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Sample records for highly enantioselective epoxidation

  1. Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

    PubMed Central

    2013-01-01

    Summary Enantioselective desymmetrization of meso-aziridines and meso-epoxides with various nucleophiles by organocatalysis has emerged as a cutting-edge approach in recent years. This review summarizes the origin and recent developments of enantioselective desymmetrization of meso-aziridines and meso-epoxides in the presence of organocatalysts. PMID:24062828

  2. Discovery of enantioselectivity of urea inhibitors of soluble epoxide hydrolase.

    PubMed

    Manickam, Manoj; Pillaiyar, Thanigaimalai; Boggu, PullaReddy; Venkateswararao, Eeda; Jalani, Hitesh B; Kim, Nam-Doo; Lee, Seul Ki; Jeon, Jang Su; Kim, Sang Kyum; Jung, Sang-Hun

    2016-07-19

    Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) in the metabolic pathway of arachidonic acid and has been considered as an important therapeutic target for chronic diseases such as hypertension, diabetes and inflammation. Although many urea derivatives are known as sEH inhibitors, the enantioselectivity of the inhibitors is not highlighted in spite of the stereoselective hydrolysis of EETs by sEH. In an effort to explore the importance of enantioselectivity in the urea scaffold, a series of enantiomers with the stereocenter adjacent to the urea nitrogen atom were prepared. The selectivity of enantiomers of 1-(α-alkyl-α-phenylmethyl)-3-(3-phenylpropyl)ureas showed wide range differences up to 125 fold with the low IC50 value up to 13 nM. The S-configuration with planar phenyl and small alkyl groups at α-position is crucial for the activity and selectivity. However, restriction of the free rotation of two α-groups with indan-1-yl or 1,2,3,4-tetrahydronaphthalen-1-yl moiety abolishes the selectivity between the enantiomers, despite the increase in activity up to 13 nM. The hydrophilic group like sulfonamido group at para position of 3-phenylpropyl motif of 1-(α-alkyl-α-phenylmethyl-3-(3-phenylpropyl)urea improves the activity as well as enantiomeric selectivity. All these ureas are proved to be specific inhibitor of sEH without inhibition against mEH. PMID:27092411

  3. Efficient alcoholysis of 5,6-dihydro-1,10-phenanthroline-5,6-epoxide with ytterbium(III) triflate and subsequent enantioselective transesterification with lipases

    PubMed Central

    Schoffers, Elke; Kohler, Lars

    2009-01-01

    New 5,6-dihydro-1,10-phenanthroline derivatives were prepared in high yield via ytterbium(III) triflate-catalyzed alcoholysis of the corresponding epoxide. Enzymatic transesterifications of racemic alkoxy alcohols afforded enantioselective separations with up to 99% ee. The lipase derived from Burkholderia cepacia (PSCI) was the most efficient, with E-values of up to 200. The steric effect of substituents in the 6-position on reaction time and enantioselectivities was assessed. PMID:20160975

  4. A broadly applicable and practical oligomeric (salen) Co catalyst for enantioselective epoxide ring-opening reactions

    PubMed Central

    White, David E.; Tadross, Pamela M.; Lu, Zhe

    2014-01-01

    The (salen) Co catalyst (4a) can be prepared as a mixture of cyclic oligomers in a short, chromatography-free synthesis from inexpensive, commercially available precursors. This catalyst displays remarkable enhancements in reactivity and enantioselectivity relative to monomeric and other multimeric (salen) Co catalysts in a wide variety of enantioselective epoxide ring-opening reactions. The application of catalyst 4a is illustrated in the kinetic resolution of terminal epoxides by nucleophilic ring-opening with water, phenols, and primary alcohols; the desymmetrization of meso epoxides by addition of water and carbamates; and the desymmetrization of oxetanes by intramolecular ring opening with alcohols and phenols. The favorable solubility properties of complex 4a under the catalytic conditions facilitated mechanistic studies, allowing elucidation of the basis for the beneficial effect of oligomerization. Finally, a catalyst selection guide is provided to delineate the specific advantages of oligomeric catalyst 4a relative to (salen) Co monomer 1 for each reaction class. PMID:25045188

  5. Highly Enantioselective Epoxidation of α,β-Unsaturated Ketones Catalyzed by Rare-Earth Amides [(Me3Si)2N]3RE(μ-Cl)Li(THF)3 with Phenoxy-Functionalized Chiral Prolinols.

    PubMed

    Zeng, Chao; Yuan, Dan; Zhao, Bei; Yao, Yingming

    2015-05-01

    A simple and efficient catalytic enantioselective epoxidation of α,β-unsaturated ketones has been successfully developed, which was catalyzed by rare-earth metal amides [(Me3Si)2N]3RE(μ-Cl)Li(THF)3 (RE = Yb (1), La (2), Sm (3), Y (4), Lu (5)) in the presence of phenoxy-functionalized chiral prolinols at room temperature using tert-butylhydroperoxide (TBHP) as the oxidant. The combination of an Yb-based amide 1 and a chiral proligand (S)-2,4-di-tert-butyl-6-((2-(hydroxydiphenylmethyl)pyrrolidin-1-yl)methyl)phenol) performed very well, and both the yields and the enantiomeric excess of the chiral epoxides reached up to 99% and 99% ee. PMID:25905674

  6. Combinatorial evolution of site- and enantioselective catalysts for polyene epoxidation

    NASA Astrophysics Data System (ADS)

    Lichtor, Phillip A.; Miller, Scott J.

    2012-12-01

    Selectivity in the catalytic functionalization of complex molecules is a major challenge in chemical synthesis. The problem is magnified when there are several possible stereochemical outcomes and when similar functional groups occur repeatedly within the same molecule. Selective polyene oxidation provides an archetypical example of this challenge. Historically, enzymatic catalysis has provided the only precedents. Although non-enzymatic catalysts that meet some of these challenges became known, a comprehensive solution has remained elusive. Here, we describe low molecular weight peptide-based catalysts, discovered through a combinatorial synthesis and screening protocol, that exhibit site- and enantioselective oxidation of certain positions of various isoprenols. This diversity-based approach, which exhibits features reminiscent of the directed evolution of enzymes, delivers catalysts that compare favourably to the state-of-the-art for the asymmetric oxidation of these compounds. Moreover, the approach culminated in catalysts that exhibit alternative-site selectivity in comparison to oxidation catalysts previously described.

  7. Enantioselective polymerization of epoxides using biaryl-linked bimetallic cobalt catalysts: a mechanistic study.

    PubMed

    Ahmed, Syud M; Poater, Albert; Childers, M Ian; Widger, Peter C B; LaPointe, Anne M; Lobkovsky, Emil B; Coates, Geoffrey W; Cavallo, Luigi

    2013-12-18

    The enantioselective polymerization of propylene oxide (PO) using biaryl-linked bimetallic salen Co catalysts was investigated experimentally and theoretically. Five key aspects of this catalytic system were examined: (1) the structural features of the catalyst, (2) the regio- and stereoselectivity of the chain-growth step, (3) the probable oxidation and electronic state of Co during the polymerization, (4) the role of the cocatalyst, and (5) the mechanism of monomer enchainment. Several important insights were revealed. First, density functional theory (DFT) calculations provided detailed structural information regarding the regio- and stereoselective chain-growth step. Specifically, the absolute stereochemistry of the binaphthol linker determines the enantiomer preference in the polymerization, and the interaction between the salen ligand and the growing polymer chain is a fundamental aspect of enantioselectivity. Second, a new bimetallic catalyst with a conformationally flexible biphenol linker was synthesized and found to enantioselectively polymerize PO, though with lower enantioselectivity than the binaphthol linked catalysts. Third, DFT calculations revealed that the active form of the catalyst has two active exo anionic ligands (chloride or carboxylate) and an endo polymer alkoxide which can ring-open an adjacent cobalt-coordinated epoxide. Fourth, calculations showed that initiation is favored by an endo chloride ligand, while propagation is favored by the presence of two exo carboxylate ligands. PMID:24199614

  8. Enantioselective cross-coupling of meso-epoxides with aryl halides.

    PubMed

    Zhao, Yang; Weix, Daniel J

    2015-03-11

    The first enantioselective cross-electrophile coupling of aryl bromides with meso-epoxides to form trans-β-arylcycloalkanols is presented. The reaction is catalyzed by a combination of (bpy)NiCl2 and a chiral titanocene under reducing conditions. Yields range from 57 to 99% with 78-95% enantiomeric excess. The 30 examples include a variety of functional groups (ether, ester, ketone, nitrile, ketal, trifluoromethyl, sulfonamide, sulfonate ester), both aryl and vinyl halides, and five- to seven-membered rings. The intermediacy of a carbon radical is strongly suggested by the conversion of cyclooctene monoxide to an aryl [3.3.0]bicyclooctanol. PMID:25716775

  9. Enantioselective ring-opening of meso-epoxides by aromatic amines catalyzed by a homochiral metal-organic framework.

    PubMed

    Regati, Sridhar; He, Yabing; Thimmaiah, Muralidhara; Li, Peng; Xiang, Shengchang; Chen, Banglin; Zhao, John Cong-Gui

    2013-10-28

    The enantioselective ring-opening of meso-epoxides by aromatic amines was achieved by using a new chiral metal-organic framework . The corresponding α-hydroxyamines were obtained with good yields and ee values (up to 89% ee). PMID:24030658

  10. Substrate range and enantioselectivity of epoxidation reactions mediated by the ethene-oxidising Mycobacterium strain NBB4.

    PubMed

    Cheung, Samantha; McCarl, Victoria; Holmes, Andrew J; Coleman, Nicholas V; Rutledge, Peter J

    2013-02-01

    Mycobacterium strain NBB4 is an ethene-oxidising micro-organism isolated from estuarine sediments. In pursuit of new systems for biocatalytic epoxidation, we report the capacity of strain NBB4 to convert a diverse range of alkene substrates to epoxides. A colorimetric assay based on 4-(4-nitrobenzyl)pyridine) has been developed to allow the rapid characterisation and quantification of biocatalytic epoxide synthesis. Using this assay, we have demonstrated that ethene-grown NBB4 cells epoxidise a wide range of alkenes, including terminal (propene, 1-butene, 1-hexene, 1-octene and 1-decene), cyclic (cyclopentene, cyclohexene), aromatic (styrene, indene) and functionalised substrates (allyl alcohol, dihydropyran and isoprene). Apparent specific activities have been determined and range from 2.5 to 12.0 nmol min(-1) per milligram of cell protein. The enantioselectivity of epoxidation by Mycobacterium strain NBB4 has been established using styrene as a test substrate; (R)-styrene oxide is produced in enantiomeric excesses greater than 95%. Thus, the ethene monooxygenase of Mycobacterium NBB4 has a broad substrate range and promising enantioselectivity, confirming its potential as a biocatalyst for alkene epoxidation. PMID:22410742

  11. Mononuclear Nonheme High-Spin Iron(III)-Acylperoxo Complexes in Olefin Epoxidation and Alkane Hydroxylation Reactions.

    PubMed

    Wang, Bin; Lee, Yong-Min; Clémancey, Martin; Seo, Mi Sook; Sarangi, Ritimukta; Latour, Jean-Marc; Nam, Wonwoo

    2016-02-24

    Mononuclear nonheme high-spin iron(III)-acylperoxo complexes bearing an N-methylated cyclam ligand were synthesized, spectroscopically characterized, and investigated in olefin epoxidation and alkane hydroxylation reactions. In the epoxidation of olefins, epoxides were yielded as the major products with high stereo-, chemo-, and enantioselectivities; cis- and trans-stilbenes were oxidized to cis- and trans-stilbene oxides, respectively. In the epoxidation of cyclohexene, cyclohexene oxide was formed as the major product with a kinetic isotope effect (KIE) value of 1.0, indicating that nonheme iron(III)-acylperoxo complexes prefer C═C epoxidation to allylic C-H bond activation. Olefin epoxidation by chiral iron(III)-acylperoxo complexes afforded epoxides with high enantioselectivity, suggesting that iron(III)-acylperoxo species, not high-valent iron-oxo species, are the epoxidizing agent. In alkane hydroxylation reactions, iron(III)-acylperoxo complexes hydroxylated C-H bonds as strong as those in cyclohexane at -40 °C, wherein (a) alcohols were yielded as the major products with high regio- and stereoselectivities, (b) activation of C-H bonds by the iron(III)-acylperoxo species was the rate-determining step with a large KIE value and good correlation between reaction rates and bond dissociation energies of alkanes, and (c) the oxygen atom in the alcohol product was from the iron(III)-acylperoxo species, not from molecular oxygen. In isotopically labeled water (H2(18)O) experiments, incorporation of (18)O from H2(18)O into oxygenated products was not observed in the epoxidation and hydroxylation reactions. On the basis of mechanistic studies, we conclude that mononuclear nonheme high-spin iron(III)-acylperoxo complexes are strong oxidants capable of oxygenating hydrocarbons prior to their conversion into iron-oxo species via O-O bond cleavage. PMID:26816269

  12. Phosphine-mediated Highly Enantioselective Spirocyclization with Ketimines as Substrates.

    PubMed

    Han, Xiaoyu; Chan, Wai-Lun; Yao, Weijun; Wang, Yongjiang; Lu, Yixin

    2016-05-23

    Phosphine-catalyzed enantioselective annulation reactions involving ketimines are a daunting synthetic challenge owing to the intrinsic low reactivity of ketimine substrates. A highly enantioselective [3+2] cycloaddition reaction that makes use of isatin-derived ketimines as reaction partners was developed. Notably, both simple and γ-substituted allenoates could be utilized, and various 3,2'-pyrrolidinyl spirooxindoles with a tetrasubstituted stereocenter were obtained in excellent yields and with nearly perfect enantioselectivity (>98 % ee in all cases). PMID:27080309

  13. Crystalline-gradient polycarbonates prepared from enantioselective terpolymerization of meso-epoxides with CO2

    NASA Astrophysics Data System (ADS)

    Liu, Ye; Ren, Wei-Min; He, Ke-Ke; Lu, Xiao-Bing

    2014-12-01

    The development of efficient processes for CO2 transformation into useful products is a long-standing goal for chemists, since CO2 is an abundant, inexpensive and non-toxic renewable C1 resource. Here we describe the enantioselective copolymerization of 3,4-epoxytetrahydrofuran with CO2 mediated by biphenol-linked dinuclear cobalt complex, affording the corresponding polycarbonate with >99% carbonate linkages and excellent enantioselectivity (up to 99% enantiomeric excess). Notably, the resultant isotactic polycarbonate is a typical semicrystalline polymer, possessing a melting point of 271 °C. Furthermore, the enantioselective terpolymerization of 3,4-epoxytetrahydrofuran, cyclopentene oxide and CO2 mediated by this dinuclear cobalt complex gives novel gradient polycarbonates, in which the decrement of one component and the increment of the other component occur sequentially from one chain end to the other end. The resultant terpolymers show perfectly isotactic structure and have unique crystalline-gradient nature, in which the crystallinity continuously varies along the main chain.

  14. Crystalline-gradient polycarbonates prepared from enantioselective terpolymerization of meso-epoxides with CO2.

    PubMed

    Liu, Ye; Ren, Wei-Min; He, Ke-Ke; Lu, Xiao-Bing

    2014-01-01

    The development of efficient processes for CO2 transformation into useful products is a long-standing goal for chemists, since CO2 is an abundant, inexpensive and non-toxic renewable C1 resource. Here we describe the enantioselective copolymerization of 3,4-epoxytetrahydrofuran with CO2 mediated by biphenol-linked dinuclear cobalt complex, affording the corresponding polycarbonate with >99% carbonate linkages and excellent enantioselectivity (up to 99% enantiomeric excess). Notably, the resultant isotactic polycarbonate is a typical semicrystalline polymer, possessing a melting point of 271 °C. Furthermore, the enantioselective terpolymerization of 3,4-epoxytetrahydrofuran, cyclopentene oxide and CO2 mediated by this dinuclear cobalt complex gives novel gradient polycarbonates, in which the decrement of one component and the increment of the other component occur sequentially from one chain end to the other end. The resultant terpolymers show perfectly isotactic structure and have unique crystalline-gradient nature, in which the crystallinity continuously varies along the main chain. PMID:25477252

  15. Towards a General Understanding of Carbonyl-Stabilised Ammonium Ylide-Mediated Epoxidation Reactions.

    PubMed

    Novacek, Johanna; Roiser, Lukas; Zielke, Katharina; Robiette, Raphaël; Waser, Mario

    2016-08-01

    The key factors for carbonyl-stabilised ammonium ylide-mediated epoxidation reactions were systematically investigated by experimental and computational means and the hereby obtained energy profiles provide explanations for the observed experimental results. In addition, we were able to identify the first tertiary amine-based chiral auxiliary that allows for high enantioselectivities and high yields for such epoxidation reactions. PMID:27381752

  16. Highly Enantioselective Rhodium-Catalyzed Addition of Arylboroxines to Simple Aryl Ketones: Efficient Synthesis of Escitalopram.

    PubMed

    Huang, Linwei; Zhu, Jinbin; Jiao, Guangjun; Wang, Zheng; Yu, Xingxin; Deng, Wei-Ping; Tang, Wenjun

    2016-03-24

    Highly enantioselective additions of arylboroxines to simple aryl ketones have been achieved for the first time with a Rh/(R,R,R,R)-WingPhos catalyst, thus providing a range of chiral diaryl alkyl carbinols with excellent ee values and yields. (R,R,R,R)-WingPhos has been proven to be crucial for the high reactivity and enantioselectivity. The method has enabled a new, concise, and enantioselective synthesis of the antidepressant drug escitalopram. PMID:26933831

  17. Highly enantioselective Henry reactions of aromatic aldehydes catalyzed by an amino alcohol-copper(II) complex.

    PubMed

    Qin, Dan-Dan; Lai, Wen-Han; Hu, Di; Chen, Zheng; Wu, An-An; Ruan, Yuan-Ping; Zhou, Zhao-Hui; Chen, Hong-Bin

    2012-08-20

    Amino alcohol-Cu(II) catalyst: Highly enantioselective Henry reactions between aromatic aldehydes and nitromethane have been developed. The reactions were catalyzed by an easily available and operationally simple amino alcohol-copper(II) catalyst. In total, 38 substrates were tested and the R-configured products were obtained in good yields with excellent enantioselectivities. PMID:22791567

  18. Redox-triggered C-C coupling of alcohols and vinyl epoxides: diastereo- and enantioselective formation of all-carbon quaternary centers via tert-(hydroxy)-prenylation.

    PubMed

    Feng, Jiajie; Garza, Victoria J; Krische, Michael J

    2014-06-25

    Iridium catalyzed primary alcohol oxidation triggers reductive C-O bond cleavage of isoprene oxide to form aldehyde-allyliridium pairs that combine to form products of tert-(hydroxy)-prenylation, a motif found in >2000 terpenoid natural products. Curtin-Hammett effects are exploited to enforce high levels of anti-diastereo- and enantioselectivity in the formation of an all-carbon quaternary center. The present redox-triggered carbonyl additions occur in the absence of stoichiometric byproducts, premetalated reagents, and discrete alcohol-to-aldehyde redox manipulations. PMID:24915473

  19. Highly Enantioselective Formation of α-Allyl-α-Arylcyclopentanones via Pd-Catalysed Decarboxylative Asymmetric Allylic Alkylation.

    PubMed

    Akula, Ramulu; Doran, Robert; Guiry, Patrick J

    2016-07-11

    A highly enantioselective Pd-catalysed decarboxylative asymmetric allylic alkylation of cyclopentanone derived α-aryl-β-keto esters employing the (R,R)-ANDEN-phenyl Trost ligand has been developed. The product (S)-α-allyl-α-arylcyclopentanones were obtained in excellent yields and enantioselectivities (up to >99.9 % ee). This represents one of the most highly enantioselective formations of an all-carbon quaternary stereogenic center reported to date. This reaction was demonstrated on a 4.0 mmol scale without any deterioration of enantioselectivity and was exploited as the key enantioselective transformation in an asymmetric formal synthesis of the natural product (+)-tanikolide. PMID:27191198

  20. Highly enantioselective trapping of zwitterionic intermediates by imines

    NASA Astrophysics Data System (ADS)

    Qiu, Huang; Li, Ming; Jiang, Li-Qin; Lv, Feng-Ping; Zan, Li; Zhai, Chang-Wei; Doyle, Michael P.; Hu, Wen-Hao

    2012-09-01

    Reactions with the unstable and highly reactive zwitterionic intermediates generated in processes catalysed by transition metals are providing new opportunities for molecular constructions. Insertion reactions involve the collapse of zwitterionic intermediates, but trapping them would allow structural elaborations that are not currently available. To synthesize complex molecules in this manner, reactive electrophiles can be used to trap the zwitterionic intermediates. Here, we describe the use of imines, activated by chiral organocatalysts, and a highly efficient integrated rhodium and chiral Brønsted acid co-catalysed process to trap zwitterionic intermediates that have been proposed previously to undergo a formal C-H insertion reaction, allowing us to obtain polyfunctionalized indole and oxindole derivatives in a single step with excellent diastereoselectivity and enantioselectivity.

  1. Short, Enantioselective Total Synthesis of Highly Oxidized Taxanes.

    PubMed

    Yuan, Changxia; Jin, Yehua; Wilde, Nathan C; Baran, Phil S

    2016-07-11

    In the realm of natural product chemistry, few isolates have risen to the level of fame justifiably accorded to Taxol (1) and its chemical siblings. This report describes the most concise route to date for accessing the highly oxidized members of this family. As representative members of taxanes containing five oxygen atoms, decinnamoyltaxinine E (2) and taxabaccatin III (3), have succumbed to enantioselective total synthesis for the first time in only 18 steps from a simple olefin starting material. The strategy holistically mimics nature's approach (two-phase synthesis) and features a carefully choreographed sequence of stereoselective oxidations and a remarkable redox-isomerization to set the key trans-diol present in 2 and 3. This work lays the critical groundwork necessary to access even higher oxidized taxanes such as 1 in a more practical fashion, thus empowering a medicinal chemistry campaign that is not wedded to semi-synthesis. PMID:27240325

  2. General, Highly Selective Synthesis of 1,3- and 1,4-Difunctionalized Building Blocks by Regiodivergent Epoxide Opening.

    PubMed

    Funken, Nico; Mühlhaus, Felix; Gansäuer, Andreas

    2016-09-19

    We describe a regiodivergent epoxide opening (REO) featuring a catalyst-controlled synthesis of enantiomerically and diastereomerically highly enriched or pure syn- and anti- 1,3- and 1,4-difunctionalized building blocks from a common epoxide precursor. The REO is attractive for natural product synthesis and as a branching reaction for diversity-oriented synthesis with epoxides. PMID:27600090

  3. Highly enantioselective conjugate addition of malononitrile to 2-enoylpyridines with bifunctional organocatalyst.

    PubMed

    Molleti, Nagaraju; Rana, Nirmal K; Singh, Vinod K

    2012-09-01

    An efficient enantioselective conjugate addition of malononitrile to a range of β-substituted 2-enoylpyridines catalyzed by cinchona alkaloid-based bifunctional urea catalysts has been developed. Both enantiomers of the products could be achieved with the same level of enantioselectivity by using pseudoenantiomeric catalysts in up to 97% ee and in excellent yields. One of the enantioenriched products has been transformed to a highly functionalized piperidone derivative. PMID:22920458

  4. Quinine-catalyzed highly enantioselective cycloannulation of o-quinone methides with malononitrile.

    PubMed

    Adili, Alafate; Tao, Zhong-Lin; Chen, Dian-Feng; Han, Zhi-Yong

    2015-02-28

    2-Amino-3-cyano-4H-chromenes show great potential as novel anticancer agents. Here we report a quinine-catalyzed highly enantioselective formal 4 + 2 cycloaddition of ortho-quinone methides and malononitrile, providing a unique approach to 4-arylvinyl, 4-aryl and 4-vinyl 2-amino-3-cyano-4H-chromenes with excellent yields and enantioselectivities. Moreover, this reaction can be performed in up to 6 mmol scale without any noticeable loss of yield and stereoselectivity. PMID:25592961

  5. Highly Active Titanocene Catalysts for Epoxide Hydrosilylation: Synthesis, Theory, Kinetics, EPR Spectroscopy.

    PubMed

    Henriques, Dina Schwarz G; Zimmer, Katharina; Klare, Sven; Meyer, Andreas; Rojo-Wiechel, Elena; Bauer, Mirko; Sure, Rebecca; Grimme, Stefan; Schiemann, Olav; Flowers, Robert A; Gansäuer, Andreas

    2016-06-27

    A catalytic system for titanocene-catalyzed epoxide hydrosilylation is described. It features a straightforward preparation of titanocene hydrides that leads to a reaction with low catalyst loading, high yields, and high selectivity of radical reduction. The mechanism was studied by a suite of methods, including kinetic studies, EPR spectroscopy, and computational methods. An unusual resting state leads to the observation of an inverse rate order with respect to the epoxide. PMID:27125466

  6. Highly Enantioselective, Intermolecular Hydroamination of Allenyl Esters Catalyzed by Bifunctional Phosphinothioureas

    PubMed Central

    2015-01-01

    Bifunctional phosphinothiourea catalysts have been developed successfully for the highly regio- and enantioselective γ-hydroamination of allenyl and propargyl esters with N-methoxy carbamate nucleophiles to yield α,β-unsaturated γ-amino acid ester products. In the case of propargyl ester substrates, the reaction proceeds through reversible phosphinothiourea-catalyzed isomerization to the corresponding allenyl ester. The high enantioselectivity of the process is attributed to a cooperative conjugate addition of a thiourea-bound carbamate anion to a vinyl phosphonium ion resulting from covalent activation of the allenyl ester substrate. PMID:25496451

  7. Diastereo- and enantioselective three-component coupling approach to highly substituted pyrrolidines.

    PubMed

    Chaulagain, Mani Raj; Felten, Albert E; Gilbert, Kevin; Aron, Zachary D

    2013-09-20

    The enantioselective synthesis of substituted pyrrolidines through a mild Lewis-acid catalyzed three-component coupling reaction between picolinaldehyde, amino acids, and activated olefins is reported. The reaction uses low catalyst loadings of commercially available chiral diamines and copper triflate proposed to self-assemble in conjunction with the chelating aldehydes, 4-substituted-2-picolinaldehydes or 4-methylthiazole-2-carboxaldehyde, to generate a catalyst complex. A model is provided to explain how this complex directs enantioselectivity. This work represents a significant advance in the ease, scope, and cost of producing highly substituted, enantioenriched pyrrolidines. PMID:23952564

  8. Asymmetric synthesis of L-carbidopa based on a highly enantioselective α-amination.

    PubMed

    Pericas, Àlex; Shafir, Alexandr; Vallribera, Adelina

    2013-04-01

    A stereoselective synthesis of L-carbidopa in seven steps and 50% overall yield from commercial compounds is described. The key step involves a highly enantioselective α-amination reaction of an acyclic β-ketoester with di-tert-butyl azodicarboxylate induced by europium and (R,R)-diphenyl-pybox. PMID:23477289

  9. Bifunctional N-heterocyclic carbene-catalyzed highly enantioselective synthesis of spirocyclic oxindolo-β-lactams.

    PubMed

    Zhang, Han-Ming; Gao, Zhong-Hua; Ye, Song

    2014-06-01

    The N-heterocyclic carbene-catalyzed Staudinger reaction of ketenes with isatin-derived ketimines was investigated. The bifunctional NHCs with a free hydroxyl group were demonstrated as efficient catalysts for the reaction, giving the corresponding spirocyclic oxindolo-β-lactams in high yields with excellent diastereo- and enantioselectivities. PMID:24856000

  10. Highly Enantioselective Direct Alkylation of Arylacetic Acids with Chiral Lithium Amides as Traceless Auxiliaries

    PubMed Central

    Stivala, Craig E.; Zakarian, Armen

    2012-01-01

    A direct, highly enantioselective alkylation of arylacetic acids via enediolates using a readily available chiral lithium amide as a stereodirecting reagent has been developed. This approach circumvents the traditional attachment and removal of chiral auxiliaries used currently for this type of transformation. The protocol is operationally simple, and the chiral reagent is readily recoverable. PMID:21744818

  11. Highly Enantioselective Iridium-Catalyzed Hydrogenation of Cyclic Enamides.

    PubMed

    Salomó, Ernest; Orgué, Sílvia; Riera, Antoni; Verdaguer, Xavier

    2016-07-01

    The MaxPHOX-Ir catalyst system provided the highest selectivity ever reported for the reduction of cyclic enamides derived from α- and β-tetralones. This result indicates that iridium catalysts are also proficient in reducing alkenes bearing metal-coordinating groups. In the present system, selectivity was pressure-dependent: In most cases, a decrease in the H2 pressure to 3 bar resulted in an increase in enantioselectivity. Moreover, the process can be carried out in environmentally friendly solvents, such as methanol and ethyl acetate, with no loss of selectivity. PMID:27186653

  12. Dynamic Kinetic Resolution of Biaryl Lactones via a Chiral Bifunctional Amine Thiourea-Catalyzed Highly Atropo-enantioselective Transesterification.

