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Sample records for enantioselective mannich-type aza

  1. Direct catalytic enantioselective Mannich-type reaction of dichloroacetonitrile using bis(imidazoline)-Pd catalysts.

    Science.gov (United States)

    Kondo, Masaru; Sugimoto, Mami; Nakamura, Shuichi

    2016-11-15

    The catalytic enantioselective Mannich-type reaction of dichloroacetonitrile with imines has been developed. Good yields and enantioselectivity were observed for the reaction with various imines using chiral bis(imidazoline) catalysts. β-Aminonitriles or β-aminoamide were obtained from products without the loss of enantiopurity.

  2. Chiral Phosphoric Acid Catalyzed Diastereo- and Enantioselective Mannich-Type Reaction between Enamides and Thiazolones.

    Science.gov (United States)

    Kikuchi, Jun; Momiyama, Norie; Terada, Masahiro

    2016-06-03

    An enantioselective Mannich-type reaction between enamides, serving as aliphatic imine equivalents, and thiazolones or an azlactone, serving as α-amino acid derived pronucleophiles, was investigated using a chiral phosphoric acid catalyst. By using thiazolones, Mannich adducts with a tetrasubstituted chiral carbon center at the α-position and an aliphatic substituent at the β-position were efficiently obtained with high diastereo- and enantioselectivities.

  3. Enantioselective Direct Mannich-Type Reactions Catalyzed by Frustrated Lewis Acid/Brønsted Base Complexes.

    Science.gov (United States)

    Shang, Ming; Cao, Min; Wang, Qifan; Wasa, Masayuki

    2017-10-16

    An enantioselective direct Mannich-type reaction catalyzed by a sterically frustrated Lewis acid/Brønsted base complex is disclosed. Cooperative functioning of the chiral Lewis acid and achiral Brønsted base components gives rise to in situ enolate generation from monocarbonyl compounds. Subsequent reaction with hydrogen-bond-activated aldimines delivers β-aminocarbonyl compounds with high enantiomeric purity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Science.gov (United States)

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

    2018-04-03

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

  5. Cinchona Alkaloid Derivative-Catalyzed Enantioselective Synthesis via a Mannich-Type Reaction and Antifungal Activity of β-Amino Esters Bearing Benzoheterocycle Moieties

    Directory of Open Access Journals (Sweden)

    Han Xiao

    2014-04-01

    Full Text Available An efficient synthesis of highly functionalized chiral β-amino ester derivatives containing benzothiophene and benzothiazole moieties is developed by a Mannich-type reaction using a cinchona alkaloid-derived thiourea catalyst. The desired products were obtained in good yields and high enantioselectivities (~86% yield, >99% ee using to the optimized reaction conditions. The synthesized compounds were characterized by 1H-NMR, 13C-NMR, IR, and HREI-MS analyses. The bioassays identified that compound 5dr has excellent antifungal activity, with a 60.53% inhibition rate against F. oxysporum, higher than that of the commercial agricultural fungicide hymexazol, whose inhibition rate was 56.12%.

  6. Enantioselective catalytic fluorinative aza-semipinacol rearrangement.

    Science.gov (United States)

    Romanov-Michailidis, Fedor; Pupier, Marion; Besnard, Céline; Bürgi, Thomas; Alexakis, Alexandre

    2014-10-03

    An efficient and highly stereoselective fluorinative aza-semipinacol rearrangement is described. The catalytic reaction requires use of Selectfluor in combination with the chiral, enantiopure phosphate anion derived from acid L3. Under optimized conditions, cyclopropylamines A were transformed into β-fluoro cyclobutylimines B in good yields and high levels of diastereo- and enantiocontrol. Furthermore, the optically active cyclobutylimines were reduced diastereoselectively with L-Selectride in the corresponding fluorinated amines C, compounds of significant interest in the pharmacological industry.

  7. An enantioselective organocatalyzed aza-Morita-Baylis-Hillman reaction of isatin-derived ketimines with acrolein.

    Science.gov (United States)

    Yoshida, Yasushi; Sako, Makoto; Kishi, Kenta; Sasai, Hiroaki; Hatakeyama, Susumi; Takizawa, Shinobu

    2015-09-14

    A highly enantioselective aza-Morita-Baylis-Hillman (aza-MBH) reaction of isatin-derived ketimines with acrolein was established using β-isocupreidine (β-ICD) or α-isocupreine (α-ICPN) as a chiral acid-base organocatalyst. The present protocol readily furnished (S) or (R)-aza-MBH adducts with a chiral tetrasubstituted carbon stereogenic center in up to 98% ee.

  8. L-Threonine-derived novel bifunctional phosphine-sulfonamide catalyst-promoted enantioselective aza-morita-Baylis-Hillman reaction

    KAUST Repository

    Zhong, Fangrui

    2011-03-18

    A series of novel bifunctional phosphine-sulfonamide organic catalysts were designed and readily prepared from natural amino acids, and they were utilized to promote enantioselective aza-Morita-Baylis-Hillman (MBH) reactions. l-Threonine-derived phosphine-sulfonamide 9b was found to be the most efficient catalyst, affording the desired aza-MBH adducts in high yields and with excellent enantioselectivities. © 2011 American Chemical Society.

  9. Direct Asymmetric Vinylogous and Bisvinylogous Mannich-Type Reaction Catalyzed by a Copper(I) Complex.

    Science.gov (United States)

    Zhang, Hai-Jun; Shi, Chang-Yun; Zhong, Feng; Yin, Liang

    2017-02-15

    A direct catalytic asymmetric vinylogous Mannich-type reaction has been disclosed in good yield, excellent regio-, diastereo- and enantioselectivity. The key to control the regioselectivity is the combination of a bulky N-acylpyrazole and a bulky bisphosphine ligand. The catalytic system was extended to a bisvinylogous Mannich-type reaction by changing the ligand. The synthetic utility of the vinylogous products was demonstrated by several transformations.

  10. The origin of enantioselectivity in the l-threonine-derived phosphine-sulfonamide catalyzed aza-Morita-Baylis-Hillman reaction: Effects of the intramolecular hydrogen bonding

    KAUST Repository

    Lee, Richmond

    2013-01-01

    l-Threonine-derived phosphine-sulfonamide 4 was identified as the most efficient catalyst to promote enantioselective aza-Morita-Baylis-Hillman (MBH) reactions, affording the desired aza-MBH adducts with excellent enantioselectivities. Density functional theory (DFT) studies were carried out to elucidate the origin of the observed enantioselectivity. The importance of the intramolecular N-H⋯O hydrogen-bonding interaction between the sulfonamide and enolate groups was identified to be crucial in inducing a high degree of stereochemical control in both the enolate addition to imine and the subsequent proton transfer step, affording aza-MBH reactions with excellent enantioselectivity. © 2013 The Royal Society of Chemistry.

  11. Chiral ammonium betaine-catalyzed asymmetric Mannich-type reaction of oxindoles.

    Science.gov (United States)

    Torii, Masahiro; Kato, Kohsuke; Uraguchi, Daisuke; Ooi, Takashi

    2016-01-01

    A highly diastereo- and enantioselective Mannich-type reaction of 3-aryloxindoles with N -Boc aldimines was achieved under the catalysis of axially chiral ammonium betaines. This catalytic method provides a new tool for the construction of consecutive quaternary and tertiary stereogenic carbon centers on biologically intriguing molecular frameworks with high fidelity.

  12. Chiral ammonium betaine-catalyzed asymmetric Mannich-type reaction of oxindoles

    Directory of Open Access Journals (Sweden)

    Masahiro Torii

    2016-09-01

    Full Text Available A highly diastereo- and enantioselective Mannich-type reaction of 3-aryloxindoles with N-Boc aldimines was achieved under the catalysis of axially chiral ammonium betaines. This catalytic method provides a new tool for the construction of consecutive quaternary and tertiary stereogenic carbon centers on biologically intriguing molecular frameworks with high fidelity.

  13. Direct Catalytic Asymmetric Mannich-Type Reaction of Alkylamides.

    Science.gov (United States)

    Arteaga, Fernando Arteaga; Liu, Zijian; Brewitz, Lennart; Chen, Jianyang; Sun, Bo; Kumagai, Naoya; Shibasaki, Masakatsu

    2016-05-20

    Direct enolate formation coupled with subsequent enantioselective C-C bond formation remains a topic of intense interest in asymmetric catalysis. This methodology is achieved even with low acidic amides without an electron-withdrawing group at the α-position in the context of a Mannich-type reaction. Acetate-, propionate-, and butyrate-type 7-azaindoline amides served as enolate precursors to afford the desired Mannich adducts with high stereoselectivity, and ligand-enabled diastereo-divergency provided access to both anti/syn diastereomers. The facile transformation of the amide moiety ensures the synthetic utility of the Mannich adducts.

  14. Organocatalytic Asymmetric Mannich/Aza-Michael Cascade Reaction of δ-Formyl-α,β-unsaturated Ketones with Cyclic N-Sulfimines: Enantioselective Synthesis of Benzosulfamidate-Fused Pyrrolidines.

    Science.gov (United States)

    Kim, Hanna; Kim, Yerin; Kim, Sung-Gon

    2017-08-04

    A catalytic highly enantioselective Mannich/aza-Michael cascade reaction of δ-formyl-α,β-unsaturated ketones with cyclic N-sulfimines, promoted by diphenylprolinol TMS ether as an organocatalyst, has been developed for the synthesis of chiral benzosulfamidate-fused pyrrolidines, which generated in good yields and with high diastero- and enantioselectivities. Further chemical transformations have been performed with chiral benzosulfamidate-fused pyrrolidines.

  15. Asymmetric NHC-catalyzed aza-Diels-Alder reactions: Highly enantioselective route to α-amino acid derivatives and DFT calculations

    KAUST Repository

    Yang, Limin

    2014-08-01

    A facile N-heterocyclic carbene catalytic enantioselective aza-Diels-Alder reaction of oxodiazenes with α-chloroaldehydes as dienophile precursors is reported, with excellent enantioselectivity (ee > 99%) and excellent yield (up to 93%). DFT study showed that cis-TSa, formed from a top face approach of oxodiazene to cis-IIa, is the most favorable transition state and is consistent with the experimental observations. © 2014 American Chemical Society.

  16. Organocatalytic asymmetric mannich-type reactions: an easy approach to optically active amine derivatives

    OpenAIRE

    Fini, Francesco

    2008-01-01

    The topics I came across during the period I spent as a Ph.D. student are mainly two. The first concerns new organocatalytic protocols for Mannich-type reactions mediated by Cinchona alkaloids derivatives (Scheme I, left); the second topic, instead, regards the study of a new approach towards the enantioselective total synthesis of Aspirochlorine, a potent gliotoxin that recent studies indicate as a highly selective and active agent against fungi (Scheme I, right). At the begin...

  17. Enantioselective aza-Morita-Baylis-Hillman reaction between acrylates and N-Boc isatin ketimines: asymmetric construction of chiral 3-substituted-3-aminooxindoles.

    Science.gov (United States)

    Zhao, Xuan; Li, Tian-Ze; Qian, Jing-Ying; Sha, Feng; Wu, Xin-Yan

    2014-10-28

    The first enantioselective aza-Morita–Baylis–Hillman reaction of acrylates with ketimines derived from isatins has been developed. With 2 mol% of chiral bifunctional phosphine-squaramide 4e, optically active 3-substituted-3-amino-2-oxindoles were obtained in excellent yields with up to 91% ee.

  18. Chemoselective Boron-Catalyzed Nucleophilic Activation of Carboxylic Acids for Mannich-Type Reactions.

    Science.gov (United States)

    Morita, Yuya; Yamamoto, Tomohiro; Nagai, Hideoki; Shimizu, Yohei; Kanai, Motomu

    2015-06-10

    The carboxyl group (COOH) is an omnipresent functional group in organic molecules, and its direct catalytic activation represents an attractive synthetic method. Herein, we describe the first example of a direct catalytic nucleophilic activation of carboxylic acids with BH3·SMe2, after which the acids are able to act as carbon nucleophiles, i.e. enolates, in Mannich-type reactions. This reaction proceeds with a mild organic base (DBU) and exhibits high levels of functional group tolerance. The boron catalyst is highly chemoselective toward the COOH group, even in the presence of other carbonyl moieties, such as amides, esters, or ketones. Furthermore, this catalytic method can be extended to highly enantioselective Mannich-type reactions by using a (R)-3,3'-I2-BINOL-substituted boron catalyst.

  19. Enantioselective, Organocatalytic Morita-Baylis-Hillman and Aza-Morita-Baylis-Hillman Reactions: Stereochemical Issues

    Directory of Open Access Journals (Sweden)

    José M. Saá

    2010-02-01

    Full Text Available Conscious of the importance that stereochemical issues may have on the design of efficient organocatalyts for both Morita-Baylis-Hillman and aza-Morita-Baylis-Hillman reaction we have analyzed them in this minireview. The so-called standard reactions involve “naked” enolates which therefore should lead to the syn adducts as the major products, irrespective of the E, Z stereochemistry of the enolate. Accordingly, provided the second step is rate determining step, the design of successful bifunctional or polyfunctional catalysts has to consider the geometrical requirements imposed by the transition structures of the second step of these reactions. On the other hand, MBH and aza-MBH reactions co-catalyzed by (S-proline and a secondary or tertiary amine (co-catalyst involve the aldol-type condensation of either a 3-amino-substituted enamine, dienamine, or both, depending on the cases. A Zimmerman-Traxler mechanism defines the stereochemical issues regarding these co-catalyzed condensations which parallel those of the well established (S-proline catalyzed aldol-like reactions.

  20. Theoretical Mechanism Studies on the Enantioselectivity of aza-MBH-type Reaction of Nitroalkene to N-tosylimine Catalyzed by Thiourea-tertiary Amine

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Nan; Wang, Huatian; Wang, Yangping [Shandong Agricultural Univ., Taian (China)

    2013-12-15

    The enantioselective aza-Morita Baylis Hillman reaction of nitroalkene and N-tosylimine catalyzed by thiourea-tertiary amine has been investigated using density functional theory. Enantioselectivity is dominated by the cooperative effect of non-covalent and weak covalent interactions imposed by different units of catalyst. As Lewis base, the tertiary amine unit activates nitroalkene via weak covalent bond. The weak covalent interaction orients the reaction in a major path with smaller variations of this bond. The aromatic ring unit activates N-tosylimine via π-π stacking. The non-covalent interaction selects the major path with smaller changes of the efficient packing areas. Thiourea unit donates more compact H-bonded network for species of the major path. The calculated ee value in xylene solution phase (97.6%) is much higher than that in N,N-Dimethylformamide (27.2%). Our conclusion is also supported by NBO analysis.

  1. α-Halo Amides as Competent Latent Enolates: Direct Catalytic Asymmetric Mannich-Type Reaction.

    Science.gov (United States)

    Sun, Bo; Balaji, Pandur Venkatesan; Kumagai, Naoya; Shibasaki, Masakatsu

    2017-06-21

    α-Halogenated carbonyl compounds are susceptible to dehalogenation and thus largely neglected as enolate precursors in catalytic enantioselective C-C bond-forming reactions. By merging the increased stability of the α-C-halogen bond of amides and the direct enolization methodology of the designed amide, we explored a direct catalytic asymmetric Mannich-type reaction of α-halo 7-azaindoline amides with N-carbamoyl imines. All α-halo substituents, α-F, -Cl, -Br, -I amides, were tolerated to provide the Mannich-adducts in a highly stereoselective manner without undesirable dehalogenation. The diastereoselectivity switched intriguingly depending on the substitution pattern of the aromatic imines, which is ascribed to stereochemical differentiation based on the open transition-state model. Functional group interconversion of the 7-azaindoline amide moiety of the Mannich-adducts and further elaboration into a diamide without dehalogenation highlight the synthetic utility of the present protocol for accessing enantioenriched halogenated chemical entities.

  2. Development of an Intermittent-Flow Enantioselective Aza-Henry Reaction Using an Arylnitromethane and Homogeneous Brønsted Acid-Base Catalyst with Recycle.

