laboratory animal models revealed that chiral POP biotransformation is seriously affected by chirality. Pronounced results of species-, tissue-, gender-, and individual-dependent differences are observed in in vivo biotransformation of chiral POPs

Synthesis of a highly dispersed CuO catalyst on CoAl-HT for the epoxidation of styrene.

PubMed

Hu, Rui; Yang, Pengfei; Pan, Yongning; Li, Yunpeng; He, Yufei; Feng, Junting; Li, Dianqing

2017-10-10

A highly dispersed CuO catalyst was prepared by the deposition-precipitation method and evaluated for the catalytic epoxidation of styrene with tert-butyl hydroperoxide (TBHP) as the oxidant under solvent acetonitrile conditions. Compared with MgAl hydrotalcite (MgAl-HT)-, MgO-, TiO 2 -, C-, and MCM-22-supported catalysts, CuO/CoAl-HT exhibited preferable activity and selectivity towards styrene oxide (72% selectivity at 99.5% styrene conversion) due to its high dispersion of CuO and surface area of Cu. The improved dispersion of CuO/CoAl-HT could be ascribed to the nature of HT support, especially the synergistic effect of acidic and basic sites on the surface, which facilitated the formation of highly dispersed CuO species. A structure-performance relationship study indicated that copper(ii) in CuO was the active site for the epoxidation and oxidation of styrene, and that Cu II of rich electronic density favored the improvement of selectivity of styrene oxide. Based on these results, a reaction mechanism was proposed. Moreover, the preferred catalytic performance of CuO/CoAl-HT could be maintained in five reused cycles.

Ring opening of epoxides with C-nucleophiles.

PubMed

Faiz, Sadia; Zahoor, Ameer Fawad

2016-11-01

Ring opening of epoxides has been an area of interest for organic chemists, owing to their reactivity toward nucleophiles. Such reactions yield important products depending on the type of nucleophiles used. This review article covers the synthetic approaches (1991-2015) used for the ring opening of epoxides via carbon nucleophiles.

Regio- and enantiofacial selectivity of epoxyeicosatrienoic acid hydration by cytosolic epoxide hydrolase.

PubMed

Zeldin, D C; Kobayashi, J; Falck, J R; Winder, B S; Hammock, B D; Snapper, J R; Capdevila, J H

1993-03-25

The hydration of cis-epoxyeicosatrienoic acids to the corresponding vic-dihydroxyeicosatrienoic acids by cytosolic epoxide hydrolase demonstrates moderate regioselectivity with rates of hydration highest for the 14,15-epoxide and lower for the 11,12- and 8,9-epoxide (4.5, 1.6, and 1.5 mumol of product/mg of protein/min, respectively). Incubations of the 8,9- and 14,15-epoxides with cytosolic epoxide hydrolase show stereoselective formation of diols (7:3 and 4:1 ratio of antipodes, respectively) and concomitant chiral enrichment of the remaining unmetabolized substrate. In contrast, hydration of the 11,12-epoxide is nonenantioselective. The Km value of the enzyme for the 14(R),15(S)-epoxide is 3 microM. Incubations of the enantiomerically pure 8,9- and 14,15-epoxides with lung or liver cytosol, followed by chiral analysis of the resulting diols demonstrate selective cleavage of the oxirane ring at C9 and C15, respectively. On the other hand, cleavage of the 11,12- oxirane ring was less selective. The stereochemical preference of the cytosolic epoxide hydrolase, together with the known chiral composition of the endogenous arachidonate epoxide pools, suggests a functional role for this enzyme in the metabolism of these important compounds.

Polymerization of epoxidized triglycerides with fluorosulfonic acid

USDA-ARS?s Scientific Manuscript database

The use of triglycerides as agri-based renewable raw materials for the development of new products is highly desirable in view of uncertain future petroleum prices. A new method of polymerizing epoxidized soybean oil has been devised with the use of fluorosulfonic acid. Depending on the reaction con...

Access to enantioenriched alpha-amino esters via rhodium-catalyzed 1,4-addition/enantioselective protonation.

PubMed

Navarre, Laure; Martinez, Rémi; Genet, Jean-Pierre; Darses, Sylvain

2008-05-14

Conjugate addition of potassium trifluoro(organo)borates 2 to dehydroalanine derivatives 1, mediated by a chiral rhodium catalyst and in situ enantioselective protonation, afforded straightforward access to a variety of protected alpha-amino esters 3 with high yields and enantiomeric excesses up to 95%. Among the tested chiral ligands and proton sources, Binap, in combination with guaiacol (2-methoxyphenol), an inexpensive and nontoxic phenol, afforded the highest asymmetric inductions. Organostannanes have also shown to participate in this reaction. By a fine-tuning of the ester moiety, and using Difluorophos as chiral ligand, increased levels of enantioselectivity, generally close to 95%, were achieved. Deuterium labeling experiments revealed, and DFT calculation supported, an unusual mechanism involving a hydride transfer from the amido substituent to the alpha carbon explaining the high levels of enantioselectivity attained in controlling this alpha chiral center.

Enantioselective α-Vinylation of Aldehydes Via the Synergistic Combination of Copper and Amine Catalysis

PubMed Central

Skucas, Eduardas; MacMillan, David W. C.

2012-01-01

The enantioselective α-vinylation of aldehydes using vinyl iodonium triflate salts has been accomplished via the synergistic combination of copper and chiral amine catalysis. These mild catalytic conditions provide a direct route for the enantioselective construction of enolizable α-formyl vinylic stereocenters without racemization or olefin transposition. These high-value coupling adducts are readily converted into a variety of useful olefin synthons. PMID:22616631

Enantioselective synthesis of cis-decalins using organocatalysis and sulfonyl Nazarov reagents.

PubMed

Peña, Javier; Silveira-Dorta, Gastón; Moro, Rosalina F; Garrido, Narciso M; Marcos, Isidro S; Sanz, Francisca; Díez, David

2015-04-10

The first organocatalytic synthesis of cis-decalins using sulfonyl Nazarov reagents is reported. The Jørgensen's catalyst directs this highly enantioselective synthesis using different cyclohexenal derivatives.

Iron-Catalyzed Enantioselective Cross-Coupling Reactions of α-Chloroesters with Aryl Grignard Reagents.

PubMed

Jin, Masayoshi; Adak, Laksmikanta; Nakamura, Masaharu

2015-06-10

The first iron-catalyzed enantioselective cross-coupling reaction between an organometallic compound and an organic electrophile is reported. Synthetically versatile racemic α-chloro- and α-bromoalkanoates were coupled with aryl Grignard reagents in the presence of catalytic amounts of an iron salt and a chiral bisphosphine ligand, giving the products in high yields with acceptable and synthetically useful enantioselectivities (er up to 91:9). The produced α-arylalkanoates were readily converted to the corresponding α-arylalkanoic acids with high optical enrichment (er up to >99:1) via simple deprotections/recrystallizations. The results of radical probe experiments are consistent with a mechanism that involves the formation of an alkyl radical intermediate, which undergoes subsequent enantioconvergent arylation in an intermolecular manner. The developed asymmetric coupling offers not only facile and practical access to various chiral α-arylalkanoic acid derivatives, which are of significant pharmaceutical importance, but also a basis of controlling enantioselectivity in an iron-catalyzed organometallic transformation.

INTERACTION OF BENZO(A)PYRENE DIOL EPOXIDE WITH SVAO MINICHROMOSOMES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gamper, Howard B.; Yokota, Hisao A.; Bartholomew, James C.

SV40 minichromosomes were reacted with (+)7{beta},8{alpha}-dihydroxy-9{alpha},10{alpha}-epoxy- 7,8,9,10-tetrahydrobenzo[a]pyrene (BaP diol epoxide). Low levels of modification (< 5 DNA adducts/minichromosome) did not detectably alter the structure of the minichromosomes but high levels (> 200 DNA adducts/minichromosome) led to extensive fragmentation. Relative to naked SV40 DNA BaP diol epoxide induced alkylation and strand scission of minichromosomal DNA was reduced or enhanced by factors of 1.5 and 2.0, respectively. The reduction in covalent binding was attributed to the presence of histones, which competed with DNA for the hydrocarbon and reduced the probability of BaP diol epoxide intercalation by tightening the helix. The enhancement ofmore » strand scission was probably due to the catalytic effect of histones on the rate of S-elimination at apurinic sites, although an altered adduct profile or the presence of a repair endonuclease were not excluded. Staphylococcal nuclease digestion indicated that BaP dial epoxide randomly alkylated the minichromosomal DNA. This is in contrast to studies with cellular chromatin where internucleosomal DNA was preferentially modified. Differences in the minichromosomal protein complement were responsible for this altered susceptibility.« less

Cu-catalyzed cross-coupling reactions of epoxides with organoboron compounds.

PubMed

Lu, Xiao-Yu; Yang, Chu-Ting; Liu, Jing-Hui; Zhang, Zheng-Qi; Lu, Xi; Lou, Xin; Xiao, Bin; Fu, Yao

2015-02-11

A copper-catalyzed cross-coupling reaction of epoxides with arylboronates is described. This reaction is not limited to aromatic epoxides, because aliphatic epoxides are also suitable substrates. In addition, N-sulfonyl aziridines can be successfully converted into the products. This reaction provides convenient access to β-phenethyl alcohols, which are valuable synthetic intermediates.

Dinuclear Zinc-Prophenol-Catalyzed Enantioselective α-Hydroxyacetate Aldol Reaction with Activated Ester Equivalents

PubMed Central

Trost, Barry M.; Michaelis, David J.; Truica, Mihai I.

2013-01-01

An enantioselective α-hydroxyacetate aldol reaction that employs N-acetyl pyrroles as activated ester equivalents and generates syn 1,2-diols in good yield and diastereoselectivity is reported. This dinuclear zinc Prophenol-catalyzed transformation proceeds with high enantioselectivity with a wide variety of substrates including aryl, alyl, and alkenyl aldehydes. The resulting α,β-dihydroxy activated esters are versatile intermediates for the synthesis of a variety of carboxylic acid derivatives including amides, esters, and unsymmetrical ketones. PMID:23947595

Oxidative enantioselective α-fluorination of aliphatic aldehydes enabled by N-heterocyclic carbene catalysis.

PubMed

Li, Fangyi; Wu, Zijun; Wang, Jian

2015-01-07

Described is the first study on oxidative enantioselective α-fluorination of simple aliphatic aldehydes enabled by N-heterocyclic carbene catalysis. N-fluorobis(phenyl)sulfonimide serves as a an oxidant and as an "F" source. The C-F bond formation occurs directly at the α position of simple aliphatic aldehydes, thus overcoming nontrivial challenges, such as competitive difluorination and nonfluorination, and proceeds with high to excellent enantioselectivities. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of epoxidation level on thermal properties and ionic conductivity of epoxidized natural rubber solid polymer nanocomposite electrolytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harun, Fatin; Chan, Chin Han; Winie, Tan

Effect of epoxide content on the thermal and conductivity properties of epoxidized natural rubber (ENR) solid polymer nanocomposite electrolytes was investigated. Commercial available epoxidized natural rubber having 25 (ENR25) and 50 mole% (ENR50) epoxide, respectively were incorporated with lithium perchlorate (LiClO{sub 4}) salt and titanium dioxide (TiO{sub 2}) nanofiller via solution casting method. The solid polymer nanocomposite electrolytes were characterized by differential scanning calorimetry (DSC) and impedance spectroscopy (IS) for their thermal properties and conductivity, respectively. It was evident that introduction of LiClO{sub 4} causes a greater increase in glass transition temperature (T{sub g}) and ionic conductivity of ENR50 asmore » compared to ENR25. Upon addition of TiO{sub 2} in ENR/LiClO{sub 4} system, a remarkable T{sub g} elevation was observed for both ENRs where ENR50 reveals a more pronounced changes. It is interesting to note that they exhibit different phenomenon in ionic conductivity with TiO{sub 2} loading where ENR25 shows enhancement of conductivity while ENR50 shows declination.« less

Catalytic enantioselective 1,6-conjugate additions of propargyl and allyl groups

NASA Astrophysics Data System (ADS)

Meng, Fanke; Li, Xiben; Torker, Sebastian; Shi, Ying; Shen, Xiao; Hoveyda, Amir H.

2016-09-01

Conjugate (or 1,4-) additions of carbanionic species to α,β-unsaturated carbonyl compounds are vital to research in organic and medicinal chemistry, and there are several chiral catalysts that facilitate the catalytic enantioselective additions of nucleophiles to enoates. Nonetheless, catalytic enantioselective 1,6-conjugate additions are uncommon, and ones that incorporate readily functionalizable moieties, such as propargyl or allyl groups, into acyclic α,β,γ,δ-doubly unsaturated acceptors are unknown. Chemical transformations that could generate a new bond at the C6 position of a dienoate are particularly desirable because the resulting products could then be subjected to further modifications. However, such reactions, especially when dienoates contain two equally substituted olefins, are scarce and are confined to reactions promoted by a phosphine-copper catalyst (with an alkyl Grignard reagent, dialkylzinc or trialkylaluminium compounds), a diene-iridium catalyst (with arylboroxines), or a bisphosphine-cobalt catalyst (with monosilyl-acetylenes). 1,6-Conjugate additions are otherwise limited to substrates where there is full substitution at the C4 position. It is unclear why certain catalysts favour bond formation at C6, and—although there are a small number of catalytic enantioselective conjugate allyl additions—related 1,6-additions and processes involving a propargyl unit are non-existent. Here we show that an easily accessible organocopper catalyst can promote 1,6-conjugate additions of propargyl and 2-boryl-substituted allyl groups to acyclic dienoates with high selectivity. A commercially available allenyl-boron compound or a monosubstituted allene may be used. Products can be obtained in up to 83 per cent yield, >98:2 diastereomeric ratio (for allyl additions) and 99:1 enantiomeric ratio. We elucidate the mechanistic details, including the origins of high site selectivity (1,6- versus 1,4-) and enantioselectivity as a function of the catalyst

Autonomic self-healing in epoxidized natural rubber.

PubMed

Rahman, Arifur; Sartore, Luciana; Bignotti, Fabio; Di Landro, Luca

2013-02-01

The development of polymers that can repair damage autonomously would be useful to improve the lifetime of polymeric materials. To date, limited attention has been dedicated to developing elastomers with autonomic self-healing ability, which can recover damages without need for an external or internal source of healing agents. This work investigates the self-healing behavior of epoxidized natural rubber (ENR) with two different epoxidation levels (25 and 50 mol % epoxidation) and of the corresponding unfunctionalized rubber, cis-1,4-polyisoprene (PISP). A self-adhesion assisted self-healing behavior was revealed by T-peel tests on slightly vulcanized rubbers. A higher epoxidation level was found to enhance self-healing. Self-healing of rubbers following ballistic damages was also investigated. A pressurized air flow test setup was used to evaluate the self-healing of ballistic damages in rubbers. Microscope (OM, SEM, and TEM) analyses were carried out to provide further evidence of healing in the impact zones. Self-healing of ballistic damages was observed only in ENR with 50 mol % epoxidation and it was found to be influenced significantly by the cross-link density. Finally, self-healing of ballistic damages was also observed in ENR50/PISP blends only when the content of the healing component (i.e., ENR50) was at least 25 wt %. From an analysis of the results, it was concluded that a synergistic effect between interdiffusion and interaction among polar groups leads to self-healing in ENR.

Versatile Synthesis of Stable, Functional Polypeptides via Reaction with Epoxides.

PubMed

Gharakhanian, Eric G; Deming, Timothy J

2015-06-08

Methodology was developed for efficient alkylation of methionine residues using epoxides as a general strategy to introduce a wide range of functional groups onto polypeptides. Use of a spacer between epoxide and functional groups further allowed addition of sterically demanding functionalities. Contrary to other methods to alkylate methionine residues, epoxide alkylations allow the reactions to be conducted in wet protic media and give sulfonium products that are stable against dealkylation. These functionalizations are notable since they are chemoselective, utilize stable and readily available epoxides, and allow facile incorporation of an unprecedented range of functional groups onto simple polypeptides using stable linkages.

The oxidation of copper catalysts during ethylene epoxidation.

PubMed

Greiner, M T; Jones, T E; Johnson, B E; Rocha, T C R; Wang, Z J; Armbrüster, M; Willinger, M; Knop-Gericke, A; Schlögl, R

2015-10-14

The oxidation of copper catalysts during ethylene epoxidation was characterized using in situ photoemission spectroscopy and electron microscopy. Gas chromatography, proton-transfer reaction mass spectrometry and electron-ionization mass spectrometry were used to characterize the catalytic properties of the oxidized copper. We find that copper corrodes during epoxidation in a 1 : 1 mixture of oxygen and ethylene. The catalyst corrosion passes through several stages, beginning with the formation of an O-terminated surface, followed by the formation of Cu2O scale and eventually a CuO scale. The oxidized catalyst exhibits measurable activity for ethylene epoxidation, but with a low selectivity of <3%. Tests on pure Cu2O and CuO powders confirm that the oxides intrinsically exhibit partial-oxidation activity. Cu2O was found to form acetaldehyde and ethylene epoxide in roughly equal amounts (1.0% and 1.2% respectively), while CuO was found to form much less ethyl aldehyde than ethylene epoxide (0.1% and 1.0%, respectively). Metallic copper catalysts were examined in extreme dilute-O2 epoxidation conditions to try and keep the catalyst from oxidizing during the reaction. It was found that in feed of 1 part O2 to 2500 parts C2H4 (PO2 = 1.2 × 10(-4) mbar) the copper surface becomes O-terminated. The O-terminated surface was found to exhibit partial-oxidation selectivity similar to that of Cu2O. With increasing O2 concentration (>8/2500) Cu2O forms and eventually covers the surface.

Asymmetric allylation of ketones and subsequent tandem reactions catalyzed by a novel polymer-supported titanium-BINOLate complex.

PubMed

Yadav, Jagjit; Stanton, Gretchen R; Fan, Xinyuan; Robinson, Jerome R; Schelter, Eric J; Walsh, Patrick J; Pericas, Miquel A

2014-06-02

By using a novel, simple, and convenient synthetic route, enantiopure 6-ethynyl-BINOL (BINOL = 1,1-binaphthol) was synthesized and anchored to an azidomethylpolystyrene resin through a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. The polystyrene (PS)-supported BINOL ligand was converted into its diisopropoxytitanium derivative in situ and used as a heterogeneous catalyst in the asymmetric allylation of ketones. The catalyst showed good activity and excellent enantioselectivity, typically matching the results obtained in the corresponding homogeneous reaction. The allylation reaction mixture could be submitted to epoxidation by simple treatment with tert-butyl hydroperoxide (TBHP), and the tandem asymmetric allylation epoxidation process led to a highly enantioenriched epoxy alcohol with two adjacent quaternary centers as a single diastereomer. A tandem asymmetric allylation/Pauson-Khand reaction was also performed, involving simple treatment of the allylation reaction mixture with Co2(CO)8/N-methyl morpholine N-oxide. This cascade process resulted in the formation of two diastereomeric tricyclic enones in high yields and enantioselectivities. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Preparation of (−)-Nutlin-3 Using Enantioselective Organocatalysis at Decagram Scale

PubMed Central

Davis, Tyler A.; Vilgelm, Anna E.; Richmond, Ann; Johnston, Jeffrey N.

2013-01-01

Chiral nonracemic cis-4,5-bis(aryl) imidazolines have emerged as a powerful platform for the development of cancer chemotherapeutics, stimulated by the Hoffmann-La Roche discovery that Nutlin-3 can restore apoptosis in cells with wild-type p53. The lack of efficient methods for the enantioselective synthesis of cis-imidazolines, however, has limited their more general use. Our disclosure of the first enantioselective synthesis of (−)-Nutlin-3 provided a basis to prepare larger amounts of this tool used widely in cancer biology. Key to the decagram-scale synthesis described here was the discovery of a novel bis(amidine) organocatalyst that provides high enantioselectivity at warmer reaction temperature (−20 °C) and low catalyst loadings. Further refinements to the procedure led to the synthesis of (−)-Nutlin-3 in a 17 gram batch, and elimination of all but three chromatographic purifications. PMID:24127627

40 CFR 721.10210 - Soybean oil, epoxidized, reaction products with diethanolamine.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Soybean oil, epoxidized, reaction... Significant New Uses for Specific Chemical Substances § 721.10210 Soybean oil, epoxidized, reaction products... chemical substance identified as soybean oil, epoxidized, reaction products with diethanolamine (PMN P-09...

Enantioselective and regiodivergent copper-catalyzed conjugate addition of trialkylaluminium reagents to extended nitro-Michael acceptors.

PubMed

Tissot, Matthieu; Müller, Daniel; Belot, Sébastien; Alexakis, Alexandre

2010-06-18

The first highly enantioselective and regiodivergent conjugate addition of trialkylaluminium reagents to nitrodienes and nitroenynes is described. By a design of the substrate and a fine-tuning of the reaction conditions, it is possible to selectively form the 1,4- or 1,6-adduct. The same combination of catalyst, copper source, and a ferrocene-based phosphine ligand afforded enantioselectivities up to 95% and 91%, respectively.

An enantioselective approach to the preparation of chiral sulfones by Ir-catalyzed asymmetric hydrogenation.

PubMed

Peters, Byron K; Zhou, Taigang; Rujirawanich, Janjira; Cadu, Alban; Singh, Thishana; Rabten, Wangchuk; Kerdphon, Sutthichat; Andersson, Pher G

2014-11-26

Several chiral sulfonyl compounds were prepared using the iridium catalyzed asymmetric hydrogenation reaction. Vinylic, allylic and homoallylic sulfone substitutions were investigated, and high enantioselectivity is maintained regardless of the location of the olefin with respect to the sulfone. Impressive stereoselectivity was obtained for dialkyl substitutions, which typically are challenging substrates in the hydrogenation. As expected, the more bulky Z-substrates were hydrogenated slower than the corresponding E isomers, and in slightly lower enantioselectivity.

Gold nanoparticle-catalyzed environmentally benign deoxygenation of epoxides to alkenes.

PubMed

Noujima, Akifumi; Mitsudome, Takato; Mizugaki, Tomoo; Jitsukawa, Koichiro; Kaneda, Kiyotomi

2011-09-28

We have developed a highly efficient and green catalytic deoxygenation of epoxides to alkenes using gold nanoparticles (NPs) supported on hydrotalcite [HT: Mg(6)Al(2)CO(3)(OH)(16)] (Au/HT) with alcohols, CO/H(2)O or H(2) as the reducing reagent. Various epoxides were selectively converted to the corresponding alkenes. Among the novel metal NPs on HT, Au/HT was found to exhibit outstanding catalytic activity for the deoxygenation reaction. Moreover, Au/HT can be separated from the reaction mixture and reused with retention of its catalytic activity and selectivity. The high catalytic performance of Au/HT was attributed to the selective formation of Au-hydride species by the cooperative effect between Au NPs and HT.

Kinetic and dynamic kinetic resolution of secondary alcohols with ionic-surfactant-coated Burkholderia cepacia lipase: substrate scope and enantioselectivity.

PubMed

Kim, Cheolwoo; Lee, Jusuk; Cho, Jeonghun; Oh, Yeonock; Choi, Yoon Kyung; Choi, Eunjeong; Park, Jaiwook; Kim, Mahn-Joo

2013-03-15

Forty-four different secondary alcohols, which can be classified into several types (II-IX), were tested as the substrates of ionic surfactant-coated Burkholderia cepacia lipase (ISCBCL) to see its substrate scope and enantioselectivity in kinetic and dynamic kinetic resolution (KR and DKR). They include 6 boron-containing alcohols, 24 chiral propargyl alcohols, and 14 diarylmethanols. The results from the studies on KR indicate that ISCBCL accepted most of them with high enantioselectivity at ambient temperature and with useful to high enantioselectivity at elevated temperatures. In particular, ISCBCL displayed high enantioselectivity toward sterically demanding secondary alcohols (types VIII and IX) which have two bulky substituents at the hydroxymethine center. DKR reactions were performed by the combination of ISCBCL with a ruthenium-based racemization catalyst at 25-60 °C. Forty-one secondary alcohols were tested for DKR. About half of them were transformed into their acetates of high enantiopurity (>90% ee) with good yields (>80%). It is concluded that ISCBCL appears to be a superb enzyme for the KR and DKR of secondary alcohols.

Stereoselective Epoxidation of 4-Deoxypentenosides: A Polarized-πModel

PubMed Central

Cheng, Gang; Boulineau, Fabien P.; Liew, Siong-Tern; Shi, Qicun; Wenthold, Paul G.; Wei, Alexander

2008-01-01

The high facioselectivity in the epoxidation of 4-deoxypentenosides (4-DPs) by dimethyldioxirane (DMDO) correlates with a stereoelectronic bias in the 4-DPs’ ground-state conformations, as elucidated by polarized-π frontier molecular orbital (PPFMO) analysis. PMID:16986946

Epoxide reduction with hydrazine on graphene: a first principles study.

PubMed

Kim, Min Chan; Hwang, Gyeong S; Ruoff, Rodney S

2009-08-14

Mechanisms for epoxide reduction with hydrazine on a single-layer graphene sheet are examined using quantum mechanical calculations within the framework of gradient-corrected spin-polarized density-functional theory. We find that the reduction reaction is mainly governed by epoxide ring opening which is initiated by H transfer from hydrazine or its derivatives. In addition, our calculations suggest that the epoxide reduction by hydrazine may predominantly follow a direct Eley-Rideal mechanism rather than a Langmuir-Hinshelwood mechanism. We also discuss the generation of various hydrazine derivatives during the reduction of graphene oxide with hydrazine and their potential contribution to lowering the barrier height of epoxide ring opening.

Robust, Chiral, and Porous BINAP-Based Metal–Organic Frameworks for Highly Enantioselective Cyclization Reactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sawano, Takahiro; Thacker, Nathan C.; Lin, Zekai

2016-05-06

We report here the design of BINAP-based metal–organic frameworks and their postsynthetic metalation with Rh complexes to afford highly active and enantioselective single-site solid catalysts for the asymmetric cyclization reactions of 1,6-enynes. Robust, chiral, and porous Zr-MOFs of UiO topology, BINAP-MOF (I) or BINAP-dMOF (II), were prepared using purely BINAP-derived dicarboxylate linkers or by mixing BINAP-derived linkers with unfunctionalized dicarboxylate linkers, respectively. Upon metalation with Rh(nbd)2BF4 and [Rh(nbd)Cl]2/AgSbF6, the MOF precatalysts I·Rh(BF4) and I·Rh(SbF6) efficiently catalyzed highly enantioselective (up to 99% ee) reductive cyclization and Alder-ene cycloisomerization of 1,6-enynes, respectively. I·Rh catalysts afforded cyclization products at comparable enantiomeric excesses (ee’s)more » and 4–7 times higher catalytic activity than the homogeneous controls, likely a result of catalytic site isolation in the MOF which prevents bimolecular catalyst deactivation pathways. However, I·Rh is inactive in the more sterically encumbered Pauson–Khand reactions between 1,6-enynes and carbon monoxide. In contrast, with a more open structure, Rh-functionalized BINAP-dMOF, II·Rh, effectively catalyzed Pauson–Khand cyclization reactions between 1,6-enynes and carbon monoxide at 10 times higher activity than the homogeneous control. II·Rh was readily recovered and used three times in Pauson–Khand cyclization reactions without deterioration of yields or ee’s. Our work has expanded the scope of MOF-catalyzed asymmetric reactions and showed that the mixed linker strategy can effectively enlarge the open space around the catalytic active site to accommodate highly sterically demanding polycyclic metallocycle transition states/intermediates in asymmetric intramolecular cyclization reactions.« less

An efficient and highly stereoselective synthesis of new P-chiral 1,5-diphosphanylferrocene ligands and their use in enantioselective hydrogenation.

PubMed

Chen, Weiping; Roberts, J Stanley M; Whittall, John; Steiner, Alexander

2006-07-21

An efficient and highly stereoselective synthesis of P-chiral 1,5-diphosphanylferrocene ligands has been developed, and the introduction of P-chirality in ferrocene-based phosphine ligands enhances the enantioselective discrimination produced by the corresponding catalyst when matching of the planar chirality, the chirality at carbon and the chirality at phosphorus occurs.

Chiral Nickel(II) Complex Catalyzed Enantioselective Doyle-Kirmse Reaction of α-Diazo Pyrazoleamides.

PubMed

Lin, Xiaobin; Tang, Yu; Yang, Wei; Tan, Fei; Lin, Lili; Liu, Xiaohua; Feng, Xiaoming

2018-03-07

Although high enantioselectivity of [2,3]-sigmatropic rearrangement of sulfonium ylides (Doyle-Kirmse reaction) has proven surprisingly elusive using classic chiral Rh(II) and Cu(I) catalysts, in principle it is due to the difficulty in fine discrimination of the heterotopic lone pairs of sulfur and chirality inversion at sulfur of sulfonium ylides. Here, we show that the synergistic merger of new α-diazo pyrazoleamides and a chiral N, N'-dioxide-nickel(II) complex catalyst enables a highly enantioselective Doyle-Kirmse reaction. The pyrazoleamide substituent serves as both an activating and a directing group for the ready formation of a metal-carbene- and Lewis-acid-bonded ylide intermediate in the assistance of a dual-tasking nickel(II) complex. An alternative chiral Lewis-acid-bonded ylide pathway greatly improves the product enantiopurity even for the reaction of a symmetric diallylsulfane. The majority of transformations over a series of aryl- or vinyl-substituted α-diazo pyrazoleamindes and sulfides proceed rapidly (within 5-20 min in most cases) with excellent results (up to 99% yield and 96% ee), providing a breakthrough in enantioselective Doyle-Kirmse reaction.

Enantioselective Syntheses of (−)-Alloyohimbane and (−)-Yohimbane by an Efficient Enzymatic Desymmetrization Process

PubMed Central

Ghosh, Arun K.; Sarkar, Anindya

2016-01-01

Enantioselective syntheses of (−)-alloyohimbane and (−)-yohimbane was accomplished in a convergent manner. The key step involved a modified mild protocol for the enantioselective enzymatic desymmetrization of meso-diacetate. The protocol provided convenient access to an optically active monoacetate in multi-gram scale in high enantiomeric purity. This monoacetate was converted to (−)-alloyohimbane. Reductive amination of the derived aldehyde causes the isomerization leading to the trans-product and allows the synthesis of (−)-yohimbane. PMID:28757804

Influence of biochar on the enantioselective behavior of the chiral fungicide metalaxyl in soil

NASA Astrophysics Data System (ADS)

Gámiz, Beatriz; Pignatello, Joseph J.; Hermosín, María Carmen; Cox, Lucía; Celis, Rafael

2015-04-01

Chiral pesticides comprise an emerging and important class of organic pollutants currently, accounting for more than a quarter of used pesticides. Consequently, the contamination problems caused by chiral pesticides are concern matter and factors affecting enantioselective processes of chiral pesticides in soil need to be understood. For example, certain soil management practices, such as the use of organic amendments, can affect the enantioselective behavior of chiral pesticides in soils. Recently, biochar (BC), i.e. organic matter subjected to pyrolysis, has been proposed as organic amendment due to beneficial properties such as its high stability against decay in soil environments and its apparent ability to influence the availability of nutrients. BC is considered to be more biologically inert as compared to otherforms of organic carbon. However, its side-effects on the enantioselectivity of processes affecting the fate of chiral pesticides is unknown. The aim of this study was to assess the effect of biochar (BC) on the enantioselectivity of sorption, degradation, and leaching of the chiral fungicide metalaxyl in an agricultural soil. Amending the soil with BC (2% w/w) resulted in 3 times higher sorption of metalaxyl enantiomers compared to unamended soil, but no enantioselectivity in the process was observed. Moreover, both enantiomers showed some resistance to be desorbed in BC-amended soil compared to unamended soil. Dissipation studies revealed that the degradation of metalaxylwas more enantioselective in the unamended soil than in BC-amended soil. In unamended soil, R-metalaxyl(biologically active) and S- metalaxyl had half-lives (t1/2) of 3 and 34 days, respectively. BC enhanced the persistence of both enantiomers in the soil, with R-metalaxyl being degraded faster (t1/2=43 days) than S-metalaxyl (t1/2= 100 days). The leaching of both S-and R-metalaxyl was almost suppressed after amending the soil with BC; less than 10% of the fungicide applied to soil

Synthesis and physicochemical properties of epoxidized Tmp trioleate by in situ method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samidin, Salma; Salimon, Jumat

2014-09-03

Tmp trioleate was initially synthesized via esterification of trimetilolprapane and oleic acid (90%) using 1.5% of H{sub 2}SO{sub 4} as a catalyst. The production of Tmp trioleate was observed at 98% (w/w). The iodine value of Tmp trioleate was analyzed for further reaction of epoxidation. Epoxide was important reaction as an intermediate for preparation of chemical modified lubricants from vegetable oils. Finding the best way of epoxidation process will give high quality for further modification of oil instead of reduce the cost and time for the preparation process during reaction of epoxidation. In this study, the epoxidation of unsaturation Tmpmore » trioleate with peroxyformic acid generated in-situ from hydrogen peroxide 30% in H{sub 2}O{sub 2} with formic acid was studied. 95% conversion to oxygen oxirane content (OOC) ring was obtained. The derivatization showed an improvement of the compound's oxidative stability evidenced from pressurized differential scanning calorimetry (PDSC) data which are 177°C to 200°C. Physicochemical properties showed increasing of temperature of flash point from 280°C to 300°C and viscosity index (VI) from 146 to 154. However, the pour point showed increasing temperature which was −58.81°C to −17.32°C. From the data obtained, these derivatives have shown better performance of lubricity properties. Overall, the data indicates that these performances are compatible to the commercial lubricants.« less

Enantiomerically enriched, polycrystalline molecular sieves

DOE PAGES

Brand, Stephen K.; Schmidt, Joel E.; Deem, Michael W.; ...

2017-05-01

Zeolite and zeolite-like molecular sieves are being used in a large number of applications such as adsorption and catalysis. Achievement of the long-standing goal of creating a chiral, polycrystalline molecular sieve with bulk enantioenrichment would enable these materials to perform enantioselective functions. Here, we report the synthesis of enantiomerically enriched samples of a molecular sieve. For this study, enantiopure organic structure directing agents are designed with the assistance of computational methods and used to synthesize enantioenriched, polycrystalline molecular sieve samples of either enantiomer. Computational results correctly predicted which enantiomer is obtained, and enantiomeric enrichment is proven by high-resolution transmission electronmore » microscopy. The enantioenriched and racemic samples of the molecular sieves are tested as adsorbents and heterogeneous catalysts. The enantioenriched molecular sieves show enantioselectivity for the ring opening reaction of epoxides and enantioselective adsorption of 2-butanol (the R enantiomer of the molecular sieve shows opposite and approximately equal enantioselectivity compared with the S enantiomer of the molecular sieve, whereas the racemic sample of the molecular sieve shows no enantioselectivity).« less

Enantiomerically enriched, polycrystalline molecular sieves

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brand, Stephen K.; Schmidt, Joel E.; Deem, Michael W.

Zeolite and zeolite-like molecular sieves are being used in a large number of applications such as adsorption and catalysis. Achievement of the long-standing goal of creating a chiral, polycrystalline molecular sieve with bulk enantioenrichment would enable these materials to perform enantioselective functions. Here, we report the synthesis of enantiomerically enriched samples of a molecular sieve. For this study, enantiopure organic structure directing agents are designed with the assistance of computational methods and used to synthesize enantioenriched, polycrystalline molecular sieve samples of either enantiomer. Computational results correctly predicted which enantiomer is obtained, and enantiomeric enrichment is proven by high-resolution transmission electronmore » microscopy. The enantioenriched and racemic samples of the molecular sieves are tested as adsorbents and heterogeneous catalysts. The enantioenriched molecular sieves show enantioselectivity for the ring opening reaction of epoxides and enantioselective adsorption of 2-butanol (the R enantiomer of the molecular sieve shows opposite and approximately equal enantioselectivity compared with the S enantiomer of the molecular sieve, whereas the racemic sample of the molecular sieve shows no enantioselectivity).« less

Formation of furan fatty alkyl esters from their bis-epoxide fatty esters

USDA-ARS?s Scientific Manuscript database

Epoxidation of vegetable oils and consecutive epoxide ring-opening reaction is a widely investigated path for producing biobased lubricants and polymers. The reaction mechanism and products are considered well-studied and known. In the current study, the reactions of epoxidized alkyl soyate with fou...

Selective and metal-free epoxidation of terminal alkenes by heterogeneous polydioxirane in mild conditions

NASA Astrophysics Data System (ADS)

Kazemnejadi, M.; Shakeri, A.; Nikookar, M.; Shademani, R.; Mohammadi, M.

2018-05-01

Polydioxirane (PDOX) was prepared by the treatment of polysalicylaldehyde with Oxone and was found as a selective, highly efficient and heterogeneous reagent for epoxidation of alkenes which can be successfully isolated. This work also introduced a simpler, safer and milder way for epoxidation of alkenes with dioxirane groups than before. PDOX can be simply recovered from the reaction mixture by plain filtration and reused for eight runs without significant reactivity loss.

Practical synthesis of Shi's diester fructose derivative for catalytic asymmetric epoxidation of alkenes.

PubMed

Nieto, N; Molas, P; Benet-Buchholz, J; Vidal-Ferran, A

2005-11-25

[reaction: see text] A practical synthesis of Shi's diester 3 for catalytic asymmetric epoxidations has been developed. The catalyst has been prepared in multigram quantities from D-fructose in four steps with a 66% overall yield. Efficiency, cost, and selectivity aspects of the reagents involved for its preparation have been taken care of during its preparation. The workup procedures have been simplified to the bare minimum, rendering a very practical preparation method. The well-known high efficiency of this catalyst 3 in the epoxidation of alpha,beta-unsaturated carbonyl compounds has also proved to be high in unfunctionalized alkenes.

Sulfuric acid as a catalyst for ring-opening of biobased bis-epoxides

USDA-ARS?s Scientific Manuscript database

Vegetable oils can be relatively and easily transformed into bio-based epoxides. Because of this, the acid-catalyzed epoxide ring-opening has been explored for the preparation of bio-based lubricants and polymers. Detailed model studies are carried out only with mono-epoxide made from methyl oleate,...

Catalytic, Enantioselective, Intramolecular Sulfenofunctionalization of Alkenes with Phenols

PubMed Central

2017-01-01

The catalytic, enantioselective, cyclization of phenols with electrophilic sulfenophthalimides onto isolated or conjugated alkenes affords 2,3-disubstituted benzopyrans and benzoxepins. The reaction is catalyzed by a BINAM-based phosphoramide Lewis base catalyst which assists in the highly enantioselective formation of a thiiranium ion intermediate. The influence of nucleophile electron density, alkene substitution pattern, tether length and Lewis base functional groups on the rate, enantio- and site-selectivity for the cyclization is investigated. The reaction is not affected by the presence of substituents on the phenol ring. In contrast, substitutions around the alkene strongly affect the reaction outcome. Sequential lengthening of the tether results in decreased reactivity, which necessitated increased temperatures for reaction to occur. Sterically bulky aryl groups on the sulfenyl moiety prevented erosion of enantiomeric composition at these elevated temperatures. Alcohols and carboxylic acids preferentially captured thiiranium ions in competition with phenolic hydroxyl groups. An improved method for the selective C(2) allylation of phenols is also described. PMID:28257203

Enantioselective Decarboxylative Alkylation Reactions: Catalyst Development, Substrate Scope, and Mechanistic Studies

PubMed Central

Behenna, Douglas C.; Mohr, Justin T.; Sherden, Nathaniel H.; Marinescu, Smaranda C.; Harned, Andrew M.; Tani, Kousuke; Seto, Masaki; Ma, Sandy; Novák, Zoltán; Krout, Michael R.; McFadden, Ryan M.; Roizen, Jennifer L.; Enquist, John A.; White, David E.; Levine, Samantha R.; Petrova, Krastina V.; Iwashita, Akihiko; Virgil, Scott C.; Stoltz, Brian M.

2012-01-01

α-Quaternary ketones are accessed through novel enantioselective alkylations of allyl and propargyl electrophiles by unstabilized prochiral enolate nucleophiles in the presence of palladium complexes with various phosphinooxazoline (PHOX) ligands. Excellent yields and high enantiomeric excesses are obtained from three classes of enolate precursors: enol carbonates, enol silanes, and racemic β-ketoesters. Each of these substrate classes functions with nearly identical efficiency in terms of yield and enantioselectivity. Catalyst discovery and development, the optimization of reaction conditions, the exploration of reaction scope, and applications in target-directed synthesis are reported. Experimental observations suggest that these alkylation reactions occur through an unusual inner-sphere mechanism involving binding of the prochiral enolate nucleophile directly to the palladium center. PMID:22083969

Enantioselective synthesis of chiral 3-aryl-1-indanones through rhodium-catalyzed asymmetric intramolecular 1,4-addition.

PubMed

Yu, Yue-Na; Xu, Ming-Hua

2013-03-15

Enantioselective synthesis of potentially useful chiral 3-aryl-1-indanones was achieved through a rhodium-catalyzed asymmetric intramolecular 1,4-addition of pinacolborane chalcone derivatives using extraordinary simple MonoPhos as chiral ligand under relatively mild conditions. This novel protocol offers an easy access to a wide variety of enantioenriched 3-aryl-1-indanone derivatives in high yields (up to 95%) with excellent enantioselectivities (up to 95% ee).

Highly Z- and Enantioselective Ring-Opening/Cross-Metathesis Reactions Catalyzed by Stereogenic-at-Mo Adamantylimido Complexes

PubMed Central

Ibrahem, Ismail; Yu, Miao; Schrock, Richard R.; Hoveyda, Amir H.

2009-01-01

The first highly Z- and enantioselective class of ring-opening/cross-metathesis (ROCM) reactions is presented. Transformations are promoted in the presence of <2 mol % of chiral stereogenic-at-Mo monoaryloxide complexes, which bear an adamantylimido ligand and are prepared and used in situ. Reactions involve meso oxabicyclic substrates and afford the desired pyrans in 50–85% yield and in up to >98:<2 enantiomer ratio (er). Importantly, the desired chiral pyrans are thus obtained bearing a Z olefin either exclusively (>98:<2 Z:E) or predominantly (≥87:13 Z:E). PMID:19249833

Asymmetric vinylogous Mukaiyama aldol reaction of isatins under bifunctional organocatalysis: enantioselective synthesis of substituted 3-hydroxy-2-oxindoles.

PubMed

Laina-Martín, Víctor; Humbrías-Martín, Jorge; Fernández-Salas, José A; Alemán, José

2018-03-13

A highly enantioselective organocatalytic vinylogous Mukaiyama aldol reaction of silyloxy dienes and isatins under bifunctional organocatalysis is presented. Substituted 3-hydroxy-2-oxindoles are synthesised in good yields and enantioselectivities. These synthetic intermediates are used for the construction of more complex molecules with biological properties such as the formal synthesis of a CB2 agonist presented.

Regio- and enantioselective palladium-catalyzed allylic alkylation of nitromethane with monosubstituted allyl substrates: synthesis of (R)-rolipram and (R)-baclofen.

PubMed

Yang, Xiao-Fei; Ding, Chang-Hua; Li, Xiao-Hui; Huang, Jian-Qiang; Hou, Xue-Long; Dai, Li-Xin; Wang, Pin-Jie

2012-10-19

The Pd-catalyzed asymmetric allylic alkylation (AAA) reaction of nitromethane with monosubstituted allyl substrates was realized for the first time to provide corresponding products in high yields with excellent regio- and enantioselectivities. The protocol was applied to the enantioselective synthesis of (R)-baclofen and (R)-rolipram.

Controlling the enantioselectivity of enzymes by directed evolution: Practical and theoretical ramifications

PubMed Central

Reetz, Manfred T.

2004-01-01

A fundamentally new approach to asymmetric catalysis in organic chemistry is described based on the in vitro evolution of enantioselective enzymes. It comprises the appropriate combination of gene mutagenesis and expression coupled with an efficient high-throughput screening system for evaluating enantioselectivity (enantiomeric excess assay). Several such cycles lead to a “Darwinistic” process, which is independent of any knowledge concerning the structure or the mechanism of the enzyme being evolved. The challenge is to choose the optimal mutagenesis methods to navigate efficiently in protein sequence space. As a first example, the combination of error-prone mutagenesis, saturation mutagenesis, and DNA-shuffling led to a dramatic enhancement of enantioselectivity of a lipase acting as a catalyst in the kinetic resolution of a chiral ester. Mutations at positions remote from the catalytically active center were identified, a surprising finding, which was explained on the basis of a novel relay mechanism. The scope and limitations of the method are discussed, including the prospect of directed evolution of stereoselective hybrid catalysts composed of robust protein hosts in which transition metal centers have been implanted. PMID:15079053

The Catalytic Enantioselective Total Synthesis of (+)-Liphagal**

PubMed Central

Day, Joshua J.; McFadden, Ryan M.; Virgil, Scott C.; Kolding, Helene; Alleva, Jennifer L.; Stoltz, Brian M.

2012-01-01

Ring a ding: The first catalytic enantioselective total synthesis of the meroterpenoid natural product (+)-liphagal is disclosed. The approach showcases a variety of technology including enantioselective enolate alkylation, a photochemical alkyne-alkene [2+2] reaction, microwave-assisted metal catalysis, and an intramolecular aryne capture cyclization reaction. Pivotal to the successful completion of the synthesis was a sequence involving ring expansion from a [6-5-4] tricycle to a [6-7] bicyclic core followed by stereoselective hydrogenation of a sterically occluded tri-substituted olefin to establish the trans homodecalin system found in the natural product. PMID:21671325

Probing Competitive and Co-operative Hydroxyl and Ammonium Hydrogen-Bonding Directed Epoxidations.

PubMed

Brambilla, Marta; Brennan, Méabh B; Csatayová, Kristína; Davies, Stephen G; Fletcher, Ai M; Kennett, Alice M R; Lee, James A; Roberts, Paul M; Russell, Angela J; Thomson, James E

2017-10-06

The diastereoselectivities and rates of epoxidation (upon treatment with Cl 3 CCO 2 H then m-CPBA) of a range of cis- and trans-4-aminocycloalk-2-en-1-ol derivatives (containing five-, six-, and seven-membered rings) have been investigated. In all cases where the two potential directing groups can promote epoxidation on opposite faces of the ring scaffold, evidence of competitive epoxidation pathways, promoted by hydrogen-bonding to either the in situ formed ammonium moiety or the hydroxyl group, was observed. In contrast to the relative directing group abilities already established for the six-membered ring system (NHBn ≫ OH > NBn 2 ), an N,N-dibenzylammonium moiety appeared more proficient than a hydroxyl group at directing the stereochemical course of the epoxidation reaction in a five- or seven-membered system. In the former case, this was rationalized by the drive to minimize torsional strain in the transition state being coupled with assistance from hydrogen-bonding to the ammonium moiety. In the latter case, this was ascribed to the steric bulk of the ammonium moiety disfavoring conformations in which hydrogen-bonding to the hydroxyl group results in direction of the epoxidation to the syn face. In cases where the two potential directing groups can promote epoxidation on the same face of the ring scaffold, an enhancement of epoxidation diastereoselectivity was not observed, while introduction of a second, allylic heteroatom to the substrate results in diminishment of the rate of epoxidation in all cases. Presumably, reduction of the nucleophilicity of the olefin by the second, inductively electron-withdrawing heteroatom is the dominant factor, and any assistance to the epoxidation reaction by the potential to form hydrogen-bonds to two directing groups rather than one is clearly unable to overwhelm it.

Ultrasound-assisted chemoenzymatic epoxidation of soybean oil by using lipase as biocatalyst.

PubMed

Bhalerao, Machhindra S; Kulkarni, Vaishali M; Patwardhan, Anand V

2018-01-01

The present work reports the use of ultrasonic irradiation for enhancing lipase catalyzed epoxidation of soybean oil. Higher degree of unsaturated fatty acids, present in the soybean oil was converted to epoxidized soybean oil by using an immobilized lipase, Candida antarctica (Novozym 435). The effects of various parameters on the relative percentage conversion of the double bond to oxirane oxygen were investigated and the optimum conditions were established. The parameters studied were temperature, hydrogen peroxide to ethylenic unsaturation mole ratio, stirring speed, solvent ratio, catalyst loading, ultrasound frequency, ultrasound input power and duty cycle. The main objective of this work was to intensify chemoenzymatic epoxidation of the soybean oil by using ultrasound, to reduce the time required for epoxidation. Epoxidation of the soybean oil was achieved under mild reaction conditions by indirect ultrasonic irradiations (using ultrasonic bath). The relative percentage conversion to oxirane oxygen of 91.22% was achieved within 5h. The lipase was remarkably stable under optimized reaction conditions, later was recovered and reused six times to produce epoxidized soybean oil (ESO). Copyright © 2017 Elsevier B.V. All rights reserved.

Highly Enantioselective Synthesis of syn-β-Hydroxy α-Dibenzylamino Esters via DKR Asymmetric Transfer Hydrogenation and Gram-Scale Preparation of Droxidopa.

PubMed

Sun, Guodong; Zhou, Zihong; Luo, Zhonghua; Wang, Hailong; Chen, Lei; Xu, Yongbo; Li, Shun; Jian, Weilin; Zeng, Jiebin; Hu, Benquan; Han, Xiaodong; Lin, Yicao; Wang, Zhongqing

2017-08-18

A highly efficient preparation of enantiomerically pure syn aryl β-hydroxy α-dibenzylamino esters is reported. The outcome was achieved via dynamic kinetic resolution and asymmetric transfer hydrogenation of aryl α-dibenzylamino β-keto esters. The desired products were obtained in high yields (up to 98%) with excellent diastereoselectivity (>20:1 dr) and enantioselectivity (up to >99% ee). Furthermore, this method was applied for the gram-scale preparation of droxidopa.

Silica-Supported Catalyst for Enantioselective Arylation of Aldehydes under Batch and Continuous-Flow Conditions.

PubMed

Watanabe, Satoshi; Nakaya, Naoyuki; Akai, Junichiro; Kanaori, Kenji; Harada, Toshiro

2018-05-04

A silica-supported 3-aryl H 8 -BINOL-derived titanium catalyst exhibited high performance in the enantioselective arylation of aromatic aldehydes using Grignard and organolithium reagents not only under batch conditions but also under continuous-flow conditions. Even with a simple pipet reactor packed with the heterogeneous catalyst, the enantioselective production of chiral diarylmethanols could be achieved through a continuous introduction of aldehydes and mixed titanium reagents generated from the organometallic precursors. The pipet reactor could be used repeatedly in different reactions without appreciable deterioration of the activity.

Preferential glutathione conjugation of a reverse diol epoxide compared to a bay region diol epoxide of phenanthrene in human hepatocytes: relevance to molecular epidemiology studies of glutathione-s-transferase polymorphisms and cancer.

PubMed

Hecht, Stephen S; Berg, Jeannette Zinggeler; Hochalter, J Bradley

2009-03-16

Bay region diol epoxides are recognized ultimate carcinogens of polycyclic aromatic hydrocarbons (PAH), and in vitro studies have demonstrated that they can be detoxified by conjugation with glutathione, leading to the widely investigated hypothesis that individuals with low activity forms of glutathione-S-transferases are at higher risk of PAH induced cancer, a hypothesis that has found at most weak support in molecular epidemiology studies. A weakness in this hypothesis was that the mercapturic acids resulting from the conjugation of PAH bay region diol epoxides had never been identified in human urine. We recently analyzed smokers' urine for mercapturic acids derived from phenanthrene, the simplest PAH with a bay region. The only phenanthrene diol epoxide-derived mercapturic acid in smokers' urine was produced from the reverse diol epoxide, anti-phenanthrene-3,4-diol-1,2-epoxide (11), not the bay region diol epoxide, anti-phenanthrene-1,2-diol-3,4-epoxide (10), which does not support the hypothesis noted above. In this study, we extended these results by examining the conjugation of phenanthrene metabolites with glutathione in human hepatocytes. We identified the mercapturic acid N-acetyl-S-(r-4,t-2,3-trihydroxy-1,2,3,4-tetrahydro-c-1-phenanthryl)-L-cysteine (14a), (0.33-35.9 pmol/mL at 10 microM 8, 24 h incubation, N = 10) in all incubations with phenanthrene-3,4-diol (8) and the corresponding diol epoxide 11, but no mercapturic acids were detected in incubations with phenanthrene-1,2-diol (7), and only trace amounts were observed in incubations with the corresponding bay region diol epoxide 10. Taken together with our previous results, these studies clearly demonstrate that glutathione conjugation of a reverse diol epoxide of phenanthrene is favored over conjugation of a bay region diol epoxide. Since reverse diol epoxides of PAH are generally weakly or nonmutagenic/carcinogenic, these results, if generalizable to other PAH, do not support the widely held

Methyltrioxorhenium-catalyzed epoxidation of homoallylic alcohols with hydrogen peroxide.

PubMed

Yamazaki, Shigekazu

2012-11-02

Homoallylic alcohols were efficiently converted to the corresponding 3,4-epoxy alcohols in excellent yields by methyltrioxorhenium (MTO)-catalyzed epoxidation with aqueous hydrogen peroxide as the terminal oxidant and 3-methylpyrazole (10 mol %) as an additive. The epoxidations of homoallylic alcohols proceeded under organic solvent-free conditions faster than those in dichloromethane.

Enantioselective Cytotoxicity Profile of o,p’-DDT in PC 12 Cells

PubMed Central

Zhang, Chunlong; Wen, Yuezhong; Liu, Weiping

2012-01-01

Background The continued uses of dichlordiphenyltrichloroethane (DDT) for indoor vector control in some developing countries have recently fueled intensive debates toward the global ban of this persistent legacy contaminant. Current approaches for ecological and health risk assessment has ignored the chiral nature of DDT. In this study by employing an array of cytotoxicity related endpoints, we investigated the enantioselective cytotoxicity of o,p’-DDT. Principal Findings we demonstrated for the first time that R-(−)-o,p’-DDT caused more neuron cell death by inducing more severe oxidative stress, which selectively imbalanced the transcription of stress-related genes (SOD1, SOD2, HSP70) and enzyme (superoxide dismutase and lactate dehydrogenase) activities, and greater cellular apoptosis compared to its enantiomer S-(+)-o,p’-DDT at the level comparable to malaria area exposure (parts per million). We further elucidated enantioselective modes of action using microarray combined with enzyme-linked immunosorbent assay. The enantioselective apoptosis might involve three signaling pathways via caspase 3, tumor protein 53 (p53) and NFkB. Conclusions Based on DDT stereochemistry and results reported for other chiral pesticides, our results pointed to the same directional enantioselectivity of chiral DDT toward mammalian cells. We proposed that risk assessment on DDT should consider the enantiomer ratio and enantioselectivities. PMID:22937105

Enantioselective construction of quaternary stereogenic carbon atoms by the Lewis base catalyzed additions of silyl ketene imines to aldehydes.