    PubMed

    Yu, Chenguang; Huang, He; Li, Xiangmin; Zhang, Yueteng; Wang, Wei

    2016-06-01

    A solution to the unmet synthetic challenge of achieving highly atropo-enantioselective transesterification of Bringmann's lactones has been realized, employing a chiral bifunctional amine thiourea as promoter. The synergistic activation of the lactones and alcohols/phenols by the respective thiourea and amine groups is crucial for achieving the highly enantioselective, high-yielding dynamic kinetic resolution process. This protocol gives highly optically pure, axially chiral biaryl compounds with a broad substrate scope under mild reaction conditions. PMID:27218264

  13. Highly enantioselective reductive cyclization of acetylenic aldehydes via rhodium catalyzed asymmetric hydrogenation.

    PubMed

    Rhee, Jong Uk; Krische, Michael J

    2006-08-23

    Catalytic hydrogenation of acetylenic aldehydes 1a-12a using chirally modified cationic rhodium catalysts enables highly enantioselective reductive cyclization to afford cyclic allylic alcohols 1b-12b. Using an achiral hydrogenation catalyst, the chiral racemic acetylenic aldehydes 13a-15a engage in highly syn-diastereoselective reductive cyclizations to afford cyclic allylic alcohols 13b-15b. Ozonolysis of cyclization products 7b and 9b allows access to optically enriched alpha-hydroxy ketones 7c and 9c. Reductive cyclization of enyne 7a under a deuterium atmosphere provides the monodeuterated product deuterio-7b, consistent with a catalytic mechanism involving alkyne-carbonyl oxidative coupling followed by hydrogenolytic cleavage of the resulting oxametallacycle. These hydrogen-mediated transformations represent the first examples of the enantioselective reductive cyclization of acetylenic aldehydes. PMID:16910650

  14. 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. PMID:19552446

  15. Highly diastereoselective and enantioselective formal [4 + 3] cycloaddition of donor-acceptor cyclobutanes with nitrones.

    PubMed

    Hu, Jiang-Lin; Wang, Lijia; Xu, Hao; Xie, Zuowei; Tang, Yong

    2015-06-01

    The first highly diastereoselective and enantioselective catalytic formal [4 + 3] cycloaddition of 1,1-cyclobutane diester with nitrone has been developed. Sterically hindered chiral SaBOX/Cu(II) complex promotes the reaction efficiently with a broad substrate scope, producing a range of multifunctionalized optically active 1,2-oxazepanes with excellent stereocontrol (up to >99/1 dr and 97% ee). PMID:25974724

  16. Organocatalytic asymmetric addition of naphthols and electron-rich phenols to isatin-derived ketimines: highly enantioselective construction of tetrasubstituted stereocenters.

    PubMed

    Montesinos-Magraner, Marc; Vila, Carlos; Cantón, Rubén; Blay, Gonzalo; Fernández, Isabel; Muñoz, M Carmen; Pedro, José R

    2015-05-18

    A quinine-derived thiourea organocatalyst promoted the highly enantioselective addition of naphthols and activated phenols to ketimines derived from isatins. The reaction afforded chiral 3-amino-2-oxindoles with a quaternary stereocenter in high yields (up to 99%) with excellent enantioselectivity (up to 99% ee). To the best of our knowledge, this transformation is the first highly enantioselective addition of naphthols to ketimines. PMID:25845341

  17. γ-Carbon Activation through N-Heterocyclic Carbene/Brønsted Acids Cooperative Catalysis: A Highly Enantioselective Route to δ-Lactams.

    PubMed

    Xiao, Yonglong; Wang, Jinxin; Xia, Wenjing; Shu, Shuangjie; Jiao, Shenchao; Zhou, Yu; Liu, Hong

    2015-08-01

    A γ-carbon activation method that operates through N-heterocyclic carbene/Brønsted acid cooperative catalysis for highly enantioselective synthesis of δ-lactams is reported. The protocol allows the challenging remote γ-carbon control of regioselectivity and enantioselectivity through introduction of an appropriate γ-leaving group in the enals. The reaction offers good yields and excellent enantioselectivities, and the resulting cyclic products can be easily converted into high-value drug-like derivatives. PMID:26213807

  18. High biobased content epoxy-anhydride thermosets from epoxidized sucrose esters of Fatty acids.

    PubMed

    Pan, Xiao; Sengupta, Partha; Webster, Dean C

    2011-06-13

    Novel highly functional biobased epoxy compounds, epoxidized sucrose esters of fatty acids (ESEFAs), were cross-linked with a liquid cycloaliphatic anhydride to prepare polyester thermosets. The degree of cure or conversion was studied using differential scanning calorimetry (DSC), and the sol content of the thermosets was determined using solvent extraction. The mechanical properties were studied using tensile testing to determine Young's modulus, tensile stress, and elongation at break. Dynamic mechanical analysis (DMA) was used to determine glass-transition temperature, storage modulus, and cross-link density. The nanomechanical properties of the surfaces were studied using nanoindentation to determine reduced modulus and indentation hardness. The properties of coatings on steel substrates were studied to determine coating hardness, adhesion, solvent resistance, and mechanical durability. Compared with the control, epoxidized soybean oil, the anhydride-cured ESEFAs have high modulus and are hard and ductile, high-performance thermoset materials while maintaining a high biobased content (71-77% in theory). The exceptional performance of the ESEFAs is attributed to the unique structure of these macromolecules: well-defined compact structures with high epoxide functionality. These biobased thermosets have potential uses in applications such as composites, adhesives, and coatings. PMID:21561167

  19. Microbiological Transformations. 33. Fungal Epoxide Hydrolases Applied to the Synthesis of Enantiopure Para-Substituted Styrene Oxides. A Mechanistic Approach.

    PubMed

    Pedragosa-Moreau, S.; Morisseau, C.; Zylber, J.; Archelas, A.; Baratti, J.; Furstoss, R.

    1996-10-18

    The biohydrolysis of differently para-substituted styrene oxide derivatives was studied, using whole cells of the fungi Aspergillus niger or Beauveria sulfurescens. These microorganisms proved to be equipped with epoxide hydrolases which are able to achieve these hydrolyses with high enantioselectivity. This allowed the preparation of the optically active epoxides and of the corresponding vicinal diols which were obtained with good to excellent enantiomeric purity. These two microorganisms proved to be enantiocomplementary. A mechanistic study, carried out using a crude lyophilized enzymatic extract from A.niger, indicated via Hammet coefficient plotting that this hydrolysis is very probably due to a general base-catalyzed process. PMID:11667667

  20. Asymmetric hydrogenation of ketones: Tactics to achieve high reactivity, enantioselectivity, and wide scope

    PubMed Central

    Ohkuma, Takeshi

    2010-01-01

    Ru complexes with chiral diphosphines and amine-based ligands achieve high catalytic activity and enantioselectivity for the hydrogenation of ketones under neutral to slightly basic conditions. The chiral environment is controllable by changing the combination of these two ligands. A concerted six-membered transition state is proposed to be the origin of the high reactivity. The η6-arene/TsDPEN–Ru and MsDPEN–Cp*Ir catalysts effect the asymmetric reaction under slightly acidic conditions. A variety of chiral secondary alcohols are obtained in high enantiomeric excess. PMID:20228621

  1. 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

    2016-05-01

    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. PMID:26990445

  2. Epoxide hydrolase of Trichoderma reesei: Biochemical properties and conformational characterization.

    PubMed

    de Oliveira, Gabriel Stephani; Adriani, Patricia Pereira; Borges, Flavia Garcia; Lopes, Adriana Rios; Campana, Patricia T; Chambergo, Felipe S

    2016-08-01

    Epoxide hydrolases (EHs) are enzymes that are present in all living organisms and catalyze the hydrolysis of epoxides to the corresponding vicinal diols. EHs have biotechnological potential in chiral chemistry. We report the cloning, purification, enzymatic activity, and conformational analysis of the TrEH gene from Trichoderma reesei strain QM9414 using circular dichroism spectroscopy. The EH gene has an open reading frame encoding a protein of 343 amino acid residues, resulting in a molecular mass of 38.2kDa. The enzyme presents an optimum pH of 7.2, and it is highly active at temperatures ranging from 23 to 50°C and thermally inactivated at 70°C (t1/2=7.4min). The Michaelis constants (Km) were 4.6mM for racemic substrate, 21.7mM for (R)-(+)-styrene oxide and 3.0mM for (S)-(-)-styrene oxide. The kcat/Km analysis indicated that TrEH is enantioselective and preferentially hydrolyzes (S)-(-)-styrene oxide. The conformational stability studies suggested that, despite the extreme conditions (high temperatures and extremely acid and basic pHs), TrEH is able to maintain a considerable part of its regular structures, including the preservation of the native cores in some cases. The recombinant protein showed enantioselectivity that was distinct from other fungus EHs, making this protein a potential biotechnological tool. PMID:27177457

  3. Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

    PubMed Central

    Zhu, Haipan; Du, Peile; Li, Jianjun; Liao, Ziyang; Liu, Guohua

    2016-01-01

    Summary A cooperative catalytic strategy of chiral iminium catalysis by regioselective activation of the C=C bond in enals and a transition metal promoting to open the 2-vinylcyclopropanes for highly regio- and enantioselective [3 + 2] cycloaddition reaction of 2-vinylcyclopropanes with α,β-unsaturated aldehydes has been developed. PMID:27559383

  4. 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.

  5. Catalytic enantioselective synthesis of chiral organic compounds of ultra-high purity of >99% ee

    PubMed Central

    NEGISHI, Ei-ichi; XU, Shiqing

    2015-01-01

    Shortly after the discovery of Zr-catalyzed carboalumination of alkynes in 1978, we sought expansion of the scope of this reaction so as to develop its alkene version for catalytic asymmetric C–C bond formation, namely the ZACA (Zr-catalyzed asymmetric carboalumination of alkenes). However, this seemingly easy task proved to be quite challenging. The ZACA reaction was finally discovered in 1995 by suppressing three competitive side reactions, i.e., (i) cyclic carbometalation, (ii) β-H transfer hydrometalation, and (iii) alkene polymerization. The ZACA reaction has been used to significantly modernize and improve syntheses of various natural products including deoxypolypropionates and isoprenoids. This review focuses on our recent progress on the development of ZACA–lipase-catalyzed acetylation–transition metal-catalyzed cross-coupling processes for highly efficient and enantioselective syntheses of a wide range of chiral organic compounds with ultra-high enantiomeric purities. PMID:26460317

  6. 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

  7. Robust, chiral, and porous BINAP-based metal-organic frameworks for highly enantioselective cyclization reactions.

    PubMed

    Sawano, Takahiro; Thacker, Nathan C; Lin, Zekai; McIsaac, Alexandra R; Lin, Wenbin

    2015-09-30

    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) 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. PMID:26335305

  8. 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

  9. Chiral Epoxides via Borane Reduction of 2-Haloketones Catalyzed By Spiroborate Ester: Application to the Synthesis of Optically Pure 1,2-Hydroxy Ethers and 1,2-Azido Alcohols

    PubMed Central

    Huang, Kun; Wang, Haiyang; Stepanenko, Viatcheslav; De Jesús, Melvin; Torruellas, Carilyn; Correa, Wildeliz; Ortiz-Marciales, Margarita

    2011-01-01

    An enantioselective borane-mediated reduction of a variety of 2-haloketones using 10% of spiroaminoborate ester 1 as catalyst is described. By a simple basic workup of 2-halohydrins, optically active epoxides are obtained in high yield and with excellent enantiopurity (up to 99% ee). Ring opening of oxiranes with phenoxides or sodium azide is investigated under different reaction conditions affording nonracemic 1,2-hydroxy ethers and 1,2-azido alcohols with excellent enantioselectivity (99% ee) and in good to high chemical yield. PMID:21294519

  10. Highly enantioselective synthesis of dihydrocoumarin-fused dihydropyrans via the phosphine-catalyzed [4 + 2] annulation of allenones with 3-aroylcoumarins.

    PubMed

    Han, Xiaoyu; Ni, Huanzhen; Chan, Wai-Lun; Gai, Xikun; Wang, Yongjiang; Lu, Yixin

    2016-06-14

    Phosphine-catalyzed [4 + 2] annulation between 3-aroylcoumarins and allenones has been developed. In the presence of a dipeptide phosphine catalyst 7, dihydrocoumarin-fused dihydropyrans were prepared in high yields and with excellent enantioselectivities. PMID:27173844

  11. N-Heterocyclic carbene-catalyzed [3 + 2] annulation of bromoenals with 3-aminooxindoles: highly enantioselective synthesis of spirocyclic oxindolo-γ-lactams.

    PubMed

    Chen, Kun-Quan; Li, Yao; Zhang, Chun-Lin; Sun, De-Qun; Ye, Song

    2016-02-14

    The chiral N-heterocyclic carbene-catalyzed [3 + 2] annulation of α-bromoenals and 3-aminooxindoles was developed, giving the corresponding spirocyclic oxindolo-γ-lactams in good yields with high diastereoselectivities and enantioselectivities. PMID:26755065

  12. Highly enantioselective synthesis of beta-heteroaryl-substituted dihydrochalcones through Friedel-Crafts alkylation of indoles and pyrrole.

    PubMed

    Wang, Wentao; Liu, Xiaohua; Cao, Weidi; Wang, Jun; Lin, Lili; Feng, Xiaoming

    2010-02-01

    A highly enantioselective Friedel-Crafts (F-C) alkylation of indoles and pyrrole with chalcone derivatives catalyzed by a chiral N,N'-dioxide-Sc(OTf)(3) complex has been developed that tolerates a wide range of substrates. The reaction proceeds in moderate to excellent yields and high enantioselectivities (85-92 % enantiomeric excess) using 2 mol % (for indole) or 0.5 mol % (for pyrrole) catalyst loading, which showed the potential value of the catalyst system. Meanwhile, a strong positive nonlinear effect was observed. On the basis of the experimental results and previous reports, a possible working model is proposed to explain the origin of the activation and asymmetric induction. PMID:20013964

  13. Highly regio- and enantioselective multiple oxy- and amino-functionalizations of alkenes by modular cascade biocatalysis.

    PubMed

    Wu, Shuke; Zhou, Yi; Wang, Tianwen; Too, Heng-Phon; Wang, Daniel I C; Li, Zhi

    2016-01-01

    New types of asymmetric functionalizations of alkenes are highly desirable for chemical synthesis. Here, we develop three novel types of regio- and enantioselective multiple oxy- and amino-functionalizations of terminal alkenes via cascade biocatalysis to produce chiral α-hydroxy acids, 1,2-amino alcohols and α-amino acids, respectively. Basic enzyme modules 1-4 are developed to convert alkenes to (S)-1,2-diols, (S)-1,2-diols to (S)-α-hydroxyacids, (S)-1,2-diols to (S)-aminoalcohols and (S)-α-hydroxyacids to (S)-α-aminoacids, respectively. Engineering of enzyme modules 1 &2, 1 &3 and 1, 2 &4 in Escherichia coli affords three biocatalysts over-expressing 4-8 enzymes for one-pot conversion of styrenes to the corresponding (S)-α-hydroxyacids, (S)-aminoalcohols and (S)-α-aminoacids in high e.e. and high yields, respectively. The new types of asymmetric alkene functionalizations provide green, safe and useful alternatives to the chemical syntheses of these compounds. The modular approach for engineering multi-step cascade biocatalysis is useful for developing other new types of one-pot biotransformations for chemical synthesis. PMID:27297777

  14. Highly regio- and enantioselective multiple oxy- and amino-functionalizations of alkenes by modular cascade biocatalysis

    PubMed Central

    Wu, Shuke; Zhou, Yi; Wang, Tianwen; Too, Heng-Phon; Wang, Daniel I. C.; Li, Zhi

    2016-01-01

    New types of asymmetric functionalizations of alkenes are highly desirable for chemical synthesis. Here, we develop three novel types of regio- and enantioselective multiple oxy- and amino-functionalizations of terminal alkenes via cascade biocatalysis to produce chiral α-hydroxy acids, 1,2-amino alcohols and α-amino acids, respectively. Basic enzyme modules 1–4 are developed to convert alkenes to (S)-1,2-diols, (S)-1,2-diols to (S)-α-hydroxyacids, (S)-1,2-diols to (S)-aminoalcohols and (S)-α-hydroxyacids to (S)-α-aminoacids, respectively. Engineering of enzyme modules 1 & 2, 1 & 3 and 1, 2 & 4 in Escherichia coli affords three biocatalysts over-expressing 4–8 enzymes for one-pot conversion of styrenes to the corresponding (S)-α-hydroxyacids, (S)-aminoalcohols and (S)-α-aminoacids in high e.e. and high yields, respectively. The new types of asymmetric alkene functionalizations provide green, safe and useful alternatives to the chemical syntheses of these compounds. The modular approach for engineering multi-step cascade biocatalysis is useful for developing other new types of one-pot biotransformations for chemical synthesis. PMID:27297777

  15. Highly enantioselective oxidative couplings of 2-naphthols catalyzed by chiral bimetallic oxovanadium complexes with either oxygen or air as oxidant.

    PubMed

    Guo, Qi-Xiang; Wu, Zhi-Jun; Luo, Zhi-Bin; Liu, Quan-Zhong; Ye, Jian-Liang; Luo, Shi-Wei; Cun, Lin-Feng; Gong, Liu-Zhu

    2007-11-14

    The chiral bimetallic oxovanadium complexes have been designed for the enantioselective oxidative coupling of 2-naphthols bearing various substituents at C6 and/or C7. The chirality transferring from the amino acid to the axis of the biphenyl in oxovanadium complexes 2 was found to occur with the use of UV and CD spectra and DFT calculation. The homo-coupling reaction with oxygen as the oxidant was promoted by 5 mol % of an oxovanadium complex derived from L-isoleucine and achiral biphenol to afford binaphthols in nearly quantitative yields with high enantioselectivities of up to 98% ee. An oxovanadium complex derived from L-isoleucine and H8-binaphthol is highly efficient at catalyzing the air-oxidized coupling of 2-naphthols with excellent enantioselectivities of up to 97% ee. 51V NMR study shows that the oxovanadium complexes have two vanadium(V) species. Kinetic studies, the cross-coupling reaction, and HRMS spectral studies on the reaction have been carried out and illustrate that two vanadium(V) species are both involved in catalysis and that the coupling reaction undergoes a radical-radical mechanism in an intramolecular manner. Quantum mechanical calculations rationalize the importance of the cooperative effects of the axial chirality matching S-amino acids on the stereocontrol of the oxidative coupling reaction. The application of the transformation in the preparation of chiral ligands and conjugated polymers confirms the importance of the current process in organic synthesis. PMID:17956093

  16. Cloning and Characterization of a Novel Esterase from Rhodococcus sp. for Highly Enantioselective Synthesis of a Chiral Cilastatin Precursor

    PubMed Central

    Zhang, Yan; Pan, Jiang; Luan, Zheng-Jiao; Park, Sunghoon

    2014-01-01

    A novel nonheme chloroperoxidase (RhEst1), with promiscuous esterase activity for enantioselective hydrolysis of ethyl (S)-2,2-dimethylcyclopropanecarboxylate, was identified from a shotgun library of Rhodococcus sp. strain ECU1013. RhEst1 was overexpressed in Escherichia coli BL21(DE3), purified to homogeneity, and functionally characterized. Fingerprinting analysis revealed that RhEst1 prefers para-nitrophenyl (pNP) esters of short-chain acyl groups. pNP esters with a cyclic acyl moiety, especially that with a cyclobutanyl group, were also substrates for RhEst1. The Km values for methyl 2,2-dimethylcyclopropanecarboxylate (DmCpCm) and ethyl 2,2-dimethylcyclopropane carboxylate (DmCpCe) were 0.25 and 0.43 mM, respectively. RhEst1 could serve as an efficient hydrolase for the bioproduction of optically pure (S)-2,2-dimethyl cyclopropane carboxylic acid (DmCpCa), which is an important chiral building block for cilastatin. As much as 0.5 M DmCpCe was enantioselectively hydrolyzed into (S)-DmCpCa, with a molar yield of 47.8% and an enantiomeric excess (ee) of 97.5%, indicating an extremely high enantioselectivity (E = 240) of this novel and unique biocatalyst for green manufacturing of highly valuable chiral chemicals. PMID:25239898

  17. Catalytic Enantioselective Carboannulation with Allylsilanes

    PubMed Central

    Ball-Jones, Nicolas R.; Badillo, Joseph J.; Tran, Ngon T.; Franz, Annaliese K.

    2015-01-01

    The first catalytic asymmetric carboannulation with allylsilanes is presented. The enantioselective [3+2] annulation is catalyzed using a Sc(III)-indapybox complex with tetrakis-[3,5-bis(trifluoromethyl)phenyl]-borate (BArF) to enhance catalytic activity and control stereoselectivity. Functionalized cyclopentanes containing a quaternary carbon are derived from alkylidene oxindole, coumarin, and malonate substrates with high stereoselectivity. The enantioselective 1,4-conjugate addition and enantioselective lactone formation (via trapping of the β-silyl carbocation) is also described. PMID:25045133

  18. Catalytic enantioselective carboannulation with allylsilanes.

    PubMed

    Ball-Jones, Nicolas R; Badillo, Joseph J; Tran, Ngon T; Franz, Annaliese K

    2014-09-01

    The first catalytic asymmetric carboannulation with allylsilanes is presented. The enantioselective [3+2] annulation is catalyzed using a scandium(III)/indapybox complex with tetrakis-[3,5-bis(trifluoromethyl)phenyl]-borate (BArF) to enhance catalytic activity and control stereoselectivity. Functionalized cyclopentanes containing a quaternary carbon center are derived from alkylidene oxindole, coumarin, and malonate substrates with high stereoselectivity. The enantioselective 1,4-conjugate addition and enantioselective lactone formation (by trapping of the β-silyl carbocation) is also described. PMID:25045133

  19. Development of Highly Active and Regioselective Catalysts for the Copolymerization of Epoxides with Cyclic Anhydrides: An Unanticipated Effect of Electronic Variation.

    PubMed

    DiCiccio, Angela M; Longo, Julie M; Rodríguez-Calero, Gabriel G; Coates, Geoffrey W

    2016-06-01

    Recent developments in polyester synthesis have established several systems based on zinc, chromium, cobalt, and aluminum catalysts for the ring-opening alternating copolymerization of epoxides with cyclic anhydrides. However, to date, regioselective processes for this copolymerization have remained relatively unexplored. Herein we report the development of a highly active, regioselective system for the copolymerization of a variety of terminal epoxides and cyclic anhydrides. Unexpectedly, electron withdrawing substituents on the salen framework resulted in a more redox stable Co(III) species and longer catalyst lifetime. Using enantiopure propylene oxide, we synthesized semicrystalline polyesters via the copolymerization of a range of epoxide/anhydride monomer pairs. PMID:27171536

  20. 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

  1. Highly enantioselective synthesis and cellular evaluation of spirooxindoles inspired by natural products

    NASA Astrophysics Data System (ADS)

    Antonchick, Andrey P.; Gerding-Reimers, Claas; Catarinella, Mario; Schürmann, Markus; Preut, Hans; Ziegler, Slava; Rauh, Daniel; Waldmann, Herbert

    2010-09-01

    In biology-oriented synthesis the underlying scaffold classes of natural products selected in evolution are used to define biologically relevant starting points in chemical structure space for the synthesis of compound collections with focused structural diversity. Here we describe a highly enantioselective synthesis of natural-product-inspired 3,3'-pyrrolidinyl spirooxindoles-which contain an all-carbon quaternary centre and three tertiary stereocentres. This synthesis takes place by means of an asymmetric Lewis acid-catalysed 1,3-dipolar cycloaddition of an azomethine ylide to a substituted 3-methylene-2-oxindole using 1-3 mol% of a chiral catalyst formed from a N,P-ferrocenyl ligand and CuPF6(CH3CN)4. Cellular evaluation has identified a molecule that arrests mitosis, induces multiple microtubule organizing centres and multipolar spindles, causes chromosome congression defects during mitosis and inhibits tubulin regrowth in cells. Our findings support the concept that compound collections based on natural-product-inspired scaffolds constructed with complex stereochemistry will be a rich source of compounds with diverse bioactivity.