    Science.gov (United States)

    Tsukanov, Sergey V; Johnson, Martin D; May, Scott A; Rosemeyer, Morgan; Watkins, Michael A; Kolis, Stanley P; Yates, Matthew H; Johnston, Jeffrey N

    2016-02-19

    A stereoselective aza-Henry reaction between an arylnitromethane and Boc-protected aryl aldimine using a homogeneous Brønsted acid-base catalyst was translated from batch format to an automated intermittent-flow process. This work demonstrates the advantages of a novel intermittent-flow setup with product crystallization and slow reagent addition which is not amenable to the standard continuous equipment: plug flow tube reactor (PFR) or continuous stirred tank reactor (CSTR). A significant benefit of this strategy was the integration of an organocatalytic enantioselective reaction with straightforward product separation, including recycle of the catalyst, resulting in increased intensity of the process by maintaining high catalyst concentration in the reactor. A continuous campaign confirmed that these conditions could effectively provide high throughput of material using an automated system while maintaining high selectivity, thereby addressing nitroalkane safety and minimizing catalyst usage.

  3. Choline-based biodegradable ionic liquid catalyst for Mannich-type ...

    Indian Academy of Sciences (India)

    A three-component Mannich-type reaction of aromatic aldehydes, ketones, and amines was cat- alyzed by a ..... ZnCl2 showed some catalytic activity and introducing. Table 1. The effects of different solvent systems to the. Mannich reaction.a. Entry. Solvent. Time (min) ... a significant role in promoting the catalytic activity of.

  4. Dehydrative Mannich-Type Reaction for the Synthesis of Azepinobisindole Alkaloid Iheyamine A.

    Science.gov (United States)

    Abe, Takumi; Yamada, Koji

    2018-03-02

    A concise synthesis of the azepinobisindole alkaloid iheyamine A from an indole-2,3-epoxide equivalent has been achieved. This method features a formal C3 electrophilic reaction of an indole-2,3-epoxide equivalent with tryptamine to form a 3-aminoindoline and a novel In-catalyzed dehydrative Mannich-type reaction of the hemiaminal to give the azepinobisindole core.

  5. ALDOL- AND MANNICH-TYPE REACTIONS VIA IN SITU OLEFIN MIGRATION IN IONIC LIQUID

    Science.gov (United States)

    An aldol-type and a Mannich-type reaction via the cross-coupling of aldehydes and imines with allylic alcohols catalyzed by RuCl2(PPh3)3 was developed with ionic liquid as the solvent. The solvent/catalyst system could be reused for at least five times with no loss of reactiv...

  6. Organocatalytic cascade aza-Michael/hemiacetal reaction between disubstituted hydrazines and α,β-unsaturated aldehydes: Highly diastereo- and enantioselective synthesis of pyrazolidine derivatives

    Directory of Open Access Journals (Sweden)

    Zhi-Cong Geng

    2012-10-01

    Full Text Available The catalytic synthesis of nitrogen-containing heterocycles is of great importance to medicinal and synthetic chemists, and also a challenge for modern chemical methodology. In this paper, we report the synthesis of pyrazolidine derivatives through a domino aza-Michael/hemiacetal sequence with chiral or achiral secondary amines as organocatalysts. Thus, a series of achiral pyrazolidine derivatives were obtained with good yields (up to 90% and high diastereoselectivities (>20:1 with pyrrolidine as an organocatalyst, and enantioenriched pyrazolidines are also achieved with good results (up to 86% yield, >10/1 regioselectivity, >20:1 dr, 99% ee in the presence of (S-diphenylprolinol trimethylsilyl ether catalyst.

  7. Direct Catalytic Asymmetric Mannich-Type Reaction of α-N3 Amide.

    Science.gov (United States)

    Sun, Zhongdong; Weidner, Karin; Kumagai, Naoya; Shibasaki, Masakatsu

    2015-12-01

    An α-N3 7-azaindoline amide serves as a latent enolate to directly engage in an asymmetric Mannich-type reaction with N-thiophosphinoyl imines by the action of a cooperative catalyst. The thus-obtained highly enantioenriched anti-adduct was transformed into β-amino-α-azido acid in high yield by simple acidic treatment. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Direct Mannich-Type Reactions Promoted by Frustrated Lewis Acid/Brønsted Base Catalysts.

    Science.gov (United States)

    Chan, Jessica Z; Yao, Wenzhi; Hastings, Brian T; Lok, Charles K; Wasa, Masayuki

    2016-10-24

    Direct Mannich-type reactions that afford both α- and β-amino esters by the reaction of a broad range of carbonyl compounds and aldimines are disclosed. The transformation is promoted by a sterically frustrated Lewis acid/Brønsted base pair, which is proposed to operate cooperatively: Within the catalyst complex, an enolate is generated that then reacts with a hydrogen-bond-activated imine. Noncovalent interactions between reactants and the catalyst provide selectivity and new opportunities for future catalyst design. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Preparation of dichlorvos-protein complete antigen by Mannich-type reaction

    Science.gov (United States)

    Feng, Qianqian; Xu, Ying; Zhou, Youxiang; Lu, Liang; Chen, Fusheng; Wang, Xiaohong

    2010-08-01

    Dichlorvos (DDVP) residues have been linked to substantial adverse health effects on several organ systems. To ensure food safety, rapid and low-cost immunological methods must be applied to detect DDVP residues in food. In immunological methods, a key step is coupling DDVP to carrier proteins to obtain a complete antigen due to DDVP being hapten. In the current research, DDVP was coupled with cationized bovine serum albumin (cBSA) using a method based on Mannich-type reaction. A DDVP-cBSA conjugate, with a molar ratio of 40:1 DDVP to cBSA was synthesized. The cationized proteins and their conjugates were identified by UV-Vis and FT-IR spectra, which showed the characteristic bands of the ethylenediamine group and DDVP, respectively. BALB/c mice were immunized with DDVP-cBSA. One hybridoma cell line secreted anti-DDVP monoclonal antibody (Mab) that had high sensitivity and specificity for DDVP. Competitive ELISA identified an IC50 of 600 ng/mL and a limit of detection of 1 ng/mL in aqueous solution. The Mab had some cross-reactivity with phosmet, but no cross-reactivity with chlorothalonil and procymidone. We also detected a trace of DDVP in waste water. In conclusion the Mannich-type reaction couples DDVP to protein, yielding an antigen for the production of Mab to detect residual DDVP in the environment.

  10. Stereoselective ZrCl4-Catalyzed Mannich-type Reaction of β-Keto Esters with Chiral Trifluoromethyl Aldimines.

    Science.gov (United States)

    Parise, Luca; Pellacani, Lucio; Sciubba, Fabio; Trulli, Laura; Fioravanti, Stefania

    2015-08-21

    A method for the synthesis of fluorinated β'-amino β-dicarbonyl compounds using a Zr-catalyzed Mannich-type reaction has been developed, starting from N-protected trifluoromethyl aldimines and cyclic or acyclic β-keto esters bearing different ester residues. The in situ generated metallic complex reacted with optically pure trifluoromethyl aldimine derived from (R)-α-methylbenzylamine, giving a highly diastereoselective asymmetric Mannich-type addition with formation of a chiral quaternary center. The absolute configuration at the new chiral centers was assigned through two-dimensional nuclear Overhauser effect spectroscopic analysis coupled with computational studies.

  11. Influence of the Organocatalyst in the Aldol/Mannich-Type Product Selectivities in C−C Bond Forming Reactions

    NARCIS (Netherlands)

    Dominguez de Maria, Pablo; Bracco, Paula; Castelhano, Luiz Fernando; Bargeman, Gerrald

    2011-01-01

    Several organocatalysts were tested in the cross condensation of isobutyraldehyde and acetone. Formation of aldol-type and Mannich-type (“aldol condensation”) products was assessed, and Aldol/Mannich proportion studied under several reaction conditions and at different conversions. Organocatalysts

  12. Enantioselective organocatalytic partial transfer hydrogenation of lactone-fused quinolines.

    Science.gov (United States)

    Aillerie, Alexandre; de Talancé, Vincent Lemau; Moncomble, Aurélien; Bousquet, Till; Pélinski, Lydie

    2014-06-06

    The first enantioselective synthesis of 4-aza-podophyllotoxin derivatives by partial transfer hydrogenation of lactone-fused quinolines was achieved using a chiral Brønsted acid catalyst. This reaction was extended to a large scope of substrates with good yields and enantioselectivities.

  13. Direct Catalytic Asymmetric Mannich-Type Reaction of α- and β-Fluorinated Amides.

    Science.gov (United States)

    Brewitz, Lennart; Arteaga, Fernando Arteaga; Yin, Liang; Alagiri, Kaliyamoorthy; Kumagai, Naoya; Shibasaki, Masakatsu

    2015-12-23

    The last two decades have witnessed the emergence of direct enolization protocols providing atom-economical and operationally simple methods to use enolates for stereoselective C-C bond-forming reactions, eliminating the inherent drawback of the preformation of enolates using stoichiometric amounts of reagents. In its infancy, direct enolization relied heavily on the intrinsic acidity of the latent enolates, and the reaction scope was limited to readily enolizable ketones and aldehydes. Recent advances in this field enabled the exploitation of carboxylic acid derivatives for direct enolization, offering expeditious access to synthetically versatile chiral building blocks. Despite the growing demand for enantioenriched fluorine-containing small molecules, α- and β-fluorinated carbonyl compounds have been neglected in direct enolization chemistry because of the competing and dominating defluorination pathway. Herein we present a comprehensive study on direct and highly stereoselective Mannich-type reactions of α- and β-fluorine-functionalized 7-azaindoline amides that rely on a soft Lewis acid/hard Brønsted base cooperative catalytic system to guarantee an efficient enolization while suppressing undesired defluorination. This protocol contributes to provide a series of fluorinated analogs of enantioenriched β-amino acids for medicinal chemistry.

  14. Direct Catalytic Asymmetric Mannich-Type Reaction en Route to α-Hydroxy-β-amino Acid Derivatives.

    Science.gov (United States)

    Sun, Bo; Pluta, Roman; Kumagai, Naoya; Shibasaki, Masakatsu

    2018-02-02

    A direct catalytic Mannich-type reaction of α-oxygen-functionalized amides was achieved. The use of 7-azaindoline amide was crucial to facilitate direct enolization and subsequent stereoselective addition to imines in a cooperative catalytic system comprising a soft Lewis acid and Brønsted base. The operationally simple room-temperature protocol furnished a syn-Mannich adduct with high stereoselectivity. Divergent functional group transformation of the amide moiety of the product allowed for expeditious access to enantioenriched syn-configured α-hydroxy-β-amino carboxylic acid derivatives, highlighting the synthetic utility of the present catalysis.

  15. Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (±-ezetimibe

    Directory of Open Access Journals (Sweden)

    Motoyuki Isoda

    2016-07-01

    Full Text Available An effective synthesis for syn-β-lactams was achieved using a Rh-catalyzed reductive Mannich-type reaction. A rhodium–hydride complex (Rh–H derived from diethylzinc (Et2Zn and a Rh catalyst was used for the 1,4-reduction of an α,β-unsaturated ester to give a Reformatsky-type reagent, which in turn, reacted with an imine to give the syn-β-lactam. Additionally, the reaction was applied to the synthesis of (±-ezetimibe, a potent β-lactamic cholesterol absorption inhibitor.

  16. Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (±)-ezetimibe.

    Science.gov (United States)

    Isoda, Motoyuki; Sato, Kazuyuki; Kunugi, Yurika; Tokonishi, Satsuki; Tarui, Atsushi; Omote, Masaaki; Minami, Hideki; Ando, Akira

    2016-01-01

    An effective synthesis for syn-β-lactams was achieved using a Rh-catalyzed reductive Mannich-type reaction. A rhodium-hydride complex (Rh-H) derived from diethylzinc (Et2Zn) and a Rh catalyst was used for the 1,4-reduction of an α,β-unsaturated ester to give a Reformatsky-type reagent, which in turn, reacted with an imine to give the syn-β-lactam. Additionally, the reaction was applied to the synthesis of (±)-ezetimibe, a potent β-lactamic cholesterol absorption inhibitor.

  17. Versatile In Situ Generated N-Boc-Imines: Application to Phase-Transfer-Catalyzed Asymmetric Mannich-Type Reactions.

    Science.gov (United States)

    Kano, Taichi; Kobayashi, Ryohei; Maruoka, Keiji

    2015-07-13

    The efficient construction of nitrogen-containing organic compounds is a major challenge in chemical synthesis. Imines are one of the most important classes of electrophiles for this transformation. However, both the available imines and applicable nucleophiles for them are quite limited given the existing preparative methods. Described herein are imine precursors which generate reactive imines with a wide variety of substituents under mild basic conditions. This approach enables the construction of various nitrogen-containing molecules which cannot be accessed by the traditional approach. The utility of the novel imine precursor was demonstrated in the asymmetric Mannich-type reaction under phase-transfer conditions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Multiple reaction pathways operating in the mechanism of vinylogous Mannich-type reaction activated by a water molecule.

    Science.gov (United States)

    Uematsu, Ryohei; Maeda, Satoshi; Taketsugu, Tetsuya

    2014-01-01

    A systematic search for reaction pathways for the vinylogous Mannich-type reaction was performed by the artificial force induced reaction method. This reaction affords δ-amino-γ-butenolide in one pot by mixing 2-trimethylsiloxyfuran, imine, and water under solvent-free conditions. Surprisingly, the search identified as many as five working pathways. Among them, two concertedly produce anti and syn isomers of the product. Another two give an intermediate, which is a regioisomer of the main product. This intermediate can undergo a retro-Mannich reaction to give a pair of intermediates: an imine and 2-furanol. The remaining pathway directly generates this intermediate pair. The imine and 2-furanol easily react with each other to afford the product. Thus, all of these stepwise pathways finally converge to give the main product. The rate-determining step of all five (two concerted and three stepwise) pathways have a common mechanism: concerted Si-O bond formation through the nucleophilic attack of a water molecule on the silicon atom followed by proton transfer from the water molecule to the imine. Therefore, these five pathways have comparable barriers and compete with each other. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. A General Asymmetric Formal Synthesis of Aza-Baylis-Hillman Type Products under Bifunctional Catalysis.

    Science.gov (United States)

    Frías, María; Carrasco, Ana Cristina; Fraile, Alberto; Alemán, José

    2018-03-02

    A new organocatalytic strategy for the synthesis of enantioenriched aza-Baylis-Hillman type products via a frustrated vinylogous reaction is presented. This process proceeds under mild conditions with good yields, completed Z/E selectivity and excellent enantioselectivities. Moreover, easy derivatizations of the final products led to important building blocks of organic synthesis such as 1,3-aminoalcohols and Lewis base catalysts. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Design and synthesis of pyrido[2,1-b][1,3,5]thiadiazine library via uncatalyzed Mannich-type reaction.

    Science.gov (United States)

    Dotsenko, Victor V; Frolov, Konstantin A; Pekhtereva, Tatyana M; Papaianina, Olena S; Suykov, Sergey Yu; Krivokolysko, Sergey G

    2014-10-13

    This Research Article describes the synthesis of an over 700-member library of (8R/8S)-3-R-8-aryl-6-oxo-3,4,7,8-tetrahydro-2H,6H-pyrido[2,1-b][1,3,5]thiadiazin-9-carbonitriles by uncatalyzed Mannich-type reaction of N-methylmorpholinium (4R/4S)-4-aryl-3-cyano-6-oxo-1,4,5,6-tetrahydropyridin-2-thiolates with a set of primary amines and excessive HCHO. The scope and limitations of the reaction were studied. Starting thiolates were obtained in yields of 53-82% by multicomponent reaction of aromatic aldehydes, cyanothioacetamide, 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid), and N-methylmorpholine, followed by heterocyclization of the resulting Michael adducts.

  1. Asymmetric synthesis of γ-chloro-α,β-diamino- and β,γ-aziridino-α-aminoacylpyrrolidines and -piperidines via stereoselective Mannich-type additions of N-(diphenylmethyleneglycinamides across α-chloro-N-sulfinylimines

    Directory of Open Access Journals (Sweden)

    Gert Callebaut

    2012-12-01

    Full Text Available The asymmetric synthesis of new chiral γ-chloro-α,β-diaminocarboxylamide derivatives by highly diastereoselective Mannich-type reactions of N-(diphenylmethyleneglycinamides across chiral α-chloro-N-p-toluenesulfinylaldimines was developed. The resulting (SS,2S,3S-γ-chloro-α,β-diaminocarboxylamides were formed with the opposite enantiotopic face selectivity as compared to the (SS,2R,3R-γ-chloro-α,β-diaminocarboxyl esters obtained via Mannich-type addition of analogous N-(diphenylmethyleneglycine esters across a chiral α-chloro-N-p-toluenesulfinylaldimine. Selective deprotection under different acidic reaction conditions and ring closure of the γ-chloro-α,β-diaminocarboxylamides was optimized, which resulted in Nα-deprotected syn-γ-chloro-α,β-diaminocarboxylamides, N-sulfinyl-β,γ-aziridino-α-aminocarboxylamide derivatives, a trans-imidazolidine, and an Nα,Nβ-deprotected syn-γ-chloro-α,β-diaminocarboxylamide.