PubMed

Denmark, Scott E; Wilson, Tyler W; Burk, Matthew T

2014-07-21

Silyl ketene imines derived from a variety of α-branched nitriles have been developed as highly useful reagents for the construction of quaternary stereogenic centers via the aldol addition reaction. In the presence of SiCl4 and the catalytic action of a chiral phosphoramide, silyl ketene imines undergo extremely rapid and high yielding addition to a wide variety of aromatic aldehydes with excellent diastereo- and enantioselectivity. Of particular note are the high yields and selectivities obtained from electron-rich, electron-poor, and hindered aldehydes. Linear aliphatic aldehydes did react with good diastereo- and enantioselectivity in the presence of nBu4N(+)I(-), but branched aldehydes were much less reactive. Semiempirical calculations provided a rationalization of the observed diastereo- and enantioselectivity via open transitions states. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lewis base activation of Lewis acids: catalytic, enantioselective vinylogous aldol addition reactions.

PubMed

Denmark, Scott E; Heemstra, John R

2007-07-20

The generality of Lewis base catalyzed, Lewis acid mediated, enantioselective vinylogous aldol addition reactions has been investigated. The combination of silicon tetrachloride and chiral phosphoramides is a competent catalyst for highly selective additions of a variety of alpha,beta-unsaturated ketone-, 1,3-diketone-, and alpha,beta-unsaturated amide-derived dienolates to aldehydes. These reactions provided high levels of gamma-site selectivity for a variety of substitution patterns on the dienyl unit. Both ketone- and morpholine amide-derived dienol ethers afforded high enantio- and diastereoselectivity in the addition to conjugated aldehydes. Although alpha,beta-unsaturated ketone-derived dienolate did not react with aliphatic aldehydes, alpha,beta-unsaturated amide-derived dienolates underwent addition at reasonable rates affording high yields of vinylogous aldol product. The enantioselectivities achieved with the morpholine derived-dienolate in the addition to aliphatic aldehydes was the highest afforded to date with the silicon tetrachloride-chiral phosphoramide system. Furthermore, the ability to cleanly convert the morpholine amide to a methyl ketone was demonstrated.

Epoxidized natural rubber toughened aqueous resole type liquefied EFB resin: Physical and chemical characterization

NASA Astrophysics Data System (ADS)

Amran, Umar Adli; Zakaria, Sarani; Chia, Chin Hua

2013-11-01

A preliminary study on the reaction between aqueous resole type resinified liquefied palm oil empty fruit bunches fibres (RLEFB) with epoxidized natural rubber (ENR). Liquefaction of empty fruit bunches (EFB) is carried out at different ratio of phenol to EFB (P:EFB). Resole type phenolic resin is prepared using sodium hydroxide (NaOH) as the catalyst with the ratio of liquefied EFB (LEFB) to formaldehyde (LEFB:F) of 1:1.8. 50% epoxidation of epoxidized natural rubber (ENR-50) is used to react with resole resin by mixing with ENR with aqueous resole resin. The cured resin is characterized with FT-IR and SEM. Aqueous system have been found to be unsuitable medium in the reaction between resin and ENR. This system produced a highly porous product when RLEFB/ENR resin is cured.

Enantioselective Reduction of Ketones and Imines Catalyzed by (CN-Box)Re(V)-Oxo Complexes

PubMed Central

Nolin, Kristine A.; Ahn, Richard W.; Kobayashi, Yusuke; Kennedy-Smith, Joshua J.

2012-01-01

The development and application of chiral, non-racemic Re(V)-oxo complexes to the enantioselective reduction of prochiral ketones is described. In addition to the enantioselective reduction of prochiral ketones, we report the application of these complexes to (1) a tandem Meyer-Schuster rearrangement/reduction to access enantioenriched allylic alcohols and (2) the enantioselective reduction of imines. PMID:20623567

Highly enantioselective rhodium(I)-catalyzed carbonyl carboacylations initiated by C-C bond activation.

PubMed

Souillart, Laetitia; Cramer, Nicolai

2014-09-01

The lactone motif is ubiquitous in natural products and pharmaceuticals. The Tishchenko disproportionation of two aldehydes, a carbonyl hydroacylation, is an efficient and atom-economic access to lactones. However, these reaction types are limited to the transfer of a hydride to the accepting carbonyl group. The transfer of alkyl groups enabling the formation of CC bonds during the ester formation would be of significant interest. Reported herein is such asymmetric carbonyl carboacylation of aldehydes and ketones, thus affording complex bicyclic lactones in excellent enantioselectivities. The rhodium(I)-catalyzed transformation is induced by an enantiotopic CC bond activation of a cyclobutanone and the formed rhodacyclic intermediate reacts with aldehyde or ketone groups to give highly functionalized lactones. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Vibrational Excitations and Low Energy Electronic Structure of Epoxide-decorated Graphene

PubMed Central

Mattson, E.C.; Johns, J.E.; Pande, K.; Bosch, R.A.; Cui, S.; Gajdardziska-Josifovska, M.; Weinert, M.; Chen, J.H.; Hersam, M.C.; Hirschmugl, C.J.

2014-01-01

We report infrared studies of adsorbed atomic oxygen (epoxide functional groups) on graphene. Two different systems are used as a platform to explore these interactions, namely, epitaxial graphene/SiC(0001) functionalized with atomic oxygen (graphene epoxide, GE) and chemically reduced graphene oxide (RGO). In the case of the model GE system, IR reflectivity measurements show that epoxide groups distort the graphene π bands around the K-point, imparting a finite effective mass and contributing to a band gap. In the case of RGO, epoxide groups are found to be present following the reduction treatment by a combination of polarized IR reflectance and transmittance measurements. Similar to the GE system, a band gap in the RGO sample is observed as well. PMID:24563725

Vibrational Excitations and Low Energy Electronic Structure of Epoxide-decorated Graphene.

PubMed

Mattson, E C; Johns, J E; Pande, K; Bosch, R A; Cui, S; Gajdardziska-Josifovska, M; Weinert, M; Chen, J H; Hersam, M C; Hirschmugl, C J

2014-01-02

We report infrared studies of adsorbed atomic oxygen (epoxide functional groups) on graphene. Two different systems are used as a platform to explore these interactions, namely, epitaxial graphene/SiC(0001) functionalized with atomic oxygen (graphene epoxide, GE) and chemically reduced graphene oxide (RGO). In the case of the model GE system, IR reflectivity measurements show that epoxide groups distort the graphene π bands around the K-point, imparting a finite effective mass and contributing to a band gap. In the case of RGO, epoxide groups are found to be present following the reduction treatment by a combination of polarized IR reflectance and transmittance measurements. Similar to the GE system, a band gap in the RGO sample is observed as well.

Highly Productive and Enantioselective Enzyme Catalysis under Continuous Supported Liquid-Liquid Conditions Using a Hybrid Monolithic Bioreactor.

PubMed

Sandig, Bernhard; Buchmeiser, Michael R

2016-10-20

Enzyme-containing ionic liquids (ILs) were immobilized in cellulose-2.5-acetate microbeads particles embedded in a porous monolithic polyurethane matrix. This bioreactor was used under continuous liquid-liquid conditions by dissolving the substrates in a nonpolar organic phase immiscible with the ILs, thereby creating a biphasic system. Lipases (candida antarctica lipase B, CALB, candida rugosa lipase, CRL) were used to catalyze the enantioselective transesterification of racemic (R,S)-1-phenylethanol with vinyl butyrate and vinyl acetate, the esterification of (+/-)-2-isopropyl-5-methylcyclohexanol with propionic anhydride and the amidation of (R,S)-1-phenylethylamine with ethyl methoxyacetate. With this unique setup, very high productivities, that is, turnover numbers (TONs) up to 5.1×10 6 and space-time yields (STYs) up to 28 g product L -1  h -1 , exceeding the corresponding values for batch-type reactions by a factor of 3100 and 40, respectively, were achieved while maintaining or even enhancing enantioselectivity compared to batch reactions via kinetic resolution. To our best knowledge, this is the first continuously operated bioreactor using supported liquid-liquid conditions that shows these features in the synthesis of chiral esters and amides. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective catalysis of photochemical reactions.

PubMed

Brimioulle, Richard; Lenhart, Dominik; Maturi, Mark M; Bach, Thorsten

2015-03-23

The nature of the excited state renders the development of chiral catalysts for enantioselective photochemical reactions a considerable challenge. The absorption of a 400 nm photon corresponds to an energy uptake of approximately 300 kJ mol(-1) . Given the large distance to the ground state, innovative concepts are required to open reaction pathways that selectively lead to a single enantiomer of the desired product. This Review outlines the two major concepts of homogenously catalyzed enantioselective processes. The first part deals with chiral photocatalysts, which intervene in the photochemical key step and induce an asymmetric induction in this step. In the second part, reactions are presented in which the photochemical excitation is mediated by an achiral photocatalyst and the transfer of chirality is ensured by a second chiral catalyst (dual catalysis). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective binding of L, D-phenylalanine to ct DNA

NASA Astrophysics Data System (ADS)

Zhang, Lijin; Xu, Jianhua; Huang, Yan; Min, Shungeng

2009-10-01

The enantioselective binding of L, D-phenylalanine to calf thymus DNA was studied by absorption, circular dichroism, fluorescence quenching, viscosity, salt effect and emission experiments. The results obtained from absorption, circular dichroism, fluorescence quenching and viscosity experiments excluded the intercalative binding and salt effect experiments did not support electrostatic binding. So the binding of L, D-phenylalanine to ct DNA should be groove binding. Furthermore, the emission spectra revealed that the binding is enantioselective.

Enantioselective binding of L,D-phenylalanine to ct DNA.

PubMed

Zhang, Lijin; Xu, Jianhua; Huang, Yan; Min, Shungeng

2009-10-15

The enantioselective binding of L,D-phenylalanine to calf thymus DNA was studied by absorption, circular dichroism, fluorescence quenching, viscosity, salt effect and emission experiments. The results obtained from absorption, circular dichroism, fluorescence quenching and viscosity experiments excluded the intercalative binding and salt effect experiments did not support electrostatic binding. So the binding of l,d-phenylalanine to ct DNA should be groove binding. Furthermore, the emission spectra revealed that the binding is enantioselective.

Enantioselective Rhodium-Catalyzed Dimerization of ω-Allenyl Carboxylic Acids: Straightforward Synthesis of C2 -Symmetric Macrodiolides.

PubMed

Steib, Philip; Breit, Bernhard

2018-04-19

Herein, we report on the first enantioselective and atom-efficient catalytic one-step dimerization method to selectively transform ω-allenyl carboxylic acids into C 2 -symmetric 14- to 28-membered bismacrolactones (macrodiolides). This convenient asymmetric access serves as an attractive route towards multiple naturally occuring homodimeric macrocyclic scaffolds and demonstrates excellent efficiency to construct the complex, symmetric core structures. By utilizing a rhodium catalyst with a modified chiral cyclopentylidene-diop ligand, the desired diolides were obtained in good to high yields, high diastereoselectivity, and excellent enantioselectivity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselectivity in tebuconazole and myclobutanil non-target toxicity and degradation in soils.

PubMed

Li, Yuanbo; Dong, Fengshou; Liu, Xingang; Xu, Jun; Han, Yongtao; Zheng, Yongquan

2015-03-01

Tebuconazole and myclobutanil are two widely used triazole fungicides, both comprising two enantiomers with different fungicidal activity. However, their non-target toxicity and environmental behavior with respect to enantioselectivity have received limited attention. In the present study, tebuconazole and myclobutanil enantiomers were isolated and used to evaluate the occurrence of enantioselectivity in their acute toxicity to three non-target organisms (Scenedesmus obliquus, Daphnia magna, and Danio rerio). Significant differences were found: R-(-)-tebuconazole was about 1.4-5.9 times more toxic than S-(+)-tebuconazole; rac-myclobutanil was about 1.3-6.1 and 1.4-7.3 more toxic than (-)-myclobutanil and (+)-myclobutanil, respectively. Enantioselectivity was further investigated in terms of fungicide degradation in seven soil samples, which were selected to cover a broad range of soil properties. In aerobic or anaerobic soils, the S-(+)-tebuconazole degraded faster than R-(-)-tebuconazole, and the enantioselectivity showed a correlation with soil organic carbon content. (+)-Myclobutanil was preferentially degraded than (-)-myclobutanil in aerobic soils, whereas both enantiomers degraded at similar rates in anaerobic soils. Apparent correlations of enantioselectivity with soil pH and soil texture were observed for myclobutanil under aerobic conditions. In addition, both fungicides were configurationally stable in soils, i.e., no enantiomerization was found. Enantioselectivity may be a common phenomenon in both aquatic toxicity and biodegradation of chiral triazole fungicides, and this should be considered when assessing ecotoxicological risks of these compounds in the environment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hydrogen-Bonding Catalysis and Inhibition by Simple Solvents in the Stereoselective Kinetic Epoxide-Opening Spirocyclization of Glycal Epoxides to Form Spiroketals

PubMed Central

Wurst, Jacqueline M.; Liu, Guodong; Tan, Derek S.

2011-01-01

Mechanistic investigations of a MeOH-induced kinetic epoxide-opening spirocyclization of glycal epoxides have revealed dramatic, specific roles for simple solvents in hydrogen-bonding catalysis of this reaction to form spiroketal products stereoselectively with inversion of configuration at the anomeric carbon. A series of electronically-tuned C1-aryl glycal epoxides was used to study the mechanism of this reaction based on differential reaction rates and inherent preferences for SN2 versus SN1 reaction manifolds. Hammett analysis of reaction kinetics with these substrates is consistent with an SN2 or SN2-like mechanism (ρ = −1.3 vs. ρ = −5.1 for corresponding SN1 reactions of these substrates). Notably, the spirocyclization reaction is second-order dependent on MeOH and the glycal ring oxygen is required for second-order MeOH catalysis. However, acetone cosolvent is a first-order inhibitor of the reaction. A transition state consistent with the experimental data is proposed in which one equivalent of MeOH activates the epoxide electrophile via a hydrogen bond while a second equivalent of MeOH chelates the sidechain nucleophile and glycal ring oxygen. A paradoxical previous observation that decreased MeOH concentration leads to increased competing intermolecular methyl glycoside formation is resolved by the finding that this side reaction is only first-order dependent on MeOH. This study highlights the unusual abilities of simple solvents to act as hydrogen-bonding catalysts and inhibitors in epoxide-opening reactions, providing both stereoselectivity and discrimination between competing reaction manifolds. This spirocyclization reaction provides efficient, stereocontrolled access to spiroketals that are key structural motifs in natural products. PMID:21539313

Organocatalytic Enantioselective Protonation for Photoreduction of Activated Ketones and Ketimines Induced by Visible Light.

PubMed

Lin, Lu; Bai, Xiangbin; Ye, Xinyi; Zhao, Xiaowei; Tan, Choon-Hong; Jiang, Zhiyong

2017-10-23

The first catalytic asymmetric photoreduction of 1,2-diketones and α-keto ketimines under visible light irradiation is reported. A transition-metal-free synergistic catalysis platform harnessing dicyanopyrazine-derived chromophore (DPZ) as the photoredox catalyst and a non-covalent chiral organocatalyst is effective for these transformations. With the flexible use of a chiral Brønsted acid or base in H + transfer interchange to control the elusive enantioselective protonation, a variety of chiral α-hydroxy ketones and α-amino ketones were obtained with high yields and enantioselectivities. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Convenient divergent strategy for the synthesis of TunePhos-type chiral diphosphine ligands and their applications in highly enantioselective Ru-catalyzed hydrogenations.

PubMed

Sun, Xianfeng; Zhou, Le; Li, Wei; Zhang, Xumu

2008-02-01

A convenient, divergent strategy for the synthesis of a series of modular and fine-tunable C3-TunePhos-type chiral diphosphine ligands and their applications in highly efficient Ru-catalyzed asymmetric hydrogenations were explored. Up to 97 and 99% ee values were achieved for the enantioselective synthesis of beta-methyl chiral amines and alpha-hydroxy acid derivatives, respectively.

Epoxidation of Short-Chain Alkenes by Resting-Cell Suspensions of Propane-Grown Bacteria

PubMed Central

Hou, Ching T.; Patel, Ramesh; Laskin, Allen I.; Barnabe, Nancy; Barist, Irene

1983-01-01

Sixteen new cultures of propane-utilizing bacteria were isolated from lake water from Warinanco Park, Linden, N.J. and from lake and soil samples from Bayway Refinery, Linden, N.J. In addition, 19 known cultures obtained from culture collections were also found to be able to grow on propane as the sole carbon and energy source. In addition to their ability to oxidize n-alkanes, resting-cell suspensions of both new cultures and known cultures grown on propane oxidize short-chain alkenes to their corresponding 1,2-epoxides. Among the substrate alkenes, propylene was oxidized at the highest rate. In contrast to the case with methylotrophic bacteria, the product epoxides are further metabolized. Propane and other gaseous n-alkanes inhibit the epoxidation of propylene. The optimum conditions for in vivo epoxidation are described. Results from inhibition studies indicate that a propane monooxygenase system catalyzes both the epoxidation and hydroxylation reactions. Experiments with cell-free extracts show that both hydroxylation and epoxidation activities are located in the soluble fraction obtained after 80,000 × g centrifugation. PMID:16346338

Stilbene epoxidation and detoxification in a Photorhabdus luminescens-nematode symbiosis

PubMed Central

Park, Hyun Bong; Sampathkumar, Parthasarathy; Perez, Corey E.; Lee, Joon Ha; Tran, Jeannie; Bonanno, Jeffrey B.; Hallem, Elissa A.; Almo, Steven C.; Crawford, Jason M.

2017-01-01

Members of the gammaproteobacterial Photorhabdus genus share mutualistic relationships with Heterorhabditis nematodes, and the pairs infect a wide swath of insect larvae. Photorhabdus species produce a family of stilbenes, with two major components being 3,5-dihydroxy-4-isopropyl-trans-stilbene (compound 1) and its stilbene epoxide (compound 2). This family of molecules harbors antimicrobial and immunosuppressive activities, and its pathway is responsible for producing a nematode “food signal” involved in nematode development. However, stilbene epoxidation biosynthesis and its biological roles remain unknown. Here, we identified an orphan protein (Plu2236) from Photorhabdus luminescens that catalyzes stilbene epoxidation. Structural, mutational, and biochemical analyses confirmed the enzyme adopts a fold common to FAD-dependent monooxygenases, contains a tightly bound FAD prosthetic group, and is required for the stereoselective epoxidation of compounds 1 and 2. The epoxidase gene was dispensable in a nematode-infective juvenile recovery assay, indicating the oxidized compound is not required for the food signal. The epoxide exhibited reduced cytotoxicity toward its producer, suggesting this may be a natural route for intracellular detoxification. In an insect infection model, we also observed two stilbene-derived metabolites that were dependent on the epoxidase. NMR, computational, and chemical degradation studies established their structures as new stilbene-l-proline conjugates, prolbenes A (compound 3) and B (compound 4). The prolbenes lacked immunosuppressive and antimicrobial activities compared with their stilbene substrates, suggesting a metabolite attenuation mechanism in the animal model. Collectively, our studies provide a structural view for stereoselective stilbene epoxidation and functionalization in an invertebrate animal infection model and provide new insights into stilbene cellular detoxification. PMID:28246174

Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pecic, Stevan; Pakhomova, Svetlana; Newcomer, Marcia E.

2013-09-27

A series of potent amide non-urea inhibitors of soluble epoxide hydrolase (sEH) is disclosed. The inhibition of soluble epoxide hydrolase leads to elevated levels of epoxyeicosatrienoic acids (EETs), and thus inhibitors of sEH represent one of a novel approach to the development of vasodilatory and anti-inflammatory drugs. Structure–activities studies guided optimization of a lead compound, identified through high-throughput screening, gave rise to sub-nanomolar inhibitors of human sEH with stability in human liver microsomal assay suitable for preclinical development.

Development of a highly enantioselective capacitive immunosensor for the detection of alpha-amino acids.

PubMed

Zhang, Song; Ding, Jingjing; Liu, Ying; Kong, Jilie; Hofstetter, Oliver

2006-11-01

This work describes a highly enantioselective and sensitive immunosensor for the detection of chiral amino acids based on capacitive measurement. The sensor was prepared by first binding mercaptoacetic acid to the surface of a gold electrode, followed by modification with tyramine utilizing carbodiimide activation. The hapten 4-amino-D-phenylalanine was then covalently immobilized onto the electrode by diazotization. Stereoselective binding of an anti-D-amino acid antibody to the hapten-modified sensor surface resulted in capacitance changes that were detected with high sensitivity by a potentiostatic step method. Using capacitance measurement, detection limits of 5 pg of antibody/mL were attained. The exquisite stereoselectivity of the antibody was also utilized in a competitive setup to quantitatively determine the concentration of the analyte d-phenylalanine in nonracemic samples containing both enantiomers of this amino acid. Trace impurities of d-phenylalanine as low as 0.001% could be detected.

Ligand-accelerated enantioselective methylene C(sp3)-H bond activation.

PubMed

Chen, Gang; Gong, Wei; Zhuang, Zhe; Andrä, Michal S; Chen, Yan-Qiao; Hong, Xin; Yang, Yun-Fang; Liu, Tao; Houk, K N; Yu, Jin-Quan

2016-09-02

Effective differentiation of prochiral carbon-hydrogen (C-H) bonds on a single methylene carbon via asymmetric metal insertion remains a challenge. Here, we report the discovery of chiral acetyl-protected aminoethyl quinoline ligands that enable asymmetric palladium insertion into prochiral C-H bonds on a single methylene carbon center. We apply these palladium complexes to catalytic enantioselective functionalization of β-methylene C-H bonds in aliphatic amides. Using bidentate ligands to accelerate C-H activation of otherwise unreactive monodentate substrates is crucial for outcompeting the background reaction driven by substrate-directed cyclopalladation, thereby avoiding erosion of enantioselectivity. The potential of ligand acceleration in C-H activation is also demonstrated by enantioselective β-C-H arylation of simple carboxylic acids without installing directing groups. Copyright © 2016, American Association for the Advancement of Science.

Biomarkers of Oxidative Stress in the Assessment of Enantioselective Toxicity of Chiral Pesticides.

PubMed

Ye, Xiaoqing; Liu, Ying; Li, Feixue

2017-01-01

In biological systems, the individual stereoisomers of chiral substances possess significantly different biochemical properties because the specific structure-activity relationships are required for a common site on biomolecules. In the past decade, there has been increasing concern over the enantioselective toxicity of environmental chiral pollutants, especially chiral pesticides. Different responses and activities of a pair of enantiomers of chiral pesticides were often observed. Therefore, assessment of the enantioselective toxicological properties of chiral pesticides is a prerequisite in application of single-isomer products and particularly important for environmental protection. The development of biomarkers that can predict enantioselective effects from chiral pesticides has recently been gained more and more attention. The biomarkers of oxidative stress have become a topic of significant interest for toxic assessments. In this review, we summarized current knowledge and advances in the understanding of enantiomeric oxidative processes in biological systems in response to chiral pesticides. The consistent results in two types of chiral insecticides (synthetic pyrethroids and organochlorine pesticides) showed the significant difference in cytotoxicity of enantiomers, suggesting the antioxidant enzymes are reliable biomarkers for the assessment of toxicity of chiral chemicals. Results indicate that antioxidant enzymes are sensitive and valid biomarkers to assess the oxidative damage caused by chiral herbicides. In addition, it can be inferred that the enantioselectivity of chiral herbicides on antioxidant enzymes exists in other species. Compared with insecticides and herbicides, researches about the enantioselectivity of oxidative stress caused by chiral fungicides are quite limited. Only two kinds of chiral fungicides has been used to study the enantioselectivity of oxidative stress by now. The current knowledge that enantioselective processes of oxidative

Recent trends in ring opening of epoxides with sulfur nucleophiles.

PubMed

Ahmad, Sajjad; Zahoor, Ameer Fawad; Naqvi, Syed Ali Raza; Akash, Muhammad

2018-02-01

Thiolysis of epoxides offers an efficient and simple synthetic approach to access [Formula: see text]-hydroxy sulfides which are valuable scaffold in the synthesis of various important molecules in medicinal chemistry. This review article presents a recent compilation of the synthetic approaches developed after 2000 for the thiolysis of epoxides.

Epoxide hydrolase-lasalocid a structure provides mechanistic insight into polyether natural product biosynthesis.

PubMed

Wong, Fong T; Hotta, Kinya; Chen, Xi; Fang, Minyi; Watanabe, Kenji; Kim, Chu-Young

2015-01-14

Biosynthesis of some polyether natural products involves a kinetically disfavored epoxide-opening cyclic ether formation, a reaction termed anti-Baldwin cyclization. One such example is the biosynthesis of lasalocid A, an ionophore antibiotic polyether. During lasalocid A biosynthesis, an epoxide hydrolase, Lsd19, converts the bisepoxy polyketide intermediate into the tetrahydrofuranyl-tetrahydropyran product. We report the crystal structure of Lsd19 in complex with lasalocid A. The structure unambiguously shows that the C-terminal domain of Lsd19 catalyzes the intriguing anti-Baldwin cyclization. We propose a general mechanism for epoxide selection by ionophore polyether epoxide hydrolases.

Epoxidation of Geraniol: An Advanced Organic Experiment that Illustrates Asymmetric Synthesis

NASA Astrophysics Data System (ADS)

Bradley, Lynn M.; Springer, Joseph W.; Delate, Gregory M.; Goodman, Andrew

1997-11-01

The Sharpless epoxidation reaction is considered one of the most powerful advances in asymmetric organic synthesis (1). It is a classic example of the use of an asymmetric catalyst to provide an enantiomerically enriched mixture of epoxy alcohols. The procedure typically uses titanium(IV) tetraisopropoxide (Ti(OiPr)4) as a catalyst, a peroxide, and dialkyl tartrates to induce asymmetry in the epoxidation reaction of allylic alcohols. The experiment described in this paper illustrates the principle of asymmetric epoxidation and enables students to determine enantiomeric product ratios using chiral shift reagents and NMR spectroscopy.

Enantioselective Effects of Chiral Pesticides on their Primary Targets and Secondary Targets.

PubMed

Yang, Ye; Zhang, Jianyun; Yao, Yijun

2017-01-01

Enantioselectivity has been well recognized in the environmental fate and effects of chiral pesticides. Enantiospecific action of the optical enantiomers on the biological molecules establishes the mechanistic basis for the enantioselective toxicity of chiral pesticides to both target and non-target organisms. We undertook a structured search of bibliographic databases for research literature concerning the enantioselective effects of chiral pesticides, including insecticides, herbicides and fungicides, on biomolecules in various species by using some key words. The results of the relevant literatures were reviewed in the text and summarized in tables. Pesticides generally exert their activity on the target organisms via disrupting the primary target biomolecules. In non-target species, effects of pesticides on the secondary targets distinguished from the primary ones make great contribution to their toxicity. Recent investigations have provided convincing evidence of enantioselective toxicity of chiral pesticides to both target and non-target species which is recognized to result from their enantiospecific action on the primary or secondary targets in organisms. This review confirms that chiral pesticides have enantiospecific effects on both primary and secondary target biomolecules in organisms. Future studies regarding toxicological effects of chiral pesticides should focus on the relationship between the enantiomeric difference in the compound-biomolecules interaction and the enantioselectivity in their toxicity.

Polyisoprenoid epoxides stimulate the biosynthesis of coenzyme Q and inhibit cholesterol synthesis.

PubMed

Bentinger, Magnus; Tekle, Michael; Brismar, Kerstin; Chojnacki, Tadeusz; Swiezewska, Ewa; Dallner, Gustav

2008-05-23

In our search for compounds that up-regulate the biosynthesis of coenzyme Q (CoQ), we discovered that irradiation of CoQ with ultraviolet light results in the formation of a number of compounds that influence the synthesis of mevalonate pathway lipids by HepG2 cells. Among the compounds that potently stimulated CoQ synthesis while inhibiting cholesterol synthesis, derivatives of CoQ containing 1-4 epoxide moieties in their polyisoprenoid side chains were identified. Subsequently, chemical epoxidation of all-trans-polyprenols of different lengths revealed that the shorter farnesol and geranylgeraniol derivatives were without effect, whereas the longer derivatives of solanesol enhanced CoQ and markedly reduced cholesterol biosynthesis. In contrast, none of the modified trans-trans-poly-cis-polyprenols exerted noticeable effects. Tocotrienol epoxides were especially potent in our system; those with one epoxide moiety in the side-chain generally up-regulated CoQ biosynthesis by 200-300%, whereas those with two such moieties also decreased cholesterol synthesis by 50-90%. Prolonged treatment of HepG2 cells with tocotrienol epoxides for 26 days elevated their content of CoQ by 30%. In addition, the levels of mRNA encoding enzymes involved in CoQ biosynthesis were also elevated by the tocotrienol epoxides. The site of inhibition of cholesterol synthesis was shown to be oxidosqualene cyclase. In conclusion, epoxide derivatives of certain all-trans-polyisoprenoids cause pronounced stimulation of CoQ synthesis and, in some cases, simultaneous reduction of cholesterol biosynthesis by HepG2 cells.

Chiral Brønsted Base-Promoted Nitroalkane Alkylation: Enantioselective Synthesis of sec-Alkyl-3-Substituted Indoles

PubMed Central

Dobish, Mark C.; Johnston, Jeffrey N.

2010-01-01

A Brønsted base-catalyzed reaction of nitroalkanes with alkyl electrophiles provides indole heterocycles substituted at C3 bearing a sec-alkyl group with good enantioselectivity (up to 90% ee). Denitration by hydrogenolysis provides a product with equally high ee. An indolenine intermediate is implicated in the addition step, and surprisingly, water cosolvent was found to have a beneficial effect in this step, leading to a one-pot protocol for elimination/enantioselective addition using PBAM, a bis(amidine) chiral nonracemic base. PMID:21090654

An efficient hybrid, nanostructured, epoxidation catalyst: titanium silsesquioxane-polystyrene copolymer supported on SBA-15.

PubMed

Zhang, Lei; Abbenhuis, Hendrikus C L; Gerritsen, Gijsbert; Bhriain, Nollaig Ní; Magusin, Pieter C M M; Mezari, Brahim; Han, Wei; van Santen, Rutger A; Yang, Qihua; Li, Can

2007-01-01

A novel interfacial hybrid epoxidation catalyst was designed with a new immobilization method for homogeneous catalysts by coating an inorganic support with an organic polymer film containing active sites. The titanium silsesquioxane (TiPOSS) complex, which contains a single-site titanium active center, was immobilized successfully by in-situ copolymerization on a mesoporous SBA-15-supported polystyrene polymer. The resulting hybrid materials exhibit attractive textural properties (highly ordered mesostructure, large specific surface area (>380 m2 g-1) and pore volume (>or==0.46 cm3 g-1)), and high activity in the epoxidation of alkenes. In the epoxidation of cyclooctene with tert-butyl hydrogen peroxide (TBHP), the hybrid catalysts have rate constants comparable with that of their homogeneous counterpart, and can be recycled at least seven times. They can also catalyze the epoxidation of cyclooctene with aqueous H2O2 as the oxidant. In two-phase reaction media, the catalysts show much higher activity than their homogeneous counterpart due to the hydrophobic environment around the active centers. They behave as interfacial catalysts due to their multifunctionality, that is, the hydrophobicity of polystyrene and the polyhedral oligomeric silsesquioxanes (POSS), and the hydrophilicity of the silica and the mesoporous structure. Combination of the immobilization of homogeneous catalysts on two conventional supports, inorganic solid and organic polymer, is demonstrated to achieve novel heterogeneous catalytic ensembles with the merits of attractive textural properties, tunable surface properties, and optimized environments around the active sites.

Gold(I)-Catalyzed Cascade Cyclization of Allenyl Epoxides

PubMed Central

Tarselli, Michael A.; Lucas Zuccarello, J

2009-01-01

Cationic gold(I) phosphite catalysts activate allenes for epoxide cascade reactions. The system is tolerant of numerous functional groups (sulfones, esters, ethers, sulfonamides) and proceeds at room temperature in dichloromethane. The cyclization pathway is sensitive to the substitution pattern of the epoxide, and the backbone structure of the A-ring. It is capable of producing medium-ring ethers, fused 6-5 bicyclic, and linked pyran-furan structures. The resulting cycloisomers are reminiscent of structures found in numerous polyether natural products. PMID:19588972

Heterogeneous enantioselective hydrogenation of beta-keto esters using chirally modified supported Ni nanoparticles

NASA Astrophysics Data System (ADS)

Acharya, Sushma

Enantioselective heterogeneous catalysis is an important and rapidly expanding research area. The two most heavily researched examples of this type of catalysis are the enantioselective hydrogenation of α-keto-esters over Pt-based catalysts and the enantioselective hydrogenation of β-keto-esters over Ni-based catalysts. These enantioselective surface reactions are controlled by the presence of adsorbed chiral molecules i.e. tartaric acid on the surface of the metal component of the catalyst. The work presented in this thesis focuses on two parts, the synthesis of pure nickel nanoparticles and enantioselective behavior of the modified nickel nanoparticles. The works on the synthesis of pure nickel nanoparticles were carried out using two methods, the reverse microemulsion and the reduction method. It was discovered that the reverse microemulsion method produced nickel oxide nanoparticles, whereas the reduction method produced pure nickel nanoparticles. Chiral modifications of Raney nickel (RNi) and C-supported catalysts were studied. The catalysts were employed in enantioselective hydrogenation of methyl acetoacetate (MAA) to (R) - and (S)-enantiomers of methyl 3-hydroxybutyrate (MHB). The effects of modification and hydrogenation parameters such as concentration of modifier temperature, pressure and solvent on the enantioselectivity of MAA hydrogenation were discussed. For RNi methanol was found to be the best solvent, with tartaric acid concentration 0.2 mol/L for achieving the highest enantiomeric excess under 8 bar at 70 oC. Characteristic features of the in-situ modification of Raney nickel and C-supported Ni were also evaluated and the results obtained were compared with the conventional (pre-modification) approach. Parameters for the conventional and in-situ methods were optimised in a series of experiments for both types of catalysts. The in-situ modified catalyst was found more active for both RNi and C-supported catalysts with 98 % and 42% enantiomeric

Concise, Enantioselective Total Synthesis of (-)-Alstonerine

PubMed Central

Miller, Kenneth A.

2008-01-01

A novel enantioselective total synthesis of (-)-alstonerine has been completed that requires only 1 5 steps from L-tryptophan. The synthesis features the first application of a Pauson-Khand reaction t o synthesize an azabridged bicyclic skeleton. PMID:17298078

A strategy for position-selective epoxidation of polyprenols.

PubMed

Gnanadesikan, Vijay; Corey, E J

2008-06-25

An effective strategy has been developed for the efficient site-selective epoxidation of poylolefinic isoprenoid alcohols, based on the use of an internal control element for intramolecular reaction. The approach is illustrated by application to a series of polyisoprenoid alcohols (polyprenols) at substrate concentration of 0.5 mM. With polyprenol substrates having the hydroxyl function at one terminus, the internal epoxidation can be directed at the double bond of the polyprenol, which is either four or five away from the terminal hydroxyprenyl subunit.

Brønsted acid-catalysed enantioselective construction of axially chiral arylquinazolinones

NASA Astrophysics Data System (ADS)

Wang, Yong-Bin; Zheng, Sheng-Cai; Hu, Yu-Mei; Tan, Bin

2017-05-01

The axially chiral arylquinazolinone acts as a privileged structural scaffold, which is present in a large number of natural products and biologically active compounds as well as in chiral ligands. However, a direct catalytic enantioselective approach to access optically pure arylquinazolinones has been underexplored. Here we show a general and efficient approach to access enantiomerically pure arylquinazolinones in one-pot fashion catalysed by chiral phosphoric acids. A variety of axially chiral arylquinazolinones were obtained in high yields with good to excellent enantioselectivities under mild condition. Furthermore, we disclosed a method for atroposelective synthesis of alkyl-substituted arylquinazolinones involving Brønsted acid-catalysed carbon-carbon bond cleavage strategy. Finally, the asymmetric total synthesis of eupolyphagin bearing a cyclic arylquinazolinone skeleton was accomplished with an overall yield of 32% in six steps by utilizing the aforementioned methodology.

Can the epoxides of cinnamyl alcohol and cinnamal show new cases of contact allergy?

PubMed

Hagvall, Lina; Niklasson, Ida B; Luthman, Kristina; Karlberg, Ann-Therese

2018-06-01

Cinnamyl alcohol is considered to be a prohapten and prehapten with cinnamal as the main metabolite. However, many individuals who are allergic to cinnamyl alcohol do not react to cinnamal. Sensitizing epoxides of cinnamyl alcohol and cinnamal have been identified as metabolites and autoxidation products of cinnamyl alcohol. To investigate the clinical relevance of contact allergy to epoxycinnamyl alcohol and epoxycinnamal. Irritative effects of the epoxides were investigated in 12 dermatitis patients. Epoxycinnamyl alcohol and epoxycinnamal were patch tested in 393 and 390 consecutive patients, respectively. In parallel, cinnamyl alcohol and cinnamal were patch tested in 607 and 616 patients, respectively. Both epoxides were irritants, but no more positive reactions were detected than when testing was performed with cinnamyl alcohol and cinnamal. Late allergic reactions to epoxycinnamyl alcohol were observed. In general, patients with late reactions showed doubtful or positive reactions to cinnamal and fragrance mix I at regular patch testing. The investigated epoxides are not important haptens in contact allergy to cinnamon fragrance. The high frequency of fragrance allergy among patients included in the irritancy study showed the difficulty of suspecting fragrance allergy on the basis of history; patch testing broadly with fragrance compounds is therefore important. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mechanism of olefin epoxidation in the presence of a titanium-containing zeolite

NASA Astrophysics Data System (ADS)

Danov, S. M.; Krasnov, V. L.; Sulimov, A. V.; Ovcharova, A. V.

2013-11-01

The effect of the nature of a solvent on the liquid-phase epoxidation of olefins with an aqueous solution of hydrogen peroxide over a titanium-containing zeolite is studied. Butanol-1, butanol-2, propanol-1, isopropanol, methanol, ethanol, water, acetone, methyl ethyl ketone, isobutanol, and tert-butanol are examined as solvents. A mechanism of olefin epoxidation with hydrogen peroxide in an alcohol medium over a titanium-containing zeolite is proposed. Epoxidation reactions involving hydrogen peroxide and different olefins are studied experimentally.

Anti-Leishmania and cytotoxic activities of perillaldehyde epoxide synthetic positional isomers.

PubMed

Keesen, Tatjana Souza Lima; da Silva, Larisse Virgolino; da Câmara Rocha, Juliana; Andrade, Luciana Nalone; Lima, Tamires Cardoso; de Sousa, Damião Pergentino

2018-03-13

Leishmaniasis belongs to a complex of zoonotic disease caused by protozoa of the genus Leishmania and is considered a major public health problem. Several essential oil chemical components have inhibitory effect against protozoa, including Leishmania donovani. Thus, the aim of this study was to evaluate for the first time the anti-Leishmania activity of two p-menthane monoterpene isomers (EPER-1: perillaldehyde 1,2-epoxide and EPER-2: perillaldehyde 8,9-epoxide) against L. donovani promastigotes as well as evaluating cytotoxic effect on mononuclear peripheral blood cells. Results of anti-Leishmania assay revealed that EPER-2 (IC 50  = 3.8 μg.mL -1 ) was 16-fold more potent than its isomer EPER-1 (IC 50  = 64.6 μg.mL -1 ). In contrast to PBMC cells, EPER-2 was not cytotoxic (IC 50  > 400 μg.mL -1 ) when compared to positive control. These data suggest that the disposition of epoxide group into the p-menthane skeleton affects the anti-Leishmania activity, being that the presence of the exocyclic epoxide group considerably increased potency. Thus, it was possible to observe that the location of the epoxide group into the p-menthane skeleton resulted in different potencies.

Integrated process and dual-function catalyst for olefin epoxidation

DOEpatents

Zhou, Bing; Rueter, Michael

2003-01-01

The invention discloses a dual-functional catalyst composition and an integrated process for production of olefin epoxides including propylene oxide by catalytic reaction of hydrogen peroxide from hydrogen and oxygen with olefin feeds such as propylene. The epoxides and hydrogen peroxide are preferably produced simultaneously in situ. The dual-functional catalyst comprises noble metal crystallites with dimensions on the nanometer scale (on the order of <1 nm to 10 nm), specially dispersed on titanium silicalite substrate particles. The dual functional catalyst catalyzes both the direct reaction of hydrogen and oxygen to generate hydrogen peroxide intermediate on the noble metal catalyst surface and the reaction of the hydrogen peroxide intermediate with the propylene feed to generate propylene oxide product. Combining both these functions in a single catalyst provides a very efficient integrated process operable below the flammability limits of hydrogen and highly selective for the production of hydrogen peroxide to produce olefin oxides such as propylene oxide without formation of undesired co-products.

Catalytic Enantioselective Synthesis of Quaternary Carbon Stereocenters

PubMed Central

Quasdorf, Kyle W.; Overman, Larry E.

2015-01-01

Preface Quaternary carbon stereocenters–carbon atoms to which four distinct carbon substituents are attached–are common features of molecules found in nature. However, prior to recent advances in chemical catalysis, there were few methods available for constructing single stereoisomers of this important structural motif. Here we discuss the many catalytic enantioselective reactions developed during the past decade for synthesizing organic molecules containing such carbon atoms. This progress now makes it possible to selectively incorporate quaternary stereocenters in many high-value organic molecules for use in medicine, agriculture, and other areas. PMID:25503231

Enantioselective Copper-Catalyzed Carboetherification of Unactivated Alkenes**

PubMed Central

Bovino, Michael T.; Liwosz, Timothy W.; Kendel, Nicole E.; Miller, Yan; Tyminska, Nina

2014-01-01

Chiral saturated oxygen heterocycles are important components of bioactive compounds. Cyclization of alcohols onto pendant alkenes is a direct route to their synthesis, but few catalytic enantioselective methods enabling cyclization onto unactivated alkenes exist. Herein is reported a highly efficient copper-catalyzed cyclization of γ-unsaturated pentenols that terminates in C-C bond formation, a net alkene carboetherification. Both intra- and intermolecular C-C bond formations are demonstrated, yielding functionalized chiral tetrahydrofurans as well as fused-ring and bridged-ring oxabicyclic products. Transition state calculations support a cis-oxycupration stereochemistry-determining step. PMID:24798697

An unexpected epoxidation of benzil derivatives in their reaction with a germene.

PubMed

El Kettani, Sakina Ech-Cherif; Lazraq, Mohamed; Ouhsaine, Fatima; Gornitzka, Heinz; Ranaivonjatovo, Henri; Escudié, Jean

2008-11-07

The germene Mes(2)Ge=CR(2) (Mes = 2,4,6-trimethylphenyl, CR(2) = fluorenylidene) reacts with various benzil derivatives to lead to germanium-containing bicyclic epoxides by an unexpected new type of epoxidation reaction.

Enantioselective Reduction of Ketones Catalyzed by Rare-Earth Metals Complexed with Phenoxy Modified Chiral Prolinols.

PubMed

Song, Peng; Lu, Chengrong; Fei, Zenghui; Zhao, Bei; Yao, Yingming

2018-06-01

Enantioselective reduction of ketones and α,β-unsaturated ketones by pinacolborane (HBpin) has been well-established by using chiral rare-earth metal catalysts with phenoxy modified prolinols. A number of highly optically active alcohols were obtained from reduction of simple ketones catalyzed by ytterbium complex 1 [L 4 Yb(L 4 H)] (H 2 L 4 = ( S)-2- tert-butyl-6-((2-(hydroxydiphenylmethyl)pyrrolidin-1-yl)methyl)phenol). Moreover, α,β-unsaturated ketones were selectively reduced to a wide range of chiral allylic alcohols with excellent yields, high enantioselectivity, and complete chemoselectivity, catalyzed by a single component chiral ytterbium complex 2 [L 1 Yb(L 1 H)] (H 2 L 1 = ( S)-2,4-di- tert-butyl-6-((2-(hydroxydiphenylmethyl)pyrrolidin-1-yl)methyl)phenol).

Enantioselective desymmetrization of prochiral cyclohexanones by organocatalytic intramolecular Michael additions to α,β-unsaturated esters.

PubMed

Gammack Yamagata, Adam D; Datta, Swarup; Jackson, Kelvin E; Stegbauer, Linus; Paton, Robert S; Dixon, Darren J

2015-04-13

A new catalytic asymmetric desymmetrization reaction for the synthesis of enantioenriched derivatives of 2-azabicyclo[3.3.1]nonane, a key motif common to many alkaloids, has been developed. Employing a cyclohexanediamine-derived primary amine organocatalyst, a range of prochiral cyclohexanone derivatives possessing an α,β-unsaturated ester moiety linked to the 4-position afforded the bicyclic products, which possess three stereogenic centers, as single diastereoisomers in high enantioselectivity (83-99% ee) and in good yields (60-90%). Calculations revealed that stepwise C-C bond formation and proton transfer via a chair-shaped transition state dictate the exclusive endo selectivity and enabled the development of a highly enantioselective primary amine catalyst. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective synthesis of tetrafluorinated ribose and fructose.

PubMed

Linclau, Bruno; Boydell, A James; Timofte, Roxana S; Brown, Kylie J; Vinader, Victoria; Weymouth-Wilson, Alexander C

2009-02-21

A perfluoroalkylidene lithium mediated cyclisation approach for the enantioselective synthesis of a tetrafluorinated aldose (ribose) and of a tetrafluorinated ketose (fructose), both in the furanose and in the pyranose form, is described.

Enantioselective α-amination of branched aldehydes promoted by simple chiral primary amino acids.

PubMed

Fu, Ji-Ya; Yang, Qing-Chuan; Wang, Qi-Lin; Ming, Jun-Nan; Wang, Fei-Ying; Xu, Xiao-Ying; Wang, Li-Xin

2011-06-03

A series of simple chiral primary amino acids were first successfully applied to promote the enantioselective α-amination of branched aldehydes with azadicarboxylates and the desired adducts bearing quaternary stereogenic centers were obtained in excellent yields (up to 99%) and enantioselectivities (up to 97% ee).

Epoxidation of Alpha-Methylstyrene and its Lewis Acid Rearrangement to 2-Phenylpropanal

NASA Astrophysics Data System (ADS)

Garin, David L.; Gamber, Melissa; Rowe, Bradley J.

1996-06-01

This undergraduate organic lab experiment includes procedures for the peracid epoxidation of an olefin and the Lewis acid rearrangement of an epoxide to a carbonyl compound. Product mixtures and transformations can be readily analyzed by several spectroscopic techniques.

Iridium-catalyzed enantioselective hydrogenation of imines in supercritical carbon dioxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kainz, S.; Brinkmann, A.; Leitner, W.

Supercritical carbon dioxide (scCO{sub 2}) was shown to be a reaction medium with unique properties for highly efficient iridium-catalyzed enantioselective hydrogenation of prochiral imines. Cationic iridium(I) complexes with chiral phosphinodihydrooxazoles, modified with perfluoroalkyl groups in the ligand or in the anion, were synthesized and tested in the hydrogenation of N-(1-phenylethylidene)aniline. Both the side chains and the lipophilic anions increased the solubility, but the choice of the anion also had a dramatic effect on the enantioselectivity with tetrakis-3,5-bis(trifluoromethyl)phenylborate (BARF) leading to the highest asymmetric induction. (R)-N-phenyl-1-phenylethylamine was formed quantitatively within 1 h in scCO{sub 2}[d(CO{sub 2}) = 0.75 g mL{sup {minus}1}]more » at 40 C and a H{sub 2} pressure of 30 bar with enantiomeric excesses of up to 81% using 0.078 mol % catalyst. The use of scCO{sub 2} instead of conventional solvents such as CH{sub 2}Cl{sub 2} allowed the catalyst loading to be lowered significantly owing to a change in the rate profile of the reaction. the homogeneous nature of the catalytically active species under the reaction conditions was demonstrated and was found to depend strongly on the composition of the reaction mixture and especially on the presence of the substrate. Utilizing the selective extractive properties of scCO{sub 2}, the product could be readily separated from the catalyst, which could be recycled several times without significant loss of activity and enantioselectivity. High-pressure FT-IR and NMR investigations revealed that the reactivity of the products to form the corresponding carbamic acids plays an important role for the application of this new methodology.« less

Stereospecific nickel-catalyzed cross-coupling reactions of alkyl ethers: enantioselective synthesis of diarylethanes.

PubMed

Taylor, Buck L H; Swift, Elizabeth C; Waetzig, Joshua D; Jarvo, Elizabeth R

2011-01-26

Secondary benzylic ethers undergo stereospecific substitution reactions with Grignard reagents in the presence of nickel catalysts. Reactions proceed with inversion of configuration and high stereochemical fidelity. This reaction allows for facile enantioselective synthesis of biologically active diarylethanes from readily available optically enriched carbinols.

Structural basis for high substrate-binding affinity and enantioselectivity of 3-quinuclidinone reductase AtQR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hou, Feng; Miyakawa, Takuya; Kataoka, Michihiko

2014-04-18

Highlights: • Crystal structure of AtQR has been determined at 1.72 Å. • NADH binding induces the formation of substrate binding site. • AtQR possesses a conserved hydrophobic wall for stereospecific binding of substrate. • Additional Glu197 residue is critical to the high binding affinity. - Abstract: (R)-3-Quinuclidinol, a useful compound for the synthesis of various pharmaceuticals, can be enantioselectively produced from 3-quinuclidinone by 3-quinuclidinone reductase. Recently, a novel NADH-dependent 3-quinuclidionone reductase (AtQR) was isolated from Agrobacterium tumefaciens, and showed much higher substrate-binding affinity (>100 fold) than the reported 3-quinuclidionone reductase (RrQR) from Rhodotorula rubra. Here, we report the crystalmore » structure of AtQR at 1.72 Å. Three NADH-bound protomers and one NADH-free protomer form a tetrameric structure in an asymmetric unit of crystals. NADH not only acts as a proton donor, but also contributes to the stability of the α7 helix. This helix is a unique and functionally significant part of AtQR and is related to form a deep catalytic cavity. AtQR has all three catalytic residues of the short-chain dehydrogenases/reductases family and the hydrophobic wall for the enantioselective reduction of 3-quinuclidinone as well as RrQR. An additional residue on the α7 helix, Glu197, exists near the active site of AtQR. This acidic residue is considered to form a direct interaction with the amine part of 3-quinuclidinone, which contributes to substrate orientation and enhancement of substrate-binding affinity. Mutational analyses also support that Glu197 is an indispensable residue for the activity.« less

Enantioselective Phytotoxicity and the Relative Mechanism of Current Chiral Herbicides.

PubMed

Wang, Cui; Lu, Dezhao; Yang, Jinhuan; Xu, Yingling; Gong, Chenxue; Li, Zhuoyu

2017-01-01

Regardless of the achievable of chiral switch, most of the chiral nature agrochemical is still sold as racemate or enantiomer-enriched pesticides. Herbicides, accounted for a large proportion in pesticide market, are of great concern due to the frequent occurrence in environment and the structure selective phyto-biochemical impact on plants. We give a systematic search on the literature database and included approximately 50 papers which were related to the review. We do careful categories for the chiral herbicides according to their structure and listed out the acute phytotoxicity endpoints. The potential mechanism for the enantioselective toxicity was concluded into 5 main points. The enantiomer-specific toxicity on plant growth and flowers are limited on phenoxyalkanoic acid herbicide, aryloxyphenoxypropanoic acid, imidazolinone herbicide, and acetamide pesticide. Data available on the potential mechanism explanation of enantioselective phytotoxicity has been concerned on the genetic transcription, oxidative stress, and photosynthesis disruption, etc. A comparison between the two enantiomers' enantioselective effects identified an organ-specific and species-specific phenomenon for several herbicides. Moreover, a more herbicidal activity enantiomer is also displayed the more toxicity than its antipode. The review elucidated a paucity of information on the enantioselective effect research on various types of plants at the different life stages. It appealed us to conduct a more holistic approach to balance the benefit between herbicidal activity and phytotoxicity when try to develop an enantio-pure herbicide.

Physio-pharmacological Investigations About the Anti-inflammatory and Antinociceptive Efficacy of (+)-Limonene Epoxide.

PubMed

de Almeida, Antonia Amanda Cardoso; Silva, Renan Oliveira; Nicolau, Lucas Antonio Duarte; de Brito, Tarcísio Vieira; de Sousa, Damião Pergentino; Barbosa, André Luiz Dos Reis; de Freitas, Rivelilson Mendes; Lopes, Luciano da Silva; Medeiros, Jand-Venes Rolim; Ferreira, Paulo Michel Pinheiro

2017-04-01

D-limonene epoxidation generates (+)-limonene epoxide, an understudied compound in the pharmacologically point of view. Herein, we investigated the anti-inflammatory and antinociceptive potentialities of (+)-limonene epoxide and suggested a mechanism of action. The anti-inflammatory potential was analyzed using agents to induce paw edema, permeability, and myeloperoxidase (MPO) activity. Pro-inflammatory cytokines and cell migration of peritoneal cells were also assessed. Antinociceptive effects were evaluated by writhing test induced by acetic acid, formalin, and hot plate assays and contribution of opioid pathways. Pretreated animals with (+)-limonene epoxide showed reduced carrageenan-induced paw edema in all doses (25, 50, and 75 mg/kg) (P < 0.05). At 75 mg/kg, it suppressed edema provoked by compound 48/80, histamine, prostaglandin E 2 , and serotonin and reduced permeability determined by Evans blue and MPO activity. It also reduced leukocytes, neutrophils, and IL-1β levels in the peritoneal cavity in comparison with carrageenan group (P < 0.05). (+)-Limonene epoxide diminished abdominal contortions induced by acetic acid (78.9%) and paw licking times in both 1 (41.8%) and 2 (51.5%) phases and a pretreatment with naloxone (3 mg/kg) reverted the antinociceptive action in morphine- and (+)-limonene epoxide-treated groups (P < 0.05). Additionally, it enlarged response times to the thermal stimulus after 60 and 90 min. In conclusion, (+)-limonene epoxide inhibited release/activity of inflammatory mediators, vascular permeability, migration of neutrophils and displayed systemic and peripheral analgesic-dependent effects of the opioid system.

Enzymatic Enantioselective Decarboxylative Protonation of Heteroaryl Malonates

PubMed Central

Lewin, Ross; Goodall, Mark; Thompson, Mark L; Leigh, James; Breuer, Michael; Baldenius, Kai; Micklefield, Jason

2015-01-01

The enzyme aryl/alkenyl malonate decarboxylase (AMDase) catalyses the enantioselective decarboxylative protonation (EDP) of a range of disubstituted malonic acids to give homochiral carboxylic acids that are valuable synthetic intermediates. AMDase exhibits a number of advantages over the non-enzymatic EDP methods developed to date including higher enantioselectivity and more environmentally benign reaction conditions. In this report, AMDase and engineered variants have been used to produce a range of enantioenriched heteroaromatic α-hydroxycarboxylic acids, including pharmaceutical precursors, from readily accessible α-hydroxymalonates. The enzymatic method described here represents an improvement upon existing synthetic chemistry methods that have been used to produce similar compounds. The relationship between the structural features of these new substrates and the kinetics associated with their enzymatic decarboxylation is explored, which offers further insight into the mechanism of AMDase. PMID:25766433

Catalytic diastereo- and enantioselective additions of versatile allyl groups to N-H ketimines

NASA Astrophysics Data System (ADS)

Jang, Hwanjong; Romiti, Filippo; Torker, Sebastian; Hoveyda, Amir H.