  2. Concise Approach to (ent)-14 β-Hydroxysteroids through Highly Diastereo-/Enantioselective Diels-Alder Reactions.

    PubMed

    Peter, Clovis; Ressault, Blandine; Geoffroy, Philippe; Miesch, Michel

    2016-07-25

    14β-Hydroxysteroids, especially 14β-hydroxyandrostane derivatives are closely related to the cardenolide skeletons. The latter were readily available through highly diastero/enantioselective Diels-Alder (DA) reactions requiring high pressure or Lewis acid activation. Moreover, in the presence of (R)- or (S)-carvone as a chiral dienophile, the DA-reaction takes place under chemodivergent parallel kinetic resolution control affording highly enantiomerically enriched 14β-hydroxysteroid derivatives or the corresponding (ent)-14β-hydroxysteroid derivatives. PMID:27192692

  3. Highly E-Selective and Enantioselective Michael Addition to Electron-Deficient Internal Alkynes Under Chiral Iminophosphorane Catalysis.

    PubMed

    Uraguchi, Daisuke; Yamada, Kohei; Ooi, Takashi

    2015-08-17

    A highly E-selective and enantioselective conjugate addition of 2-benzyloxythiazol-5(4H)-ones to β-substituted alkynyl N-acyl pyrazoles is achieved under the catalysis of a P-spiro chiral iminophosphorane. Simultaneous control of the newly generated central chirality and olefin geometry is possible with a wide array of the alkynyl Michael acceptors possessing different aromatic and aliphatic β-substituents, as well as the various α-amino acid-derived thiazolone nucleophiles. This protocol provides access to structurally diverse, optically active α-amino acids bearing a geometrically defined trisubstituted olefinic component at the α-position. PMID:26138611

  4. Exploring the Enantioselective Mechanism of Halohydrin Dehalogenase from Agrobacterium radiobacter AD1 by Iterative Saturation Mutagenesis

    PubMed Central

    Guo, Chao; Chen, Yanpu; Zheng, Yu; Zhang, Wei; Tao, Yunwen; Feng, Juan

    2015-01-01

    Halohydrin dehalogenase from Agrobacterium radiobacter AD1 (HheC) shows great potential in producing valuable chiral epoxides and β-substituted alcohols. The wild-type (WT) enzyme displays a high R-enantiopreference toward most aromatic substrates, whereas no S-selective HheC has been reported to date. To obtain more enantioselective enzymes, seven noncatalytic active-site residues were subjected to iterative saturation mutagenesis (ISM). After two rounds of screening aspects of both activity and enantioselectivity (E), three outstanding mutants (Thr134Val/Leu142Met, Leu142Phe/Asn176His, and Pro84Val/Phe86Pro/Thr134Ala/Asn176Ala mutants) with divergent enantioselectivity were obtained. The two double mutants displayed approximately 2-fold improvement in R-enantioselectivity toward 2-chloro-1-phenylethanol (2-CPE) without a significant loss of enzyme activity compared with the WT enzyme. Strikingly, the Pro84Val/Phe86Pro/Thr134Ala/Asn176Ala mutant showed an inverted enantioselectivity (from an ER of 65 [WT] to an ES of 101) and approximately 100-fold-enhanced catalytic efficiency toward (S)-2-CPE. Molecular dynamic simulation and docking analysis revealed that the phenyl side chain of (S)-2-CPE bound at a different location than that of its R-counterpart; those mutations generated extra connections for the binding of the favored enantiomer, while the eliminated connections reduced binding of the nonfavored enantiomer, all of which could contribute to the observed inverted enantiopreference. PMID:25681194

  5. Enantioselective polyene cyclizations.

    PubMed

    Ungarean, Chad N; Southgate, Emma H; Sarlah, David

    2016-06-28

    The cyclization of polyolefins represents a powerful tool for the rapid generation of molecular complexity. Within the last decade, significant discoveries have been made in the development of methods for converting prochiral polyene substrates into the corresponding polycyclic products with high levels of enantiocontrol. This review highlights advances in the area of enantioselective polyene cyclizations and their use in the synthesis of complex secondary metabolites. PMID:27143099

  6. Highly Enantioselective Fluorescent Recognition of Both Unfunctionalized and Functionalized Chiral Amines by a Facile Amide Formation from a Perfluoroalkyl Ketone.

    PubMed

    Wang, Chao; Anbaei, Parastoo; Pu, Lin

    2016-05-17

    The H8 BINOL-based perfluoroalkyl ketone (S)-2 is found to exhibit highly enantioselective fluorescent enhancements toward both unfunctionalized and functionalized chiral amines. It greatly expands the substrate scope of the corresponding BINOL-based sensor. A dramatic solvent effect was observed for the reaction of the amines with compound (S)-2. In DMF, cleavage of the perfluoroalkyl group of compound (S)-2 to form amides was observed but not in other solvents, such as methylene chloride, chloroform, THF, hexane, and perfluorohexane. Thus, the addition of another solvent, such as THF, can effectively quench the reaction of compound (S)-2 with amines in DMF to allow stable fluorescent measurement. This is the first example that the formation of strong amide bonds under very mild conditions is used for the enantioselective recognition of chiral amines. The mechanism of the reaction of compound (S)-2 with chiral amines is investigated by using various analytical methods including mass spectrometry as well as NMR and UV/Vis absorption spectroscopy. PMID:27061205

  7. A Divergent Enantioselective Strategy for the Synthesis of Griseusins

    PubMed Central

    Zhang, Yinan; Ye, Qing; Wang, Xiachang; She, Qing-Bai; Thorson, Jon S.

    2015-01-01

    The first enantioselective total synthesis of griseusin A, griseusin C, 4′-deacetyl-griseusin A, and two non-native counterparts in 11–14 steps is reported. This strategy highlights a key hydroxy-directed C–H olefination of 1-methylene isochroman with an α,β-unsaturated ketone followed by subsequent stereoselective epoxidation and regioselective cyclization to afford the signature tetrahydro-spiropyran ring. Colorectal cancer cell cytotoxicities of the final products highlight the impact of the griseusin tetrahydro-spiropyran ring on bioactivity. As the first divergent enantioselective synthesis, the strategy put forth sets the stage for further griseusin mechanism-of-action and SAR studies. PMID:26230189

  8. Characterization of an epoxide hydrolase from the Florida red tide dinoflagellate, Karenia brevis.

    PubMed

    Sun, Pengfei; Leeson, Cristian; Zhi, Xiaoduo; Leng, Fenfei; Pierce, Richard H; Henry, Michael S; Rein, Kathleen S

    2016-02-01

    Epoxide hydrolases (EH, EC 3.3.2.3) have been proposed to be key enzymes in the biosynthesis of polyether (PE) ladder compounds such as the brevetoxins which are produced by the dinoflagellate Karenia brevis. These enzymes have the potential to catalyze kinetically disfavored endo-tet cyclization reactions. Data mining of K. brevis transcriptome libraries revealed two classes of epoxide hydrolases: microsomal and leukotriene A4 (LTA4) hydrolases. A microsomal EH was cloned and expressed for characterization. The enzyme is a monomeric protein with molecular weight 44kDa. Kinetic parameters were evaluated using a variety of epoxide substrates to assess substrate selectivity and enantioselectivity, as well as its potential to catalyze the critical endo-tet cyclization of epoxy alcohols. Monitoring of EH activity in high and low toxin producing cultures of K. brevis over a three week period showed consistently higher activity in the high toxin producing culture implicating the involvement of one or more EH in brevetoxin biosynthesis. PMID:26626160

  9. Direct and Highly Regioselective and Enantioselective Allylation of β-Diketones

    PubMed Central

    Chalifoux, Wesley A.; Reznik, Samuel K.; Leighton, James L.

    2012-01-01

    The enantioselective allylation of ketones represents both a problem of fundamental importance in asymmetric reaction design and one of only a very small number of available methods to access valuable tertiary carbinols. Despite the vast amount of attention from chemists that this problem has elicited,1-8 however, success has generally been limited to just a few simple ketone types thus limiting the utility of these methods. A method for the selective allylation of functionally complex ketones would be expected to increase the utility of ketone allylation methods in the chemical synthesis of important targets. Here we describe the operationally simple, direct, regioselective, and enantioselective allylation of β-diketones. The strong tendency of β-diketones to act as nucleophilic species was overcome by the co-optation of their enol form to provide the necessary Brønsted acid activation. This unprecedented reaction thus not only significantly expands the pool of enantiomerically enriched and functionally complex tertiary carbinols that may be easily accessed, but also overturns more than a century of received wisdom regarding the reactivity of β-diketones. PMID:22763452

  10. Hg(2+) -induced in situ generated radical cation of (S)-BINOL-based polymer for highly enantioselective recognition of phenylalaninol.

    PubMed

    Jiao, Jiemin; Li, Fei; Zhang, Shuwei; Quan, Yiwu; Zheng, Wenhua; Cheng, Yixiang; Zhu, Chengjian

    2014-08-01

    Phenylalaninol enantiomers are one of the most important chiral compounds due to its presence in biologically active molecules and pharmaceutical products. In this paper, a novel chiral fluorescence polymer sensor incorporating (S)-BINOL and oligomeric aniline via a nucleophilic addition-elimination reaction is designed and synthesized. Polymer sensor exhibits "turn-off" fluorescence quenching response upon the addition of Hg(2+) , and "turn-on" moderate fluorescence enhancement behavior towards phenylalaninol enantiomers. Meanwhile, this kind of (S)-BINOL-based polymer sensor can exhibit highly selective enantioselective recognition response towards (L)-phenylalaninol upon the addition of Hg(2+) and the value of ef can reach as high as 5.4, which can be attributed to the formation of in situ generated radical cation arisen from oligomeric aniline moiety by Hg(2+) induction. PMID:25048009

  11. Biomimetic iron-catalyzed asymmetric epoxidation of aromatic alkenes by using hydrogen peroxide.

    PubMed

    Gelalcha, Feyissa Gadissa; Anilkumar, Gopinathan; Tse, Man Kin; Brückner, Angelika; Beller, Matthias

    2008-01-01

    A novel and general biomimetic non-heme Fe-catalyzed asymmetric epoxidation of aromatic alkenes by using hydrogen peroxide is reported herein. The catalyst consists of ferric chloride hexahydrate (FeCl(3)6 H(2)O), pyridine-2,6-dicarboxylic acid (H(2)(pydic)), and readily accessible chiral N-arenesulfonyl-N'-benzyl-substituted ethylenediamine ligands. The asymmetric epoxidation of styrenes with this system gave high conversions but poor enantiomeric excesses (ee), whereas larger alkenes gave high conversions and ee values. For the epoxidation of trans-stilbene (1 a), the ligands (S,S)-N-(4-toluenesulfonyl)-1,2-diphenylethylenediamine ((S,S)-4 a) and its N'-benzylated derivative ((S,S)-5 a) gave opposite enantiomers of trans-stilbene oxide, that is, (S,S)-2 a and (R,R)-2 a, respectively. The enantioselectivity of alkene epoxidation is controlled by steric and electronic factors, although steric effects are more dominant. Preliminary mechanistic studies suggest the in situ formation of several chiral Fe-complexes, such as [FeCl(L*)(2)(pydic)]HCl (L*=(S,S)-4 a or (S,S)-5 a in the catalyst mixture), which were identified by ESIMS. A UV/Vis study of the catalyst mixture, which consisted of FeCl(3)6 H(2)O, H(2)(pydic), and (S,S)-4 a, suggested the formation of a new species with an absorbance peak at lambda=465 nm upon treatment with hydrogen peroxide. With the aid of two independent spin traps, we could confirm by EPR spectroscopy that the reaction proceeds via radical intermediates. Kinetic studies with deuterated styrenes showed inverse secondary kinetic isotope effects, with values of k(H)/k(D)=0.93 for the beta carbon and k(H)/k(D)=0.97 for the alpha carbon, which suggested an unsymmetrical transition state with stepwise O transfer. Competitive epoxidation of para-substituted styrenes revealed a linear dual-parameter Hammett plot with a slope of 1.00. Under standard conditions, epoxidation of 1 a in the presence of ten equivalents of H(2) (18)O resulted in an absence

  12. Colorimetric high-throughput assay for alkene epoxidation catalyzed by cytochrome P450 BM-3 variant 139-3.

    PubMed

    Alcalde, Miguel; Farinas, Edgardo T; Arnold, Frances H

    2004-03-01

    Cytochrome P450 BM-3 variant 139-3 is highly active in the hydroxylation of alkanes and fatty acids (AGlieder, ET Farinas, and FH Arnold, Nature Biotech 2002;20:1135-1139); it also epoxidizes various alkenes, including styrene. Here the authors describe a colorimetric, high-throughput assay suitable for optimizing this latter activity by directed evolution. The product of styrene oxidation by 139-3, styrene oxide, reacts with the nucleophile gamma-(4-nitrobenzyl)pyridine (NBP) to form a purple-colored precursor dye, which can be monitored spectrophotometrically in cell lysates. The sensitivity limit of this assay is 50-100 microM of product, and the detection limit for P450 BM-3 139-3 is ~0.2 microM of enzyme. To validate the assay, activities in a small library of random mutants were compared to those determined using an NADPH depletion assay for initial turnover rates. PMID:15006137

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

    SciTech Connect

    Hou, Feng; Miyakawa, Takuya; Kataoka, Michihiko; Takeshita, Daijiro; Kumashiro, Shoko; Uzura, Atsuko; Urano, Nobuyuki; Nagata, Koji; Shimizu, Sakayu; Tanokura, Masaru

    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 crystal 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.

  14. Dysprosium(III)-Catalyzed Ring-Opening of meso-Epoxides: Desymmetrization by Remote Stereocontrol in a Thiolysis/Elimination Sequence.

    PubMed

    Yao, Lu; Zhu, Qiao; Wei, Liang; Wang, Zuo-Fei; Wang, Chun-Jiang

    2016-05-01

    An unprecedented asymmetric desymmetrization of meso-epoxides, derived from cyclopentene-1,3-diones, with 2-mercaptobenzothiazoles has been realized. It was efficiently catalyzed by a chiral Dy(III) /N,N'-dioxide complex through a thiolysis/elimination sequence. This remote stereocontrol strategy provides facile access to synthetically versatile cyclopentene derivatives bearing an all-carbon quaternary stereogenic center in high yield and excellent enantioselectivity. Intriguingly, optically active thiophene could be readily generated from the obtained product through an efficient one-pot protocol. PMID:27060603

  15. 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.

  16. N-Heterocyclic carbene-catalyzed [3+3] cyclocondensation of bromoenals with aldimines: highly enantioselective synthesis of dihydropyridinones.

    PubMed

    Gao, Zhong-Hua; Chen, Xiang-Yu; Zhang, Han-Ming; Ye, Song

    2015-08-01

    The N-heterocyclic carbene-catalyzed [3+3] cyclocondensation of bromoenals and aldimines was developed to give the corresponding dihydropyridinones in good yields with excellent enantioselectivities. PMID:26121224

  17. Simple strategy for synthesis of optically active allylic alcohols and amines by using enantioselective organocatalysis

    PubMed Central

    Jiang, Hao; Holub, Nicole; Anker Jørgensen, Karl

    2010-01-01

    A simple organocatalytic one-pot protocol for the construction of optically active allylic alcohols and amines using readily available reactants and catalyst is presented. The described reaction is enabled by an enantioselective enone epoxidation/aziridination-Wharton-reaction sequence affording two highly privileged and synthetically important classes of compounds in an easy and benign way. The advantages of the described sequence include easy generation of stereogenic allylic centers, also including quaternary stereocenters, with excellent enantio- and diastereomeric-control and high product diversity. Furthermore, using monosubstituted enones as substrates, having moderate enantiomeric excess, the one-pot reaction sequence proceeds with an enantioenrichment of the products and high diastereoselectivity was achieved. PMID:20547884

  18. Enantioselective Vinylogous Organocascade Reactions.

    PubMed

    Hepburn, Hamish B; Dell'Amico, Luca; Melchiorre, Paolo

    2016-08-01

    Cascade reactions are powerful tools for rapidly assembling complex molecular architectures from readily available starting materials in a single synthetic operation. Their marriage with asymmetric organocatalysis has led to the development of novel techniques, which are now recognized as reliable strategies for the one-pot enantioselective synthesis of stereochemically dense molecules. In recent years, even more complex synthetic challenges have been addressed by applying the principle of vinylogy to the realm of organocascade catalysis. The key to the success of vinylogous organocascade reactions is the unique ability of the chiral organocatalyst to transfer reactivity to a distal position without losing control on the stereo-determining events. This approach has greatly expanded the synthetic horizons of the field by providing the possibility of forging multiple stereocenters in remote positions from the catalyst's point of action with high selectivity, while simultaneously constructing multiple new bonds. This article critically describes the developments achieved in the field of enantioselective vinylogous organocascade reactions, charting the ideas, the conceptual advances, and the milestone reactions that have been essential for reaching highly practical levels of synthetic efficiency. PMID:27256039

  19. Stereochemical features of the hydrolysis of 9,10-epoxystearic acid catalysed by plant and mammalian epoxide hydrolases.

    PubMed

    Summerer, Stephan; Hanano, Abdulsamie; Utsumi, Shigeru; Arand, Michael; Schuber, Francis; Blée, Elizabeth

    2002-09-01

    cis-9,10-epoxystearic acid was used as a tool to probe the active sites of epoxide hydrolases (EHs) of mammalian and plant origin. We have compared the stereochemical features of the hydrolysis of this substrate catalysed by soluble and membrane-bound rat liver EHs, by soluble EH (purified to apparent homogeneity) obtained from maize seedlings or celeriac roots, and by recombinant soybean EH expressed in yeast. Plant EHs were found to differ in their enantioselectivity, i.e. their ability to discriminate between the two enantiomers of 9,10-epoxystearic acid. For example, while the maize enzyme hydrated both enantiomers at the same rate, the EH from soybean exhibited very high enantioselectivity in favour of 9R,10S-epoxystearic acid. This latter enzyme also exhibited a strict stereoselectivity, i.e. it hydrolysed the racemic substrate with a very high enantioconvergence, yielding a single chiral diol product, threo-9R,10R-dihydroxystearic acid. Soybean EH shared these distinctive stereochemical features with the membrane-bound rat liver EH. The stereochemical outcome of these enzymes probably results from a stereoselective attack by the nucleophilic residue on the oxirane ring carbon having the (S)-configuration, leading to the presumed (in plant EH) covalent acyl-enzyme intermediate. In sharp contrast, the reactions catalysed by cytosolic rat liver EH exhibited a complete absence of enantioselectivity and enantioconvergence; this latter effect might be ascribed to a regioselective formation of the acyl-enzyme intermediate involving C-10 of 9,10-epoxystearic acid, independent of its configuration. Thus, compared with soybean EH, the active site of rat liver soluble EH displays a very distinct means of anchoring the oxirane ring of the fatty acid epoxides, and therefore appears to be a poor model for mapping the catalytic domain of plant EHs. PMID:12020347

  20. Stereochemical features of the hydrolysis of 9,10-epoxystearic acid catalysed by plant and mammalian epoxide hydrolases.

    PubMed Central

    Summerer, Stephan; Hanano, Abdulsamie; Utsumi, Shigeru; Arand, Michael; Schuber, Francis; Blée, Elizabeth

    2002-01-01

    cis-9,10-epoxystearic acid was used as a tool to probe the active sites of epoxide hydrolases (EHs) of mammalian and plant origin. We have compared the stereochemical features of the hydrolysis of this substrate catalysed by soluble and membrane-bound rat liver EHs, by soluble EH (purified to apparent homogeneity) obtained from maize seedlings or celeriac roots, and by recombinant soybean EH expressed in yeast. Plant EHs were found to differ in their enantioselectivity, i.e. their ability to discriminate between the two enantiomers of 9,10-epoxystearic acid. For example, while the maize enzyme hydrated both enantiomers at the same rate, the EH from soybean exhibited very high enantioselectivity in favour of 9R,10S-epoxystearic acid. This latter enzyme also exhibited a strict stereoselectivity, i.e. it hydrolysed the racemic substrate with a very high enantioconvergence, yielding a single chiral diol product, threo-9R,10R-dihydroxystearic acid. Soybean EH shared these distinctive stereochemical features with the membrane-bound rat liver EH. The stereochemical outcome of these enzymes probably results from a stereoselective attack by the nucleophilic residue on the oxirane ring carbon having the (S)-configuration, leading to the presumed (in plant EH) covalent acyl-enzyme intermediate. In sharp contrast, the reactions catalysed by cytosolic rat liver EH exhibited a complete absence of enantioselectivity and enantioconvergence; this latter effect might be ascribed to a regioselective formation of the acyl-enzyme intermediate involving C-10 of 9,10-epoxystearic acid, independent of its configuration. Thus, compared with soybean EH, the active site of rat liver soluble EH displays a very distinct means of anchoring the oxirane ring of the fatty acid epoxides, and therefore appears to be a poor model for mapping the catalytic domain of plant EHs. PMID:12020347

  1. Immobilization of lipases on hydrophobilized zirconia nanoparticles: highly enantioselective and reusable biocatalysts.

    PubMed

    Chen, Yi Zhao; Yang, Cai Ting; Ching, Chi Bun; Xu, Rong

    2008-08-19

    Our study has demonstrated for the first time that zirconia nanoparticles modified by a simple carboxylic surfactant of a very long alkyl chain can significantly enhance the activity of the immobilized lipases for asymmetric synthesis in organic media. Zirconia nanoparticles of ca. 20 nm diameter were grafted with carboxylic surfactant modifiers from Tween 85 and erucic acid. The surface of nanoparticles was successfully changed from hydrophilic to hydrophobic. Lipases from Candida rugosa and Pseudomonas cepacia were immobilized on the modified zirconia nanoparticles by adsorption in aqueous solution. The immobilized lipases were used for the resolution of ( R, S)-ibuprofen and ( R, S)-1-phenylethanol through esterification and acylation, respectively, in isooctane organic solvent. When immobilized on erucic acid-modified zirconia, both lipases gave significantly higher activity and enantioselectivity compared with those from their corresponding crude lipase powders. The nanohybrid biocatalysts are stable and can be reused for eight cycles without loss in activity and selectivity. The interaction between the hydrophobic surface of zirconia support and lipases probably induces the conformational rearrangement of lipases into an active, stable form. PMID:18656972

  2. (Salen)Mn(III) Catalyzed Asymmetric Epoxidation Reactions by Hydrogen Peroxide in Water: A Green Protocol

    PubMed Central

    Ballistreri, Francesco Paolo; Gangemi, Chiara M. A.; Pappalardo, Andrea; Tomaselli, Gaetano A.; Toscano, Rosa Maria; Trusso Sfrazzetto, Giuseppe

    2016-01-01

    Enantioselective epoxidation reactions of some chosen reactive alkenes by a chiral Mn(III) salen catalyst were performed in H2O employing H2O2 as oxidant and diethyltetradecylamine N-oxide (AOE-14) as surfactant. This procedure represents an environmentally benign protocol which leads to e.e. values ranging from good to excellent (up to 95%). PMID:27420047

  3. Improvement of enantioselectivity of the B-type halohydrin hydrogen-halide-lyase from Corynebacterium sp. N-1074.

    PubMed

    Watanabe, Fumiaki; Yu, Fujio; Ohtaki, Akashi; Yamanaka, Yasuaki; Noguchi, Keiichi; Odaka, Masafumi; Yohda, Masafumi

    2016-09-01

    Halohydrin hydrogen-halide-lyase (H-Lyase) is a bacterial enzyme involved in the degradation of halohydrins. This enzyme catalyzes the intramolecular nucleophilic displacement of a halogen by a vicinal hydroxyl group in halohydrins, producing the corresponding epoxides. The H-Lyases have been classified into A, B and C subtypes based on amino acid sequence similarities. These enzymes have attracted much attention as industrial catalysts in the synthesis of chiral chemicals from prochiral halohydrins. In the present study, we constructed mutants of B-type H-Lyase from Corynebacterium sp. N-1074 (HheB) displaying higher enantioselectivity by structure-based site-directed mutagenesis and random mutagenesis. A triple mutant of HheB exhibited 98.5% enantioselectivity, the highest ever reported, toward (R)-4-chloro-3-hydroxy-butyronitrile production, with the yield reaching approximately two-fold that of the wild-type enzyme. We discuss the structural basis of the high enantioselectivity and productivity of the mutant by comparing the crystal structures of the mutant HheB and the wild-type enzyme in complex with or without the substrate analogue. PMID:27215832

  4. Double substituted variant of Bacillus amyloliquefaciens esterase with enhanced enantioselectivity and high activity towards 1-(3',4'-methylenedioxyphenyl)ethyl acetate.

    PubMed

    Liu, Jia-Yan; Bian, Han-Ping; Tang, Yun; Bai, Yun-Peng; Xu, Jian-He

    2015-02-01

    Bacillus amyloliquefaciens esterase (BAE) was applied to produce (R)-1-(3',4'-methylenedioxyphenyl)ethanol, a chiral drug intermediate. In this study, we improved the enantioselectivity of BAE by protein engineering instead of process engineering as used in our previous work. Saturation mutagenesis was carried out on eight positions of BAE based on structure modeling and substrate docking. A double substituted variant V10 (K358D/A396C) showed an excellent enantioselectivity without decreasing the activity. The functions of these two mutations (K358D and A396C) were investigated, revealing a synergic effect on the BAE enantioselectivity. Using the variant V10, enantiopure (R)-1-(3',4'-methylenedioxyphenyl)ethanol could be readily prepared in >97 % ee, affording a high space-time yield (123 g L(-1) day(-1)) and a high ratio of substrate/catalyst (40 g g(-1)) in 1-L reaction. PMID:25104035

  5. 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.

  6. Discovery and application of new bacterial strains for asymmetric synthesis of L-tert-butyl leucine in high enantioselectivity.

    PubMed

    Jin, Jian-Zhong; Chang, Dong-Liang; Zhang, Jie

    2011-06-01

    Discovery of new bacterial strains with fast identification in a miniaturized system was performed for the synthesis of optically active L-tert-butyl leucine. With tert-butyl leucine amide as nitrogen source, one bacterial strain with high conversion and high enantioselectivity was discovered among 120 isolated microorganisms from local soils and identified as Mycobacterium sp. JX009. Glucose and ammonium chloride were examined as the good carbon source and nitrogen source for the cells' growth separately. The cells grew better at 30 °C and at pH 7.5 with higher activity of 2,650 U/l in comparison with other conditions. Cells' stability was improved by immobilization on synthetic resin 0730 without pretreatment. Tert-butyl leucine amide (30 mM) was successfully hydrolyzed by immobilized cells and examined as the highest chemical concentration that cells could endure. After six reaction cycles, the immobilized cells retained 90% activity with production of L-tert-butyl leucine in 98% ee. The results firstly reported the application of new bacterial strain in the hydrolysis of tert-butyl leucine amide to produce optically active L-tert-butyl leucine in an efficient way with investigation in detail. PMID:21153891

  7. Copper(II)-catalyzed hydrosilylation of ketones using chiral dipyridylphosphane ligands: highly enantioselective synthesis of valuable alcohols.