  2. CATALYTIC ENANTIOSELECTIVE ALLYLIC OXIDATION

    NARCIS (Netherlands)

    Rispens, Minze T.; Zondervan, Charon; Feringa, Bernard

    Several chiral Cu(II)-complexes of cyclic amino acids catalyse the enantioselective allylic oxidation of cyclohexene to cyclohexenyl esters. Cyclohexenyl propionate was obtained in 86% yield with e.e.'s up to 61%.

  3. Diversity-oriented synthesis of azapeptides with basic amino acid residues: aza-lysine, aza-ornithine, and aza-arginine.

    Science.gov (United States)

    Traoré, Mariam; Doan, Ngoc-Duc; Lubell, William D

    2014-07-03

    Aza-peptides with basic amino acid residues (lysine, ornithine, arginine) and derivatives were synthesized by an effective approach featuring alkylation of a hydrazone-protected aza-glycine residue with α-bromo ω-chloro propane and butane to provide the corresponding alkyl chloride side chains. Displacement of the chloride with azide and various amines gave entry to azaOrn, azaLys, and azaArg containing peptides as demonstrated by the solution and solid-phase syntheses of 29 examples, including an aza-library of Growth Hormone Releasing Peptide-6 analogs.

  4. Group-Assisted Purification Chemistry for Asymmetric Mannich-type Reaction of Chiral N-Phosphonyl Imines with Azlactones Leading to Syntheses of α-Quaternary α,β-Diamino Acid Derivatives †.

    Science.gov (United States)

    Zhang, Haowei; Yang, Zhen; Zhao, Brian Nlong; Li, Guigen

    2018-01-19

    An asymmetric Mannich-type reaction between chiral N-phosphonyl imines and azlactones [oxazol-5(4H)-ones] has been established under convenient conditions at room temperature. The reaction was performed without using any bases, additives, or catalysts to achieve up to excellent chemical yields and diastereoselectivity for 32 examples. The α-quaternary syn-α,β-diamino acid products were purified simply by washing the crude mixtures with cosolvents, following the group-assisted purification chemistry/technology, without involving traditional chromatography or recrystallization methods. The auxiliary can be readily removed and recycled for reuse. The absolute configuration was unambiguously assigned by X-ray structural analysis.

  5. SHORT COMMUNICATION FACILE ENANTIOSELECTIVE ...

    African Journals Online (AJOL)

    ABSTRACT. An efficient and enantioselective method for catalytic transfer hydrogenation of the C=C double bond of α-methylcinnamic acid with the aid of chiral organic acids as the hydrogen donors and palladium(II) chloride as the catalyst is reported. Enantiomeric excess was assayed using optical rotation measurements ...

  6. Catalytic Wittig and aza-Wittig reactions

    Directory of Open Access Journals (Sweden)

    Zhiqi Lao

    2016-11-01

    Full Text Available This review surveys the literature regarding the development of catalytic versions of the Wittig and aza-Wittig reactions. The first section summarizes how arsenic and tellurium-based catalytic Wittig-type reaction systems were developed first due to the relatively easy reduction of the oxides involved. This is followed by a presentation of the current state of the art regarding phosphine-catalyzed Wittig reactions. The second section covers the field of related catalytic aza-Wittig reactions that are catalyzed by both phosphine oxides and phosphines.

  7. Catalytic Wittig and aza-Wittig reactions.

    Science.gov (United States)

    Lao, Zhiqi; Toy, Patrick H

    2016-01-01

    This review surveys the literature regarding the development of catalytic versions of the Wittig and aza-Wittig reactions. The first section summarizes how arsenic and tellurium-based catalytic Wittig-type reaction systems were developed first due to the relatively easy reduction of the oxides involved. This is followed by a presentation of the current state of the art regarding phosphine-catalyzed Wittig reactions. The second section covers the field of related catalytic aza-Wittig reactions that are catalyzed by both phosphine oxides and phosphines.

  8. A highly enantioselective amino acid-catalyzed route to functionalized alpha-amino acids.

    Science.gov (United States)

    Córdova, Armando; Notz, Wolfgang; Zhong, Guofu; Betancort, Juan M; Barbas, Carlos F

    2002-03-06

    The development of syntheses providing enantiomerically pure alpha-amino acids has intrigued generations of chemists and been the subject of intense research. This report describes a general approach to functionalized alpha-amino acids based on catalytic asymmetric synthesis. Proline catalyzed Mannich-type reactions of N-PMP-protected alpha-imino ethyl glyoxylate with a variety of unmodified ketones to provide functionalized alpha-amino acids in high yields with excellent regio-, diastereo-, and enantioselectivities. Study of seven examples yielded six with product ee values of > or = 99%. In reactions involving ketone donors where diastereoisomeric products could be formed, two adjacent stereogenic centers were created simultaneously upon carbon-carbon bond formation with complete syn-stereocontrol. Significantly, this methodology utilizes readily available and rather inexpensive starting materials, does not require any preactivation of substrates or metal ion assistance, and can be carried out on a gram scale under operationally simple reaction conditions. The keto-functionality present in the products provides a particularly attractive site for versatile modifications. This study compliments and extends our bioorganic approach to asymmetric synthesis to a versatile synthon class. Given that we have shown that a variety of optically active amino acids can be synthesized with proline catalysis, where an L-amino acid begets other L-amino acids, our results may stimulate thoughts concerning prebiotic syntheses of optically active amino acids based on this route.

  9. Aza-Michael reaction: achievements and prospects

    International Nuclear Information System (INIS)

    Rulev, Alexander Yu

    2011-01-01

    Data published in the last 10 years on the use of the aza-Michael reaction in organic synthesis are described systematically. The attention is focused on environmentally friendly processes following green chemistry principles and on methods for the synthesis of compounds that are difficult to access by other routes.

  10. Aza-Michael reaction: achievements and prospects

    Science.gov (United States)

    Rulev, Alexander Yu

    2011-03-01

    Data published in the last 10 years on the use of the aza-Michael reaction in organic synthesis are described systematically. The attention is focused on environmentally friendly processes following green chemistry principles and on methods for the synthesis of compounds that are difficult to access by other routes.

  11. Application of 7-azaisatins in enantioselective Morita–Baylis–Hillman reaction

    Directory of Open Access Journals (Sweden)

    Qing He

    2016-02-01

    Full Text Available 7-Azaisatin and 7-azaoxindole skeletons are valuable building blocks in diverse biologically active substances. Here 7-azaisatins turned out to be more efficient electrophiles than the analogous isatins in the enantioselective Morita–Baylis–Hillman (MBH reactions with maleimides using a bifunctional tertiary amine, β-isocupreidine (β-ICD, as the catalyst. This route allows a convenient approach to access multifunctional 3-hydroxy-7-aza-2-oxindoles with high enantiopurity (up to 94% ee. Other types of activated alkenes, such as acrylates and acrolein, could also be efficiently utilized.

  12. Enantioselective Synthesis of Isoquinolines: Merging Chiral-Phosphine and Gold Catalysis.

    Science.gov (United States)

    Gao, Yu-Ning; Shi, Feng-Chen; Xu, Qin; Shi, Min

    2016-05-10

    The highly enantioselective synthesis of dihydroisoquinoline derivatives from aromatic sulfonated imines tethered with an alkyne moiety, through a one-pot asymmetric relay catalysis of chiral-phosphine and gold catalysts, is reported. Enantiomerically enriched dihydroisoquinoline derivatives were afforded in good yields and good-to-excellent ee values under mild conditions, based on the asymmetric aza-Morita-Baylis-Hillman reaction. Dihydroisoquinoline derivatives containing two chiral centers were also synthesized through further transformations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Application of 7-azaisatins in enantioselective Morita-Baylis-Hillman reaction.

    Science.gov (United States)

    He, Qing; Zhan, Gu; Du, Wei; Chen, Ying-Chun

    2016-01-01

    7-Azaisatin and 7-azaoxindole skeletons are valuable building blocks in diverse biologically active substances. Here 7-azaisatins turned out to be more efficient electrophiles than the analogous isatins in the enantioselective Morita-Baylis-Hillman (MBH) reactions with maleimides using a bifunctional tertiary amine, β-isocupreidine (β-ICD), as the catalyst. This route allows a convenient approach to access multifunctional 3-hydroxy-7-aza-2-oxindoles with high enantiopurity (up to 94% ee). Other types of activated alkenes, such as acrylates and acrolein, could also be efficiently utilized.

  14. Luminescent Lariat Aza-Crown Ether Carboxylic Acid

    Directory of Open Access Journals (Sweden)

    Burkhard König

    2010-03-01

    Full Text Available Lariat ethers are interesting recognition motifs in supramolecular chemistry. The synthesis of a luminescent lariat aza-crown ether with a carboxyl group appended by azide-alkyne (Huisgen cycloaddition is presented.

  15. One-Pot Lipase-Catalyzed Enantioselective Synthesis of (R-(−-N-Benzyl-3-(benzylaminobutanamide: The Effect of Solvent Polarity on Enantioselectivity

    Directory of Open Access Journals (Sweden)

    Marina A. Ortega-Rojas

    2017-12-01

    Full Text Available The use of the solvent engineering has been applied for controlling the resolution of lipase-catalyzed synthesis of β-aminoacids via Michael addition reactions. The strategy consisted of the thermodynamic control of products at equilibrium using the lipase CalB as a catalyst. The enzymatic chemo- and enantioselective synthesis of (R-(−-N-benzyl-3-(benzylaminobutanamide is reported, showing the influence of the solvent on the chemoselectivity of the aza-Michael addition and the subsequent kinetic resolution of the Michael adduct; both processes are catalyzed by CalB and both are influenced by the nature of the solvent medium. This approach allowed us to propose a novel one-pot strategy for the enzymatic synthesis of enantiomerically enriched β-aminoesters and β-aminoacids.

  16. Catalytic enantioselective Reformatsky reaction with ketones

    NARCIS (Netherlands)

    Fernandez-Ibanez, M. Angeles; Macia, Beatriz; Minnaard, Adriaan J.; Feringa, Ben L.

    2008-01-01

    Chiral tertiary alcohols were obtained with good yields and enantioselectivities via a catalytic Reformatsky reaction with ketones, including the challenging diaryl ketones, using chiral BINOL derivatives.

  17. Structural Basis for Aza-Glycine Stabilization of Collagen.

    Science.gov (United States)

    Kasznel, Alexander J; Zhang, Yitao; Hai, Yang; Chenoweth, David M

    2017-07-19

    Previously, we have demonstrated that replacement of the strictly conserved glycine in collagen with aza-glycine provides a general solution for stabilizing triple helical collagen peptides (Chenoweth, D. M.; et al. J. Am. Chem. Soc. 2016, 138, 9751 ; 2015, 137, 12422 ). The additional hydrogen bond and conformational constraints provided by aza-glycine increases the thermal stability and rate of folding in collagen peptides composed of Pro-Hyp-Gly triplet repeats, allowing for truncation to the smallest self-assembling peptide systems observed to date. Here we show that aza-glycine substitution enhances the stability of an arginine-containing collagen peptide and provide a structural basis for this stabilization with an atomic resolution crystal structure. These results demonstrate that a single nitrogen atom substitution for a glycine alpha-carbon increases the peptide's triple helix melting temperature by 8.6 °C. Furthermore, we provide the first structural basis for stabilization of triple helical collagen peptides containing aza-glycine and we demonstrate that minimal alteration to the peptide backbone conformation occurs with aza-glycine incorporation.

  18. The enantioselective total synthesis of (+)-clusianone.

    Science.gov (United States)

    Horeischi, Fiene; Guttroff, Claudia; Plietker, Bernd

    2015-02-11

    (+)-Clusianone, an exo-type B PPAP with reported anti-HIV and chemoprotective activities, was synthesized in eleven steps with 97% ee starting from acetylacetone. An enantioselective decarboxylative Tsuji-Trost-allylation and a Ru-catalyzed ring-closing metathesis-decarboxylative allylation were used to control both diastereo- and enantioselectivity.

  19. Enantioselective Transport by a Steroidal Guanidinium Receptor

    NARCIS (Netherlands)

    Baragaña, Beatriz; Blackburn, Adrian G.; Breccia, Perla; Davis, Anthony P.; Mendoza, Javier de; Padrón-Carrillo, José M.; Prados, Pilar; Riedner, Jens; Vries, Johannes G. de

    2002-01-01

    The cationic steroidal receptors 9 and 11 have been synthesized from cholic acid 3. Receptor 9 extracts N-acetyl-α-amino acids from aqueous media into chloroform with enantioselectivities (L:D) of 7-10:1. The lipophilic variant 11 has been employed for the enantioselective transport of

  20. Enantioselective solvent-free Robinson annulation reactions

    Indian Academy of Sciences (India)

    The enantioselective cyclization of the prochiral cyclic substrates 1 to 7 and 26, can be carried out in the neat using -proline as catalyst. The substrates 18 to 22 and 27 could not be cyclized with S-proline but could be cyclized with a mixture of -phenylalanine and -camphorsulphonic acid. The enantioselective ...

  1. Enantioselective Dialkylation of 1,2-Phthalicdicarboxaldehyde

    NARCIS (Netherlands)

    Koten, G. van; Kleijn, H.; Jastrzebski, J.T.B.H.; Boersma, J.

    2001-01-01

    A new two-step, one-pot procedure is reported for the enantioselective synthesis of C{2}-symmetric diols derived from 1, 2-phthalicdicarboxaldehyde. The first step involves the enantioselective addition of a dialkylzinc compound to one of the aldehyde groups, affording a lactol organozinc

  2. Aza-Michael Reaction for an Undergraduate Organic Chemistry Laboratory

    Science.gov (United States)

    Nigam, Manisha; Rush, Brittney; Patel, Jay; Castillo, Raul; Dhar, Preeti

    2016-01-01

    A green, aza-Michael reaction is described that can be used to teach undergraduate students conjugate addition of nitrogen nucleophile to an a,ß-unsaturated ester. Students analyze spectral data of the product obtained from the assigned reaction to determine product structure and propose the mechanism of its formation. The experiment requires…

  3. Synthesis of 7-arylethyl-5-arylpyrazolo pyrimidines through an aza ...

    Indian Academy of Sciences (India)

    ZHENG LI

    2017-10-09

    Oct 9, 2017 ... This result indicated that. 1,3-hydrogen transfer also occurred for the reaction of. 1a and pyrazol-3-amine in addition to 1,4-aza-Michael addition and nucleophilic addition. The possible reason is that compared to structure A, the product 2a has more stable aromatic fused heterocycle. This implied that the.

  4. Enantioselective, transition metal catalyzed cycloisomerizations.

    Science.gov (United States)

    Marinetti, Angela; Jullien, Hélène; Voituriez, Arnaud

    2012-07-21

    This review illustrates enantioselective transition-metal promoted skeletal rearrangements of polyunsaturated substrates possessing olefin, alkyne or allene functions. These processes are classified according to the number of carbon atoms involved in the cyclization, from (1C+1C) to (2C+2C+2C) or (2C+5C) cyclizations. Thus, for instance, (1C+1C) processes are typified notably by Alder-ene type reactions taking place mainly under palladium and rhodium catalysis, in the presence of chiral phosphorus ligands. Also, rhodium, platinum, and gold promoted insertions of unsaturated carbon-carbon bonds into C-H bonds belong to this class. For each class of reactions or substrate type the best ligand-metal pairs are highlighted. Unfortunately, unlike other transition metal promoted reactions, the mechanisms of chiral induction and stereochemical pathways have not been established so far in any of these reactions. In only a few instances, qualitative heuristic models have been tentatively proposed. Although the available stereochemical information is systematically given here, the paper focuses mainly on synthetic aspects of enantioselective cycloisomerizations.