2017-12-01

There are many biologically active organic molecules that contain one or more nitrogen-containing moieties, and broadly applicable and efficient catalytic transformations that deliver them diastereoselectively and/or enantioselectively are much sought after. Various methods for enantioselective synthesis of α-secondary amines are available (for example, from additions to protected/activated aldimines), but those involving ketimines are much less common. There are no reported additions of carbon-based nucleophiles to unprotected/unactivated (or N-H) ketimines. Here, we report a catalytic, diastereo- and enantioselective three-component strategy for merging an N-H ketimine, a monosubstituted allene and B2(pin)2, affording products in up to 95% yield, >98% diastereoselectivity and >99:1 enantiomeric ratio. The utility of the approach is highlighted by synthesis of the tricyclic core of a class of compounds that have been shown to possess anti-Alzheimer activity. Stereochemical models developed with the aid of density functional theory calculations, which account for the observed trends and levels of enantioselectivity, are presented.

Enantioselective remote meta-C-H arylation and alkylation via a chiral transient mediator.

PubMed

Shi, Hang; Herron, Alastair N; Shao, Ying; Shao, Qian; Yu, Jin-Quan

2018-06-18

Enantioselective carbon-hydrogen (C-H) activation reactions by asymmetric metallation could provide new routes for the construction of chiral molecules 1,2 . However, current methods are typically limited to the formation of five- or six-membered metallacycles, thereby preventing the asymmetric functionalization of C-H bonds at positions remote to existing functional groups. Here we report enantioselective remote C-H activation using a catalytic amount of a chiral norbornene as a transient mediator, which relays initial ortho-C-H activation to the meta position. This was used in the enantioselective meta-C-H arylation of benzylamines, as well as the arylation and alkylation of homobenzylamines. The enantioselectivities obtained using the chiral transient mediator are comparable across different classes of substrates containing either neutral σ-donor or anionic coordinating groups. This relay strategy could provide an alternative means to remote chiral induction, one of the most challenging problems in asymmetric catalysis 3,4 .

Thermochemical Studies of Epoxides and Related Compounds

PubMed Central

Morgan, Kathleen M.; Ellis, Jamie A.; Lee, Joseph; Fulton, Ashley; Wilson, Shavonda L.; Dupart, Patrick S.; Dastoori, Rosanna

2013-01-01

Gas phase heats of formation for the our butene oxide isomers are reported. They were obtained by measuring the condensed-phase heat of reduction to the corresponding alcohol using reaction calorimetry. Heats of vaporization were determined, and allow gas-phase heats of formation to be obtained. The experimental measurements are compared to calculations obtained using a variety of computational methods. Overall, the G3 and CBS-APNO methods agree quite well with the experimental data. The influence of alkyl substituents on epoxide stability is discussed. Comparisons to alkenes, cyclopropanes, aziridines, thiiranes and phosphiranes are also made. Isodesmic-type reactions were used to determine strain energies of the epoxides and related compounds with various substituents. PMID:23551240

Kinetics and mechanism of styrene epoxidation by chlorite: role of chlorine dioxide.

PubMed

Leigh, Jessica K; Rajput, Jonathan; Richardson, David E

2014-07-07

An investigation of the kinetics and mechanism for epoxidation of styrene and para-substituted styrenes by chlorite at 25 °C in the pH range of 5-6 is described. The proposed mechanism in water and water/acetonitrile includes seven oxidation states of chlorine (-I, 0, I, II, III, IV, and V) to account for the observed kinetics and product distributions. The model provides an unusually detailed quantitative mechanism for the complex reactions that occur in mixtures of chlorine species and organic substrates, particularly when the strong oxidant chlorite is employed. Kinetic control of the reaction is achieved by the addition of chlorine dioxide to the reaction mixture, thereby eliminating a substantial induction period observed when chlorite is used alone. The epoxidation agent is identified as chlorine dioxide, which is continually formed by the reaction of chlorite with hypochlorous acid that results from ClO produced by the epoxidation reaction. The overall stoichiometry is the result of two competing chain reactions in which the reactive intermediate ClO reacts with either chlorine dioxide or chlorite ion to produce hypochlorous acid and chlorate or chloride, respectively. At high chlorite ion concentrations, HOCl is rapidly eliminated by reaction with chlorite, minimizing side reactions between HOCl and Cl2 with the starting material. Epoxide selectivity (>90% under optimal conditions) is accurately predicted by the kinetic model. The model rate constant for direct reaction of styrene with ClO2(aq) to produce epoxide is (1.16 ± 0.07) × 10(-2) M(-1) s(-1) for 60:40 water/acetonitrile with 0.20 M acetate buffer. Rate constants for para substituted styrenes (R = -SO3(-), -OMe, -Me, -Cl, -H, and -NO2) with ClO2 were determined. The results support the radical addition/elimination mechanism originally proposed by Kolar and Lindgren to account for the formation of styrene oxide in the reaction of styrene with chlorine dioxide.

Exploiting nanospace for asymmetric catalysis: confinement of immobilized, single-site chiral catalysts enhances enantioselectivity.

PubMed

Thomas, John Meurig; Raja, Robert

2008-06-01

In the mid-1990s, it became possible to prepare high-area silicas having pore diameters controllably adjustable in the range ca. 20-200 Å. Moreover, the inner walls of these nanoporous solids could be functionalized to yield single-site, chiral, catalytically active organometallic centers, the precise structures of which could be determined using in situ X-ray absorption and FTIR and multinuclear magic angle spinning (MAS) NMR spectroscopy. This approach opened up the prospect of performing heterogeneous enantioselective conversions in a novel manner, under the spatial restrictions imposed by the nanocavities within which the reactions occur. In particular, it suggested an alternative method for preparing pharmaceutically and agrochemically useful asymmetric products by capitalizing on the notion, initially tentatively perceived, that spatial confinement of prochiral reactants (and transition states formed at the chiral active center) would provide an altogether new method of boosting the enantioselectivity of the anchored chiral catalyst. Initially, we anchored chiral single-site heterogeneous catalysts to nanopores covalently via a ligand attached to Pd(II) or Rh(I) centers. Later, we employed a more convenient and cheaper electrostatic method, relying in part on strong hydrogen bonding. This Account provides many examples of these processes, encompassing hydrogenations, oxidations, and aminations. Of particular note is the facile synthesis from methyl benzoylformate of methyl mandelate, which is a precursor in the synthesis of pemoline, a stimulant of the central nervous system; our procedure offers several viable methods for reducing ketocarboxylic acids. In addition to relying on earlier (synchrotron-based) in situ techniques for characterizing catalysts, we have constructed experimental procedures involving robotically controlled catalytic reactors that allow the kinetics of conversion and enantioselectivity to be monitored continually, and we have access to

Highly enantioselective arylation of aldehydes and ketones using AlArEt(2)(THF) as aryl sources.

PubMed

Zhou, Shuangliu; Wu, Kuo-Hui; Chen, Chien-An; Gau, Han-Mou

2009-05-01

A series of AlArEt(2)(THF) (Ar = Ph (1a), 4-MeC(6)H(4) (1b), 4-MeOC(6)H(4) (1c), 4-Me(3)SiC(6)H(4) (1d), 2-naphthyl (1e)) were synthesized from reactions of AlEt(2)Br(THF) with ArMgBr. In CDCl(3) solution, the (1)H NMR spectra showed that AlArEt(2)(THF) compounds exist as a mixture of four species of formulas of AlAr(x)Et(3-x) (THF) (x = 0, 1, 2, or 3). AlArEt(2)(THF) compounds were found to be superior and atom-economic reagents for asymmetric aryl additions to organic carbonyls. Aryl additions of AlArEt(2)(THF) to aldehydes catalyzed by the titanium(IV) complex of (R)-H(8)-BINOL were efficient with a short reaction time of 1 h, affording aryl addition products as exclusive or main products in high yields and excellent enantioselectivities of up to 98% ee. Although ethyl additions to aldehydes occurred in minor extent, this study demonstrates that increasing the amount of AlArEt(2)(THF) from 1.2 to 1.4 or to 1.6 equiv significantly improved the aryl addition products of up to >99%. On the other hand, asymmetric arylations of AlArEt(2)(THF) to ketones employing a titanium(IV) catalyst of (S)-BINOL produced optically active tertiary alcohols exclusively in excellent enantioselectivities of up to 94% ee.

A combination of directing groups and chiral anion phase-transfer catalysis for enantioselective fluorination of alkenes

PubMed Central

Wu, Jeffrey; Wang, Yi-Ming; Drljevic, Amela; Rauniyar, Vivek; Phipps, Robert J.; Toste, F. Dean

2013-01-01

We report a catalytic enantioselective electrophilic fluorination of alkenes to form tertiary and quaternary C(sp3)-F bonds and generate β-amino- and β-aryl-allylic fluorides. The reaction takes advantage of the ability of chiral phosphate anions to serve as solid–liquid phase transfer catalysts and hydrogen bond with directing groups on the substrate. A variety of heterocyclic, carbocyclic, and acyclic alkenes react with good to excellent yields and high enantioselectivities. Further, we demonstrate a one-pot, tandem dihalogenation–cyclization reaction, using the same catalytic system twice in series, with an analogous electrophilic brominating reagent in the second step. PMID:23922394

Combining silver- and organocatalysis: an enantioselective sequential catalytic approach towards pyrano-annulated pyrazoles.

PubMed

Hack, Daniel; Chauhan, Pankaj; Deckers, Kristina; Mizutani, Yusuke; Raabe, Gerhard; Enders, Dieter

2015-02-11

A one-pot asymmetric Michael addition/hydroalkoxylation sequence, catalyzed by a sequential catalytic system consisting of a squaramide and a silver salt, provides a new series of chiral pyrano-annulated pyrazole derivatives in excellent yields (up to 95%) and high enantioselectivities (up to 97% ee).

Benzil, a potent activator of microsomal epoxide hydrolase in vitro.

PubMed

Seidegård, J; DePierre, J W

1980-12-01

Benzil was found to be a very potent activator of microsomal epoxide hydrolase activity (measured with styrene oxide as substrate) in vitro. The activating effect was uncompetitive and benzil causes approximately ninefold increases in both the apparent V and the apparent Km of the enzyme(s). The half-maximal effect on activity was obtained as a 0.3 mM concentration of benzil. The activating effect obtained with benzil was found to be very specific, since a variety of structurally related compounds had little or no effect on microsomal epoxide hydrolase activity. In order to obtain indications for the existence of more than one microsomal epoxide hydrolase the effect of benzil on this activity from rats induced with phenobarbital, 3-methylcholanthrene, 2-acetylaminofluorene, trans-stilbene oxide, and benzil was tested. The differences observed were minor.

In-Situ Generated Graphene as the Catalytic Site for Visible-Light Mediated Ethylene Epoxidation on AG Nanocatalysts

NASA Astrophysics Data System (ADS)

Zhang, Xueqiang Alex; Jain, Prashant

2017-06-01

Despite the harsh conditions for chemical conversion, ethylene oxide produced from ethylene epoxidation on Ag-based heterogeneous catalyst constitutes one of the largest volume chemicals in chemical industry. Recently, photocatalytic epoxidation of ethylene over plasmonic Ag nanoparticles enables the chemical conversion under significantly decreased temperature and ambient pressure conditions. Yet a detailed understanding of the photocatalytic process at the reactant/catalyst interface is under debate. Surface enhanced Raman spectroscopy (SERS) is a powerful vibrational spectroscopy technique that enables the localized detection of rare and/or transient chemical species with high sensitivity under in situ and ambient conditions. Using SERS, we are able to monitor at individual sites of an Ag nanocatalyst the visible-light-mediated adsorption and epoxidation of ethylene. From detected intermediates, we find that the primary step in the photoepoxidation is the transient formation of graphene catalyzed by the Ag surface. Density functional theory (DFT) simulations that model the observed SERS spectra suggest that the defective edge sites of the graphene formed on Ag constitute the active site for C2H4 adsorption and epoxidation. Further studies with pre-formed graphene/Ag catalyst composites confirm the indispensable role of graphene in visible-light-mediated ethylene epoxidation. Carbon is often thought to be either an innocent support or a poison for metallic catalysts; however our studies reveal a surprising role for crystalline carbon layers as potential co-catalysts.

Enantioselective Cyanation of Benzylic C–H Bonds via Copper-Catalyzed Radical Relay

PubMed Central

Zhang, Wen; Wang, Fei; McCann, Scott D.; Wang, Dinghai; Chen, Pinhong; Stahl, Shannon; Liu, Guosheng

2017-01-01

Direct methods for stereoselective functionalization of C(sp3)–H bonds in complex organic molecules could facilitate much more efficient preparation of therapeutics and agrochemicals. Here, we report a copper-catalyzed radical relay pathway for enantioselective conversion of benzylic C–H bonds into benzylic nitriles. Hydrogen-atom abstraction affords an achiral benzylic radical that undergoes asymmetric C(sp3)–CN bond upon reaction with a chiral copper catalyst. The reactions proceed efficiently at room temperature with the benzylic substrate as limiting reagent, exhibit broad substrate scope with high enantioselectivity (typically 90-99% enantiomeric excess), and afford products that are key precursors to important bioactive molecules. Mechanistic studies provide evidence for diffusible organic radicals and highlight the difference between these reactions and C–H oxidations mediated by enzymes and other catalysts that operate via radical rebound pathways. PMID:27701109

Enantioselective Total Syntheses of (−)-Palau’amine, (−)- Axinellamines, and (−)-Massadines

PubMed Central

Seiple, Ian B.; Su, Shun; Young, Ian S.; Nakamura, Akifumi; Yamaguchi, Junichiro; Jørgensen, Lars; Rodriguez, Rodrigo A.; O’Malley, Daniel P.; Gaich, Tanja; Köck, Matthias; Baran, Phil S.

2011-01-01

Dimeric pyrrole-imidazole alkaloids represent a rich and topologically unique class of marine natural products. This full account will follow the progression of efforts that culminated in the enantioselective total syntheses of the most structurally ornate members of this family: the axinellamines, the massadines, and palau’amine. A bio-inspired approach capitalizing on the pseudo-symmetry of the members of this class is recounted, delivering a deschloro derivative of the natural product core. Next, the enantioselective synthesis of the chlorocyclopentane core featuring a scalable, catalytic, enantioselective Diels–Alder reaction of a 1-siloxydiene is outlined in detail. Finally, the successful divergent conversion of this core to each of the aforementioned natural products, and the ensuing methodological developments are described. PMID:21861522

Enantioselective N-Heterocyclic Carbene Catalysis via the Dienyl Acyl Azolium.

PubMed

Gillard, Rachel M; Fernando, Jared E M; Lupton, David W

2018-04-16

Herein we report the enantioselective N-heterocyclic carbene catalyzed (4+2) annulation of the dienyl acyl azolium with enolates. The reaction exploits readily accessible acyl fluorides and TMS enol ethers to give a range of highly enantio- and diastereo-enriched cyclohexenes (most >97:3 er and >20:1 dr). The reaction was found to require high nucleophilicity NHC catalysts with mechanistic studies supporting a stepwise 1,6-addition/β-lactonization. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective Analysis in instruments onboard ROSETTA/PHILAE and ExoMars

NASA Astrophysics Data System (ADS)

Hendrik Bredehöft, Jan; Thiemann, Wolfram; Meierhenrich, Uwe; Goesmann, Fred

It has been suggested a number of times in the past, to look for chirality as a biomarker. So far, for lack of appropriate instrumentation, space missions have never included enantioselective analysis. The distinction between enantiomers is of crucial importance to the question of the origin of the very first (pre)biotic molecules. If molecules detected in situ on another celestial body were found to exhibit a chiral bias, this would mean that at least partial asymmetric synthesis could take place abiotically. If this chiral bias should be found to be near 100For the currently flying ESA mission ROSETTA an enantioselective instrument was built, to try for the first time to detect and separate chiral molecules in situ. This instrument is COSAC, the Cometary Sampling and Acquisition Experiment, an enantioselective GCMS device[1,2], which is included in the lander PHLIAE that will eventually in 2014 land on the nucleus of comet 67P/Churyumov-Gerasimenko. A similar but even more powerful type of enantioselective GC-MS is in preparation for ESA's ExoMars mission. This instrument is part of MOMA, the Mars Organic Molecules Analyser. It has the objective of identifying and quantifying chiral organic molecules in surface and subsurface samples of Mars. Currently ExoMars is scheduled for 2018. The newly developed enantioselective technique utilized by both COSAC and MOMA will be described, including sample acquisition, derivatization, and separation in space-resistant chiral stationary capillary columns with time-of-flight mass spectrometric detection. Results of enantioselective analyses of representative test samples with special emphasis on amino acids[3], the building blocks of protein polymers, will be presented and we will discuss potential results of space missions Rosetta and ExoMars. [1] Thiemann W.H.-P., Meierhenrich U.: ESA Mission ROSETTA Will Probe for Chirality of Cometary Amino Acids. Origins of Life and Evolution of Biospheres 31 (2001), 199-210. [2

ENANTIOSELECTIVITY IN THE BIODEGRADATION OF PCB ATROPISOMERS

EPA Science Inventory

Microcosms inoculated with sediment from two locations in a contaminated reservoir, Lake Hartwell, SC, USA, degraded certain PCB atropisomers enantioselectively while other atropisomers were degraded in racemic proportions. The microcosms were spiked with either 234-236 PCB (PCB...

Enantioselective inhibition of microbial lipolytic enzymes by nonracemic monocyclic enolphosphonate analogues of cyclophostin.

PubMed

Point, Vanessa; Malla, Raj K; Carrière, Frederic; Canaan, Stéphane; Spilling, Christopher D; Cavalier, Jean-François

2013-06-13

Four nonracemic enolphosphonate analogues of Cyclophostin were obtained by asymmetric synthesis, and their absolute configurations at both phosphorus and C-5 carbon chiral centers were unambiguously assigned. The influence of chirality was studied by testing the inhibitory effects of these four stereoisomers toward the lipolytic activity of three microbial lipases: Fusarium solani cutinase, Rv0183, and LipY from Mycobacterium tuberculosis . Cutinase was highly diastereoselective for the (Sp) configuration using (Sc) inhibitors, whereas no obvious stereopreference at phosphorus was observed with (Rc) compounds. Conversely, Rv0183 exhibited strong enantioselective discrimination for (Sp) configuration regardless of the chirality at the asymmetric carbon atom. Lastly, LipY discriminated only the unusual diastereoisomeric configuration (Rc, Rp) leading to the most potent inhibitor. This work, which provides a fundamental premise for the understanding of the stereoselective relationships between nonracemic enolphosphonates and their inhibitory activity, also opens new prospects on the design and synthesis of highly specific enantioselective antimicrobial agents.

Microbial production of epoxides

DOEpatents

Clark, Thomas R.; Roberto, Francisco F.

2003-06-10

A method for microbial production of epoxides and other oxygenated products is disclosed. The method uses a biocatalyst of methanotrophic bacteria cultured in a biphasic medium containing a major amount of a non-aqueous polar solvent. Regeneration of reducing equivalents is carried out by using endogenous hydrogenase activity together with supplied hydrogen gas. This method is especially effective with gaseous substrates and cofactors that result in liquid products.

Development of epoxide compound from kapok oil for enhanced oil recovery

NASA Astrophysics Data System (ADS)

Anam, M. K.; Supranto; Murachman, B.; Purwono, S.

2017-06-01

Epoxide compound is made by reacting Kapok Oil with acetic acid and hydrogen peroxide with in situ method. The epoxidation reaction was varied at temperatures of 60 °C, 70 °C and 80 °C, while the time of reaction time was varied at 15 minutes, 30 minutes, 60 minutes and 90 minutes. The reaction rate coefficient for the epoxide was obtained as {\\boldsymbol{k}}{\\boldsymbol{=}}{{124}}{\\boldsymbol{,}}{{82}} {{\\exp }} {\\boldsymbol{\\bigg(}}\\frac{{\\boldsymbol-}{{24}}{\\boldsymbol{,}}{{14}}}{{\\boldsymbol{R}}{\\boldsymbol{T}}}{\\boldsymbol{\\bigg)}}. The addition of the epoxide compound 0.5 w/w in the formulation of SLS was able to reduce the IFT value up to 9.95 x 10-2 m N/m. The addition of co-surfactant (1-octanol) was varied between 0.1 and 0.4 of the total mass of the main formulation (SLS + epoxide + water formation). The smallest interfacial tension value is obtained on the addition of co-surfactants as much as 0.2 w/w, with the IFT value is 2.43 x 10-3 m N/m. The effectiveness of the chemicals was tested through micro displacement using artificial porous medium. The experimental results show that some chemicals developed in the laboratory can be used as EOR chemicals. The oil displacement experiments show that as much as 20 to 80 of remaining oil can be recovered by flooding it with the chemicals. The results also show that the oil recovery depends on type of chemicals and chemical concentration.

Enantioselective syntheses of cryptocarya triacetate, cryptocaryolone, and cryptocaryolone diacetate.

PubMed

Smith, Catherine M; O'Doherty, George A

2003-05-29

[reaction: see text] The enantioselective syntheses of three natural products from Cryptocarya latifolia have been achieved in 13-15 steps from ethyl sorbate. The route relies upon an enantio- and regioselective Sharpless dihydroxylation and a palladium-catalyzed reduction to establish the absolute stereochemistry. The route also relies upon a highly (E)-selective olefin cross-metathesis reaction to form trans-delta-hydroxy-1-enoates. The resulting delta-hydroxy-1-enoates were subsequently converted into cryptocarya triacetate, cryptocaryolone, and cryptocaryolone diacetate.

Ozonides and epoxides from ozonization of pyrethroids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruzo, L.O.; Kimmel, E.C.; Casida, J.E.

Ozonization of pyrethroids as solutions or thin films yields products proposed to be epoxides from the 2,2-dihalovinyl substituents of deltamethrin and permethrin and transitory ozonides from these compounds and more stable ozonides from the 2-methyl-1-propenyl and 2-chloro-3,3,3-trifluoropropenyl substituents of phenothrin and descyanocyhalothrin, respectively. The unstable epoxydeltamethrin from ozonization is identified by /sup 1/H nuclear magnetic resonance spectroscopy and chemical ionization-mass spectroscopy and by reversion to deltamethrin on treatment of reaction mixtures with triphenylphosphine. Degradation of the ozonides yields the corresponding caronaldehyde in each case and trifluoroacetyl chloride from the chlorotrifluoropropenyl analogues. The ozonolysis mixtures are direct acting but weak bacterialmore » mutagens presumable due to their epoxide and ozonide components.« less

Enantioselective total synthesis of hyperforin.

PubMed

Sparling, Brian A; Moebius, David C; Shair, Matthew D

2013-01-16

A modular, 18-step total synthesis of hyperforin is described. The natural product was quickly accessed using latent symmetry elements, whereby a group-selective, Lewis acid-catalyzed epoxide-opening cascade cyclization was used to furnish the bicyclo[3.3.1]nonane core and set two key quaternary stereocenters.

Optical properties and indentation hardness of thin-film acrylated epoxidized oil

NASA Astrophysics Data System (ADS)

Rahman, Mohammad Syuhaimi Ab.; Shaktur, Khaled Mohamed; Mohammad, Rahmah; Zalikha, Wan Aimi; Nawi, Norwimie; Mohd, Ahmad Faiza

2012-02-01

Epoxy acrylate has been widely used as optical resin for applications such as cladding, the core of a waveguide, and other photonic devices. In this study, sustainable resin from edible oil was used as an alternative to epoxy acrylate. Structural features and the transmission of planar thin-film resin from an ultraviolet-visible spectroscopy (UV-VIS) spectrometer were investigated upon UV exposure. It was found that high transmission still persists for all samples with and without an UV absorber for exposed and unexposed samples. The film was found to absorb strongly below 400 nm. A change in the cut-off wavelength was observed upon exposure. Thin-film hardness and its dynamic indentation in the load-unload mode with different test forces were evaluated. Vickers hardness and the elastic modulus were determined for unacrylated epoxidized soybean oil (ESO) and acrylated epoxidized soybean oil (AESO). It was found that the AESO has a higher Vickers hardness and elastic modulus than those of unacrylated thin film. The Vickers hardness and elastic modulus were found to increase as the applied test force increased. The refractive index, thickness, and modes present were characterized from a spin-coated planar thin film. The refractive index in the transverse electric mode (TE) and transverse magnetic mode (TM) were determined and compared for unacrylated and acrylated epoxidized oil.

Epoxide-mediated differential packaging of Cif and other virulence factors into outer membrane vesicles.

PubMed

Ballok, Alicia E; Filkins, Laura M; Bomberger, Jennifer M; Stanton, Bruce A; O'Toole, George A

2014-10-01

Pseudomonas aeruginosa produces outer membrane vesicles (OMVs) that contain a number of secreted bacterial proteins, including phospholipases, alkaline phosphatase, and the CFTR inhibitory factor (Cif). Previously, Cif, an epoxide hydrolase, was shown to be regulated at the transcriptional level by epoxides, which serve as ligands of the repressor, CifR. Here, we tested whether epoxides have an effect on Cif levels in OMVs. We showed that growth of P. aeruginosa in the presence of specific epoxides but not a hydrolysis product increased Cif packaging into OMVs in a CifR-independent fashion. The outer membrane protein, OprF, was also increased under these conditions, but alkaline phosphatase activity was not significantly altered. Additionally, we demonstrated that OMV shape and density were affected by epoxide treatment, with two distinct vesicle fractions present when cells were treated with epibromohydrin (EBH), a model epoxide. Vesicles isolated from the two density fractions exhibited different protein profiles in Western blotting and silver staining. We have shown that a variety of clinically or host-relevant treatments, including antibiotics, also alter the proteins packaged in OMVs. Proteomic analysis of purified OMVs followed by an analysis of transposon mutant OMVs yielded mutants with altered vesicle packaging. Finally, epithelial cell cytotoxicity was reduced in the vesicles formed in the presence of EBH, suggesting that this epoxide alters the function of the OMVs. Our data support a model whereby clinically or host-relevant signals mediate differential packaging of virulence factors in OMVs, which results in functional consequences for host-pathogen interactions. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Persistence and changes in bioavailability of dieldrin, DDE and heptachlor epoxide in earthworms over 45 years

USGS Publications Warehouse

Beyer, W. Nelson; Gale, Robert W.

2013-01-01

The finding of dieldrin (88 ng/g), DDE (52 ng/g), and heptachlor epoxide (19 ng/g) in earthworms from experimental plots after a single moderate application (9 kg/ha) 45 years earlier attests to the remarkable persistence of these compounds in soil and their continued uptake by soil organisms. Half-lives (with 95 % confidence intervals) in earthworms, estimated from exponential decay equations, were as follows: dieldrin 4.9 (4.3-5.7) years, DDE 5.3 (4.7-6.1) years, and heptachlor epoxide 4.3 (3.8-4.9) years. These half-lives were not significantly different from those estimated after 20 years. Concentration factors (dry weight earthworm tissue/dry weight soil) were initially high and decreased mainly during the first 11 years after application. By the end of the study, average concentration factors were 1.5 (dieldrin), 4.0 (DDE), and 1.8 (heptachlor epoxide), respectively.

Highly efficient sulfated Zr-doped titanoniobate nanoplates for the alcoholysis of styrene epoxide at room temperature

NASA Astrophysics Data System (ADS)

Zhang, Lihong; Hu, Chenhui; Mei, Weigang; Zhang, Junfeng; Cheng, Liyuan; Xue, Nianhua; Ding, Weiping; Chen, Jing; Hou, Wenhua

2015-12-01

Sulfated Zr-doped titanoniobate nanoplates were prepared and evaluated as a solid acid catalyst in the alcoholysis of styrene epoxide at room temperature. Compared with undoped and Zr-doped nanosheets, the resulting sulfated catalyst exhibited an excellent catalytic performance to afford corresponding β-alkoxyalcohols (99% yield with methanol as nucleophile in only 10 min) due to the high dispersion of zirconia species on nanosheets, appropriate Lewis acid strength and amount from the strong interaction between zirconia and sulfate species, and greatly increased surface area arisen from the exfoliation and house-of-cards restacking of nanosheets. The corresponding catalytic mechanism was proposed and discussed. The obtained material may act as a promising catalyst in many acid catalyzed reactions.

Methods of producing epoxides from alkenes using a two-component catalyst system

DOEpatents

Kung, Mayfair C.; Kung, Harold H.; Jiang, Jian

2013-07-09

Methods for the epoxidation of alkenes are provided. The methods include the steps of exposing the alkene to a two-component catalyst system in an aqueous solution in the presence of carbon monoxide and molecular oxygen under conditions in which the alkene is epoxidized. The two-component catalyst system comprises a first catalyst that generates peroxides or peroxy intermediates during oxidation of CO with molecular oxygen and a second catalyst that catalyzes the epoxidation of the alkene using the peroxides or peroxy intermediates. A catalyst system composed of particles of suspended gold and titanium silicalite is one example of a suitable two-component catalyst system.

Bidirectional enantioselective effects of the GABAB receptor agonist baclofen in two mouse models of excessive ethanol consumption

PubMed Central

Kasten, Chelsea R.; Blasingame, Shelby N.; Boehm, Stephen L.

2014-01-01

The GABAB receptor agonist baclofen has been studied extensively in preclinical models of alcohol use disorders, yet results on its efficacy have been uncertain. Racemic baclofen, which is used clinically, can be broken down into separate enantiomers of the drug. Baclofen has been shown to produce enantioselective effects in behavioral assays including those modeling reflexive and sexual behavior. The current studies sought to characterize the enantioselective effects of baclofen in two separate models of ethanol consumption. The first was a Drinking-in-the-Dark procedure that provides “binge-like” ethanol access to mice by restricting access to a two hour period, three hours into the dark cycle. The second was a two-bottle choice procedure that utilized selectively bred High Alcohol Preferring 1 (HAP1) mice to model chronic ethanol access. HAP1 mice are selectively bred to consume pharmacologically relevant amounts of ethanol in a 24-hour two-bottle choice paradigm. The results showed that baclofen yields enantioselective effects on ethanol intake in both models, and that these effects are bidirectional. Total ethanol intake was decreased by R(+)- baclofen, while total intake was increased by S(-)-baclofen in the binge-like and chronic drinking models. Whereas overall binge-like saccharin intake was significantly reduced by R(+)- baclofen, chronic intake was not significantly altered. S(-)- baclofen did not significantly alter saccharin intake. Neither enantiomer significantly affected locomotion during binge-like reinforcer consumption. Collectively, these results demonstrate that baclofen produces enantioselective effects on ethanol consumption. More importantly, the modulation of consumption is bidirectional. The opposing enantioselective effects may explain some of the variance seen in published baclofen literature. PMID:25557834

Bidirectional enantioselective effects of the GABAB receptor agonist baclofen in two mouse models of excessive ethanol consumption.

PubMed

Kasten, Chelsea R; Blasingame, Shelby N; Boehm, Stephen L

2015-02-01

The GABAB receptor agonist baclofen has been studied extensively in preclinical models of alcohol-use disorders, yet results on its efficacy have been uncertain. Racemic baclofen, which is used clinically, can be broken down into separate enantiomers of the drug. Baclofen has been shown to produce enantioselective effects in behavioral assays, including those modeling reflexive and sexual behavior. The current studies sought to characterize the enantioselective effects of baclofen in two separate models of ethanol consumption. The first was a Drinking-in-the-Dark procedure that provides "binge-like" ethanol access to mice by restricting access to a 2-h period, 3 h into the dark cycle. The second was a two-bottle choice procedure that utilized selectively bred High Alcohol Preferring 1 (HAP1) mice to model chronic ethanol access. HAP1 mice are selectively bred to consume pharmacologically relevant amounts of ethanol in a 24-h two-bottle choice paradigm. The results showed that baclofen yields enantioselective effects on ethanol intake in both models, and that these effects are bidirectional. Total ethanol intake was decreased by R(+)-baclofen, while total intake was increased by S(-)-baclofen in the binge-like and chronic drinking models. Whereas overall binge-like saccharin intake was significantly reduced by R(+)-baclofen, chronic intake was not significantly altered. S(-)-baclofen did not significantly alter saccharin intake. Neither enantiomer significantly affected locomotion during binge-like reinforcer consumption. Collectively, these results demonstrate that baclofen produces enantioselective effects on ethanol consumption. More importantly, the modulation of consumption is bidirectional. The opposing enantioselective effects may explain some of the variance seen in published baclofen literature. Copyright © 2015 Elsevier Inc. All rights reserved.

Cooperative catalysis by tertiary amino-thioureas: mechanism and basis for enantioselectivity of ketone cyanosilylation.

PubMed

Zuend, Stephan J; Jacobsen, Eric N

2007-12-26

The mechanism of the enantioselective cyanosilylation of ketones catalyzed by tertiary amino-thiourea derivatives was investigated using a combination of experimental and theoretical methods. The kinetic analysis is consistent with a cooperative mechanism in which both the thiourea and the tertiary amine of the catalyst are involved productively in the rate-limiting cyanide addition step. Density functional theory calculations were used to distinguish between mechanisms involving thiourea activation of ketone or of cyanide in the enantioselectivity-determining step. The strong correlation obtained between experimental and calculated ee's for a range of substrates and catalysts provides support for the most favorable calculated transition structures involving amine-bound HCN adding to thiourea-bound ketone. The calculations suggest that enantioselectivity arises from direct interactions between the ketone substrate and the amino-acid derived portion of the catalyst. On the basis of this insight, more enantioselective catalysts with broader substrate scope were prepared and evaluated experimentally.

Enantioconvergent production of (R)-1-phenyl-1,2-ethanediol from styrene oxide by combining the Solanum tuberosum and an evolved Agrobacterium radiobacter AD1 epoxide hydrolases.

PubMed

Cao, Li; Lee, Jintae; Chen, Wilfred; Wood, Thomas K

2006-06-20

Soluble epoxide hydrolase (EH) from the potato Solanum tuberosum and an evolved EH of the bacterium Agrobacterium radiobacter AD1, EchA-I219F, were purified for the enantioconvergent hydrolysis of racemic styrene oxide into the single product (R)-1-phenyl-1,2-ethanediol, which is an important intermediate for pharmaceuticals. EchA-I219F has enhanced enantioselectivity (enantiomeric ratio of 91 based on products) for converting (R)-styrene oxide to (R)-1-phenyl-1,2-ethanediol (2.0 +/- 0.2 micromol/min/mg), and the potato EH converts (S)-styrene oxide primarily to the same enantiomer, (R)-1-phenyl-1,2-ethanediol (22 +/- 1 micromol/min/mg), with an enantiomeric ratio of 40 +/- 17 (based on substrates). By mixing these two purified enzymes, inexpensive racemic styrene oxide (5 mM) was converted at 100% yield to 98% enantiomeric excess (R)-1-phenyl-1,2-ethanediol at 4.7 +/- 0.7 micromol/min/mg. Hence, at least 99% of substrate is converted into a single stereospecific product at a rapid rate. 2006 Wiley Periodicals, Inc.

Functionalization of multi-walled carbon nanotubes by epoxide ring-opening polymerization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin Fanlong; Rhee, Kyong Yop; Park, Soo-Jin, E-mail: sjpark@inha.ac.kr

2011-12-15

In this study, covalent functionalization of carbon nanotubes (CNTs) was accomplished by surface-initiated epoxide ring-opening polymerization. FT-IR spectra showed that polyether and epoxide group covalently attached to the sidewalls of CNTs. TGA results indicated that the polyether was successfully grown from the CNT surface, with the final products having a polymer weight percentage of ca. 14-74 wt%. The O/C ratio of CNTs increased significantly from 5.1% to 29.8% after surface functionalization of CNTs. SEM and TEM images of functionalized CNTs exhibited that the tubes were enwrapped by polymer chains with thickness of several nanometers, forming core-shell structures with CNTs atmore » the center. - Graphical abstract: Functionalized CNTs were enwrapped by polymer chains with thickness of several nanometers, forming core-shell structures with CNTs at the center. Highlights: Black-Right-Pointing-Pointer CNTs were functionalized by epoxide ring-opening polymerization. Black-Right-Pointing-Pointer Polyether and epoxide group covalently attached to the sidewalls of CNTs. Black-Right-Pointing-Pointer Functionalized CNTs have a polymer weight percentage of ca. 14-74 wt%. Black-Right-Pointing-Pointer Functionalized CNTs were enwrapped by polymer chains with thickness of several nanometers.« less

Combinatorial library based engineering of Candida antarctica lipase A for enantioselective transacylation of sec-alcohols in organic solvent.

PubMed

Wikmark, Ylva; Svedendahl Humble, Maria; Bäckvall, Jan-E

2015-03-27

A method for determining lipase enantioselectivity in the transacylation of sec-alcohols in organic solvent was developed. The method was applied to a model library of Candida antarctica lipase A (CalA) variants for improved enantioselectivity (E values) in the kinetic resolution of 1-phenylethanol in isooctane. A focused combinatorial gene library simultaneously targeting seven positions in the enzyme active site was designed. Enzyme variants were immobilized on nickel-coated 96-well microtiter plates through a histidine tag (His6-tag), screened for transacylation of 1-phenylethanol in isooctane, and analyzed by GC. The highest enantioselectivity was shown by the double mutant Y93L/L367I. This enzyme variant gave an E value of 100 (R), which is a dramatic improvement on the wild-type CalA (E=3). This variant also showed high to excellent enantioselectivity for other secondary alcohols tested. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Enantioselective oxidative biaryl coupling reactions catalyzed by 1,5-diazadecalin metal complexes.

PubMed

Li, X; Yang, J; Kozlowski, M C

2001-04-19

[reaction: see text]. Chiral 1,5-diaza-cis-decalins have been examined as ligands in the enantioselective oxidative biaryl coupling of substituted 2-naphthol derivatives. Under the optimal conditions employing a 1,5-diaza-cis-decalin copper(I) iodide complex with oxygen as the oxidant, rapid and highly selective couplings could be achieved (90-93% ee, 85% yield).

Resolution and some properties of enzymes involved in enantioselective transformation of 1,3-dichloro-2-propanol to (R)-3-chloro-1,2-propanediol by Corynebacterium sp. strain N-1074.

PubMed Central

Nakamura, T; Nagasawa, T; Yu, F; Watanabe, I; Yamada, H

1992-01-01

During the course of the transformation of 1,3-dichloro-2-propanol (DCP) into (R)-3-chloro-1,2-propanediol [(R)-MCP] with the cell extract of Corynebacterium sp. strain N-1074, epichlorohydrin (ECH) was transiently formed. The cell extract was fractionated into two DCP-dechlorinating activities (fractions Ia and Ib) and two ECH-hydrolyzing activities (fractions IIa and IIb) by TSKgel DEAE-5PW column chromatography. Fractions Ia and Ib catalyzed the interconversion of DCP to ECH, and fractions IIa and IIb catalyzed the transformation of ECH into MCP. Fractions Ia and IIa showed only low enantioselectivity for each reaction, whereas fractions Ib and IIb exhibited considerable enantioselectivity, yielding R-rich ECH and MCP, respectively. Enzymes Ia and Ib were isolated from fractions Ia and Ib, respectively. Enzyme Ia had a molecular mass of about 108 kDa and consisted of four subunits identical in molecular mass (about 28 kDa). Enzyme Ib was a protein of 115 kDa, composed of two different polypeptides (about 35 and 32 kDa). The specific activity of enzyme Ib for DCP was about 30-fold higher than that of enzyme Ia. Both enzymes catalyzed the transformation of several halohydrins into the corresponding epoxides with liberation of halides and its reverse reaction. Their substrate specificities and immunological properties differed from each other. Enzyme Ia seemed to be halohydrin hydrogen-halide-lyase which was already purified from Escherichia coli carrying a gene from Corynebacterium sp. strain N-1074. Images PMID:1447132

Copper-catalyzed cross-coupling reactions of epoxides with gem-diborylmethane: access to γ-hydroxyl boronic esters.

PubMed

Ebrahim-Alkhalil, Ahmed; Zhang, Zhen-Qi; Gong, Tian-Jun; Su, Wei; Lu, Xiao-Yu; Xiao, Bin; Fu, Yao

2016-04-07

Herein, we describe a novel copper-catalyzed epoxide opening reaction with gem-diborylmethane. Aliphatic, aromatic epoxides as well as aziridines are converted to the corresponding γ-pinacolboronate alcohols or amines in moderate to excellent yields. This new reaction provides beneficial applications for classic epoxide substrates as well as interesting gem-diborylalkane reagents.

Synthesis of Enantiomerically Pure Lignin Dimer Models for Catalytic Selectivity Studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Njiojob, Costyl N.; Rhinehart, Jennifer L.; Bozell, Joseph J.

2015-02-06

A series of highly enantioselective transformations, such as the Sharpless asymmetric epoxidation and Jacobsen hydrolytic kinetic resolution, were utilized to achieve the complete stereoselective synthesis of β-O-4 lignin dimer models containing the S, G, and H subunits with excellent ee (>99%) and moderate to high yields. This unprecedented synthetic method can be exploited for enzymatic, microbial, and chemical investigations into lignin’s degradation and depolymerization as related to its stereochemical constitution. Preliminary degradation studies using enantiopure Co(salen) catalysts are also reported.

Derivatization of castor oil based estolide esters: Preparation of epoxides and cyclic carbonates

USDA-ARS?s Scientific Manuscript database

Estolides that are based on castor oil and oleic acid are versatile starting points for the production of industrial fluids with new properties. A variety of unsaturated estolides were derivatized by epoxidation with hydrogen peroxide. The epoxidized estolides were further modified using supercritic...

Highly enantioselective production of (R)-halohydrins with whole cells of Rhodotorula rubra KCh 82 culture.

PubMed

Janeczko, Tomasz; Dymarska, Monika; Kostrzewa-Susłow, Edyta

2014-12-04

Biotransformation of ten α-haloacetophenones in the growing culture of the strain Rhodotorula rubra KCh 82 has been carried out. Nine of the substrates underwent an effective enantioselective reduction to the respective (R)-alcohols according to Prelog's rule, with the exception of 2-chloro-1,2-diphenylethan-1-one that was not transformed by this strain. The expected reduction proceeded without dehalogenation, leading to the respective (R)-halohydrins in high yields. The use of this biocatalyst yielded (R)-2-bromo-1-phenyl-ethan-1-ol (enantiomeric excess (ee) = 97%) and its derivatives: 4'-Bromo- (ee = 99%); 4'-Chloro- (ee > 99%); 4'-Methoxy- (ee = 96%); 3'-Methoxy- (ee = 93%); 2'-Methoxy- (ee = 98%). There were also obtained and characterized 2,4'-dichloro-, 2,2',4'-trichloro- and 2-chloro-4'-fluoro-phenyetan-1-ol with >99% of enantiomeric excesses.

Highly Enantioselective Production of (R)-Halohydrins with Whole Cells of Rhodotorula rubra KCh 82 Culture

PubMed Central

Janeczko, Tomasz; Dymarska, Monika; Kostrzewa-Susłow, Edyta

2014-01-01

Biotransformation of ten α-haloacetophenones in the growing culture of the strain Rhodotorula rubra KCh 82 has been carried out. Nine of the substrates underwent an effective enantioselective reduction to the respective (R)-alcohols according to Prelog’s rule, with the exception of 2-chloro-1,2-diphenylethan-1-one that was not transformed by this strain. The expected reduction proceeded without dehalogenation, leading to the respective (R)-halohydrins in high yields. The use of this biocatalyst yielded (R)-2-bromo-1-phenyl-ethan-1-ol (enantiomeric excess (ee) = 97%) and its derivatives: 4'-Bromo- (ee = 99%); 4'-Chloro- (ee > 99%); 4'-Methoxy- (ee = 96%); 3'-Methoxy- (ee = 93%); 2'-Methoxy- (ee = 98%). There were also obtained and characterized 2,4'-dichloro-, 2,2',4'-trichloro- and 2-chloro-4'-fluoro-phenyetan-1-ol with >99% of enantiomeric excesses. PMID:25486054

Enantioselective Cobalt-Catalyzed Sequential Nazarov Cyclization/Electrophilic Fluorination: Access to Chiral α-Fluorocyclopentenones.

PubMed

Zhang, Heyi; Cheng, Biao; Lu, Zhan

2018-06-20

A newly designed thiazoline iminopyridine ligand for enantioselective cobalt-catalyzed sequential Nazarov cyclization/electrophilic fluorination was developed. Various chiral α-fluorocyclopentenones were prepared with good yields and diastereo- and enantioselectivities. Further derivatizations could be easily carried out to provide chiral cyclopentenols with three contiguous stereocenters. Furthermore, a direct deesterification of fluorinated products could afford chiral α-single fluorine-substituted cyclopentenones.

Regio- and Enantioselective N-Allylations of Imidazole, Benzimidazole, and Purine Heterocycles Catalyzed by Single-Component Metallacyclic Iridium Complexes

PubMed Central

Stanley, Levi M.

2010-01-01

Highly regio- and enantioselective iridium-catalyzed N-allylations of benzimidazoles, imidazoles, and purines have been developed. N-Allylated benzimidazoles and imidazoles were isolated in high yields (up to 97%) with high branched-to-linear selectivity (up to 99:1) and enantioselectivity (up to 98% ee) from the reactions of benzimidazole and imidazole nucleophiles with unsymmetrical allylic carbonates in the presence of single component, ethylene-bound, metallacyclic iridium catalysts. N-Allylated purines were also obtained in high yields (up to 91%) with high N9:N7 selectivity (up to 96:4), high branched-to-linear selectivity (98:2), and high enantioselectivity (up to 98% ee) under similar conditions. The reactions encompass a range of benzimidazole, imidazole, and purine nucleophiles, as well as a variety of unsymmetrical aryl, heteroaryl, and aliphatic allylic carbonates. Competition experiments between common amine nucleophiles and the heterocyclic nitrogen nucleophiles studied in this work illustrate the effect of nucleophile pKa on the rate of iridium-catalyzed N-allylation reactions. Kinetic studies on the allylation of benzimidazole catalyzed by metallacyclic iridium-phosphoramidite complexes, in combination with studies on the deactivation of these catalysts in the presence of heterocyclic nucleophiles, provide insight into the effects of the structure of the phosphoramidite ligands on the stability of the metallacyclic catalysts. The data obtained from these studies has led to the development of N-allylations of benzimidazoles and imidazoles in the absence of an exogenous base. PMID:19480431

Signature Motifs Identify an Acinetobacter Cif Virulence Factor with Epoxide Hydrolase Activity*

PubMed Central

Bahl, Christopher D.; Hvorecny, Kelli L.; Bridges, Andrew A.; Ballok, Alicia E.; Bomberger, Jennifer M.; Cady, Kyle C.; O'Toole, George A.; Madden, Dean R.

2014-01-01

Endocytic recycling of the cystic fibrosis transmembrane conductance regulator (CFTR) is blocked by the CFTR inhibitory factor (Cif). Originally discovered in Pseudomonas aeruginosa, Cif is a secreted epoxide hydrolase that is transcriptionally regulated by CifR, an epoxide-sensitive repressor. In this report, we investigate a homologous protein found in strains of the emerging nosocomial pathogens Acinetobacter nosocomialis and Acinetobacter baumannii (“aCif”). Like Cif, aCif is an epoxide hydrolase that carries an N-terminal secretion signal and can be purified from culture supernatants. When applied directly to polarized airway epithelial cells, mature aCif triggers a reduction in CFTR abundance at the apical membrane. Biochemical and crystallographic studies reveal a dimeric assembly with a stereochemically conserved active site, confirming our motif-based identification of candidate Cif-like pathogenic EH sequences. Furthermore, cif expression is transcriptionally repressed by a CifR homolog (“aCifR”) and is induced in the presence of epoxides. Overall, this Acinetobacter protein recapitulates the essential attributes of the Pseudomonas Cif system and thus may facilitate airway colonization in nosocomial lung infections. PMID:24474692

Microsomal epoxide hydrolase of rat liver. Purification and characterization of enzyme fractions with different chromatographic characteristics.

PubMed Central

Bulleid, N J; Graham, A B; Craft, J A

1986-01-01

Microsomal epoxide hydrolase was purified from rat liver, and different fractions of the purified enzyme, which varied in their contents of phospholipid, were obtained by ion-exchange chromatography. One fraction (A), which did not bind to CM-cellulose, had a high phospholipid content, and a second fraction (B), which was eluted from CM-cellulose at high ionic strength, had a low phospholipid content. Removal of most of the phospholipid from fraction A altered its chromatographic behaviour. When the delipidated material was re-applied to CM-cellulose, most of the enzyme bound to the cation-exchanger. The specific activities of all the fractions described (with styrene epoxide [(1,2-epoxyethyl)benzene] as substrate) were altered by adding the non-ionic detergent Lubrol PX or phospholipid. Lubrol PX inhibited enzyme activity, and phospholipid reversed this inhibition. The various enzyme fractions isolated appeared to be different forms of the same protein, as judged by their minimum Mr values and immunochemical properties. These results indicate that different fractions of epoxide hydrolase isolated by ion-exchange chromatography probably are not different isoenzyme forms. Images Fig. 2. Fig. 3. PMID:3082328

N-(4-(4-(2,3-Dichloro- or 2-methoxyphenyl)piperazin-1-yl)-butyl)-heterobiarylcarboxamides with Functionalized Linking Chains as High Affinity and Enantioselective D3 Receptor Antagonistsγ

PubMed Central

Newman, Amy Hauck; Grundt, Peter; Cyriac, George; Deschamps, Jeffrey R.; Taylor, Michelle; Kumar, Rakesh; Ho, David; Luedtke, Robert R.

2009-01-01

In the present report, the D3 receptor pharmacophore is modified in the 2,3-diCl-and 2-OCH3-phenyl piperazine class of compounds with the goal to improve D3 receptor affinity and selectivity. This extension of structure-activity relationships (SAR) has resulted in the identification of the first enantioselective D3 antagonists (R- and S-22) to be reported, wherein enantioselectivity is more pronounced at D3 than at D2, and that a binding region on the second extracellular loop (E2) may play a role in both enantioselectivity and D3 receptor selectivity. Moreover, we have discovered some of the most D3-selective compounds reported to date that show high affinity (Ki =1 nM) for D3 and ∼400-fold selectivity over the D2 receptor subtype. Several of these analogues showed exquisite selectivity for D3 receptors over >60 other receptors further underscoring their value as in vivo research tools. These lead compounds also have appropriate physical characteristics for in vivo exploration and therefore will be useful in determining how intrinsic activity at D3 receptors tested in vitro is related to behaviors in animal models of addiction and other neuropsychiatric disorders. PMID:19331412

Enantioselective copper-catalyzed carboetherification of unactivated alkenes.

PubMed

Bovino, Michael T; Liwosz, Timothy W; Kendel, Nicole E; Miller, Yan; Tyminska, Nina; Zurek, Eva; Chemler, Sherry R

2014-06-16

Chiral saturated oxygen heterocycles are important components of bioactive compounds. Cyclization of alcohols onto pendant alkenes is a direct route to their synthesis, but few catalytic enantioselective methods enabling cyclization onto unactivated alkenes exist. Herein reported is a highly efficient copper-catalyzed cyclization of γ-unsaturated pentenols which terminates in C-C bond formation, a net alkene carboetherification. Both intra- and intermolecular C-C bond formations are demonstrated, thus yielding functionalized chiral tetrahydrofurans as well as fused-ring and bridged-ring oxabicyclic products. Transition-state calculations support a cis-oxycupration stereochemistry-determining step. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective Diels-Alder reactions of unsaturated beta-ketoesters catalyzed by chiral ruthenium PNNP complexes.

PubMed

Schotes, Christoph; Mezzetti, Antonio

2011-01-01

We report here dicationic ruthenium PNNP complexes that promote the enantioselective Diels-Alder reaction of alpha-methylene beta-ketoesters with various dienes. Complex [Ru(OEt2)2(PNNP)](PF6)2, formed in situ from [RuCl2,(PNNP)] and (Et3O)PF6 (2 equiv.), catalyzes the Diels-Alder reaction of such unsaturated beta-ketoesters to give novel alkoxycarbonyltetrahydro-1-indanone derivatives (nine examples) with up to 93% ee. The crystal structure of the substrate-catalyst adduct shows that the lower face of the substrate is shielded by a phenyl ring of the PNNP ligand, which accounts for the high enantioselectivity. The attack of the diene from the open re enantioface of the unsaturated beta-ketoester is consistent with the absolute configuration of the product. A useful application of this method is the reaction with Dane's diene to give estrone derivatives with up to 99% ee and an ester-exo:endo ratio of up to 145:1 (after recrystallization). Besides the enantioselective formation of all-carbon quaternary centers, this methodology is notable because unsaturated beta-ketoesters have been rarely used in Diels-Alder reactions. Furthermore, enantiomerically pure estrone derivatives are interesting in view of their potential applications, including the treatment of breast cancer.

Synthesis of 1-[bis(trifluoromethyl)phosphine]-1'-oxazolinylferrocene ligands and their application in regio- and enantioselective Pd-catalyzed allylic alkylation of monosubstituted allyl substrates.

PubMed

Lai, Zeng-Wei; Yang, Rong-Fei; Ye, Ke-Yin; Sun, Hongbin; You, Shu-Li

2014-01-01

A class of novel, easily accessible and air-stable 1-[bis(trifluoromethyl)phosphine]-1'-oxazolinylferrocene ligands has been synthesized from ferrocene. It became apparent that these ligands can be used in the regio- and enantioselective Pd-catalyzed allylic alkylation of monosubstituted allyl substrates in a highly efficient manner. Excellent regio- and enantioselectivity could be obtained for a wide range of substrates.

Enantioselective Synthesis of Polycyclic Nitrogen Heterocycles by Rh-Catalyzed Alkene Hydroacylation: Constructing Six-Membered Rings in the Absence of Chelation Assistance

PubMed Central

2015-01-01

Catalytic, enantioselective hydroacylations of N-allylindole-2-carboxaldehydes and N-allylpyrrole-2-carboxaldehydes are reported. In contrast to many alkene hydroacylations that form six-membered rings, these annulative processes occur in the absence of ancillary functionality to stabilize the acylrhodium(III) hydride intermediate. The intramolecular hydroacylation reactions generate 7,8-dihydropyrido[1,2-a]indol-9(6H)ones and 6,7-dihydroindolizin-8(5H)-ones in moderate to high yields with excellent enantioselectivities. PMID:25020184

Patulin biosynthesis: Epoxidation of toluquinol and gentisyl alcohol by particulate preparations from Penicillium patulum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Priest, J.W.; Light, R.J.