    PubMed

    Yu, Feng; Zhou, Ji-Ning; Zhang, Xi-Chang; Sui, Yao-Zong; Wu, Fei-Fei; Xie, Lin-Jie; Chan, Albert S C; Wu, Jing

    2011-12-01

    In the presence of PhSiH(3) as the reductant, the combination of enantiomeric dipyridylphosphane ligands and Cu(OAc)(2)·H(2)O, which is an easy-to-handle and inexpensive copper salt, led to a remarkably practical and versatile chiral catalyst system. The stereoselective formation of a selection of synthetically interesting β-, γ- or δ-halo alcohols bearing high degrees of enantiopurity (up to 99.9% enantiomeric excess (ee)) was realized with a substrate-to-ligand molar ratio (S/L) of up to 10,000. The present protocol also allowed the hydrosilylation of a diverse spectrum of alkyl aryl ketones with excellent enantioselectivities (up to 98% ee) and exceedingly high turn-over rates (up to 50,000 S/L molar ratio in 50 min reaction time) in air, under very mild conditions, which offers great opportunities for the preparation of various physiologically active targets. The synthetic utility of the chiral products obtained was highlighted by the efficient conversion of optically enriched β-halo alcohols into the corresponding styrene oxide, β-amino alcohol, and β-azido alcohol, respectively. PMID:22065457

  8. Enantioselective Total Synthesis of (−)-Citrinadin A and Revision of its Stereochemical Structure

    PubMed Central

    Bian, Zhiguo; Marvin, Christopher C.; Martin, Stephen F.

    2013-01-01

    The first enantioselective total synthesis of (−)-citrinadin A has been accomplished in 20 steps from commercially available materials via an approach that minimizes refunctionalization and protection/deprotection operations. The cornerstone of this synthesis features an asymmetric vinylogous Mannich addition of a dienolate to a chiral pyridinium salt to set the initial chiral center. A sequence of substrate-controlled reactions, including a highly stereoselective epoxidation/ring opening sequence and an oxidative rearrangement of an indole to furnish a spirooxindole, are then used to establish the remaining stereocenters in the pentacyclic core of (−)-citrinadin A. The successful synthesis of citrinadin A led to a revision of the stereochemical structure of the core substructure of the citrinadins. PMID:23837457

  9. Expanding the scope of Metal-Free enantioselective allylic substitutions: Anthrones

    PubMed Central

    Ceban, Victor; Tauchman, Jiří; Meazza, Marta; Gallagher, Greg; Light, Mark E.; Gergelitsová, Ivana; Veselý, Jan; Rios, Ramon

    2015-01-01

    The highly enantioselective asymmetric allylic alkylation of Morita–Baylis–Hillman carbonates with anthrones is presented. The reaction is simply catalyzed by cinchona alkaloid derivatives affording the final alkylated products in good yields and excellent enantioselectivities. PMID:26592555

  10. Fabrication and characterization of the Ag-based high technologymodel nanocluster catalyst for ethylene epoxidation manufactured byelectron beam lithography

    SciTech Connect

    Avoyan, Armen; Rupprechter, Gunther; Eppler, Aston; Somorjai,Gabor A.

    1999-06-01

    Nanocluster catalysis is an area where greater fundamental knowledge is needed to understand the behavior of aggregates of metal atoms in determining product selectivity of chemical reactions. While catalysis is practiced industrially with economic success there is still a great need to eliminate wasteful side-reactions which hurt overall yields. Here we report on fabrication of a Ag-based high-technology model nanocluster catalyst by using electron beam lithography (EBL) designed for systematic studies of the ethylene epoxidation reaction. The catalyst is made of a square array of cylinder-shaped Ag nanoclusters that are 200 Angstrom in diameter, deposited on a four inch silicon wafer, precovered with a 100 Angstrom thick film of alpha-alumina. The height of the particles and interparticle distance can vary, and were chosen to be 150-300 and 1000 Angstrom, respectively. The high technology catalyst was characterized by X-ray photoelectron spectroscopy (XPS), high-resolution transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The thermal stability of Ag nanoclusters in vacuo was investigated.

  11. Expression and characterization of an epoxide hydrolase from Anopheles gambiae with high activity on epoxy fatty acids

    PubMed Central

    Xu, Jiawen; Morisseau, Christophe; Hammock, Bruce D.

    2014-01-01

    In insects, epoxide hydrolases (EHs) play critical roles in the metabolism of xenobiotic epoxides from the food resources and in the regulation of endogenous chemical mediators, such as juvenile hormones. Using the baculovirus expression system, we expressed and characterized an epoxide hydrolase from Anopheles gambiae (AgEH) that is distinct in evolutionary history from insect juvenile hormone epoxide hydrolases (JHEHs). We partially purified the enzyme by ion exchange chromatography and isoelectric focusing. The experimentally determined molecular weight and pI were estimated to be 35kD and 6.3 respectively, different than the theoretical ones. The AgEH had the greatest activity on long chain epoxy fatty acids such as 14,15-epoxyeicosatrienoic acids (14,15-EET) and 9,10-epoxy-12Z-octadecenoic acids (9,10-EpOME or leukotoxin) among the substrates evaluated. Juvenile hormone III, a terpenoid insect growth regulator, was the next best substrate tested. The AgEH showed kinetics comparable to the mammalian soluble epoxide hydrolases, and the activity could be inhibited by AUDA [12-(3-adamantan-1-yl-ureido) dodecanoic acid], a urea-based inhibitor designed to inhibit the mammalian soluble epoxide hydrolases. The rabbit serum generated against the soluble epoxide hydrolase of Mus musculus can both cross-react with natural and denatured forms of the AgEH, suggesting immunologically they are similar. The study suggests there are mammalian sEH homologs in insects, and epoxy fatty acids may be important chemical mediators in insects. PMID:25173592

  12. Efficient synthesis of high purity homo-arm and mikto-arm poly(ethylene glycol) stars using epoxide and azide-alkyne coupling chemistry.

    PubMed

    Zhang, Boyu; Zhang, Hong; Elupula, Ravinder; Alb, Alina M; Grayson, Scott M

    2014-01-01

    High purity homo-arm and mikto-arm poly(ethylene glycol) (PEG) stars are successfully prepared by the combination of epoxide ring-openings and azide-alkyne click reactions. First, monohydroxy-PEG was modified via epoxide chemistry to bear one hydroxyl and one azide functionality at the same end. An alkyne-functionalized PEG chain was then coupled to the azide. Subsequently, the remaining hydroxyl could be reactivated to an azide again and again to enable stepwise addition of alkyne-functionalized polymer arms. The use of efficient reactions for this iterative route provides star polymers with an exact number of arms, and a tailorable degree of polymerization for each arm. Detailed characterization confirms the high purity of multi-arm polyethylene glycol products. PMID:24272944

  13. Reproducible Preparation of Au/TS-1 with High Reaction Rate for Gas Phase Epoxidation of Propylene

    SciTech Connect

    Lee W. S.; Stach E.; Akatay, M.C.; Ribeiro, F.H.; Delgass, N.

    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 at 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.

  14. Catalytic Enantioselective Synthesis of Halocyclopropanes.

    PubMed

    Pons, Amandine; Ivashkin, Pavel; Poisson, Thomas; Charette, André B; Pannecoucke, Xavier; Jubault, Philippe

    2016-04-25

    A catalytic asymmetric synthesis of halocyclopropanes is described. The developed method is based on a carbenoid cyclopropanation of 2-haloalkenes with tert-butyl α-cyano-α-diazoacetate using a chiral rhodium catalyst that permits access to a broad range of highly functionalized chiral halocyclopropanes (F, Cl, Br, and I) in good yields, moderate diastereoselectivity, and excellent enantiomeric ratios. The reported methodology represents the first general catalytic enantioselective approach to halocyclopropanes. PMID:26945553

  15. Iridium-catalyzed enantioselective hydrogenation of unsaturated heterocyclic acids.

    PubMed

    Song, Song; Zhu, Shou-Fei; Pu, Liu-Yang; Zhou, Qi-Lin

    2013-06-01

    Spiral binding: A highly enantioselective hydrogenation of unsaturated heterocyclic acids has been developed by using chiral iridium/spirophosphino oxazoline catalysts (see scheme; BArF(-) =tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, Boc=tert-butoxycarbonyl). This reaction provided an efficient method for the preparation of optically active heterocyclic acids with excellent enantioselectivities. PMID:23610004

  16. Organocatalytic Enantioselective Synthesis of Pyrazoles Bearing a Quaternary Stereocenter.

    PubMed

    Vila, Carlos; Amr, Fares Ibrahim; Blay, Gonzalo; Muñoz, M Carmen; Pedro, José R

    2016-05-20

    An efficient one-pot asymmetric synthesis of pyrazoles bearing a chiral quaternary stereocenter has been developed. Quinine-derived thiourea catalyzed the enantioselective addition of pyrazolones to isatin-derived ketimines, providing the corresponding acetylated pyrazoles after in situ treatment with Ac2 O/Et3 N. The corresponding pyrazoles were afforded in high yields and excellent enantioselectivities. PMID:27038062

  17. Determinants of Reactivity and Selectivity in Soluble Epoxide Hydrolase from Quantum Mechanics/Molecular Mechanics Modeling

    PubMed Central

    2012-01-01

    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. PMID:22280021

  18. Epoxide composites with thermally reduced graphite oxide and their properties

    NASA Astrophysics Data System (ADS)

    Arbuzov, A. A.; Muradyan, V. E.; Tarasov, B. P.; Sokolov, E. A.; Babenko, S. D.

    2016-05-01

    The properties of epoxide composites modified by thermal reduced graphite oxide are studied. The dielectric permittivities of epoxide composites with additives of up to 1.5 wt % of reduced graphite oxide are studied at a frequency of 9.8 GHz. It is shown that despite its low electrical conductivity, the large specific surface area of reduced graphite oxide allows us to create epoxide composites with high complex dielectric permittivities and dielectric loss tangents.

  19. Succinic anhydrides from epoxides

    SciTech Connect

    Coates, Geoffrey W; Rowley, John M

    2014-12-30

    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.

  20. Succinic anhydrides from epoxides

    SciTech Connect

    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.

  1. Exceptionally active yttrium-salen complexes for the catalyzed ring opening of epoxides by TMSCN and TMSN(3).

    PubMed

    Saha, Biswajit; Lin, Mei-Huey; RajanBabu, T V

    2007-11-01

    Halide or alkoxide free yttrium-salen complexes are excellent catalysts for the ring opening of epoxides mediated by TMSCN and TMSN3. Substrate to catalyst ratios up to 10000 have been realized in these potentially useful reactions, which can be run under solvent-free conditions. Even though the enantioselectivities for the TMSCN-mediated reaction remains modest (best 77% ee), these studies with a highly tunable ligand system may provide further impetus for work in this important area of catalysis. Even though attempts to isolate a Y-cyanide complex, which was detected by in situ IR spectroscopy, failed, a related dimeric hydroxide complex was isolated. A kinetic study using in situ IR spectroscopy did not provide conclusive data to assign an order with respect to Y in this reaction. PMID:17929974

  2. The electron-impact promoted fragmentation of aurone epoxides.

    NASA Technical Reports Server (NTRS)

    Brady, B. A.; O'Sullivan, W. I.; Duffield, A. M.

    1972-01-01

    The mass spectra of six aurone epoxides have been rationalized with the aid of high resolution mass spectrometry and metastable ion evidence. These compounds fragment in a well defined manner and mechanisms are proposed for the formation of their characteristic ions. Some similarity was observed between the mass spectra of 6-methoxyaurone epoxide (II), 4-hydroxy-7-methoxy-3-phenylcoumarin (VII) and 7-methoxyflavonol (IX). The possibility that VII and IX are intermediates in the fragmentation of epoxide II is discussed. Thermal rearrangement of aurone epoxide II was shown to yield the corresponding flavonol IX and coumarin VII.

  3. Brønsted Acid Catalyzed [3+2]-Cycloaddition of 2-Vinylindoles with In Situ Generated 2-Methide-2H-indoles: Highly Enantioselective Synthesis of Pyrrolo[1,2-a]indoles.

    PubMed

    Bera, Kalisankar; Schneider, Christoph

    2016-05-17

    Pyrrolo[1,2-a]indoles are privileged structural elements of many natural products and pharmaceuticals. An efficient one-step process for their highly diastereo- and enantioselective synthesis, comprising a direct [3+2]-cycloaddition, has been developed. A chiral BINOL-derived phosphoric acid catalyzes the reaction of in situ-generated 2-methide-2H-indoles with 2-vinylindoles, furnishing the target products incorporating three contiguous stereogenic centers as single diastereoisomers and with excellent yields and enantioselectivities. PMID:26991961

  4. Enantioselective synthesis of fluorinated branched allylic compounds via Ir-catalyzed allylations of functionalized fluorinated methylene derivatives.

    PubMed

    Zhang, Hongbo; Chen, Jiteng; Zhao, Xiao-Ming

    2016-08-14

    Enantioselective introduction of the functionalized monofluorinated methylenes into the allylic fragment under Ir catalysis has been realized, which gave the fluorinated branched allyl products in good to high yields with excellent regio- and enantioselectivities. PMID:27383920

  5. Asymmetric epoxidation of allylic alcohols catalyzed by vanadium-binaphthylbishydroxamic Acid complex.

    PubMed

    Noji, Masahiro; Kobayashi, Toshihiro; Uechi, Yuria; Kikuchi, Asami; Kondo, Hisako; Sugiyama, Shigeo; Ishii, Keitaro

    2015-03-20

    A vanadium-binaphthylbishydroxamic acid (BBHA) complex-catalyzed asymmetric epoxidation of allylic alcohols is described. The optically active binaphthyl-based ligands BBHA 2a and 2b were synthesized from (S)-1,1'-binaphthyl-2,2'-dicarboxylic acid and N-substituted-O-trimethylsilyl (TMS)-protected hydroxylamines via a one-pot, three-step procedure. The epoxidations of 2,3,3-trisubstituted allylic alcohols using the vanadium complex of 2a were easily performed in toluene with a TBHP water solution to afford (2R)-epoxy alcohols in good to excellent enantioselectivities. PMID:25714329

  6. Enantioselective Olefin Metathesis with Cyclometalated Ruthenium Complexes

    PubMed Central

    2015-01-01

    The success of enantioselective olefin metathesis relies on the design of enantioenriched alkylidene complexes capable of transferring stereochemical information from the catalyst structure to the reactants. Cyclometalation of the NHC ligand has proven to be a successful strategy to incorporate stereogenic atoms into the catalyst structure. Enantioenriched complexes incorporating this design element catalyze highly Z- and enantioselective asymmetric ring opening/cross metathesis (AROCM) of norbornenes and cyclobutenes, and the difference in ring strain between these two substrates leads to different propagating species in the catalytic cycle. Asymmetric ring closing metathesis (ARCM) of a challenging class of prochiral trienes has also been achieved. The extent of reversibility and effect of reaction setup was also explored. Finally, promising levels of enantioselectivity in an unprecedented Z-selective asymmetric cross metathesis (ACM) of a prochiral 1,4-diene was demonstrated. PMID:25137310

  7. Highly Enantioselective Iron-Catalyzed cis-Dihydroxylation of Alkenes with Hydrogen Peroxide Oxidant via an Fe(III) -OOH Reactive Intermediate.

    PubMed

    Zang, Chao; Liu, Yungen; Xu, Zhen-Jiang; Tse, Chun-Wai; Guan, Xiangguo; Wei, Jinhu; Huang, Jie-Sheng; Che, Chi-Ming

    2016-08-22

    The development of environmentally benign catalysts for highly enantioselective asymmetric cis-dihydroxylation (AD) of alkenes with broad substrate scope remains a challenge. By employing [Fe(II) (L)(OTf)2 ] (L=N,N'-dimethyl-N,N'-bis(2-methyl-8-quinolyl)-cyclohexane-1,2-diamine) as a catalyst, cis-diols in up to 99.8 % ee with 85 % isolated yield have been achieved in AD of alkenes with H2 O2 as an oxidant and alkenes in a limiting amount. This "[Fe(II) (L)(OTf)2 ]+H2 O2 " method is applicable to both (E)-alkenes and terminal alkenes (24 examples >80 % ee, up to 1 g scale). Mechanistic studies, including (18) O-labeling, UV/Vis, EPR, ESI-MS analyses, and DFT calculations lend evidence for the involvement of chiral Fe(III) -OOH active species in enantioselective formation of the two C-O bonds. PMID:27457506

  8. Enantioselective Total Synthesis of (+)-Reserpine

    PubMed Central

    Rajapaksa, Naomi S.; McGowan, Meredeth A.; Rienzo, Matthew

    2013-01-01

    A catalytic, enantioselective synthesis of (+)-reserpine is reported. The route features a highly diastereoselective, chiral catalyst-controlled formal aza-Diels–Alder reaction between a 6-methoxytryptamine-derived dihydro-β-carboline and an enantioenriched α-substituted enone to form a key tetracyclic intermediate. This approach addresses the challenge of setting the C3 stereogenic center by using catalyst control. Elaboration of the tetracycle to (+)-reserpine includes an intramolecular aldol cyclization and a highly diastereoselective hydrogenation of a sterically hindered enoate. PMID:23331099

  9. Enantioselective Total Synthesis of (-)-Terengganensine A.

    PubMed

    Piemontesi, Cyril; Wang, Qian; Zhu, Jieping

    2016-05-23

    A seven-step enantioselective total synthesis of (-)-terengganensine A, a complex heptacyclic monoterpene indole alkaloid, was accomplished. Key steps included: a) Noyori's catalytic enantioselective transfer hydrogenation of the iminium salt to set up the absolute configuration at the C21 position; b) a highly diastereoselective C7 benzoyloxylation with dibenzoyl peroxide under mild conditions; and c) an integrated one-pot oxidative cleavage of cyclopentene/triple cyclization/hydrolysis sequence for the construction of the dioxa azaadamantane motif with complete control of four newly generated stereocenters. PMID:27094030

  10. Highly Active and Robust Metalloporphyrin Catalysts for the Synthesis of Cyclic Carbonates from a Broad Range of Epoxides and Carbon Dioxide.

    PubMed

    Maeda, Chihiro; Shimonishi, Junta; Miyazaki, Ray; Hasegawa, Jun-Ya; Ema, Tadashi

    2016-05-01

    Bifunctional metalloporphyrins with quaternary ammonium bromides (nucleophiles) at the meta, para, or ortho positions of meso-phenyl groups were synthesized as catalysts for the formation of cyclic carbonates from epoxides and carbon dioxide under solvent-free conditions. The meta-substituted catalysts exhibited high catalytic performance, whereas the para- and ortho-substituted catalysts showed moderate and low activity, respectively. DFT calculations revealed the origin of the advantage of the meta-substituted catalyst, which could use the flexible quaternary ammonium cation at the meta position to stabilize various anionic species generated during catalysis. A zinc(II) porphyrin with eight nucleophiles at the meta positions showed very high catalytic activity (turnover number (TON)=240 000 at 120 °C, turnover frequency (TOF)=31 500 h(-1) at 170 °C) at an initial CO2 pressure of 1.7 MPa; catalyzed the reaction even at atmospheric CO2 pressure (balloon) at ambient temperature (20 °C); and was applicable to a broad range of substrates, including terminal and internal epoxides. PMID:26990557

  11. Bioconversion of hydrophobic compounds in a continuous closed-gas-loop bioreactor: feasibility assessment and epoxide production.

    PubMed

    Steinig, G H; Livingston, A G; Stuckey, D C

    2000-12-01

    Microorganisms can be used as catalysts to produce organic compounds in a highly chemo-, regio- and enantioselective manner, and whole cells do not require the costly addition of cofactors for redox reactions. However, bioconversions are slow compared to alternative chemical reactions, and the biocatalyst works at its best in an aqueous medium, while the transformations of interest frequently involve compounds with a low-aqueous solubility and that are toxic to microorganisms. This results in low-volumetric productivity in classical bioreactors. The Continuous Closed-Gas-Loop Bioreactor is described here-a reactor system with high productivity, but without the problems associated with two-phase systems, such as an emulsified product stream and phase toxicity. Its working principle is to recirculate a gas phase through a bioreaction compartment and a saturator/absorber module where the product accumulates as a clear organic solution. A wide range of bioconversions should be possible in this set-up, and proof of concept was established for the epoxidation of 1,7-octadiene to (R)-1,2-epoxyoct-7-ene by a native strain of Pseudomonas oleovorans. This reaction represents a group of terminal alkene epoxidations where the bioconversion substrate does not support growth of the microorganism. Practical results at a 5l-scale are presented for this bioconversion for both batch and continuous operation with respect to the aqueous phase, showing continuous stable epoxidation at productivities >14 micromol min(-1) L(-1) (U L(-1)). The results confirm that the metabolism does not allow a simple optimization strategy, because growth and biotransformation substrates compete for the same enzyme sites, and conversely growth on a substrate using this very enzyme system is necessary for longterm bioconversion. Integrated removal of the CO(2) formed via the liquid overflow was estimated from theory and verified in experimental work. PMID:11042552

  12. Salen Promoted Enantioselective Nazarov Cyclizations of Activated and Unactivated Dienones

    PubMed Central

    2013-01-01

    A novel class of chiral 5,5′-di(2,4,6-trialkyl)aryl salen-metal complexes have been developed and shown to catalyze highly enantioselective Nazarov cyclization reactions, giving rise to cyclopentenoids in 90:10–98:2 er. Significantly, the catalysts also promote, for the first time, highly enantioselective Nazarov reactions of “unactivated” dienones, producing hydrindenone products having in place three contiguous chiral centers. PMID:23506509

  13. 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. PMID:25959033

  14. Enantioselective Michael Addition of Water

    PubMed Central

    Chen, Bi-Shuang; Resch, Verena; Otten, Linda G; Hanefeld, Ulf

    2015-01-01

    The enantioselective Michael addition using water as both nucleophile and solvent has to date proved beyond the ability of synthetic chemists. Herein, the direct, enantioselective Michael addition of water in water to prepare important β-hydroxy carbonyl compounds using whole cells of Rhodococcus strains is described. Good yields and excellent enantioselectivities were achieved with this method. Deuterium labeling studies demonstrate that a Michael hydratase catalyzes the water addition exclusively with anti-stereochemistry. PMID:25529526

  15. 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. PMID:26809615

  16. Enantioselective Hydrogenation of Diarylmethanimines for Synthesis of Chiral Diarylmethylamines.

    PubMed

    Kong, Duanyang; Li, Meina; Zi, Guofu; Hou, Guohua; He, Yong

    2016-08-01

    An enantioselective hydrogenation of N-substituted diarylmethanimines under mild conditions has been first realized by using an iridium catalyst with a chiral f-spiroPhos ligand. This method provides an efficient access to the asymmetric synthesis of a variety of chiral diarylmethylamines and their derivatives with excellent enantioselectivities (up to 99.4% ee) and high turnover numbers (TON up to 4000). PMID:27410993

  17. Enantioselective Sulfoxidation Catalyzed by a Bisguanidinium Diphosphatobisperoxotungstate Ion Pair.

    PubMed

    Ye, Xinyi; Moeljadi, Adhitya Mangala Putra; Chin, Kek Foo; Hirao, Hajime; Zong, Lili; Tan, Choon-Hong

    2016-06-13

    The first enantioselective tungstate-catalyzed oxidation reaction is presented. High enantioselectivities were achieved for a variety of drug-like phenyl and heterocyclic sulfides under mild conditions with H2 O2 , a cheap and environmentally friendly oxidant. Synthetic utility was demonstrated through the preparation of (S)-Lansoprazole, a commercial proton-pump inhibitor. The active ion-pair catalyst was identified to be bisguanidinium diphosphatobisperoxotungstate using Raman spectroscopy and computational studies. PMID:27150978

  18. Polymerization of epoxidized triglycerides with fluorosulfonic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  19. Enantioselective oxidative boron Heck reactions.

    PubMed

    Lee, A-L

    2016-06-28

    This review highlights the use of the oxidative boron Heck reaction in enantioselective Heck-type couplings. The enantioselective oxidative boron Heck reaction overcomes several limitations of the traditional Pd(0)-catalysed Heck coupling and has subsequently allowed for intermolecular couplings of challenging systems such as cyclic enones, acyclic alkenes, and even site selectively on remote alkenes. PMID:26529247

  20. Friction reducing properties and stability of epoxidized oleochemicals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have studied the properties of epoxidized oleochemical methyl esters including epoxidized soybean oil, epoxidized methyl oleate, epoxidized methyl linoleate, and epoxidized methyl linolenate. We have compared these materials to a similar series of unmodified olefins. Several interesting trends ...

  1. 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.

  2. Werner Complexes with ω-Dimethylaminoalkyl Substituted Ethylenediamine Ligands: Bifunctional Hydrogen-Bond-Donor Catalysts for Highly Enantioselective Michael Additions.

    PubMed

    Ghosh, Subrata K; Ganzmann, Carola; Bhuvanesh, Nattamai; Gladysz, John A

    2016-03-18

    The racemic carbonate complex [Co(en)2 O2 CO](+) Cl(-) (en=1,2-ethylenediamine) and (S)-[H3 NCH((CH2 )n NHMe2 )CH2 NH3 ](3+) 3 Cl(-) (n=1-4) react (water, charcoal, 100 °C) to give [Co(en)2 ((S)-H2 NCH((CH2 )n NHMe2 )CH2 NH2 )](4+) 4 Cl(-) (3 a-d H(4+) 4 Cl(-) ) as a mixture of Λ/Δ diastereomers that separate on chiral-phase Sephadex columns. These are treated with NaOH/Na(+) BArf (-) (BArf =B(3,5-C6 H3 (CF3 )2 )4 ) to give lipophilic Λ- and Δ-3 a-d(3+) 3 BArf (-) , which are screened as catalysts (10 mol %) for additions of dialkyl malonates to nitroalkenes. Optimal results are obtained with Λ-3 c(3+) 3 BArf (-) (CH2 Cl2 , -35 °C; 98-82 % yields and 99-93 % ee for six β-arylnitroethenes). The monofunctional catalysts Λ- and Δ-[Co(en)3 ](3+) 3 BArf (-) give enantioselectivities of <10 % ee with equal loadings of Et3 N. The crystal structure of Δ-3 a H(4+) 4 Cl(-) provides a starting point for speculation regarding transition-state assemblies. PMID:26918320

  3. Bacterial Expression and HTS Assessment of Soluble Epoxide Hydrolase Phosphatase.

    PubMed

    Klingler, Franca-Maria; Wolf, Markus; Wittmann, Sandra; Gribbon, Philip; Proschak, Ewgenij

    2016-08-01

    Soluble epoxide hydrolase (sEH) is a bifunctional enzyme that possesses an epoxide hydrolase and lipid phosphatase activity (sEH-P) at two distinct catalytic domains. While the physiological role of the epoxide hydrolase domain is well understood, the consequences of the phosphatase activity remain unclear. Herein we describe the bacterial expression of the recombinant N-terminal domain of sEH-P and the development of a high-throughput screening protocol using a sensitive and commercially available substrate fluorescein diphosphate. The usability of the assay system was demonstrated and novel inhibitors of sEH-P were identified. PMID:27009944

  4. Enantioselective aldol reactions with masked fluoroacetates.

    PubMed

    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. PMID:26892561

  5. 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.