  5. Kinetic investigation on enantioselective hydrolytic resolution of ...

    African Journals Online (AJOL)

    Kinetic investigation on enantioselective hydrolytic resolution of epichlorohydrin by crude epoxide hydrolase from domestic duck liver. X Ling, D Lu, J Wang, J Chen, L Ding, J Chen, H Chai, P Ouyang ...

  6. The Development of an Aza-C-Glycoside Library Based on a Tandem Staudinger/Aza-Wittig/Ugi Three-Component Reaction

    NARCIS (Netherlands)

    Wennekes, Tom; Bonger, Kimberley M.; Vogel, Katrin; van den Berg, Richard J. B. H. N.; Strijland, Anneke; Donker-Koopman, Wilma E.; Aerts, Johannes M. F. G.; van der Marel, Gijsbert A.; Overkleeft, Herman S.

    2012-01-01

    We report the tandem Staudinger/aza-Wittig/Ugi three-component reaction mediated synthesis of a 64-member compound library of aza-C-glycosides. The library is composed of four pyrrolidine and three piperidine scaffolds, onto which a number of functional groups is grafted to form seven sublibraries.

  7. Reversal of the sense of enantioselectivity between 1-and 2-aza[6]helicenes used as chiral inducers of asymmetric autocatalysis

    Czech Academy of Sciences Publication Activity Database

    Matsumoto, A.; Yonemitsu, K.; Ozaki, H.; Míšek, Jiří; Starý, Ivo; Stará, Irena G.; Soai, K.

    2017-01-01

    Roč. 15, č. 6 (2017), s. 1321-1324 ISSN 1477-0520 R&D Projects: GA ČR(CZ) GA14-29667S Institutional support: RVO:61388963 Keywords : azahelicene * Soai reaction * asymmetric autocatalysis Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 3.564, year: 2016 http://pubs.rsc.org/en/content/articlehtml/2013/ob/c6ob02745h

  8. Enantioselective olefin metathesis with cyclometalated ruthenium complexes.

    Science.gov (United States)

    Hartung, John; Dornan, Peter K; Grubbs, Robert H

    2014-09-17

    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.

  9. Enantioselective Biotransformation of Chiral Persistent Organic Pollutants.

    Science.gov (United States)

    Zhang, Ying; Ye, Jing; Liu, Min

    2017-01-01

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

  10. Aza-Morita-Baylis-Hillman reactions catalyzed by a cyclopropenylidene.

    Science.gov (United States)

    Lu, Xun; Schneider, Uwe

    2016-10-27

    Catalysis using a bis(dialkylamino)cyclopropenylidene (BAC) has been developed, which relies on a formal umpolung activation of Michael acceptor pro-nucleophiles. Various aza-Morita-Baylis-Hillman reactions between aromatic, heteroaromatic, or aliphatic imines and acyclic or cyclic α,β-unsaturated ketones and carboxylic acid derivatives have been catalyzed by a BAC under mild conditions. Functionalities such as unprotected amino and hydroxy groups have been tolerated. The catalyst loading was decreased to 1 mol% without loss of activity. The BAC catalyst was shown to be substantially more active than a cyclic (alkyl)(amino) carbene (CAAC), N-heterocyclic carbenes (NHCs), and P- or N-centered Lewis bases.

  11. Reaction of aryne with aza-Morita–Baylis–Hillman adducts: Synthesis of 4-quinolones and N-arylation products

    Directory of Open Access Journals (Sweden)

    Li-Li Liu

    2017-05-01

    Full Text Available The reaction of aryne with aza-Morita–Baylis–Hillman (aza-MBH adducts has been studied. Aryne reacts with aza-MBH adducts through a cascade insertion–cyclization–ene reaction to produce 4-quinolones in 18–44% yields; meanwhile, aza-MBH adducts undergo N-insertion reaction with aryne to afford N-arylation products in 27–77% yields.

  12. Synthesis of Triazole Derivatives of Levoglucosenone As Promising Anticancer Agents: Effective Exploration of the Chemical Space through retro-aza-Michael//aza-Michael Isomerizations.

    Science.gov (United States)

    Tsai, Yi-Hsuan; Borini Etichetti, Carla M; Di Benedetto, Carolina; Girardini, Javier E; Martins, Felipe Terra; Spanevello, Rolando A; Suárez, Alejandra G; Sarotti, Ariel M

    2018-03-08

    The design and synthesis of biomass-derived triazoles and the in vitro evaluation as potential anticancer agents are described. The discovery of base-catalyzed retro-aza-Michael//aza-Michael isomerizations allowed the exploration of the chemical space by affording novel types of triazoles, difficult to obtain otherwise. Following this strategy, 2,4-disubstituted 1,2,3-triazoles could be efficiently obtained from the corresponding 1,4-disubstituted analogues.

  13. Optimization of enantioselective production of chiral epichlorohydrin ...

    African Journals Online (AJOL)

    Optimization of enantioselective production of chiral epichlorohydrin catalyzed by a novel epoxide hydrolase from domestic duck liver by response surface methodology. ... Enantiopure epichlorohydrin is a valuable epoxide intermediate for preparing optically active pharmaceuticals. In the present study, a novel epoxide ...

  14. Catalytic enantioselective conjugate addition with Grignard reagents

    NARCIS (Netherlands)

    Lopez, Fernando; Minnaard, Adriaan J.; Feringa, Ben L.

    In this Account, recent advances in catalytic asymmetric conjugate addition of Grignard reagents are discussed. Synthetic methodology to perform highly enantioselective Cu-catalyzed conjugate addition of Grignard reagents to cyclic enones with ee's up to 96% was reported in 2004 from our

  15. The Catalytic Enantioselective Total Synthesis of (+)-Liphagal

    KAUST Repository

    Day, Joshua J.

    2011-06-10

    Ring a ding: The meroterpenoid natural product (+)-liphagal has been synthesized enantioselectively in 19 steps from commercially available materials. The trans-homodecalin system was achieved by ring expansion followed by stereoselective hydrogenation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Enantioselectivity in environmental risk assessment of modern chiral pesticides

    Energy Technology Data Exchange (ETDEWEB)

    Ye Jing [MOE Key Lab of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Science, Zhejiang University, Hangzhou 310027 (China); Zhao Meirong [Research Center of Environmental Science, Zhejiang University of Technology, Hangzhou 310032 (China); Liu Jing [MOE Key Lab of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Science, Zhejiang University, Hangzhou 310027 (China); Liu Weiping, E-mail: wliu@zju.edu.c [MOE Key Lab of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Science, Zhejiang University, Hangzhou 310027 (China); Research Center of Environmental Science, Zhejiang University of Technology, Hangzhou 310032 (China)

    2010-07-15

    Chiral pesticides comprise a new and important class of environmental pollutants nowadays. With the development of industry, more and more chiral pesticides will be introduced into the market. But their enantioselective ecotoxicology is not clear. Currently used synthetic pyrethroids, organophosphates, acylanilides, phenoxypropanoic acids and imidazolinones often behave enantioselectively in agriculture use and they always pose unpredictable enantioselective ecological risks on non-target organisms or human. It is necessary to explore the enantioselective toxicology and ecological fate of these chiral pesticides in environmental risk assessment. The enantioselective toxicology and the fate of these currently widely used pesticides have been discussed in this review article. - Chiral pesticides could pose unpredictable enantioselective toxicity on non-target organisms.

  17. Enantioselectivity in environmental risk assessment of modern chiral pesticides

    International Nuclear Information System (INIS)

    Ye Jing; Zhao Meirong; Liu Jing; Liu Weiping

    2010-01-01

    Chiral pesticides comprise a new and important class of environmental pollutants nowadays. With the development of industry, more and more chiral pesticides will be introduced into the market. But their enantioselective ecotoxicology is not clear. Currently used synthetic pyrethroids, organophosphates, acylanilides, phenoxypropanoic acids and imidazolinones often behave enantioselectively in agriculture use and they always pose unpredictable enantioselective ecological risks on non-target organisms or human. It is necessary to explore the enantioselective toxicology and ecological fate of these chiral pesticides in environmental risk assessment. The enantioselective toxicology and the fate of these currently widely used pesticides have been discussed in this review article. - Chiral pesticides could pose unpredictable enantioselective toxicity on non-target organisms.

  18. Molecular Bases of Enantioselectivity of Haloalkane Dehalogenase DbjA

    Science.gov (United States)

    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.

  19. A general enantioselective route to the chamigrene natural product family

    KAUST Repository

    White, David E.

    2010-06-01

    Described in this report is an enantioselective route toward the chamigrene natural product family. The key disconnections in our synthetic approach include sequential enantioselective decarboxylative allylation and ring-closing olefin metathesis to form the all-carbon quaternary stereocenter and spirocyclic core present in all members of this class of compounds. The generality of this strategy is demonstrated by the first total syntheses of elatol and the proposed structure of laurencenone B, as well as the first enantioselective total syntheses of laurencenone C and α-chamigrene. A brief exploration of the substrate scope of the enantioselective decarboxylative allylation/ring-closing metathesis sequence with fully substituted vinyl chlorides is also presented.

  20. Enantioselective disposition of clenbuterol in rats

    OpenAIRE

    Hirosawa, Iori; Ishikawa, Mai; Ogino, Mio; Ito, Hiroshi; Hirao, Takuya; Yamada, Harumi; Asahi, Mariko; Kotaki, Hajime; Sai, Yoshimichi; Miyamoto, Ken-ichi

    2014-01-01

    Clenbuterol is a long-acting β2-adrenoceptor agonist and bronchodilator that is used for the treatment of asthma, but the desired activities reside almost exclusively in the (-)-R-enantiomer. This study examined enantioselectivity in the disposition of clenbuterol following administration of clenbuterol racemate to rats. Concentrations of clenbuterol enantiomers in plasma, urine and bile were determined by LC-MS/MS assay with a Chirobiotic T column. This method was confirmed to show high sens...

  1. Chiral separation by enantioselective liquid-liquid extraction

    NARCIS (Netherlands)

    Schuur, B.; Verkuijl, B. J. V.; Minnaard, A. J.; De Vries, J. G.; Heeres, H. J.; Feringa, B. L.

    2011-01-01

    The literature on enantioselective liquid-liquid extraction (ELLE) spans more than half a century of research. Nonetheless, a comprehensive overview has not appeared during the past few decades. Enantioselective liquid-liquid extraction is a technology of interest for a wide range of chemists and

  2. Loop grafting of Bacillus subtilis lipase A : Inversion of enantioselectivity

    NARCIS (Netherlands)

    Boersma, Y.L.; Pijning, Tjaard; Bosma, Margriet; van der Sloot, Almer Martinus; da Silva Godinho, Luis; Dröge, Melloney; Winter, R.T.; van Pouderoyen, Gertie; Dijkstra, B.W.; Quax, Wim

    2008-01-01

    Lipases are successfully applied in enantioselective biocatalysis. Most lipases contain a lid domain controlling access to the active site, but Bacillus subtilis Lipase A (LipA) is a notable exception: its active site is solvent exposed. To improve the enantioselectivity of LipA in the kinetic

  3. Chiral N-Phosphonyl Imines for an Aza-Morita-Baylis-Hillman Reaction via Group-Assisted Purification (GAP) Chemistry.

    Science.gov (United States)

    Yang, Bing; Shen, Minxing; Ji, Xiaozhou; Xu, Ziyan; Sun, Hao; Jiang, Bo; Li, Guigen

    2016-03-18

    Seventeen examples of aza-Morita-Baylis-Hillman (aza-MBH) adducts have been synthesized by reacting chiral N-phosphonyl imines with acrylonitrile in good to excellent yields (up to 96%) and high diastereoselectivity (up to 99:1 dr). The synthesis of these adducts followed the method of group-assisted purification (GAP) chemistry, in which the pure aza-MBH products were readily obtained by washing the crude products with cosolvents of hexane and ethyl acetate.

  4. Conjugate addition–enantioselective protonation reactions

    Directory of Open Access Journals (Sweden)

    James P. Phelan

    2016-06-01

    Full Text Available The addition of nucleophiles to electron-deficient alkenes represents one of the more general and commonly used strategies for the convergent assembly of more complex structures from simple precursors. In this review the addition of diverse protic and organometallic nucleophiles to electron-deficient alkenes followed by enantioselective protonation is summarized. Reactions are first categorized by the type of electron-deficient alkene and then are further classified according to whether catalysis is achieved with chiral Lewis acids, organocatalysts, or transition metals.

  5. Iminium and enamine catalysis in enantioselective photochemical reactions

    Science.gov (United States)

    Hörmann, Fabian M.

    2018-01-01

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

  6. Synthesis and antiviral activity of 8-aza analogs of chiral [2-(phosphonomethoxy) propyl]guanines.

    Science.gov (United States)

    Franchetti, P; Sheikha, G A; Cappellacci, L; Grifantini, M; De Montis, A; Piras, G; Loi, A G; La Colla, P

    1995-09-29

    (R)- And (S)-8-aza-9(-)[2-(phosphonomethoxy)propyl]guanine [(R)-and (S)-8-aza-PMPG] were synthesized and tested in vitro for anti-human immunodeficiency virus (HIV) activity. The synthesis of the above compounds and of (R)-9(-)[2-(phosphonomethoxy)propyl]guanine [(R)-PMPG] was carried out through the alkylation of 8-azaguanine or guanine with (R)- and (S)-2-O(-)[(diisopropylphosphono)methyl]-1-O-(tolylsulfonyl) -1,2-propanediol followed by deprotection of the phosphonic moiety. A different, even more convenient synthesis of (R)-8-aza-PMPG starting from 2-amino-6-chloro-5-nitro-4(3H)-pyrimidinone and (R)(-)[2(-)[(diisopropylphosphono)-methoxy]propyl]amine is also reported. Both (R)-8-aza-PMPG and (R)-PMPG demonstrated anti-HIV activity in the MTT assay with EC50 values of 12 and 4.5 microM, respectively. The corresponding S enantiomers were found to be less potent. When evaluated in combination with AZT, ddI, or DABO 603, (R)-8-aza-PMPG gave additive, additive, and synergistic anti-HIV-1 effects, respectively.

  7. Examination of the Potential for Adaptive Chirality of the Nitrogen Chiral Center in Aza-Aspartame

    Directory of Open Access Journals (Sweden)

    Samir H. Bouayad-Gervais

    2013-11-01

    Full Text Available The potential for dynamic chirality of an azapeptide nitrogen was examined by substitution of nitrogen for the α-carbon of the aspartate residue in the sweetener S,S-aspartame. Considering that S,S- and R,S-aspartame possess sweet and bitter tastes, respectively, a bitter-sweet taste of aza-aspartame 9 could be indicative of a low isomerization barrier for nitrogen chirality inter-conversion. Aza-aspartame 9 was synthesized by a combination of hydrazine and peptide chemistry. Crystallization of 9 indicated a R,S-configuration in the solid state; however, the aza-residue chiral center was considerably flattened relative to its natural amino acid counterpart. On tasting, the authors considered aza-aspartame 9 to be slightly bitter or tasteless. The lack of bitter sweet taste of aza-aspartame 9 may be due to flattening from sp2 hybridization in the urea as well as a high barrier for sp3 nitrogen inter-conversion, both of which may interfere with recognition by taste receptors.

  8. Enantioselective Fluorination of Spirocyclic β-Prolinals Using Enamine Catalysis

    DEFF Research Database (Denmark)

    Fjelbye, Kasper; Marigo, Mauro; Clausen, Rasmus Prætorius

    2017-01-01

    A series of spirocyclic carbaldehydes were successfully fluorinated using enamine catalysis, furnishing the corresponding tertiary fluorides in both high yields and enantioselectivities. The fluorinated spirocycles provide a set of novel building blocks interesting from a medicinal chemistry point...