1989-11-14

A crude extract that catalyzes the epoxidation of toluquinol and gentisyl alcohol was isolated from cultures of Penicillium patulum. About 60% of the activity sedimented from crude extract upon centrifugation at 105000g for 2 h, and at 30000g for 30 min after precipitation with 30% ammonium sulfate and resuspension in buffer. The quinone epoxide phyllostine, a product of gentisyl alcohol epoxidation, has previously been shown to be an intermediate in the biosynthesis of patulin and was shown to be further converted to neopatulin by the extract. The epoxide product of toluquinol, desoxyphyllostine (2-methyl-5,6-epoxy-1,4-benzoquinone), has not been reported previously from fungalmore » cultures. Its structure was confirmed by GC-mass spectrometry and proton and {sup 13}C NMR. Its CD spectrum showed the same shape and signs as that of phyllostine, indicating that it too is an enzymatic product with a similar absolute configuration. Whereas chemical epoxidation of toluquinone and gentisly quinone occurs with hydrogen peroxide, the enzymatic epoxidation utilized oxygen and the hydroquinone. The epoxidation was inhibited by 1,10-phenanthroline, EDTA, and {rho}-(chloromercuri)benzenesulfonic acid and by degassing with nitrogen, but no inhibition was observed with KCN, catalase, or CO. The apparent K{sub m}'s were similar for the two substrates with both substrates showing inhibition at 1.0 mM. The rate of desoxyphyllostine formation was more than 10 times that of phyllostine formation at equivalent substrate concentrations. Gentisaldehyde was not a substrate for the enzyme. The epoxidase was induced in late fermentor cultures of P. patulum with the same kinetics as m-hydroxybenzyl alcohol dehydrogenase, another enzyme associated with the induction of patulin biosynthesis.« less

Bifunctional Asymmetric Catalysis with Hydrogen Chloride: Enantioselective Ring-Opening of Aziridines Catalyzed by a Phosphinothiourea

PubMed Central

Mita, Tsuyoshi; Jacobsen, Eric N.

2009-01-01

Ring-opening of aziridines with hydrogen chloride to form β-chloroamine derivatives is catalyzed by a chiral phosphinothiourea derivative in high yields and with high enantioselectivities. On the basis of 31P NMR studies, activation of HCl appears to proceed via quantitative protonation of the catalyst to afford a phosphonium chloride complex. PMID:20161432

Silica-supported, single-site titanium catalysts for olefin epoxidation. A molecular precursor strategy for control of catalyst structure.

PubMed

Jarupatrakorn, Jonggol; Don Tilley, T

2002-07-17

A molecular precursor approach involving simple grafting procedures was used to produce site-isolated titanium-supported epoxidation catalysts of high activity and selectivity. The tris(tert-butoxy)siloxy titanium complexes Ti[OSi(O(t)Bu)(3)](4) (TiSi4), ((i)PrO)Ti[OSi(O(t)Bu)(3)](3) (TiSi3), and ((t)BuO)(3)TiOSi(O(t)Bu)(3) (TiSi) react with the hydroxyl groups of amorphous Aerosil, mesoporous MCM-41, and SBA-15 via loss of HO(t)Bu and/or HOSi(O(t)Bu)(3) and introduction of titanium species onto the silica surface. Powder X-ray diffraction, nitrogen adsorption/desorption, infrared, and diffuse reflectance ultraviolet spectroscopies were used to investigate the structures and chemical natures of the surface-bound titanium species. The titanium species exist mainly in isolated, tetrahedral coordination environments. Increasing the number of siloxide ligands in the molecular precursor decreases the amount of titanium that can be introduced this way, but also enhances the catalytic activity and selectivity for the epoxidation of cyclohexene with cumene hydroperoxide as oxidant. In addition, the high surface area mesoporous silicas (MCM-41 and SBA-15) are more effective than amorphous silica as supports for these catalysts. Supporting TiSi3 on the SBA-15 affords highly active cyclohexene epoxidation catalysts (0.25-1.77 wt % Ti loading) that provide turnover frequencies (TOFs) of 500-1500 h(-1) after 1 h (TOFs are reduced by about half after calcination). These results demonstrate that oxygen-rich siloxide complexes of titanium are useful as precursors to supported epoxidation catalysts.

Enantioselective Brønsted Acid Catalysis as a Tool for the Synthesis of Natural Products and Pharmaceuticals.

PubMed

Merad, Jérémy; Lalli, Claudia; Bernadat, Guillaume; Maury, Julien; Masson, Géraldine

2018-03-15

Synthesis of biologically active molecules (whether at laboratory or industrial scale) remains a highly appealing area of modern organic chemistry. Nowadays, the need to access original bioactive scaffolds goes together with the desire to improve synthetic efficiency, while reducing the environmental footprint of chemical activities. Long neglected in the field of total synthesis, enantioselective organocatalysis has recently emerged as an environmentally friendly and indispensable tool for the construction of relevant bioactive molecules. Notably, enantioselective Brønsted acid catalysis has offered new opportunities in terms of both retrosynthetic disconnections and controlling stereoselectivity. The present report attempts to provide an overview of enantioselective total or formal syntheses designed around Brønsted acid-catalyzed transformations. To demonstrate the versatility of the reactions promoted and the diversity of the accessible motifs, this Minireview draws a systematic parallel between methods and retrosynthetic analysis. The manuscript is organized according to the main reaction types and the nature of newly-formed bonds. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Purification and characterization of enantioselective N-acetyl-β-Phe acylases from Burkholderia sp. AJ110349.

PubMed

Imabayashi, Yuki; Suzuki, Shun'ichi; Kawasaki, Hisashi; Nakamatsu, Tsuyoshi

2016-01-01

For the production of enantiopure β-amino acids, enantioselective resolution of N-acyl β-amino acids using acylases, especially those recognizing N-acetyl-β-amino acids, is one of the most attractive methods. Burkholderia sp. AJ110349 had been reported to exhibit either (R)- or (S)-enantiomer selective N-acetyl-β-Phe amidohydrolyzing activity, and in this study, both (R)- and (S)-enantioselective N-acetyl-β-Phe acylases were purified to be electrophoretically pure and determined the sequences, respectively. They were quite different in terms of enantioselectivities and in their amino acids sequences and molecular weights. Although both the purified acylases were confirmed to catalyze N-acetyl hydrolyzing activities, neither of them show sequence similarities to the N-acetyl-α-amino acid acylases reported thus far. Both (R)- and (S)-enantioselective N-acetyl-β-Phe acylase were expressed in Escherichia coli. Using these recombinant strains, enantiomerically pure (R)-β-Phe (>99% ee) and (S)-β-Phe (>99% ee) were obtained from the racemic substrate.

Modification and simulation of Rhizomucor miehei lipase: the influence of surficial electrostatic interaction on enantioselectivity.

PubMed

Xu, Gang; Meng, Xiao; Xu, Lin-Jie; Guo, Li; Wu, Jian-Ping; Yang, Li-Rong

2015-04-01

Surface residues have a significant impact on the enantioselectivity of lipases. But the molecular basis of this has never been explained. In this work, transition state complexes of Rhizomucor miehei lipase (RmL) and (R)- or (S)-n-butyl 2-phenxypropinate were studied using molecular dynamics. According to comparison between B-factor of the two simulated complexes, the β 1-β 2 loop and α 2 helix were considered the enantioselectivity-determining domains of RmL. Interaction analysis of these domains suggested an Asp(61)-Arg(86) electrostatic interaction linking the loop and helix strongly impacting enantioselectivity of RmL. Modification of Arg(86) by 1, 2-cyclohexanedione weakening this interaction decreased the E ratio from 6 to 1, modification by 1-iodo-2, 3-butanedione covalently bonding Asp(61) and Arg(86) strengthening the interaction increased the E ratio to 45. Dynamics simulation and energy calculation of the modified lipases also displayed corresponding decreases or increases of enantioselectivity.

Reaction Mechanism for Direct Propylene Epoxidation by Alumina-Supported Silver Aggregates. The Role of the Particle / Support Interface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Lei; Yin, Chunrong; Mehmood, Faisal

2013-11-21

Sub-nanometer Ag aggregates on alumina supports have been found to be active toward direct propylene epoxidation to propylene oxide by molecular oxygen at low temperatures, with a negligible amount of carbon dioxide formation (Science 328, p. 224, 2010). In this work, we computationally and experimentally investigate the origin of the high reactivity of the sub-nanometer Ag aggregates. Computationally, we study O 2 dissociation and propylene epoxidation on unsupported Ag 19 and Ag 20 clusters, as well as alumina-supported Ag 19. The O 2 dissociation and propylene epoxidation apparent barriers at the interface between the Ag aggregate and the alumina supportmore » are calculated to be 0.2 and 0.2~0.4 eV, respectively. These barriers are somewhat lower than those on sites away from the interface. The mechanism at the interface is similar to what was previously found for the silver trimer on alumina and can account for the high activity observed for the direct oxidation of propylene on the Ag aggregates. The barriers for oxygen dissociation on these model systems both at the interface and on the surfaces are small compared to crystalline surfaces, indicating that availability of oxygen will not be a rate limiting step for the aggregates, as in the case of the crystalline surfaces. Experimentally, we investigate Ultrananocrystalline Diamond (UNCD)-supported silver aggregates under reactive conditions of propylene partial oxidation. The UNCD-supported Ag clusters are found to be not measurably active toward propylene oxidation, in contrast to the alumina supported Ag clusters. This suggests that the lack of metal-oxide interfacial sites of the Ag-UNCD catalyst, limits the epoxidation catalytic activity. This combined computational and experimental study shows the importance of the metal-oxide interface as well as the non-crystalline nature of the alumina-supported sub-nanometer Ag aggregate catalysts for propylene epoxidation.« less

Covalent Heterogenization of a Discrete Mn(II) Bis-Phen Complex by a Metal-Template/Metal-Exchange Method: An Epoxidation Catalyst with Enhanced Reactivity

PubMed Central

Terry, Tracy J.; Stack, T. Daniel P.

2009-01-01

Considerable attention has been devoted to the immobilization of discrete epoxidation catalysts onto solid supports due to the possible benefits of site isolation such as increased catalyst stability, catalyst recycling, and product separation. A synthetic metal-template/metal-exchange method to imprint a covalently attached bis-1,10-phenanthroline coordination environment onto high-surface area, mesoporous SBA-15 silica is reported herein along with the epoxidation reactivity once reloaded with manganese. Comparisons of this imprinted material with material synthesized by random grafting of the ligand show that the template method creates more reproducible, solution-like bis-1,10-phenanthroline coordination at a variety of ligand loadings. Olefin epoxidation with peracetic acid shows the imprinted manganese catalysts have improved product selectivity for epoxides, greater substrate scope, more efficient use of oxidant, and higher reactivity than their homogeneous or grafted analogues independent of ligand loading. The randomly grafted manganese catalysts, however, show reactivity that varies with ligand loading while the homogeneous analogue degrades trisubstituted olefins and produces trans-epoxide products from cis-olefins. Efficient recycling behavior of the templated catalysts is also possible. PMID:18351763

Enantioselective determination of (R)-zopiclone and (S)-zopiclone (eszopiclone) in human hair by micropulverized extraction and chiral liquid chromatography/high resolution mass spectrometry.

PubMed

Miyaguchi, Hajime; Kuwayama, Kenji

2017-10-13

Zopiclone and its (S)-enantiomer (eszopiclone) are commonly prescribed for insomnia. Despite the high demand for enantioselective differentiation, the chiral analysis of zopiclone in hair has not been reported. In this study, a method for the enantioselective quantification of zopiclone in human hair was developed. The extraction medium and duration were optimized using real eszopiclone-positive hair samples. Specifically, micropulverized extraction with 3.0M ammonium phosphate buffer (pH 8.4) involving salting-out assisted liquid-liquid extraction with acetonitrile was utilized to minimize the degradation of zopiclone and for rapid and facile operation. On the other hand, recovery of the conventional solid-liquid extraction involved overnight soaking in 3.0M ammonium phosphate buffer (pH 8.4) was only 0.58±0.12% of the maximum recovery achieved by the present method due to the decomposition in the phosphate buffer. An excellent chiral separation (Rs=5.0) was achieved using a chiral stationary phase comprising cellulose tris(3,5-dichlorophenylcarbamate) and a volatile mobile phase of 10mM ammonium carbonate (pH 8.0)-acetonitrile (25:75, v/v). Detection was carried out using liquid chromatography/high resolution mass spectrometry (LC/HRMS) with electrospray ionization. A Q Exactive mass spectrometer equipped with a quadrupole-Orbitrap analyzer was used for detection. The concentration of 0.50pg/mg was defined as the lowest limit of quantification using 5mg of hair sample. Using the developed approach, the concentration of eszopiclone in hair after a single 2-mg dose was found to be 441pg/mg, which was higher than all the reported values regarding a single administration of zopiclone. After daily administration of racemic zopiclone (3.75mg/day), the concentrations of (R)-enantiomer and (S)-enantiomer in the black hair were 5.30-8.31ng/mg and 7.96-12.8ng/mg, respectively, and the concentration of the (S)-enantiomer was always higher than that of the (R

Teaching Green Chemistry with Epoxidized Soybean Oil

ERIC Educational Resources Information Center

Barcena, Homar; Tuachi, Abraham; Zhang, Yuanzhuo

2017-01-01

The synthesis of epoxidized soybean oil (ESO) provides students a vantage point on the application of green chemistry principles in a series of experiments. Qualitative tests review the reactions of alkenes, whereas spectroscopic analyses provide insight in monitoring functional group transformations.

40 CFR 721.2685 - Polyisobutene epoxide (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

....2685 Section 721.2685 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.2685 Polyisobutene epoxide (generic). (a) Chemical substances and significant new uses...

4D printing smart biomedical scaffolds with novel soybean oil epoxidized acrylate

PubMed Central

Miao, Shida; Zhu, Wei; Castro, Nathan J.; Nowicki, Margaret; Zhou, Xuan; Cui, Haitao; Fisher, John P.; Zhang, Lijie Grace

2016-01-01

Photocurable, biocompatible liquid resins are highly desired for 3D stereolithography based bioprinting. Here we solidified a novel renewable soybean oil epoxidized acrylate, using a 3D laser printing technique, into smart and highly biocompatible scaffolds capable of supporting growth of multipotent human bone marrow mesenchymal stem cells (hMSCs). Porous scaffolds were readily fabricated by simply adjusting the printer infill density; superficial structures of the polymerized soybean oil epoxidized acrylate were significantly affected by laser frequency and printing speed. Shape memory tests confirmed that the scaffold fixed a temporary shape at −18 °C and fully recovered its original shape at human body temperature (37 °C), which indicated the great potential for 4D printing applications. Cytotoxicity analysis proved that the printed scaffolds had significant higher hMSC adhesion and proliferation than traditional polyethylene glycol diacrylate (PEGDA), and had no statistical difference from poly lactic acid (PLA) and polycaprolactone (PCL). This research is believed to significantly advance the development of biomedical scaffolds with renewable plant oils and advanced 3D fabrication techniques. PMID:27251982

Synthesis of an Epoxide Carbonylation Catalyst: Exploration of Contemporary Chemistry for Advanced Undergraduates

ERIC Educational Resources Information Center

Getzler, Yutan D. Y. L.; Schmidt, Joseph A. R.; Coates, Geoffrey W.

2005-01-01

A class of highly active, well-defined compounds for the catalytic carbonylation of epoxides and aziridines to beta-lactones and beta-lactams are introduced. The synthesis of one of the catalysts involves a simple imine condensation to form the ligand followed by air-sensitive metalation and salt metathesis steps.

Enantioselective synthesis of allylic esters via asymmetric allylic substitution with metal carboxylates using planar-chiral cyclopentadienyl ruthenium catalysts.

PubMed

Kanbayashi, Naoya; Onitsuka, Kiyotaka

2010-02-03

An asymmetric allylic substitution with sodium carboxylate using a planar-chiral cyclopentadienyl ruthenium complex has been developed. Optically active allylic esters were prepared in good yields with high regio- and enantioselectivities.

Synthesis of Quaternary Carbon Stereogenic Centers through Enantioselective Cu-Catalyzed Allylic Substitutions with Vinylaluminum Reagents

PubMed Central

Gao, Fang; McGrath, Kevin P.; Lee, Yunmi; Hoveyda, Amir H.

2010-01-01

Catalytic enantioselective allylic substitution (EAS) reactions, which involve the use of alkyl- or aryl-substituted vinylaluminum reagents and afford 1,4-dienes containing a quaternary carbon stereogenic center at their C-3 site, are disclosed. The C–C bond forming transformations are promoted by 0.5–2.5 mol % of sulfonate bearing chiral bidentate N-heterocyclic carbene (NHC) complexes, furnishing the desired products efficiently (66–97% yield of isolated products) and in high site- (>98% SN2′) and enantioselectivity [up to 99:1 enantiomer ratio (er)]. To the best of our knowledge, the present report puts forward the first cases of allylic substitution reactions that result in the generation of all-carbon quaternary stereogenic centers through the addition of a vinyl unit. The aryl- and vinyl-substituted vinylaluminum reagents, which cannot be prepared in high efficiency through direct reaction with diisobutylaluminum hydride, are accessed through a recently introduced Ni-catalyzed reaction of the corresponding terminal alkynes with the same inexpensive metal-hydride agent. Sequential Ni-catalyzed hydrometallations and Cu-catalyzed C–C bond forming reactions allow for efficient and selective synthesis of a range of enantiomerically enriched EAS products, which cannot cannot be accessed by previously disclosed strategies (due to inefficient vinylmetal synthesis or low reactivity and/or selectivity with Si-substituted derivatives). The utility of the protocols developed is demonstrated through a concise enantioselective synthesis of natural product bakuchiol. PMID:20860365

Enantioselective Total Synthesis of Natural Isoflavans: Asymmetric Transfer Hydrogenation/Deoxygenation of Isoflavanones with Dynamic Kinetic Resolution.

PubMed

Keßberg, Anton; Lübken, Tilo; Metz, Peter

2018-05-02

A concise and highly enantioselective synthesis of structurally diverse isoflavans from a single chromone is described. The key transformation is a single-step conversion of racemic isoflavanones into virtually enantiopure isoflavans by domino asymmetric transfer hydrogenation/deoxygenation with dynamic kinetic resolution.

Enantioselective behaviour of the herbicide fluazifop-butyl in vegetables and soil.

PubMed

Qi, Yanli; Liu, Donghui; Liu, Chang; Liang, Yiran; Zhan, Jing; Zhou, Zhiqiang; Wang, Peng

2017-04-15

The enantioselective dissipation of the enantiomers of fluazifop-butyl in tomato, cucumber, pakchoi, rape and soil under field condition was investigated to elucidate the enantioselective environmental behaviours and chiral stability of the optical pure product. Fluazifop, the major chiral metabolite of fluazifop-butyl, was also detected. Fluazifop-butyl dissipated rapidly in the vegetables and soil with the half-lives of the enantiomers ranging from 1.62 to 2.84days. Enantioselective degradations of fluazifop-butyl were found. In tomato and cucumber, S-fluazifop-butyl dissipated faster than R-enantiomer, while R-fluazifop-butyl showed a faster degradation in pakchoi, rape and soil. Fluazifop was found almost immediately after the application of fluazifop-butyl and had relatively longer persistent time. When the optical pure product fluazifop-P-butyl was applied, rapid degradation to R-fluazifop was found with half-lives from 1.24 to 2.28days, and no S-fluazifop-butyl or S-fluazifop was detected showing the herbicidally active fluazifop-P-butyl and R-fluazifop were configurationally stable. Copyright © 2016 Elsevier Ltd. All rights reserved.

An ylide transformation of rhodium(I) carbene: enantioselective three-component reaction through trapping of rhodium(I)-associated ammonium ylides by β-nitroacrylates.

PubMed

Ma, Xiaochu; Jiang, Jun; Lv, Siying; Yao, Wenfeng; Yang, Yang; Liu, Shunying; Xia, Fei; Hu, Wenhao

2014-11-24

The chiral Rh(I)-diene-catalyzed asymmetric three-component reaction of aryldiazoacetates, aromatic amines, and β-nitroacrylates was achieved to obtain γ-nitro-α-amino-succinates in good yields and with high diastereo- and enantioselectivity. This reaction is proposed to proceed through the enantioselective trapping of Rh(I)-associated ammonium ylides by nitroacrylates. This new transformation represents the first example of Rh(I)-carbene-induced ylide transformation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective Rhodium Enolate Protonations. A New Methodology for the Synthesis of β2-Amino Acids

PubMed Central

Sibi, Mukund P.; Tatamidani, Hiroto; Patil, Kalyani

2008-01-01

Rhodium catalyzed conjugate addition of an aryl boronic acid to α-methylamino acrylates followed by enantioselective protonation of the oxa-π-allylrhodium intermediate provides access to aryl substituted β2-amino acids. The impact of the different variables of the reaction on the levels of enantioselectivity has been assessed. PMID:15957893

Ring-opening Polymerization of Epoxidized Soybean Oil

USDA-ARS?s Scientific Manuscript database

Ring opening polymerization of epoxidized soybean oil (ESO) initiated by boron trifluoride diethyl etherate, (BF3•OEt2), in methylene chloride was conducted in an effort to develop useful biodegradable polymers. The resulting polymers (PESO) were characterized using Infrared (IR), differential scan...

A chiral Brønsted acid-catalyzed highly enantioselective Mannich-type reaction of α-diazo esters with in situ generated N-acyl ketimines.

PubMed

Unhale, Rajshekhar A; Sadhu, Milon M; Ray, Sumit K; Biswas, Rayhan G; Singh, Vinod K

2018-04-03

A chiral phosphoric acid-catalyzed asymmetric Mannich-type reaction of α-diazo esters with in situ generated N-acyl ketimines, derived from 3-hydroxyisoindolinones has been demonstrated in this communication. A variety of isoindolinone-based α-amino diazo esters bearing a quaternary stereogenic center were afforded in high yields (up to 99%) with excellent enantioselectivities (up to 99% ee). Furthermore, the synthetic utility of the products has been depicted by the hydrogenation of the diazo moiety of adducts.

Evaluation of reversible interconversion in comprehensive two-dimensional gas chromatography using enantioselective columns in first and second dimensions.

PubMed

Kröger, Sabrina; Wong, Yong Foo; Chin, Sung-Tong; Grant, Jacob; Lupton, David; Marriott, Philip J

2015-07-24

The reversible molecular interconversion behaviour of a synthesised oxime (2-phenylpropanaldehyde oxime; (C6H5)CH(CH3)CHN(OH)) was investigated by both, single dimensional gas chromatography (1D GC) and comprehensive two-dimensional gas chromatography (GC×GC). Previous studies on small molecular weight oximes were extended to this larger aromatic oxime (molar mass 149.19gmol(-1)) with interest in the extent of interconversion, enantioselective resolution, and retention time. On a polyethylene glycol (PEG; wax-type) column, a characteristic interconversion zone between two antipodes of E and Z isomers was formed by molecules which have undergone isomerisation on the column (E⇌Z). The extent of interconversion was investigated by varying chromatographic conditions (oven temperature and carrier flow rate) to understand the nature of the behaviour observed. The extent of interconversion was negligible in both enantioselective and methyl-phenylpolysiloxane phase-columns, correlating with the low polarity of the stationary phase. In order to obtain isomerisation along with enantio-resolution, a wax-type and an enantioselective column were coupled in either enantioselective-wax or wax-enantioselective order. The most appropriate column arrangement was selected for study by using a GC×GC experiment with either a wax-phase or phenyl-methylpolysiloxane phase as (2)D column. In addition to evaluation of these fast elution columns, a long narrow-bore enantioselective column (10m) was introduced as (2)D, providing an enantioselective-PEG (coupled-column ensemble: (1)D1+(1)D2)×enantioselective ((2)D) column combination. In this instance, the (1)D1 enantioselective column provides enantiomeric separation of the corresponding enantiomers ((R) and (S)) of (E)- and (Z)-2-phenylpropanaldehyde oxime, followed by E/Z isomerisation in the coupled (1)D2 PEG (reactor) column. The resulting chromatographic interconversion region was modulated and separated into either E/Z isomers

Synthesis of 1-[bis(trifluoromethyl)phosphine]-1’-oxazolinylferrocene ligands and their application in regio- and enantioselective Pd-catalyzed allylic alkylation of monosubstituted allyl substrates

PubMed Central

Lai, Zeng-Wei; Yang, Rong-Fei; Ye, Ke-Yin

2014-01-01

Summary A class of novel, easily accessible and air-stable 1-[bis(trifluoromethyl)phosphine]-1’-oxazolinylferrocene ligands has been synthesized from ferrocene. It became apparent that these ligands can be used in the regio- and enantioselective Pd-catalyzed allylic alkylation of monosubstituted allyl substrates in a highly efficient manner. Excellent regio- and enantioselectivity could be obtained for a wide range of substrates. PMID:24991277

FAD C(4a)-hydroxide stabilized in a naturally fused styrene monooxygenase

PubMed Central

Schlömann, Michael; van Berkel, Willem J.H.; Gassner, George T.

2013-01-01

StyA2B represents a new class of styrene monooxygenases that integrates flavin-reductase and styrene-epoxidase activities into a single polypeptide. This naturally-occurring fusion protein offers new avenues for studying and engineering biotechnologically relevant enantioselective biochemical epoxidation reactions. Stopped-flow kinetic studies of StyA2B reported here identify reaction intermediates similar to those reported for the separate reductase and epoxidase components of related two-component systems. Our studies identify substrate epoxidation and elimination of water from the FAD C(4a)-hydroxide as rate-limiting steps in the styrene epoxidation reaction. Efforts directed at accelerating these reaction steps are expected to greatly increase catalytic efficiency and the value of StyA2B as biocatalyst. PMID:24157359

Alkene epoxidation employing metal nitro complexes

DOEpatents

Andrews, M.A.; Cheng, C.W.; Kelley, K.P.

1982-07-15

Process for converting alkenes to form epoxides utilizes transition metal nitro complexes of the formula: M(RCN)/sub 2/XNO/sub 2/ wherein M is palladium or platinum, R is an alkyl or aryl group containing up to 12 carbon atoms, and X is a monoanionic, monodentate ligand such as chlorine, optionally in the presence of molecular oxygen.

Enantioselective bioaccumulation of diniconazole in Tenebrio molitor larvae.

PubMed

Liu, Chen; LV, Xiao Tian; Zhu, Wen Xue; QU, Hao Yang; Gao, Yong Xin; Guo, Bao Yuan; Wang, Hui Li

2013-12-01

The enantioselective bioaccumulation of diniconazole in Tenebrio molitor Linne larva was investigated with liquid chromatography tandem mass spectrometry based on the ChiralcelOD-3R[cellulose tri-(3,5-dimethylphenyl carbamate)] column. In this study we documented the effects of dietary supplementation with wheat bran contaminated by racemic diniconazole at two dose levels of 20 mg kg(-1) and 2 mg kg(-1) (dry weight) in Tenebrio molitor. The results showed that both doses of diniconazole were taken up by Tenebrio molitor rapidly in the first few days, the concentrations of R-enantiomer and S-enantiomer at high doses reached the highest level of 0.55 mg kg(-1) and 0.48 mg kg(-1) , respectively, on the 1(st) d, and the concentrations of them obtained a maxima of 0.129 mg kg(-1) and 0.128 mg kg(-1) at low dose, respectively, on the 3(rd) d, which means that the concentration of diniconazole was proportional to the time of achieving the highest accumulated level. It afterwards attained equilibrium after a sharp decline at both 20 mg kg(-1) and 2 mg kg(-1) of diniconazole. The determination results from the feces of Tenebrio molitor demonstrated that the extraction recovery (ER) values of the high dose group were higher than that of the low dose group and the values were all above 1; therefore, it could be inferred that enantiomerization existed in Tenebrio molitor. Additionally, the biota accumulation factor was used to evaluate the bioaccumulation of diniconazole enantiomers, showing that the bioaccumulation of diniconazole in Tenebrio molitor was enantioselective with preferential accumulation of S-enantiomer. © 2013 Wiley Periodicals, Inc.

A computational study on the role of chiral N-oxides in enantioselective Pauson-Khand reactions.

PubMed

Fjermestad, Torstein; Pericàs, Miquel A; Maseras, Feliu

2011-08-29

Density functional calculations were carried out to ascertain the origin of enantioselectivity in the brucine N-oxide (BNO)-assisted enantioselective Pauson-Khand reaction (PKR) of norbornene with 2-methyl-3-butyn-2-ol. The computed ee value in acetone is 68 % (R), which compares well to the previously reported experimental value of 58 % (R). In DME the computed ee value of 76 % (R) is in excellent agreement with the experimentally determined value of 78 % (R). The mechanism of enantioselectivity consists of several steps. First, the dicobalt complex is activated by BNO with chirality transfer from enantiopure BNO to the dicobalt complex. Second, competition occurs between a racemization process and complexation with the olefin reagent, which leads to the products. The lower ee value in acetone is due to the lower energy barrier of the racemization process. Calculations show that replacement of BNO by a hypothetical more enantioselective chiral N-oxide will hardly increase the ee value beyond 90 %. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective Synthesis of (-)-Vallesine: Late-Stage C17-Oxidation via Complex Indole Boronation.

PubMed

Antropow, Alyssa H; Garcia, Nicholas R; White, Kolby L; Movassaghi, Mohammad

2018-06-04

The first enantioselective total synthesis of (-)-vallesine via a strategy that features a late-stage regioselective C17-oxidation followed by a highly stereoselective transannular cyclization is reported. The versatility of this approach is highlighted by the divergent synthesis of the archetypal alkaloid of this family, (+)-aspidospermidine, and an A-ring-oxygenated derivative, (+)-deacetylaspidospermine, the precursor to (-)-vallesine, from a common intermediate.

Alphatic 3,4-epoxyalcohols. Metabolism by epoxide hydrase and mutagenic activity.

PubMed

Ortiz de Montellano, P R; Boparai, A S

1978-12-18

Rabbit hepatic microsomal epoxide hydrase catalyzes the rapid hydrolysis of 1,2-epoxy-4-heptanol to 1,2,4-heptanetriol. Both diastereomers of the substrate are hydrolyzed, and both product diastereomers are formed. Similarly both cis- and trans-3,4-epoxy-1-hexanol are hydrolyzed, albeit more slowly, to give 1,3,4-hexanetriol. The trans isomer gives exclusively one diastereomer (erythro) of the triol, while the cis isomer gives the other diastereomer (threo). The product expected if a primary cationic intermediate were to be formed and trapped intramolecularly during the hydrolysis of 1,2-epoxy-4-heptanol, 2-propyl-4-tetrahydrofuranol, was not observed. A comparison of the mutagenic activity in the Ames test of 1-heptane, 1-hepten-4-ol, 1,2-epoxyheptane, and 1,2-epoxy-4-heptanol revealed that only the latter is a detectable mutagen. A vicinal hydroxyl therefore does not interfere significantly with enzymatic epoxide hydrolysis, but it does enhance the bioalkylating potential of even an aliphatic epoxide.

Enantioselectivity of anteiso-fatty acids in hitherto uninspected sample matrices.

PubMed

Eibler, Dorothee; Seyfried, Carolin; Vetter, Walter

2017-09-01

Anteiso-fatty acids (aFAs) are chiral molecules due to a methyl substituent on the antepenultimate carbon of the otherwise straight acyl chain. 12-Methyltetradecanoic acid (a15:0) and 14-methylhexadecanoic acid (a17:0) are the predominant aFAs in nature but their individual contributions e.g. to food lipids are usually low. Enantioselective data has been collected in fish, bovine milk/cheese, and Brussels sprouts. In this study, we determined the enantioselectivity of a15:0 and a17:0 in shea butter, moose and camel milk, two soil samples and mold (collected from contaminated cheese). For this purpose, sample lipids were extracted and containing fatty acids were converted into methyl esters. Methyl esters of aFAs were selectively enriched by hydrogenation, urea complexation and/or RP-HPLC-fractionation. Enantioselective gas chromatography with mass spectrometry operated in the selected ion monitoring mode using a chiral stationary phase consisting of 66% tert.-butyldimethylsilylated β-cyclodextrin in OV-1701. While a15:0 and a17:0 in moose milk were (S)-enantiopure, all other determined samples contained up to 10% (R)-aFAs. The highest proportions of (R)-enantiomers were detected in the soil samples (ee=80%). Copyright © 2017 Elsevier B.V. All rights reserved.

Enantioconvergent biohydrolysis of racemic styrene oxide to R-phenyl-1, 2-ethanediol by a newly isolated filamentous fungus Aspergillus tubingensis TF1.

PubMed

Duarah, Aparajita; Goswami, Amrit; Bora, Tarun C; Talukdar, Madhumita; Gogoi, Binod K

2013-08-01

An effort was made to isolate biocatalysts hydrolyzing epoxides from various ecological niches of northeast India, a biodiversity hot spot zone of the world and screened for epoxide hydrolase activity to convert different racemic epoxides to the corresponding 1, 2-vicinal diols. Screening of a total of 450 microorganisms isolated was carried out using NBP colorimetric assay. One of the strains TF1, after internal transcribed spacer sequence analysis, identified as Aspergillus tubingensis, showed promising enantioconvergent epoxide hydrolase activity. The hydrolysis of unsubstituted styrene oxide (1) occurred to give 97 % ee of R-(-)-1-phenylethane-1, 2-diol (6) with more than 99 % conversion within 45 min incubation. It is shown to be a cheap and practical biocatalyst for one step asymmetric synthesis of chiral R-diol. The other representative substrates (2-5), although underwent hydrolysis with more than 99 % conversion beyond 15 h, exhibited poor enantioselectivity.

Rh(I)-Catalyzed Intermolecular Hydroacylation: Enantioselective Cross-Coupling of Aldehydes and Ketoamides

PubMed Central

2015-01-01

Under Rh(I) catalysis, α-ketoamides undergo intermolecular hydroacylation with aliphatic aldehydes. A newly designed Josiphos ligand enables access to α-acyloxyamides with high atom-economy and enantioselectivity. On the basis of mechanistic and kinetic studies, we propose a pathway in which rhodium plays a dual role in activating the aldehyde for cross-coupling. A stereochemical model is provided to rationalize the sense of enantioinduction observed. PMID:24937681

Catalytic, Enantioselective Synthesis of Stilbene cis-Diamines: A Concise Preparation of (–)-Nutlin-3, a Potent p53/MDM2 Inhibitor

PubMed Central

Davis, Tyler A.

2012-01-01

The first highly diastereo- and enantioselective additions of aryl nitromethane pronucleophiles to aryl aldimines are described. Identification of an electron rich chiral Bis(Amidine) catalyst for this aza-Henry variant was key to this development, leading ultimately to differentially protected cis-stilbene diamines in two steps. This method then became the lynchpin for an enantioselective synthesis of (–)-Nutlin-3 (Hoffmann-LaRoche), a potent cis-imidazoline small molecule inhibitor of p53-MDM2 used extensively as a probe of cell biology and currently in drug development. PMID:22708054

Rhodium-Catalyzed Asymmetric N-H Functionalization of Quinazolinones with Allenes and Allylic Carbonates: The First Enantioselective Formal Total Synthesis of (-)-Chaetominine.

PubMed

Zhou, Yirong; Breit, Bernhard

2017-12-22

An unprecedented asymmetric N-H functionalization of quinazolinones with allenes and allylic carbonates was successfully achieved by rhodium catalysis with the assistance of chiral bidentate diphosphine ligands. The high efficiency and practicality of this method was demonstrated by a low catalyst loading of 1 mol % as well as excellent chemo-, regio-, and enantioselectivities with broad functional group compatibility. Furthermore, this newly developed strategy was applied as key step in the first enantioselective formal total synthesis of (-)-chaetominine. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Copper(II)-catalyzed enantioselective hydrosilylation of halo-substituted alkyl aryl and heteroaryl ketones: asymmetric synthesis of (R)-fluoxetine and (S)-duloxetine.

PubMed

Zhou, Ji-Ning; Fang, Qiang; Hu, Yi-Hu; Yang, Li-Yao; Wu, Fei-Fei; Xie, Lin-Jie; Wu, Jing; Li, Shijun

2014-02-14

A set of reaction conditions has been established to facilitate the non-precious copper-catalyzed enantioselective hydrosilylation of a number of structurally diverse β-, γ- or ε-halo-substituted alkyl aryl ketones and α-, β- or γ-halo-substituted alkyl heteroaryl ketones under air to afford a broad spectrum of halo alcohols in high yields and good to excellent enantioselectivities (up to 99% ee). The developed procedure has been successfully applied to the asymmetric synthesis of antidepressant drugs (R)-fluoxetine and (S)-duloxetine, which highlighted its synthetic utility.

Catalytic allylic oxidation of internal alkenes to a multifunctional chiral building block

NASA Astrophysics Data System (ADS)

Bayeh, Liela; Le, Phong Q.; Tambar, Uttam K.

2017-07-01

The stereoselective oxidation of hydrocarbons is one of the most notable advances in synthetic chemistry over the past fifty years. Inspired by nature, enantioselective dihydroxylations, epoxidations and other oxidations of unsaturated hydrocarbons have been developed. More recently, the catalytic enantioselective allylic carbon-hydrogen oxidation of alkenes has streamlined the production of pharmaceuticals, natural products, fine chemicals and other functional materials. Allylic functionalization provides a direct path to chiral building blocks with a newly formed stereocentre from petrochemical feedstocks while preserving the olefin functionality as a handle for further chemical elaboration. Various metal-based catalysts have been discovered for the enantioselective allylic carbon-hydrogen oxidation of simple alkenes with cyclic or terminal double bonds. However, a general and selective allylic oxidation using the more common internal alkenes remains elusive. Here we report the enantioselective, regioselective and E/Z-selective allylic oxidation of unactivated internal alkenes via a catalytic hetero-ene reaction with a chalcogen-based oxidant. Our method enables non-symmetric internal alkenes to be selectively converted into allylic functionalized products with high stereoselectivity and regioselectivity. Stereospecific transformations of the resulting multifunctional chiral building blocks highlight the potential for rapidly converting internal alkenes into a broad range of enantioenriched structures that can be used in the synthesis of complex target molecules.

Simple Epoxide Formation for the Organic Laboratory Using Oxone

ERIC Educational Resources Information Center

Broshears, Williams C.; Esteb, John J.; Richter, Jeremy; Wilson, Anne M.

2004-01-01

Epoxide chemistry is widely used in organic synthesis and regularly discussed in organic chemistry textbooks. An experiment to generate dimethyldioxirane in situ from acetone using Oxone is explained.

Enantioselective conjugate additions of α-amino radicals via cooperative photoredox and Lewis acid catalysis.

PubMed

Ruiz Espelt, Laura; McPherson, Iain S; Wiensch, Eric M; Yoon, Tehshik P

2015-02-25

We report the highly enantioselective addition of photogenerated α-amino radicals to Michael acceptors. This method features a dual-catalyst protocol that combines transition metal photoredox catalysis with chiral Lewis acid catalysis. The combination of these two powerful modes of catalysis provides an effective, general strategy to generate and control the reactivity of photogenerated reactive intermediates.

Enantioselective Conjugate Additions of α-Amino Radicals via Cooperative Photoredox and Lewis Acid Catalysis

PubMed Central

Espelt, Laura Ruiz; McPherson, Iain S.; Wiensch, Eric M.; Yoon, Tehshik P.

2015-01-01

We report the highly enantioselective addition of photogenerated α-amino radicals to Michael acceptors. This method features a dual-catalyst protocol that combines transition metal photoredox catalysis with chiral Lewis acid catalysis. The combination of these two powerful modes of catalysis provides an effective, general strategy to generate and control the reactivity of photogenerated reactive intermediates. PMID:25668687

Enantioselective accumulation of chiral polychlorinated biphenyls in lotus plant (Nelumbonucifera spp.).

PubMed

Dai, Shouhui; Wong, Charles S; Qiu, Jing; Wang, Min; Chai, Tingting; Fan, Li; Yang, Shuming

2014-09-15

Enantioselective accumulation of chiral polychlorinated biphenyls (PCBs) 91, 95, 136, 149, 176 and 183 was investigated in lotus plants (Nelumbonucifera spp.) exposed to these chemicals via spiked sediment, to determine uptake and possible biotransformation for aquatic phytoremediation purposes. The concentrations of most PCBs were greatest in roots at 60 d (19.6 ± 1.51-70.6 ± 6.14 μg kg(-1)), but were greatest in stems and leaves at 120 d (25.3 ± 6.14-95.5 ± 19.4 μg kg(-1) and 17.4 ± 4.41-70.4 ± 10.4 μg kg(-1), respectively). Total amounts were greatest at 120 d and significantly higher in roots than those in stems and in leaves (1,457 ± 220-5,852 ± 735 ng, 237 ± 47.1-902 ± 184 ng and 202 ± 60.3-802 ± 90.2 ng, respectively), but represented less than 0.51% of the total mass of PCBs added to sediments, indicating that lotus plants were unlikely to remove appreciable amounts of PCBs from contaminated sediments. Racemic PCB residues in sediment indicate no enantioselective biodegradation by sedimentary microbial consortia over the entire experiment. Preferential accumulation of the (-)-enantiomers of PCBs 91, 95 and 136 were observed in roots, stems and leaves, but non-enantioselective accumulation was observed for PCBs 149, 176 and 183. These results indicate that aquatic plants can accumulate PCBs enantioselectively via root uptake, possibly by biotransformation within plant tissues as observed for terrestrial plants. This is also the first report to identify optical rotation of the atropisomers of PCBs 91 and 95. Copyright © 2014 Elsevier B.V. All rights reserved.

21 CFR 172.723 - Epoxidized soybean oil.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Epoxidized soybean oil. 172.723 Section 172.723 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN...

21 CFR 172.723 - Epoxidized soybean oil.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Epoxidized soybean oil. 172.723 Section 172.723 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN...

The permeability P-glycoprotein: a focus on enantioselectivity and brain distribution.

PubMed

Choong, Eva; Dobrinas, Maria; Carrupt, Pierre-Alain; Eap, Chin B

2010-08-01

The permeability glycoprotein (P-gp) is an important protein transporter involved in the disposition of many drugs with different chemical structures, but few studies have examined a possible stereoselectivity in its activity. P-gp can have a major impact on the distribution of drugs in selected organs, including the brain. Polymorphisms of the ABCB1 gene, which encodes for P-gp, can influence the kinetics of several drugs. A search including publications from 1990 up to 2009 was performed on P-gp stereoselectivity and on the impact of ABCB1 polymorphisms on enantiomer brain distribution. Despite stereoselectivity not being expected because of the large variability of chemical structures of P-gp substrates, structure-activity relationships suggest different P-gp-binding sites for enantiomers. Enantioselectivity in the activity of P-gp has been demonstrated by in vitro studies and in animal models (preferential transport of one enantiomer or different inhibitory potencies towards P-gp activity between enantiomers). There is also in vivo evidence of an enantioselective drug transport at the human blood-brain barrier. The significant enantioselective activity of P-gp might be clinically relevant and must be taken into account in future studies.

Chiral separation and enantioselective degradation of vinclozolin in soils.

PubMed

Liu, Hui; Liu, Donghui; Shen, Zhigang; Sun, Mingjing; Zhou, Zhiqiang; Wang, Peng

2014-03-01

Vinclozolin is a chiral fungicide with potential environmental problems. The chiral separation of the enantiomers and enantioselective degradation in soil were investigated in this work. The enantiomers were separated by high-performance liquid chromatography (HPLC) on Chiralpak IA, IB, and AZ-H chiral columns under normal phase and the influence of the mobile phase composition on the separation was also studied. Complete resolutions were obtained on all three chiral columns under optimized conditions with the same elution order of (+)/(-). The residual analysis of the enantiomers in soil was conducted using accelerate solvent extraction followed by HPLC determination. The recoveries of the enantiomers ranged from 85.7-105.7% with relative standard deviation (SD) of 0.12-3.83%, and the limit of detection (LOD) of the method was 0.013 µg/g. The results showed that the degradations of vinclozolin enantiomers in the soils followed first-order kinetics. Preferential degradation of the (-)-enantiomer was observed only in one soil with the largest |ES| value of 0.047, and no obvious enantioselective degradation was observed in other soils. It was found that the persistence of vinclozolin in soil was related to pH values based on the half-lives. The two enantiomers disappeared about 8 times faster in basic soils than that in neutral or acidic soils. © 2014 Wiley Periodicals, Inc.

Direct organocatalytic enantioselective functionalization of SiOx surfaces.

PubMed

Parkin, John David; Chisholm, Ross; Frost, Aileen B; Bailey, Richard G; Smith, Andrew David; Hähner, Georg

2018-06-05

Traditional methods to prepare chiral surfaces involve either the adsorption of a chiral molecule onto an achiral surface, or adsorption of a species that forms a chiral template creating lattices with long range order. To date only limited alternative strategies to prepare chiral surfaces have been studied. In this manuscript a "bottom up" approach is developed that allows the preparation of chiral surfaces by direct enantioselective organocatalysis on a functionalized Si-oxide supported self-assembled monolayer (SAM). The efficient catalytic generation of enantiomerically enriched organic surfaces is achieved using a commercially available homogeneous isothiourea catalyst (HyperBTM) that promotes an enantioselective Michael-lactonization process upon a Si-oxide supported self-assembled monolayer functionalized with a reactive trifluoroenone group. Chiral atomic force microscopy (chi-AFM) is used to probe the enantiomeric enrichment of the organic films by measurement of the force distributions arising from interaction of D- or L-cysteine modified AFM tips and the organic films. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective gamma- and delta-Borylation of Unsaturated Carbonyl Derivatives: Synthesis, Mechanistic Insights, and Applications

NASA Astrophysics Data System (ADS)

Hoang, Gia L.

Chiral boronic esters are valuable synthetic intermediates widely used in a variety of stereospecific transformations. Transition metal-catalyzed asymmetric hydroboration (CAHB) of alkenes is among the most popular methods for their preparation. Enantioselective hydroboration of activated alkenes (i.e., vinyl arene derivatives or conjugated carbonyl compounds) have been extensively studied by many research groups. We, on the other hand, are interested in enantioselective hydroboration of unactivated alkenes utilizing coordinating functional groups (e.g., carbonyl derivatives) to give functionalized, chiral boronic esters. While conjugate addition and C-H activation methodologies provide efficient alternatives to CAHB for enantioselective beta-borylation of carbonyl compounds, direct gamma- and delta-borylations were essentially unknown prior to our wok on CAHB. The gamma-borylated products were used for understanding stereochemical aspects of Suzuki-Miyaura cross-coupling reactions resulting in stereoretention and in contrast to similar beta-borylated carbonyl derivatives reported in literature. Some other selected transformations were carried out to construct a number of biologically relevant structural motifs, such as lignan precursors, 1,4-amino alcohols, gamma-amino acid derivatives, 5-substitued-gamma-lactone and lactam ring systems. In addition, collaborative experimental and computational studies of the enantioselective desymmetrization via CAHB gain a better understanding of the mechanistic pathways.

Mechanism of epoxide hydrolysis in microsolvated nucleotide bases adenine, guanine and cytosine: a DFT study.

PubMed

Vijayalakshmi, Kunduchi P; Mohan, Neetha; Ajitha, Manjaly J; Suresh, Cherumuttathu H

2011-07-21

Six water molecules have been used for microsolvation to outline a hydrogen bonded network around complexes of ethylene epoxide with nucleotide bases adenine (EAw), guanine (EGw) and cytosine (ECw). These models have been developed with the MPWB1K-PCM/6-311++G(3df,2p)//MPWB1K/6-31+G(d,p) level of DFT method and calculated S(N)2 type ring opening of the epoxide due to amino group of the nucleotide bases, viz. the N6 position of adenine, N2 position of guanine and N4 position of cytosine. Activation energy (E(act)) for the ring opening was found to be 28.06, 28.64, and 28.37 kcal mol(-1) respectively for EAw, EGw and ECw. If water molecules were not used, the reactions occurred at considerably high value of E(act), viz. 53.51 kcal mol(-1) for EA, 55.76 kcal mol(-1) for EG and 56.93 kcal mol(-1) for EC. The ring opening led to accumulation of negative charge on the developing alkoxide moiety and the water molecules around the charge localized regions showed strong hydrogen bond interactions to provide stability to the intermediate systems EAw-1, EGw-1 and ECw-1. This led to an easy migration of a proton from an activated water molecule to the alkoxide moiety to generate a hydroxide. Almost simultaneously, a proton transfer chain reaction occurred through the hydrogen bonded network of water molecules and resulted in the rupture of one of the N-H bonds of the quaternized amino group. The highest value of E(act) for the proton transfer step of the reaction was 2.17 kcal mol(-1) for EAw, 2.93 kcal mol(-1) for EGw and 0.02 kcal mol(-1) for ECw. Further, the overall reaction was exothermic by 17.99, 22.49 and 13.18 kcal mol(-1) for EAw, EGw and ECw, respectively, suggesting that the reaction is irreversible. Based on geometric features of the epoxide-nucleotide base complexes and the energetics, the highest reactivity is assigned for adenine followed by cytosine and guanine. Epoxide-mediated damage of DNA is reported in the literature and the present results suggest that

First-principles chemical kinetic modeling of methyl trans-3-hexenoate epoxidation by HO 2

DOE PAGES

Cagnina, S.; Nicolle, Andre; de Bruin, T.; ...

2017-02-16

The design of innovative combustion processes relies on a comprehensive understanding of biodiesel oxidation kinetics. The present study aims at unraveling the reaction mechanism involved in the epoxidation of a realistic biodiesel surrogate, methyl trans-3-hexenoate, by hydroperoxy radicals using a bottom-up theoretical kinetics methodology. The obtained rate constants are in good agreement with experimental data for alkene epoxidation by HO 2. The impact of temperature and pressure on epoxidation pathways involving H-bonded and non-H-bonded conformers was assessed. As a result, the obtained rate constant was finally implemented into a state-of-the-art detailed combustion mechanism, resulting in fairly good agreement with enginemore » experiments.« less

Direct enantioselective conjugate addition of carboxylic acids with chiral lithium amides as traceless auxiliaries.

PubMed

Lu, Ping; Jackson, Jeffrey J; Eickhoff, John A; Zakarian, Armen

2015-01-21

Michael addition is a premier synthetic method for carbon-carbon and carbon-heteroatom bond formation. Using chiral dilithium amides as traceless auxiliaries, we report the direct enantioselective Michael addition of carboxylic acids. A free carboxyl group in the product provides versatility for further functionalization, and the chiral reagent can be readily recovered by extraction with aqueous acid. The method has been applied in the enantioselective total synthesis of the purported structure of pulveraven B.

Tuning and Switching Enantioselectivity of Asymmetric Carboligation in an Enzyme through Mutational Analysis of a Single Hot Spot.

PubMed

Wechsler, Cindy; Meyer, Danilo; Loschonsky, Sabrina; Funk, Lisa-Marie; Neumann, Piotr; Ficner, Ralf; Brodhun, Florian; Müller, Michael; Tittmann, Kai

2015-12-01

Enantioselective bond making and breaking is a hallmark of enzyme action, yet switching the enantioselectivity of the reaction is a difficult undertaking, and typically requires extensive screening of mutant libraries and multiple mutations. Here, we demonstrate that mutational diversification of a single catalytic hot spot in the enzyme pyruvate decarboxylase gives access to both enantiomers of acyloins acetoin and phenylacetylcarbinol, important pharmaceutical precursors, in the case of acetoin even starting from the unselective wild-type protein. Protein crystallography was used to rationalize these findings and to propose a mechanistic model of how enantioselectivity is controlled. In a broader context, our studies highlight the efficiency of mechanism-inspired and structure-guided rational protein design for enhancing and switching enantioselectivity of enzymatic reactions, by systematically exploring the biocatalytic potential of a single hot spot. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Catalytic epoxidation activity of keplerate polyoxomolybdate nanoball toward aqueous suspension of olefins under mild aerobic conditions.

PubMed

Rezaeifard, Abdolreza; Haddad, Reza; Jafarpour, Maasoumeh; Hakimi, Mohammad

2013-07-10

Catalytic efficiency of a sphere-shaped nanosized polyoxomolybdate {Mo132} in the aerobic epoxidation of olefins in water at ambient temperature and pressure in the absence of reducing agent is exploited which resulted good-to-high yields and desired selectivity.

Enantioselective syntheses of carbanucleosides from the Pauson-Khand adduct of trimethylsilylacetylene and norbornadiene.

PubMed

Vázquez-Romero, Ana; Rodríguez, Julia; Lledó, Agustí; Verdaguer, Xavier; Riera, Antoni

2008-10-16

A new enantioselective approach to carbanucleosides from Pauson-Khand (PK) adduct 1 is disclosed. The chiral cyclopentenone 1 is readily accessible in enantiomerically pure form via PK reaction of trimethylsilylacetylene and norbornadiene using N-benzyl-N-diphenylphosphino-tert-butyl-sulfinamide as a chiral P,S ligand. (-)-Carbavir and (-)-Abacavir were enantioselectively synthesized starting from (-)-1. The key steps of the sequence are a photochemical conjugate addition of a hydroxymethyl radical, a retro-Diels-Alder reaction, and a palladium catalyzed allylic substitution to introduce the nucleobase.

Discovery and characterization of a highly efficient enantioselective mandelonitrile hydrolase from Burkholderia cenocepacia J2315 by phylogeny-based enzymatic substrate specificity prediction.

PubMed

Wang, Hualei; Sun, Huihui; Wei, Dongzhi

2013-02-18

A nitrilase-mediated pathway has significant advantages in the production of optically pure (R)-(-)-mandelic acid. However, unwanted byproduct, low enantioselectivity, and specific activity reduce its value in practical applications. An ideal nitrilase that can efficiently hydrolyze mandelonitrile to optically pure (R)-(-)-mandelic acid without the unwanted byproduct is needed. A novel nitrilase (BCJ2315) was discovered from Burkholderia cenocepacia J2315 through phylogeny-based enzymatic substrate specificity prediction (PESSP). This nitrilase is a mandelonitrile hydrolase that could efficiently hydrolyze mandelonitrile to (R)-(-)-mandelic acid, with a high enantiomeric excess of 98.4%. No byproduct was observed in this hydrolysis process. BCJ2315 showed the highest identity of 71% compared with other nitrilases in the amino acid sequence. BCJ2315 possessed the highest activity toward mandelonitrile and took mandelonitrile as the optimal substrate based on the analysis of substrate specificity. The kinetic parameters Vmax, Km, Kcat, and Kcat/Km toward mandelonitrile were 45.4 μmol/min/mg, 0.14 mM, 15.4 s(-1), and 1.1×10(5) M(-1)s(-1), respectively. The recombinant Escherichia coli M15/BCJ2315 had a strong substrate tolerance and could completely hydrolyze mandelonitrile (100 mM) with fewer amounts of wet cells (10 mg/ml) within 1 h. PESSP is an efficient method for discovering an ideal mandelonitrile hydrolase. BCJ2315 has high affinity and catalytic efficiency toward mandelonitrile. This nitrilase has great advantages in the production of optically pure (R)-(-)-mandelic acid because of its high activity and enantioselectivity, strong substrate tolerance, and having no unwanted byproduct. Thus, BCJ2315 has great potential in the practical production of optically pure (R)-(-)-mandelic acid in the industry.