  6. Enantioselective Synthesis of (-)-Dysiherbaine.

    PubMed

    Do, Ha; Kang, Chang Won; Cho, Joon Hyung; Gilbertson, Scott R

    2015-08-21

    Dysiherbaine, a natural product isolated from the Marine sponge Dysidea herbacea, has been shown to be a selective agonist of non-NMDA type glutamate receptors, kainate receptors. An enantioselective synthesis of dysiherbaine is reported. Metathesis of the diene followed by conversion of the resulting alkene to the amino alcohol and addition of the amino acid provides the natural product. This synthesis differs from previous approaches to the molecule in that the functionality on the tetrahydropyran ring is installed late in the route. PMID:26258884

  7. Asymmetric synthesis of trifluoromethylated amines via catalytic enantioselective isomerization of imines.

    PubMed

    Wu, Yongwei; Deng, Li

    2012-09-01

    A new approach toward the asymmetric synthesis of optically active trifluoromethylated amines was enabled by an unprecedented, highly enantioselective catalytic isomerization of trifluoromethyl imines with a new chiral organic catalyst. Not only aryl but also alkyl trifluoromethylated amines could be obtained in high enantioselectivities. PMID:22906148

  8. Quinine-thiourea catalyzed enantioselective hydrophosphonylation of trifluoromethyl 2(1H)-quinazolinones.

    PubMed

    Xie, Hexin; Song, Aiguo; Zhang, Xinshuai; Chen, Xiaobei; Li, Hao; Sheng, Chunquan; Wang, Wei

    2013-01-30

    An organocatalytic enantioselective addition reaction of cyclic ketoimines with phosphites has been developed for the first time. The process, catalyzed by Soós' quinine thiourea, affords synthetically and medicinally interesting enantioenriched trifluoromethyl dihydroquinazolinones in high yields and with high enantioselectivities. PMID:23248060

  9. Molecular Epoxidation Reactions Catalyzed by Rhenium, Molybdenum, and Iron Complexes.

    PubMed

    Kück, Jens W; Reich, Robert M; Kühn, Fritz E

    2016-02-01

    Epoxidations are of high relevance in many organic syntheses, both in industry and academia. In this personal account, the development of rhenium, molybdenum, and iron complexes in molecular epoxidation catalysis is presented. Methyltrioxorhenium (MTO) is the benchmark catalyst for these reactions, with a thoroughly investigated mechanism and reactivity profile. More recently, highly active molecular molybdenum and iron catalysts have emerged, challenging the extraordinary role of MTO in epoxidation catalysis with high turnover frequencies (TOFs). This development is highlighted in its use of cheaper, more readily available metals, and the challenges of using base metals in catalysis are discussed. These results show the promise that relatively cheap and abundant metals, such as molybdenum and iron, hold for the future of epoxidation catalysis. PMID:26776087

  10. Palladium-Catalyzed, Enantioselective Heine Reaction

    PubMed Central

    2016-01-01

    Aziridines are important synthetic intermediates for the generation of nitrogen-containing molecules. N-Acylaziridines undergo rearrangement by ring expansion to produce oxazolines, a process known as the Heine reaction. The first catalytic, enantioselective Heine reaction is reported for meso-N-acylaziridines where a palladium(II)–diphosphine complex is employed. The highly enantioenriched oxazoline products are valuable organic synthons and potential ligands for transition-metal catalysis. PMID:27398262

  11. Short, Enantioselective Total Synthesis of Chatancin**

    PubMed Central

    Zhao, Yu-Ming

    2014-01-01

    An enantioselective total synthesis of the polycyclic diterpene chatancin (1), a potent PAF antagonist, is reported. Proceeding in seven steps from dihydrofarnesal, this synthetic route was designed to circumvent macrocyclization-based strategies to complex, cyclized cembranoids. The described synthesis requires only six chromatographic purifications, is high yielding, and avoids protecting group chemistry. An X-ray crystal structure of this fragile marine natural product was obtained. PMID:25470723

  12. Enantioselective effects in coordination compounds

    NASA Astrophysics Data System (ADS)

    Kurganov, Alexander A.; Ponomareva, T. M.; Davankov, Vadim A.

    1990-02-01

    The information that has appeared during the last 15 years relating to enantioselectivity in the formation and reactions of kinetically inert and kinetically labile complexes is classified in the present review. Attention is mainly given to chiral discrimination of ligands that are exchanged in the internal or external coordination spheres of the complexes. The occurrence of enantioselective effects has also been recorded in reactions of coordination compounds that occur without ligand exchange, in particular, in photochemical processes. The variety of forms in which enantioselectivity is displayed is shown and methods for studying it are described. The bibliography includes 223 references.

  13. Enantioselective determination of selfotel in human urine by high-performance liquid chromatography on a chiral stationary phase after derivatization with 9-fluorenylmethyl chloroformate.

    PubMed

    Knoche, B; Milosavljev, S; Gropper, S; Brunner, L A; Powell, M L

    1997-08-01

    An analytical method for the enantioselective determination of selfotel in human urine has been developed and validated. The method is based on high-performance liquid chromatography and utilizes CGS 20005 (a selfotel analog) as the internal standard. Urine samples were derivatized in situ with o-phthalic dicarboxaldehyde-3-mercaptopropionic acid and 9-fluorenylmethyl chloroformate (FMOC). Chromatographic separations of the FMOC derivatives of selfotel enantiomers and the internal standard were achieved using a column switching system consisting of an Inertsil ODS-2 column (75x4.6 mm I.D., 5 microm) and a Chiralcel OD-R column (250x4.6 mm I.D., 10 microm). The composition of the mobile phase was acetonitrile-0.1 M phosphate buffer, pH 2.50 (35:65) for the Inertsil ODS-2 column and acetonitrile-0.1 M phosphate buffer, pH 2.00 (35:65) for the Chiralcel OD-R column. The analytes were monitored using fluorescence detection at an excitation wavelength of 262 nm and an emission wavelength of 314 nm. The limit of quantification (LOQ) for this method is 0.25 microg/ml for each selfotel enantiomer. The method was successfully utilized to determine preliminary selfotel stereospecific pharmacokinetics. PMID:9300872

  14. Palladium(II)/Brønsted Acid-Catalyzed Enantioselective Oxidative Carbocyclization-Borylation of Enallenes.

    PubMed

    Jiang, Tuo; Bartholomeyzik, Teresa; Mazuela, Javier; Willersinn, Jochen; Bäckvall, Jan-E

    2015-05-11

    An enantioselective oxidative carbocyclization-borylation of enallenes that is catalyzed by palladium(II) and a Brønsted acid was developed. Biphenol-type chiral phosphoric acids were superior co-catalysts for inducing the enantioselective cyclization. A number of chiral borylated carbocycles were synthesized in high enantiomeric excess. PMID:25808996

  15. Palladium(II)/Brønsted Acid-Catalyzed Enantioselective Oxidative Carbocyclization–Borylation of Enallenes**

    PubMed Central

    Jiang, Tuo; Bartholomeyzik, Teresa; Mazuela, Javier; Willersinn, Jochen; Bäckvall, Jan-E

    2015-01-01

    An enantioselective oxidative carbocyclization–borylation of enallenes that is catalyzed by palladium(II) and a Brønsted acid was developed. Biphenol-type chiral phosphoric acids were superior co-catalysts for inducing the enantioselective cyclization. A number of chiral borylated carbocycles were synthesized in high enantiomeric excess. PMID:25808996

  16. Enantioselective addition of diphenyl phosphonate to ketimines derived from isatins catalyzed by binaphthyl-modified organocatalysts

    PubMed Central

    Jang, Hee Seung; Kim, Yubin

    2016-01-01

    Summary Chiral binaphthyl-modified squaramide-catalyzed enantioselective addition of diphenyl phosphonate to ketimines derived from isatins has been achieved. This method affords practical and efficient access to chiral 3-amino-3-phosphonyl-substituted oxindole derivatives in high yields with excellent enantioselectivities (up to 99% ee). PMID:27559405

  17. Enantioselective carbenoid insertion into C(sp3)–H bonds

    PubMed Central

    Santiago, J V

    2016-01-01

    Summary The enantioselective carbenoid insertion into C(sp3)–H bonds is an important tool for the synthesis of complex molecules due to the high control of enantioselectivity in the formation of stereogenic centers. This paper presents a brief review of the early issues, related mechanistic studies and recent applications on this chemistry area. PMID:27340479

  18. Chiral Brønsted Acid Catalyzed Enantioselective Phosphonylation of Allylamine via Oxidative Dehydrogenation Coupling.

    PubMed

    Cheng, Ming-Xing; Ma, Ran-Song; Yang, Qiang; Yang, Shang-Dong

    2016-07-01

    A new strategy for the synthesis of chiral α-amino phosphonates by enantioselective C-H phosphonylation of allylamine with phosphite in the presence of a chiral Brønsted acid catalyst has been developed. This protocol successfully integrates direct C-H oxidation with asymmetric phosphonylation and exhibits high enantioselectivity. PMID:27331612

  19. Enantioselective Selenocyclization via Dynamic Kinetic Resolution of Seleniranium Ions by Hydrogen-Bond Donor Catalysts

    PubMed Central

    2015-01-01

    Highly enantioselective selenocyclization reactions are promoted by the combination of a new chiral squaramide catalyst, a mineral acid, and an achiral Lewis base. Mechanistic studies reveal that the enantioselectivity originates from the dynamic kinetic resolution of seleniranium ions through anion-binding catalysis. PMID:25380129

  20. Organocatalytic enantioselective desymmetrization of cyclic enones via phosphine promoted [3+2] annulations.

    PubMed

    Pinto, Nathalie; Retailleau, Pascal; Voituriez, Arnaud; Marinetti, Angela

    2011-01-21

    Phosphine catalyzed enantioselective [3+2] cyclizations on 4-substituted 2,6-diarylidenecyclohexanones and 2,4-diarylidene-bicyclo[3.1.0]hexan-3-ones take place with high diastereo- and enantioselectivity levels. The process affords spirocyclic compounds with excellent stereochemical control of up to five stereogenic centres. PMID:21063612

  1. Enantioselective acylation of silyl ketene acetals through fluoride anion-binding catalysis.

    PubMed

    Birrell, James A; Desrosiers, Jean-Nicolas; Jacobsen, Eric N

    2011-09-01

    A highly enantioselective acylation of silyl ketene acetals with acyl fluorides has been developed to generate useful α,α-disubstituted butyrolactone products. This transformation is promoted by a new thiourea catalyst and 4-pyrrolidinopyridine and represents the first example of enantioselective thiourea anion-binding catalysis with fluoride. PMID:21800916

  2. Enantioselective hydrolysis of epichlorohydrin using whole Aspergillus niger ZJB-09173 cells in organic solvents.

    PubMed

    Jin, Huo-Xi; Hu, Zhong-Ce; Zheng, Yu-Guo

    2012-09-01

    The enantioselective hydrolysis of racemic epichlorohydrin for the production of enantiopure (S)-epichlorohydrin using whole cells of Aspergillus niger ZJB-09173 in organic solvents was investigated. Cyclohexane was used as the reaction medium based on the excellent enantioselectivity of epoxide hydrolase from A. niger ZJB- 09173 in cyclohexane. However, cyclohexane had a negative effect on the stability of epoxide hydrolase from A. niger ZJB-09173. In the cyclohexane medium, substrate inhibition, rather than product inhibition of catalysis, was observed in the hydrolysis of racemic epichlorohydrin using A. niger ZJB-09173. The racemic epichlorohydrin concentration was markedly increased by continuous feeding of substrate without significant decline of the yield. Ultimately, 18.5% of (S)-epichlorohydrin with 98 percent enantiomeric excess from 153.6 mM of racemic epichlorohydrin was obtained by the dry cells of A. niger ZJB-09173, which was the highest substrate concentration in the production of enantiopure (S)-epichlorohydrin by epoxide hydrolases using an organic solvent medium among the known reports. PMID:22922194

  3. Modeling Epoxidation of Drug-like Molecules with a Deep Machine Learning Network

    PubMed Central

    2015-01-01

    Drug toxicity is frequently caused by electrophilic reactive metabolites that covalently bind to proteins. Epoxides comprise a large class of three-membered cyclic ethers. These molecules are electrophilic and typically highly reactive due to ring tension and polarized carbon–oxygen bonds. Epoxides are metabolites often formed by cytochromes P450 acting on aromatic or double bonds. The specific location on a molecule that undergoes epoxidation is its site of epoxidation (SOE). Identifying a molecule’s SOE can aid in interpreting adverse events related to reactive metabolites and direct modification to prevent epoxidation for safer drugs. This study utilized a database of 702 epoxidation reactions to build a model that accurately predicted sites of epoxidation. The foundation for this model was an algorithm originally designed to model sites of cytochromes P450 metabolism (called XenoSite) that was recently applied to model the intrinsic reactivity of diverse molecules with glutathione. This modeling algorithm systematically and quantitatively summarizes the knowledge from hundreds of epoxidation reactions with a deep convolution network. This network makes predictions at both an atom and molecule level. The final epoxidation model constructed with this approach identified SOEs with 94.9% area under the curve (AUC) performance and separated epoxidized and non-epoxidized molecules with 79.3% AUC. Moreover, within epoxidized molecules, the model separated aromatic or double bond SOEs from all other aromatic or double bonds with AUCs of 92.5% and 95.1%, respectively. Finally, the model separated SOEs from sites of sp2 hydroxylation with 83.2% AUC. Our model is the first of its kind and may be useful for the development of safer drugs. The epoxidation model is available at http://swami.wustl.edu/xenosite. PMID:27162970

  4. Modeling Epoxidation of Drug-like Molecules with a Deep Machine Learning Network.

    PubMed

    Hughes, Tyler B; Miller, Grover P; Swamidass, S Joshua

    2015-07-22

    Drug toxicity is frequently caused by electrophilic reactive metabolites that covalently bind to proteins. Epoxides comprise a large class of three-membered cyclic ethers. These molecules are electrophilic and typically highly reactive due to ring tension and polarized carbon-oxygen bonds. Epoxides are metabolites often formed by cytochromes P450 acting on aromatic or double bonds. The specific location on a molecule that undergoes epoxidation is its site of epoxidation (SOE). Identifying a molecule's SOE can aid in interpreting adverse events related to reactive metabolites and direct modification to prevent epoxidation for safer drugs. This study utilized a database of 702 epoxidation reactions to build a model that accurately predicted sites of epoxidation. The foundation for this model was an algorithm originally designed to model sites of cytochromes P450 metabolism (called XenoSite) that was recently applied to model the intrinsic reactivity of diverse molecules with glutathione. This modeling algorithm systematically and quantitatively summarizes the knowledge from hundreds of epoxidation reactions with a deep convolution network. This network makes predictions at both an atom and molecule level. The final epoxidation model constructed with this approach identified SOEs with 94.9% area under the curve (AUC) performance and separated epoxidized and non-epoxidized molecules with 79.3% AUC. Moreover, within epoxidized molecules, the model separated aromatic or double bond SOEs from all other aromatic or double bonds with AUCs of 92.5% and 95.1%, respectively. Finally, the model separated SOEs from sites of sp(2) hydroxylation with 83.2% AUC. Our model is the first of its kind and may be useful for the development of safer drugs. The epoxidation model is available at http://swami.wustl.edu/xenosite. PMID:27162970

  5. Direct epoxidation of propylene over stabilized Cu(+) surface sites on titanium-modified Cu2O.

    PubMed

    Yang, Xiaofang; Kattel, Shyam; Xiong, Ke; Mudiyanselage, Kumudu; Rykov, Sergei; Senanayake, Sanjaya D; Rodriguez, José A; Liu, Ping; Stacchiola, Dario J; Chen, Jingguang G

    2015-10-01

    Direct propylene epoxidation by O2 is a challenging reaction because of the strong tendency for complete combustion. Results from the current study demonstrate that by generating highly dispersed and stabilized Cu(+) active sites in a TiCuOx mixed oxide the epoxidation selectivity can be tuned. The TiCuOx surface anchors the key surface intermediate, an oxametallacycle, leading to higher selectivity for epoxidation of propylene. PMID:26215635

  6. Direct Epoxidation of Propylene over Stabilized Cu+ Surface Sites on Ti Modified Cu2O

    DOE PAGESBeta

    Yang, X.; Kattel, S.; Xiong, K.; Mudiyanselage, K.; Rykov, S.; Senanayake, S. D.; Rodriguez, J. A.; Liu, P.; Stacchiola, D. J.; Chen, J. G.

    2015-07-17

    Direct propylene epoxidation by O2 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 TiCuOx mixed oxide. The TiCuOx surface anchors the key surface intermediate, oxametallacycle, leading to higher selectivity for epoxidation of propylene.

  7. Highly enantioselective hydrogenation of α-oxy functionalized α,β-unsaturated acids catalyzed by a ChenPhos-Rh complex in CF3CH2OH.

    PubMed

    Yao, Lin; Wen, Jialin; Liu, Shaodong; Tan, Renchang; Wood, Noel Marie; Chen, Weiping; Zhang, Shengyong; Zhang, Xumu

    2016-02-01

    Rhodium complexes coordinated by Chenphos are very effective catalysts for the enantioselective hydrogenation of α-aryloxy- and α-alkoxy-substituted α,β-unsaturated carboxylic acids under mild conditions in CF3CH2OH. The catalytic system could be successfully employed in building the core structure of a new FDA approved drug LCZ 696. PMID:26730444

  8. Catalysis of potato epoxide hydrolase, StEH1

    PubMed Central

    Elfström, Lisa T.; Widersten, Mikael

    2005-01-01

    The kinetic mechanism of epoxide hydrolase (EC 3.3.2.3) from potato, StEH1 (Solanum tuberosum epoxide hydrolase 1), was studied by presteady-state and steady-state kinetics as well as by pH dependence of activity. The specific activities towards the different enantiomers of TSO (trans-stilbene oxide) as substrate were 43 and 3 μmol·min−1·mg−1 with the R,R- or S,S-isomers respectively. The enzyme was, however, enantioselective in favour of the S,S enantiomer due to a lower Km value. The pH dependences of kcat with R,R or S,S-TSO were also distinct and supposedly reflecting the pH dependences of the individual kinetic rates during substrate conversion. The rate-limiting step for TSO and cis- and trans-epoxystearate was shown by rapid kinetic measurements to be the hydrolysis of the alkylenzyme intermediate. Functional characterization of point mutants verified residues Asp105, Tyr154, Tyr235 and His300 as crucial for catalytic activity. All mutants displayed drastically decreased enzymatic activities during steady state. Presteady-state measurements revealed the base-deficient H300N (His300→Asn) mutant to possess greatly reduced efficiencies in catalysis of both chemical steps (alkylation and hydrolysis). PMID:15882148

  9. A Catalytic, Enantioselective Formal Synthesis of (+)-Dichroanone and (+)-Taiwaniaquinone H

    PubMed Central

    2015-01-01

    A catalytic, enantioselective formal synthesis of (+)-dichroanone and (+)-taiwaniaquinone H is reported. The all-carbon quaternary stereocenter was constructed by asymmetric conjugate addition catalyzed by a palladium(II) (S)-tert-butylpyridinooxazoline complex. The unexpected formation of a [3.2.1] bicyclic intermediate required the identification of a new route. Analysis of the Hammett constants for para-substituted arenes enabled the rational design of a highly enantioselective conjugate addition substrate that led to the completion of the formal synthesis. PMID:25489925

  10. Catalytic Enantioselective Functionalization of Unactivated Terminal Alkenes.

    PubMed

    Coombs, John R; Morken, James P

    2016-02-18

    Terminal alkenes are readily available functional groups which appear in α-olefins produced by the chemical industry, and they appear in the products of many contemporary synthetic reactions. While the organic transformations that apply to alkenes are amongst the most studied reactions in all of chemical synthesis, the number of reactions that apply to nonactivated terminal alkenes in a catalytic enantioselective fashion is small in number. This Minireview highlights the cases where stereocontrol in catalytic reactions of 1-alkenes is high enough to be useful for asymmetric synthesis. PMID:26764019

  11. 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

  12. Enantioselective [4 + 2]-Annulation of Oxadienes and Allenones Catalyzed by an Amino Acid Derived Phosphine: Synthesis of Functionalized Dihydropyrans.

    PubMed

    Ni, Huanzhen; Yao, Weijun; Waheed, Abdul; Ullah, Nisar; Lu, Yixin

    2016-05-01

    An enantioselective [4 + 2]-annulation process between cyano-activated oxadienes and allenones is developed. An l-valine-derived phosphine was efficient in catalyzing the reaction, and a wide range of highly functionalized dihydropyrans were prepared in high yields and with excellent enantioselectivities. PMID:27091405

  13. Enantioselective intermolecular cross Rauhut-Currier reactions of activated alkenes with acrolein.

    PubMed

    Zhou, Wei; Chen, Peng; Tao, Mengna; Su, Xiao; Zhao, Qingjie; Zhang, Junliang

    2016-06-18

    The enantioselective intermolecular cross Rauhut-Currier reaction of acrolein with active olefins has been a long-standing challenge because of the competitive MBH reaction and polymerization. Herein a highly enantioselective intermolecular cross Rauhut-Currier reaction of acrolein with 3-acyl acrylates and 2-ene-1,4-diones, which is enabled by newly designed Peng-Phos catalysts. This method is scalable and highly enantioselective (up to 96% ee). Several transformations of the R-C products are carried out to showcase the synthetic utility. PMID:27225510

  14. 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. PMID:22967461

  15. Enantioselective Claisen rearrangements with a hydrogen-bond donor catalyst.

    PubMed

    Uyeda, Christopher; Jacobsen, Eric N

    2008-07-23

    N,N'-Diphenylguanidinium ion associated with the noncoordinating BArF counterion is shown to be an effective catalyst for the [3,3]-sigmatropic rearrangement of a variety of substituted allyl vinyl ethers. Highly enantioselective catalytic Claisen rearrangements of ester-substituted allyl vinyl ethers are then documented using a new C2-symmetric guanidinium ion derivative. PMID:18576616

  16. Cyclopalladated complexes in enantioselective catalysis

    NASA Astrophysics Data System (ADS)

    Dunina, Valeria V.; Gorunova, Olga N.; Zykov, P. A.; Kochetkov, Konstantin A.

    2011-01-01

    The results of the use of optically active palladacycles in enantioselective catalysis of [3,3]-sigmatropic rearrangements, aldol condensation, the Michael reaction and cross-coupling are analyzed. Reactions with allylic substrates or reagents and some other transformations are considered.

  17. Photopolymerizations of multicomponent epoxide and acrylate/epoxide hybrid systems for controlled kinetics and enhanced material properties

    NASA Astrophysics Data System (ADS)

    Eom, Ho Seop

    2011-12-01

    Cationic photopolymerization of multifunctional epoxides is very useful for efficient cure at room temperature and has been widely used in coatings and adhesives. Despite excellent properties of the final cured polymers, cationic photopolymerizations of epoxides have seen limited application due to slow reactions (relative to acrylates) and brittleness associated with a highly crosslinked, rigid network. To address these issues, two reaction systems were studied in this thesis: photoinitiated cationic copolymerizations of a cycloaliphatic diepoxide with epoxidized elastomers and acrylate/epoxide hybrid photopolymerizations. Oligomer/monomer structures, viscosity, compositions, and photoinitiator system were hypothesized to play important roles in controlling photopolymerizations of the epoxide-based mixtures. A fundamental understanding of the interplay between these variables for the chosen systems will provide comprehensive guidelines for the future development of photopolymerization systems comparable to the epoxide-based mixtures in this research. For diepoxide/oligomer mixtures, the observed overall enhancement in polymerization rate and ultimate conversion of the cycloaliphatic diepoxide was attributed to the activated monomer mechanism associated with hydroxyl terminal groups in the epoxidized oligomers. This enhancement increased with increasing oligomer content. The mixture viscosity influenced the initial reactivity of the diepoxide for oligomer content above 50 wt.%. Real-time consumption of internal epoxides in the oligomers was successfully determined using Raman spectroscopy. Initial reactivity and ultimate conversion of the internal epoxides decreased with increasing the diepoxide content. This trend was more pronounced for the oligomer containing low internal epoxide content. These results indicate that the reactivity of the hydroxyl groups is higher toward cationic active centers of the diepoxide than those of the internal epoxides in the oligomers

  18. 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. PMID:11414316

  19. Highly regio- and enantioselective synthesis of N-substituted 2-pyridones: iridium-catalyzed intermolecular asymmetric allylic amination.

    PubMed

    Zhang, Xiao; Yang, Ze-Peng; Huang, Lin; You, Shu-Li

    2015-02-01

    The first iridium-catalyzed intermolecular asymmetric allylic amination reaction with 2-hydroxypyridines has been developed, thus providing a highly efficient synthesis of enantioenriched N-substituted 2-pyridone derivatives from readily available starting materials. This protocol features a good tolerance of functional groups in both the allylic carbonates and 2-hydroxypyridines, thereby delivering multifunctionalized heterocyclic products with up to 98% yield and 99% ee. PMID:25504907

  20. Catalytic asymmetric reductive coupling of alkynes and aldehydes: enantioselective synthesis of allylic alcohols and alpha-hydroxy ketones.

    PubMed

    Miller, Karen M; Huang, Wei-Sheng; Jamison, Timothy F

    2003-03-26

    A highly enantioselective method for catalytic reductive coupling of alkynes and aldehydes is described. Allylic alcohols are afforded with complete E/Z selectivity, generally >95:5 regioselectivity, and in up to 96% ee. In conjunction with ozonolysis, this process is complementary to existing methods of enantioselective alpha-hydroxy ketone synthesis. PMID:12643701

  1. Enantioselective Addition of Diethylzinc to Aldehydes Catalyzed by Chiral O,N,O-tridentate Phenol Ligands Derived From Camphor.

    PubMed

    Lee, Dong-Sheng; Chang, Shu-Ming; Ho, Chun-Ying; Lu, Ta-Jung

    2016-01-01

    Chiral O,N,O-tridentate phenol ligands bearing a camphor backbone were found to be effective chiral catalysts for the enantioselective addition of diethylzinc to aromatic aldehydes, resulting in high enantioselectivities (80-95% ee) at room temperature. PMID:26487505

  2. Enantioselective analysis of D- and L-amino acids from mouse macrophages using high performance liquid chromatography.