  9. Enantioselective cyclizations and cyclization cascades of samarium ketyl radicals

    Science.gov (United States)

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

    2017-12-01

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

  10. Calcium(ii)-catalyzed enantioselective conjugate additions of amines.

    Science.gov (United States)

    Uno, Brice E; Dicken, Rachel D; Redfern, Louis R; Stern, Charlotte M; Krzywicki, Greg G; Scheidt, Karl A

    2018-02-14

    The direct enantioselective chiral calcium(ii)·phosphate complex (Ca[CPA] 2 )-catalyzed conjugate addition of unprotected alkyl amines to maleimides was developed. This mild catalytic system represents a significant advance towards the general convergent asymmetric amination of α,β-unsaturated electrophiles, providing medicinally relevant chiral aminosuccinimide products in high yields and enantioselectivities. Furthermore, the catalyst can be reused directly from a previously chromatographed reaction and still maintain both high yield and selectivity.

  11. Turinese stereochemistry: Eligio Perucca's enantioselectivity and Primo Levi's asymmetry.

    Science.gov (United States)

    Kahr, Bart; Bing, Yonghong; Kaminsky, Werner; Viterbo, Davide

    2009-01-01

    A reputation restored: Eligio Perucca (see photo) first observed the enantioselective adsorption of a racemic mixture to a chiral crystal (NaClO(3)) in Turin in 1919. However, this milestone in enantioselective chemistry and chiroptics went unnoticed. Identified previously as a coward who refused in 1941 to supervise the research of the budding stereochemist Primo Levi because of the race laws, Perucca was opposed to the fascist regime.

  12. Enantioselective biotransformations of nitriles in organic synthesis.

    Science.gov (United States)

    Wang, Mei-Xiang

    2015-03-17

    The hydration and hydrolysis of nitriles are valuable synthetic methods used to prepare carboxamides and carboxylic acids. However, chemical hydration and hydrolysis of nitriles involve harsh reaction conditions, have low selectivity, and generate large amounts of waste. Therefore, researchers have confined the scope of these reactions to simple nitrile substrates. However, biological transformations of nitriles are highly efficient, chemoselective, and environmentally benign, which has led synthetic organic chemists and biotechologists to study these reactions in detail over the last two decades. In nature, biological systems degrade nitriles via two distinct pathways: nitrilases catalyze the direct hydrolysis of nitriles to afford carboxylic acids with release of ammonia, and nitrile hydratases catalyze the conversion of nitriles into carboxamides, which then furnish carboxylic acids via hydrolysis in the presence of amidases. Researchers have subsequently developed biocatalytic methods into useful industrial processes for the manufacture of commodity chemicals, including acrylamide. Since the late 1990s, research by my group and others has led to enormous progress in the understanding and application of enantioselective biotransformations of nitriles in organic synthesis. In this Account, I summarize the important advances in enantioselective biotransformations of nitriles and amides, with a primary focus on research from my laboratory. I describe microbial whole-cell-catalyzed kinetic resolution of various functionalized nitriles, amino- and hydroxynitriles, and nitriles that contain small rings and the desymmetrization of prochiral and meso dinitriles and diamides. I also demonstrate how we can apply the biocatalytic protocol to synthesize natural products and bioactive compounds. These nitrile biotransformations offer an attractive and unique protocol for the enantioselective synthesis of polyfunctionalized organic compounds that are not readily obtainable by

  13. Enantioselective Bronsted Acid Catalysis with Chiral Pentacarboxycyclopentadienes

    Science.gov (United States)

    Gheewala, Chirag

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

  14. Enantioselective disposition of clenbuterol in rats.

    Science.gov (United States)

    Hirosawa, Iori; Ishikawa, Mai; Ogino, Mio; Ito, Hiroshi; Hirao, Takuya; Yamada, Harumi; Asahi, Mariko; Kotaki, Hajime; Sai, Yoshimichi; Miyamoto, Ken-Ichi

    2014-05-01

    Clenbuterol is a long-acting β2-adrenoceptor agonist and bronchodilator that is used for the treatment of asthma, but the desired activities reside almost exclusively in the (-)-R-enantiomer. This study examined enantioselectivity in the disposition of clenbuterol following administration of clenbuterol racemate to rats. Concentrations of clenbuterol enantiomers in plasma, urine and bile were determined by LC-MS/MS assay with a Chirobiotic T column. This method was confirmed to show high sensitivity, specificity and precision, and clenbuterol enantiomers in 0.1 ml volumes of plasma were precisely quantified at concentrations as low as 0.25 ng/ml. The pharmacokinetic profiles of clenbuterol enantiomers following intravenous and intraduodenal administration of clenbuterol racemate (2 mg/kg) in rats were significantly different. The distribution volume of (-)-R-clenbuterol (9.17 l/kg) was significantly higher than that of (+)-S-clenbuterol (4.14 l/kg). The total body clearance of (-)-R-clenbuterol (13.5 ml/min/kg) was significantly higher than that of the (+)-S-enantiomer (11.5 ml/min/kg). An in situ absorption study in jejunal loops showed no difference in the residual amount between the (-)-R- and (+)-S-enantiomers. Urinary clearance was the same for the two enantiomers, but biliary excretion of (-)-R-clenbuterol was higher than that of the (+)-S-enantiomer. The fractions of free (non-protein-bound) (-)-R- and (+)-S-clenbuterol in rat plasma were 48.8% and 33.1%, respectively. These results indicated that there are differences in the distribution and excretion of the clenbuterol enantiomers, and these may be predominantly due to enantioselective protein binding. Copyright © 2013 John Wiley & Sons, Ltd.

  15. Assessing Process Mass Intensity and Waste via an "aza"-Baylis-Hillman Reaction

    Science.gov (United States)

    Go´mez-Biagi, Rodolfo F.; Dicks, Andrew P.

    2015-01-01

    A synthetic procedure is outlined where upper-level undergraduate organic chemistry students perform a two-week, semimicroscale "aza"-Baylis-Hillman reaction to generate an allylic sulfonamide product. Students evaluate several green chemistry reaction metrics of industrial importance (process mass intensity (PMI), E factor, and reaction…

  16. Preparation of alpha-5-aza-2'-deoxy-[6-3H]cytidine

    Czech Academy of Sciences Publication Activity Database

    Elbert, Tomáš; Černý, B.

    2008-01-01

    Roč. 73, č. 5 (2008), s. 701-704 ISSN 0010-0765 Institutional research plan: CEZ:AV0Z40550506 Keywords : alfa-5aza-2'-deoxy-cytidine Subject RIV: CC - Organic Chemistry Impact factor: 0.784, year: 2008

  17. Enol esters: versatile substrates for Mannich-type multicomponent reactions.

    Science.gov (United States)

    Isambert, Nicolas; Cruz, Montse; Arévalo, María José; Gómez, Elena; Lavilla, Rodolfo

    2007-10-11

    The interaction of cyclic enol esters with diversely substituted anilines and ethyl glyoxalate yields, under Sc(OTf)3 catalysis, disubstituted N-aryl lactams in a multicomponent reaction. The protocol allows access to the trans stereoisomers after an epimerization of the initial mixture in which the cis isomers predominate. Vinyl acetate yields quinoline derivatives, whereas isopropenyl acetate leads to the corresponding Mannich adducts.

  18. Synthesis of polyfluoroalkyl aza-polycyclic aromatic hydrocarbons enabled by addition of perfluoroalkyl radicals onto vinyl azides.

    Science.gov (United States)

    Wang, Yi-Feng; Lonca, Geoffroy Hervé; Le Runigo, Maïwenn; Chiba, Shunsuke

    2014-08-15

    Radical perfluoroalkylation of α-(biaryl-2-yl)vinyl azides is capable of supplying polyfluoroalkyl aza-polycyclic aromatic hydrocarbons (aza-PAHs). Commercially available Me3SiRf (Rf = CF3, C2F5, and C3F7) are employed as the sources of perfluoroalkyl radicals upon oxidation with PhI(OAc)2. The addition of perfluoroalkyl radicals to biarylvinyl azides generates the corresponding iminyl radicals, which subsequently cyclize with the intramolecular arene moiety, furnishing aza-PAH skeletons having polyfluoroalkyl (RfCH2) function.

  19. Exploring Nitrilase Sequence Space for Enantioselective Catalysis†

    Science.gov (United States)

    Robertson, Dan E.; Chaplin, Jennifer A.; DeSantis, Grace; Podar, Mircea; Madden, Mark; Chi, Ellen; Richardson, Toby; Milan, Aileen; Miller, Mark; Weiner, David P.; Wong, Kelvin; McQuaid, Jeff; Farwell, Bob; Preston, Lori A.; Tan, Xuqiu; Snead, Marjory A.; Keller, Martin; Mathur, Eric; Kretz, Patricia L.; Burk, Mark J.; Short, Jay M.

    2004-01-01

    Nitrilases are important in the biosphere as participants in synthesis and degradation pathways for naturally occurring, as well as xenobiotically derived, nitriles. Because of their inherent enantioselectivity, nitrilases are also attractive as mild, selective catalysts for setting chiral centers in fine chemical synthesis. Unfortunately, nitrilases have been reported in the scientific and patent literature, and because of stability or specificity shortcomings, their utility has been largely unrealized. In this study, 137 unique nitrilases, discovered from screening of >600 biotope-specific environmental DNA (eDNA) libraries, were characterized. Using culture-independent means, phylogenetically diverse genomes were captured from entire biotopes, and their genes were expressed heterologously in a common cloning host. Nitrilase genes were targeted in a selection-based expression assay of clonal populations numbering 106 to 1010 members per eDNA library. A phylogenetic analysis of the novel sequences discovered revealed the presence of at least five major sequence clades within the nitrilase subfamily. Using three nitrile substrates targeted for their potential in chiral pharmaceutical synthesis, the enzymes were characterized for substrate specificity and stereospecificity. A number of important correlations were found between sequence clades and the selective properties of these nitrilases. These enzymes, discovered using a high-throughput, culture-independent method, provide a catalytic toolbox for enantiospecific synthesis of a variety of carboxylic acid derivatives, as well as an intriguing library for evolutionary and structural analyses. PMID:15066841

  20. Azaña versus Telefónica : los límites del poder

    Directory of Open Access Journals (Sweden)

    Antonio Martínez Ovejero

    2004-01-01

    Full Text Available Azaña versus Telefónica, los límites del poder, pretender explicar el conflicto diplomático entre el gobierno de la II República presidido por Manuel Azaña y el de Estados Unidos, durante 1931 y 1932. El Directorio militar de Primo de Rivera otorgó, en 1924, a la Compañía Telefónica Nacional de España, filial de la norteamericana ITandT, la concesión en régimen de monopolio del servicio telefónico, por adjudicación directa, mediante un procedimiento que los republicanos consideraban ilegal e irregular, y en unas condiciones excesivamente perjudiciales para el Estado español. La coalición republicano-socialista, primero en la oposición, y, después en el gobierno, hizo de la derogación del Contrato y la nacionalización de la Telefónica, una de sus propuestas más emblemáticas. Cuando Azaña quiso llevar a la práctica esta política, se encontró con la tenaz oposición del gobierno de los EE.UU. que amenazó con interrumpir las inversiones norteamericanas en España, si el gobierno republicano llevaba a cabo su propósito.This article covers the diplomatic conflict between Azaña s Spanish Second Republican and the US Governments, from 1931 to 1932, about Telefónica, Co. subsidiary of International Telegraph and Telephone, Co, ITandT In 1924, the concession to exploit the telephonic service in Spain under a monopollstic system was granted by Primo de Rivera´s military Directorate to the «Compañía Telefónica Nacional de España» (CTNE subsidiary of ITandT This concession was consldered by the Republicans not only as illegal and irregular but also under unreasonable damaging conditions for Spain. For these reasons, the Republican - Socialist coalition took both the repeal of this concession and the nationalization of Telefónica as two ofits most emblematic proposals. Once in power, Azaña tried to Implement both of them. His government ran into the strong opposition of the American government which even threatened

  1. Pentanidium-catalyzed enantioselective phase-transfer conjugate addition reactions

    KAUST Repository

    Ma, Ting

    2011-03-09

    A new chiral entity, pentanidium, has been shown to be an excellent chiral phase-transfer catalyst. The enantioselective Michael addition reactions of tert-butyl glycinate-benzophenone Schiff base with various α,β- unsaturated acceptors provide adducts with high enantioselectivities. A successful gram-scale experiment at a low catalyst loading of 0.05 mol % indicates the potential for practical applications of this methodology. Phosphoglycine ester analogues can also be utilized as the Michael donor, affording enantioenriched α-aminophosphonic acid derivatives and phosphonic analogues of (S)-proline. © 2011 American Chemical Society.

  2. Tuning the Annulation Reactivity of Vinyl Azides and Carbazates: A Divergent Synthesis of Aza-pyrimidinones and Imidazoles.

    Science.gov (United States)

    Shao, Jiaan; Liu, Xingyu; Shu, Ke; Tang, Pai; Luo, Jing; Chen, Wenteng; Yu, Yongping

    2015-09-18

    A divergent cascade annulation has been developed using readily available vinyl azides and carbazates with a wide range of substituents. Vinyl azides were successfully applied as bifunctional partners to prepare aza-pyrimidinones via 6-ring closure with carbazates as well as to construct polyfunctionalized imidazoles via 5-ring closure with N-substituted carbazates. The aza-heterocycles were obtained with high levels of chemoselectivity and excellent yields.

  3. Equitoxic doses of 5-azacytidine and 5-aza-2'deoxycytidine induce diverse immediate and overlapping heritable changes in the transcriptome.

    Directory of Open Access Journals (Sweden)

    Xiangning Qiu

    2010-09-01

    Full Text Available The hypomethylating agent 5-Azacytidine (5-Aza-CR is the first drug to prolong overall survival in patients with myelodysplastic syndrome (MDS. Surprisingly, the deoxyribonucleoside analog 5-Aza-2'deoxycytidine (5-Aza-CdR did not have a similar effect on survival in a large clinical trial. Both drugs are thought to exert their effects after incorporation into DNA by covalent binding of DNA methyltransferase (DNMT. While 5-Aza-CdR is incorporated into only DNA, 5-Aza-CR is also incorporated into RNA. Here, we have analyzed whether this difference in nucleic acid incorporation may influence the capacities of these drugs to regulate the expression of mRNA and microRNAs (miRNA, which may potentially affect the activities of the drugs in patients.A hematopoietic (HL-60; acute myeloid leukemia and a solid (T24; transitional cell carcinoma cancer cell line were treated with equitoxic doses of 5-Aza-CR and 5-Aza-CdR for 24 hrs, and the immediate (day 2 and lasting (day 8 effects on RNA expression examined. There was considerable overlap between the RNAs heritably upregulated by both drugs on day 8 but more RNAs were stably induced by the deoxy analog. Both drugs strongly induced expression of cancer testis antigens. On day 2 more RNAs were downregulated by 5-Aza-CR, particularly at higher doses. A remarkable downregulation of miRNAs and a significant upregulation of tRNA synthetases and other genes involved in amino acid metabolism was observed in T24 cells.Overall, this suggests that significant differences exist in the immediate action of the two drugs, however the dominant pattern of the lasting, and possible heritable changes, is overlapping.

  4. Methods for the synthesis of aza(deaza)xanthines as a basis of biologically active compounds

    International Nuclear Information System (INIS)

    Babkov, D A; Geisman, A N; Novikov, M S; Khandazhinskaya, A L

    2016-01-01

    The review covers methods for the synthesis of aza(deaza)xanthines, i.e., fused pyrrolo-, pyrazolo- and triazolopyrimidine heterocyclic systems, which are common core structures of various biologically active compounds. The extensive range of modern synthetic approaches is organized according to target structures and starting building blocks. The presented material is intended to benefit broad audience of specialists in the fields of organic, medicinal and pharmaceutical chemistry. The bibliography includes 195 references

  5. An Efficient One-Pot Multicomponent Synthesis of 4-Aza-Podophyllotoxin Derivatives in Ionic Liquid

    Directory of Open Access Journals (Sweden)

    Hossein Naeimi

    2013-01-01

    Full Text Available A simple, green, and efficient procedure for the synthesis of 4-aza-podophyllotoxin derivatives by using a one-pot three-component reaction of benzaldehydes, 1,3-cyclohexanediones, and anilinolactones in the presence of catalytic amount of alum in 1-butyl-3-methylimidazolium triflate as green media is described. This reaction proceeded under mild conditions with the use of an inexpensive and readily available catalyst, high to excellent yields, and simple workup procedure.

  6. Methods for the synthesis of aza(deaza)xanthines as a basis of biologically active compounds

    Science.gov (United States)

    Babkov, D. A.; Geisman, A. N.; Khandazhinskaya, A. L.; Novikov, M. S.