Enantioselective complexation of chiral propylene oxide by an enantiopure water-soluble cryptophane.

PubMed

Bouchet, Aude; Brotin, Thierry; Linares, Mathieu; Ågren, Hans; Cavagnat, Dominique; Buffeteau, Thierry

2011-05-20

ECD and NMR experiments show that the complexation of propylene oxide (PrO) within the cavity of an enantiopure water-soluble cryptophane 1 in NaOH solution is enantioselective and that the (R)-PrO@PP-1 diastereomer is more stable than the (S)-PrO@PP-1 diastereomer with a free energy difference of 1.7 kJ/mol. This result has been confirmed by molecular dynamics (MD) and ab initio calculations. The enantioselectivity is preserved in LiOH and KOH solutions even though the binding constants decrease, whereas PrO is not complexed in CsOH solution.

Fast evaluation of enantioselective drug metabolism by electrophoretically mediated microanalysis: application to fluoxetine metabolism by CYP2D6.

PubMed

Asensi-Bernardi, Lucía; Martín-Biosca, Yolanda; Escuder-Gilabert, Laura; Sagrado, Salvador; Medina-Hernández, María José

2013-12-01

In this work, a capillary electrophoretic methodology for the enantioselective in vitro evaluation of drugs metabolism is applied to the evaluation of fluoxetine (FLX) metabolism by cytochrome 2D6 (CYP2D6). This methodology comprises the in-capillary enzymatic reaction and the chiral separation of FLX and its major metabolite, norfluoxetine enantiomers employing highly sulfated β-CD and the partial filling technique. The methodology employed in this work is a fast way to obtain a first approach of the enantioselective in vitro metabolism of racemic drugs, with the additional advantage of an extremely low consumption of enzymes, CDs and all the reagents involved in the process. Michaelis-Menten kinetic parameters (Km and Vmax ) for the metabolism of FLX enantiomers by CYP2D6 have been estimated by nonlinear fitting of experimental data to the Michaelis-Menten equation. Km values have been found to be 30 ± 3 μM for S-FLX and 39 ± 5 μM for R-FLX. Vmax estimations were 28.6 ± 1.2 and 34 ± 2 pmol·min(-1) ·(pmol CYP)(-1) for S- and R-FLX, respectively. Similar results were obtained using a single enantiomer (R-FLX), indicating that the use of the racemate is a good option for obtaining enantioselective estimations. The results obtained show a slight enantioselectivity in favor of R-FLX. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of metals on enantioselective toxicity and biotransformation of cis-bifenthrin in zebrafish.

PubMed

Yang, Ye; Ji, Dapeng; Huang, Xin; Zhang, Jianyun; Liu, Jing

2017-08-01

Co-occurrence of pyrethroids and metals in watersheds previously has been reported to pose great risk to aquatic species. Pyrethroids are a class of chiral insecticides that have been shown to have enantioselective toxicity and biotransformation. However, the influence of metals on enantioselectivity of pyrethroids has not yet been evaluated. In the present study, the effects of cadmium (Cd), copper (Cu), and lead (Pb) on the enantioselective toxicity and metabolism of cis-bifenthrin (cis-BF) were investigated in zebrafish at environmentally relevant concentrations. The addition of Cd, Cu, or Pb significantly increased the mortality of zebrafish in racemate and R-enantiomer of cis-BF-treated groups. In rac-cis-BF- or 1R-cis-BF-treated groups, the addition of Cd, Cu, or Pb caused a decrease in enantiomeric fraction (EF) and an increased ratio of R-enantiomer residues in zebrafish. In 1S-cis-BF-treated groups, coexposure to Cd led to a lower EF and decreased residue levels of S-enantiomer. In addition, coexposure to the 3 metals resulted in different biodegradation characteristics of each enantiomer accompanied with differential changes in the expression of cytochrome P450 (CYP)1, CYP2, and CYP3 genes, which might be responsible for the enantioselective biodegradation of cis-BF in zebrafish. These results suggest that the influence of coexistent metals should be considered in the ecological risk assessment of chiral pyrethroids in aquatic environments. Environ Toxicol Chem 2017;36:2139-2146. © 2017 SETAC. © 2017 SETAC.

Functionalized metal-organic framework nanocomposites for dispersive solid phase extraction and enantioselective capture of chiral drug intermediates.

PubMed

Ma, Xue; Zhou, Xiaohua; Yu, Ajuan; Zhao, Wuduo; Zhang, Wenfen; Zhang, Shusheng; Wei, Linlin; Cook, Debra J; Roy, Anirban

2018-02-16

The facile preparation, characterization and application of a novel magnetic graphene oxide- metal organic framework [Zn 2 (d-Cam) 2 (4, 4'-bpy)] n (MGO-ZnCB) as a sorbent for fast, simple and enantioselective capture of chiral drug intermediates are presented in this paper. The MGO-ZnCB nanocomposite, developed by encapsulating MGO nanoparticles into the homochiral metal organic framework of ZnCB, can integrate the advantages from each component endowing the hybrids with improved synergystic effects. The enantioselective performance of MGO-ZnCB was evaluated by dispersive magnetic nanoparticle solid phase extraction (d-MNSPE) of 1, 1'-bi-2-naphthol (BN) and 2, 2'-furoin (Furoin) racemic solutions. Due to the excellent dispersive capability, high stability, relatively larger saturation magnetization and distinct enrichment capacity of MGO-ZnCB, the d-MNSPE method provids good enantioselective separation of these compounds with enantiomeric excess (ee) values as high as 74.8% and 57.4%, respectively. The entire process with BN or Furoin can be completed within 3 min or less. After washing with methanol, the host MGO-ZnCB can be easily recycled and reused six times without any apparent loss of performance. Furthermore, the adsorbed BN and Furoin in nanodomains of the MGO-ZnCB composite were directly investigated for the first time by atomic force microscopy-infrared (AFM-IR) technique. Copyright © 2017 Elsevier B.V. All rights reserved.

Direct Enantioselective Conjugate Addition of Carboxylic Acids with Chiral Lithium Amides as Traceless Auxiliaries

PubMed Central

2016-01-01

Michael addition is a premier synthetic method for carbon–carbon and carbon–heteroatom bond formation. Using chiral dilithium amides as traceless auxiliaries, we report the direct enantioselective Michael addition of carboxylic acids. A free carboxyl group in the product provides versatility for further functionalization, and the chiral reagent can be readily recovered by extraction with aqueous acid. The method has been applied in the enantioselective total synthesis of the purported structure of pulveraven B. PMID:25562717

High enantioselective Novozym 435-catalyzed esterification of (R,S)-flurbiprofen monitored with a chiral stationary phase.

PubMed

Siódmiak, Tomasz; Mangelings, Debby; Vander Heyden, Yvan; Ziegler-Borowska, Marta; Marszałł, Michał Piotr

2015-03-01

Lipases form Candida rugosa and Candida antarctica were tested for their application in the enzymatic kinetic resolution of (R,S)-flurbiprofen by enantioselective esterification. Successful chromatographic separation with well-resolved peaks of (R)- and (S)-flurbiprofen and their esters was achieved in one run on chiral stationary phases by high-performance liquid chromatography (HPLC). In this study screening of enzymes was performed, and Novozym 435 was selected as an optimal catalyst for obtaining products with high enantiopurity. Additionally, the influence of organic solvents (dichloromethane, dichloroethane, dichloropropane, and methyl tert-butyl ether), primary alcohols (methanol, ethanol, n-propanol, and n-butanol), reaction time, and temperature on the enantiomeric ratio and conversion was tested. The high values of enantiomeric ratio (E in the range of 51.3-90.5) of the esterification of (R,S)-flurbiprofen were obtained for all tested alcohols using Novozym 435, which have a great significance in the field of biotechnological synthesis of drugs. The optimal temperature range for the performed reactions was from 37 to 45 °C. As a result of the optimization, (R)-flurbiprofen methyl ester was obtained with a high optical purity, eep = 96.3 %, after 96 h of incubation. The enantiomeric ratio of the reaction was E = 90.5 and conversion was C = 35.7 %.

Cholesterol-5,6-epoxides: chemistry, biochemistry, metabolic fate and cancer.

PubMed

Poirot, Marc; Silvente-Poirot, Sandrine

2013-03-01

In the nineteen sixties it was proposed that cholesterol might be involved in the etiology of cancers and cholesterol oxidation products were suspected of being causative agents. Researchers had focused their attention on cholesterol-5,6-epoxides (5,6-ECs) based on several lines of evidence: 1) 5,6-ECs contained an oxirane group that was supposed to confer alkylating properties such as those observed for aliphatic and aromatic epoxides. 2) cholesterol-5,6-epoxide hydrolase (ChEH) was induced in pre-neoplastic lesions of skin from rats exposed to ultraviolet irradiations and ChEH was proposed to be involved in detoxification processes like other epoxide hydrolases. However, 5,6-ECs failed to induce carcinogenicity in rodents which ruled out a potent carcinogenic potential for 5,6-ECs. Meanwhile, clinical studies revealed an anomalous increase in the concentrations of 5,6β-EC in the nipple fluids of patients with pre-neoplastic breast lesions and in the blood of patients with endometrious cancers, suggesting that 5,6-ECs metabolism could be linked with cancer. Paradoxically, ChEH has been recently shown to be totally inhibited by therapeutic concentrations of tamoxifen (Tam), which is one of the main drugs used in the hormonotherapy and the chemoprevention of breast cancers. These data would suggest that the accumulation of 5,6-ECs could represent a risk factor, but we found that 5,6-ECs were involved in the induction of breast cancer cell differentiation and death induced by Tam suggesting a positive role of 5,6-ECs. These observations meant that the biochemistry and the metabolism of 5,6-ECs needed to be extensively studied. We will review the current knowledge and the future direction of 5,6-ECs chemistry, biochemistry, metabolism, and relationship with cancer. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Enantioselective synthesis of substituted piperidines by addition of aryl Grignard reagents to pyridine N-oxides.

PubMed

Hussain, Munawar; Banchelin, Thomas Sainte-Luce; Andersson, Hans; Olsson, Roger; Almqvist, Fredrik

2013-01-04

The synthesis of optically active piperidines by enantioselective addition of aryl Grignard reagents to pyridine N-oxides and lithium binolate followed by reduction is reported for the first time. The reaction results in high yields (51-94%) in combination with good ee (54-80%). Some of these products were subsequently recrystallized, affording enhanced optical purities (>99% ee).

Arabidopsis thaliana EPOXIDE HYDROLASE1 (AtEH1) is a cytosolic epoxide hydrolase involved in the synthesis of poly-hydroxylated cutin monomers.

PubMed

Pineau, Emmanuelle; Xu, Lin; Renault, Hugues; Trolet, Adrien; Navrot, Nicolas; Ullmann, Pascaline; Légeret, Bertrand; Verdier, Gaëtan; Beisson, Fred; Pinot, Franck

2017-07-01

Epoxide hydrolases (EHs) are present in all living organisms. They have been extensively characterized in mammals; however, their biological functions in plants have not been demonstrated. Based on in silico analysis, we identified AtEH1 (At3g05600), a putative Arabidopsis thaliana epoxide hydrolase possibly involved in cutin monomer synthesis. We expressed AtEH1 in yeast and studied its localization in vivo. We also analyzed the composition of cutin from A. thaliana lines in which this gene was knocked out. Incubation of recombinant AtEH1 with epoxy fatty acids confirmed its capacity to hydrolyze epoxides of C18 fatty acids into vicinal diols. Transfection of Nicotiana benthamiana leaves with constructs expressing AtEH1 fused to enhanced green fluorescent protein (EGFP) indicated that AtEH1 is localized in the cytosol. Analysis of cutin monomers in loss-of-function Ateh1-1 and Ateh1-2 mutants showed an accumulation of 18-hydroxy-9,10-epoxyoctadecenoic acid and a concomitant decrease in corresponding vicinal diols in leaf and seed cutin. Compared with wild-type seeds, Ateh1 seeds showed delayed germination under osmotic stress conditions and increased seed coat permeability to tetrazolium red. This work reports a physiological role for a plant EH and identifies AtEH1 as a new member of the complex machinery involved in cutin synthesis. © 2017 CNRS New Phytologist © 2017 New Phytologist Trust.

Enantioselective Construction of 3-Hydroxypiperidine Scaffolds by Sequential Action of Light and Rhodium upon N-Allylglyoxylamides.

PubMed

Ishida, Naoki; Nečas, David; Masuda, Yusuke; Murakami, Masahiro

2015-06-15

3-Hydroxypiperidine scaffolds were enantioselectively constructed in an atom-economical way by sequential action of light and rhodium upon N-allylglyoxylamides. In a formal sense, the allylic C-H bond was selectively cleaved and enantioselectively added across the ketonic carbonyl group with migration of the double bond (carbonyl-ene-type reaction). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective Bronsted Acid Catalysis with Chiral Pentacarboxycyclopentadienes

NASA Astrophysics Data System (ADS)

Gheewala, Chirag

This thesis details the design and development of pentacarboxycyclopentadienes (PCCPs) as a new platform for enantioselective Bronsted acid catalysis. Prior to this research, enantioselective Bronsted acid catalysis was limited to the BINOL (and variations thereof) framework. While this catalyst platform has paved the way for a myriad of novel asymmetric chemical transformations, the utility of this catalyst scaffold has suffered from its lengthy and expensive preparations. As an alternative, starting from readily available 1,2,3,4,5-pentacarbomethoxycyclopentadiene and various chiral alcohols and amines, the synthesis of a library of strongly acidic chiral catalysts is described. The utility of these novel acid catalysts is explored in various transformations. As a prelude to the heart of this work, Chapter 1 focuses on the advancements made in asymmetric Bronsted acid catalysis through BINOL-phosphate derived catalysts, focusing on the major accomplishments made by researchers since 2004. The provided review highlights the utility of these chiral acid catalysts but also reveals the need for a new scaffold that is more affordable and accessible. Chapter 2 discusses the background of PCCPs, including its initial discovery and subsequent applications. Our work in developing novel transesterified and amidated derivatives is discussed with accompanying crystal structures of achiral and chiral PCCPs. pKa measurements demonstrate the capacity of PCCPs to be used as strong Bronsted acid catalysts and are compared to literature values of known Bronsted acid catalysts. Chapter 3 focuses on the utility of PCCPs as enantioselective Bronsted acid catalysts in a variety of chemical transformations including the Mukaiyama-Mannich reaction, transfer hydrogenation, Pictet-Spengler reaction, diaryl alcohol substitution, Mukayaiama oxocarbenium aldol reaction, and [4+2]-cycloaddition. Catalyst loadings down to 0.01 mol% and reaction scale up to 25 grams in the Mukaiyama

Lipase catalyzed epoxidation of fatty acid methyl esters derived from unsaturated vegetable oils in absence of carboxylic acid.

PubMed

Sustaita-Rodríguez, Alejandro; Ramos-Sánchez, Víctor H; Camacho-Dávila, Alejandro A; Zaragoza-Galán, Gerardo; Espinoza-Hicks, José C; Chávez-Flores, David

2018-04-11

Nowadays the industrial chemistry reactions rely on green technologies. Enzymes as lipases are increasing its use in diverse chemical processes. Epoxidized fatty acid methyl esters obtained from transesterification of vegetable oils have recently found applications as polymer plasticizer, agrochemical, cosmetics, pharmaceuticals and food additives. In this research article, grapeseed, avocado and olive oils naturally containing high percents of mono and poly unsaturations were used as starting materials for the production of unsaturated fatty acid methyl esters. The effect of lauric acid as an active oxygen carrier was studied on epoxidation reactions where unsaturated fatty acid methyl esters were converted to epoxy fatty acid methyl esters using immobilized Candida antarctica Lipase type B as catalyst and hydrogen peroxide as oxygen donor at mild temperature and pressure conditions. After this study it was confirmed by 1 H NMR, 13 C NMR and GC-MS that the addition of lauric acid to the enzymatic reaction is unnecessary to transform the alkenes in to epoxides. It was found that quantitative conversions were possible in despite of a carboxylic acid absence.

Production of epoxide hydrolases in batch fermentations of Botryosphaeria rhodina.

PubMed

Melzer, Guido; Junne, Stefan; Wohlgemuth, Roland; Hempel, Dietmar C; Götz, Peter

2008-06-01

The filamentous fungus Botryosphaeria rhodina (ATCC 9055) was investigated related to its ability for epoxide hydrolase (EH) production. Epoxide hydrolase activity is located at two different sites of the cells. The larger part is present in the cytosol (70%), while the smaller part is associated to membranes (30%). In media optimization experiments, an activity of 3.5 U/gDW for aromatic epoxide hydrolysis of para-nitro-styrene oxide (pNSO) could be obtained. Activity increased by 30% when pNSO was added to the culture during exponential growth. An increase of enzyme activity up to 6 U/gDW was achieved during batch-fermentations in a bioreactor with 2.7 l working volume. Evaluation of fermentations with 30 l working volume revealed a relation of oxygen uptake rate to EH expression. Oxygen limitation resulted in a decreased EH activity. Parameter estimation by the linearization method of Hanes yielded Km values of 2.54 and 1.00 mM for the substrates S-pNSO and R-pNSO, respectively. vmax was 3.4 times higher when using R-pNSO. A protein purification strategy leading to a 47-fold increase in specific activity (940 U/mgProtein) was developed as a first step to investigate molecular and structural characteristics of the EH.

Application of a Heterogeneous Chiral Titanium Catalyst Derived from Silica-Supported 3-Aryl H8-BINOL to Enantioselective Alkylation and Arylation of Aldehydes.

PubMed

Akai, Junichiro; Watanabe, Satoshi; Michikawa, Kumiko; Harada, Toshiro

2017-07-07

A 3-aryl H 8 -BINOL was grafted on the surface of silica gel using a hydrosilane derivative as a precursor, and the resulting silica-supported ligand (6 mol %) was employed in the enantioselective alkylation and arylation of aldehydes in the presence of Ti(O i Pr) 4 . The reactions using Et 2 Zn, Et 3 B, and aryl Grignard reagents all afforded the corresponding adducts in high enantioselectivities and yields. The silica-immobilized titanium catalyst could be reused up to 14 times without appreciable deterioration of the activity.

COMPARATIVE STUDIES OF THE EFFECT OF POLYCYCLIC AROMATIC HYDROCARBON GEOMETRY ON THE HYDROLYSIS OF DIOL EPOXIDES

EPA Science Inventory

Comparative studies of the effect of polycyclic aromatic hydrocarbon geometry on the hydrolysis of diol epoxides

The interaction of the diol epoxides (DEs) of both planar and non-planar PAHs with water have been examined using quantum mechanical and molecular dynamics. Th...

Asymmetric Epoxidation: A Twinned Laboratory and Molecular Modeling Experiment for Upper-Level Organic Chemistry Students

ERIC Educational Resources Information Center

Hii, King Kuok; Rzepa, Henry S.; Smith, Edward H.

2015-01-01

The coupling of a student experiment involving the preparation and use of a catalyst for the asymmetric epoxidation of an alkene with computational simulations of various properties of the resulting epoxide is set out in the form of a software toolbox from which students select appropriate components. At the core of these are the computational…

6-Azabicyclo[3.2.1]octanes Via Copper-Catalyzed Enantioselective Alkene Carboamination

PubMed Central

Casavant, Barbara J.; Hosseini, Azade S.

2014-01-01

Bridged bicyclic rings containing nitrogen heterocycles are important motifs in bioactive small organic molecules. An enantioselective copper-catalyzed alkene carboamination reaction that creates bridged heterocycles is reported herein. Two new rings are formed in this alkene carboamination reaction where N-sulfonyl-2-aryl-4-pentenamines are converted to 6-azabicyclo[3.2.1]octanes using [Ph-Box-Cu](OTf)2 or related catalysts in the presence of MnO2 as stoichiometric oxidant in moderate to good yields and generally excellent enantioselectivities. Two new stereocenters are formed in the reaction, and the C-C bond-forming arene addition is a net C-H functionalization. PMID:25484848

Dynamic kinetic asymmetric transformation (DYKAT) by combined amine- and transition-metal-catalyzed enantioselective cycloisomerization.

PubMed

Zhao, Gui-Ling; Ullah, Farman; Deiana, Luca; Lin, Shuangzheng; Zhang, Qiong; Sun, Junliang; Ibrahem, Ismail; Dziedzic, Pawel; Córdova, Armando

2010-02-01

The first examples of one-pot highly chemo- and enantioselective dynamic kinetic asymmetric transformations (DYKATs) involving alpha,beta-unsaturated aldehydes and propargylated carbon acids are presented. These DYKATs, which proceed by a combination of catalytic iminium activation, enamine activation, and Pd(0)-catalyzed enyne cycloisomerization, give access to functionalized cyclopentenes with up to 99 % ee and can be used for the generation of all-carbon quaternary stereocenters.

Monolithic Nickel (II) Oxide Aerogels Using an Organic Epoxide: The Importance of the Counter Ion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gash, A E; Satcher, J H; Simpson, R L

2004-01-13

The synthesis and characterization of nickel (II) oxide aerogel materials prepared using the epoxide addition method is described. The addition of the organic epoxide propylene oxide to an ethanolic solution of NiCl{sub 2} 6H{sub 2}O resulted in the formation of an opaque light green monolithic gel and subsequent drying with supercritical CO{sub 2} gave a monolithic aerogel material of the same color. This material has been characterized using powder X-ray diffraction, electron microscopy, elemental analysis, and nitrogen adsorption/desorption analysis. The results indicate that the nickel (II) oxide aerogel has very low bulk density (98 kg/m{sup 3} ({approx}98 %porous)), high surfacemore » area (413 m{sup 2}/g), and has a particulate-type aerogel microstructure made up of very fine spherical particles with an open porous network. By comparison, a precipitate of Ni{sub 3}(NO{sub 3}){sub 2}(OH){sub 4} is obtained when the same preparation is attempted with the common Ni(NO{sub 3}){sub 2} 6H{sub 2}O salt as the precursor. The implications of the difference of reactivity of the two different precursors are discussed in the context of the mechanism of gel formation via the epoxide addition method. The synthesis of nickel (II) oxide aerogel, using the epoxide addition method, is especially unique in our experience. It is our first example of the successful preparation of a metal oxide aerogel using a metal divalent metal ion and may have implications for the application of this method to the preparation of aerogels or nanoparticles of other divalent metal oxides. To our knowledge this is the first report of a monolithic pure nickel (II) oxide aerogel materials.« less

Chiral Brønsted Acid‐Catalyzed Enantioselective α‐Amidoalkylation Reactions: A Joint Experimental and Predictive Study

PubMed Central

Aranzamendi, Eider; Arrasate, Sonia; Sotomayor, Nuria

2016-01-01

Abstract Enamides with a free NH group have been evaluated as nucleophiles in chiral Brønsted acid‐catalyzed enantioselective α‐amidoalkylation reactions of bicyclic hydroxylactams for the generation of quaternary stereocenters. A quantitative structure–reactivity relationship (QSRR) method has been developed to find a useful tool to rationalize the enantioselectivity in this and related processes and to orient the catalyst choice. This correlative perturbation theory (PT)‐QSRR approach has been used to predict the effect of the structure of the substrate, nucleophile, and catalyst, as well as the experimental conditions, on the enantioselectivity. In this way, trends to improve the experimental results could be found without engaging in a long‐term empirical investigation. PMID:28032023

Capsanthone 3,6-epoxide, a new carotenoid from the fruits of the red paprika Capsicum annuum L.

PubMed

Maoka, T; Fujiwara, Y; Hashimoto, K; Akimoto, N

2001-08-01

The structure of a new carotenoid, isolated from the fruits of the red tomato-shaped paprika Capsicum annuum L., was elucidated to be (3S,5R,6S,5'R)-3,6-epoxy-5,6-dihydro-5-hydroxy-beta,kappa-carotene-3',6'-dione by spectroscopic analyses, including fast atom bombardment collision-induced dissociation-mass spectrometry/mass spectrometry (FAB CID-MS/MS) and was designated capsanthone 3,6-epoxide. Capsanthone 3,6-epoxide is assumed to be an oxidative metabolite of capsanthin 3,6-epoxide in paprika.

Chiral N,N'-Dioxide-Organocatalyzed Regio-, Diastereo- and Enantioselective Michael Addition-Alkylation Reaction.

PubMed

Feng, Juhua; Yuan, Xiao; Luo, Weiwei; Lin, Lili; Liu, Xiaohua; Feng, Xiaoming

2016-10-24

A highly regio-, diastereo- and enantioselective Michael addition-alkylation reaction between α-substituted cyano ketones and (Z)-bromonitrostyrenes has been realized by using a chiral N,N'-dioxide as organocatalyst. A variety of substrates performed well in this reaction, and the corresponding multifunctionalized chiral 2,3-dihydrofurans were obtained in up to 95 % yield with 95:5 dr and 93 % ee. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

EXPRESSION AND CHARACTERIZATION OF THE RECOMBINANT JUVENILE HORMONE EPOXIDE HYDROLASE (JHEH) FROM MANDUCA SEXTA. (R825433)

EPA Science Inventory

The cDNA of the microsomal Juvenile Hormone Epoxide Hydrolase (JHEH) from Manduca sexta was expressed in vitro in the baculovirus system. In insect cell culture, the recombinant enzyme (Ms-JHEH) was produced at a high level (100 fold over background EH catalytic activit...

Bioinspired enantioselective synthesis of crinine-type alkaloids via iridium-catalyzed asymmetric hydrogenation of enones† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc02112g Click here for additional data file.

PubMed Central

Zuo, Xiao-Dong; Guo, Shu-Min; Yang, Rui

2017-01-01

A bioinspired enantioselective synthesis of crinine-type alkaloids has been developed by iridium-catalyzed asymmetric hydrogenation of racemic cycloenones. The method features a biomimetic stereodivergent resolution of the substrates bearing a remote arylated quaternary stereocenter. Using this protocol, 24 crinine-type alkaloids and 8 analogues were synthesized in a concise and rapid way with high yield and high enantioselectivity. PMID:28989653

O-nitroso aldol synthesis: Catalytic enantioselective route to α-aminooxy carbonyl compounds via enamine intermediate

PubMed Central

Momiyama, Norie; Torii, Hiromi; Saito, Susumu; Yamamoto, Hisashi

2004-01-01

The approach using pyrrolidine enamine as substrate has been studied for this synthesis, and an important catalyst structural feature has been developed. After survey of pyrrolidine-based Brønsted acid catalyst, tetrazole catalyst (3f) was found to be optimal in synthesis of aminooxy carbonyl compounds in high yields, with complete enantioselectivity not only for aldehydes but also for ketones. PMID:15067138

Boosting Chemical Stability, Catalytic Activity, and Enantioselectivity of Metal-Organic Frameworks for Batch and Flow Reactions.

PubMed

Chen, Xu; Jiang, Hong; Hou, Bang; Gong, Wei; Liu, Yan; Cui, Yong

2017-09-27

A key challenge in heterogeneous catalysis is the design and synthesis of heterogeneous catalysts featuring high catalytic activity, selectivity, and recyclability. Here we demonstrate that high-performance heterogeneous asymmetric catalysts can be engineered from a metal-organic framework (MOF) platform by using a ligand design strategy. Three porous chiral MOFs with the framework formula [Mn 2 L(H 2 O) 2 ] are prepared from enantiopure phosphono-carboxylate ligands of 1,1'-biphenol that are functionalized with 3,5-bis(trifluoromethyl)-, bismethyl-, and bisfluoro-phenyl substituents at the 3,3'-position. For the first time, we show that not only chemical stability but also catalytic activity and stereoselectivity of the MOFs can be tuned by modifying the ligand structures. Particularly, the MOF incorporated with -CF 3 groups on the pore walls exhibits enhanced tolerance to water, weak acid, and base compared with the MOFs with -F and -Me groups. Under both batch and flow reaction systems, the CF 3 -containing MOF demonstrated excellent reactivity, selectivity, and recyclability, affording high yields and enantioselectivities for alkylations of indoles and pyrrole with a range of ketoesters or nitroalkenes. In contrast, the corresponding homogeneous catalysts gave low enantioselectivity in catalyzing the tested reactions.

Enantioselective analysis of citalopram and escitalopram in postmortem blood together with genotyping for CYP2D6 and CYP2C19.

PubMed

Carlsson, Björn; Holmgren, Anita; Ahlner, Johan; Bengtsson, Finn

2009-03-01

Citalopram is marketed as a racemate (50:50) mixture of the S(+)-enantiomer and R(-)-enantiomer and the active S(+)-enantiomer (escitalopram) that possess inhibitory effects. Citalopram was introduced in Sweden in 1992 and is the most frequently used antidepressant to date in Sweden. In 2002, escitalopram was introduced onto the Swedish market for treatment of depression and anxiety disorders. The main objective of this study was to investigate S(+)-citalopram [i.e., the racemic drug (citalopram) or the enantiomer (escitalopram)] present in forensic autopsy cases positive for the presence of citalopram in routine screening using a non-enantioselective bioanalytical method. Fifty out of the 270 samples found positive by gas chromatography-nitrogen-phosphorus detection were further analyzed using enantioselective high-performance liquid chromatography. The 50 cases were genotyped for CYP2D6 and CYP2C19, as these isoenzymes are implicated in the metabolism of citalopram and escitalopram. In samples positive for racemic citalopram using the screening method for forensic autopsy cases, up to 20% would have been misinterpreted in the absence of an enantioselective method. An enantioselective method is thus necessary for correct interpretation of autopsy cases, after the enantiomer has been introduced onto the market. The percentage of poor metabolizers was 6% for CYP2D6 and 8% for CYP2C19.

Thermostable Alcohol Dehydrogenase from Thermococcus kodakarensis KOD1 for Enantioselective Bioconversion of Aromatic Secondary Alcohols

PubMed Central

Wu, Xi; Zhang, Chong; Orita, Izumi; Imanaka, Tadayuki

2013-01-01

A novel thermostable alcohol dehydrogenase (ADH) showing activity toward aromatic secondary alcohols was identified from the hyperthermophilic archaeon Thermococcus kodakarensis KOD1 (TkADH). The gene, tk0845, which encodes an aldo-keto reductase, was heterologously expressed in Escherichia coli. The enzyme was found to be a monomer with a molecular mass of 31 kDa. It was highly thermostable with an optimal temperature of 90°C and a half-life of 4.5 h at 95°C. The apparent Km values for the cofactors NAD(P)+ and NADPH were similar within a range of 66 to 127 μM. TkADH preferred secondary alcohols and accepted various ketones and aldehydes as substrates. Interestingly, the enzyme could oxidize 1-phenylethanol and its derivatives having substituents at the meta and para positions with high enantioselectivity, yielding the corresponding (R)-alcohols with optical purities of greater than 99.8% enantiomeric excess (ee). TkADH could also reduce 2,2,2-trifluoroacetophenone to (R)-2,2,2-trifluoro-1-phenylethanol with high enantioselectivity (>99.6% ee). Furthermore, the enzyme showed high resistance to organic solvents and was particularly highly active in the presence of H2O–20% 2-propanol and H2O–50% n-hexane or n-octane. This ADH is expected to be a useful tool for the production of aromatic chiral alcohols. PMID:23354700

ULTRASOUND-ASSISTED ORGANIC SYNTHESIS: ALCOHOL OXIDATION AND OLEFIN EPOXIDATION

EPA Science Inventory

Ultrasound-assisted Organic Synthesis: Alcohol Oxidation and Olefin Epoxidation

Unnikrishnan R Pillai, Endalkachew Sahle-Demessie , Vasudevan Namboodiri, Quiming Zhao, Juluis Enriquez
U.S. EPA , 26 W. Martin Luther King Dr. , Cincinnati, OH 45268
Phone: 513-569-773...

Enantioselective synthesis of (S)-naproxen using immobilized lipase on chitosan beads.

PubMed

Gilani, Saeedeh L; Najafpour, Ghasem D; Heydarzadeh, Hamid D; Moghadamnia, Aliakbar

2017-06-01

S-naproxen by enantioselective hydrolysis of racemic naproxen methyl ester was produced using immobilized lipase. The lipase enzyme was immobilized on chitosan beads, activated chitosan beads by glutaraldehyde, and Amberlite XAD7. In order to find an appropriate support for the hydrolysis reaction of racemic naproxen methyl ester, the conversion and enantioselectivity for all carriers were compared. In addition, effects of the volumetric ratio of two phases in different organic solvents, addition of cosolvent and surfactant, optimum pH and temperature, reusability, and inhibitory effect of methanol were investigated. The optimum volumetric ratio of two phases was defined as 3:2 of aqueous phase to organic phase. Various water miscible and water immiscible solvents were examined. Finally, isooctane was chosen as an organic solvent, while 2-ethoxyethanol was added as a cosolvent in the organic phase of the reaction mixture. The optimum reaction conditions were determined to be 35 °C, pH 7, and 24 h. Addition of Tween-80 in the organic phase increased the accessibility of immobilized enzyme to the reactant. The optimum organic phase compositions using a volumetric ratio of 2-ethoxyethanol, isooctane and Tween-80 were 3:7 and 0.1% (v/v/v), respectively. The best conversion and enantioselectivity of immobilized enzyme using chitosan beads activated by glutaraldehyde were 0.45 and 185, respectively. © 2017 Wiley Periodicals, Inc.

Epoxidation of cottonseed oil by aqueous hydrogen peroxide catalysed by liquid inorganic acids.

PubMed

Dinda, Srikanta; Patwardhan, Anand V; Goud, Vaibhav V; Pradhan, Narayan C

2008-06-01

The kinetics of epoxidation of cottonseed oil by peroxyacetic acid generated in situ from hydrogen peroxide and glacial acetic acid in the presence of liquid inorganic acid catalysts were studied. It was possible to obtain up to 78% relative conversion to oxirane with very less oxirane cleavage by in situ technique. The rate constants for sulphuric acid catalysed epoxidation of cottonseed oil were in the range 0.39-5.4 x 10(-6)L mol(-1)s(-1) and the activation energy was found to be 11.7 kcal mol(-1). Some thermodynamic parameters such as enthalpy, entropy, and free energy of activation were determined to be of 11.0 kcal mol(-1), -51.4 cal mol(-1)K(-1) and 28.1 kcal mol(-1), respectively. The order of effectiveness of catalysts was found to be sulphuric acid>phosphoric acid>nitric acid>hydrochloric acid. Acetic acid was found to be superior to formic acid for the in situ cottonseed oil epoxidation.

Enantioselective Dissipation of Acephate and Its Metabolite, Methamidophos, during Tea Cultivation, Manufacturing, and Infusion.

PubMed

Pan, Rong; Chen, Hongping; Wang, Chen; Wang, Qinghua; Jiang, Ying; Liu, Xin

2015-02-04

The enantioselective dissipation of acephate and its metabolite, methamidophos, was investigated during tea cultivation, manufacturing, and infusion, using QuEChERS sample preparation technique and gas chromatography coupled with a BGB-176 chiral column. Results showed that (+)-acephate and (-)-acephate dissipated following first-order kinetics in fresh tea leaves with half-lives of 1.8 and 1.9 days, respectively. Acephate was degraded into a more toxic metabolite, methamidophos. Preferential dissipation and translocation of (+)-acephate may exist in tea shoots, and (-)-methamidophos was degraded more rapidly than (+)-methamidophos. During tea manufacturing, drying and spreading (or withering) played important roles in the dissipation of acephate enantiomers. The enantiometic fractions of acephate changed from 0.495-0.496 to 0.479-0.486 (P ≤ 0.0081), whereas those of methamidophos changed from 0.576-0.630 to 0.568-0.645 (P ≤ 0.0366 except for green tea manufacturing on day 1), from fresh tea leaves to made tea. In addition, high transfer rates (>80%) and significant enantioselectivity (P ≤ 0.0042) of both acephate and its metabolite occurred during tea brewing.

Catalytic Efficiency of Titanium Dioxide (TiO2) and Zeolite ZSM-5 Catalysts in the in-situ Epoxidation of Palm Olein

NASA Astrophysics Data System (ADS)

Yunus, M. Z. Mohd; Jamaludin, S. K.; Abd. Karim, S. F.; Gani, A. Abd; Sauki, A.

2018-05-01

Titanium dioxide and zeolite ZSM-5 are the commonly used heterogeneous catalysts in many chemical reactions. They have several advantages such as low cost and environmental friendly. In this study, titanium dioxide and zeolite ZSM-5 act as catalyst in the in-situ epoxidation of palm olein. Epoxidation of palm olein was carried out by using in-situ generated performic acid to produce epoxidized palm olein in a semi-batch reactor at different temperatures (45°C and 60°C) and agitation speed of 400 rpm. The effects of both catalysts are studied to compare their efficiency in catalyzing the in-situ epoxidation. Epoxidized palm olein was analyzed by using percent of relative conversion to oxirane (RCO%) and fourier transform infrared spectroscopy (FTIR). Surface area of the catalysts used were then characterized by using BET. The results indicated that titanium dioxide is a better catalyst in the in-situ epoxidation of palm olein since it provides higher RCO% compared to Zeolite ZSM-5 at 45°C.

Enantioselective synthesis of chiral oxazolines from unactivated ketones and isocyanoacetate esters by synergistic silver/organocatalysis.

PubMed

Martínez-Pardo, Pablo; Blay, Gonzalo; Muñoz, M Carmen; Pedro, José R; Sanz-Marco, Amparo; Vila, Carlos

2018-03-15

A multicatalytic approach that combines a bifunctional Brønsted base-squaramide organocatalyst and Ag + as Lewis acid has been applied in the reaction of unactivated ketones with tert-butyl isocyanoacetate to give chiral oxazolines bearing a quaternary stereocenter. The formal [3+2] cycloaddition provided high yields of the corresponding cis-oxazolines with good diastereoselectivity and excellent enantioselectivity, being applied to aryl-alkyl and alkyl-alkyl ketones.

Enantioselective Fluorescent Recognition of Chiral Acids by Cyclohexane-1,2-diamine-Based Bisbinaphthyl Molecules

PubMed Central

Li, Zi-Bo; Lin, Jing; Sabat, Michal; Hyacinth, Marilise; Pu, Lin

2008-01-01

The cyclohexane-1,2-diamine-based bisbinaphthyl macrocycles (S)-/(R)-5 and their cyclic and acyclic analogs are synthesized. The interactions of these compounds with various chiral acids are studied. Compounds (S)-/(R)-5 exhibit highly enantioselective fluorescent responses and high fluorescent sensitivity toward α-hydroxycarboxylic acids and N-protected amino acids. Among these interactions, (S)-mandelic acid (10−3 M) led to over 20 fold fluorescence enhancement of (S)-5 (1.0 × 10−5 M in benzene/0.05% DME) at the monomer emission and (S)-hexahydromandelic acid (10−3 M) led to over 80 fold fluorescence enhancement. These results demonstrate that (S)-5 is useful as an enantioselective fluorescent sensor for the recognition of the chiral acids. On the basis of the study of the structures of (S)-5 and the previously reported 1,2-diphenylethylenediamine-based bisbinaphthyl macrocycle (S)-4, the large fluorescence enhancement of (S)-5 with achirality-matched α-hydroxycarboxylic acid is attributed to the formation of a structurally rigidified host-guest complex and the further interaction of this complex with the acid to suppress the photo-induced electron transfer fluorescent quenching caused by the nitrogens in (S)-5. PMID:17530897

Heterogeneous epoxide carbonylation by cooperative ion-pair catalysis in Co(CO) 4 –-incorporated Cr-MIL-101

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Hoyoung D.; Dinca, Mircea; Roman-Leshkov, Yuriy

Here, despite the commercial desirability of epoxide carbonylation to β-lactones, the reliance of this process on homogeneous catalysts makes its industrial application challenging. Here we report the preparation and use of a Co(CO) 4 –-incorporated Cr-MIL-101 (Co(CO) 4cCr-MIL-101, Cr-MIL-101 = Cr 3O(BDC) 3F, H2BDC = 1,4-benzenedicarboxylic acid) heterogeneous catalyst for the ring-expansion carbonylation of epoxides, whose activity, selectivity, and substrate scope are on par with those of the reported homogeneous catalysts. We ascribe the observed performance to the unique cooperativity between the postsynthetically introduced Co(CO) 4 – and the site-isolated Lewis acidic Cr(III) centers in the metal–organic framework (MOF). Themore » heterogeneous nature of Co(CO) 4cCr-MIL-101 allows the first demonstration of gas-phase continuous-flow production of β-lactones from epoxides, attesting to the potential applicability of the heterogeneous epoxide carbonylation strategy.« less

Heterogeneous epoxide carbonylation by cooperative ion-pair catalysis in Co(CO) 4 –-incorporated Cr-MIL-101

DOE PAGES

Park, Hoyoung D.; Dinca, Mircea; Roman-Leshkov, Yuriy

2017-03-21

Here, despite the commercial desirability of epoxide carbonylation to β-lactones, the reliance of this process on homogeneous catalysts makes its industrial application challenging. Here we report the preparation and use of a Co(CO) 4 –-incorporated Cr-MIL-101 (Co(CO) 4cCr-MIL-101, Cr-MIL-101 = Cr 3O(BDC) 3F, H2BDC = 1,4-benzenedicarboxylic acid) heterogeneous catalyst for the ring-expansion carbonylation of epoxides, whose activity, selectivity, and substrate scope are on par with those of the reported homogeneous catalysts. We ascribe the observed performance to the unique cooperativity between the postsynthetically introduced Co(CO) 4 – and the site-isolated Lewis acidic Cr(III) centers in the metal–organic framework (MOF). Themore » heterogeneous nature of Co(CO) 4cCr-MIL-101 allows the first demonstration of gas-phase continuous-flow production of β-lactones from epoxides, attesting to the potential applicability of the heterogeneous epoxide carbonylation strategy.« less

A Bimetallic Aluminium(Salphen) Complex for the Synthesis of Cyclic Carbonates from Epoxides and Carbon Dioxide.

PubMed

Wu, Xiao; North, Michael

2017-01-10

A bimetallic aluminium(salphen) complex is reported as a sustainable, efficient and inexpensive catalyst for the synthesis of cyclic carbonates from epoxides and carbon dioxide. In the presence of this complex and tetrabutylammonium bromide, terminal and internal epoxides reacted at 50 °C and 10 bar carbon dioxide pressure to afford their corresponding cyclic carbonates in yields of 50-94 % and 30-71 % for terminal and internal cyclic carbonates, respectively. Mechanistic studies using deuterated epoxides and an analogous monometallic aluminium(salphen) chloride complex support a mechanism for catalysis by the bimetallic complex, which involves intramolecular cooperative catalysis between the two aluminium centres. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Kinetic Resolution of α-Hydroxy-Substituted Oxime Ethers by Enantioselective Cu-H-Catalyzed Si-O Coupling.

PubMed

Dong, Xichang; Kita, Yuji; Oestreich, Martin

2018-04-12

A catalyst-controlled enantioselective alcohol silylation by Cu-H-catalyzed dehydrogenative Si-O coupling of hydroxy groups α to an oxime ether and simple hydrosilanes is reported. The selectivity factors reached in this kinetic resolution are generally high (s≈50), and these reactions thereby provide reliable access to highly enantioenriched α-hydroxy-substituted oxime ethers. The synthetic usefulness of these compounds is also demonstrated. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective Synthesis of SNAP-7941

PubMed Central

Goss, Jennifer M.; Schaus, Scott E.

2009-01-01

An enantioselective synthesis of SNAP-7941, a potent melanin concentrating hormone receptor antagonist, was achieved using two organocatalytic methods. The first method utilized to synthesize the enantioenriched dihydropyrimidone core was the Cinchona alkaloid-catalyzed Mannich reaction of β-keto esters to acyl imines and the second was chiral phosphoric acid-catalyzed Biginelli reaction. Completion of the synthesis was accomplished via selective urea formation at the N3 position of the dihydropyrimidone with the 3-(4-phenylpiperidin-1-yl)propyl amine side chain fragment. The synthesis of SNAP-7921 highlights the utility of asymmetric organocatalytic methods in the construction of an important class of chiral heterocycles. PMID:18767801

Anti-inflammatory Effects of Omega-3 Polyunsaturated Fatty Acids and Soluble Epoxide Hydrolase Inhibitors in Angiotensin-II Dependent Hypertension

PubMed Central

Ulu, Arzu; Harris, Todd R; Morisseau, Christophe; Miyabe, Christina; Inoue, Hiromi; Schuster, Gertrud; Dong, Hua; Iosif, Ana-Maria; Liu, Jun-Yan; Weiss, Robert H; Chiamvimonvat, Nipavan; Imig, John D; Hammock, Bruce D

2013-01-01

The mechanisms underlying the anti-inflammatory and anti-hypertensive effects of long chain ω-3 polyunsaturated fatty acids (PUFAs) are still unclear. The epoxides of an ω-6 fatty acid, arachidonic acid (epoxyeicosatrienoic acids; EETs) also exhibit anti-hypertensive and anti-inflammatory effects. Thus, we hypothesized that the major ω-3 PUFAs including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may lower blood pressure and attenuate renal markers of inflammation through their epoxide metabolites. Here, we supplemented mice with an ω-3 rich diet for three weeks in a murine model of angiotensin-II dependent hypertension. Also, since EPA and DHA epoxides are metabolized by soluble epoxide hydrolase (sEH), we tested the combination of a sEH inhibitor and the ω-3 rich diet. Our results show that ω-3 rich diet in combination with the sEH inhibitor lowered Ang-II increased blood pressure, further increased renal levels of EPA and DHA epoxides, reduced renal markers of inflammation (i.e. prostaglandins and MCP-1), down-regulated an epithelial sodium channel and up-regulated Angiotensin converting enzyme-2 message (ACE-2) and significantly modulated cyclooxygenase and lipoxygenase metabolic pathways. Overall, our findings suggest that epoxides of the ω-3 PUFAs contribute to lowering SBP and attenuating inflammation in part by reduced prostaglandins and MCP-1 and by up-regulation of ACE-2 in angiotensin-II dependent hypertension. PMID:23676336

40 CFR 63.1427 - Process vent requirements for processes using extended cookout as an epoxide emission reduction...

Code of Federal Regulations, 2012 CFR

2012-07-01

... reactor liquid at the beginning of the time period, weight percent. k = Reaction rate constant, 1/hr. t = Time, hours. Note: This equation assumes a first order reaction with respect to epoxide concentration... measuring the concentration of the unreacted epoxide, or by using process knowledge, reaction kinetics, and...

Species differences in the hydrolysis of 2-cyanoethylene oxide, the epoxide metabolite of acrylonitrile.

PubMed

Kedderis, G L; Batra, R

1993-04-01

The carcinogenic effects of acrylonitrile in rats are believed to be mediated by its DNA-reactive epoxide metabolite, 2-cyanoethylene oxide (CEO). Previous studies have shown that conjugation with glutathione is the major detoxication pathway for both acrylonitrile and CEO. This study investigated the role of epoxide hydrolase in the hydrolysis of CEO by HPLC analysis of the products from [2,3-14C]CEO. CEO is a relatively stable epoxide with a half-life of 99 min at 37 degrees C in sodium phosphate buffer (0.1 M), pH 7.3. Incubation with hepatic microsomes or cytosols from male F-344 rats or B6C3F1 mice did not enhance the rate of hydrolysis of CEO (0.69 nmol/min). Human hepatic microsomes significantly increased the rate of hydrolysis of CEO, whereas human hepatic cytosols did not. Human hepatic microsomal hydrolysis activity was heat-sensitive and potently inhibited by 1,1,1-trichloropropene oxide (IC50 of 23 microM), indicating that epoxide hydrolase was the catalyst. The hydrolysis of CEO catalyzed by hepatic microsomes from six individuals exhibited normal saturation kinetics with KM ranging from 0.6 to 3.2 mM and Vmax from 8.3 to 18.8 nmol hydrolysis products/min/mg protein. Pretreatment of rodents with phenobarbital or acetone induced hepatic microsomal hydrolysis activity toward CEO, whereas treatment with beta-naphthoflavone, dexamethasone or acrylonitrile itself was without effect. These data show that humans possess an additional detoxication pathway for CEO that is not active in rodents (but is inducible). The presence of an active epoxide hydrolase hydrolysis activity toward CEO in humans should be considered in assessments of cancer risk from acrylonitrile exposure.

Modeling of Toxicity-Relevant Electrophilic Reactivity for Guanine with Epoxides: Estimating the Hard and Soft Acids and Bases (HSAB) Parameter as a Predictor.

PubMed

Zhang, Jing; Wang, Chenchen; Ji, Li; Liu, Weiping

2016-05-16

According to the electrophilic theory in toxicology, many chemical carcinogens in the environment and/or their active metabolites are electrophiles that exert their effects by forming covalent bonds with nucleophilic DNA centers. The theory of hard and soft acids and bases (HSAB), which states that a toxic electrophile reacts preferentially with a biological macromolecule that has a similar hardness or softness, clarifies the underlying chemistry involved in this critical event. Epoxides are hard electrophiles that are produced endogenously by the enzymatic oxidation of parent chemicals (e.g., alkenes and PAHs). Epoxide ring opening proceeds through a SN2-type mechanism with hard nucleophile DNA sites as the major facilitators of toxic effects. Thus, the quantitative prediction of chemical reactivity would enable a predictive assessment of the molecular potential to exert electrophile-mediated toxicity. In this study, we calculated the activation energies for reactions between epoxides and the guanine N7 site for a diverse set of epoxides, including aliphatic epoxides, substituted styrene oxides, and PAH epoxides, using a state-of-the-art density functional theory (DFT) method. It is worth noting that these activation energies for diverse epoxides can be further predicted by quantum chemically calculated nucleophilic indices from HSAB theory, which is a less computationally demanding method than the exacting procedure for locating the transition state. More importantly, the good qualitative/quantitative correlations between the chemical reactivity of epoxides and their bioactivity suggest that the developed model based on HSAB theory may aid in the predictive hazard evaluation of epoxides, enabling the early identification of mutagenicity/carcinogenicity-relevant SN2 reactivity.

Interaction of water, alkyl hydroperoxide, and allylic alcohol with a single-site homogeneous Ti-Si epoxidation catalyst: A spectroscopic and computational study.

PubMed

Urakawa, Atsushi; Bürgi, Thomas; Skrabal, Peter; Bangerter, Felix; Baiker, Alfons

2005-02-17

Tetrakis(trimethylsiloxy)titanium (TTMST, Ti(OSiMe3)4) possesses an isolated Ti center and is a highly active homogeneous catalyst in epoxidation of various olefins. The structure of TTMST resembles that of the active sites in some heterogeneous Ti-Si epoxidation catalysts, especially silylated titania-silica mixed oxides. Water cleaves the Ti-O-Si bond and deactivates the catalyst. An alkyl hydroperoxide, TBHP (tert-butyl hydroperoxide), does not cleave the Ti-O-Si bond, but interacts via weak hydrogen-bonding as supported by NMR, DOSY, IR, and computational studies. ATR-IR spectroscopy combined with computational investigations shows that more than one, that is, up to four, TBHP can undergo hydrogen-bonding with TTMST, leading to the activation of the O-O bond of TBHP. The greater the number of TBHP molecules that form hydrogen bonds to TTMST, the more electrophilic the O-O bond becomes, and the more active the complex is for epoxidation. An allylic alcohol, 2-cyclohexen-1-ol, does not interact strongly with TTMST, but the interaction is prominent when it interacts with the TTMST-TBHP complex. On the basis of the experimental and theoretical findings, a hydrogen-bond-assisted epoxidation mechanism of TTMST is suggested.

Enantioselective Synthesis of Chiral Cyclopent-2-enones by Nickel-Catalyzed Desymmetrization of Malonate Esters.

PubMed

Karad, Somnath Narayan; Panchal, Heena; Clarke, Christopher; Lewis, William; Lam, Hon Wai

2018-05-16

The enantioselective synthesis of highly functionalized chiral cyclopent-2-enones by the reaction of alkynyl malonate esters with arylboronic acids is described. These desymmetrizing arylative cyclizations are catalyzed by a chiral phosphinooxazoline-nickel complex, and cyclization is enabled by the reversible E/Z isomerization of alkenylnickel species. The general methodology is also applicable to the synthesis of 1,6-dihydropyridin-3(2H)-ones. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective synthesis of pactamycin, a complex antitumor antibiotic.

PubMed

Malinowski, Justin T; Sharpe, Robert J; Johnson, Jeffrey S

2013-04-12

Medicinal application of many complex natural products is precluded by the impracticality of their chemical synthesis. Pactamycin, the most structurally intricate aminocyclopentitol antibiotic, displays potent antiproliferative properties across multiple phylogenetic domains, but it is highly cytotoxic. A limited number of analogs produced by genetic engineering technologies show reduced cytotoxicity against mammalian cells, renewing promise for therapeutic applications. For decades, an efficient synthesis of pactamycin amenable to analog derivatizations has eluded researchers. Here, we present a short asymmetric total synthesis of pactamycin. An enantioselective Mannich reaction and symmetry-breaking reduction sequence was designed to enable assembly of the entire carbon core skeleton in under five steps and control critical three-dimensional (stereochemical) functional group relationships. This modular route totals 15 steps and is immediately amenable for structural analog synthesis.

A Tunable and Enantioselective Hetero-Diels-Alder Reaction Provides Access to Distinct Piperidinoyl Spirooxindoles.

PubMed

Jayakumar, Samydurai; Louven, Kathrin; Strohmann, Carsten; Kumar, Kamal

2017-12-11

The active complexes of chiral N,N'-dioxide ligands with dysprosium and magnesium salts catalyze the hetero-Diels-Alder reaction between 2-aza-3-silyloxy-butadienes and alkylidene oxindoles to selectively form 3,3'- and 3,4'-piperidinoyl spirooxindoles, respectively, in very high yields and with excellent enantioselectivities. The exo-selective asymmetric cycloaddition successfully regaled the construction of sp 3 -rich and highly substituted natural-product-based spirooxindoles supporting many chiral centers, including contiguous all-carbon quaternary centers. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dynamic control of chirality in phosphine ligands for enantioselective catalysis

PubMed Central

Zhao, Depeng; Neubauer, Thomas M.; Feringa, Ben L.