    PubMed

    Kato, Shiro; Masuda, Yuki; Konishi, Morichika; Oikawa, Tadao

    2015-12-10

    The intrinsic D-amino acid profile of mouse macrophages extracted from the peritoneal cavity was analyzed using high performance liquid chromatography. Six D-amino acids (D-Asp, D-Ser, D-Ala, D-Leu, D-Gln and D-Lys) were detected in cell lysates of mouse macrophages. The content and the D/D+L ratio differed depending on the type of D-amino acid and were approximately 3.5-22 nmol/g cells, and approximately 1-20%, respectively. The D-amino acid composition of RAW 264.7 cells, which is a model macrophage cell line, was similar to that of the mouse macrophage. These results suggest that macrophages and RAW 264.7 cells with macrophage-like functions have a similar D-amino acid profile. PMID:25982753

  3. Enantioselective Intermolecular Cyclopropanations for the Synthesis of Chiral Pyrimidine Carbocyclic Nucleosides.

    PubMed

    Xie, Ming-Sheng; Zhou, Peng; Niu, Hong-Ying; Qu, Gui-Rong; Guo, Hai-Ming

    2016-09-01

    A direct route to chiral cyclopropylpyrimidine carbocyclic nucleoside analogues has been reported via highly enantioselective intermolecular cyclopropanation reactions of N1-vinylpyrimidines with α-diazoesters. With chiral ruthenium(II)-phenyloxazoline complex (2 mol %) as the catalyst, cyclopropyl pyrimidine nucleoside analogues could be obtained in good yields (71-96% yields) with high levels of diastereo- and enantioselectivities (10:1 to >20:1 dr and 96-99% ee) in 1 min. PMID:27526779

  4. Acetylphosphonate as a Surrogate of Acetate or Acetamide in Organocatalyzed Enantioselective Aldol Reactions

    PubMed Central

    Guang, Jie; Guo, Qunsheng

    2012-01-01

    Highly enantioselective aldol reactions of acetylphosphonates and activated carbonyl compounds was realized with cinchona alkaloid derived catalysts, in which the acetylphosphonate was directly used as an enolate precursor for the first time. The aldol product obtained was converted in situ to its corresponding ester or amide through methanolysis or aminolysis. The overall process may be viewed as formal highly enantioselective acetate or acetamide aldol reactions, which are very difficult to achieve directly with organocatalytic methods. PMID:22650245

  5. Enantiodivergent Combination of Natural Product Scaffolds Enabled by Catalytic Enantioselective Cycloaddition.

    PubMed

    Xu, Hao; Golz, Christopher; Strohmann, Carsten; Antonchick, Andrey P; Waldmann, Herbert

    2016-06-27

    An efficient strategy has been established for the enantiodivergent synthesis of natural product inspired compounds embodying both tropane and pyrrolidine natural product fragments. This strategy includes the enantioselective kinetic resolution of racemic tropanes by means of a copper(I)-catalyzed [3+2] cycloaddition and allows the preparation of two enantiopure products in a one-pot reaction in high yield and with high diastereo- and enantioselectivity by using one chiral catalyst. PMID:27193834

  6. Enantioselective analysis of tolvaptan in rat and dog sera by high-performance liquid chromatography and application to pharmacokinetic study.

    PubMed

    Furukawa, Masayuki; Yamasaki, Yuko; Hirao, Yukihiro; Umehara, Ken

    2014-08-15

    Tolvaptan is a competitive vasopressin V2-receptor antagonist that inhibits water reabsorption in the renal collecting ducts. A selective high-performance liquid chromatography method for determining tolvaptan enantiomers in rat and dog sera was developed and validated. Benzyl salicylate was used as an internal standard. Sample preparation involved liquid-liquid extraction with an n-hexane:diethyl ether (1:1, v/v) solution, followed by solid-phase extraction using a silica-gel cartridge. Chromatographic separation was performed on a cellulose-based chiral stationary phase in the reversed phase mode. The analytes were monitored with UV detection. The calibration curve showed linearity over the concentration range from 0.025 to 2.5 μg/mL for each analyte. Precision as the percentage coefficient of variation did not exceed 14.8%, and accuracy as relative error was within ±14.6% for the analytes. The validated method was successfully applied to evaluate the pharmacokinetics of oral tolvaptan enantiomers in rats and dogs, indicating gender and species differences in the systemic exposure to tolvaptan enantiomers. PMID:25016163

  7. Catalytic, Enantioselective, Intramolecular Carbosulfenylation of Olefins. Preparative and Stereochemical Aspects

    PubMed Central

    Denmark, Scott E.; Jaunet, Alex

    2014-01-01

    The first catalytic, enantioselective, intramolecular carbosulfenylation of isolated alkenes with aromatic nucleophiles is described. The combination of N-phenylsulfenylphthalimide, a chiral selenophosphoramide derived from BINAM, and ethanesulfonic acid as a co-catalytic Brønsted acid induced an efficient and selective cyclofunctionalization of various alkenes (aliphatic and aromatic) tethered to a 3,4-methylenedioxyphenyl ring. Under these conditions, 6-phenylthio-5,6,7,8-tetrahydronaphthalenes are formed diastereospecifically in good yields (50–92%) and high enantioselectivities (71:29 – 97:3 er). E-Alkenes reacted much more rapidly and with much higher selectivity than Z-alkenes, whereas electron rich alkenes reacted more rapidly but with comparable selectivity to electron-neutral alkenes and electron deficient alkenes. The Brønsted acid played a critical role in effecting reproducible enantioselectivity. A model for the origin of enantioselectivity and the dependence of rate and selectivity on alkene structure is proposed along with a rationale for the site selectivity in reactions with mono-activated arene nucleophiles. PMID:24328051

  8. Carcinogenicity and mechanistic insights on the behavior of epoxides and epoxide-forming chemicals.

    PubMed

    Melnick, Ronald L

    2002-12-01

    Many epoxides and their precursors are high production volume chemicals that have major uses in the polymer industry and as intermediates in the manufacture of other chemicals. Several of these chemicals were demonstrated to be carcinogenic in laboratory animal studies conducted by the Ramazzini Foundation (e.g., vinyl chloride, acrylonitrile, styrene, styrene oxide, and benzene) and by the National Toxicology Program (e.g., ethylene oxide, 1,3-butadiene, isoprene, chloroprene, acrylonitrile, glycidol, and benzene). The most common sites of tumor induction were lung, liver, harderian gland, and circulatory system in mice; Zymbal's gland and brain in rats; and mammary gland and forestomach in both species. Differences in cancer outcome among studies of epoxide chemicals may be related to differences in study design (e.g., dose, duration, and route of exposure; observation period; animal strains), as well as biological factors affecting target organ dosimetry of the DNA-reactive epoxide (toxicokinetics) and tissue response (toxicodynamics). N7-Alkylguanine, N1-alkyladenine, and cyclic etheno adducts, as well as K-ras and p53 mutations, have been detected in animals and/or workers exposed to several of these chemicals. The classifications of these chemical carcinogens by IARC and NTP are based on animal and human data and results of mechanistic studies. Reducing occupational and environmental exposures to these chemicals will certainly reduce human cancer risks. PMID:12562636

  9. Enantioselective Synthesis of (+)-Peganumine A.

    PubMed

    Piemontesi, Cyril; Wang, Qian; Zhu, Jieping

    2016-09-01

    A gram-scale enantioselective total synthesis of (+)-peganumine A was accomplished in 7 steps from commercially available 6-methoxytryptamine. Key steps included (a) a Liebeskind-Srogl cross-coupling; (b) a one-pot construction of the tetracyclic skeleton from an ω-isocyano-γ-oxo-aldehyde via a sequence of an unprecedented C-C bond forming lactamization and a transannular condensation; (c) a one-pot organocatalytic process merging two achiral building blocks into an octacyclic structure via a sequence of enantioselective Pictet-Spengler reaction followed by a transannular cyclization. This last reaction created two spirocycles and a 2,7-diazabicyclo[2.2.1]heptan-3-one unit with excellent control of both the absolute and relative stereochemistry of the two newly created quaternary stereocenters. PMID:27558528

  10. Enantioselective Total Synthesis of (-)-Pironetin

    PubMed Central

    Crimmins, Michael T.; Dechert, Anne-Marie R.

    2009-01-01

    The enantioselective total synthesis of pironetin has been achieved in 11 steps from known aldehyde 2. The synthesis relies on the formation of 5 out of 6 stereocenters through titanium mediated iterative aldol reactions. Key steps in this synthesis include an acetal aldol reaction to establish the stereochemistry at C8 and C9, an acetate aldol reaction, and “Evans” syn aldol reaction. PMID:19281219

  11. Conformational diversity and enantioconvergence in potato epoxide hydrolase 1.

    PubMed

    Bauer, P; Carlsson, Å Janfalk; Amrein, B A; Dobritzsch, D; Widersten, M; Kamerlin, S C L

    2016-06-28

    Potato epoxide hydrolase 1 (StEH1) is a biocatalytically important enzyme that exhibits rich enantio- and regioselectivity in the hydrolysis of chiral epoxide substrates. In particular, StEH1 has been demonstrated to enantioconvergently hydrolyze racemic mixes of styrene oxide (SO) to yield (R)-1-phenylethanediol. This work combines computational, crystallographic and biochemical analyses to understand both the origins of the enantioconvergent behavior of the wild-type enzyme, as well as shifts in activities and substrate binding preferences in an engineered StEH1 variant, R-C1B1, which contains four active site substitutions (W106L, L109Y, V141K and I155V). Our calculations are able to reproduce both the enantio- and regioselectivities of StEH1, and demonstrate a clear link between different substrate binding modes and the corresponding selectivity, with the preferred binding modes being shifted between the wild-type enzyme and the R-C1B1 variant. Additionally, we demonstrate that the observed changes in selectivity and the corresponding enantioconvergent behavior are due to a combination of steric and electrostatic effects that modulate both the accessibility of the different carbon atoms to the nucleophilic side chain of D105, as well as the interactions between the substrate and protein amino acid side chains and active site water molecules. Being able to computationally predict such subtle effects for different substrate enantiomers, as well as to understand their origin and how they are affected by mutations, is an important advance towards the computational design of improved biocatalysts for enantioselective synthesis. PMID:27049844

  12. Cobalt-Catalyzed Enantioselective Vinylation of Activated Ketones and Imines.

    PubMed

    Huang, Yuan; Huang, Rui-Zhi; Zhao, Yu

    2016-05-25

    We present here an unprecedented cobalt-catalyzed enantioselective vinylation of α-ketoesters, isatins, and imines to deliver a range of synthetically useful allylic alcohols and amines in high enantiopurity. This method employs commercially available and easy to handle catalysts and reagents and exhibits a high degree of practicality. The efficiency, selectivity, and operational simplicity of this catalytic system coupled with the substrate generality render this method a valuable tool in organic synthesis. PMID:27139596

  13. Hydroxyl-Substituted Ladder Polyethers via Selective Tandem Epoxidation/Cyclization Sequence

    PubMed Central

    Czabaniuk, Lara C.; Jamison, Timothy F.

    2015-01-01

    A new and highly selective method for the synthesis of hydroxyl-substituted tetrahydropyrans is described. This method utilizes titanium(IV) iso-propoxide and diethyl tartrate to perform a diastereoselective epoxidation followed by in situ epoxide activation and highly selective endo-cyclization to form the desired tetrahydropyran ring. The HIJ ring fragment of the marine ladder polyether yessotoxin was synthesized using this two-stage tactic that proceeds with high efficiency and excellent regioselectivity. PMID:25647091

  14. Organocatalytic asymmetric epoxidation and tandem epoxidation/Passerini reaction under eco-friendly reaction conditions.

    PubMed

    Deobald, Anna Maria; Corrêa, Arlene G; Rivera, Daniel G; Paixão, Márcio Weber

    2012-10-14

    An eco-friendly synthesis of highly functionalized epoxides and their incorporation into an organocatalytic multicomponent approach are reported. For this, a modified class of diarylprolinol silyl ethers was designed to enable high catalytic activity in an environmentally benign solvent system. The one-pot procedure showed great efficiency in promoting stereoselective multicomponent transformations in a tandem, 'green' fashion. Because of its non-residual, efficient and selective character, this synthetic design shows promise for large-scale applications in both diversity and target-oriented syntheses. PMID:22918441

  15. Enantioselective Rhodium-Catalyzed Atom-Economical Macrolactonization.

    PubMed

    Ganss, Stephanie; Breit, Bernhard

    2016-08-01

    A highly attractive route toward macrolactones, which form the cyclic scaffold of a multitude of diverse natural compounds, is described. Although many chemical approaches to this structural motif have been explored, an asymmetric variant of the cyclization is unprecedented. Herein we present an enantioselective macrolactonization through an intramolecular atom-economical rhodium-catalyzed coupling of ω-allenyl-substituted carboxylic acids. The use of a modified diop ligand, chiral DTBM-diop, led to high enantioselectivity (up to 93 % ee). The reaction tolerated a large variety of functionalities, including α,β-unsaturated carboxylic acids and depsipeptides, and provided the desired macrocycles with very high enantio- and diastereoselectivity. PMID:27383766

  16. Enantioselective Hydrolysis of Amino Acid Esters Promoted by Bis(β-cyclodextrin) Copper Complexes.

    PubMed

    Xue, Shan-Shan; Zhao, Meng; Ke, Zhuo-Feng; Cheng, Bei-Chen; Su, Hua; Cao, Qian; Cao, Zhen-Kun; Wang, Jun; Ji, Liang-Nian; Mao, Zong-Wan

    2016-01-01

    It is challenging to create artificial catalysts that approach enzymes with regard to catalytic efficiency and selectivity. The enantioselective catalysis ranks the privileged characteristic of enzymatic transformations. Here, we report two pyridine-linked bis(β-cyclodextrin) (bisCD) copper(II) complexes that enantioselectively hydrolyse chiral esters. Hydrolytic kinetic resolution of three pairs of amino acid ester enantiomers (S1-S3) at neutral pH indicated that the "back-to-back" bisCD complex CuL(1) favoured higher catalytic efficiency and more pronounced enantioselectivity than the "face-to-face" complex CuL(2). The best enantioselectivity was observed for N-Boc-phenylalanine 4-nitrophenyl ester (S2) enantiomers promoted by CuL(1), which exhibited an enantiomer selectivity of 15.7. We observed preferential hydrolysis of L-S2 by CuL(1), even in racemic S2, through chiral high-performance liquid chromatography (HPLC). We demonstrated that the enantioselective hydrolysis was related to the cooperative roles of the intramolecular flanking chiral CD cavities with the coordinated copper ion, according to the results of electrospray ionization mass spectrometry (ESI-MS), inhibition experiments, rotating-frame nuclear Overhauser effect spectroscopy (ROESY), and theoretical calculations. Although the catalytic parameters lag behind the level of enzymatic transformation, this study confirms the cooperative effect of the first and second coordination spheres of artificial catalysts in enantioselectivity and provides hints that may guide future explorations of enzyme mimics. PMID:26916830

  17. Enantioselective Hydrolysis of Amino Acid Esters Promoted by Bis(β-cyclodextrin) Copper Complexes

    NASA Astrophysics Data System (ADS)

    Xue, Shan-Shan; Zhao, Meng; Ke, Zhuo-Feng; Cheng, Bei-Chen; Su, Hua; Cao, Qian; Cao, Zhen-Kun; Wang, Jun; Ji, Liang-Nian; Mao, Zong-Wan

    2016-02-01

    It is challenging to create artificial catalysts that approach enzymes with regard to catalytic efficiency and selectivity. The enantioselective catalysis ranks the privileged characteristic of enzymatic transformations. Here, we report two pyridine-linked bis(β-cyclodextrin) (bisCD) copper(II) complexes that enantioselectively hydrolyse chiral esters. Hydrolytic kinetic resolution of three pairs of amino acid ester enantiomers (S1-S3) at neutral pH indicated that the “back-to-back” bisCD complex CuL1 favoured higher catalytic efficiency and more pronounced enantioselectivity than the “face-to-face” complex CuL2. The best enantioselectivity was observed for N-Boc-phenylalanine 4-nitrophenyl ester (S2) enantiomers promoted by CuL1, which exhibited an enantiomer selectivity of 15.7. We observed preferential hydrolysis of L-S2 by CuL1, even in racemic S2, through chiral high-performance liquid chromatography (HPLC). We demonstrated that the enantioselective hydrolysis was related to the cooperative roles of the intramolecular flanking chiral CD cavities with the coordinated copper ion, according to the results of electrospray ionization mass spectrometry (ESI-MS), inhibition experiments, rotating-frame nuclear Overhauser effect spectroscopy (ROESY), and theoretical calculations. Although the catalytic parameters lag behind the level of enzymatic transformation, this study confirms the cooperative effect of the first and second coordination spheres of artificial catalysts in enantioselectivity and provides hints that may guide future explorations of enzyme mimics.

  18. Molecular cloning and heterologous expression of a cDNA encoding a mouse glutathione S-transferase Yc subunit possessing high catalytic activity for aflatoxin B1-8,9-epoxide.

    PubMed Central

    Hayes, J D; Judah, D J; Neal, G E; Nguyen, T

    1992-01-01

    Resistance to the carcinogenic effects of aflatoxin B1 (AFB1) in the mouse is due to the constitutive expression of an Alpha-class glutathione S-transferase (GST), YcYc, with high detoxification activity towards AFB1-8,9-epoxide. A cDNA clone (pmusGST Yc) for a murine GST Yc polypeptide has been isolated. Sequencing has shown the cDNA insert of pmusGST Yc to be 922 bp in length, with an open reading frame of 663 bp that encodes a polypeptide of M(r) 25358. The primary structure of the murine GST Yc subunit predicted by pmusGST Yc is in complete agreement with the partial amino acid sequence of the aflatoxin-metabolizing mouse liver GST described previously [McLellan, Kerr, Cronshaw & Hayes (1991) Biochem. J. 276, 461-469]. A plasmid, termed pKK-musGST Yc, which permits the expression of the murine Yc subunit in Escherichia coli, has been constructed. The murine GST expressed in E. coli was purified and found to be catalytically active towards several GST substrates, including AFB1-8,9-epoxide. This enzyme was also found to possess electrophoretic and immunochemical properties closely similar to those of the GST Yc subunit from mouse liver. However, the GST synthesized in E. coli and the constitutive mouse liver Alpha-class GST exhibited small differences in their chromatographic behaviour during reverse-phase h.p.l.c. Automated Edman degradation revealed alanine to be the N-terminal amino acid in the GST Yc subunit expressed in E. coli, whereas the enzyme in mouse liver possesses a blocked N-terminus. Although sequencing showed that the purified Yc subunit from E. coli lacked the initiator methionine, the amino acid sequence obtained over the first eleven N-terminal residues agreed with that predicted from the cDNA clone, pmusGST Yc. Comparison of the deduced amino acid sequence of the mouse Yc polypeptide with the primary structures of the rat Alpha-class GST enzymes revealed that it is more closely related to the ethoxyquin-induced rat liver Yc2 subunit than to

  19. An asymmetric assembly of spirooxindole dihydropyranones through a direct enantioselective organocatalytic vinylogous aldol-cyclization cascade reaction of 3-alkylidene oxindoles with isatins.

    PubMed

    Han, Jeng-Liang; Chang, Chia-Hao

    2016-02-01

    A highly enantioselective organocatalytic vinylogous aldol-cyclization cascade reaction of 3-alkylidene oxindoles to isatins has been achieved by using bifunctional organocatalysts. The unexpected intramolecular lactonization which follows the initial aldol reaction, leading to the cleavage of the oxindole ring and generation of enantioenriched spirooxindole dihydropyranones in good to excellent yields with high enantioselectivities. PMID:26728396

  20. Rapid, high performance method for the determination of vitamin K(1), menaquinone-4 and vitamin K(1) 2,3-epoxide in human serum and plasma using liquid chromatography-hybrid quadrupole linear ion trap mass spectrometry.

    PubMed

    Gentili, Alessandra; Cafolla, Arturo; Gasperi, Tecla; Bellante, Simona; Caretti, Fulvia; Curini, Roberta; Fernández, Virginia Pérez

    2014-04-18

    Unlike the other fat-soluble vitamins, vitamin K circulates in the human bloodstream at very low levels because of a low intake in the diet. Mammals have developed an efficient recycling system, known as vitamin K-epoxide cycle, which involve quinone, hydroquinone and epoxide forms of the vitamin. Phylloquinone (K(1)) is the main homologue, while menaquinone-4 (MK-4) is both a member of the vitamin K(2) family and metabolite of K(1) in extra-hepatic tissues. Notwithstanding the recent advances, many aspects of the complex vitamin K physiology still remain to be investigated. Therefore, there is a critical need to develop more reliable analytical methods for determining the vitamin K and its metabolites in biological fluids and tissues. Nevertheless, relatively low concentrations, unavailability of some authentic standards and occurrence of interfering lipids make this a challenging task. The method proposed in the present paper can directly and accurately estimate K(1), K(1) 2,3-epoxide (K(1)O), and MK-4 in human serum and plasma at concentrations in the ng/L-μg/L range, using labelled internal standards and a quadrupole linear ion trap instrument operated in multiple reaction monitoring (MRM) mode. High sensitivity was achieved by removing signal "endogenous suppressors" and making the composition of the non-aqueous mobile phase suitable to support the positive atmospheric pressure chemical ionization of the analytes. An excellent selectivity resulted from the combination of some factors: the MRM acquisition, the adoption of an identification point system, an extraction optimized to remove most of the lipids and a tandem-C18 column-system necessary to separate isobaric interferences from analytes. The method was validated according to the Food and Drug Administration (FDA) guidelines and its accuracy was assessed by analysing 9 samples from the Vitamin K External Quality Assessment Scheme (KEQAS). Its feasibility in evaluating vitamin K status in human serum was

  1. Rhodium-Catalyzed Enantioselective Arylation of Aliphatic Imines.

    PubMed

    Kato, Naoya; Shirai, Tomohiko; Yamamoto, Yasunori

    2016-06-01

    Chiral rhodium(I)-catalyzed highly enantioselective arylation of aliphatic N-sulfonyl aldimines with arylboronic acids has been developed. This transformation is achieved by the use of a rhodium/bis(phosphoramidite) catalyst to give enantiomerically enriched α-branched amines (up to 99 % ee). In addition, this system enables efficient synthesis of (+)-NPS R-568 and Cinacalcet which are calcimimetic agents. PMID:27119262

  2. Enantioselective hydrolyzation and photolyzation of dufulin in water

    PubMed Central

    2013-01-01

    Background Dufulin is a novel, highly effective antiviral agent that activatives systemic acquired resistance of plants. This compound is widely used in China to prevent and control viral diseases in tobacco, vegetable and rice. Dufulin can treat plants infected by the tobacco mosaic virus and the cucumber mosaic virus. However, the achiral analysis and residue determination of dufulin remain underdeveloped because of its high enantioselectivity rates and high control costs. The enantioselectivity of an antiviral compound is an important factor that should be considered when studying the effect of chiral pesticides on the environment. The enantioselective degradation of dufulin in water remains an important objective in pesticide science. Results The configuration of dufulin enantiomers was determined in this study based on its circular dichroism spectra. The S-(+)-dufulin and R-(−)-dufulin enantiomers were separated and identified using an amylose tris-(3,5-dimethylphenylcarbamate) chiral column by normal phase high-performance liquid chromatography. The degradation of the rac-dufulin racemate and its separate enantiomers complied with first-order reaction kinetics and demonstrated acceptable linearity. The enantioselective photolysis of rac-dufulin allowed for the faster degradation of R-(−)-dufulin, as compared with S-(+)-dufulin. However, S-(+)-dufulin was hydrolyzed faster than its antipode. Conclusion The photolysation and hydrolyzation of dufulin in water samples normally complied with the first-order kinetics and demonstrated acceptable linearity (R2>0.66). A preferential photolysation of the R-(−)-enantiomer was observed in water samples. Moreover, the S-(+)-enantiomer was hydrolyzed faster than its antipode. PMID:23680125

  3. Rhodium-Catalyzed Enantioselective Hydroamination of Alkynes with Indolines

    PubMed Central

    Chen, Qing-An; Chen, Zhiwei; Dong, Vy M.

    2016-01-01

    The hydroamination of internal alkynes via tandem rhodium-catalysis gives branched N-allylic indolines with high regio- and enantioselectivity. An acid-switch provides access to the linear isomer in preference to the branched isomer by an isomerization mechanism. Mechanistic studies suggest formation of an allene intermediate, which undergoes hydroamination to generate allylic amines instead of the enamine or imine products typically observed in alkyne hydroaminations. PMID:26107923

  4. Epoxidation of alkenes through oxygen activation over a bifunctional CuO/Al2O3 catalyst.

    PubMed

    Scotti, Nicola; Ravasio, Nicoletta; Zaccheria, Federica; Psaro, Rinaldo; Evangelisti, Claudio

    2013-03-01

    The epoxidation of alkenes was carried out over a CuO/Al(2)O(3) catalyst using cumene as an oxygen carrier, through a one-pot reaction, giving high conversion and selectivity with different substrates. Trans-β-methylstyrene gave the corresponding epoxide in 95% yield after 3 h. PMID:23358661

  5. Enantioselective tandem reaction over a site-isolated bifunctional catalyst.

    PubMed

    Xu, Jianyou; Cheng, Tanyu; Zhang, Kun; Wang, Ziyun; Liu, Guohua

    2016-05-21

    Construction of a site-isolated heterogeneous catalyst to realize the compatibility of bimetallic complexes for a feasible tandem reaction is a significant challenge in heterogeneous asymmetric catalysis. Herein, taking advantage of yolk-shell-structured mesoporous silica, we assemble an active site-isolated bifunctional catalyst through assembly of organopalladium-functionality into silicate channels as an outer shell and chiral organoruthenium-functionality onto silicate yolk as an inner core, realizing the one-pot enantioselective tandem reaction from Pd-catalyzed Sonogashira coupling to Ru-catalyzed asymmetric transfer hydrogenation. As presented in this study, this tandem Sonogashira coupling-asymmetric transfer hydrogenation of haloacetophenones and arylacetylenes affords various chiral conjugated alkynols with high yields and up to 99% enantioselectivity. Moreover, a catalyst can also be recovered easily and recycled repeatedly, making it an interesting feature in a practical organic transformation. PMID:27063335

  6. Enantioselective iron-catalysed O-H bond insertions

    NASA Astrophysics Data System (ADS)

    Zhu, Shou-Fei; Cai, Yan; Mao, Hong-Xiang; Xie, Jian-Hua; Zhou, Qi-Lin

    2010-07-01

    The ready availability, low price and environmentally benign character of iron mean that it is an ideal alternative to precious metals in catalysis. Recent growth in the number of iron-catalysed reactions reported reflects an increasing demand for sustainable chemistry. Only a limited number of chiral iron catalysts have been reported and these have, in general, proven less enantioselective than other transition-metal catalysts, thus limiting their appeal. Here, we report that iron complexes of spiro-bisoxazoline ligands are highly efficient catalysts for asymmetric O-H bond insertion reactions. These complexes catalyse insertions into the O-H bond of a wide variety of alcohols and even water, with exceptional enantioselectivities under mild reaction conditions. The selectivities surpass those obtained with other transition-metal catalysts. This study should inspire and encourage the use of iron instead of traditional precious metals in the development of greener catalysts for catalytic asymmetric synthesis.