    2016-03-01

    The review covers methods for the synthesis of aza(deaza)xanthines, i.e., fused pyrrolo-, pyrazolo- and triazolopyrimidine heterocyclic systems, which are common core structures of various biologically active compounds. The extensive range of modern synthetic approaches is organized according to target structures and starting building blocks. The presented material is intended to benefit broad audience of specialists in the fields of organic, medicinal and pharmaceutical chemistry. The bibliography includes 195 references.

  7. Hypomethylating agent 5-aza-2'-deoxycytidine (DAC) ameliorates multiple sclerosis in mouse models

    DEFF Research Database (Denmark)

    Mangano, Katia; Fagone, Paolo; Bendtzen, Klaus

    2014-01-01

    Increasing evidence supports the role of epigenetics in the development of autoimmune disorders and the possibility of using epigenetic modifying drugs in the context of MS has not yet been investigated. We have explored the effect of the hypomethylating agent 5-aza-2'-deoxycytidine (DAC) in two ....... Finally, DAC treatment increased the percentage of circulating regulatory T cells by inducing Foxp3 expression via demethylation of a CpG island in Foxp3....

  8. Phosphorescence for Sensitive Enantioselective Detection in Chiral Capillary Electrophoresis

    NARCIS (Netherlands)

    Lammers, I.; Buijs, J.; van der Zwan, G.; Ariese, F.; Gooijer, C.

    2009-01-01

    Enantioselective phosphorescence lifetime detection was combined with chiral cyclodextrin-based electrokinetic chromatography for the analysis of camphorquinone (CQ). A time-gated detection system based on a pulsed light-emitting diode for excitation at 465 nm was developed for the online lifetime

  9. Enantioselective Symmetry Breaking Directed by the Order of Process Steps

    NARCIS (Netherlands)

    Noorduin, Wim L.; Meekes, Hugo; Enckevort, Willem J.P. van; Kaptein, Bernard; Kellogg, Richard M.; Vlieg, Elias

    2010-01-01

    Going forward in reverse: The configuration of the product of grinding-induced symmetry breaking can be controlled simply by the order in which the different reaction-mixture components are combined. The underlying mechanism is based on a subtle balance between enantioselective crystal growth and

  10. Schiff base complex-catalysed enantioselective epoxidation of ...

    Indian Academy of Sciences (India)

    Administrator

    Chiral Ru(II) Schiff base complex-catalysed enantioselective epoxidation of styrene derivatives. R I KURESHY, N H KHAN, S H R ABDI, S T PATEL, P IYER and. R V JASRA. Silicates and Catalysis Discipline, Central Salt and Marine Chemicals. Research Institute, Bhavnagar 364 002, India. Ruthenium(II) chiral Schiff base ...

  11. DNA and RNA induced enantioselectivity in chemical synthesis

    NARCIS (Netherlands)

    Roelfes, Gerard

    One of the hallmarks of DNA and RNA structures is their elegant chirality. Using these chiral structures to induce enantioselectivity in chemical synthesis is as enticing as it is challenging. In recent years, three general approaches have been developed to achieve this, including chirality transfer

  12. Organocatalytic highly enantioselective synthesis of secondary alpha-hydroxyphosphonates.

    Science.gov (United States)

    Dodda, Rajasekhar; Zhao, Cong-Gui

    2006-10-12

    [reaction: see text] The first organocatalytic cross aldol reaction of ketones and diethyl formylphosphonate hydrate has been realized by using readily available l-prolinamide as the catalyst. Secondary alpha-hydroxyphosphonates have been synthesized in high enantioselective (up to >99% ee) and good diastereoselectivity.

  13. Organocatalytic Highly Enantioselective Synthesis of Secondary α-Hydroxyphosphonates†

    Science.gov (United States)

    Dodda, Rajasekhar; Cong-Gui, Zhao

    2008-01-01

    The first organocatalytic cross aldol reaction of ketones and diethyl formylphosphonate hydrate has been realized by using readily available L-prolinamide as the catalyst. Secondary α-hydroxyphosphonates have been synthesized in high enantioselective (up to >99% ee) and good diastereoselectivity. PMID:17020334

  14. Enantioselective Phytotoxicity and the Relative Mechanism of Current Chiral Herbicides.

    Science.gov (United States)

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

    2017-01-01

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

  15. Guanidine-catalyzed enantioselective desymmetrization of meso-aziridines

    KAUST Repository

    Zhang, Yan

    2011-01-01

    An amino-indanol derived chiral guanidine was developed as an efficient Brønsted base catalyst for the desymmetrization of meso-aziridines with both thiols and carbamodithioic acids as nucleophiles, which provided 1,2-difunctionalized ring-opened products in high yields and enantioselectivities. © The Royal Society of Chemistry.

  16. A Green Enantioselective Aldol Condensation for the Undergraduate Organic Laboratory

    Science.gov (United States)

    Bennett, George D.

    2006-01-01

    A number of laboratory exercises for the organic chemistry curriculum that emphasize enantioselective synthesis of the aldol condensation which involves the proline-catalyzed condensation between acetone and isobutyraldehyde are explored. The experiment illustrates some of the trade-offs involved in green chemistry like the use of acetone in large…

  17. Global demethylation of rat chondrosarcoma cells after treatment with 5-aza-2'-deoxycytidine results in increased tumorigenicity.

    Directory of Open Access Journals (Sweden)

    Christopher A Hamm

    Full Text Available Abnormal patterns of DNA methylation are observed in several types of human cancer. While localized DNA methylation of CpG islands has been associated with gene silencing, the effect that genome-wide loss of methylation has on tumorigenesis is not completely known. To examine its effect on tumorigenesis, we induced DNA demethylation in a rat model of human chondrosarcoma using 5-aza-2-deoxycytidine. Rat specific pyrosequencing assays were utilized to assess the methylation levels in both LINEs and satellite DNA sequences following 5-aza-2-deoxycytidine treatment. Loss of DNA methylation was accompanied by an increase in invasiveness of the rat chondrosarcoma cells, in vitro, as well as by an increase in tumor growth in vivo. Subsequent microarray analysis provided insight into the gene expression changes that result from 5-aza-2-deoxycytidine induced DNA demethylation. In particular, two genes that may function in tumorigenesis, sox-2 and midkine, were expressed at low levels in control cells but upon 5-aza-2-deoxycytidine treatment these genes became overexpressed. Promoter region DNA analysis revealed that these genes were methylated in control cells but became demethylated following 5-aza-2-deoxycytidine treatment. Following withdrawal of 5-aza-2-deoxycytidine, the rat chondrosarcoma cells reestablished global DNA methylation levels that were comparable to that of control cells. Concurrently, invasiveness of the rat chondrosarcoma cells, in vitro, decreased to a level indistinguishable to that of control cells. Taken together these experiments demonstrate that global DNA hypomethylation induced by 5-aza-2-deoxycytidine may promote specific aspects of tumorigenesis in rat chondrosarcoma cells.

  18. Effects of 5-aza-2′deoxycytidine on RECK gene expression and tumor invasion in salivary adenoid cystic carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, X.Q. [Department of Oral and Maxillofacial Surgery, School of Stomatology, Shandong University, Jinan (China); Department of Oral and Maxillofacial Surgery, The First People' s Hospital of Jining, Shandong (China); Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital, Affiliated to Shandong University, Jinan (China); Huang, S.Y. [Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital, Affiliated to Shandong University, Jinan (China); Zhang, D.S. [Department of Oral and Maxillofacial Surgery, School of Stomatology, Shandong University, Jinan (China); Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital, Affiliated to Shandong University, Jinan (China); Zhang, S.Z.; Li, W.G.; Chen, Z.W.; Wu, H.W. [Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital, Affiliated to Shandong University, Jinan (China)

    2014-12-12

    Reversion-inducing cysteine-rich protein with kazal motifs (RECK), a novel tumor suppressor gene that negatively regulates matrix metalloproteinases (MMPs), is expressed in various normal human tissues but downregulated in several types of human tumors. The molecular mechanism for this downregulation and its biological significance in salivary adenoid cystic carcinoma (SACC) are unclear. In the present study, we investigated the effects of a DNA methyltransferase (DNMT) inhibitor, 5-aza-2′deoxycytidine (5-aza-dC), on the methylation status of the RECK gene and tumor invasion in SACC cell lines. Methylation-specific PCR (MSP), Western blot analysis, and quantitative real-time PCR were used to investigate the methylation status of the RECK gene and expression of RECK mRNA and protein in SACC cell lines. The invasive ability of SACC cells was examined by the Transwell migration assay. Promoter methylation was only found in the ACC-M cell line. Treatment of ACC-M cells with 5-aza-dC partially reversed the hypermethylation status of the RECK gene and significantly enhanced the expression of mRNA and protein, and 5-aza-dC significantly suppressed ACC-M cell invasive ability. Our findings showed that 5-aza-dC inhibited cancer cell invasion through the reversal of RECK gene hypermethylation, which might be a promising chemotherapy approach in SACC treatment.

  19. Development of catalysts and ligands for enantioselective gold catalysis.

    Science.gov (United States)

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

    2014-03-18

    During the past decade, the use of Au(I) complexes for the catalytic activation of C-C π-bonds has been investigated intensely. Over this time period, the development of homogeneous gold catalysis has been extraordinarily rapid and has yielded a host of mild and selective methods for the formation of carbon-carbon and carbon-heteroatom bonds. The facile formation of new bonds facilitated by gold naturally led to efforts toward rendering these transformations enantioselective. In this Account, we survey the development of catalysts and ligands for enantioselective gold catalysis by our research group as well as related work by others. We also discuss some of our strategies to address the challenges of enantioselective gold(I) catalysis. Early on, our work with enantioselective gold-catalyzed transformations focused on bis(phosphinegold) complexes derived from axially chiral scaffolds. Although these complexes were highly successful in some reactions like cyclopropanation, the careful choice of the weakly coordinating ligand (or counterion) was necessary to obtain high levels of enantioselectivity for the case of allene hydroamination. These counterion effects led us to use the anion itself as a source of chirality, which was successful in the case of allene hydroalkoxylation. In general, these tactics enhance the steric influence around the reactive gold center beyond the two-coordinate ligand environment. The use of binuclear complexes allowed us to use the second gold center and its associated ligand (or counterion) to exert a further steric influence. In a similar vein, we employed a chiral anion (in place of or in addition to a chiral ligand) to move the chiral information closer to the reactive center. In order to expand the scope of reactions amenable to enantioselective gold catalysis to cycloadditions and other carbocyclization processes, we also developed a new class of mononuclear phosphite and phosphoramidite ligands to supplement the previously widely

  20. Enantioselective conjugate addition of diethylzinc to chalcone catalyzed by Co(acac)2 and chiral amino alcohols

    NARCIS (Netherlands)

    Vries, André H.M. de; Feringa, Bernard

    1997-01-01

    Co(acac)2 in the presence of chiral ligands has been employed as catalyst for the enantioselective conjugate addition of diethylzinc to chalcone. With chiral amino alcohols derived from (+)-camphor, enantioselectivities up to 83% were achieved.

  1. Aza-annulation of enynyl azides: a new approach to substituted pyridines.

    Science.gov (United States)

    Reddy, Chada Raji; Panda, Sujatarani A; Reddy, Motatipally Damoder

    2015-02-20

    Synthesis of substituted pyridines through a novel aza-annulation of 2-en-4-ynyl azides, derived from MBH-acetates of acetylenic aldehydes, is described. A variety of enynyl azides having aryl, heteroaryl, and alkyl groups on the alkyne functionality successfully participated in the Ag-mediated annulation reaction to provide the corresponding 3,6-disubstituted pyridines. I2-mediated cyclization was found to be controlled by the substituent on the alkyne functionality, which offered the 5-iodo-3,6-disubstituted pyridines from enynyl azides having an electron-rich substituent on the alkyne functionality.

  2. Nitrogen-Containing Coronenes: Theoretical Evaluation of the Influence of Aza-substitution on their Aromaticity

    Science.gov (United States)

    Pop, Raluca; van Staden, Jacobus; Diudea, Mircea

    2015-03-01

    The aromaticity of coronene derivatives where two C atoms of each outer six-membered ring are replaced by N have been investigated. Three types of substitution, namely 1,2-, 1,3-, and 1,4- are proposed. Computations of the geometric (HOMA index), energetic (HOMO-LUMO gap), and magnetic indices (NICS(0) and NICS(1)) were performed, and the results compared to the ones obtained for the all-carbon species. The results outline that the aza-derivatives have aromatic character comparable to the all-carbon species and an enlarged HOMO-LUMO gap.

  3. Molecular Rearrangement of an Aza-Scorpiand Macrocycle Induced by pH: A Computational Study

    Directory of Open Access Journals (Sweden)

    Jesus Vicente De Julián-Ortiz

    2016-07-01

    Full Text Available Rearrangements and their control are a hot topic in supramolecular chemistry due to the possibilities that these phenomena open in the design of synthetic receptors and molecular machines. Macrocycle aza-scorpiands constitute an interesting system that can reorganize their spatial structure depending on pH variations or the presence of metal cations. In this study, the relative stabilities of these conformations were predicted computationally by semi-empirical and density functional theory approximations, and the reorganization from closed to open conformations was simulated by using the Monte Carlo multiple minimum method.

  4. BINOL Macrocycle Derivatives: Synthesis of New Dinaphthyl Sulfide Aza Oxa Thia Crowns (Lariats

    Directory of Open Access Journals (Sweden)

    Abbas Shockravi

    2013-01-01

    Full Text Available In this research work, dinaphthyl sulfide diester was prepared from the reaction of 1,1′-thiobis (2-hydroxy naphthalene and methylchloroacetate. Its aza-macrocyclic derivative was synthesized from the reaction of dinaphthyl sulfide diester and diethylenetriamine. Lariats were prepared from the reaction of chloroamides (four derivatives and initial macrocycle. Chloroamides were synthesized from the reaction of amines (aniline, benzylamine, 8-amino quinoline and 4-amino azobenzene and chloroacetyl chloride. All the materials were identified by IR, 1H NMR, 13C NMR, and mass spectroscopies, and elemental analysis.

  5. Aza-Michael Mono-addition Using Acidic Alumina under Solventless Conditions

    Directory of Open Access Journals (Sweden)

    Giovanna Bosica

    2016-06-01

    Full Text Available Aza-Michael reactions between primary aliphatic and aromatic amines and various Michael acceptors have been performed under environmentally-friendly solventless conditions using acidic alumina as a heterogeneous catalyst to selectively obtain the corresponding mono-adducts in high yields. Ethyl acrylate was the main acceptor used, although others such as acrylonitrile, methyl acrylate and acrylamide were also utilized successfully. Bi-functional amines also gave the mono-adducts in good to excellent yields. Such compounds can serve as intermediates for the synthesis of anti-cancer and antibiotic drugs.

  6. Protecting-Group-Free Synthesis of 2-Deoxy-Aza-Sugars

    Directory of Open Access Journals (Sweden)

    Mattie Simon Maria Timmer

    2009-12-01

    Full Text Available The protecting-group-free asymmetric synthesis of 1,2,4-trideoxy-1,4-imino-L-xylitol is readily achieved in five steps from 2-deoxy-D-ribose and with an overall yield of 48%. Key in this synthesis is the application of our recently developed Vasella-reductive amination and carbamate annulation methodologies to the synthesis of 2-deoxy-aza-sugars. The carbamate annulation occurred with excellent yield and diastereoselectively (>20:1 d.r., in favour of the 3,4-cis isomer.

  7. Enantioselective Epoxide Polymerization Using a Bimetallic Cobalt Catalyst

    KAUST Repository

    Thomas, Renee M.

    2010-11-24

    A highly active enantiopure bimetallic cobalt complex was explored for the enantioselective polymerization of a variety of monosubstituted epoxides. The polymerizations were optimized for high rates and stereoselectivity, with s-factors (kfast/kslow) for most epoxides exceeding 50 and some exceeding 300, well above the threshold for preparative utility of enantiopure epoxides and isotactic polyethers. Values for mm triads of the resulting polymers are typically greater than 95%, with some even surpassing 98%. In addition, the use of a racemic catalyst allowed the preparation of isotactic polyethers in quantitative yields. The thermal properties of these isotactic polyethers are presented, with many polymers exhibiting high T m values. This is the first report of the rapid synthesis of a broad range of highly isotactic polyethers via the enantioselective polymerization of racemic epoxides. © 2010 American Chemical Society.