2015-01-01

Chirality plays a fundamental role in biology and chemistry and the precise control of chirality in a catalytic conversion is a key to modern synthesis most prominently seen in the production of pharmaceuticals. In enantioselective metal-based catalysis, access to each product enantiomer is commonly achieved through ligand design with chiral bisphosphines being widely applied as privileged ligands. Switchable phosphine ligands, in which chirality is modulated through an external trigger signal, might offer attractive possibilities to change enantioselectivity in a catalytic process in a non-invasive manner avoiding renewed ligand synthesis. Here we demonstrate that a photoswitchable chiral bisphosphine based on a unidirectional light-driven molecular motor, can be used to invert the stereoselectivity of a palladium-catalysed asymmetric transformation. It is shown that light-induced changes in geometry and helicity of the switchable ligand enable excellent selectivity towards the racemic or individual enantiomers of the product in a Pd-catalysed desymmetrization reaction. PMID:25806856

A Green Enantioselective Aldol Condensation for the Undergraduate Organic Laboratory

ERIC Educational Resources Information Center

Bennett, George D.

2006-01-01

A number of laboratory exercises for the organic chemistry curriculum that emphasize enantioselective synthesis of the aldol condensation which involves the proline-catalyzed condensation between acetone and isobutyraldehyde are explored. The experiment illustrates some of the trade-offs involved in green chemistry like the use of acetone in large…

Bifunctional Iminophosphorane Organocatalysts for Enantioselective Synthesis: Application to the Ketimine Nitro-Mannich Reaction

PubMed Central

2013-01-01

The design, synthesis, and development of a new class of modular, strongly basic, and tunable bifunctional Brønsted base/H-bond-donor organocatalysts are reported. These catalysts incorporate a triaryliminophosphorane as the Brønsted basic moiety and are readily synthesized via a last step Staudinger reaction of a chiral organoazide and a triarylphosphine. Their application to the first general enantioselective organocatalytic nitro-Mannich reaction of nitromethane to unactivated ketone-derived imines allows the enantioselective construction of β-nitroamines possessing a fully substituted carbon atom. The reaction is amenable to multigram scale-up, and the products are useful for the synthesis of enantiopure 1,2-diamine and α-amino acid derivatives. PMID:24107070

40 CFR 63.1427 - Process vent requirements for processes using extended cookout as an epoxide emission reduction...

Code of Federal Regulations, 2010 CFR

2010-07-01

... obtaining the liquid sample, along with the test method used to determine the epoxide concentration. This... pressures, the owner or operator shall determine the time when the pressure has fallen to half its total pressure by using Equation 13: ER08MY00.008 Where: Phalf1 = Half the total pressure of the epoxide for...

Secondary Organic Aerosol Formation from 2-Methyl-3-Buten-2-ol Photooxidation: Evidence of Acid-Catalyzed Reactive Uptake of Epoxides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Haofei; Zhang, Zhenfa; Cui, Tianqu

2014-04-08

Secondary organic aerosol (SOA) formation from 2-methyl-3-buten-2-ol (MBO) photooxidation has recently been observed in both field and laboratory studies. Similar to isoprene, MBO-derived SOA increases with elevated aerosol acidity in the absence of nitric oxide; therefore, an epoxide intermediate, (3,3-dimethyloxiran-2-yl)methanol (MBO epoxide) was synthesized and tentatively proposed here to explain this enhancement. In the present study, the potential of the synthetic MBO epoxide to form SOA via reactive uptake was systematically examined. SOA was observed only in the presence of acidic aerosols. Major SOA constituents, 2,3-dihydroxyisopentanol (DHIP) and MBO-derived organosulfate isomers, were chemically characterized in both laboratory-generated SOA and inmore » ambient fine aerosols collected from the BEACHON-RoMBAS field campaign during summer 2011, where MBO emissions are substantial. Our results support epoxides as potential products of MBO photooxidation leading to formation of atmospheric SOA and suggest that reactive uptake of epoxides may generally explain acid enhancement of SOA observed from other biogenic hydrocarbons.« less

Changes in antioxidant capacity and colour associated with the formation of β-carotene epoxides and oxidative cleavage derivatives.

PubMed

Gurak, Poliana D; Mercadante, Adriana Z; González-Miret, M L; Heredia, Francisco J; Meléndez-Martínez, Antonio J

2014-03-15

In this study HPLC-DAD-MS/MS was applied for the identification of compounds derived from (all-E)-β-carotene following epoxidation and oxidative cleavage. The consequences on the CIELAB colour parameters and antioxidant capacity (AC) were also evaluated. Five apocarotenoids, three secocarotenoids, seven Z isomers and two epoxides were detected as a result of the oxidative cleavage. Four epoxides and three Z isomers were detected as a consequence of the epoxidation reaction. Some compounds were detected for the first time as a result of oxidation reactions. Both treatments led to a marked decrease in b(∗) and Cab(∗) values, indicating that these colour parameters can be used for the rapid assessment of β-carotene oxidation. The oxidative cleavage of β-carotene resulted in increased capacity to both scavenge ABTS(+) and quench singlet oxygen. These results suggest that the study of the AC of these oxidative derivatives and their possible usefulness as food ingredients deserves further attention. Copyright © 2013 Elsevier Ltd. All rights reserved.

Microdroplets Accelerate Ring Opening of Epoxides

NASA Astrophysics Data System (ADS)

Lai, Yin-Hung; Sathyamoorthi, Shyam; Bain, Ryan M.; Zare, Richard N.

2018-05-01

The nucleophilic opening of an epoxide is a classic organic reaction that has widespread utility in both academic and industrial applications. We have studied the reaction of limonene oxide with morpholine to form 1-methyl-2-morpholino-4-(prop-1-en-2-yl) cyclohexan-1-ol in bulk solution and in electrosprayed microdroplets with a 1:1 v/ v water/methanol solvent system. We find that even after 90 min at room temperature, there is no product detected by nuclear magnetic resonance spectroscopy in bulk solution whereas in room-temperature microdroplets (2-3 μm in diameter), the yield is already 0.5% in a flight time of 1 ms as observed by mass spectrometry. This constitutes a rate acceleration of 105 in the microdroplet environment, if we assume that as much as 5% of product is formed in bulk after 90 min of reaction time. We examine how the reaction rate depends on droplet size, solvent composition, sheath gas pressure, and applied voltage. These factors profoundly influence the extent of reaction. This dramatic acceleration is not limited to just one system. We have also found that the nucleophilic opening of cis-stilbene oxide by morpholine is similarly accelerated. Such large acceleration factors in reaction rates suggest the use of microdroplets for ring opening of epoxides in other systems, which may have practical significance if such a procedure could be scaled. [Figure not available: see fulltext.

40 CFR 63.1427 - Process vent requirements for processes using extended cookout as an epoxide emission reduction...

Code of Federal Regulations, 2011 CFR

2011-07-01

... epoxides, and that are using ECO as a control technique to reduce epoxide emissions in order to comply with... provisions of this section. The owner or operator that is using ECO in order to comply with the emission... used to further reduce the HAP emissions from a process vent already controlled by ECO, then the owner...

Enantioselective reductive transformation of climbazole: A concept towards quantitative biodegradation assessment in anaerobic biological treatment processes.

PubMed

Brienza, Monica; Chiron, Serge

2017-06-01

An efficient chiral method-based using liquid chromatography-high resolution-mass spectrometry analytical method has been validated for the determination of climbazole (CBZ) enantiomers in wastewater and sludge with quantification limits below the 1 ng/L and 2 ng/g range, respectively. On the basis of this newly developed analytical method, the stereochemistry of CBZ was investigated over time in sludge biotic and sterile batch experiments under anoxic dark and light conditions and during wastewater biological treatment by subsurface flow constructed wetlands. CBZ stereoselective degradation was exclusively observed under biotic conditions, confirming the specificity of enantiomeric fraction variations to biodegradation processes. Abiotic CBZ enantiomerization was insignificant at circumneutral pH and CBZ was always biotransformed into CBZ-alcohol due to the specific and enantioselective reduction of the ketone function of CBZ into a secondary alcohol function. This transformation was almost quantitative and biodegradation gave good first order kinetic fit for both enantiomers. The possibility to apply the Rayleigh equation to enantioselective CBZ biodegradation processes was investigated. The results of enantiomeric enrichment allowed for a quantitative assessment of in situ biodegradation processes due to a good fit (R 2  > 0.96) of the anoxic/anaerobic CBZ biodegradation to the Rayleigh dependency in all the biotic microcosms and was also applied in subsurface flow constructed wetlands. This work extended the concept of applying the Rayleigh equation towards quantitative biodegradation assessment of organic contaminants to enantioselective processes operating under anoxic/anaerobic conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Investigation of Enantioselective Membrane Permeability of α-Lipoic Acid in Caco-2 and MDCKII Cell.

PubMed

Uchida, Ryota; Okamoto, Hinako; Ikuta, Naoko; Terao, Keiji; Hirota, Takashi

2016-01-26

α-Lipoic acid (LA) contains a chiral carbon and exists as two enantiomers (R-α-lipoic acid (RLA) and S-α-lipoic acid (SLA)). We previously demonstrated that oral bioavailability of RLA is better than that of SLA. This difference arose from the fraction absorbed multiplied by gastrointestinal availability (F(a) × F(g)) and hepatic availability (F(h)) in the absorption phase. However, it remains unclear whether F(a) and/or F(g) are involved in enantioselectivity. In this study, Caco-2 cells and Madin-Darby canine kidney strain II cells were used to assess the enantioselectivity of membrane permeability. LA was actively transported from the apical side to basal side, regardless of the differences in its steric structure. Permeability rates were proportionally increased in the range of 10-250 µg LA/mL, and the permeability coefficient did not differ significantly between enantiomers. Hence, we conclude that enantioselective pharmacokinetics arose from the metabolism (F(h) or F(g) × F(h)), and definitely not from the membrane permeation (F(a)) in the absorption phase.

Enantioselective determination of metconazole in multi matrices by high-performance liquid chromatography.

PubMed

He, Rujian; Fan, Jun; Tan, Qi; Lai, Yecai; Chen, Xiaodong; Wang, Tai; Jiang, Ying; Zhang, Yaomou; Zhang, Weiguang

2018-02-01

A reliable and effective HPLC analytical method has been developed to stereoselectively quantify metconazole in soil and flour matrices. Effects of polysaccharide chiral stationary phase, type and content of alcoholic modifier on separation of racemic metconazole have been discussed in detail. Resolution and quantitative determination of metconazole stereoisomers were performed by using an Enantiopak OD column, with the n-hexane-ethanol mixture (97:3, v/v) at the flow rate of 1.0mL/min. Then, extraction and cleanup procedures followed by the modified QuEChERS (quick, easy, cheap, effective, rugged and safe) method were used for metconazole racemate in soil and flour matrices. The residual analysis method was validated. Good linearity (R 2 ≥ 0.9997) and recoveries (94.98-104.89%, RSD ≤ 2.0%) for four metconazole stereoisomers were obtained. In brief, this proposed method showed good accuracy and precision, which might be applied in enantioselective determination, residual quantitative analysis, and degradation of metconazole in food and environmental matrices. Copyright © 2017 Elsevier B.V. All rights reserved.

A dual-catalysis approach to enantioselective [2 + 2] photocycloadditions using visible light.

PubMed

Du, Juana; Skubi, Kazimer L; Schultz, Danielle M; Yoon, Tehshik P

2014-04-25

In contrast to the wealth of catalytic systems that are available to control the stereochemistry of thermally promoted cycloadditions, few similarly effective methods exist for the stereocontrol of photochemical cycloadditions. A major unsolved challenge in the design of enantioselective catalytic photocycloaddition reactions has been the difficulty of controlling racemic background reactions that occur by direct photoexcitation of substrates while unbound to catalyst. Here, we describe a strategy for eliminating the racemic background reaction in asymmetric [2 + 2] photocycloadditions of α,β-unsaturated ketones to the corresponding cyclobutanes by using a dual-catalyst system consisting of a visible light-absorbing transition-metal photocatalyst and a stereocontrolling Lewis acid cocatalyst. The independence of these two catalysts enables broader scope, greater stereochemical flexibility, and better efficiency than previously reported methods for enantioselective photochemical cycloadditions.

A Dual-Catalysis Approach to Enantioselective [2+2] Photocycloadditions Using Visible Light

PubMed Central

Du, Juana; Skubi, Kazimer L.; Schultz, Danielle M.; Yoon, Tehshik P.

2015-01-01

In contrast to the wealth of catalytic systems that are available to control the stereochemistry of thermally promoted cycloadditions, few similarly effective methods exist for the stereocontrol of photochemical cycloadditions. A major unsolved challenge in the design of enantioselective catalytic photocycloaddition reactions has been the difficulty of controlling racemic background reactions that occur by direct photoexcitation of substrates while unbound to catalyst. Here we describe a strategy for eliminating the racemic background reaction in asymmetric [2+2] photocycloadditions of α,β-unsaturated ketones to the corresponding cyclobutanes by employing a dual-catalyst system consisting of a visible light-absorbing transition metal photocatalyst and a stereocontrolling Lewis acid co-catalyst. The independence of these two catalysts enables broader scope, greater stereochemical flexibility, and better efficiency than previously reported methods for enantioselective photochemical cycloadditions. PMID:24763585

The asymmetric synthesis of terminal aziridines by methylene transfer from sulfonium ylides to imines.

PubMed

Kavanagh, Sarah A; Piccinini, Alessandro; Connon, Stephen J

2013-06-07

A new ylide-based protocol for the asymmetric aziridination of imines via methylene transfer has been developed involving the use of a simple chiral sulfonium salt and an organic strong base. A systematic study identified triisopropylphenyl sulfonylimines as optimal substrates for the process. Unexpectedly, hindered C2-symmetric sulfonyl salts incorporating bulky ethers at C-2 and C-5--which had previously been useful in the corresponding epoxidation chemistry--decomposed in these aziridination reactions via competing elimination pathways. Under optimised conditions it was found that a simple salt derived from (2R,5R)-2,5-diisopropyl thiolane could mediate asymmetric methylene transfer to a range of imines with uniformly excellent yields with 19-30% ee. Since this is a similar level of enantiomeric excess to that obtained using these same salts in epoxidation chemistry, it was concluded that if more bulky sulfonium salts could be devised which were resistant to decomposition under the reaction conditions, that highly enantioselective aziridine formation by methylene transfer would be possible.

Asymmetric synthesis of N-allylic indoles via regio- and enantioselective allylation of aryl hydrazines

PubMed Central

Xu, Kun; Gilles, Thomas; Breit, Bernhard

2015-01-01

The asymmetric synthesis of N-allylic indoles is important for natural product synthesis and pharmaceutical research. The regio- and enantioselective N-allylation of indoles is a true challenge due to the favourable C3-allylation. We develop here a new strategy to the asymmetric synthesis of N-allylic indoles via rhodium-catalysed N-selective coupling of aryl hydrazines with allenes followed by Fischer indolization. The exclusive N-selectivities and good to excellent enantioselectivities are achieved applying a rhodium(I)/DTBM-Segphos or rhodium(I)/DTBM-Binap catalyst. This method permits the practical synthesis of valuable chiral N-allylated indoles, and avoids the N- or C-selectivity issue. PMID:26137886

Layered transition metal carboxylates: efficient reusable heterogeneous catalyst for epoxidation of olefins.

PubMed

Sen, Rupam; Bhunia, Susmita; Mal, Dasarath; Koner, Subratanath; Miyashita, Yoshitaro; Okamoto, Ken-Ichi

2009-12-01

Layered metal carboxylates [M(malonato)(H(2)O)(2)](n) (M = Ni(II) and Mn(II)) that have a claylike structure have been synthesized hydrothermally and characterized. The interlayer separation in these layered carboxylates is comparable to that of the intercalation distance of the naturally occurring clay materials or layered double hydroxides (LDHs). In this study, we have demonstrated that, instead of intercalating the metal complex into layers of the clay or LDH, layered transition metal carboxylates, [M(malonato)(H(2)O)(2)](n), as such can be used as a recyclable heterogeneous catalyst in olefin epoxidation reaction. Metal carboxylates [M(malonato)(H(2)O)(2)](n) exhibit excellent catalytic performance in olefin epoxidation reaction.

Synthesis of CuPF6 -(S)-BINAP loaded resin and its enantioselectivity toward phenylalanine enantiomers.

PubMed

Liu, Xiong; Zhou, Wenqi; Xu, Longqi

2017-09-01

A type of resin-anchored CuPF 6 -(S)-BINAP was synthesized and identified. The PS-CuPF 6 -(S)-BINAP resin was used to adsorb the phenylalanine enantiomers. The results showed that the adsorption capacity of PS-CuPF 6 -(S)-BINAP resin toward L-phenylalanine was higher than that of resin toward D-phenylalanine. PS-CuPF 6 -(S)-BINAP resin exhibited good enantioselectivity toward L-phenylalanine and D-phenylalanine. The influence of phenylalanine concentration, pH, adsorption time, and temperature on the enantioselectivity of the resin were investigated. The results showed that the enantioselectivity of the resin increased with increasing the phenylalanine concentration, pH, and adsorption time, while it decreased with an increase in temperature. The causes for these influences are discussed. The highest enantioselectivity (α = 2.81) was obtained when the condition of phenylalanine concentration was 0.05 mmol/mL, pH was 8, adsorption time was 12 h, and temperature 5°C. The desorption test for removing D/L-phenylalanine on PS-CuPF 6 -(S)-BINAP resin was also investigated. The desorption ratios of D-phenylalanine and L-phenylalanine at pH of 1 were 95.7% and 94.3%, respectively. This result indicated that the PS-CuPF 6 -(S)-BINAP resin could be regenerated by shaking with an acidic solution. The reusability of the PS-CuPF 6 -(S)-BINAP resin was also assessed and the resin exhibited considerable reusability. © 2017 Wiley Periodicals, Inc.

Novel smart chiral magnetic microspheres for enantioselective adsorption of tryptophan enantiomers

NASA Astrophysics Data System (ADS)

Guo, Lian-Di; Song, Ya-Ya; Yu, Hai-Rong; Pan, Li-Ting; Cheng, Chang-Jing

2017-06-01

Multifunctional microspheres simultaneously possessing chirality, magnetism and thermosensitivity show great potentials in direct enantiomeric separation. Herein we report a novel type of smart chiral magnetic microspheres with core/shell/shell structures (Fe3O4@SiO2@PNCD) and its application in enantioselective adsorption of tryptophan (Trp) enantiomers. The prepared Fe3O4@SiO2@PNCD are composed of a Fe3O4 nanoparticle core, an acidic-resistant SiO2 middle shell and a thermosensitive microgel functional shell (PNCD). The PNCD plays an important role in the enantioselective adsorption of Trp enantiomers. The β-cyclodextrin (β-CD) molecules on the PNCD act as smart receptors or chiral selectors, and can selectively recognize and bind L-Trp enantiomers into their cavities by forming host-guest inclusion complexes. The poly(N-isopropylacrylamide) (PNIPAM) chains on the PNCD serve as microenvironmental adjustors for the association constants of β-CD/L-Trp complexes. The fabricated Fe3O4@SiO2@PNCD demonstrate fascinating temperature-responsive chiral recognition and adsorption selectivity toward Trp enantiomers. Most importantly, the desorption of Trp enantiomers and the regeneration of the Fe3O4@SiO2@PNCD can be easily achieved via simply changing the operation temperature. Moreover, the regenerated Fe3O4@SiO2@PNCD can be readily recovered from the amino acids enantiomeric solution under an external magnetic field for reuse. The present study provides a novel strategy for the direct enantioselective adsorption and separation of various enantiomeric compounds.

Peroxotantalate-Based Ionic Liquid Catalyzed Epoxidation of Allylic Alcohols with Hydrogen Peroxide.

PubMed

Ma, Wenbao; Chen, Chen; Kong, Kang; Dong, Qifeng; Li, Kun; Yuan, Mingming; Li, Difan; Hou, Zhenshan

2017-05-29

The efficient and environmentally benign epoxidation of allylic alcohols has been attained by using new kinds of monomeric peroxotantalate anion-functionalized ionic liquids (ILs=[P 4,4,4,n ] 3 [Ta(O) 3 (η-O 2 )], P 4,4,4,n =quaternary phosphonium cation, n=4, 8, and 14), which have been developed and their structures determined accordingly. This work revealed the parent anions of the ILs underwent structural transformation in the presence of H 2 O 2 . The formed active species exhibited excellent catalytic activity, with a turnover frequency for [P 4,4,4,4 ] 3 [Ta(O) 3 (η-O 2 )] of up to 285 h -1 , and satisfactory recyclability in the epoxidation of various allylic alcohols under very mild conditions by using only one equivalent of hydrogen peroxide as an oxidant. NMR studies showed the reaction was facilitated through a hydrogen-bonding mechanism, in which the peroxo group (O-O) of the peroxotantalate anion served as the hydrogen-bond acceptor and hydroxyl group in the allylic alcohols served as the hydrogen-bond donor. This work demonstrates that simple monomeric peroxotantalates can catalyze epoxidation of allylic alcohols efficiently. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Catalytic enantioselective alkene aminohalogenation/cyclization involving atom transfer.

PubMed

Bovino, Michael T; Chemler, Sherry R

2012-04-16

Problem solved: the title reaction was used for the synthesis of chiral 2-bromo, chloro, and iodomethyl indolines and 2-iodomethyl pyrrolidines. Stereocenter formation is believed to occur by enantioselective cis aminocupration and C-X bond formation is believed to occur by atom transfer. The ultility of the products as versatile synthetic intermediates was demonstrated, as was a radical cascade cyclization sequence. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Direct characterization of cotton fabrics treated with di-epoxide by nuclear magnetic resonance.

PubMed

Xiao, Min; Chéry, Joronia; Keresztes, Ivan; Zax, David B; Frey, Margaret W

2017-10-15

A non-acid-based, di-functional epoxide, neopentyl glycol diglycidyl ether (NPGDGE), was used to modify cotton fabrics. Direct characterization of the modified cotton was conducted by Nuclear Magnetic Resonance (NMR) without grinding the fabric into a fine powder. NaOH and MgBr 2 were compared in catalyzing the reaction between the epoxide groups of NPGDGE and the hydroxyl groups of cellulose. Possible reaction routes were discussed. Scanning electron microscopy (SEM) images showed that while the MgBr 2 -catalyzed reaction resulted in self-polymerization of NPGDGE, the NaOH-catalyzed reaction did not. Fourier transform infrared spectroscopy (FTIR) showed that at high NaOH concentration cellulose restructures from allomorph I to II. NMR studies verified the incorporation of NPGDGE into cotton fabrics with a clear NMR signal, and confirmed that at higher NaOH concentration the efficiency of grafting of NPGDGE was increased. This demonstrates that use of solid state NMR directly on woven fabric samples can simultaneously characterize chemical modification and crystalline polymorph of cotton. No loss of tensile strength was observed for cotton fabrics modified with NPGDGE. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bioaccumulation and enantioselectivity of type I and type II pyrethroid pesticides in earthworm.

PubMed

Chang, Jing; Wang, Yinghuan; Wang, Huili; Li, Jianzhong; Xu, Peng

2016-02-01

In this study, the bioavailability and enantioselectivity differences between bifenthrin (BF, typeⅠpyrethroid) and lambad-cyhalothrin (LCT, type Ⅱ pyrethroid) in earthworm (Eisenia fetida) were investigated. The bio-soil accumulation factors (BSAFs) of BF was about 4 times greater than that of LCT. LCT was degraded faster than BF in soil while eliminated lower in earthworm samples. Compound sorption plays an important role on bioavailability in earthworm, and the soil-adsorption coefficient (K(oc)) of BF and LCT were 22 442 and 42 578, respectively. Metabolic capacity of earthworm to LCT was further studied as no significant difference in the accumulation of LCT between the high and low dose experiment was found. 3-phenoxybenzoic acid (PBCOOH), a metabolite of LCT produced by earthworm was detected in soil. The concentration of PBCOOH at high dose exposure was about 4.7 times greater than that of in low dose level at the fifth day. The bioaccumulation of BF and LCT were both enantioselective in earthworm. The enantiomer factors of BF and LCT in earthworm were approximately 0.12 and 0.65, respectively. The more toxic enantiomers ((+)-BF and (-)-LCT) had a preferential degradation in earthworm and leaded to less toxicity on earthworm for racemate exposure. In combination with other studies, a liner relationship between Log BSAF(S) and Log K(ow) was observed, and the Log BSAF(S) decreased with the increase of Log K(ow). Copyright © 2015 Elsevier Ltd. All rights reserved.

Organocatalytic sequential alpha-amination-Horner-Wadsworth-Emmons olefination of aldehydes: enantioselective synthesis of gamma-amino-alpha,beta-unsaturated esters.

PubMed

Kotkar, Shriram P; Chavan, Vilas B; Sudalai, Arumugam

2007-03-15

A novel and highly enantioselective method for the synthesis of gamma-amino-alpha,beta-unsaturated esters via tandem alpha-amination-Horner-Wadsworth-Emmons (HWE) olefination of aldehydes is described. The one-pot assembly has been demonstrated for the construction of functionalized chiral 2-pyrrolidones, subunits present in several alkaloids. [structure: see text

Rhodium-catalyzed enantioselective intramolecular C-H silylation for the syntheses of planar-chiral metallocene siloles.

PubMed

Zhang, Qing-Wei; An, Kun; Liu, Li-Chuan; Yue, Yuan; He, Wei

2015-06-01

Reported herein is the rhodium-catalyzed enantioselective C-H bond silylation of the cyclopentadiene rings in Fe and Ru metallocenes. Thus, in the presence of (S)-TMS-Segphos, the reactions took place under very mild conditions to afford metallocene-fused siloles in good to excellent yields and with ee values of up to 97%. During this study it was observed that the steric hindrance of chiral ligands had a profound influence on the reactivity and enantioselectivity of the reaction, and might hold the key to accomplishing conventionally challenging asymmetric C-H silylations. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An enantioselective approach toward 3,4-dihydroisocoumarin through the bromocyclization of styrene-type carboxylic acids.

PubMed

Chen, Jie; Zhou, Ling; Tan, Chong Kiat; Yeung, Ying-Yeung

2012-01-20

A facile and enantioselective approach toward 3,4-dihydroisocoumarin was developed. The method involved an amino-thiocarbamate catalyzed enantioselective bromocyclization of styrene-type carboxylic acids, yielding 3-bromo-3,4-dihydroisocoumarins with good yields and ee's. 3-Bromo-3,4-dihydroisocoumarins are versatile building blocks for various dihydroisocoumarin derivatives in which the Br group can readily be modified to achieve biologically important 4-O-type and 4-N-type 3,4-dihydroisocoumarin systems. In addition, studies indicated that, by refining some parameters, the synthetically useful 5-exo phthalide products could be achieved with good yields and ee's.

A Green, Enantioselective Synthesis of Warfarin for the Undergraduate Organic Laboratory

ERIC Educational Resources Information Center

Wong, Terence C.; Sultana, Camille M.; Vosburg, David A.

2010-01-01

The enantioselective synthesis of drugs is of fundamental importance in the pharmaceutical industry. In this experiment, students synthesize either enantiomer of warfarin, a widely used anticoagulant, in a single step from inexpensive starting materials. Stereoselectivity is induced by a commercial organocatalyst, ("R","R")- or…

Enantioselective Degradation and Chiral Stability of Metalaxyl-M in Tomato Fruits.

PubMed

Jing, Xu; Yao, Guojun; Wang, Peng; Liu, Donghui; Qi, Yanli; Zhou, Zhiqiang

2016-05-01

Metalaxyl is an important chiral acetanilide fungicide, and the activity almost entirely originates from the R-enantiomer. Racemic metalaxyl has been gradually replaced by the enantiopure R-enantiomer (metalaxyl-M). In this study a chiral residue analysis method for metalaxyl and the metabolite metalaxyl acid was set up based on high-performance liquid chromatography tandem mass spectroscopy (HPLC-MS/MS). The enantioselective degradation and chiral stability of metalaxyl-M in tomato fruits in two geographically distinct regions of China (Heilongjiang and Hunan Province) were evaluated and the enantioselectivity of metalaxyl acid was also investigated. Tomato plants grew under field conditions with a one-time spray application of metalaxyl-M wettable powder. It was found that R-metalaxyl was not chirally stable and the inactive S-metalaxyl was detected in tomato fruits. At day 40, S-metalaxyl derived from R-metalaxyl accounted for 32% and 26% of the total amount of metalaxyl, respectively. The metabolites R-metalaxyl acid and S-metalaxyl acid were both observed in tomato, and the ratio of S-metalaxyl acid to the sum of S- and R-metalaxyl acid was 36% and 28% at day 40, respectively. For both metalaxyl and metalaxyl acid, the half-life of the S-enantiomer was longer than the R-enantiomer. The results indicated that the enantiomeric conversion should be considered in the bioactivity evaluation and environmental pollution assessment. Chirality 28:382-386, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

In Silico Prediction of Cytochrome P450-Mediated Biotransformations of Xenobiotics: A Case Study of Epoxidation.

PubMed

Zhang, Jing; Ji, Li; Liu, Weiping

2015-08-17

Predicting the biotransformation of xenobiotics is important in toxicology; however, as more compounds are synthesized than can be investigated experimentally, powerful computational methods are urgently needed to prescreen potentially useful candidates. Cytochrome P450 enzymes (P450s) are the major enzymes involved in xenobiotic metabolism, and many substances are bioactivated by P450s to form active compounds. An example is the conversion of olefinic substrates to epoxides, which are intermediates in the metabolic activation of many known or suspected carcinogens. We have calculated the activation energies for epoxidation by the active species of P450 enzymes (an iron-oxo porphyrin cation radical oxidant, compound I) for a diverse set of 36 olefinic substrates with state-of-the-art density functional theory (DFT) methods. Activation energies can be estimated by the computationally less demanding method of calculating the ionization potentials of the substrates, which provides a useful and simple predictive model based on the reaction mechanism; however, the preclassification of these diverse substrates into weakly polar and strongly polar groups is a prerequisite for the construction of specific predictive models with good predictability for P450 epoxidation. This approach has been supported by both internal and external validations. Furthermore, the relation between the activation energies for the regioselective epoxidation and hydroxylation reactions of P450s and experimental data has been investigated. The results show that the computational method used in this work, single-point energy calculations with the B3LYP functional including zero-point energy and solvation and dispersion corrections based on B3LYP-optimized geometries, performs well in reproducing the experimental trends of the epoxidation and hydroxylation reactions.

Lysophosphatidic acids are new substrates for the phosphatase domain of soluble epoxide hydrolase.

PubMed

Oguro, Ami; Imaoka, Susumu

2012-03-01

Soluble epoxide hydrolase (sEH) is a bifunctional enzyme that has a C-terminus epoxide hydrolase domain and an N-terminus phosphatase domain. The endogenous substrates of epoxide hydrolase are known to be epoxyeicosatrienoic acids, but the endogenous substrates of the phosphatase activity are not well understood. In this study, to explore the substrates of sEH, we investigated the inhibition of the phosphatase activity of sEH toward 4-methylumbelliferyl phosphate by using lecithin and its hydrolyzed products. Although lecithin itself did not inhibit the phosphatase activity, the hydrolyzed lecithin significantly inhibited it, suggesting that lysophospholipid or fatty acid can inhibit it. Next, we investigated the inhibition of phosphatase activity by lysophosphatidyl choline, palmitoyl lysophosphatidic acid, monopalmitoyl glycerol, and palmitic acid. Palmitoyl lysophosphatidic acid and fatty acid efficiently inhibited phosphatase activity, suggesting that lysophosphatidic acids (LPAs) are substrates for the phosphatase activity of sEH. As expected, palmitoyl, stearoyl, oleoyl, and arachidonoyl LPAs were efficiently dephosphorylated by sEH (Km, 3-7 μM; Vmax, 150-193 nmol/min/mg). These results suggest that LPAs are substrates of sEH, which may regulate physiological functions of cells via their metabolism.

Enantioselective α-Alkylation of Aldehydes via Photoredox Organocatalysis: Rapid Access to Pharmacophore Fragments from β-Cyanoaldehydes**

PubMed Central

Welin, Eric R.; Warkentin, Alexander A.; Conrad, Jay C.

2015-01-01

The combination of photoredox catalysis and enamine catalysis has enabled the development of an enantioselective α-cyanoalkylation of aldehydes. This synergistic catalysis protocol allows for the coupling of two highly versatile yet orthogonal functionalities, allowing rapid diversification of the oxonitrile products to a wide array of medicinally relevant derivatives and heterocycles. This methodology has also been applied to the total synthesis of the lignan natural product (−)-bursehernin. PMID:26130043

Remote Enantioselection Transmitted by an Achiral Peptide Nucleic Acid Backbone

NASA Technical Reports Server (NTRS)

Kozlov, Igor A.; Orgel, Leslie E.; Nielsen, Peter E.

2000-01-01

short homochiral segment of DNA into a PNA helix could have guaranteed that the next short segment of DNA to be incorporated would have the same handedness as the first. Once two segments of the same handedness were present, the probability that a third segment would have the same handedness would increase, and so on. Evolution could then slowly dilute out the PNA part. This scenario would ultimately allow the formation of a chiral oligonucleotide by processes that are largely resistant to enantiomeric crossinhibition. It is important to note that the ligation of homochiral dinucleotides on a nucleic acid template would probably be at least as enantiospecific as the reaction that we have studied. The disadvantage of using chiral monomers as components of a replicating system arises from the difficulty of generating a first long homochiral template from a racemic mixture of monomers, although results of experiments designed to overcome this difficulty by employing homochiral tetramers have been reported.l l The probability of obtaining a homochiral n-mer from achiral substrates is approximately 1P-I if the nontemplate-directed extension of the primer is not enantioselective. Hence, it would be very hard to get started with a homochiral 40-mer, for example. No such difficulty exists in a scenario that originates with an achiral genetic material and in which the incorporation of very few chiral monomers in this achiral background gradually progresses towards homochirality. It seems possible that some PNA sequences could act as catalysts, analogous to ribozymes, even though PNA lacks clear metal binding sites. Although such catalysts could not be enantioselective, the incorporation of as few as two chiral nucleotides could then impose chiral specificity on the system. Furthermore, such patch chimeras could help to bridge the gap in catalytic potential between PNA and RNA, while guaranteeing enantioselectivity.

Ladder Polyether Synthesis via Epoxide-Opening Cascades Directed by a Disappearing Trimethylsilyl Group

PubMed Central

Heffron, Timothy P.; Simpson, Graham L.; Merino, Estibaliz; Jamison, Timothy F.

2010-01-01

Epoxide-opening cascades offer the potential to construct complex polyether natural products expeditiously and in a manner that emulates the biogenesis proposed for these compounds. Herein we provide a full account of our development of a strategy that addresses several important challenges of such cascades. The centerpiece of the method is a trimethylsilyl (SiMe3) group that serves several purposes and leaves no trace of itself by the time the cascade has come to an end. The main function of the SiMe3 group is to dictate the regioselectivity of epoxide opening. This strategy is the only general method of effecting endo-selective cascades under basic conditions. PMID:20302314

The Productive Merger of Iodonium Salts and Organocatalysis. A Non-Photolytic Approach to the Enantioselective α-Trifluoromethylation of Aldehydes

PubMed Central

Allen, Anna E.; MacMillan, David W. C.

2010-01-01

An enantioselective organocatalytic α-trifluoromethylation of aldehydes has been accomplished using a commercially available, electrophilic trifluoromethyl source. The merging of Lewis acid and organocatalysis provides a new strategy for the enantioselective construction of trifluoromethyl stereogenicity, an important chiral synthon for pharmaceutical, material, and agrochemical applications. This mild and operationally simple protocol allows rapid access to enantioenriched α-trifluoromethylated aldehydes through a non-photolytic pathway. PMID:20297822

Room-temperature enantioselective C-H iodination via kinetic resolution.

PubMed

Chu, Ling; Xiao, Kai-Jiong; Yu, Jin-Quan

2014-10-24

Asymmetric carbon-hydrogen (C-H) activation reactions often rely on desymmetrization of prochiral C-H bonds on the same achiral molecule, using a chiral catalyst. Here, we report a kinetic resolution via palladium-catalyzed enantioselective C-H iodination in which one of the enantiomers of a racemic benzylic amine substrates undergoes faster aryl C-H insertion with the chiral catalysts than the other. The resulting enantioenriched C-H functionalization products would not be accessible through desymmetrization of prochiral C-H bonds. The exceedingly high relative rate ratio (k(fast)/k(slow) up to 244), coupled with the subsequent iodination of the remaining enantiomerically enriched starting material using a chiral ligand with the opposite configuration, enables conversion of both substrate enantiomers into enantiomerically pure iodinated products. Copyright © 2014, American Association for the Advancement of Science.

Enantioselective cellular uptake of chiral semiconductor nanocrystals

NASA Astrophysics Data System (ADS)

Martynenko, I. V.; Kuznetsova, V. A.; Litvinov, I. K.; Orlova, A. O.; Maslov, V. G.; Fedorov, A. V.; Dubavik, A.; Purcell-Milton, F.; Gun'ko, Yu K.; Baranov, A. V.

2016-02-01

The influence of the chirality of semiconductor nanocrystals, CdSe/ZnS quantum dots (QDs) capped with L- and D-cysteine, on the efficiency of their uptake by living Ehrlich Ascite carcinoma cells is studied by spectral- and time-resolved fluorescence microspectroscopy. We report an evident enantioselective process where cellular uptake of the L-Cys QDs is almost twice as effective as that of the D-Cys QDs. This finding paves the way for the creation of novel approaches to control the biological properties and behavior of nanomaterials in living cells.

Nanobody based immunoassay for human soluble epoxide hydrolase detection using polyHRP for signal enhancement—the rediscovery of polyHRP

USDA-ARS?s Scientific Manuscript database

Soluble epoxide hydrolase (sEH) is a potential pharmacological target for treating hypertension, vascular inflammation, cancer, pain and multiple cardiovascular related diseases. A variable domain of a heavy chain only antibody (termed sdAb, nanobody or VHH) possesses advantages of small size, high ...

Enhancing the potential of enantioselective organocatalysis with light

NASA Astrophysics Data System (ADS)

Silvi, Mattia; Melchiorre, Paolo

2018-02-01

Organocatalysis—catalysis mediated by small chiral organic molecules—is a powerful technology for enantioselective synthesis, and has extensive applications in traditional ionic, two-electron-pair reactivity domains. Recently, organocatalysis has been successfully combined with photochemical reactivity to unlock previously inaccessible reaction pathways, thereby creating new synthetic opportunities. Here we describe the historical context, scientific reasoning and landmark discoveries that were essential in expanding the functions of organocatalysis to include one-electron-mediated chemistry and excited-state reactivity.

Environmental fate of the fungicide metalaxyl in soil amended with composted olive-mill waste and its biochar: An enantioselective study.

PubMed

Gámiz, Beatriz; Pignatello, Joseph J; Cox, Lucía; Hermosín, María C; Celis, Rafael

2016-01-15

A large number of pesticides are chiral and reach the environment as mixtures of optical isomers or enantiomers. Agricultural practices can affect differently the environmental fate of the individual enantiomers. We investigated how amending an agricultural soil with composted olive-mill waste (OMWc) or its biochar (BC) at 2% (w:w) affected the sorption, degradation, and leaching of each of the two enantiomers of the chiral fungicide metalaxyl. Sorption of metalaxyl enantiomers was higher on BC (Kd ≈ 145 L kg(-1)) than on OMWc (Kd ≈ 22 L kg(-1)) and was not enantioselective in either case, and followed the order BC-amended>OMWc-amended>unamended soil. Both enantiomers showed greater resistance to desorption from BC-amended soil compared to unamended and OMWc-amended soil. Dissipation studies revealed that the degradation of metalaxyl was more enantioselective (R>S) in unamended and OMWc-amended soil than in BC-amended soil. The leaching of both S- and R-metalaxyl from soil columns was almost completely suppressed after amending the soil with BC and metalaxyl residues remaining in the soil columns were more racemic than those in soil column leachates. Our findings show that addition of BC affected the final enantioselective behavior of metalaxyl in soil indirectly by reducing its bioavailability through sorption, and to a greater extent than OMWc. BC showed high sorption capacity to remove metalaxyl enantiomers from water, immobilize metalaxyl enantiomers in soil, and mitigate the groundwater contamination problems particularly associated with the high leaching potential of the more persistent enantiomer. Copyright © 2015 Elsevier B.V. All rights reserved.

Enhanced metal loading in SBA-15-type catalysts facilitated by salt addition. Synthesis, characterization and catalytic epoxide alcoholysis activity of molybdenum incorporated porous silica

DOE Office of Scientific and Technical Information (OSTI.GOV)

Budhi, Sridhar; Peeraphatdit, Chorthip; Pylypenko, Svitlana

2014-02-07

We report a novel method to increase the metal loading in SBA-15 silica matrix via direct synthesis. It was demonstrated through the synthesis and characterization of a series of molybdenum containing SBA-15 mesoporous silica catalysts prepared with and without diammonium hydrogen phosphate (DHP) as an additive. Catalysts prepared with DHP show a 2–3 times increase in incorporation of molybdenum in the silica matrix and pore size enlargement. The synthesized catalysts were characterized using nitrogen sorption, X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and inductively coupled plasma–optical emission spectroscopy (ICP–OES). Themore » catalytic activity of catalysts prepared with DHP for alcoholysis of epoxides was superior than the catalyst prepared without DHP. Alcoholysis of epoxides was demonstrated for a range of alcohols and epoxides under ambient conditions in as little as 30 min with high selectivity.« less

Expanding the Catalytic Triad in Epoxide Hydrolases and Related Enzymes.

PubMed

Amrein, Beat A; Bauer, Paul; Duarte, Fernanda; Janfalk Carlsson, Åsa; Naworyta, Agata; Mowbray, Sherry L; Widersten, Mikael; Kamerlin, Shina C L

2015-10-02

Potato epoxide hydrolase 1 exhibits rich enantio- and regioselectivity in the hydrolysis of a broad range of substrates. The enzyme can be engineered to increase the yield of optically pure products as a result of changes in both enantio- and regioselectivity. It is thus highly attractive in biocatalysis, particularly for the generation of enantiopure fine chemicals and pharmaceuticals. The present work aims to establish the principles underlying the activity and selectivity of the enzyme through a combined computational, structural, and kinetic study using the substrate trans -stilbene oxide as a model system. Extensive empirical valence bond simulations have been performed on the wild-type enzyme together with several experimentally characterized mutants. We are able to computationally reproduce the differences between the activities of different stereoisomers of the substrate and the effects of mutations of several active-site residues. In addition, our results indicate the involvement of a previously neglected residue, H104, which is electrostatically linked to the general base H300. We find that this residue, which is highly conserved in epoxide hydrolases and related hydrolytic enzymes, needs to be in its protonated form in order to provide charge balance in an otherwise negatively charged active site. Our data show that unless the active-site charge balance is correctly treated in simulations, it is not possible to generate a physically meaningful model for the enzyme that can accurately reproduce activity and selectivity trends. We also expand our understanding of other catalytic residues, demonstrating in particular the role of a noncanonical residue, E35, as a "backup base" in the absence of H300. Our results provide a detailed view of the main factors driving catalysis and regioselectivity in this enzyme and identify targets for subsequent enzyme design efforts.

The Enantioselectivity of Odor Sensation: Some Examples for Undergraduate Chemistry Courses

ERIC Educational Resources Information Center

Kraft, Philip; Mannschreck, Albrecht

2010-01-01

This article discusses seven chiral odorants that demonstrate the enantioselectivity of odor sensation: carvone, Celery Ketone, camphor, Florhydral, 3-methyl-3-sulfanylhexan-1-ol, muscone, and methyl jasmonate. After a general introduction of the odorant-receptor interaction and the combinatorial code of olfaction, the olfactory properties of the…

Enantioselective direct α-amination of aldehydes via a photoredox mechanism: a strategy for asymmetric amine fragment coupling.

PubMed

Cecere, Giuseppe; König, Christian M; Alleva, Jennifer L; MacMillan, David W C

2013-08-07

The direct, asymmetric α-amination of aldehydes has been accomplished via a combination of photoredox and organocatalysis. Photon-generated N-centered radicals undergo enantioselective α-addition to catalytically formed chiral enamines to directly produce stable α-amino aldehyde adducts bearing synthetically useful amine substitution patterns. Incorporation of a photolabile group on the amine precursor obviates the need to employ a photoredox catalyst in this transformation. Importantly, this photoinduced transformation allows direct and enantioselective access to α-amino aldehyde products that do not require postreaction manipulation.

Enantioselective small molecule synthesis by carbon dioxide fixation using a dual Brønsted acid/base organocatalyst.

PubMed

Vara, Brandon A; Struble, Thomas J; Wang, Weiwei; Dobish, Mark C; Johnston, Jeffrey N

2015-06-17

Carbon dioxide exhibits many of the qualities of an ideal reagent: it is nontoxic, plentiful, and inexpensive. Unlike other gaseous reagents, however, it has found limited use in enantioselective synthesis. Moreover, unprecedented is a tool that merges one of the simplest biological approaches to catalysis-Brønsted acid/base activation-with this abundant reagent. We describe a metal-free small molecule catalyst that achieves the three component reaction between a homoallylic alcohol, carbon dioxide, and an electrophilic source of iodine. Cyclic carbonates are formed enantioselectively.

A new efficient iron catalyst for olefin epoxidation with hydrogen peroxide.

PubMed

Mikhalyova, Elena A; Makhlynets, Olga V; Palluccio, Taryn D; Filatov, Alexander S; Rybak-Akimova, Elena V

2012-01-18

A new aminopyridine ligand derived from bipiperidine (the product of full reduction of bipyridine, bipy) coordinates to iron(II) in a cis-α fashion, yielding a new selective catalyst for olefin epoxidation with H(2)O(2) under limiting substrate conditions.

Catalytic enantioselective addition of Grignard reagents to aromatic silyl ketimines

NASA Astrophysics Data System (ADS)

Rong, Jiawei; Collados, Juan F.; Ortiz, Pablo; Jumde, Ravindra P.; Otten, Edwin; Harutyunyan, Syuzanna R.

2016-12-01

α-Chiral amines are of significant importance in medicinal chemistry, asymmetric synthesis and material science, but methods for their efficient synthesis are scarce. In particular, the synthesis of α-chiral amines with the challenging tetrasubstituted carbon stereocentre is a long-standing problem and catalytic asymmetric additions of organometallic reagents to ketimines that would give direct access to these molecules are underdeveloped. Here we report a highly enantioselective catalytic synthesis of N-sulfonyl protected α-chiral silyl amines via the addition of inexpensive, easy to handle and readily available Grignard reagents to silyl ketimines. The key to this success was our ability to suppress any unselective background addition reactions and side reduction pathway, through the identification of an inexpensive, chiral Cu-complex as the catalytically active structure.

Sequential rhodium/palladium catalysis: enantioselective formation of dihydroquinolinones in the presence of achiral and chiral ligands.

PubMed

Zhang, Lei; Qureshi, Zafar; Sonaglia, Lorenzo; Lautens, Mark

2014-12-08

Compatible combinations of achiral and chiral ligands can be used in rhodium/palladium catalysis to achieve highly enantioselective domino reactions. The difference in rates of catalysis and minimal effects of ligand interference confer control in the domino sequence. The "all-in-one" 1,4-conjugate arylation and C-N cross-coupling through sequential Rh/Pd catalysis provides access to enantioenriched dihydroquinolinone building blocks. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

AN IN SILICO INVESTIGATION OF THE ENANTIOSELECTIVE METABOLISM RATES OF TRIAZOLE FUGICIDES

EPA Science Inventory

The objective of this work is to use in silico methods such as ab initio quantum and classical force-field methods to explore and develop an understanding for the enantioselective metabolism rates experimentally observed in the triazole fungicide bromuconazole. This directed stud...

Ring-Opening Copolymerization of Epoxides and Cyclic Anhydrides with Discrete Metal Complexes: Structure-Property Relationships.

PubMed

Longo, Julie M; Sanford, Maria J; Coates, Geoffrey W

2016-12-28

Polyesters synthesized through the alternating copolymerization of epoxides and cyclic anhydrides compose a growing class of polymers that exhibit an impressive array of chemical and physical properties. Because they are synthesized through the chain-growth polymerization of two variable monomers, their syntheses can be controlled by discrete metal complexes, and the resulting materials vary widely in their functionality and physical properties. This polymer-focused review gives a perspective on the current state of the field of epoxide/anhydride copolymerization mediated by discrete catalysts and the relationships between the structures and properties of these polyesters.

Disruption of the hormonal network and the enantioselectivity of bifenthrin in trophoblast: maternal-fetal health risk of chiral pesticides.

PubMed

Zhao, Meirong; Zhang, Ying; Zhuang, Shulin; Zhang, Quan; Lu, Chengsheng; Liu, Weiping

2014-07-15

Endocrine-disrupting chemicals (EDCs) can interfere with normal hormone signaling to increase health risks to the maternal-fetal system, yet few studies have been conducted on the currently used chiral EDCs. This work tested the hypothesis that pyrethroids could enantioselectively interfere with trophoblast cells. Cell viability, hormone secretion, and steroidogenesis gene expression of a widely used pyrethroid, bifenthrin (BF), were evaluated in vitro, and the interactions of BF enantiomers with estrogen receptor (ER) were predicted. At low or noncytotoxic concentrations, both progesterone and human chorionic gonadotropin secretion were induced. The expression levels of progesterone receptor and human leukocyte antigen G genes were significantly stimulated. The key regulators of the hormonal cascade, GnRH type-I and its receptor, were both upregulated. The expression levels of selected steroidogenic genes were also significantly altered. Moreover, a consistent enantioselective interference of hormone signaling was observed, and S-BF had greater effects than R-BF. Using molecular docking, the enantioselective endocrine disruption of BF was predicted to be partially due to enantiospecific ER binding affinity. Thus, BF could act through ER to enantioselectively disturb the hormonal network in trophoblast cells. These converging results suggest that the currently used chiral pesticides are of significant concern with respect to maternal-fetal health.

Enantioselective Direct α-Amination of Aldehydes via a Photoredox Mechanism: A Strategy for Asymmetric Amine Fragment Coupling

PubMed Central

Cecere, Giuseppe; Koenig, Christian M.; Alleva, Jennifer L.

2013-01-01

The direct, asymmetric α-amination of aldehydes has been accomplished via a combination of photoredox and organocatalysis. Photon-generated, nitrogen-centered radicals undergo enantioselective α-addition to catalytically formed chiral enamines to directly produce stable α-amino aldehyde adducts bearing synthetically useful amine substitution patterns. Incorporation of a photolabile group on the amine precursor obviates the need to employ a photoredox catalyst in this transformation. Importantly, this photoinduced transformation allows direct and enantioselective access to α-amino aldehyde products that do not require post-reaction manipulation. PMID:23869694

Chemo-Enzymatic Synthesis of Chiral Epoxides Ethyl and Methyl (S)-3-(Oxiran-2-yl)propanoates from Renewable Levoglucosenone: An Access to Enantiopure (S)-Dairy Lactone.

PubMed

Peru, Aurélien A M; Flourat, Amandine L; Gunawan, Christian; Raverty, Warwick; Jevric, Martyn; Greatrex, Ben W; Allais, Florent

2016-07-29

Chiral epoxides-such as ethyl and methyl (S)-3-(oxiran-2-yl)propanoates ((S)-1a/1b)-are valuable precursors in many chemical syntheses. Until recently, these compounds were synthesized from glutamic acid in four steps (deamination, reduction, tosylation and epoxide formation) in low to moderate overall yield (20%-50%). Moreover, this procedure requires some harmful reagents such as sodium nitrite ((eco)toxic) and borane (carcinogen). Herein, starting from levoglucosenone (LGO), a biobased chiral compound obtained through the flash pyrolysis of acidified cellulose, we propose a safer and more sustainable chemo-enzymatic synthetic pathway involving lipase-mediated Baeyer-Villiger oxidation, palladium-catalyzed hydrogenation, tosylation and treatment with sodium ethoxide/methoxide as key steps. This route afforded ethyl and methyl (S)-3-(oxiran-2-yl)propanoates in 57% overall yield, respectively. To demonstrate the potentiality of this new synthetic pathway from LGO, the synthesis of high value-added (S)-dairy lactone was undertaken from these epoxides and provided the target in 37% overall yield from LGO.

RNA-Cleaving DNA Enzymes with Altered Regio- or Enantioselectivity

NASA Technical Reports Server (NTRS)

Ordoukhanian, Phillip; Joyce, Gerald F.

2002-01-01

In vitro evolution methods were used to obtain DNA enzymes that cleave either a 2',5' - phosphodiester following a wibonucleotide or a 3',5' -phosphodiester following an L-ribonucleotide. Both enzymes can operate in an intermolecular reaction format with multiple turnover. The DNA enzyme that cleaves a 2',5' -phosphodiester exhibits a k(sub cat) of approx. 0.01/ min and catalytic efficiency, k(sub cat)/k(sub m) of approx. 10(exp 5)/ M min. The enzyme that cleaves an L-ribonudeotide is about 10-fold slower and has a catalytic efficiency of approx. 4 x 10(exp 5)/ M min. Both enzymes require a divalent metal cation for their activity and have optimal catalytic rate at pH 7-8 and 35-50 C. In a comparison of each enzyme s activity with either its corresponding substrate that contains an unnatural ribonudeotide or a substrate that instead contains a standard ribonucleotide, the 2',5' -phosphodiester-deaving DNA enzyme exhibited a regioselectivity of 6000- fold, while the L-ribonucleotide-cleaving DNA enzyme exhibited an enantioselectivity of 50-fold. These molecules demonstrate how in vitro evolution can be used to obtain regio- and enantioselective catalysts that exhibit specificities for nonnatural analogues of biological compounds.

Quantitation of enantiomers of r-7,t-8,9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]-pyrene in human urine: evidence supporting metabolic activation of benzo[a]pyrene via the bay region diol epoxide.

PubMed

Hecht, Stephen S; Hochalter, Jon Bradley

2014-09-01

Benzo[a]pyrene (BaP), a potent polycyclic aromatic hydrocarbon carcinogen, is widely distributed in the human environment. All humans are exposed to BaP through the diet and contact with the general environment; cigarette smokers have higher exposure. An important pathway of BaP metabolism proceeds through formation of diol epoxides including the 'bay region diol epoxide' 7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [BaP-(7R,8S)-diol-(9S,10R)-epoxide] and the 'reverse diol epoxide' 9S,10R-dihydroxy-7R,8S-epoxy-7,8,9,10-tetrahydrobenzo [a]pyrene [BaP-(9S,10R)-diol-(7R,8S)-epoxide]. The bay region diol epoxide is considered a major ultimate carcinogen of BaP based on studies in cell culture and laboratory animals, but the available data in humans are less convincing. The bay region diol epoxide and the reverse diol epoxide react with H2O to produce enantiomeric BaP-tetraols that are excreted in the urine. We used chiral stationary-phase high-performance liquid chromatography and gas chromatography-negative ion chemical ionisation-tandem mass spectrometry to quantify these enantiomeric BaP-tetraols in the urine of 25 smokers and 25 non-smokers. The results demonstrated that the BaP-tetraol enantiomer representing the carcinogenic bay region diol epoxide pathway accounted for 68±6% (range 56-81%) of total BaP-tetraol in smokers and 64±6% (range 46-78%) in non-smokers. Levels of the major BaP-tetraol enantiomer decreased by 75% in smokers who quit smoking. These data provide convincing evidence in support of the bay region diol epoxide mechanism of BaP carcinogenesis in humans. © The Author 2014. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Enantioselective synthesis of anti-β-hydroxy-α-amido esters via transfer hydrogenation.