  7. Enantioselective Phase-Transfer-Catalyzed Synthesis of Chiral N-Substituted 3,3-Dinitroazetidines by Aza-Michael Reaction.

    PubMed

    Lee, Hyo-Jun; Cho, Chang-Woo

    2015-11-20

    An efficient and highly enantioselective phase-transfer-catalyzed aza-Michael reaction of 3,3-dinitroazetidine, as N-centered nucleophile, to α,β-unsaturated ketones has been achieved using a quinidine-based phase-transfer catalyst (0.5-1 mol %), providing chiral N-substituted 3,3-dinitroazetidines in good yields (up to 99%) and excellent enantioselectivities (90-95% ee). This is the first example of the use of azetidines as N-centered nucleophiles in catalytic enantioselective aza-Michael reactions. PMID:26503134

  8. Catalytic, Enantioselective Sulfenylation of Ketone-Derived Enoxysilanes

    PubMed Central

    2015-01-01

    A catalytic, enantioselective, Lewis base-catalyzed α-sulfenylation of silyl enol ethers has been developed. To avoid acidic hydrolysis of the silyl enol ether substrates, a sulfenylating agent that did not require additional Brønsted acid activation, namely N-phenylthiosaccharin, was developed. Three classes of Lewis bases—tertiary amines, sulfides, and selenophosphoramides—were identified as active catalysts for the α-sulfenylation reaction. Among a wide variety of chiral Lewis bases in all three classes, only chiral selenophosphoramides afforded α-phenylthio ketones in generally high yield and with good enantioselectivity. The selectivity of the reaction does not depend on the size of the silyl group but is highly sensitive to the double bond geometry and the bulk of the substituents on the double bond. The most selective substrates are those containing a geminal bulky substituent on the enoxysilane. Computational analysis revealed that the enantioselectivity arises from an intriguing interplay among sterically guided approach, distortion energy, and orbital interactions. PMID:25192220

  9. Enantioselective synthesis of 1,2,4-triazolines by chiral iron(II)-complex catalyzed cyclization of α-isocyano esters and azodicarboxylates.

    PubMed

    Wang, Min; Liu, Xiaohua; He, Peng; Lin, Lili; Feng, Xiaoming

    2013-03-28

    Enantioselective cyclization of α-isocyano esters with azodicarboxylates catalyzed by Fe(II)-N,N'-dioxide complexes has been developed. Under mild conditions, a variety of 1,2,4-triazoline derivatives was obtained in high yields and enantioselectivities. PMID:23423581

  10. N-Heterocyclic Carbene-Catalyzed [3 + 4] Annulation of Enals and Alkenyl Thiazolones: Enantioselective Synthesis of Thiazole-Fused ε-Lactones.

    PubMed

    Liang, Zhi-Qin; Yi, Liang; Chen, Kun-Quan; Ye, Song

    2016-06-01

    The bifunctional N-heterocyclic carbene catalyzed [3 + 4] annulation of enals and 5-alkenyl thiazolones was developed, giving the corresponding thiazole-fused ε-lactones in high yields with excellent diastereoselectivties and enantioselectivities. The thiazole-fused ε-lactone could be isomerized to the spirocyclic thiazolone-cyclopentanone without erosion of enantioselectivity. PMID:27159734

  11. Enantioselective [3 + 2] annulation of α-substituted allenoates with β,γ-unsaturated N-sulfonylimines catalyzed by a bifunctional dipeptide phosphine

    PubMed Central

    Ni, Huanzhen; Yao, Weijun

    2016-01-01

    Summary The first enantioselective [3 + 2] annulation of α-substituted allenoates with β,γ-unsaturated N-sulfonylimines is described. In the presence of a dipeptide phosphine catalyst, a wide range of highly functionalized cyclopentenes bearing an all-carbon quaternary center were obtained in moderate to good yields and with good to excellent enantioselectivities. PMID:26977194

  12. Organocatalytic enantioselective decarboxylative reaction of malonic acid half thioesters with cyclic N-sulfonyl ketimines by using N-heteroarenesulfonyl cinchona alkaloid amides.

    PubMed

    Nakamura, Shuichi; Sano, Masahide; Toda, Ayaka; Nakane, Daisuke; Masuda, Hideki

    2015-03-01

    The organocatalytic enantioselective decarboxylative Mannich reaction of malonic acid half thioesters (MAHTs) with cyclic N-sulfonyl ketimines by using N-heteroarenesulfonyl cinchona alkaloid amides afforded products with high enantioselectivity. Both enantiomers of the products could be obtained by using pseudoenantiomeric chiral catalysts. The reaction proceeds through a nucleophilic addition of the MAHTs to the ketimines prior to decarboxylation. PMID:25614368

  13. 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. PMID:25643169

  14. 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. PMID:19194597

  15. Regio- and Stereoselective Monoepoxidation of Dienes using Methyltrioxorhenium: Synthesis of Allylic Epoxides

    PubMed Central

    2015-01-01

    Methyltrioxorhenium (MTO) complexed with pyridine was shown to be a highly effective catalyst for the regioselective monoepoxidation of conjugated di- and trienes using 30% H2O2 at or below room temperature. The resultant allylic epoxides, and the triols derived from them, are versatile synthetic intermediates as well as substructures present in many bioactive natural products. The site of epoxidation was dependent upon olefin substitution, olefin geometry (Z vs E), and the presence of electron-withdrawing substituents on adjacent carbons. For 1-acyl(silyl)oxypenta-2,4-dienes, epoxidation of the distal olefin was generally favored in contrast to the adjacent regioselectivity characteristic of Sharpless, peracid, and other directed epoxidations of hydroxylated dienes. PMID:25321319

  16. Purified form of cytochrome P-450 from rainbow trout with high activity toward conversion of aflatoxin B1 to aflatoxin B1-2,3-epoxide.

    PubMed

    Williams, D E; Buhler, D R

    1983-10-01

    Aflatoxin B1, the most potent hepatic chemical carcinogen known, is activated to the putative product aflatoxin B1-2,3-epoxide via a cytochrome P-450-dependent reaction. Mt. Shasta rainbow trout is the most sensitive species known to the hepatocarcinogenic effects of aflatoxin B1. We have previously isolated and purified a minor form of cytochrome P-450 from this strain of rainbow trout, with a lambda max in the carbon monoxide-reduced difference spectrum of 449.5 nm and a molecular weight of 54,000. In this study, we have compared in a reconstituted system this trout P-450 to trout cytochrome P-448 and rat cytochrome P-450 and P-448 for metabolism and activation of aflatoxin B1. Trout cytochrome P-450 had much higher activity towards aflatoxin B1 and a greater degree of regioselectivity in the formation of aflatoxin B1-2,3-dihydroxy-2,3-dihydrodiol and was much more efficient in producing aflatoxin B1 covalent adducts with DNA. The existence of such a form of cytochrome P-450 in Mt. Shasta rainbow trout may be responsible for the acute sensitivity of this strain to the carcinogenic effects of aflatoxin B1. PMID:6411332

  17. Enantioselective Total Synthesis of (+)-Psiguadial B.

    PubMed

    Chapman, Lauren M; Beck, Jordan C; Wu, Linglin; Reisman, Sarah E

    2016-08-10

    The first enantioselective total synthesis of the cytotoxic natural product (+)-psiguadial B is reported. Key features of the synthesis include (1) the enantioselective preparation of a key cyclobutane intermediate by a tandem Wolff rearrangement/asymmetric ketene addition, (2) a directed C(sp(3))-H alkenylation reaction to strategically forge the C1-C2 bond, and (3) a ring-closing metathesis to build the bridging bicyclo[4.3.1]decane terpene framework. PMID:27452034

  18. Enantioselective Steglich Rearrangement of Oxindole Derivatives by Easily Accessible Chiral N,N-4-(Dimethylamino)pyridine Derivatives.

    PubMed

    Mandai, Hiroki; Fujiwara, Takuma; Noda, Katsuaki; Fujii, Kazuki; Mitsudo, Koichi; Korenaga, Toshinobu; Suga, Seiji

    2015-09-18

    Chiral N,N-4-(dimethylamino)pyridine (DMAP) derivatives, which can be readily prepared by the Ugi multicomponent reaction in a one-pot manner, have been efficiently applied to the enantioselective Steglich rearrangement of oxindole derivatives to give the desired products bearing a quaternary carbon center in high yield (>98% yield) and with high enantioselectivity (up to 99:1 er). PMID:26356582

  19. Catalytic, enantioselective, vinylogous aldol reactions.

    PubMed

    Denmark, Scott E; Heemstra, John R; Beutner, Gregory L

    2005-07-25

    In 1935, R. C. Fuson formulated the principle of vinylogy to explain how the influence of a functional group may be felt at a distant point in the molecule when this position is connected by conjugated double-bond linkages to the group. In polar reactions, this concept allows the extension of the electrophilic or nucleophilic character of a functional group through the pi system of a carbon-carbon double bond. This vinylogous extension has been applied to the aldol reaction by employing "extended" dienol ethers derived from gamma-enolizable alpha,beta-unsaturated carbonyl compounds. Since 1994, several methods for the catalytic, enantioselective, vinylogous aldol reaction have appeared, with which varying degrees of regio- (site), enantio-, and diastereoselectivity can be attained. In this Review, the current scope and limitations of this transformation, as well as its application in natural product synthesis, are discussed. PMID:15940727

  20. Enantioselective Transesterification Catalysis by Nanosized Serine Protease Subtilisin Carlsberg Particles in Tetrahydrofuran

    PubMed Central

    Castillo, Betzaida; Delgado, Yamixa; Barletta, Gabriel; Griebenow, Kai

    2010-01-01

    Enzyme catalysis in organic solvents is a powerful tool for stereo-selective synthesis but the enantioselectivity is still hard to predict. To overcome this obstacle, we employed a nanoparticulate formulation of subtilisin Carlsberg (SC) and designed a series of 14 structurally related racemic alcohols. They were employed in the model transesterification reaction with vinyl butyrate and the enantioselectivities were determined. In general, short alcohol side chains led to low enantioselectivties, while larger and bulky side chains caused better discrimination of the enantiomers by the enzyme. With several bulky substrates high enantioselectivities with E>100 were obtained. Computational modeling highlighted that key to high enantioselectivity is the discrimination of the R and S substrates by the sole hydrophobic binding pocket based on their size and bulkiness. While bulky S enantiomer side chains could be accommodated within the binding pocket, bulky R enantiomer side chains could not. However, when also the S enantiomer side chain becomes too large and does not fit into the binding pocket anymore, enantioselectivity accordingly drops. PMID:20661313

  1. Direct Epoxidation of Propylene over Stabilized Cu+ Surface Sites on Ti Modified Cu2O

    SciTech Connect

    Yang, X.; Kattel, S.; Xiong, K.; Mudiyanselage, K.; Rykov, S.; Senanayake, S. D.; Rodriguez, J. A.; Liu, P.; Stacchiola, D. J.; Chen, J. G.

    2015-07-17

    Direct propylene epoxidation by O2 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 TiCuOx mixed oxide. The TiCuOx surface anchors the key surface intermediate, oxametallacycle, leading to higher selectivity for epoxidation of propylene.

  2. Highly enantioselective synthesis of γ-, δ-, and ε-chiral 1-alkanols via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA)-Cu- or Pd-catalyzed cross-coupling.

    PubMed

    Xu, Shiqing; Oda, Akimichi; Kamada, Hirofumi; Negishi, Ei-ichi

    2014-06-10

    Despite recent advances of asymmetric synthesis, the preparation of enantiomerically pure (≥99% ee) compounds remains a challenge in modern organic chemistry. We report here a strategy for a highly enantioselective (≥99% ee) and catalytic synthesis of various γ- and more-remotely chiral alcohols from terminal alkenes via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA reaction)-Cu- or Pd-catalyzed cross-coupling. ZACA-in situ oxidation of tert-butyldimethylsilyl (TBS)-protected ω-alkene-1-ols produced both (R)- and (S)-α,ω-dioxyfunctional intermediates (3) in 80-88% ee, which were readily purified to the ≥99% ee level by lipase-catalyzed acetylation through exploitation of their high selectivity factors. These α,ω-dioxyfunctional intermediates serve as versatile synthons for the construction of various chiral compounds. Their subsequent Cu-catalyzed cross-coupling with various alkyl (primary, secondary, tertiary, cyclic) Grignard reagents and Pd-catalyzed cross-coupling with aryl and alkenyl halides proceeded smoothly with essentially complete retention of stereochemical configuration to produce a wide variety of γ-, δ-, and ε-chiral 1-alkanols of ≥99% ee. The MαNP ester analysis has been applied to the determination of the enantiomeric purities of δ- and ε-chiral primary alkanols, which sheds light on the relatively undeveloped area of determination of enantiomeric purity and/or absolute configuration of remotely chiral primary alcohols. PMID:24912191

  3. Enantioselective construction of a 2,2'-bisindolylmethane scaffold via catalytic asymmetric reactions of 2-indolylmethanols with 3-alkylindoles.

    PubMed

    Gong, Yu-Xin; Wu, Qiong; Zhang, Hong-Hao; Zhu, Qiu-Ning; Shi, Feng

    2015-08-01

    A chiral phosphoric acid-catalyzed asymmetric reaction of 2-indolylmethanols with 3-alkylindoles has been established, which constructed a biologically important 2,2'-bisindolylmethane scaffold in high yields and good enantioselectivities (up to 98% yield, 94:6 er). This protocol not only provides an efficient method for constructing a 2,2'-bisindolylmethane framework in an enantioselective form, but also promotes the development of 2-indolylmethanol-involved catalytic asymmetric transformations. PMID:26111901

  4. Enantioselective degradation of chiral insecticide dinotefuran in greenhouse cucumber and soil.

    PubMed

    Chen, Xiu; Dong, Fengshou; Xu, Jun; Liu, Xingang; Wang, Yunhao; Zheng, Yongquan

    2015-02-01

    The enantioselective degradation behavior of the chiral insecticide dinotefuran in cucumber and soil was investigated under greenhouse conditions based on the method established with a normal-phase high-performance chromatography (HPLC) on a ChromegaChiral CCA column (250 × 4.6 mm, 5 µm, ES Industries). The linearity range, matrix effect, precision, and accuracy of the method were evaluated and the method was then successfully applied for the enantioselective analysis of dinotefuran in cucumber and soil. Significant enantioselectivity of degradation was observed in soil according to the results. The (+)-dinotefuran was more persistent in soil with half-life of 21.7 d, which is much longer than that of (-)-dinotefuran (16.5 d). In cucumber, the (-)-dinotefuran also tended to be preferentially degraded both in foliar and douche treatment. However, the statistical analysis indicated the enantioselectivity of degradation in cucumber was not significant. The research provides the first report concerning the enantioselective degradation of dinotefuran enantiomers and the results can be used for understanding the insect-controlling effect and food safety evaluation. PMID:25378099

  5. Characterization of Diastereo- and Enantioselectivity in Degradation of Synthetic Pyrethroids in Soils.

    PubMed

    Li, Shaotong; Li, Zhaoyang; Li, Qiaoling; Zhao, Jiahe; Li, Sen

    2016-01-01

    Permethrin (PM), cypermethrin (CP), and cyfluthrin (CF) are three important synthetic pyrethroids, which contain two, four, and four enantiomeric pairs (diastereomers) and thus have four, eight, and eight stereoisomers, respectively. In this study, the stereo- and enantioselective degradation of PM, CP, and CF in a Shijiazhuang alkaline yellow soil and a Wuhan acidic red soil were studied in detail by a combination of achiral and chiral high-performance liquid chromatography (HPLC). The results showed that PM, CP, and CF degraded faster in Shijiazhuang soil than in Wuhan soil, and the dissipation rate followed an order of PM > CF > CP in both soils. The three pyrethroids exhibited similar diastereomer selectivity, while CP and CF showed higher enantioselectivity than PM. Moreover, the trans-diastereomers degraded faster, and showed higher enantioselectivity than the corresponding cis-diastereomers. For PM, the enantiomer 1S-trans-PM degraded most rapidly in both soils. As for CP and CF, the highest enantioselectivity was observed for diastereomer trans-3, and the insecticidally active enantiomer 1R-trans-αS degraded fastest among the 8 CP or CF stereoisomers in both soils. In addition, the Wuhan acidic soil displayed higher diastereomer and enantiomer selectivity than the Shijiazhuang alkaline soil for the three pyrethroids. Further incubation of CF in an alkaline-treated Wuhan soil showed that the dissipation rate greatly increased and the diastereo- and enantioselectivity significantly decreased after the alkaline treatment process. PMID:26497288

  6. Catalytic Enantioselective Peroxidation of α, β-Unsaturated Aldehydes for the Asymmetric Synthesis of Biologically Important Chiral Endoperoxides

    PubMed Central

    Hu, Lin; Lu, Xiaojie; Deng, Li

    2015-01-01

    We have developed an unprecedented highly enantioselective catalytic peroxidation of enals. Critical to this development is the discovery that varying the structure of the hydroperoxides has a significant impact on the enantioselectivity of the organocatalytic asymmetric peroxidation. This novel transformation enabled the development of the enantioselective route toward the core structure shared by all members of the stolonoxides family of anticancer natural products, a connected trans-3,6-disubstituted-1,2-dioxane and trans-2,5-disubstituted-tetrahydrofuran ring system. Our route also features an unprecedented cyclization cascade of a chiral bis(epoxy)hydroperoxide. The new methodology and synthetic strategy established from the current studies should be applicable to the enantioselective synthesis of a broad range of chiral 1,2-dioxolanes and 1, 2-dioxanes, thereby facilitating the biological and medicinal chemistry studies of peroxy natural products. PMID:26101971

  7. Enantioselective synthesis of chiral heterocycles containing both chroman and pyrazolone derivatives catalysed by a chiral squaramide.

    PubMed

    Li, Jun-Hua; Du, Da-Ming

    2015-05-28

    An efficient chiral squaramide-catalysed enantioselective Michael addition of pyrazolin-5-ones to 3-nitro-2H-chromenes for the synthesis of chiral heterocyclic systems containing both chroman and pyrazolone derivatives has been developed. This reaction afforded the desired products in high to excellent yields (up to 98%) with high enantioselectivities (up to 96%) and excellent diastereoselectivities (up to 99 : 1) under very low catalyst loading (0.2 mol%). This catalytic asymmetric reaction provides an efficient route toward the synthesis of chiral heterocyclic systems containing both chroman and pyrazolone derivatives, which possess potential pharmaceutical activities. PMID:25882378

  8. Toluene Monooxygenase-Catalyzed Epoxidation of Alkenes

    PubMed Central

    McClay, Kevin; Fox, Brian G.; Steffan, Robert J.

    2000-01-01

    Several toluene monooxygenase-producing organisms were tested for their ability to oxidize linear alkenes and chloroalkenes three to eight carbons long. Each of the wild-type organisms degraded all of the alkenes that were tested. Epoxides were produced during the oxidation of butene, butadiene, and pentene but not hexene or octadiene. A strain of Escherichia coli expressing the cloned toluene-4-monooxygenase (T4MO) of Pseudomonas mendocina KR1 was able to oxidize butene, butadiene, pentene, and hexene but not octadiene, producing epoxides from all of the substrates that were oxidized. A T4MO-deficient variant of P. mendocina KR1 oxidized alkenes that were five to eight carbons long, but no epoxides were detected, suggesting the presence of multiple alkene-degrading enzymes in this organism. The alkene oxidation rates varied widely (ranging from 0.01 to 0.33 μmol of substrate/min/mg of cell protein) and were specific for each organism-substrate pair. The enantiomeric purity of the epoxide products also varied widely, ranging from 54 to >90% of a single epoxide enantiomer. In the absence of more preferred substrates, such as toluene or alkenes, the epoxides underwent further toluene monooxygenase-catalyzed transformations, forming products that were not identified. PMID:10788354

  9. Amino Acid-Derived Bifunctional Phosphines for Enantioselective Transformations.

    PubMed

    Wang, Tianli; Han, Xiaoyu; Zhong, Fangrui; Yao, Weijun; Lu, Yixin

    2016-07-19

    Even though seminal reports on phosphine catalysis appeared in the 1960s, in the last few decades of the past century trivalent phosphines were viewed primarily as useful ligands for transition-metal-mediated processes. The 1990s saw revived interest in using phosphines in organic catalysis, but the key advances in asymmetric phosphine catalysis have all come within the past decade. The uniqueness of phosphine catalysis can be attributed to the high nucleophilicity of the phosphorus atom. In typical phosphine-catalyzed reactions, nucleophilic attacks of the phosphorus atom on electron-deficient multiple bonds create different reactive ylide-type intermediates. When such structurally diverse zwitterionic species react with a variety of suitable substrates, new reaction patterns are often discovered and a diverse array of reactions can be developed. In recent years, substantial progress has been made in the field of asymmetric phosphine catalysis; many new reactions have been discovered, and numerous enantioselective processes have been reported. However, we felt that powerful and versatile phosphine catalysts that can work for a wide range of asymmetric reactions are still lacking. We therefore set our goal to develop a family of easily derived phosphine catalysts that are efficient in asymmetric induction for a broad range of phosphine-mediated transformations. This Account describes our efforts in the past few years on the development of amino acid-based bifunctional phosphines and their applications to enantioselective processes. Building upon our previous success in primary-amine-mediated enamine catalysis, we first established that bifunctional phosphines could be readily prepared from amino acids. In most of our studies, we chose threonine as the key backbone for catalyst development, and threonine-based monoamino acid or dipeptide bifunctional phosphines have displayed remarkable stereochemical control. We began our investigations by demonstrating the

  10. The Nature of the Reaction Intermediates in the FAD-Dependent Epoxidation Mechanism of Styrene Monooxygenase*

    PubMed Central

    Kantz, Auric; Gassner, George T.

    2010-01-01

    Styrene monooxygenase (SMO) is a two-component flavoenzyme composed of an NADH-specific flavin reductase (SMOB) and FAD-specific styrene epoxidase (NSMOA). NSMOA binds tightly to reduced FAD and catalyzes the stereospecific addition of one atom of molecular oxygen to the vinyl side chain of styrene in the enantioselective synthesis of S-styrene oxide. In this mechanism, molecular oxygen first reacts with NSMOA(FADred) to yield an FAD C(4a)- peroxide intermediate. This species is non-fluorescent and has an absorbance maximum of 382 nm. Styrene then reacts with the peroxide intermediate with a second order rate constant of 2.6 × 106 ± 0.1 × 106 M−1 s−1 to yield a fluorescent intermediate with an absorbance maximum of 368 nm. We compute an activation free energy of 8.7 kcal.mol∙−1 for the oxygenation step in good agreement with that expected for a peroxide-catalyzed epoxidation, and acid-quenched samples recovered at defined time points in the single-turnover reaction indicate that styrene oxide synthesis is coincident with the formation phase of the fluorescent intermediate. These findings support FAD C(4a)-peroxide as the oxygen atom donor and identity of the fluorescent intermediate as an FAD C(4a)-hydroxide product of the styrene epoxidation. Overall, four pH-dependent rate constants corresponding to peroxyflavin formation (pKa = 7.2), styrene epoxidation (pKa = 7.7), styrene oxide dissociation (pKa = 8.3), and hydroxyflavin dehydration (pKa 7.6) are needed to fit the single-turnover kinetics. PMID:21166448

  11. Evaluation of the enantioselective binding of imazalil to human serum albumin by capillary electrophoresis.

    PubMed

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

    2015-11-01

    In this work, a methodology for the evaluation of enantioselective binding of imazalil (IMA) enantiomers to human serum albumin (HSA) that does not require the separation of free and bound to HSA fractions is developed. This methodology comprises the incubation of IMA-HSA designed mixtures for 30 min directly in the capillary electrophoresis system and the subsequent direct injection and chiral separation of IMA employing highly sulfated β-cyclodextrin as chiral selector and the complete filling technique. Two mathematical approaches were used to estimate apparent affinity constants (K1), protein binding and enantioselectivity (ES) for both enantiomers of IMA. Moderate enantioselective binding of IMA enantiomers to HSA (ES = 2.0) was shown by the 1:1 stoichiometry and log K1 values of 3.4 ± 0.4 and 3.1 ± 0.3 for the first and second eluted enantiomers, respectively. PMID:25857268

  12. 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

  13. Enantioselective Rhodium-Catalyzed Cycloisomerization of (E)-1,6-Enynes.

    PubMed

    Deng, Xu; Ni, Shao-Fei; Han, Zheng-Yu; Guan, Yu-Qing; Lv, Hui; Dang, Li; Zhang, Xu-Mu

    2016-05-17

    An enantioselective rhodium(I)-catalyzed cycloisomerization reaction of challenging (E)-1,6-enynes is reported. This novel process enables (E)-1,6-enynes with a wide range of functionalities, including nitrogen-, oxygen-, and carbon-tethered (E)-1,6-enynes, to undergo cycloisomerization with excellent enantioselectivity, in a high-yielding and operationally simple manner. Moreover, this Rh(I) -diphosphane catalytic system also exhibited superior reactivity and enantioselectivity for (Z)-1,6-enynes. A rationale for the striking reactivity difference between (E)- and (Z)-1,6-enynes using Rh(I) -BINAP and Rh(I) -TangPhos is outlined using DFT studies to provide the necessary insight for the design of new catalyst systems and the application to synthesis. PMID:27061132

  14. Mirror symmetry breaking with limited enantioselective autocatalysis and temperature gradients: a stability survey.

    PubMed

    Blanco, Celia; Ribó, Josep M; Crusats, Joaquim; El-Hachemi, Zoubir; Moyano, Albert; Hochberg, David

    2013-02-01

    We analyze limited enantioselective (LES) autocatalysis in a temperature gradient and with internal flow/recycling of hot and cold material. Microreversibility forbids broken mirror symmetry for LES in the presence of a temperature gradient alone. This symmetry can be broken however when the auto-catalysis and limited enantioselective catalysis are each localized within the regions of low and high temperature, respectively. This scheme has been recently proposed as a plausible model for spontaneous emergence of chirality in abyssal hydrothermal vents. Regions in chemical parameter space are mapped out in which the racemic state is unstable and bifurcates to chiral solutions. PMID:23238372

  15. Diastereodivergent and Enantioselective [4+2] Annulations of γ-Butenolides with Cyclic 1-Azadienes.

    PubMed

    Li, Chao; Jiang, Kun; Chen, Ying-Chun

    2015-01-01

    An asymmetric annulation reaction of γ-butenolides and cyclic 1-azadienes containing a 1,2-benzoisothiazole-1,1-dioxide motif has been studied, proceeding in a tandem Michael addition-aza-Michael addition sequence. Endo-type cycloadducts bearing fused tetracyclic skeletons were isolated in fair yields and with high enantioselectivity (up to >99% ee) under the catalysis of modified cinchona alkaloid (DHQD)2PHAL. Besides, exo-type diastereomers could be produced using β-isocupreidine (β-ICD) as the catalyst, though with moderate enantioselectivity. PMID:26225947

  16. Enantioselective CuH-catalyzed anti-Markovnikov hydroamination of 1,1-disubstituted alkenes.

    PubMed

    Zhu, Shaolin; Buchwald, Stephen L

    2014-11-12

    Enantioselective synthesis of β-chiral amines has been achieved via copper-catalyzed hydroamination of 1,1-disubstituted alkenes with hydroxylamine esters in the presence of a hydrosilane. This mild process affords a range of structurally diverse β-chiral amines, including β-deuterated amines, in excellent yields with high enantioselectivities. Furthermore, catalyst loading as low as 0.4 mol% could be employed to deliver product in undiminished yield and selectivity, demonstrating the practicality of this method for large-scale synthesis. PMID:25339089

  17. Enantioselective conjugate addition of alkylboranes catalyzed by a copper-N-heterocyclic carbene complex.

    PubMed

    Yoshida, Mika; Ohmiya, Hirohisa; Sawamura, Masaya

    2012-07-25

    The first catalytic enantioselective conjugate addition of alkylboron compounds has been achieved. Reactions between alkylboranes and imidazol-2-yl α,β-unsaturated ketones proceeded with high enantioselectivity under the influence of a Cu(I) catalyst system, prepared in situ from CuCl, a new chiral imidazolium salt as a precursor for the N-heterocyclic carbene ligand, and PhOK. Alkylboranes are widely obtained via alkene hydroboration. A variety of functional groups are tolerated in alkylboranes and α,β-unsaturated ketones. PMID:22746339

  18. Catalytic enantioselective aziridoarylation of aryl cinnamyl ethers toward synthesis of trans-3-amino-4-arylchromans.