  8. Enantioselective Polyene Cyclization via Organo-SOMO Catalysis

    Science.gov (United States)

    Rendler, Sebastian; MacMillan, David W. C.

    2010-01-01

    The first organocatalytic enantioselective radical polycyclization has been accomplished using singly occupied molecular orbital (SOMO) catalysis. The presented strategy relies on a selective single-electron oxidation of chiral enamines formed by condensation of polyenals with an imidazolidinone catalyst employing a suitable copper(II) oxidant. The reaction proceeds under mildly acidic conditions at room temperature and shows compatibility with an array of electron-poor as well as electron-rich functional groups. Upon termination by radical arylation, followed by subsequent oxidation and rearomatization, a range of polycyclic aldehydes has been accessed (12 examples, 54-77% yield, 85-93% ee). The enantioselective formation of up to six new carbocycles in a single catalyst-controlled cascade is described. Evidence for a radical-based cascade mechanism is indicated by a series of experimental results. PMID:20334384

  9. Enantioselective degradation of tebuconazole in cabbage, cucumber, and soils.

    Science.gov (United States)

    Wang, Xinquan; Wang, Xuesong; Zhang, Hu; Wu, Changxing; Wang, Xiangyun; Xu, Hao; Wang, Xiaofu; Li, Zhen

    2012-02-01

    The enantioselective degradation of tebuconazole has been investigated to elucidate the behaviors in agricultural soils, cabbage, and cucumber fruit. Rac-tebuconazole was fortified into three types of agricultural soils and sprayed foliage of cabbage and cucumber, respectively. The degradation kinetics, enantiomer fraction and enantiomeric selectivity were determined by reverse-phase high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) on a Lux amylose-2 chiral column. The process of the degradation of tebuconazole enantiomers followed first-order kinetic in the test soils and vegetables. It has been shown that the degradation of tebuconazole was enantioselective. The results indicated that the (+)-S-tebuconazole showed a faster degradation in cabbage, while the (-)-R-tebuconazole dissipated faster than (+)-S-form in cucumber fruit and the test soils. Copyright © 2011 Wiley-Liss, Inc.

  10. Enantioselective enzymic reduction of a prochiral cyclic ketone using yeasts

    Czech Academy of Sciences Publication Activity Database

    Wimmer, Zdeněk; Zarevúcka, Marie; Reitmayerová, Pavla

    2003-01-01

    Roč. 97, č. 6 (2003), s. 466-467 ISSN 0009-2770. [International Symposium on Biocatalysis and Biotransformations /6./. 28.06.2003-03.07.2003, Olomouc] R&D Projects: GA AV ČR IBS4055104; GA ČR GA203/02/0166 Institutional research plan: CEZ:AV0Z4055905 Keywords : enantioselective enzymic reduction Subject RIV: CC - Organic Chemistry

  11. Phosphathiahelicenes: synthesis and uses in enantioselective gold catalysis.

    Science.gov (United States)

    Aillard, Paul; Voituriez, Arnaud; Dova, Davide; Cauteruccio, Silvia; Licandro, Emanuela; Marinetti, Angela

    2014-09-22

    Enantiomerically pure thiahelicenes displaying a terminal phosphole unit and a stereogenic phosphorus center have been prepared by oxidative photocyclization of a diaryl-olefin precursor. Starting from one of these phosphathiahelicene oxides, the corresponding trivalent phosphine-Au(I) complex is obtained with complete diastereoselectivity. It affords a new, excellent precatalyst for the enantioselective cycloisomerization of N-tethered enynes (up to 96 % ee). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Organocatalytic High Enantioselective Synthesis of β-Formyl-α-hydroxyphosphonates

    Science.gov (United States)

    Perera, Sandun; Naganaboina, Vijaya Kumar; Wang, Long; Zhang, Bin; Guo, Qunsheng; Rout, Laxmidhar; Zhao, Cong-Gui

    2011-01-01

    The cross aldol reaction between enolizable aldehydes and α-ketophosphonates was achieved for the first time by using 9-amino-9-deoxy-epi-quinine as the catalyst. β-Formyl-α-hydroxyphosphonates were obtained in high to excellent enantioselectivities. The reaction works especially well with acetaldehyde, which is a tough substrate for organocatalyzed cross aldol reactions. The products were demonstrated to have anticancer activities. PMID:21918646

  13. Organocatalytic High Enantioselective Synthesis of β-Formyl-α-hydroxyphosphonates.

    Science.gov (United States)

    Perera, Sandun; Naganaboina, Vijaya Kumar; Wang, Long; Zhang, Bin; Guo, Qunsheng; Rout, Laxmidhar; Zhao, Cong-Gui

    2011-06-30

    The cross aldol reaction between enolizable aldehydes and α-ketophosphonates was achieved for the first time by using 9-amino-9-deoxy-epi-quinine as the catalyst. β-Formyl-α-hydroxyphosphonates were obtained in high to excellent enantioselectivities. The reaction works especially well with acetaldehyde, which is a tough substrate for organocatalyzed cross aldol reactions. The products were demonstrated to have anticancer activities.

  14. The enantioselective b-keto ester reductions by Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    HASSAN TAJIK

    2006-09-01

    Full Text Available The enantioselective yeast reduction of aromatic b-keto esters, by use of potassium dihydrogen phosphate, calcium phosphate (monobasic, magnesium sulfate and ammonium tartrate (diammonium salt (10:1:1:50 in water at pH 7 as a buffer for 72–120 h with 45–90 % conversion to the corresponding aromatic -hydroxy esters was achieved by means of Saccharomyces cerevisiae.

  15. Enhancing the potential of enantioselective organocatalysis with light

    Science.gov (United States)

    Silvi, Mattia; Melchiorre, Paolo

    2018-02-01

    Organocatalysis—catalysis mediated by small chiral organic molecules—is a powerful technology for enantioselective synthesis, and has extensive applications in traditional ionic, two-electron-pair reactivity domains. Recently, organocatalysis has been successfully combined with photochemical reactivity to unlock previously inaccessible reaction pathways, thereby creating new synthetic opportunities. Here we describe the historical context, scientific reasoning and landmark discoveries that were essential in expanding the functions of organocatalysis to include one-electron-mediated chemistry and excited-state reactivity.

  16. Highly Efficient Synthesis of Allopurinol Locked Nucleic Acid Monomer by C6 Deamination of 8-Aza-7-bromo-7-deazaadenine Locked Nucleic Acid Monomer

    DEFF Research Database (Denmark)

    Kosbar, Tamer Reda El-Saeed; Sofan, M.; Abou-Zeid, L.

    2013-01-01

    An allopurinol locked nucleic acid (LNA) monomer was prepared by a novel strategy through C6 deamination of the corresponding 8-aza-7-bromo-7-deazaadenine LNA monomer with aqueous sodium hydroxide. An 8-aza-7-deazaadenine LNA monomer was also synthesized by a modification of the new synthetic...

  17. Cyclodextrin Derivatives as Chiral Supramolecular Receptors for Enantioselective Sensing

    Directory of Open Access Journals (Sweden)

    Uwe Pieles

    2006-06-01

    Full Text Available In view of the chiral nature of many bio-molecules (and all bio-macromolecules,most of therapeutically active compounds which target these molecules need to be chiraland “good handed” to be effective. In addition to asymmetric synthetic and separationmethodologies, enantioselective chemical sensors, able to distinguish between twoenantiomers of the same molecule, are of relevance. In order to design these sensing tools,two major classes of enantioselective layers have been developed. The first is based onmolecularly imprinted polymers which are produced (polymerized in the presence of theirtarget, thus the polymeric material keep in “memory” the size and the shape of this moleculeand the system could be used for sensing (not reviewed here. The second approach makesuse of sensitive layers containing chiral macrocyclic receptors able of stereoselectivemolecular recognition; these receptors are mainly based on cyclodextrins. In thiscontribution, are reviewed achievements in the use of native or chemically modifiedcyclodextrins for chiral sensing purposes (at interfaces. Potentialities of other chiralmacrocycles based on calixarenes, calix-resorcinarenes or crown-ethers as supramolecularreceptors for enantioselective sensing are discussed.

  18. Enantiomerization and enantioselective bioaccumulation of metalaxyl in Tenebrio molitor larvae.

    Science.gov (United States)

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

    2014-02-01

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

  19. Equitoxic Doses of 5-Azacytidine and 5-Aza-2 ′ Deoxycytidine Induce Diverse Immediate and Overlapping Heritable Changes in the Transcriptome

    DEFF Research Database (Denmark)

    Qiu, X.; Hother, C.; Ralfkiær, U. M.

    2010-01-01

    influence the capacities of these drugs to regulate the expression of mRNA and microRNAs (miRNA), which may potentially affect the activities of the drugs in patients. METHODOLOGY/PRINCIPAL FINDINGS: A hematopoietic (HL-60; acute myeloid leukemia) and a solid (T24; transitional cell carcinoma) cancer cell......BACKGROUND: The hypomethylating agent 5-Azacytidine (5-Aza-CR) is the first drug to prolong overall survival in patients with myelodysplastic syndrome (MDS). Surprisingly, the deoxyribonucleoside analog 5-Aza-2'deoxycytidine (5-Aza-CdR) did not have a similar effect on survival in a large clinical...... trial. Both drugs are thought to exert their effects after incorporation into DNA by covalent binding of DNA methyltransferase (DNMT). While 5-Aza-CdR is incorporated into only DNA, 5-Aza-CR is also incorporated into RNA. Here, we have analyzed whether this difference in nucleic acid incorporation may...

  20. Crystal structure of 2-(aza­niumylmeth­yl)pyridinium bis(hydrogen squarate)

    Science.gov (United States)

    Salamzadeh, Nina; Demircioglu, Zeynep; Korkmaz, Ufuk; Büyükgüngör, Orhan

    2017-01-01

    The asymmetric unit of the title compound, C6H10N2 2+·2C4HO4 −, comprises two hydrogen squarate (Hsq−; systematic name: 2-hy­droxy-3,4-dioxo­cyclo­butano­late) anions and a 2-(aza­niumylmeth­yl)pyridinium dication. The squaric acid mol­ecules each donate an H atom to the N atoms of the pyridine ring and the amino­methyl units of a 2-(amino­meth­yl)pyridine mol­ecule, forming the 1:2 salt. The Hsq− anions are linked by strong O—H⋯O hydrogen bonds and an N—H⋯O hydrogen bond links the 2-(aza­niumylmeth­yl)pyridinium cation to one of the squaric acid anions. The crystal structure features additional N—H⋯O and O—H⋯O hydrogen bonds, π–π stacking and unusual weak C—O⋯π(ring) inter­actions. PMID:28435726

  1. Enantioselective α-Arylation of Carbonyls via Cu(I)-Bisoxazoline Catalysis

    Science.gov (United States)

    Harvey, James S.; Simonovich, Scott P.; Jamison, Christopher R.; MacMillan, David W. C.

    2011-01-01

    The enantioselective α-arylation of both lactones and acyl oxazolidones has been accomplished using a combination of diaryliodonium salts and copper catalysis. These mild catalytic conditions provide a new strategy for the enantioselective construction and retention of enolizable α-carbonyl benzylic stereocenters, a valuable synthon for the production of medicinal agents. PMID:21848265

  2. Enantioselective 1,2-Difunctionalization of 1,3-Butadiene by Sequential Alkylation and Carbonyl Allylation.

    Science.gov (United States)

    Xiong, Yang; Zhang, Guozhu

    2018-02-28

    A highly enantioselective three-component coupling of 1,3-butadiene with a variety of fluorinated or nonfluorinated alkyl halides and aldehydes has been achieved relying on a Cr/Co bimetallic catalysis system. The strategy established here facilitates straightforward introduction of the privileged fluoro functionalities into homoallylic alcohols from bulk feedstock materials in a highly anti-diastereo and enantioselective manner.

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

    Science.gov (United States)

    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.

  4. Catalytic enantioselective syn hydration of enones in water using a DNA-based catalyst

    NARCIS (Netherlands)

    Boersma, Arnold J.; Coquière, David; Geerdink, Danny; Rosati, Fiora; Roelfes, Gerard; Feringa, Bernard

    2010-01-01

    The enantioselective addition of water to olefins in an aqueous environment is a common transformation in biological systems, but was beyond the ability of synthetic chemists. Here, we present the first examples of a non-enzymatic catalytic enantioselective hydration of enones, for which we used a

  5. Enantioselective Copper-Catalyzed Arylation-Driven Semipinacol Rearrangement of Tertiary Allylic Alcohols with Diaryliodonium Salts.

    Science.gov (United States)

    Lukamto, Daniel H; Gaunt, Matthew J

    2017-07-12

    A copper-catalyzed enantioselective arylative semipinacol rearrangement of allylic alcohols using diaryliodonium salts is reported. Chiral Cu(II)-bisoxazoline catalysts initiate an electrophilic alkene arylation, triggering a 1,2-alkyl migration to afford a range of nonracemic spirocyclic ketones with high yields, diastereo- and enantioselectivities.

  6. An effective enantioselective approach to the securinega alkaloids: total synthesis of (-)-norsecurinine.

    Science.gov (United States)

    Alibés, Ramón; Bayón, Pau; de March, Pedro; Figueredo, Marta; Font, Josep; García-García, Elena; González-Gálvez, David

    2005-10-27

    [reaction: see text] A highly versatile approach to the enantioselective synthesis of securinega alkaloids is presented. Crucial steps are a palladium-catalyzed enantioselective imide alkylation, a vinylogous Mannich reaction, and a ring-closing metathesis process. Through this strategy, the synthesis of (-)-norsecurinine has been accomplished in nine steps and 11% overall yield.

  7. Copper-catalyzed enantioselective conjugate addition of organometallic reagents to acyclic dienones

    NARCIS (Netherlands)

    Sebesta, Radovan; Pizzuti, M. Gabriella; Minnaard, Adriaan J.; Feringa, Ben L.; Šebesta, Radovan

    The enantioselective, copper/phosphoramidite-catalyzed 1,4-addition of dialkylzinc reagents to acyclic dienones is described. The products of this reaction, obtained with enantioselectivities of up to 95%, can be further functionalized by a second conjugate addition, or employed in an enolate

  8. A One-Pot Oxidation/Enantioselective Oxa-Michael Cascade

    NARCIS (Netherlands)

    Willemsen, Jorgen S.; Megens, Rik P.; Roelfes, Gerard; van Hest, Jan C. M.; Rutjes, Floris P. J. T.

    A laccase/(2,2,6,6-tetramethylpiperidin-1-yl)oxy (TEMPO) mediated oxidation was combined with an aqueous, enantioselective copper-catalyzed Michael addition reaction of water in one pot. The copper catalyst was also immobilized onto DNA to induce enantioselectivity in the reaction. Low conversions

  9. Enhancement of the enantioselectivity of carboxylesterase A by structure-based mutagenesis

    NARCIS (Netherlands)

    Godinho, Luis F.; Reis, Carlos R.; Rozeboom, Henriette J.; Dekker, Frank J.; Dijkstra, Bauke W.; Poelarends, Gerrit J.; Quax, Wim J.

    2012-01-01

    Previously studied Bacillus subtilis carboxylesterases (CesA and CesB) have potential for the kinetic resolution of racemic esters of 1,2-O-isopropylideneglycerol (IPG). CesA exhibits high activity but low enantioselectivity towards IPG-butyrate and IPG-caprylate, while the more enantioselective

  10. Solvent-free, catalyst-free aza-Michael addition of cyclohexylamine to diethyl maleate: reaction mechanism and kinetics

    Czech Academy of Sciences Publication Activity Database

    Bláha, Michal; Trhlíková, Olga; Podešva, Jiří; Abbrent, Sabina; Steinhart, Miloš; Dybal, Jiří; Dušková-Smrčková, Miroslava

    2018-01-01

    Roč. 74, č. 1 (2018), s. 58-67 ISSN 0040-4020 Institutional support: RVO:61389013 Keywords : Aza-Michael addition * solvent-free * catalyst-free Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 2.651, year: 2016

  11. Enzyme active site mimics based on TriAzaCyclophane (TAC)-scaffolded peptides and amino acid residues

    NARCIS (Netherlands)

    Albada, H.B.