PubMed

Seashore-Ludlow, Brinton; Villo, Piret; Häcker, Christine; Somfai, Peter

2010-11-19

The asymmetric transfer hydrogenation of α-amido-β-keto esters to provide the corresponding anti-β-hydroxy-α-amido esters in good to excellent yields, diastereoselectivity, and enantioselectivity is reported. The procedure is operationally simple, and delicate handling of the catalyst is not necessary.

Hybrid networks based on epoxidized camelina oil

PubMed Central

Balanuca, Brindusa; Stan, Raluca; Lungu, Adriana; Vasile, Eugeniu; Iovu, Horia

2017-01-01

Abstract Lately, renewable resources received great attention in the macromolecular compounds area, regarding the design of the monomers and polymers with different applications. In this study the capacity of several modified vegetable oil-based monomers to build competitive hybrid networks was investigate, taking into account thermal and mechanical behavior of the designed materials. In order to synthesize such competitive nanocomposites, the selected renewable raw material, camelina oil, was employed due to the non-toxicity and biodegradability behavior. General properties of epoxidized camelina oil-based materials were improved by loading of different types of organic-inorganic hybrid compounds – polyhedral oligomeric silsesquioxane (POSS) bearing one (POSS1Ep) or eight (POSS8Ep) epoxy rings on the cages. In order to identify the chemical changes occurring after the thermal curing reactions, FT-IR spectrometry was employed. The new synthesized nanocomposites based on epoxidized camelina oil (ECO) were characterized by dynamic mechanical analyze and thermogravimetric analyze. The morphology of the ECO-based materials was investigate by scanning electron microscopy and supplementary information regarding the presence of the POSS compounds were establish by energy dispersive X-ray analysis and X-ray photoelectron spectroscopy. The smooth materials without any separation phase indicates a well dispersion of the Si–O–Si cages within the organic matrix and the incorporation of this hybrid compounds into the ECO network demonstrates to be a well strategy to improve the thermal and mechanical properties, simultaneously. PMID:29491775

Lysophosphatidic acids are new substrates for the phosphatase domain of soluble epoxide hydrolase[S

PubMed Central

Oguro, Ami; Imaoka, Susumu

2012-01-01

Soluble epoxide hydrolase (sEH) is a bifunctional enzyme that has a C-terminus epoxide hydrolase domain and an N-terminus phosphatase domain. The endogenous substrates of epoxide hydrolase are known to be epoxyeicosatrienoic acids, but the endogenous substrates of the phosphatase activity are not well understood. In this study, to explore the substrates of sEH, we investigated the inhibition of the phosphatase activity of sEH toward 4-methylumbelliferyl phosphate by using lecithin and its hydrolyzed products. Although lecithin itself did not inhibit the phosphatase activity, the hydrolyzed lecithin significantly inhibited it, suggesting that lysophospholipid or fatty acid can inhibit it. Next, we investigated the inhibition of phosphatase activity by lysophosphatidyl choline, palmitoyl lysophosphatidic acid, monopalmitoyl glycerol, and palmitic acid. Palmitoyl lysophosphatidic acid and fatty acid efficiently inhibited phosphatase activity, suggesting that lysophosphatidic acids (LPAs) are substrates for the phosphatase activity of sEH. As expected, palmitoyl, stearoyl, oleoyl, and arachidonoyl LPAs were efficiently dephosphorylated by sEH (Km, 3–7 μM; Vmax, 150–193 nmol/min/mg). These results suggest that LPAs are substrates of sEH, which may regulate physiological functions of cells via their metabolism. PMID:22217705

Origin of Enantioselectivity in CF3-PIP-Catalyzed Kinetic Resolution of Secondary Benzylic Alcohols

PubMed Central

Li, Ximin; Liu, Peng; Houk, K. N.; Birman, Vladimir B.

2009-01-01

Computational studies provide support for the involvement of intermolecular π–interactions in the chiral recognition of secondary benzylic alcohols by the enantioselective acyl transfer catalyst CF3-PIP. PMID:18817392

Enantioselective rhodium/ruthenium photoredox catalysis en route to chiral 1,2-aminoalcohols.

PubMed

Ma, Jiajia; Harms, Klaus; Meggers, Eric

2016-08-09

A rhodium-based chiral Lewis acid catalyst combined with [Ru(bpy)3](PF6)2 as a photoredox sensitizer allows for the visible-light-activated redox coupling of α-silylamines with 2-acyl imidazoles to afford, after desilylation, 1,2-amino-alcohols in yields of 69-88% and with high enantioselectivity (54-99% ee). The reaction is proposed to proceed via an electron exchange between the α-silylamine (electron donor) and the rhodium-chelated 2-acyl imidazole (electron acceptor), followed by a stereocontrolled radical-radical reaction. Substrate scope and control experiments reveal that the trimethylsilyl group plays a crucial role in this reductive umpolung of the carbonyl group.

Efficient epoxidation of a terminal alkene containing allylic hydrogen atoms: trans-methylstyrene on Cu{111}.

PubMed

Cropley, Rachael L; Williams, Federico J; Urquhart, Andrew J; Vaughan, Owain P H; Tikhov, Mintcho S; Lambert, Richard M

2005-04-27

The selective oxidation of trans-methylstyrene, a phenyl-substituted propene that contains labile allylic hydrogen atoms, has been studied on Cu{111}. Mass spectrometry and synchrotron fast XPS were used to detect, respectively, desorbing gaseous products and the evolution of surface species as a function of temperature and time. Efficient partial oxidation occurs yielding principally the epoxide, and the behavior of the system is sensitive to the order in which reactants are adsorbed. The latter is understandable in terms of differences in the spatial distribution of oxygen adatoms; isolated adatoms lead to epoxidation, while islands of "oxidic" oxygen do not. NEXAFS data taken over a range of coverages and in the presence and absence of coadsorbed oxygen indicate that the adsorbed alkene lies essentially flat with the allylic hydrogen atoms close to the surface. The photoemission results and comparison with the corresponding behavior of styrene on Cu{111} strongly suggest that allylic hydrogen abstraction is indeed a critical factor that limits epoxidation selectivity. An overall mechanism consistent with the structural and reactive properties is proposed.

Enantioselective Access to Spirocyclic Sultams by Chiral Cp(x) -Rhodium(III)-Catalyzed Annulations.

PubMed

Pham, Manh V; Cramer, Nicolai

2016-02-12

Chiral spirocyclic sultams are a valuable compound class in organic and medicinal chemistry. A rapid entry to this structural motif involves a [3+2] annulation of an N-sulfonyl ketimine and an alkyne. Although the directing-group properties of the imino group for C-H activation have been exploited, the developments of related asymmetric variants have remained very challenging. The use of rhodium(III) complexes equipped with a suitable atropchiral cyclopentadienyl ligand, in conjunction with a carboxylic acid additive, enables an enantioselective and high yielding access to such spirocyclic sultams. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Epoxidation of 1-Octene with hydrogen peroxide aqueous catalyzed by titania supported sulfonated coal

NASA Astrophysics Data System (ADS)

Nurhadi, Mukhamad

2017-02-01

Titania supported sulfonated coal was created as heterogeneous catalyst for epoxidation of 1-octene with aqueous hydrogen peroxide as oxidant at room temperature. The catalysts were prepared from coal that was sulfonated with H2SO4 (97%) and impregnated 7.2%wt with titanium(IV) isopropoxide (Ti(PrO)4). All catalysts coal (C), CS, Ti(7.2)-CS and Ti(7.2)-CSC were characterized by FTIR. The catalytic performance was tested for epoxidation of 1-octene with H2O2 aqueous as oxidant. It is found that Ti(7.2)-CS possessed the best catalytic performance and it gave the highest 1,2 epoxyoctene 322 µmol.

Diastereoselective Synthesis of a Strawberry Flavoring Agent by Epoxidation of Ethyl trans-b-Methylcinnamate

NASA Astrophysics Data System (ADS)

Pageau, Gayle J.; Mabaera, Rodwell; Kosuda, Kathryn M.; Sebelius, Tamara A.; Ghaffari, Ali H.; Kearns, Kenneth A.; McIntyre, Jean P.; Beachy, Tina M.; Thamattoor, Dasan M.

2002-01-01

The diastereoselective synthesis of ethyl (E)-3-methyl-3-phenylglycidate, a strawberry flavoring agent, is carried out by epoxidizing ethyl trans-b-methylcinnamate with m-chloroperbenzoic acid. This epoxidation is appropriate for the introductory organic laboratory and augments the small number of such experiments currently available for undergraduate education. In the course of performing this exercise, students are exposed to many important facets of organic chemistry such as synthesis, reaction mechanism, stereochemistry, chromatography, quantitative analysis, spectroscopy, and computational chemistry. The 1H NMR spectrum of this compound is especially interesting and presents instructive examples of diastereotopic protons and shielding effects of the aromatic ring current.

Trimeprazine is enantioselectively degraded by an activated sludge in ready biodegradability test conditions.

PubMed

Escuder-Gilabert, Laura; Martín-Biosca, Yolanda; Perez-Baeza, Mireia; Sagrado, Salvador; Medina-Hernández, María José

2018-05-09

A great number of available pharmaceuticals are chiral compounds. Although they are usually manufactured as racemic mixtures, they can be enantioselectively biodegraded as a result of microbial processes. In this paper, a biodegradability assay in similar conditions to those recommended in OECD tests of enantiomers of trimeprazine (a phenothiazine employed as a racemate) is carried out. Experiments were performed in batch mode using a minimal salts medium inoculated with an activated sludge (collected from a Valencian Waste Water Treatment Plant, WWTP) and supplemented with the racemate. The concentration of the enantiomers of trimeprazine were monitored by means of a chiral HPLC method using a cellulose-based chiral stationary phase and 0.5 M NaClO 4 /acetonitrile (60:40, v/v) mobile phases. Experiments were performed at three concentration levels of the racemate. In parallel, the optical density at 600 nm (OD600) was measured to control the biomass growth and to connect it with enantioselectivity. The calculated enantiomeric fractions (EF) offer the first evidence of enantioselective biodegradation of trimeprazine. A simplified Monod equation was used as a curve fitting approach for concentration (S), biodegradation (BD), and for the first time, EF experimental data in order to expand the usefulness of the results. Precision studies on S (repeatability conditions) and, for the first time, EF (intermediate precision conditions) were also performed. Copyright © 2018 Elsevier Ltd. All rights reserved.

Novel beta-cyclodextrin derivative functionalized polymethacrylate-based monolithic columns for enantioselective separation of ibuprofen and naproxen enantiomers in capillary electrochromatography.

PubMed

Tian, Yun; Zhong, Cheng; Fu, Enqin; Zeng, Zhaorui

2009-02-06

A novel enantioselective polymethacrylate-based monolithic column for capillary electrochromatography was prepared by ring-opening reaction of epoxy groups from poly(glycidyl methacrylate-co-ethylene dimethacrylate) monolith with a novel beta-cyclodextrin derivative bearing 4-dimethylamino-1,8-naphthalimide functionalities. Conditions for the ring-opening reaction with respect to different reaction parameters were thoroughly optimized to obtain high electroosmotic flow, separation efficiency and enantioselectivity for the analytes. The nonaqueous mobile phase composition regarding acetonitrile-methanol ratio and the concentration of electrolyte were examined to manipulate the hydrophobic inclusion and anion-exchange interaction between the analytes and chiral stationary phase. It was observed that in addition to beta-cyclodextrin cavity, the electrostatic interaction exhibited pronounced influence on the enantioseparation of acidic analytes. Acidic enantiomers (ibuprofen and naproxen) could be separated with separation factor (alpha) values up to 1.08 and a maximum separation efficiency of 86000 plates/m could be achieved.

Enantioselective α-Alkylation of Aldehydes by Photoredox Organocatalysis: Rapid Access to Pharmacophore Fragments from β-Cyanoaldehydes.

PubMed

Welin, Eric R; Warkentin, Alexander A; Conrad, Jay C; MacMillan, David W C

2015-08-10

The combination of photoredox catalysis and enamine catalysis has enabled the development of an enantioselective α-cyanoalkylation of aldehydes. This synergistic catalysis protocol allows for the coupling of two highly versatile yet orthogonal functionalities, allowing rapid diversification of the oxonitrile products to a wide array of medicinally relevant derivatives and heterocycles. This methodology has also been applied to the total synthesis of the lignan natural product (-)-bursehernin. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Iron-catalyzed olefin epoxidation in the presence of acetic acid: insights into the nature of the metal-based oxidant.

PubMed

Mas-Ballesté, Rubén; Que, Lawrence

2007-12-26

The iron complexes [(BPMEN)Fe(OTf)2] (1) and [(TPA)Fe(OTf)2] (2) [BPMEN = N,N'-bis-(2-pyridylmethyl)-N,N'-dimethyl-1,2-ethylenediamine; TPA = tris-(2-pyridylmethyl)amine] catalyze the oxidation of olefins by H2O2 to yield epoxides and cis-diols. The addition of acetic acid inhibits olefin cis-dihydroxylation and enhances epoxidation for both 1 and 2. Reactions carried out at 0 degrees C with 0.5 mol % catalyst and a 1:1.5 olefin/H2O2 ratio in a 1:2 CH3CN/CH3COOH solvent mixture result in nearly quantitative conversions of cyclooctene to epoxide within 1 min. The nature of the active species formed in the presence of acetic acid has been probed at low temperature. For 2, in the absence of substrate, [(TPA)FeIII(OOH)(CH3COOH)]2+ and [(TPA)FeIVO(NCCH3)]2+ intermediates can be observed. However, neither is the active epoxidizing species. In fact, [(TPA)FeIVO(NCCH3)]2+ is shown to form in competition with substrate oxidation. Consequently, it is proposed that epoxidation is mediated by [(TPA)FeV(O)(OOCCH3)]2+, generated from O-O bond heterolysis of the [(TPA)FeIII(OOH)(CH3COOH)]2+ intermediate, which is promoted by the protonation of the terminal oxygen atom of the hydroperoxide by the coordinated carboxylic acid.

Engineering the Enantioselectivity and Thermostability of a (+)-γ-Lactamase from Microbacterium hydrocarbonoxydans for Kinetic Resolution of Vince Lactam (2-Azabicyclo[2.2.1]hept-5-en-3-one)

PubMed Central

Gao, Shuaihua; Zhu, Shaozhou; Huang, Rong; Li, Hongxia; Wang, Hao

2017-01-01

ABSTRACT To produce promising biocatalysts, natural enzymes often need to be engineered to increase their catalytic performance. In this study, the enantioselectivity and thermostability of a (+)-γ-lactamase from Microbacterium hydrocarbonoxydans as the catalyst in the kinetic resolution of Vince lactam (2-azabicyclo[2.2.1]hept-5-en-3-one) were improved. Enantiomerically pure (−)-Vince lactam is the key synthon in the synthesis of antiviral drugs, such as carbovir and abacavir, which are used to fight against HIV and hepatitis B virus. The work was initialized by using the combinatorial active-site saturation test strategy to engineer the enantioselectivity of the enzyme. The approach resulted in two mutants, Val54Ser and Val54Leu, which catalyzed the hydrolysis of Vince lactam to give (−)-Vince lactam, with 99.2% (enantiomeric ratio [E] > 200) enantiomeric excess (ee) and 99.5% ee (E > 200), respectively. To improve the thermostability of the enzyme, 11 residues with high temperature factors (B-factors) calculated by B-FITTER or high root mean square fluctuation (RMSF) values from the molecular dynamics simulation were selected. Six mutants with increased thermostability were obtained. Finally, the mutants generated with improved enantioselectivity and mutants evolved for enhanced thermostability were combined. Several variants showing (+)-selectivity (E value > 200) and improved thermostability were observed. These engineered enzymes are good candidates to serve as enantioselective catalysts for the preparation of enantiomerically pure Vince lactam. IMPORTANCE Enzymatic kinetic resolution of the racemic Vince lactam using (+)-γ-lactamase is the most often utilized means of resolving the enantiomers for the preparation of carbocyclic nucleoside compounds. The efficiency of the native enzymes could be improved by using protein engineering methods, such as directed evolution and rational design. In our study, two properties (enantioselectivity and

Engineering the Enantioselectivity and Thermostability of a (+)-γ-Lactamase from Microbacterium hydrocarbonoxydans for Kinetic Resolution of Vince Lactam (2-Azabicyclo[2.2.1]hept-5-en-3-one).

PubMed

Gao, Shuaihua; Zhu, Shaozhou; Huang, Rong; Li, Hongxia; Wang, Hao; Zheng, Guojun

2018-01-01

To produce promising biocatalysts, natural enzymes often need to be engineered to increase their catalytic performance. In this study, the enantioselectivity and thermostability of a (+)-γ-lactamase from Microbacterium hydrocarbonoxydans as the catalyst in the kinetic resolution of Vince lactam (2-azabicyclo[2.2.1]hept-5-en-3-one) were improved. Enantiomerically pure (-)-Vince lactam is the key synthon in the synthesis of antiviral drugs, such as carbovir and abacavir, which are used to fight against HIV and hepatitis B virus. The work was initialized by using the combinatorial active-site saturation test strategy to engineer the enantioselectivity of the enzyme. The approach resulted in two mutants, Val54Ser and Val54Leu, which catalyzed the hydrolysis of Vince lactam to give (-)-Vince lactam, with 99.2% (enantiomeric ratio [E] > 200) enantiomeric excess (ee) and 99.5% ee (E > 200), respectively. To improve the thermostability of the enzyme, 11 residues with high temperature factors (B-factors) calculated by B-FITTER or high root mean square fluctuation (RMSF) values from the molecular dynamics simulation were selected. Six mutants with increased thermostability were obtained. Finally, the mutants generated with improved enantioselectivity and mutants evolved for enhanced thermostability were combined. Several variants showing (+)-selectivity (E value > 200) and improved thermostability were observed. These engineered enzymes are good candidates to serve as enantioselective catalysts for the preparation of enantiomerically pure Vince lactam. IMPORTANCE Enzymatic kinetic resolution of the racemic Vince lactam using (+)-γ-lactamase is the most often utilized means of resolving the enantiomers for the preparation of carbocyclic nucleoside compounds. The efficiency of the native enzymes could be improved by using protein engineering methods, such as directed evolution and rational design. In our study, two properties (enantioselectivity and thermostability) of a �

Enantioselective and Regioselective Indium(III)-Catalyzed Addition of Pyrroles to Isatins

PubMed Central

Gutierrez, Elisa G.; Wong, Casey J.; Sahin, Aziza H.

2011-01-01

The indium(III)-catalyzed enantioselective and regioselective addition of pyrroles to isatins is described. The effects of metal and solvent on the reactivity and selectivity are compared and discussed, demonstrating that the indium(III)-indapybox complex provides the most effective catalyst. A case of divergent reactivity between pyrroles and indoles is presented. PMID:21992567

Infrared spectroscopy and molecular simulations of a polymeric sorbent and its enantioselective interactions with benzoin enantiomers.

PubMed

Tsui, Hung-Wei; Willing, Jonathan N; Kasat, Rahul B; Wang, Nien-Hwa Linda; Franses, Elias I

2011-11-10

Retention factors, k(R) and k(S), and enantioselectivities, S ≡ k(R)/k(S), of amylose tris[(S)-α-methylbenzylcarbamate] (AS) sorbent for benzoin (B) enantiomers were measured for various isopropyl alcohol (IPA)/n-hexane compositions of the high-performance liquid chromatography (HPLC) mobile phase. Novel data for pure n-hexane show that k(R) = 106, k(S) = 49.6, and S = 2.13. With some IPA from 0.5 to 10 vol %, with S = 1.8-1.4, the retention factors were smaller. Infrared spectra showed evidence of substantial hydrogen bonding (H-bonding) interactions in the pure polymer phase and additional H-bonding interactions between AS and benzoin. Density functional theory (DFT) was used to model the chain-chain and chain-benzoin H-bonding and other interactions. DFT was also used to predict fairly well the IR wavenumber shifts caused by the H-bonds. DFT simulations of IR bands of NH and C═O allowed for the first time the predictions of relative intensities and relative populations of H-bonding strengths. Molecular dynamics (MD) simulations were used to model a single 12-mer polymer chain. MD simulations predicted the existence of various potentially enantioselective cavities, two of which are sufficiently large to accommodate a benzoin molecule. Then "docking" studies of benzoin in AS with MD, Monte Carlo (MC), and MC/MD simulations were done to probe the AS-B interactions. The observed enantioselectivities are predicted to be primarily due to two H-bonds, of the kind AS CO···HO (R)-benzoin and AS NH···OC (R)-benzoin, and two π-π (phenyl-phenyl) interactions for (R)-benzoin and one H-bond, of type AS CO···HO (S)-benzoin, and one π-π interaction for (S)-benzoin. The MC/MD predictions are consistent with the HPLC and IR results.

Tandem Reactions for Streamlining Synthesis

PubMed Central

HUSSAIN, MAHMUD M.; WALSH, PATRICK J.

2009-01-01

CONSPECTUS In 1980 Sharpless and Katsuki introduced the asymmetric epoxidation of prochiral allylic alcohols (the Sharpless-Katsuki Asymmetric Epoxidation), which enabled the rapid synthesis of highly enantioenriched epoxy alcohols. This reaction was a milestone in the development of asymmetric catalysis because it was the first highly enantioselective oxidation reaction. Furthermore, it provided access to enantioenriched allylic alcohols that are now standard starting materials in natural product synthesis. In 1981 Sharpless and coworkers made another seminal contribution by describing the kinetic resolution (KR) of racemic allylic alcohols. This work demonstrated that small-molecule catalysts could compete with enzymatic catalysts in KRs. For these pioneering works, Sharpless was awarded the 2001 Nobel Prize with Knowles and Noyori. Despite these achievements, the Sharpless KR is not an efficient method to prepare epoxy alcohols with high enantiomeric excess (ee). First, the racemic allylic alcohol must be prepared and purified. KR of the racemic allylic alcohol must be stopped at low conversion, because the ee of the product epoxy alcohol decreases as the KR progresses. Thus, better methods to prepare epoxy alcohols containing stereogenic carbinol carbons are needed. This Account summarizes our efforts to develop one-pot methods for the synthesis of various epoxy alcohols and allylic epoxy alcohols with high enantio-, diastereo-, and chemoselectivity. Our laboratory developed titanium-based catalysts for use in the synthesis of epoxy alcohols with tertiary carbinols. The catalysts are involved in the first step, which is an asymmetric alkyl or allyl addition to enones. The resulting intermediates are then subjected to a titanium-directed diastereoselective epoxidation to provide tertiary epoxy alcohols. Similarly, the synthesis of acyclic epoxy alcohols begins with asymmetric additions to enals and subsequent epoxidation. The methods described here enable the

A Computational Study of Acid Catalyzed Aerosol Reactions of Atmospherically Relevant Epoxides

EPA Science Inventory

Epoxides are important intermediates of atmospheric isoprene oxidation. Their subsequent reactions in the particle phase lead to the production of organic compounds detected in ambient aerosols. We apply density functional theory to determine the important kinetic factors that ...

The application of chiral ultra-high-performance liquid chromatography tandem mass spectrometry to the separation of the zoxamide enantiomers and the study of enantioselective degradation process in agricultural plants.

PubMed

Pan, Xinglu; Dong, Fengshou; Chen, Zenglong; Xu, Jun; Liu, Xingang; Wu, Xiaohu; Zheng, Yongquan

2017-11-24

In this study, an effective and sensitive chiral analytical method was developed to detect zoxamide enantiomers in vegetables, fruits and environmental matrices using ultra-high-performance liquid chromatography-tandem mass spectrometry. Optimal separation conditions were achieved with Lux Amylose-2 chiral column using acetonitrile/water (70:30v/v) as mobile phase with a flow rate and column temperature of 0.5mL/min and 25°C. The absolute configuration, optical rotation and elution order were confirmed for the first time. The average recoveries in all matrices at four spiking levels (0.5, 5, 50, 250μg/kg) ranged from 89.7 to 117.4%, with relative standard deviations being less than 10.9% for two enantiomers. The enantioselective dissipation of zoxamide in tomato showed that (-)-R-zoxamide was preferentially degraded leading to an enrichment of (+)-S-isomer, with half-lives of 3.80 d and 5.17 d, respectively. Inversely, (+)-S-zoxamide degraded faster than (-)-R-zoxamide in pepper (1.95day and 2.28day, respectively) and grape (2.03day and 2.87day). No significant enantioselectivity was observed in cucumber. The results of this study could help facilitate more accurate risk assessments of zoxamide in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

Enantioselective Effects of o,p'-DDT on Cell Invasion and Adhesion of Breast Cancer Cells: Chirality in Cancer Development.

PubMed

He, Xiangming; Dong, Xiaowu; Zou, Dehong; Yu, Yang; Fang, Qunying; Zhang, Quan; Zhao, Meirong

2015-08-18

The o,p'-dichlorodiphenyltrichloroethane (DDT) with a chiral center possesses enantioselective estrogenic activity, in which R-(-)-o,p'-DDT exerts a more potent estrogenic effect than S-(+)-o,p'-DDT. Although concern regarding DDT exposure and breast cancer has increased in recent decades, the mode of enantioselective action of o,p'-DDT in breast cancer development is still unknown. Herein, we conducted a systematic study of the effect of o,p'-DDT on stereoselective breast tumor cell progression in a widely used in vitro breast tumor cell model, MCF-7 cells. We demonstrated that R-(-)-o,p'-DDT promoted more cancer cell invasion mediated by the human estrogen receptor (ER) by inducing invasion-promoted genes (matrix metalloproteinase-2 and -9 and human telomerase reverse transcriptase) and inhibiting invasion-inhibited genes (tissue inhibitor of metalloproteinase-1 and -4). Molecular docking verified that the binding affinity between R-(-)-o,p'-DDT and human ER was stronger than that of S-(+)-o,p'-DDT. The enantioselective-induced decrease in cell-to-cell adhesion may involve the downregulation of adhesion-promoted genes (E-cadherin and β-catenin). For the first time, these results reveal that estrogenic-like chiral compounds are of significant concern in the progression of human cancers and that human health risk assessment of chiral chemicals should consider enantioselectivity.

Enantioselective modular synthesis of cyclohexenones: total syntheses of (+)-crypto- and (+)-infectocaryone.

PubMed

Franck, Géraldine; Brödner, Kerstin; Helmchen, Günter

2010-09-03

A modular synthesis of cyclohexenones is described and applied to the first enantioselective total syntheses of (+)-crypto- and (+)-infectocaryone. Key steps in the synthesis of cyclohexenones are an iridium-catalyzed allylic alkylation, nucleophilic allylation, and ring-closing metathesis. On the way to (+)-cryptocaryone, a catch and release strategy involving an iodolactonization/elimination and a regioselective C-acylation were used.

Enantioselective biodegradation of the pyrethroid (±)-lambda-cyhalothrin by marine-derived fungi.

PubMed

Birolli, Willian G; Vacondio, Bruna; Alvarenga, Natália; Seleghim, Mirna H R; Porto, André L M

2018-04-01

The contamination of agricultural lands by pesticides is a serious environmental issue. Consequently, the development of bioremediation methods for different active ingredients, such as pyrethroids, is essential. In this study, the enantioselective biodegradation of (±)-lambda-cyhalothrin ((±)-LC) by marine-derived fungi was studied. Experiments were performed with different fungi strains (Aspergillus sp. CBMAI 1829, Acremonium sp. CBMAI 1676, Microsphaeropsis sp. CBMAI 1675 and Westerdykella sp. CBMAI 1679) in 3% malt liquid medium with 100 mg L -1 of (±)-LC. All strains biodegraded this insecticide and the residual concentrations of (±)-LC (79.2-55.2 mg L -1 , i.e., 20.8-44.8% biodegradation), their enantiomeric excesses (2-42% ee) and the 3-phenoxybenzoic acid (PBAc) concentrations (0.0-4.1 mg L -1 ) were determined. In experiments for 28 days of biodegradation in the absence and presence of artificial seawater (ASW) with the most efficient strain Aspergillus sp. CBMAI 1829, increasing concentrations of PBAc with (0.0-4.8 mg L -1 ) and without ASW (0.0-15.3 mg L -1 ) were observed. In addition, a partial biodegradation pathway was proposed. All the evaluated strains biodegraded preferentially the (1R,3R,αS)-gamma-cyhalothrin enantiomer. Therefore, marine-derived fungi enantioselectively biodegraded (±)-LC and can be applied in future studies for bioremediation of contaminated areas. This enantioselective biodegradation indicates that the employment of the most active enantiomer GC as insecticide not only enable the use of a lower amount of pesticide, but also a more easily biodegradable product, reducing the possibility of environmental contamination. Copyright © 2018 Elsevier Ltd. All rights reserved.

Enantioselective organocatalytic one-pot amination/aza-Michael/aldol condensation reaction sequence: synthesis of 3-pyrrolines with a quaternary stereocenter.

PubMed

Desmarchelier, Alaric; Coeffard, Vincent; Moreau, Xavier; Greck, Christine

2012-10-08

Primary amine-catalyzed direct conversion of α,α-disubstituted aldehydes into 3-pyrrolines with a quaternary stereocenter is reported. The one-pot enantioselective sequence is based on a α-amination, an aza-Michael addition of hydrazine, an aldol condensation dehydratation and proceeds with good yields and excellent levels of enantioselectivity. Synthetically attractive applications including the formation of aziridinopyrrolidine or epoxypyrrolidine derivatives with good yields and selectivities are also described. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Förster resonance energy transfer competitive displacement assay for human soluble epoxide hydrolase

PubMed Central

Lee, Kin Sing Stephen; Morisseau, Christophe; Yang, Jun; Wang, Peng; Hwang, Sung Hee; Hammock, Bruce D.

2013-01-01

The soluble epoxide hydrolase (sEH), responsible for the hydrolysis of various fatty acid epoxides to their corresponding 1,2-diols, is becoming an attractive pharmaceutical target. These fatty acid epoxides, particularly epoxyeicosatrienoic acids (EETs), play an important role in human homeostatic and inflammation processes. Therefore, inhibition of human sEH, which stabilizes EETs in vivo, brings several beneficial effects to human health. Although there are several catalytic assays available to determine the potency of sEH inhibitors, measuring the in vitro inhibition constant (Ki) for these inhibitors using catalytic assay is laborious. In addition, koff, which has been recently suggested to correlate better with the in vivo potency of inhibitors, has never been measured for sEH inhibitors. To better measure the potency of sEH inhibitors, a reporting ligand, 1-(adamantan-1-yl)-3-(1-(2-(7-hydroxy-2-oxo-2H-chromen-4-yl)acetyl) piperidin-4-yl)urea (ACPU), was designed and synthesized. With ACPU, we have developed a Förster resonance energy transfer (FRET)-based competitive displacement assay using intrinsic tryptophan fluorescence from sEH. In addition, the resulting assay allows us to measure the Ki values of very potent compounds to the picomolar level and to obtain relative koff values of the inhibitors. This assay provides additional data to evaluate the potency of sEH inhibitors. PMID:23219719

Conazole Fungicides as Chiral Environmental Contaminants: Enantiomer Analysis and Enantioselectivity in Soil Slurries

EPA Science Inventory

Conazoles are triazole compounds, many of which are in wide use as agricultural and medicinal fungicides. Opportunities exist for them to contaminate the environment and, since they are all chiral molecules, they are apt to be degraded enantioselectively by indigenous microbes. T...

Towards the Synthesis of Dihydrooxepino[4,3-b]pyrrole-Containing Natural Products via Cope Rearrangement of Vinyl Pyrrole Epoxides.

PubMed

Cameron, Alex; Fisher, Brendan; Fisk, Nicholas; Hummel, Jessica; White, Jonathan M; Krenske, Elizabeth H; Rizzacasa, Mark A

2015-12-18

An approach to the dihydrooxepino[4,3-b]pyrrole core of diketopiperazine natural products which utilizes a vinyl pyrrole epoxide Cope rearrangement was investigated. It was found that an ester substituent on the epoxide was essential for the [3,3]-rearrangement to occur. Density functional calculations with M06-2X provided explanations for the effects of the pyrrole and ester groups on these rearrangements.

Enantioselective toxic effects of cyproconazole enantiomers against Chlorella pyrenoidosa.

PubMed

Zhang, Wenjun; Cheng, Cheng; Chen, Li; Di, Shanshan; Liu, Chunxiao; Diao, Jinling; Zhou, Zhiqiang

2016-09-01

Enantioselectivity in ecotoxicity, digestion and uptake of chiral pesticide cyproconazole to Chlorella pyrenoidosa was studied. The 96h-EC50 values of rac- and the four enantiomers were 9.005, 6.616, 8.311, 4.290 and 9.410 mg/L, respectively. At the concentrations of 8 mg/L and 14 mg/L, the contents of pigments exposed in rac-, enantiomer-2 and 4 were higher than that exposed in enantiomer-1 and 3. The superoxide dismutase (SOD) and catalase (CAT) activity of algae exposed to enantiomer-1 and 3 was higher than that exposed to the rac-, enantiomer-2 and 4 at three levels. In addition, the malondialdehyde (MDA) concentrations in algae disposed with enantiomer-1 and 3 were increased remarkably at three levels. For the digestion experiment, the half-lives of four enantiomers in algae suspension were 28.06, 19.10, 21.13, 15.17 days, respectively. During the uptake experiment, the order of the concentrations of cyproconazole in algae cells was enantiomer-4, 2, 3 and 1. Based on these data, we concluded that ecotoxicity, digestion and uptake of chiral pesticide cyproconazole to C. pyrenoidosa were enantioselective, and such enantiomeric differences must be taken into consideration when assessing the risk of cyproconazole to environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Simple Primary Amine Catalyst for Enantioselective α-Hydroxylations and α-Fluorinations of Branched Aldehydes

PubMed Central

Witten, Michael R.; Jacobsen, Eric N.

2016-01-01

A new primary amine catalyst for the asymmetric α-hydroxylation and α-fluorination of α-branched aldehydes is described. The products of the title transformations are generated in excellent yields and with high enantioselectivities. Both processes can be performed within short reaction times and on gram scale. The similarity in the results obtained in both reactions, combined with computational evidence, implies a common basis for stereoinduction and the possibility of a general catalytic mechanism for α-functionalizations. Promising initial results in α-amination and α-chlorination reactions support this hypothesis. PMID:25952578

A Simple Primary Amine Catalyst for Enantioselective α-Hydroxylations and α-Fluorinations of Branched Aldehydes.

PubMed

Witten, Michael R; Jacobsen, Eric N

2015-06-05

A new primary amine catalyst for the asymmetric α-hydroxylation and α-fluorination of α-branched aldehydes is described. The products of the title transformations are generated in excellent yields with high enantioselectivities. Both processes can be performed within short reaction times and on gram scale. The similarity in results obtained in both reactions, combined with computational evidence, implies a common basis for stereoinduction and the possibility of a general catalytic mechanism for α-functionalizations. Promising initial results in α-amination and α-chlorination reactions support this hypothesis.

Epoxidation with Possibilities: Discovering Stereochemistry in Organic Chemistry via Coupling Constants

ERIC Educational Resources Information Center

Treadwell, Edward M.; Yan, Zhiqing; Xiao, Xiao

2017-01-01

A one-day laboratory epoxidation experiment, requiring no purification, is described, wherein the students are given an "unknown" stereoisomer of 3-hexen-1-ol, and use [superscript 1]H NMR coupling constants to determine the stereochemistry of their product. From this they work backward to determine the stereochemistry of their starting…

Acute toxicity, bioactivity, and enantioselective behavior with tissue distribution in rabbits of myclobutanil enantiomers.

PubMed

Sun, Mingjing; Liu, Donghui; Qiu, Xinxu; Zhou, Qian; Shen, Zhigang; Wang, Peng; Zhou, Zhiqiang

2014-12-01

The enantioselective bioactivity against pathogens (Cercospora arachidicola, Fulvia fulva, and Phytophthora infestans) and acute toxicity to Daphnia magna of the fungicide myclobutanil enantiomers were studied. The (+)-enantiomer in an antimicrobial activity test was about 1.79-1.96 times more active than the (-)-enantiomer. In the toxicity assay, the calculated 24-h LC50 values of the (-)-form, rac-form and (+)-form were 16.88, 13.17, and 11.91 mg/L, and the 48-h LC50 values were 10.15, 9.24, and 5.48 mg/L, respectively, showing that (+)-myclobutanil was more toxic. Meanwhile, the enantioselective metabolism of myclobutanil enantiomers following a single intravenous (i.v.) administration was investigated in rabbits. Total plasma clearance value (CL) of the (+)-enantiomer was 1.68-fold higher than its antipode. Significant differences in pharmacokinetics parameters between the two enantiomers indicated that the high bioactive (+)-enantiomer was preferentially metabolized and eliminated in plasma. Consistent consequences were found in the tissues (liver, brain, heart, kidney, fat, and muscle), resulting in a relative enrichment of the low-activity (-)-myclobutanil. These systemic assessments of the stereoisomers of myclobutanil cannot be used only to investigate environmental and biological behavior, but also have human health implications because of the long persistence of triazole fungicide and enantiomeric enrichment in mammals and humans. © 2014 Wiley Periodicals, Inc.

Is the mu-oxo-mu-peroxodiiron intermediate of a ribonucleotide reductase biomimetic a possible oxidant of epoxidation reactions?

PubMed

de Visser, Sam P

2008-01-01

Density functional calculations on a mu-oxo-mu-peroxodiiron complex (1) with a tetrapodal ligand BPP (BPP=N,N-bis(2-pyridylmethyl)-3-aminopropionate) are presented that is a biomimetic of the active site region of ribonucleotide reductase (RNR). We have studied all low-lying electronic states and show that it has close-lying broken-shell singlet and undecaplet (S=0, 5) ground states with essentially two sextet spin iron atoms. In strongly distorted electronic systems in which the two iron atoms have different spin states, the peroxo group moves considerably out of the plane of the mu-oxodiiron group due to orbital rearrangements. The calculated absorption spectra of (1,11)1 are in good agreement with experimental studies on biomimetics and RNR enzyme systems. Moreover, vibrational shifts in the spectrum due to (18)O(2) substitution of the oxygen atoms in the peroxo group follow similar trends as experimental observations. To identify whether the mu-oxo-mu-1,2-peroxodiiron or the mu-oxo-mu-1,1-peroxodiiron complexes are able to epoxidize substrates, we studied the reactivity patterns versus propene. Generally, the reactions are stepwise via radical intermediates and proceed by two-state reactivity patterns on competing singlet and undecaplet spin state surfaces. However, both the mu-oxo-mu-1,2-peroxodiiron and mu-oxo-mu-1,1-peroxodiiron complex are sluggish oxidants with high epoxidation barriers. The epoxidation barriers for the mu-oxo-mu-1,1-peroxodiiron complex are significantly lower than the ones for the mu-oxo-mu-1,2-peroxodiiron complex but still are too high to be considered for catalytic properties. Thus, theory has ruled out two possible peroxodiiron catalysts as oxidants in RNR enzymes and biomimetics and the quest to find the actual oxidant in the enzyme mechanism continues.

Reproducible Preparation of Au/TS-1 with High Reaction Rate for Gas Phase Epoxidation of Propylene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee W. S.; Stach E.; Akatay, M.C.

2012-03-01

A refined and reliable synthesis procedure for Au/TS-1(Si/Ti molar ratio {approx}100) with high reaction rate for the direct gas phase epoxidation of propylene has been developed by studying the effects of pH of the gold slurry solution, mixing time, and preparation temperature for deposition precipitation (DP) of Au on TS-1 supports. Au/TS-1 catalysts prepared at optimal DP conditions (pH {approx} 7.3, mixing for 9.5 h, room temperature) showed an average PO rate {approx} 160 g{sub PO} h{sup -1} kg{sub Cat}{sup -1} at 200 C at 1 atm. A reproducibility better than {+-}10% was demonstrated by nine independent samples prepared atmore » the same conditions. These are the highest rates yet reported at 200 C. No visible gold particles were observed by the HRTEM analysis in the fresh Au/TS-1 with gold loading up to {approx}0.1 wt%, indicating that the gold species were smaller than 1 nm. Additionally, the rate per gram of Au and the catalyst stability increased as the Au loading decreased, giving a maximum value of 500 g{sub PO} h{sup -1} g{sub Au}{sup -1}, and Si/Ti molar ratios of {approx}100 gave the highest rates.« less

Enantioselective column coupled electrophoresis employing large bore capillaries hyphenated with tandem mass spectrometry for ultra-trace determination of chiral compounds in complex real samples.

PubMed

Piešťanský, Juraj; Maráková, Katarína; Kovaľ, Marián; Havránek, Emil; Mikuš, Peter

2015-12-01

A new multidimensional analytical approach for the ultra-trace determination of target chiral compounds in unpretreated complex real samples was developed in this work. The proposed analytical system provided high orthogonality due to on-line combination of three different methods (separation mechanisms), i.e. (1) isotachophoresis (ITP), (2) chiral capillary zone electrophoresis (chiral CZE), and (3) triple quadrupole mass spectrometry (QqQ MS). The ITP step, performed in a large bore capillary (800 μm), was utilized for the effective sample pretreatment (preconcentration and matrix clean-up) in a large injection volume (1-10 μL) enabling to obtain as low as ca. 80 pg/mL limits of detection for the target enantiomers in urine matrices. In the chiral CZE step, the different chiral selectors (neutral, ionizable, and permanently charged cyclodextrins) and buffer systems were tested in terms of enantioselectivity and influence on the MS detection response. The performance parameters of the optimized ITP - chiral CZE-QqQ MS method were evaluated according to the FDA guidance for bioanalytical method validation. Successful validation and application (enantioselective monitoring of renally eliminated pheniramine and its metabolite in human urine) highlighted great potential of this chiral approach in advanced enantioselective biomedical applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselectivity in CPA-catalyzed Friedel-Crafts reaction of indole and N-tosylimines: a challenge for guiding models.

PubMed

Simón, Luis

2018-03-28

Qualitative reaction models or predicting guides are a very useful outcome of theoretical investigations of organocatalytic reaction mechanism that allow forecasting of the degree and sense of the enantioselectivity of reactions involving novel substrates. However, application of these models can be unexpectedly challenging in reactions affected by a large number of conformations and potential control of the enantioselectivity by different reaction steps. The QM/MM study of the Friedel-Crafts reaction between indole and the N-tosylimide of benzaldehyde catalysed by different CPA reveals that the reaction consists of two CPA-assisted steps: the addition of the two reagents to yield a Wheland intermediate, and its re-aromatization. The relevance of the second step depends on the catalyst: it changes the sense of the expected stereoselectivity for a BINOP-derived CPA but is irrelevant in the reaction catalysed by a VAPOL-derived imidodiphosphoric acid catalyst. Although the relative energies of the TSs can be rationalized considering the steric interactions with the catalyst, the possibility of additional H-bonds, or the relative stability of the conformation of the reagents, predicting the enantioselectivity is not possible using qualitative guides.

40 CFR 63.1431 - Process vent annual epoxides emission factor plan requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., recovery, or recapture device, along with the expected percent efficiency. (iii) Annual emissions after the... section, kg/yr. R = Expected control efficiency of the combustion, recovery, or recapture device, percent....1426(c) to determine the epoxide control efficiency of the combustion, recovery, or recapture device...

40 CFR 63.1431 - Process vent annual epoxides emission factor plan requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., recovery, or recapture device, along with the expected percent efficiency. (iii) Annual emissions after the... section, kg/yr. R = Expected control efficiency of the combustion, recovery, or recapture device, percent....1426(c) to determine the epoxide control efficiency of the combustion, recovery, or recapture device...

Formation of furan fatty alkyl esters from their bis-epoxide fatty esters

USDA-ARS?s Scientific Manuscript database

Reactions of epoxidized alkyl soyate with four different alcohols: ethanol, isopropyl alcohol, 2-ethylhexanol, and benzyl alcohol were investigated in the presence of Bronsted acid catalyst. Products not reported in prior studies of similar reactions were found. These were furan fatty acid alkyl est...

Formation of furan fatty alkyl esters from their bis-epoxide fatty esters

USDA-ARS?s Scientific Manuscript database

Reactions of epoxidized alkyl soyate with four different alcohols: ethanol, isopropyl alcohol, 2-ethylhexanol, benzyl alcohol, in the presence of Bronsted acid catalyst, were investigated. Products that were not reported in prior studies of similar reactions were found. These were furan fatty acid a...

Rhodium-catalyzed sequential allylic amination and olefin hydroacylation reactions: enantioselective synthesis of seven-membered nitrogen heterocycles.

PubMed

Arnold, Jeffrey S; Mwenda, Edward T; Nguyen, Hien M

2014-04-01

Dynamic kinetic asymmetric amination of branched allylic acetimidates has been applied to the synthesis of 2-alkyl-dihydrobenzoazepin-5-ones. These seven-membered-ring aza ketones are prepared in good yield with high enantiomeric excess by rhodium-catalyzed allylic substitution with 2-amino aryl aldehydes followed by intramolecular olefin hydroacylation of the resulting alkenals. This two-step procedure is amenable to varied functionality and proves useful for the enantioselective preparation of these ring systems. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective Bioaccumulation and Toxicity of the Neonicotinoid Insecticide Dinotefuran in Earthworms ( Eisenia fetida).

PubMed

Liu, Tong; Chen, Dan; Li, Yiqiang; Wang, Xiuguo; Wang, Fenglong

2018-05-02

The enantioselective bioaccumulation and toxicity of dinotefuran in earthworms were studied in this study. The results showed that S-dinotefuran accumulated faster than Rac-dinotefuran and R-dinotefuran in earthworms. The acute toxicity of S-dinotefuran was 1.49 and 2.67 times that of the Rac-dinotefuran and R-dinotefuran in artificial soil during 14 days of exposure. At 1.0 mg/kg, the three tested chemicals inhibited the growth and reproduction as well as induced oxidative stress effects in earthworms; however, the toxic effects induced by S-dinotefuran were the most serious. The transcriptome sequencing results showed that S-dinotefuran had stronger interactions to biomacromolecules and influences on the endoplasmic reticulum (ER) than R-dinotefuran, which may be the main reason for enantioselectivities between the two enantiomers. The present results indicated that the risk of S-dinotefuran was higher than that of Rac-dinotefuran and R-dinotefuran in the soil environment to earthworms. Risk assessment of dinotefuran should be evaluated at the enantiomer level.

Enantioselective toxic effects and degradation of myclobutanil enantiomers in Scenedesmus obliquus.

PubMed

Cheng, Cheng; Huang, Ledan; Diao, Jinling; Zhou, Zhiqiang

2013-12-01

Research on the enantioselective environmental behavior of chiral pesticides has been a hot spot of environmental chemistry recently. In this study, the acute toxicity of myclobutanil enantiomers was investigated with the aquatic algae Scendesmus obliquus. After exposure for 96 h, the EC50 values for (-)-myclobutanil, rac-myclobutanil and (+)-myclobutanil were 3.951, 2.760, and 2.128 mg/L, respectively. The photosynthetic pigment (chlorophyll a, chlorophyll b, and carotenoids) and antioxidant enzyme activities catalase (CAT) were determined to evaluate the different toxic effects when S. obliquus were exposed to 1.5, 5 and 15 mg/L of rac-myclobutanil, (-)-myclobutanil, and (+)-myclobutanil for 96 h, respectively. In addition, the degradation of myclobutanil enantiomers in S. obliquus was also studied. Myclobutanil in the medium inoculated with algae degraded faster than in the uninoculated medium. The degradation of (-)-myclobutanil was faster than that of (+)-myclobutanil at a concentration of 3 mg/L. On the basis of these data, the acute toxicity and toxic effects of myclobutanil against S. obliquus were concluded to be enantioselective, and such enantiomeric differences should be taken into consideration in pesticide risk assessment. © 2013 Wiley Periodicals, Inc.

Enantioselective construction of quaternary stereogenic carbons by the Lewis base catalyzed additions of silyl ketene imines to aldehydes.

PubMed

Denmark, Scott E; Wilson, Tyler W; Burk, Matthew T; Heemstra, John R

2007-12-05

Silyl ketene imines derived from a variety of alpha-branched nitriles have been developed as highly useful reagents for the construction of quaternary stereogenic centers via the aldol addition reaction. In the presence of SiCl4 and the catalytic action of chiral phosphoramide (R,R)-5, silyl ketene imines undergo extremely rapid and high yielding addition to a wide variety of aromatic aldehydes with excellent diastereo- and enantioselectivity. Of particular note is the high yields and selectivities obtained from electron-rich, electron-poor, and hindered aldehydes. The nitrile function serves as a useful precursor for further synthetic manipulation.

Biobased composites from thermoplastic polyurethane elastomer and cross-linked acrylated-epoxidized soybean oil

USDA-ARS?s Scientific Manuscript database

Soybean oil is an important sustainable material. Crosslinked acrylated epoxidized soybean oil (AESO) is brittle without flexibility and the incorporation of thermoplastic polyurethane improves its toughness for industrial applications. The hydrophilic functional groups from both oil and polyurethan...

Kinetic Resolution of sec-Thiols by Enantioselective Oxidation with Rationally Engineered 5-(Hydroxymethyl)furfural Oxidase.

PubMed

Pickl, Mathias; Swoboda, Alexander; Romero, Elvira; Winkler, Christoph K; Binda, Claudia; Mattevi, Andrea; Faber, Kurt; Fraaije, Marco W

2018-03-05

Various flavoprotein oxidases were recently shown to oxidize primary thiols. Herein, this reactivity is extended to sec-thiols by using structure-guided engineering of 5-(hydroxymethyl)furfural oxidase (HMFO). The variants obtained were employed for the oxidative kinetic resolution of racemic sec-thiols, thus yielding the corresponding thioketones and nonreacted R-configured thiols with excellent enantioselectivities (E≥200). The engineering strategy applied went beyond the classic approach of replacing bulky amino acid residues with smaller ones, as the active site was additionally enlarged by a newly introduced Thr residue. This residue established a hydrogen-bonding interaction with the substrates, as verified in the crystal structure of the variant. These strategies unlocked HMFO variants for the enantioselective oxidation of a range of sec-thiols. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Organocatalytic Enantioselective Michael/Cyclization Domino Reaction between 3-Amideoxindoles and α,β-Unsaturated Aldehydes: One-Pot Preparation of Chiral Spirocyclic Oxindole-γ-lactams.

PubMed

Yang, Peng; Wang, Xiao; Chen, Feng; Zhang, Zheng-Bing; Chen, Chao; Peng, Lin; Wang, Li-Xin

2017-04-07

The first organocatalytic enantioselective Michael/cyclization domino reaction between 3-amideoxindoles and α,β-unsaturated aldehydes is described. After sequential oxidation with pyridinium chlorochromate, a direct and one-pot preparation of highly sterically hindered spirocyclic oxindole-γ-lactams was achieved in 51-81% yields with 75-97% ee and ≤80/20 dr.

Enantioselective recognition of mandelic acid by a 3,6-dithiophen-2-yl-9H-carbazole-based chiral fluorescent bisboronic acid sensor.

PubMed

Wu, Yubo; Guo, Huimin; James, Tony D; Zhao, Jianzhang

2011-07-15

We have prepared chiral fluorescent bisboronic acid sensors with 3,6-dithiophen-2-yl-9H-carbazole as the fluorophore. The thiophene moiety was used to extend the π-conjugation framework of the fluorophore in order to red-shift the fluorescence emission and, at the same time, to enhance the novel process where the fluorophore serves as the electron donor of the photoinduced electron transfer process (d-PET) of the boronic acid sensors; i.e., the background fluorescence of the sensor 1 at acidic pH is weaker compared to that at neutral or basic pH, in stark contrast to the typical a-PET boronic acid sensors (where the fluorophore serves as the electron acceptor of the photoinduced electron transfer process). The benefit of the d-PET boronic acid sensors is that the recognition of the hydroxylic acids can be achieved at acidic pH. We found that the thiophene moiety is an efficient π-conjugation linker and electron donor; as a result, the d-PET contrast ratio of the sensors upon variation of the pH is improved 10-fold when compared to the previously reported d-PET sensors without the thiophene moiety. Enantioselective recognition of tartaric acid was achieved at acid pH, and the enantioselectivity (total response K(D)I(F)(D)/K(L)I(F)(L)) is 3.3. The fluorescence enhancement (I(F)(Sample)/I(F)(Blank)) of sensor 1 upon binding with tartaric acid is 3.5-fold at pH 3.0. With the fluorescent bisboronic acid sensor 1, enantioselective recognition of mandelic acid was achieved for the first time. To the best of our knowledge, this is the first time that the mandelic acid has been enantioselectively recognized using a chiral fluorescent boronic acid sensor. Chiral monoboronic acid sensor 2 and bisboronic acid sensor 3 without the thiophene moiety failed to enantioselectively recognize mandelic acid. Our findings with the thiophene-incorporated boronic acid sensors will be important for the design of d-PET fluorescent sensors for the enantioselective recognition of �

A dual Lewis base activation strategy for enantioselective carbene-catalyzed annulations.

PubMed

Izquierdo, Javier; Orue, Ane; Scheidt, Karl A

2013-07-24

A dual activation strategy integrating N-heterocyclic carbene (NHC) catalysis and a second Lewis base has been developed. NHC-bound homoenolate equivalents derived from α,β-unsaturated aldehydes combine with transient reactive o-quinone methides in an enantioselective formal [4 + 3] fashion to access 2-benzoxopinones. The overall approach provides a general blueprint for the integration of carbene catalysis with additional Lewis base activation modes.

Direct, enantioselective α-alkylation of aldehydes using simple olefins.

PubMed

Capacci, Andrew G; Malinowski, Justin T; McAlpine, Neil J; Kuhne, Jerome; MacMillan, David W C

2017-11-01

Although the α-alkylation of ketones has already been established, the analogous reaction using aldehyde substrates has proven surprisingly elusive. Despite the structural similarities between the two classes of compounds, the sensitivity and unique reactivity of the aldehyde functionality has typically required activated substrates or specialized additives. Here, we show that the synergistic merger of three catalytic processes-photoredox, enamine and hydrogen-atom transfer (HAT) catalysis-enables an enantioselective α-aldehyde alkylation reaction that employs simple olefins as coupling partners. Chiral imidazolidinones or prolinols, in combination with a thiophenol, iridium photoredox catalyst and visible light, have been successfully used in a triple catalytic process that is temporally sequenced to deliver a new hydrogen and electron-borrowing mechanism. This multicatalytic process enables both intra- and intermolecular aldehyde α-methylene coupling with olefins to construct both cyclic and acyclic products, respectively. With respect to atom and step-economy ideals, this stereoselective process allows the production of high-value molecules from feedstock chemicals in one step while consuming only photons.