    PubMed

    Hajra, Saumen; Sinha, Debarshi

    2011-09-16

    Catalytic enantioselective one-pot aziridoarylation reaction of aryl cinnamyl ethers has been demonstrated in detail. Combination of suitable copper catalyst and chiral bis-oxazoline ligand was found to be very efficient for asymmetric aziridination followed by intramolecular arylation (Friedel-Crafts) reaction to provide a general and direct method for the synthesis of trans-3-amino-4-arylchromans with high regio-, diastereo- (dr > 99:1), and enantioselectivity (up to 95% ee) with moderate yield. trans-3-Amino-4-arylchroman is an advanced intermediate for the synthesis of chromenoisoquinoline compounds such as doxanthrine, a potent and selective full agonist for the dopamine-D(1) receptor. PMID:21797274

  19. Scalable, enantioselective taxane total synthesis

    PubMed Central

    Mendoza, Abraham; Ishihara, Yoshihiro; Baran, Phil S.

    2011-01-01

    Taxanes are a large family of terpenes comprising over 350 members, the most famous of which is Taxol (paclitaxel) — a billion-dollar anticancer drug. Here, we describe the first practical and scalable synthetic entry to these natural products via a concise preparation of (+)-taxa-4(5),11(12)-dien-2-one, which possesses a suitable functional handle to access more oxidised members of its family. This route enabled a gram-scale preparation of the ”parent” taxane, taxadiene, representing the largest quantity of this naturally occurring terpene ever isolated or prepared in pure form. The taxane family’s characteristic 6-8-6 tricyclic system containing a bridgehead alkene is forged via a vicinal difunctionalisation/Diels–Alder strategy. Asymmetry is introduced by means of an enantioselective conjugate addition that forms an all-carbon quaternary centre, from which all other stereocentres are fixed via substrate control. This study lays a critical foundation for a planned access to minimally oxidised taxane analogs and a scalable laboratory preparation of Taxol itself. PMID:22169867

  20. Rhodium-Catalyzed Atroposelective [2 + 2 + 2] Cycloaddition of Ortho-Substituted Phenyl Diynes with Nitriles: Effect of Ortho Substituents on Regio- and Enantioselectivity.

    PubMed

    Kashima, Kenichi; Teraoka, Kota; Uekusa, Hidehiro; Shibata, Yu; Tanaka, Ken

    2016-05-01

    Axially chiral 3-(2-halophenyl)pyridines were successfully synthesized in high yields with excellent enantioselectivity by the cationic rhodium(I)/(S)-H8-BINAP complex-catalyzed atroposelective [2 + 2 + 2] cycloaddition of (o-halophenyl)diynes with nitriles. Interestingly, regio- and enantioselectivity highly depend on ortho substituents on the phenyl group of diynes. When the ortho substituents were methoxy and methoxycarbonyl groups, axially chiral 3-arylpyridines were obtained as a major product, while enantioselectivity was lowered significantly. On the other hand, when the ortho substituents were alkyl groups, regioselectivity was switched to give achiral 6-arylpyridines in high yields. PMID:27074498

  1. Regioselective Isomerization of 2,3-Disubstituted Epoxides to Ketones: An Alternative to the Wacker Oxidation of Internal Alkenes.

    PubMed

    Lamb, Jessica R; Mulzer, Michael; LaPointe, Anne M; Coates, Geoffrey W

    2015-12-01

    We report an alternative pathway to the Wacker oxidation of internal olefins involving epoxidation of trans-alkenes followed by a mild and highly regioselective isomerization to give the major ketone isomers in 66-98% yield. Preliminary kinetics and isotope labeling studies suggest epoxide ring opening as the turnover limiting step in our proposed mechanism. A similar catalytic system was applied to the kinetic resolution of select trans-epoxides to give synthetically useful selectivity factors of 17-23 for benzyl-substituted substrates. PMID:26522052

  2. Enantioselective Total Synthesis of Secalonic Acid E.

    PubMed

    Ganapathy, Dhandapani; Reiner, Johannes R; Löffler, Lorenz E; Ma, Ling; Gnanaprakasam, Boopathy; Niepötter, Benedikt; Koehne, Ingo; Tietze, Lutz F

    2015-11-16

    The first enantioselective synthesis of a secalonic acid containing a dimeric tetrahydroxanthenone skeleton is described, using a Wacker-type cyclization of a methoxyphenolic compound to form a chiral chroman with a quaternary carbon stereogenic center with >99% ee. Further steps are a Sharpless dihydroxylation and a Dieckmann condensation to give a tetrahydroxanthenone. A late-stage one-pot palladium-catalyzed Suzuki-dimerization reaction leads to the 2,2'-biphenol linkage to complete the enantioselective total synthesis of secalonic acid E in 18 steps with 8% overall yield. PMID:26447631

  3. 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

  4. Enantioselective Total Synthesis of Tricyclic Myrmicarin Alkaloids

    PubMed Central

    Movassaghi, Mohammad; Ondrus, Alison E.

    2010-01-01

    An enantioselective gram-scale synthesis of a key dihydroindolizine intermediate for the preparation of myrmicarin alkaloids is described. Key transformations in this convergent approach include a stereospecific palladium–catalyzed N-vinylation of a pyrrole with a vinyl triflate, a copper–catalyzed enantioselective conjugate reduction of a β-pyrrolyl enoate, and a regioselective Friedel-Crafts reaction. The synthesis of optically active and isomerically pure samples of (4aR)-myrmicarins 215A, 215B, and 217 in addition to their respective C4a-epimers is presented. PMID:16178549

  5. Enantioselective Hydrolysis of Amino Acid Esters Promoted by Bis(β-cyclodextrin) Copper Complexes

    PubMed Central

    Xue, Shan-Shan; Zhao, Meng; Ke, Zhuo-Feng; Cheng, Bei-Chen; Su, Hua; Cao, Qian; Cao, Zhen-Kun; Wang, Jun; Ji, Liang-Nian; Mao, Zong-Wan

    2016-01-01

    It is challenging to create artificial catalysts that approach enzymes with regard to catalytic efficiency and selectivity. The enantioselective catalysis ranks the privileged characteristic of enzymatic transformations. Here, we report two pyridine-linked bis(β-cyclodextrin) (bisCD) copper(II) complexes that enantioselectively hydrolyse chiral esters. Hydrolytic kinetic resolution of three pairs of amino acid ester enantiomers (S1–S3) at neutral pH indicated that the “back-to-back” bisCD complex CuL1 favoured higher catalytic efficiency and more pronounced enantioselectivity than the “face-to-face” complex CuL2. The best enantioselectivity was observed for N-Boc-phenylalanine 4-nitrophenyl ester (S2) enantiomers promoted by CuL1, which exhibited an enantiomer selectivity of 15.7. We observed preferential hydrolysis of L-S2 by CuL1, even in racemic S2, through chiral high-performance liquid chromatography (HPLC). We demonstrated that the enantioselective hydrolysis was related to the cooperative roles of the intramolecular flanking chiral CD cavities with the coordinated copper ion, according to the results of electrospray ionization mass spectrometry (ESI-MS), inhibition experiments, rotating-frame nuclear Overhauser effect spectroscopy (ROESY), and theoretical calculations. Although the catalytic parameters lag behind the level of enzymatic transformation, this study confirms the cooperative effect of the first and second coordination spheres of artificial catalysts in enantioselectivity and provides hints that may guide future explorations of enzyme mimics. PMID:26916830

  6. Kinetic Resolution in Asymmetric Epoxidation using Iminium Salt Catalysis

    PubMed Central

    2013-01-01

    The first reported examples of kinetic resolution in epoxidation reactions using iminium salt catalysis are described, providing up to 99% ee in the epoxidation of racemic cis-chromenes. PMID:23862687

  7. 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

  8. Structurally Defined Molecular Hypervalent Iodine Catalysts for Intermolecular Enantioselective Reactions

    PubMed Central

    Haubenreisser, Stefan; Wöste, Thorsten H.; Martínez, Claudio; Ishihara, Kazuaki

    2015-01-01

    Abstract Molecular structures of the most prominent chiral non‐racemic hypervalent iodine(III) reagents to date have been elucidated for the first time. The formation of a chirally induced supramolecular scaffold based on a selective hydrogen‐bonding arrangement provides an explanation for the consistently high asymmetric induction with these reagents. As an exploratory example, their scope as chiral catalysts was extended to the enantioselective dioxygenation of alkenes. A series of terminal styrenes are converted into the corresponding vicinal diacetoxylation products under mild conditions and provide the proof of principle for a truly intermolecular asymmetric alkene oxidation under iodine(I/III) catalysis. PMID:26596513

  9. 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. PMID:24798697

  10. Enantioselective Hydrosilylation of Imines Catalyzed by Chiral Zinc Acetate Complexes.

    PubMed

    Bezłada, Agata; Szewczyk, Marcin; Mlynarski, Jacek

    2016-01-01

    A series of zinc acetate complexes with optically pure diphenylethanediamine (DPEDA)-derived ligands have been employed as enantioselective catalyst for the hydrosilylation of various imines. High control of stereoselectivity (up to 97% ee) and excellent yields (up to 96%) were gained for a broad range of N-phosphinoylimines by using (R,R)-N,N'-dibenzyl-1,2-diphenylethane-1,2-diamine. This is the first successful application of an air-stable and environmentally friendly chiral Zn(OAc)2 complex instead of the previously used harmful diethylzinc in the asymmetric reduction of the C═N double bond. PMID:26667387

  11. Zirconium phenylphosphonate-anchored methyltrioxorhenium as novel heterogeneous catalyst for epoxidation of cyclohexene.

    PubMed

    He, Sha; Liu, Xin; Zhao, Hongyue; Zhu, Yue; Zhang, Fazhi

    2015-01-01

    Epoxidation of olefins to epoxides is widely recognized as an important unit process in the manufacture of fine chemicals and intermediates. Developing an environmentally benign heterogeneous catalytic system for olefin epoxidation with high activity and selectivity is still a challenge in this research field. Herein, we report our attempts to synthesize novel zirconium phenylphosphonate-anchored methyltrioxorhenium (MTO/ZrPP) heterogeneous catalysts by a conventional impregnation method and evaluate their catalytic performance for epoxidation of cyclohexene using urea-hydrogen peroxide adduct (UHP) as oxidant without the addition of base ligands. The MTO/ZrPP catalyst samples are characterized by powder X-ray diffraction (XRD), Fourier transform infrared (FT-IR), inductively coupled plasma emission spectrometry (ICP-ES), high resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), and solid-state (1)H magic-angle spinning nuclear magnetic resonance ((1)H MAS NMR) techniques. Meanwhile, the density functional theory (DFT) calculation is carried out to further understand the structure feature and interactions of the MTO/ZrPP catalyst. It is revealed that MTO is anchored on support surface by the favored hydrogen-bonding interaction between two oxo ligands of MTO and two H atoms from the adjacent phenyls of ZrPP. MTO/ZrPP catalyst displays excellent catalytic activity for cyclohexene epoxidation. Moreover, only cyclohexene oxide production can be obtained under the employed reaction conditions. PMID:25313467

  12. Organocatalytic enantioselective γ-aminoalkylation of unsaturated ester: access to pipecolic acid derivatives.

    PubMed

    Xu, Jianfeng; Jin, Zhichao; Chi, Yonggui Robin

    2013-10-01

    The direct γ-carbon functionalization of α,β-unsaturated esters via N-Heterocyclic Carbene (NHC) catalysis is disclosed. This catalytically generated nucleophilic γ-carbon undergoes highly enantioselective additions to hydrazones. The resulting δ-lactam products can be readily transformed to optically enriched pipecolic acid derivatives. PMID:24067098

  13. Biphenol-based phosphoramidite ligands for the enantioselective copper-catalyzed conjugate addition of diethylzinc.

    PubMed

    Alexakis, Alexandre; Polet, Damien; Rosset, Stéphane; March, Sébastien

    2004-08-20

    Phosphoramidite ligands, based on ortho-substituted biphenols and a chiral amine, induce high enantioselectivities (ee's up to 99%) in the copper-catalyzed conjugate addition of dialkylzinc reagents to a variety of Michael acceptors. Particularly, the best reported ee's were obtained for acyclic nitroolefins. PMID:15307737

  14. Enantioselective 1,1-Arylborylation of Alkenes: Merging Chiral Anion Phase Transfer with Pd Catalysis

    PubMed Central

    Miró, Javier; Toste, F. Dean

    2015-01-01

    A palladium-catalyzed three-component coupling of α-olefins, aryldiazonium salts, and bis-(pinacolato)diboron affords direct access to chiral benzylic boronic esters. This process is rendered highly enantioselective using an unprecedented example of cooperative chiral anion phase transfer and transition-metal catalysis. PMID:25723255

  15. 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). PMID:25564304

  16. Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

    PubMed Central

    Liu, Jixin; Dasgupta, Srimoyee

    2015-01-01

    Summary The development of enantioselective, copper-catalyzed alkynylations of cyclic iminium and oxocarbenium ions is reviewed. The use of chiral copper-based catalysts has enabled high yields and enantioselectivites in the formation of nitrogen- and oxygen-containing heterocycles with α-stereogenic centers. This review highlights both the accomplishments and the future work needed in this important area. PMID:26877791

  17. Enantioselective Transaminations by Dendrimeric Enzyme Mimics

    PubMed Central

    Wei, Sujun; Kenesky, Craig

    2007-01-01

    PAMAM dendrimers have been constructed with a pyridoxamine core, and chiral capping amino groups. Transamination to form phenylalanine and alanine from their related ketoacids produced enantioselectivities induced by the formally remote chiral caps, supporting computer models that indicate folding of the dendrimer chains back into the core region. PMID:18596840

  18. Enantioselective Synthesis of L-CCG-I.

    PubMed

    Chavan, Subhash P; Sharma, Pallavi; Sivappa, Rasapalli; Bhadbhade, Mohan M; Gonnade, Rajesh G; Kalkote, Uttam R

    2003-08-22

    Introduction of natural menthol as the chiral auxiliary in a gamma-Br-alpha,beta-unsaturated ester leads to enantioselective generation of three chiral centers in a single step on reaction with a glycine anion equivalent to provide L-CCG-I in 94% ee. PMID:12919057

  19. Enantioselective Functionalization of Allylic C-H Bonds Following a Strategy of Functionalization and Diversification

    PubMed Central

    Sharma, Ankit; Hartwig, John F.

    2013-01-01

    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 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 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. PMID:24156776

  20. Increased Silver Activity for Direct Propylene Epoxidation via Subnanometer Size Effects

    SciTech Connect

    Lei, Y.; Mehmood, Faisal; Lee, Sang Soo; Greeley, Jeffrey P.; Lee, Byeongdu; Seifert, Soenke; Winans, R. E.; Elam, J. W.; Meyer, R. J.; Redfern, Paul C.; Teschner, D.; Schlogl, Robert; Pellin, M. J.; Curtiss, Larry A.; Vajda, S.

    2010-04-09

    Production of the industrial chemical propylene oxide is energy-intensive and environmentally unfriendly. Catalysts based on bulk silver surfaces with direct propylene epoxidation by molecular oxygen have not resolved these problems because of substantial formation of carbon dioxide. We found that unpromoted, size-selected Ag3 clusters and ~3.5-nanometer Ag nanoparticles on alumina supports can catalyze this reaction with only a negligible amount of carbon dioxide formation and with high activity at low temperatures. Density functional calculations show that, relative to extended silver surfaces, oxidized silver trimers are more active and selective for epoxidation because of the open-shell nature of their electronic structure. The results suggest that new architectures based on ultrasmall silver particles may provide highly efficient catalysts for propylene epoxidation.

  1. A Chiral N,N'-Dioxide-Zn(II) Complex Catalyzes the Enantioselective [2+2] Cycloaddition of Alkynones with Cyclic Enol Silyl Ethers.

    PubMed

    Kang, Tengfei; Ge, Shulin; Lin, Lili; Lu, Yan; Liu, Xiaohua; Feng, Xiaoming

    2016-04-25

    A highly efficient enantioselective [2+2] cycloaddition between alkynones and cyclic enol silyl ethers was developed by using a chiral N,N'-dioxide-zinc(II) complex as a catalyst. This method functions well for a variety of terminal alkynes as well as cyclic enol silyl ethers, with good to excellent enantioselectivity (up to 97 % ee). This is also the first successful example for the catalytic enantioselective [2+2] cycloaddition of internal alkynes with cyclic enol silyl ethers to give fully substituted cyclobutenes. Meanwhile, the desired cyclobutene product can easily be transformed into fused cyclobutane derivatives. PMID:27059528

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

    NASA Astrophysics Data System (ADS)

    Samidin, Salma; Salimon, Jumat

    2014-09-01

    Tmp trioleate was initially synthesized via esterification of trimetilolprapane and oleic acid (90%) using 1.5% of H2SO4 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 Tmp trioleate with peroxyformic acid generated in-situ from hydrogen peroxide 30% in H2O2 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.

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

    SciTech Connect

    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 Tmp 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.

  4. Early postnatal treatment with soluble epoxide hydrolase inhibitor or 15-deoxy-Δ(12,14)-prostagandin J2 prevents prenatal dexamethasone and postnatal high saturated fat diet induced programmed hypertension in adult rat offspring.

    PubMed

    Lu, Pei-Chen; Sheen, Jiunn-Ming; Yu, Hong-Ren; Lin, Yu-Ju; Chen, Chih-Cheng; Tiao, Mao-Meng; Tsai, Ching-Chou; Huang, Li-Tung; Tain, You-Lin

    2016-07-01

    Prenatal dexamethasone (DEX) exposure, postnatal high-fat (HF) intake, and arachidonic acid pathway are closely related to hypertension. We tested whether a soluble epoxide hydrolase (SEH) inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) or 15-deoxy-Δ(12,14)-prostagandin J2 (15dPGJ2) therapy can rescue programmed hypertension in the DEX+HF two-hit model. Four groups of Sprague Dawley rats were studied: control, DEX+HF, AUDA, and 15dPGJ2. Dexamethasone (0.1mg/kg body weight) was intraperitoneally administered to pregnant rats from gestational day 16-22. Male offspring received high-fat diet (D12331, Research Diets) from weaning to 4 months of age. In AUDA group, mother rats received 25mg/L in drinking water during lactation. In the 15dPGJ2 group, male offspring received 15dPGJ2 1.5mg/kg BW by subcutaneous injection once daily for 1 week after birth. We found postnatal HF diet aggravated prenatal DEX-induced programmed hypertension, which was similarly prevented by early treatment with AUDA or 15dPGJ2. The beneficial effects of AUDA and 15d-PGJ2 therapy include inhibition of SEH, increases of renal angiotensin converting enzyme-2 (ACE2) and angiotensin II type 2 receptor (AT2R) protein levels, and restoration of nitric oxide bioavailability. Better understanding of the impact of arachidonic acid pathway in the two-hit model will help prevent programmed hypertension in children exposed to corticosteroids and postnatal HF intake. PMID:27210044

  5. Synthesis of beta-lactones by the regioselective, cobalt and Lewis acid catalyzed carbonylation of simple and functionalized epoxides.

    PubMed

    Lee, J T; Thomas, P J; Alper, H

    2001-08-10

    The PPNCo(CO)(4) and BF(3) x Et(2)O catalyzed carbonylation of simple and functionalized epoxides in DME gives the corresponding beta-lactones regioselectively in good to high yields. The carbonylation occurred selectively at the unsubstituted C-O bond of the epoxide ring, and this reaction tolerates various functional groups such as alkenyl, halide, hydroxy, and alkyl ether. PMID:11485465

  6. Nazarov cyclization of divinyl and arylvinyl epoxides: application in the synthesis of resveratrol-based natural products.

    PubMed

    Sudhakar, Gangarajula; Satish, Kovela

    2015-04-20

    New variation in the Nazarov cyclization has been developed by preparing divinyl and arylvinyl epoxides as pentadienyl cation precursors for the first time. Highly substituted cyclopentadienes, hydrindienes, and indenes were synthesized to demonstrate the compatibility of this reaction with substrates bearing a variety of substitutions and having different types of epoxides. Application of this method in the synthesis of resveratrol-based natural products was also demonstrated. PMID:25760544

  7. Enantioselective acyl transfer catalysis by a combination of common catalytic motifs and electrostatic interactions

    PubMed Central

    Mandai, Hiroki; Fujii, Kazuki; Yasuhara, Hiroshi; Abe, Kenko; Mitsudo, Koichi; Korenaga, Toshinobu; Suga, Seiji

    2016-01-01

    Catalysts that can promote acyl transfer processes are important to enantioselective synthesis and their development has received significant attention in recent years. Despite noteworthy advances, discovery of small-molecule catalysts that are robust, efficient, recyclable and promote reactions with high enantioselectivity can be easily and cost-effectively prepared in significant quantities (that is, >10 g) has remained elusive. Here, we demonstrate that by attaching a binaphthyl moiety, appropriately modified to establish H-bonding interactions within the key intermediates in the catalytic cycle, and a 4-aminopyridyl unit, exceptionally efficient organic molecules can be prepared that facilitate enantioselective acyl transfer reactions. As little as 0.5 mol% of a member of the new catalyst class is sufficient to generate acyl-substituted all-carbon quaternary stereogenic centres in quantitative yield and in up to 98:2 enantiomeric ratio (er) in 5 h. Kinetic resolution or desymmetrization of 1,2-diol can be performed with high efficiency and enantioselectivity as well. PMID:27079273

  8. Mechanistic basis for the enantioselectivity of the anaerobic hydroxylation of alkylaromatic compounds by ethylbenzene dehydrogenase.

    PubMed

    Szaleniec, Maciej; Dudzik, Agnieszka; Kozik, Bartłomiej; Borowski, Tomasz; Heider, Johann; Witko, Małgorzata

    2014-10-01

    The enantioselectivity of reactions catalyzed by ethylbenzene dehydrogenase, a molybdenum enzyme that catalyzes the oxygen-independent hydroxylation of many alkylaromatic and alkylheterocyclic compounds to secondary alcohols, was studied by chiral chromatography and theoretical modeling. Chromatographic analyses of 22 substrates revealed that this enzyme exhibits remarkably high reaction enantioselectivity toward (S)-secondary alcohols (18 substrates converted with >99% ee). Theoretical QM:MM modeling was used to elucidate the structure of the catalytically active form of the enzyme and to study the reaction mechanism and factors determining its high degree of enantioselectivity. This analysis showed that the enzyme imposes strong stereoselectivity on the reaction by discriminating the hydrogen atom abstracted from the substrate. Activation of the pro(S) hydrogen atom was calculated to be 500 times faster than of the pro(R) hydrogen atom. The actual hydroxylation step (i.e., hydroxyl group rebound reaction to a carbocation intermediate) does not appear to be enantioselective enough to explain the experimental data (the calculated rate ratios were in the range of only 2-50 for pro(S): pro(R)-oriented OH rebound). PMID:24950385

  9. Organic co-solvents affect activity, stability and enantioselectivity of haloalkane dehalogenases.

    PubMed

    Stepankova, Veronika; Damborsky, Jiri; Chaloupkova, Radka

    2013-06-01

    Haloalkane dehalogenases are microbial enzymes with a wide range of biotechnological applications, including biocatalysis. The use of organic co-solvents to solubilize their hydrophobic substrates is often necessary. In order to choose the most compatible co-solvent, the effects of 14 co-solvents on activity, stability and enantioselectivity of three model enzymes, DbjA, DhaA, and LinB, were evaluated. All co-solvents caused at high concentration loss of activity and conformational changes. The highest inactivation was induced by tetrahydrofuran, while more hydrophilic co-solvents, such as ethylene glycol and dimethyl sulfoxide, were better tolerated. The effects of co-solvents at low concentration were different for each enzyme-solvent pair. An increase in DbjA activity was induced by the majority of organic co-solvents tested, while activities of DhaA and LinB decreased at comparable concentrations of the same co-solvent. Moreover, a high increase of DbjA enantioselectivity was observed. Ethylene glycol and 1,4-dioxane were shown to have the most positive impact on the enantioselectivity. The favorable influence of these co-solvents on both activity and enantioselectivity makes DbjA suitable for biocatalytic applications. This study represents the first investigation of the effects of organic co-solvents on the biocatalytic performance of haloalkane dehalogenases and will pave the way for their broader use in industrial processes. PMID:23420811

  10. A cinchona alkaloid catalyzed enantioselective sulfa-Michael/aldol cascade reaction of isoindigos: construction of chiral bispirooxindole tetrahydrothiophenes with vicinal quaternary spirocenters.

    PubMed

    Gui, Yong-Yuan; Yang, Jian; Qi, Liang-Wen; Wang, Xiao; Tian, Fang; Li, Xiao-Nian; Peng, Lin; Wang, Li-Xin

    2015-06-14

    A cinchona alkaloid catalyzed diastereoselective and enantioselective sulfa-Michael/aldol cascade reaction between 1,4-dithiane-2,5-diol and isoindigos has been successfully developed to afford the highly congested bispirooxindole tetrahydrothiophenes with vicinal quaternary spirocenters in high yields (up to 91%), excellent diastereoselectivities (up to >20 : 1 dr), and good enantioselectivities (up to 98% ee). Some synthetic transformations of the reaction products were also studied. PMID:25974840