Direct, enantioselective α-alkylation of aldehydes using simple olefins

NASA Astrophysics Data System (ADS)

Capacci, Andrew G.; Malinowski, Justin T.; McAlpine, Neil J.; Kuhne, Jerome; MacMillan, David W. C.

2017-11-01

Although the α-alkylation of ketones has already been established, the analogous reaction using aldehyde substrates has proven surprisingly elusive. Despite the structural similarities between the two classes of compounds, the sensitivity and unique reactivity of the aldehyde functionality has typically required activated substrates or specialized additives. Here, we show that the synergistic merger of three catalytic processes—photoredox, enamine and hydrogen-atom transfer (HAT) catalysis—enables an enantioselective α-aldehyde alkylation reaction that employs simple olefins as coupling partners. Chiral imidazolidinones or prolinols, in combination with a thiophenol, iridium photoredox catalyst and visible light, have been successfully used in a triple catalytic process that is temporally sequenced to deliver a new hydrogen and electron-borrowing mechanism. This multicatalytic process enables both intra- and intermolecular aldehyde α-methylene coupling with olefins to construct both cyclic and acyclic products, respectively. With respect to atom and step-economy ideals, this stereoselective process allows the production of high-value molecules from feedstock chemicals in one step while consuming only photons.

Catalysts for CO2/epoxide ring-opening copolymerization

PubMed Central

Trott, G.; Saini, P. K.; Williams, C. K.

2016-01-01

This article summarizes and reviews recent progress in the development of catalysts for the ring-opening copolymerization of carbon dioxide and epoxides. The copolymerization is an interesting method to add value to carbon dioxide, including from waste sources, and to reduce pollution associated with commodity polymer manufacture. The selection of the catalyst is of critical importance to control the composition, properties and applications of the resultant polymers. This review highlights and exemplifies some key recent findings and hypotheses, in particular using examples drawn from our own research. PMID:26755758

Copper-catalysed enantioselective stereodivergent synthesis of amino alcohols.

PubMed

Shi, Shi-Liang; Wong, Zackary L; Buchwald, Stephen L

2016-04-21

The chirality, or 'handedness', of a biologically active molecule can alter its physiological properties. Thus it is routine procedure in the drug discovery and development process to prepare and fully characterize all possible stereoisomers of a drug candidate for biological evaluation. Despite many advances in asymmetric synthesis, developing general and practical strategies for obtaining all possible stereoisomers of an organic compound that has multiple contiguous stereocentres remains a challenge. Here, we report a stereodivergent copper-based approach for the expeditious construction of amino alcohols with high levels of chemo-, regio-, diastereo- and enantioselectivity. Specifically, we synthesized these amino-alcohol products using sequential, copper-hydride-catalysed hydrosilylation and hydroamination of readily available enals and enones. This strategy provides a route to all possible stereoisomers of the amino-alcohol products, which contain up to three contiguous stereocentres. We leveraged catalyst control and stereospecificity simultaneously to attain exceptional control of the product stereochemistry. Beyond the immediate utility of this protocol, our strategy could inspire the development of methods that provide complete sets of stereoisomers for other valuable synthetic targets.

Implication of substrate-assisted catalysis on improving lipase activity or enantioselectivity in organic solvents.

PubMed

Tsai, Shau-Wei; Chen, Chun-Chi; Yang, Hung-Shien; Ng, I-Son; Chen, Teh-Liang

2006-08-01

In comparison with the biocatalyst engineering and medium engineering approaches, very few examples have been reported on using the substrate engineering approach such as substrate-assisted catalysis (SAC) for naturally occurring or engineered lipases and serine proteases to improve the enzyme activity and enantioselectivity. By employing lipase-catalyzed hydrolysis of (R,S)-naproxen esters in water-saturated isooctane as the model system, we demonstrate the proton shuttle device to the leaving alcohol of the substrate as a new means of SAC to effectively improve the lipase activity or enantioselectivity. The result cannot only provide a strong evidence for the rate-limiting proton transfer for the bond-breaking of tetrahedron intermediate of the acylation step, but also sheds light for performing the hydrolysis, transesterification or aminolysis in organic solvents for the ester substrate that originally lipases cannot catalyze, but now can after introducing the device.

Enantioselective Bioaccumulation, Tissue Distribution, and Toxic Effects of Myclobutanil Enantiomers in Pelophylax nigromaculatus Tadpole.

PubMed

Cheng, Cheng; Di, Shanshan; Chen, Li; Zhang, Wenjun; Diao, Jinling; Zhou, Zhiqiang

2017-04-19

Research on the enantioselective behavior of chiral pesticides on amphibians has received growing attention, because amphibians are experiencing a population decline and amphibian metamorphosis shares many similarities with human fetal development. In this study, the enantioselective behavior of myclobutanil on Pelophylax nigromaculatus tadpole was studied. The antioxidant enzyme (SOD, GST) activities and malondialdehyde (MDA) content were investigated to assess the different toxic effects when tadpoles were exposed to myclobutanil enantiomers for 96 h. In the chronic exposure experiment, the bioaccumulation concentration of (-)-myclobutanil in tadpoles is significantly higher than that of (+)-myclobutanil, and the concentration of myclobutanil in tadpole intestine and liver was higher compared with other tissues. During the elimination experiment, about 95% of myclobutanil in tadpoles was eliminated within only 24 h. On the basis of these data, the enantiomeric differences should be taken into consideration in the risk assessment of myclobutanil.

Dual catalysis for enantioselective convergent synthesis of enantiopure vicinal amino alcohols.

PubMed

Ye, Chen-Xi; Melcamu, Yared Yohannes; Li, Heng-Hui; Cheng, Jiang-Tao; Zhang, Tian-Tian; Ruan, Yuan-Ping; Zheng, Xiao; Lu, Xin; Huang, Pei-Qiang

2018-01-29

Enantiopure vicinal amino alcohols and derivatives are essential structural motifs in natural products and pharmaceutically active molecules, and serve as main chiral sources in asymmetric synthesis. Currently known asymmetric catalytic protocols for this class of compounds are still rare and often suffer from limited scope of substrates, relatively low regio- or stereoselectivities, thus prompting the development of more effective methodologies. Herein we report a dual catalytic strategy for the convergent enantioselective synthesis of vicinal amino alcohols. The method features a radical-type Zimmerman-Traxler transition state formed from a rare earth metal with a nitrone and an aromatic ketyl radical in the presence of chiral N,N'-dioxide ligands. In addition to high level of enantio- and diastereoselectivities, our synthetic protocol affords advantages of simple operation, mild conditions, high-yielding, and a broad scope of substrates. Furthermore, this protocol has been successfully applied to the concise synthesis of pharmaceutically valuable compounds (e.g., ephedrine and selegiline).

Exploring the origins of selectivity in soluble epoxide hydrolase from Bacillus megaterium† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7ob01847a

PubMed Central

Serrano-Hervás, Eila

2017-01-01

Epoxide hydrolase (EH) enzymes catalyze the hydration of racemic epoxides to yield their corresponding vicinal diols. These enzymes present different enantio- and regioselectivity depending upon either the substrate structure or the substitution pattern of the epoxide ring. In this study, we computationally investigate the Bacillus megaterium epoxide hydrolase (BmEH)-mediated hydrolysis of racemic styrene oxide (rac-SO) and its para-nitro styrene oxide (rac-p-NSO) derivative using density functional theory (DFT) and an active site cluster model consisting of 195 and 197 atoms, respectively. Full reaction mechanisms for epoxide ring opening were evaluated considering the attack at both oxirane carbons and considering two possible orientations of the substrate at the BmEH active site. Our results indicate that for both SO and p-NSO substrates the BmEH enantio- and regioselectivity is opposite to the inherent (R)-BmEH selectivity, the attack at the benzylic position (C1) of the (S)-enantiomer being the most favoured chemical outcome. PMID:29026902

Efficient reductive amination process for enantioselective synthesis of L-phosphinothricin applying engineered glutamate dehydrogenase.

PubMed

Yin, Xinjian; Wu, Jianping; Yang, Lirong

2018-05-01

The objective of this study was to identify and exploit a robust biocatalyst that can be applied in reductive amination for enantioselective synthesis of the competitive herbicide L-phosphinothricin. Applying a genome mining-based library construction strategy, eight NADPH-specific glutamate dehydrogenases (GluDHs) were identified for reductively aminating 2-oxo-4-[(hydroxy)(methyl)phosphinoyl]butyric acid (PPO) to L-phosphinothricin. Among them, the glutamate dehydrogenase cloned from Pseudomonas putida (PpGluDH) exhibited relatively high catalytic activity and favorable soluble expression. This enzyme was purified to homogeneity for further characterization. The specific activity of PpGluDH was 296.1 U/g-protein, which is significantly higher than the reported value for a GluDH. To the best of our knowledge, there has not been any report on protein engineering of GluDH for PPO-oriented activity. Taking full advantage of the available information and the diverse characteristics of the enzymes in the enzyme library, PpGluDH was engineered by site-directed mutation based on multiple sequence alignment. The mutant I170M, which had 2.1-fold enhanced activity, was successfully produced. When the I170M mutant was applied in the batch production of L-phosphinothricin, it showed markedly improved catalytic efficiency compared with the wild type enzyme. The conversion reached 99% (0.1 M PPO) with an L-phosphinothricin productivity of 1.35 g/h·L, which far surpassed the previously reported level. These results show that PpGluDH I170M is a promising biocatalyst for highly enantioselective synthesis of L-phosphinothricin by reductive amination.

Enantioselective Desymmetrization via Carbonyl-Directed Catalytic Asymmetric Hydroboration and Suzuki-Miyaura Cross-Coupling

PubMed Central

Hoang, Gia L.; Yang, Zhao-Di; Smith, Sean M.; Pal, Rhitankar; Miska, Judy L.; Pérez, Damaris E.; Pelter, Libbie S. W.; Zeng, Xiao Cheng; Takacs, James M.

2015-01-01

The rhodium-catalyzed enantioselective desymmetrization of symmetric γ,δ–unsaturated amides via carbonyl-directed catalytic asymmetric hydroboration (directed CAHB) affords chiral secondary organoboronates with up to 98% ee. The chiral γ–borylated products undergo palladium-catalyzed Suzuki-Miyaura cross-coupling via the trifluoroborate salt with stereoretention. PMID:25642639

Enantioselective Synthesis of All-Carbon Quaternary Centers Structurally Related to Amaryllidaceae Alkaloids.

PubMed

Mikušek, Jiří; Jansa, Petr; Jagtap, Pratap R; Vašíček, Tomáš; Císařová, Ivana; Matoušová, Eliška

2018-05-18

Enantioselective synthesis of all-carbon quaternary centers remains a considerable challenge for synthetic organic chemists. Here, we report a two-step protocol to synthesize such centers including tandem cyclization/Suzuki cross-coupling followed by halocarbocyclization. During this process, two rings, three new C-C bonds and a stereochemically defined all-carbon quaternary center are formed. The absolute configuration of this center is controlled by the stereochemistry of the adjacent stereocenter, which derives from an appropriate enantioenriched starting material. Using this method, we synthesized polycyclic compounds structurally similar to Amaryllidaceae alkaloids in high enantiomeric excesses. Because these products resemble naturally occurring compounds, our protocol can be used to synthesize various potentially bioactive compounds. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Further characterization of benzo[a]pyrene diol-epoxide (BPDE)-induced comet assay effects.

PubMed

Bausinger, Julia; Schütz, Petra; Piberger, Ann Liza; Speit, Günter

2016-03-01

The present study aims to further characterize benzo[a]pyrene diol-epoxide (BPDE)-induced comet assay effects. Therefore, we measured DNA effects by the comet assay and adduct levels by high-performance liquid chromatography (HPLC) in human lymphocytes and A549 cells exposed to (±)-anti-benzo[a]pyrene-7,8-diol 9,10-epoxide [(±)-anti-BPDE] or (+)-anti-benzo[a]pyrene-7,8-diol 9,10-epoxide [(+)-anti-BPDE]. Both, the racemic form and (+)-anti-BPDE, which is the most relevant metabolite with regard to mutagenicity and carcinogenicity, induced DNA migration in cultured lymphocytes in the same range of concentrations to a similar extent in the alkaline comet assay after exposure for 2h. Nevertheless, (+)-anti-BPDE induced significantly enhanced DNA migration after 16 and 18h post-cultivation which was not seen in response to (±)-anti-BPDE. Combination of the comet assay with the Fpg (formamidopyrimidine-DNA glycosylase) protein did not enhance BPDE-induced effects and thus indicated the absence of Fpg-sensitive sites (oxidized purines, N7-guanine adducts, AP-sites). The aphidicolin (APC)-modified comet assay suggested significant excision repair activity of cultured lymphocytes during the first 18h of culture after a 2 h-exposure to BPDE. In contrast to these repair-related effects measured by the comet assay, HPLC analysis of stable adducts did not reveal any significant removal of (+)-anti-BPDE-induced adducts from lymphocytes during the first 22h of culture. On the other hand, HPLC measurements indicated that A549 cells repaired about 70% of (+)-anti-BPDE-induced DNA-adducts within 22h of release. However, various experiments with the APC-modified comet assay did not indicate significant repair activity during this period in A549 cells. The conflicting results obtained with the comet assay and the HPLC-based adduct analysis question the real cause for BPDE-induced DNA migration in the comet assay and the reliability of the APC-modified comet assay for the

Stereoselective reactions. XXXII. Enantioselective deprotonation of 4-tert-butylcyclohexanone by fluorine-containing chiral lithium amides derived from 1-phenylethylamine and 1-(1-naphthyl)ethylamine.

PubMed

Aoki, K; Koga, K

2000-04-01

Enantioselective deprotonation of 4-tert-butylcyclohexanone was examined using 1-phenylethylamine- and 1-(1-naphthyl)ethylamine-derived chiral lithium amides having an alkyl or a fluoroalkyl substituent at the amide nitrogen. The lithium amides having a 2,2,2-trifluoroethyl group on the amide nitrogen are easily accessible in both enantiomeric forms, and were found to induce good enantioselectivity in the present reaction.

Asymmetric allylation of α-ketoester-derived N-benzoylhydrazones promoted by chiral sulfoxides/N-oxides Lewis bases: highly enantioselective synthesis of quaternary α-substituted α-allyl-α-amino acids.

PubMed

Reyes-Rangel, Gloria; Bandala, Yamir; García-Flores, Fred; Juaristi, Eusebio

2013-09-01

Chiral sulfoxides/N-oxides (R)-1 and (R,R)-2 are effective chiral promoters in the enantioselective allylation of α-keto ester N-benzoylhydrazone derivatives 3a-g to generate the corresponding N-benzoylhydrazine derivatives 4a-g, with enantiomeric excesses as high as 98%. Representative hydrazine derivatives 4a-b were subsequently treated with SmI2, and the resulting amino esters 5a-b with LiOH to obtain quaternary α-substituted α-allyl α-amino acids 6a-b, whose absolute configuration was assigned as (S), with fundament on chemical correlation and electronic circular dichroism (ECD) data. © 2013 Wiley Periodicals, Inc.

CAPILLARY ELECTROPHORESIS FOR ENANTIOMER SEPARATION AND MEASUREMENT OF ENANTIOSELECTIVITY OF CHIRAL POLLUTANTS IN THE ENVIRONMENT

EPA Science Inventory

Chiral pollutants exist as 2 species, -- enantiomers - that have identical physical and chemical properties except when they interact with enzymes or other chiral molecules; then they usually react selectively. This enantioselectivity results in different rates of microbial trans...

Simultaneous enantioselective determination of phenylpyrazole insecticide flufiprole and its chiral metabolite in paddy field ecosystem by ultra-high performance liquid chromatography/tandem mass spectrometry.

PubMed

Li, Jing; Zhang, Yuting; Cheng, Youpu; Yuan, Shankui; Liu, Lei; Shao, Hui; Li, Hui; Li, Na; Zhao, Pengyue; Guo, Yongze

2016-03-20

A novel and sensitive ultra-high performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous enantioselective determination of flufiprole and its hydrolysis metabolite in paddy field ecosystem. The separation and determination were performed using reversed-phase chromatography on a novel cellulose chiral stationary phase, a Lux Cellulose-4 (150 mm × 2.0 mm) column, under isocratic conditions at 0.25 mL/min flow rate. The effects of other four different polysaccharide-based chiral stationary phases (CSPs) on the separation and simultaneous enantioseparation of the two target compounds were also evaluated. The elution orders of the eluting enantiomers were identified by an optical rotation detector. Modified QuEChERS (acronym for Quick, Easy, Cheap, Effective, Rugged and Safe) method and solid-phase extraction (SPE) were used for the enrichment and cleanup of paddy water, rice straw, brown rice and paddy soil samples, respectively. Parameters including the matrix effect, linearity, precision, accuracy and stability were evaluated. Under the optimal conditions, the mean recoveries for all enantiomers from the above four sample matrix were ranged from 83.6% to 107%, with relative standard deviations (RSD) in the range of 1.0-5.8%. Coefficients of determination R(2)≥0.998 were achieved for each enantiomer in paddy water, rice straw, brown rice and paddy soil matrix calibration curves within the range of 5-500 μg/kg. The limits of quantification (LOQ) for all stereoisomers in the above four matrices were all below 2.0 μg/kg. The methodology was successfully applied for simultaneously enantioselective analysis of flufiprole enantiomers and their chiral metabolite in the real samples, indicating its efficacy in investigating the environmental stereochemistry of flufiprole in paddy field ecosystem. Copyright © 2016 Elsevier B.V. All rights reserved.

Tungsten-catalyzed asymmetric epoxidation of allylic and homoallylic alcohols with hydrogen peroxide.

PubMed

Wang, Chuan; Yamamoto, Hisashi

2014-01-29

A simple, efficient, and environmentally friendly asymmetric epoxidation of primary, secondary, tertiary allylic, and homoallylic alcohols has been accomplished. This process was promoted by a tungsten-bishydroxamic acid complex at room temperature with the use of aqueous 30% H2O2 as oxidant, yielding the products in 84-98% ee.

Enantioselective accumulation, metabolism and phytoremediation of lactofen by aquatic macrophyte Lemna minor.

PubMed

Wang, Fang; Yi, Xiaotong; Qu, Han; Chen, Li; Liu, Donghui; Wang, Peng; Zhou, Zhiqiang

2017-09-01

Pesticides are frequently detected in water bodies due to the agricultural application, which may pose impacts on aquatic organisms. The enantioselective bioaccumulation and metabolism of the herbicide lactofen in aquatic floating macrophyte Lemna minor (L. minor) were studied and the potential L. minor phytoremediation was investigated. Ultra-high performance liquid chromatography - tandem mass spectrometry (UHPLC-MS-MS) analysis for lactofen and its two known metabolites in L. minor was performed. The initial concentrations of racemic lactofen, R-lactofen and S-lactofen were all 30μgL -1 in the growth solution. The distribution of lactofen and its metabolites in growth solution and L. minor was determined throughout a 5-d laboratory trial. It was observed that S-lactofen was preferentially taken up and metabolized in L. minor. After rac-lactofen exposure, the accumulation amount of S-lactofen was approximately 3-fold more than that of R-lactofen in L. minor and the metabolism rate of S-lactofen (T 1/2 =0.92 d) was significantly faster than R-lactofen (T 1/2 =1.55 d). L. minor could only slightly accelerate the metabolism and removal of lactofen in the growth solution. As for the metabolites, desethyl lactofen was found to be the major metabolite in L. minor and the growth solution, whereas the metabolite acifluorfene was undetectable. No interconversion of the two enantiomers was observed after individual enantiomer exposure, indicating they were configurationally stable. The findings of this work represented that the accumulation and metabolism of lactofen in L. minor were enantioselective, and L. minor had limited capacity for the removal of lactofen and its metabolite in water. Copyright © 2017. Published by Elsevier Inc.

Enantioselective Michael Addition of Pyrroles with Nitroalkenes in Aqueous Media Catalyzed by a Water-soluble Catalyst.

PubMed

Gui, Yang; Li, Yanan; Sun, Jianan; Zha, Zhenggen; Wang, Zhiyong

2018-06-11

A new water-soluble catalytic system were developed and therefor used in an enantioselective Michael addition of pyrroles with nitroalkenes in water to afford the nitroethylpyrrole derivatives with both excellent yields and ee values.

Mechanism of amido-thiourea catalyzed enantioselective imine hydrocyanation: transition state stabilization via multiple non-covalent interactions.

PubMed

Zuend, Stephan J; Jacobsen, Eric N

2009-10-28

An experimental and computational investigation of amido-thiourea promoted imine hydrocyanation has revealed a new and unexpected mechanism of catalysis. Rather than direct activation of the imine by the thiourea, as had been proposed previously in related systems, the data are consistent with a mechanism involving catalyst-promoted proton transfer from hydrogen isocyanide to imine to generate diastereomeric iminium/cyanide ion pairs that are bound to catalyst through multiple noncovalent interactions; these ion pairs collapse to form the enantiomeric alpha-aminonitrile products. This mechanistic proposal is supported by the observation of a statistically significant correlation between experimental and calculated enantioselectivities induced by eight different catalysts (P < 0.01). The computed models reveal a basis for enantioselectivity that involves multiple stabilizing and destabilizing interactions between substrate and catalyst, including thiourea-cyanide and amide-iminium interactions.

Enantioselectivity in the Metabolism of Cyclophosphamide in Patients With Multiple or Systemic Sclerosis.

PubMed

de Castro, Francine Attié; Simões, Belinda Pinto; Coelho, Eduardo Barbosa; Lanchote, Vera Lucia

2017-06-01

The aim of this study was to evaluate the enantioselective pharmacokinetics of cyclophosphamide and its metabolites 4-hydroxycyclophosphamide and carboxyethylphosphoramide mustard in patients with systemic or multiple sclerosis. Patients with systemic sclerosis (n = 10) or multiple sclerosis (n = 10), genotyped for the allelic variants of CYP2C9*2 and CYP2C9*3 and of the CYP2B6 G516T polymorphism, were treated with 50 mg cyclophosphamide/kg daily for 4 days. Serial blood samples were collected up to 24 hours after administration of the last cyclophosphamide dose. Cyclophosphamide, 4-hydroxycyclophosphamide, and carboxyethylphosphoramide enantiomers were analyzed in plasma samples using liquid chromatography-tandem mass spectrometry coupled to chiral column Chiralcel OD-R or Chiralpak AD-RH. Cytokines IL-2, IL-4, IL-6, IL-8, IL-10, IL- 12p70, IL-17, TNF-α, and INT-δ in the plasma samples collected before cyclophosphamide infusion were analyzed by Milliplex MAP human cytokine/chemokine. Pharmacokinetic parameters showed higher plasma concentrations of (S)-(-)-cyclophosphamide (AUC 215.0 vs 186.2 μg·h/mL for multiple sclerosis patients and 219.1 vs 179.2 μg·h/mL for systemic sclerosis patients) and (R)-4-hydroxycyclophosphamide (AUC 5.6 vs 3.7 μg·h/mL for multiple sclerosis patients and 6.3 vs 5.6 μg·h/mL for systemic sclerosis patients) when compared to their enantiomers in both groups of patients, whereas the pharmacokinetics of the carboxyethylphosphoramide metabolite was not enantioselective. Cytokines' plasma concentrations were similar between multiple and systemic sclerosis groups. The pharmacokinetics of cyclophosphamide is enantioselective in patients with systemic sclerosis and multiple sclerosis, with higher plasma concentrations of the (S)-(-)-cyclophosphamide enantiomer due to the preferential formation of the (R)-4-hydroxycyclophosphamide metabolite. © 2017, The American College of Clinical Pharmacology.

Identification of new metabolic pathways in the enantioselective fungicide tebuconazole biodegradation by Bacillus sp. 3B6.

PubMed

Youness, Mohamed; Sancelme, Martine; Combourieu, Bruno; Besse-Hoggan, Pascale

2018-06-05

The use of triazole fungicides in various fields ranging from agriculture to therapy, can cause long-term undesirable effects on different organisms from various environmental compartments and lead to resistance phenomena (even in humans) due to their extensive use and persistence. Their occurrence in various water bodies has increased and tebuconazole, in particular, is often detected, sometimes in high concentration. Only a few bacterial and fungal strains have been isolated and found to biotransform this fungicide, described as not easily biodegradable. Nevertheless, the knowledge of efficient degrading-strains and metabolites potentially formed could improve bioremediation process and global overview of risk assessment. Therefore, a broad screening of microorganisms, isolated from various environmental compartments or from commercially-available strain collections, allowed us to find six bacterial strains able to biotransform tebuconazole. The most efficient one was studied further: this environmental strain Bacillus sp. 3B6 biotransforms the fungicide enantioselectively (ee = 18%) into two hydroxylated metabolites, one of them being transformed in its turn to alkene by a biotic dehydration reaction. This original enantioselective pathway shows that racemic pesticides should be treated by the environmental risk assessment authorities as a mixture of two compounds because persistence, biodegradation, bioaccumulation and toxicity often show chiral dependence. Copyright © 2018 Elsevier B.V. All rights reserved.

Enantioselective Metabolism and Interference on Tryptophan Metabolism of Myclobutanil in Rat Hepatocytes.

PubMed

Wang, Yao; Qiu, Jing; Zhu, Wentao; Wang, Xinru; Zhang, Ping; Wang, Dezhen; Zhou, Zhiqiang

2015-09-01

Myclobutanil, (RS)-2-(4-chlorophenyl)-2-(1H-1, 2, 4-triazol-1-ylmethyl) hexanenitrile is a widely used triazole fungicide. In this study, enantioselective metabolism and cytotoxicity were investigated in rat hepatocytes by chiral HPLC-MS/MS and the methyl tetrazolium (MTT) assay, respectively. Furthermore, tryptophan metabolism disturbance in rat hepatocytes after myclobutanil exposure was also evaluated by target metabolomics method. The half-life (t1/2) of (+)-myclobutanil was 10.66 h, whereas that for (-)-myclobutanil was 15.07 h. Such results indicated that the metabolic process of myclobutanil in rat hepatocytes was enantioselective with an enrichment of (-)-myclobutanil. For the cytotoxicity research, the calculated EC50 (12 h) values for rac-myclobutanil, (+)- and (-)-myclobutanil were 123.65, 150.65 and 152.60 µM, respectively. The results of tryptophan metabolites profiling showed that the levels of kynurenine (KYN) and XA were both up-regulated compared to the control, suggesting the activation effect of the KYN pathway by myclobutanil and its enantiomers which may provide an important insight into its toxicity mechanism. The data presented here could be useful for the environmental hazard assessment of myclobutanil. © 2015 Wiley Periodicals, Inc.

Synthesis of epoxidized cardanol and its antioxidative properties for vegetable oils and biodiesel

USDA-ARS?s Scientific Manuscript database

A novel antioxidant epoxidized cardanol (ECD), derived from cardanol, was synthesized and characterized by FT-IR, 1H-NMR and 13C-NMR. Oxidative stability of ECD used in vegetable oils and biodiesel was evaluated by pressurized differential scanning calorimetry (PDSC) and the Rancimat method, respect...

Epoxide metabolism in the liver of mice treated with clofibrate (ethyl-alpha-(p-chlorophenoxyisobutyrate)), a peroxisome proliferator.

PubMed

Moody, D E; Loury, D N; Hammock, B D

1985-05-01

An increase in cytosolic epoxide hydrolase (cEH) activity occurs in the livers of mice treated with peroxisome proliferating-hypolipidemic-nongenotoxic carcinogens. As increases in activity of epoxide metabolizing enzymes may reflect the carcinogenic mechanism, a detailed comparison of the response of cEH, microsomal epoxide hydrolase (mEH), and cytosolic glutathione S-transferase (cGST) activities using the geometrical isomers trans- and cis-stilbene oxide as substrates has been performed in livers from mice treated with clofibrate (ethyl-alpha-(p-chlorophenoxyisobutyrate]. The maximal increase of cEH activity occurred at lower dietary doses of clofibrate (0.5%) and within a shorter time (5 days) than mEH and cGST (2%, 14 days) activity. After 14 days at 0.5% clofibrate, cEH, mEH, and cGST activities were 250, 175, and 165% and 290, 220, and 75% of control values in male and female mice, respectively. Withdrawal of clofibrate from the diet resulted in a reversion of activities to control values within 7 days. Clofibrate treatment shifted the apparent subcellular compartmentation of all three enzymatic activities with an increase in the ratio of soluble to particulate activity. In particular, the relative specific activity of all three enzymes decreased in the light mitochondrial (peroxisomal) cell fraction, and an increase of a mEH-like activity (benzo[a]pyrene-4,5-oxide and cis-stilbene oxide hydrolysis) in the cytosol occurred. Both the increase of cEH activity and the appearance of mEH-like activity in the cytosol are novel responses of epoxide metabolizing enzymes, which may be related to the novel cellular responses that follow clofibrate treatment, peroxisome proliferation, hypolipidemia, and nongenotoxic carcinogenesis.

The mechanism of epoxide carbonylation by [Lewis Acid]+[Co(CO)4]- catalysts.

PubMed

Church, Tamara L; Getzler, Yutan D Y L; Coates, Geoffrey W

2006-08-09

A detailed mechanistic investigation of epoxide carbonylation by the catalyst [(salph)Al(THF)2]+ [Co(CO)4]- (1, salph = N,N'-o-phenylenebis(3,5-di-tert-butylsalicylideneimine), THF = tetrahydrofuran) is reported. When the carbonylation of 1,2-epoxybutane (EB) to beta-valerolactone is performed in 1,2-dimethoxyethane solution, the reaction rate is independent of the epoxide concentration and the carbon monoxide pressure but first order in 1. The rate of lactone formation varies considerably in different solvents and depends primarily on the coordinating ability of the solvent. In mixtures of THF and cis/trans-2,5-dimethyltetrahydrofuran, the reaction is first order in THF. From spectroscopic and kinetic data, the catalyst resting state was assigned to be the neutral (beta-aluminoxy)acylcobalt species (salph)AlOCH(Et)CH2COCo(CO)4 (3a), which was successfully trapped with isocyanates. As the formation of 3a from EB, CO, and 1 is rapid, lactone ring closing is rate-determining. The favorable impact of donating solvents was attributed to the necessity of stabilizing the aluminum cation formed upon generation of the lactone.

Artificial sunlight and ultraviolet light induced photo-epoxidation of propylene over V-Ti/MCM-41 photocatalyst

PubMed Central

Nguyen, Van-Huy; Bai, Hsunling

2014-01-01

Summary The light irradiation parameters, including the wavelength spectrum and intensity of light source, can significantly influence a photocatalytic reaction. This study examines the propylene photo-epoxidation over V-Ti/MCM-41 photocatalyst by using artificial sunlight (Xe lamp with/without an Air Mass 1.5 Global Filter at 1.6/18.5 mW·cm−2) and ultraviolet light (Mercury Arc lamp with different filters in the range of 0.1–0.8 mW·cm−2). This is the first report of using artificial sunlight to drive the photo-epoxidation of propylene. Over V-Ti/MCM-41 photocatalyst, the propylene oxide (PO) formation rate is 193.0 and 112.1 µmol·gcat −1·h−1 with a PO selectivity of 35.0 and 53.7% under UV light and artificial sunlight, respectively. A normalized light utilization (NLU) index is defined and found to correlate well with the rate of both PO formation and C3H6 consumption in log–log scale. The light utilization with a mercury arc lamp is better than with a xenon lamp. The selectivity to PO remains practically unchanged with respect to NLU, suggesting that the photo-epoxidation occurs through the same mechanism under the conditions tested in this study. PMID:24991493

Different effects of clopidogrel and clarithromycin on the enantioselective pharmacokinetics of sibutramine and its active metabolites in healthy subjects.

PubMed

Shinde, Dhananjay D; Kim, Ho-Sook; Choi, Jae-Seok; Pan, Wei; Bae, Soo Kyung; Yeo, Chang-Woo; Shon, Ji-Hong; Kim, Dong-Hyun; Shin, Jae Gook

2013-05-01

In this study, we assessed the effects of clopidogrel and clarithromycin, known CYP2B6 and CYP3A inhibitors, respectively, on the enantioselective disposition of racemic sibutramine in conjunction with CYP2B6 polymorphisms in humans. Sibutramine showed enantioselective plasma profiles with consistently higher concentrations of R-enantiomers. Clopidogrel and clarithromycin significantly increased the sibutramine plasma concentration, but their effects differed between enantiomers; a 2.2-fold versus 4.1-fold increase in the AUC in S-enantiomer and 1.8-fold versus 2.0-fold for the R-enantiomer, respectively. The AUCs of S- and R-desmethyl metabolites changed significantly during the clopidogrel phase (P < .001 and P < .001, respectively) but not during the clarithromycin phase (P = .099 and P = .090, respectively). Exposure to sibutramine was higher in subjects with the CYP2B6*6/*6 genotype, but no statistical difference was observed among the CYP2B6 genotypes. These results suggest that the enantioselective disposition of sibutramine and its active metabolites are influenced by the altered genetic and environmental factors of CYP2B6 and CYP3A activity in vivo. © The Author(s) 2013.

An iron/amine-catalyzed cascade process for the enantioselective functionalization of allylic alcohols.

PubMed

Quintard, Adrien; Constantieux, Thierry; Rodriguez, Jean

2013-12-02

Three is a lucky number: An enantioselective transformation of allylic alcohols into β-chiral saturated alcohols has been developed by combining two distinct metal- and organocatalyzed catalytic cycles. This waste-free triple cascade process merges an iron-catalyzed borrowing-hydrogen step with an aminocatalyzed nucleophilic addition reaction. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

N719 dye-sensitized organophotocatalysis: enantioselective tandem Michael addition/oxyamination of aldehydes.

PubMed

Yoon, Hyo-Sang; Ho, Xuan-Huong; Jang, Jiyeon; Lee, Hwa-Jung; Kim, Seung-Joo; Jang, Hye-Young

2012-07-06

A remarkably efficient photosensitizer, N719 dye, was used in asymmetric tandem Michael addition/oxyamination of aldehydes, rendering α,β-substituted aldehydes in good yields with excellent levels of enantioselectivity and diastereoselectivity. This is the first report of a multiorganocatalytic reaction involving iminium catalysis and photoinduced singly occupied molecular orbital (SOMO) catalysis. This reaction is expected to expand the scope of tandem organocatalytic reactions.

Effect of formulation and repeated applications on the enantioselectivity of metalaxyl dissipation and leaching in soil.

PubMed

Celis, Rafael; Gámiz, Beatriz; Adelino, María A; Cornejo, Juan; Hermosín, María C

2015-11-01

Soil incubation and column leaching experiments were conducted to address the question of whether the type of formulation (unsupported versus clay supported) and repeated applications of the chiral fungicide (RS)-metalaxyl affected the enantioselectivity of its dissipation and leaching in a slightly alkaline, loamy sand agricultural soil. Regardless of the type of formulation and the number of fungicide applications, the R-enantiomer of metalaxyl was degraded faster than the S-enantiomer, but the individual degradation rates of R- and S-metalaxyl were highly affected by the different application regimes assayed (t1/2 = 2-104 days). Repeated applications accelerated the degradation of the biologically active R-metalaxyl enantiomer, whereas they led to slower degradation of the non-active S-metalaxyl enantiomer. The type of formulation had less influence on the dissipation rates of the enantiomers. For all formulations tested, soil column leachates became increasingly enriched in S-enantiomer as the number of fungicide applications was increased, and application of metalaxyl to soil columns as clay-based formulations reduced the leaching of both enantiomers. Pesticide application conditions can greatly influence the enantioselective dissipation of chiral pesticides in soil, and hence are expected to exert a great impact on both the biological efficacy and the environmental chiral signatures of pesticides applied as mixtures of enantiomers or racemates to agricultural soils. © 2014 Society of Chemical Industry.

Engineering characterisation of epoxidized natural rubber-modified hot-mix asphalt

PubMed Central

Al-Mansob, Ramez A.; Ismail, Amiruddin; Yusoff, Nur Izzi Md.; Rahmat, Riza Atiq O. K.; Borhan, Muhamad Nazri; Albrka, Shaban Ismael; Azhari, Che Husna; Karim, Mohamed Rehan

2017-01-01

Road distress results in high maintenance costs. However, increased understandings of asphalt behaviour and properties coupled with technological developments have allowed paving technologists to examine the benefits of introducing additives and modifiers. As a result, polymers have become extremely popular as modifiers to improve the performance of the asphalt mix. This study investigates the performance characteristics of epoxidized natural rubber (ENR)-modified hot-mix asphalt. Tests were conducted using ENR–asphalt mixes prepared using the wet process. Mechanical testing on the ENR–asphalt mixes showed that the resilient modulus of the mixes was greatly affected by testing temperature and frequency. On the other hand, although rutting performance decreased at high temperatures because of the increased elasticity of the ENR–asphalt mixes, fatigue performance improved at intermediate temperatures as compared to the base mix. However, durability tests indicated that the ENR–asphalt mixes were slightly susceptible to the presence of moisture. In conclusion, the performance of asphalt pavement can be enhanced by incorporating ENR as a modifier to counter major road distress. PMID:28182724

Engineering characterisation of epoxidized natural rubber-modified hot-mix asphalt.

PubMed

Al-Mansob, Ramez A; Ismail, Amiruddin; Yusoff, Nur Izzi Md; Rahmat, Riza Atiq O K; Borhan, Muhamad Nazri; Albrka, Shaban Ismael; Azhari, Che Husna; Karim, Mohamed Rehan

2017-01-01

Road distress results in high maintenance costs. However, increased understandings of asphalt behaviour and properties coupled with technological developments have allowed paving technologists to examine the benefits of introducing additives and modifiers. As a result, polymers have become extremely popular as modifiers to improve the performance of the asphalt mix. This study investigates the performance characteristics of epoxidized natural rubber (ENR)-modified hot-mix asphalt. Tests were conducted using ENR-asphalt mixes prepared using the wet process. Mechanical testing on the ENR-asphalt mixes showed that the resilient modulus of the mixes was greatly affected by testing temperature and frequency. On the other hand, although rutting performance decreased at high temperatures because of the increased elasticity of the ENR-asphalt mixes, fatigue performance improved at intermediate temperatures as compared to the base mix. However, durability tests indicated that the ENR-asphalt mixes were slightly susceptible to the presence of moisture. In conclusion, the performance of asphalt pavement can be enhanced by incorporating ENR as a modifier to counter major road distress.

Binding Specificity Determines the Cytochrome P450 3A4 Mediated Enantioselective Metabolism of Metconazole.

PubMed

Zhuang, Shulin; Zhang, Leili; Zhan, Tingjie; Lu, Liping; Zhao, Lu; Wang, Haifei; Morrone, Joseph A; Liu, Weiping; Zhou, Ruhong

2018-01-25

Cytochrome P450 3A4 (CYP3A4) is a promiscuous enzyme, mediating the biotransformations of ∼50% of clinically used drugs, many of which are chiral molecules. Probing the interactions between CYP3A4 and chiral chemicals is thus essential for the elucidation of molecular mechanisms of enantioselective metabolism. We developed a stepwise-restrained-molecular-dynamics (MD) method to model human CYP3A4 in a complex with cis-metconazole (MEZ) isomers and performed conventional MD simulations with a total simulation time of 2.2 μs to probe the molecular interactions. Our current study, which employs a combined experimental and theoretical approach, reports for the first time on the distinct conformational changes of CYP3A4 that are induced by the enantioselective binding of cis-MEZ enantiomers. CYP3A4 preferably metabolizes cis-RS MEZ over the cis-SR isomer, with the resultant enantiomer fraction for cis-MEZ increasing rapidly from 0.5 to 0.82. cis-RS MEZ adopts a more extended structure in the active pocket with its Cl atom exposed to the solvent, whereas cis-SR MEZ sits within the hydrophobic core of the active pocket. Free-energy-perturbation calculations indicate that unfavorable van der Waals interactions between the cis-MEZ isomers and the CYP3A4 binding pocket predominantly contribute to their binding-affinity differences. These results demonstrate that binding specificity determines the cytochrome P450 3A4 mediated enantioselective metabolism of cis-MEZ.

Chiral 1-phenylethylamine-derived phosphine-phosphoramidite ligands for highly enantioselective Rh-catalyzed hydrogenation of beta-(acylamino)acrylates: significant effect of substituents on 3,3'-positions of binaphthyl moiety.

PubMed

Zhou, Xiao-Mao; Huang, Jia-Di; Luo, Li-Bin; Zhang, Chen-Lu; Hu, Xiang-Ping; Zheng, Zhuo

2010-05-21

A series of new chiral phosphine-phosphoramidite ligands with a 3,3'-substituted binaphthyl moiety were prepared from 1-phenylethylamine, and successfully applied in the Rh-catalyzed asymmetric hydrogenation of beta-(acylamino)-acrylates. The research disclosed that the substituents on the 3,3'-positions of binaphthyl moiety significantly influenced the enantioselectivity.

Theoretical study of photoinduced epoxidation of olefins catalyzed by ruthenium porphyrin.

PubMed

Ishikawa, Atsushi; Sakaki, Shigeyoshi

2011-05-12

Epoxidation of olefin by [Ru(TMP)(CO)(O)](-) (TMP = tetramesitylporphine), which is a key step of the photocatalyzed epoxidation of olefin by [Ru(TMP)(CO)], is studied mainly with the density functional theory (DFT) method, where [Ru(Por)(CO)] is employed as a model complex (Por = unsubstituted porphyrin). The CASSCF method was also used to investigate the electronic structure of important species in the catalytic cycle. In all of the ruthenium porphyrin species involved in the catalytic cycle, the weight of the main configuration of the CASSCF wave function is larger than 85%, suggesting that the static correlation is not very large. Also, unrestricted-DFT-calculated natural orbitals are essentially the same as CASSCF-calculated ones, here. On the basis of these results, we employed the DFT method in this work. Present computational results show characteristic features of this reaction, as follows: (i) The epoxidation reaction occurs via carboradical-type transition state. Neither carbocation-type nor concerted oxene-insertion-type character is observed in the transition state. (ii) Electron and spin populations transfer from the olefin moiety to the porphyrin ring in the step of the C-O bond formation. (iii) Electron and spin populations of the olefin and porphyrin moieties considerably change around the transition state. (iv) The atomic and spin populations of Ru change little in the reaction, indicating that the Ru center keeps the +II oxidation state in the whole catalytic cycle. (v) The stability of the olefin adduct [Ru(Por)(CO)(O)(olefin)](-) considerably depends on the kind of olefin, such as ethylene, n-hexene, and styrene. In particular, styrene forms a stable olefin adduct. And, (vi) interestingly, the difference in the activation barrier among these olefins is small in the quantitative level (within 5 kcal/mol), indicating that this catalyst can be applied to various substrates. This is because the stabilities and electronic structures of both the

Transition metal-catalyzed C-H activation reactions: diastereoselectivity and enantioselectivity.

PubMed

Giri, Ramesh; Shi, Bing-Feng; Engle, Keary M; Maugel, Nathan; Yu, Jin-Quan

2009-11-01

This critical review discusses historical and contemporary research in the field of transition metal-catalyzed carbon-hydrogen (C-H) bond activation through the lens of stereoselectivity. Research concerning both diastereoselectivity and enantioselectivity in C-H activation processes is examined, and the application of concepts in this area for the development of novel carbon-carbon and carbon-heteroatom bond-forming reactions is described. Throughout this review, an emphasis is placed on reactions that are (or may soon become) relevant in the realm of organic synthesis (221 references).

Dissipation and enantioselective degradation of plant growth retardants paclobutrazol and uniconazole in open field, greenhouse, and laboratory soils.

PubMed

Wu, Chengwang; Sun, Jianqiang; Zhang, Anping; Liu, Weiping

2013-01-15

Greenhouses are increasingly important in human food supply. Pesticides used in greenhouses play important roles in horticulture; however, little is known about their behavior in greenhouse environments. This work investigates the dissipation and enantioselctive degradation of plant growth retardants including paclobutrazol and uniconazole in soils under three conditions (i.e., open field, greenhouse, and laboratory). The dissipation and enantioselective degradation of paclobutrazol and uniconazole in greenhouse were different from those in open field; they were more persistent in greenhouse than in open field soil. Leaching produced by rainfall is responsible for the difference in dissipation. Thus, local environmental impacts may occur more easily inside greenhouses, while groundwater may be more contaminated in open field. Spike concentrations of 5, 10, and 20 times the concentrations of native residues were tested for the enantioselective dissipation of the two pesticides; the most potent enantioselective degradation of paclobutrazol and uniconazole occurred at the 10 times that of the native residues in the greenhouse environments and at 20 times native residues in open field environments. The higher soil activity in greenhouses than in open fields was thought to be responsible for such a difference. The environmental risk and regulation of paclobutrazol and uniconazole should be considered at the enantiomeric level.

Lipid Sulfates and Sulfonates Are Allosteric Competitive Inhibitors of the N-Terminal Phosphatase Activity of the Mammalian Soluble Epoxide Hydrolase†

PubMed Central

Tran, Katherine L.; Aronov, Pavel A.; Tanaka, Hiromasa; Newman, John W.; Hammock, Bruce D.; Morisseau, Christophe

2006-01-01

The EPXH2 gene encodes for the soluble epoxide hydrolase (sEH), a homodimeric enzyme with each monomer containing two domains with distinct activities. The C-terminal domain, containing the epoxide hydrolase activity (Cterm-EH), is involved in the metabolism of arachidonic acid epoxides, endogenous chemical mediators that play important roles in blood pressure regulation, cell growth, and inflammation. We recently demonstrated that the N-terminal domain contains a Mg2+-dependent lipid phosphate phosphatase activity (Nterm-phos). However, the biological role of this activity is unknown. The inability of known phosphatase inhibitors to inhibit the Nterm-phos constitutes a significant barrier to the elucidation of its function. We describe herein sulfate, sulfonate, and phosphonate lipids as novel potent inhibitors of Nterm-phos. These compounds are allosteric competitive inhibitors with KI in the hundred nanomolar range. These inhibitors may provide a valuable tool to investigate the biological role of the Nterm-phos. We found that polyisoprenyl phosphates are substrates of Nterm-phos, suggesting a possible role in sterol synthesis or inflammation. Furthermore, some of these compounds inhibit the C-terminal sEH activity through a noncompetitive inhibition mechanism involving a new binding site on the C-terminal domain. This novel site may play a role in the natural in vivo regulation of epoxide hydrolysis by sEH. PMID:16142916

Catalytic, Enantioselective Sulfenofunctionalisation of Alkenes: Mechanistic, Crystallographic, and Computational Studies

PubMed Central

Denmark, Scott E.; Hartmann, Eduard; Kornfilt, David J. P.; Wang, Hao

2015-01-01

The stereocontrolled introduction of vicinal heteroatomic substituents into organic molecules is one of the most powerful ways of adding value and function. Whereas many methods exist for the introduction of oxygen- and nitrogen-containing substituents, the number stereocontrolled methods for the introduction of sulfur-containing substituents pales by comparison. Previous reports from these laboratories have described the sulfenofunctionalization of alkenes that construct vicinal carbon-sulfur and carbon-oxygen, carbon-nitrogen as well as carbon-carbon bonds with high levels of diastereospecificity and enantioselectivity. This process is enabled by the concept of Lewis base activation of Lewis acids that provides activation of Group 16 electrophiles. To provide a foundation for expansion of substrate scope and improved selectivities, we have undertaken a comprehensive study of the catalytically active species. Insights gleaned from kinetic, crystallographic and computational methods have led to the introduction of a new family of sulfenylating agents that provide significantly enhanced selectivities. PMID:25411883

Physical-Chemical Properties of the Chiral Fungicide Fenamidone and Strategies for Enantioselective Crystallization.

PubMed

Kort, Anne-Kathleen; Lorenz, Heike; Seidel-Morgenstern, Andreas

2016-06-01

Thermodynamic and kinetic parameters are of prime importance for designing crystallization processes. In this article, Preferential Crystallization, as a special approach to carry out enantioselective crystallization, is described to resolve the enantiomers of the chiral fungicide fenamidone. In preliminary investigations the melting behavior and solid-liquid equilibria in the presence of solvents were quantified. The analyses revealed a stable solid phase behavior of fenamidone in the applied solvents. Based on the results obtained, a two-step crystallization route was designed and realized capable of providing highly pure enantiomers. An initial Preferential Crystallization of the racemate was performed prior to crystallizing the target enantiomer preferentially out of the enriched mother liquor. Chirality 28:514-520, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Catalytic enantioselective synthesis of atropisomeric biaryls by a cation-directed O-alkylation

NASA Astrophysics Data System (ADS)

Jolliffe, John D.; Armstrong, Roly J.; Smith, Martin D.

2017-06-01

Axially chiral biaryls, as exemplified by 1,1‧-bi-2-naphthol (BINOL), are key components of catalysts, natural products and medicines. These materials are synthesized conventionally in enantioenriched form through metal-mediated cross coupling, de novo construction of an aromatic ring, point-to-axial chirality transfer or an atropselective transformation of an existing biaryl. Here, we report a highly enantioselective organocatalytic method for the synthesis of atropisomeric biaryls by a cation-directed O-alkylation. Treatment of racemic 1-aryl-2-tetralones with a chiral quinidine-derived ammonium salt under basic conditions in the presence of an alkylating agent leads to atropselective O-alkylation with e.r. up to 98:2. Oxidation with DDQ gives access to C2-symmetric and non-symmetric BINOL derivatives without compromising e.r. We propose that the chiral ammonium counterion differentiates between rapidly equilibrating atropisomeric enolates, leading to highly atropselective O-alkylation. This dynamic kinetic resolution process offers a general approach to the synthesis of enantioenriched atropisomeric materials.

Mechanism of Amido-Thiourea Catalyzed Enantioselective Imine Hydrocyanation: Transition State Stabilization via Multiple Non-Covalent Interactions

PubMed Central

Zuend, Stephan J.

2009-01-01

An experimental and computational investigation of amido-thiourea promoted imine hydrocyanation has revealed a new and unexpected mechanism of catalysis. Rather than direct activation of the imine by the thiourea, as had been proposed previously in related systems, the data are consistent with a mechanism involving catalyst-promoted proton transfer from hydrogen isocyanide to imine to generate diastereomeric iminium/cyanide ion pairs that are bound to catalyst through multiple non-covalent interactions; these ion pairs collapse to form the enantiomeric α-aminonitrile products. This mechanistic proposal is supported by the observation of a statistically significant correlation between experimental and calculated enantioselectivities induced by eight different catalysts (P ≪ 0.01). The computed models reveal a basis for enantioselectivity that involves multiple stabilizing and destabilizing interactions between substrate and catalyst, including thiourea-cyanide and amide-iminium interactions. PMID:19778044

Enantioselective total synthesis of (-)-strychnine using the catalytic asymmetric Michael reaction and tandem cyclization.

PubMed

Ohshima, Takashi; Xu, Youjun; Takita, Ryo; Shimizu, Satoshi; Zhong, Dafang; Shibasaki, Masakatsu

2002-12-11

The enantioselective total synthesis of (-)-strychnine was accomplished through the use of the highly practical catalytic asymmetric Michael reaction (0.1 mol % of (R)-ALB, more than kilogram scale, without chromatography, 91% yield and >99% ee) as well as a tandem cyclization that simultaneously constructed B- and D-rings (>77% yield). Moreover, newly developed reaction conditions for thionium ion cyclization, NaBH3CN reduction of the imine moiety in the presence of Lewis acid to prevent ring opening reaction, and chemoselective reduction of the thioether (desulfurization) in the presence of exocyclic olefin were pivotal to complete the synthesis. The described chemistry paves the way for the synthesis of more advanced Strychnos alkaloids.

Direct, enantioselective α-alkylation of aldehydes using simple olefins

PubMed Central

Capacci, Andrew G.; Malinowski, Justin T.; McAlpine, Neil J.; Kuhne, Jerome; MacMillan, David W. C.

2017-01-01

Although the α-alkylation of ketones has already been established, the analogous reaction using aldehyde substrates has proven surprisingly elusive. Despite the structural similarities between the two classes of compounds, the sensitivity and unique reactivity of the aldehyde functionality has typically required activated substrates or specialized additives. Here, we show that the synergistic merger of three catalytic processes—photoredox, enamine and hydrogen-atom transfer (HAT) catalysis—enables an enantioselective α-aldehyde alkylation reaction that employs simple olefins as coupling partners. Chiral imidazolidinones or prolinols, in combination with a thiophenol, iridium photoredox catalyst and visible light, have been successfully used in a triple catalytic process that is temporally sequenced to deliver a new hydrogen and electron-borrowing mechanism. This multicatalytic process enables both intra- and intermolecular aldehyde α-methylene coupling with olefins to construct both cyclic and acyclic products, respectively. With respect to atom and step-economy ideals, this stereoselective process allows the production of high-value molecules from feedstock chemicals in one step while consuming only photons. PMID:29064486

Direct enantioselective three-component synthesis of optically active propargylamines in water.

PubMed

Ohara, Mutsuyo; Hara, Yoshichika; Ohnuki, Tohru; Nakamura, Shuichi

2014-07-14

An enantioselective three-component reaction of aldehydes, amines, and alkynes in water by using a bis(imidazoline)-Cu(I) catalysts having a hydrophobic substituent and sodium dodecyl sulfate as a surfactant was developed. The reaction was applied to a broad range of aldehydes and alkynes to give optically active propargylamines with excellent yields (up to 99 %) and enantiomeric excesses (up to 99 % ee). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective piezoelectric quartz crystal sensor for d-methamphetamine based on a molecularly imprinted polymer.

PubMed

Arenas, Leveriza F; Ebarvia, Benilda S; Sevilla, Fortunato B

2010-08-01

A piezoelectric quartz crystal (PQC) sensor based on a molecularly imprinted polymer (MIP) has been developed for enantioselective and quantitative analysis of d-(+)-methamphetamine (d(+)-MA). The sensor was produced by bulk polymerization and the resulting MIP was then coated on the gold electrode of an AT-cut quartz crystal. Conditions such as volume of polymer coating, curing time, type of PQC, baseline solvent, pH, and buffer type were found to affect the sensor response and were therefore optimized. The PQC-MIP gave a stable response to different concentrations of d(+)-MA standard solutions (response time = 10 to 100 s) with good repeatability (RSD = 0.03 to 3.09%; n = 3), good reproducibility (RSD = 3.55%; n = 5), and good reversibility (RSD = 0.36%; n = 3). The linear range of the sensor covered five orders of magnitude of analyte concentration, ranging from 10(-5) to 10(-1) microg mL(-1), and the limit of detection was calculated as 11.9 pg d(+)-MA mL(-1) . The sensor had a highly enantioselective response to d(+)-MA compared with its response to l(-)-MA, racemic MA, and phentermine. The developed sensor was validated by applying it to human urine samples from drug-free individuals spiked with standard d(+)-MA and from a confirmed MA user. Use of the standard addition method (SAM) and samples spiked with d(+)-MA at levels ranging from 1 x 10(-3) to 1 x 10(-2) microg mL(-1) showed recovery was good (95.3 to 110.9%).