    2009-01-01

    This thesis describes the scope and limitations of the application of TriAzaCyclophane (TAC)-scaffolded peptides or amino acid residues as enzyme active site mimics, as ligands in asymmetric catalysis and as hydrolysis catalysts attached to vancomycin. For the mimicry of functional group enzymes, of

  12. Simultaneous determination of biotoxins DSP and AZAs in bivalve molluscs and fish by liquid chromatography/tandem mass spectrometry.

    Science.gov (United States)

    Zhuo, Liyang; Fu, Wusheng; Yang, Yiqiang; Qiu, Bin; Lin, Zhenyu; Shan, Liyang; Zheng, Lemin; Li, Jianrong; Chen, Guonan

    2014-07-15

    A method has been developed for simultaneous determination of the toxins OA, DTX-1, AZA-1, AZA-2 and AZA-3 in various aquatic products as these can cause diarrhoetic shellfish poisoning (DSP) in humans, an intoxication characterized by vomiting and diarrhea. Separation of the toxins was achieved on a C18 column (150 mm × 2.1 mm, 3.5 µm) using an acetonitrile/water gradient with formic acid as an eluent modifier. Electrospray ionisation (ESI) in negative mode was used to generate the molecule related ion [M-H](-), for OA and DTX-1, while ESI in positive mode was used to generate the molecule related ion [M+H](+) for AZAs. Samples were extracted with 80% methanol, followed by partitioning with ethyl acetate, purified on a Poly-Sery MAX cartridge and finally analyzed by LC/ESI-MS/MS in the multiple reaction monitoring (MRM) mode. The limit of detection (LOD) and limit of qualification (LOQ) of the method were in the range of 0.02-0.79 µg/kg and 0.07-2.64 µg/kg in Scomberomorus niphonius, blood clam and oyster, respectively, recoveries of the toxins at three fortification levels ranged from 71.3% to 104.8% with relative standard deviation from 1.0% to 12.5%. The calibration curves were well linear between the LC peak area of the selected ion pair and the concentration of the toxins, with the correlation coefficient over 0.99. The method was sufficiently sensitive to permit the determination of the toxins DSP and AZA in sea food. Copyright © 2014 John Wiley & Sons, Ltd.

  13. Azacoccones A-E, five new aza-epicoccone derivatives from Aspergillus flavipes.

    Science.gov (United States)

    Zou, Shupeng; Wang, Zhongbo; Wang, Jing; Wei, Guangzheng; Wang, Wenjing; Zang, Yi; Zeng, Fanrong; Chen, Keliang; Liu, Junjun; Wang, Jianping; Luo, Zengwei; Xue, Yongbo; Zhu, Hucheng; Yin, Chunping; Chen, Chunmei; Zhang, Yonghui

    2018-01-01

    Azacoccones A-E (1-5), five new aza-epicoccone derivatives, were isolated from the culture of Aspergillus flavipes. Their structures were determined by extensive NMR spectroscopic analyses and the absolute configuration of 5 was determined by electronic circular dichroism (ECD) calculation. Compounds 1-5 are proposed to be generated via a Pictet-Spengler reaction-based biosynthetic route starting from the precursor flavipin. Pictet-Spengler reaction is rarely found in the fungal kingdom, which indicated the distinctive nature of 1-5. Compounds 3 and 5 exhibit significant free radical scavenging activities with IC 50 values of 4.0 and 2.4μg/mL, respectively, which are better than the positive control trolox (4.55μg/mL). Copyright © 2017. Published by Elsevier B.V.

  14. Aza Cope Rearrangement of Propargyl Enammonium Cations Catalyzed By a Self-Assembled `Nanozyme

    Energy Technology Data Exchange (ETDEWEB)

    Hastings, Courntey J.; Fiedler, Dorothea; Bergman, Robert G.; Raymond, Kenneth N.

    2008-02-27

    The tetrahedral [Ga{sub 4}L{sub 6}]{sup 12-} assembly (L = N,N-bis(2,3-dihydroxybenzoyl)-1,5-diaminonaphthalene) encapsulates a variety of cations, including propargyl enammonium cations capable of undergoing the aza Cope rearrangement. For propargyl enammonium substrates that are encapsulated in the [Ga{sub 4}L{sub 6}]{sup 12-} assembly, rate accelerations of up to 184 are observed when compared to the background reaction. After rearrangement, the product iminium ion is released into solution and hydrolyzed allowing for catalytic turnover. The activation parameters for the catalyzed and uncatalyzed reaction were determined, revealing that a lowered entropy of activation is responsible for the observed rate enhancements. The catalyzed reaction exhibits saturation kinetics; the rate data obey the Michaelis-Menten model of enzyme kinetics, and competitive inhibition using a non-reactive guest has been demonstrated.

  15. Mass analyzed threshold ionization spectroscopy of aza-aromatic bicyclic molecules: Benzimidazole and benzotriazole

    Energy Technology Data Exchange (ETDEWEB)

    Lin, J.L.; Li, Y.C. [Institute of Atomic and Molecular Sciences, Academia Sinica, P.O. Box 23-166, 1 Section 4, Roosevelt Road, Taipei 10617, Taiwan (China); Tzeng, W.B. [Institute of Atomic and Molecular Sciences, Academia Sinica, P.O. Box 23-166, 1 Section 4, Roosevelt Road, Taipei 10617, Taiwan (China)], E-mail: wbt@po.iams.sinica.edu.tw

    2007-04-20

    We report the vibrationally resolved cation spectra of benzimidazole and benzotriazole, which give the respective adiabatic ionization energies (IEs) to be 67552 {+-} 5 cm{sup -1} and 70474 {+-} 5 cm{sup -1}. Comparing these data with that of indole, one finds that the IE of these aza-aromatic bicyclic molecules increases with the number of the N atoms. Most of the active modes of the benzimidazole cation are related to the in-plane ring vibrations. In contrast, the observed spectral bands of the benzotriazole cation correspond to the out-of-plane N2-H and skeleton N1N2N3 bending vibrations. These experimental findings may be attributed to the nature and the N atoms in the five-membered ring.

  16. Mass analyzed threshold ionization spectroscopy of aza-aromatic bicyclic molecules: Benzimidazole and benzotriazole

    Science.gov (United States)

    Lin, Jung Lee; Li, Yi Chang; Tzeng, Wen Bih

    2007-04-01

    We report the vibrationally resolved cation spectra of benzimidazole and benzotriazole, which give the respective adiabatic ionization energies (IEs) to be 67552 ± 5 cm -1 and 70474 ± 5 cm -1. Comparing these data with that of indole, one finds that the IE of these aza-aromatic bicyclic molecules increases with the number of the N atoms. Most of the active modes of the benzimidazole cation are related to the in-plane ring vibrations. In contrast, the observed spectral bands of the benzotriazole cation correspond to the out-of-plane N2-H and skeleton N1N2N3 bending vibrations. These experimental findings may be attributed to the nature and the N atoms in the five-membered ring.

  17. Oxy-Allyl Cation Catalysis: An Enantioselective Electrophilic Activation Mode

    Science.gov (United States)

    Liu, Chun; Oblak, E. Zachary; Vander Wal, Mark N.; Dilger, Andrew K.; Almstead, Danielle K.; MacMillan, David W. C.

    2016-01-01

    A generic activation mode for asymmetric LUMO-lowering catalysis has been developed using the long-established principles of oxy-allyl cation chemistry. Here, the enantioselective conversion of racemic α-tosyloxy ketones to optically enriched α-indolic carbonyls has been accomplished using a new amino alcohol catalyst in the presence of electron-rich indole nucleophiles. Kinetic studies reveal that the rate-determining step in this SN1 pathway is the catalyst-mediated α-tosyloxy ketone deprotonation step to form an enantiodiscriminant oxy-allyl cation prior to the stereodefining nucleophilic addition event. PMID:26797012

  18. A Disulfonimide Catalyst for Highly Enantioselective Mukaiyama-Mannich Reaction.

    Science.gov (United States)

    Zhou, Fengtao; Yamamoto, Hisashi

    2016-10-07

    A new BINOL-derived chiral disulfonimide has been developed by introducing 4-methyl-3,5-dinitrophenyl substituents at its 3- and 3'-positions. This chiral disulfonimide catalyst displays high catalytic efficacy toward the asymmetric Mukaiyama-Mannich reaction of imines with ketene silyl acetals leading to β-amino acid esters in good yields (up to 99%) with high diastereoselectivities (syn/anti up to 97:3) and enantioselectivities (up to 98% ee). The long-standing problem of the chiral phosphoric acid-catalyzed asymmetric Mukaiyama-Mannich reaction that requires a 2-hydroxyphenyl moiety was solved by this disulfonimide catalyst.

  19. On the formation of 4-[N,N-bis(2-chloroethyl)amino]phenyl acetic acid esters of hecogenin and aza-homo-hecogenin and their antileukemic activity.

    Science.gov (United States)

    Camoutsis, Charalambos; Trafalis, Dimitrios; Pairas, George; Papageorgiou, Athanasios

    2005-10-01

    The p-[N,N-bis(2-chloroethyl)amino]phenylacetic acid esters of hecogenin and aza-homo-hecogenin have been prepared and their antineoplastic activity was evaluated against two basic drug screening systems in rodents, P388 lymphocytic and L1210 lymphoid murine leukemias. Among the compounds tested, the p-[N,N-bis(2-chloroethyl)amino]phenylacetic acid ester of aza-homo-hecogenin was appeared to possess a significant higher antileukemic effect. These results support that the alkylating esters of hecogenin produce important antitumor activity as well as, indicate that the aza-homo-hecogenin ester exhibits significantly higher activity due to lactam group (-NHCO-) modification.

  20. Un archéologue capucin en Éthiopie (1922-1936 : François Bernardin Azaïs A Capuchin archaeologist in Ethiopia (1922-1936: François Bernardin Azaïs

    Directory of Open Access Journals (Sweden)

    Amélie Chekroun

    2011-01-01

    Full Text Available En 1922, François Bernardin Azaïs, moine capucin et ancien missionnaire dans la province de Hārar de 1897 à 1913, est envoyé par le gouvernement français en Éthiopie afin de réaliser des recherches archéologiques. Au total, il y accomplit dix missions archéologiques et ethnographiques couvrant les parties est et sud du pays. Seules ses quatre premières expéditions sont connues aujourd’hui, grâce à son ouvrage Cinq Années de recherches archéologiques en Éthiopie (1931. Pourtant, au cours des onze années suivantes, F.B. Azaïs a rédigé de nombreux rapports et articles inédits, conservés actuellement dans les archives capucines de Rome, qui permettent de retracer son parcours et ses découvertes. Cette nouvelle documentation permet au chercheur de compléter nos connaissances sur l’ensemble des sites archéologiques de la moitié sud du pays, de retracer l’origine d’institutions éthiopiennes comme la Bibliothèque nationale et le Musée national mais aussi d’un Institut d’archéologie. À la lumière de ces nouvelles informations, F.B. Azaïs mérite d’être reconnu comme le père de l’archéologie du Sud de l’Éthiopie.In 1922, the Capuchin monk François Bernardin Azaïs, a former missionary of the Province of Hārar between 1897 and 1913, was commissioned by the French government to realise some archaeological researches in Ethiopia. In total, he achieved ten archaeological and ethnological missions in the South and the East of the country. Only his first four expeditions are known today, thanks to his book Cinq Années de recherches archéologiques en Éthiopie (1931. During the other eleven years, Azaïs wrote numerous progress reports and articles, still unpublished and kept in the Capuchin archives in Roma. This new documentation will help the researcher to increase the knowledge about the archaeological sites of southern Ethiopia and the history of Ethiopian institutions like the National Library

  1. Dual Enantioselective Control using D-phenylglycine-L-proline-derived Catalysts for the Enantioselective Addition of Diethylzinc to Aldehyde

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Seock Yong; Park, Yong Sun [Konkuk University, Seoul (Korea, Republic of)

    2016-01-15

    Dipeptide-derived catalysts are of great interest in various asymmetric transformations because of their short and simple preparation and easy modification of their modular structure by using different α-amino acids. We recently reported the first example of dipeptide-catalyzed enantioselective addition of dialkylzinc to aldehydes. We have developed a novel D-Phg-L-Pro dipeptide-derived catalyst for the addition of diethylzinc to aromatic aldehydes. We also disclosed an effective chiral switching by simply modifying nonchiral part of D-Phg-L-Pro dipeptide.

  2. Organocatalytic highly enantioselective nitroaldol reaction of alpha-ketophosphonates and nitromethane.

    Science.gov (United States)

    Mandal, Tanmay; Samanta, Sampak; Zhao, Cong-Gui

    2007-03-01

    [reaction: see text] The first organocatalytic highly enantioselective nitroaldol reaction of alpha-ketophosphonates and nitromethane has been realized by using cupreine (2) or 9-O-benzylcupreine (3) as the catalyst. Both catalysts are highly reactive and highly enantioselective. alpha-Hydroxy-beta-nitrophosphonates have been synthesized in good yields and excellent enantioselectivities (>or=90% ee) at a low catalyst loading (5 mol %). These nitroaldol products may be reduced to the biologically significant beta-amino-alpha-hydroxyphosphonates with complete retention of the stereochemistry.

  3. Enantioselective degradation and enantiomerization of indoxacarb in soil.

    Science.gov (United States)

    Sun, Dali; Pang, Junxiao; Qiu, Jing; Li, Li; Liu, Chenglan; Jiao, Bining

    2013-11-27

    In this study, the enantioselective degradation and enantiomerizaton of indoxacarb were investigated in two soils under nonsterilized and sterilized conditions using a chiral OD-RH column on a reversed-phase HPLC. Under nonsterilized conditions, the degradation of indoxacarb in two soils was enantioselective. In acidic soil, the half-lives of R-(-)- and S-(+)-indoxacarb were 10.43 and 14.00 days, respectively. Acidic soil was preferential to the degradation of R-(-)-indoxacarb. In alkaline soil, the half-lives of R-(-)- and S-(+)-indoxacarb were 12.14 and 4.88 days, respectively. S-(+)-Indoxacarb was preferentially degraded. Under sterilized conditions, approximately 5-10% of the initial concentration degraded after 75 days of incubation in acidic soil, whereas in alkaline soil, approximately half of the initial concentration degraded due to chemical hydrolysis under alkaline conditions. Enantiomerization was also discovered in acidic and alkaline soils. The results showed that mutual transformation existed between two enantiomers and that S-(+)-indoxacarb had a significantly higher inversion rate to R-(-)-indoxacarb than its antipode.

  4. Diastereoselective and enantioselective reduction of tetralin-1,4-dione

    Directory of Open Access Journals (Sweden)

    2008-10-01

    Full Text Available BackgroundThe chemistry of tetralin-1,4-dione, the stable tautomer of 1,4-dihydroxynaphthalene, has not been explored previously. It is readily accessible and offers interesting opportunities for synthesis.ResultsThe title reactions were explored. L-Selectride reduced the diketone to give preferentially the cis-diol (d.r. 84 : 16. Red-Al gave preferentially the trans-diol (d.r. 13 : 87. NaBH4, LiAlH4, and BH3 gave lower diastereoselectivities (yields: 76–98%. Fractional crystallization allowed isolation of the cis-diol and the trans-diol (55% and 66% yield, respectively. Borane was used to cleanly give the mono-reduction product. Highly enantioselective CBS reductions afforded the trans-diol (72% yield, 99% ee and the mono-reduction product (81%, 95% ee.ConclusionDiastereoselective and enantioselective reductions of the unexplored tetralin-1,4-dione provides a very convenient entry into a number of synthetically highly attractive 1,4-tetralindiols and 4-hydroxy-1-tetralone.

  5. Diastereoselective and enantioselective reduction of tetralin-1,4-dione.

    Science.gov (United States)

    Kündig, E Peter; Enriquez-Garcia, Alvaro

    2008-01-01

    The chemistry of tetralin-1,4-dione, the stable tautomer of 1,4-dihydroxynaphthalene, has not been explored previously. It is readily accessible and offers interesting opportunities for synthesis. The title reactions were explored. L-Selectride reduced the diketone to give preferentially the cis-diol (d.r. 84 : 16). Red-Al gave preferentially the trans-diol (d.r. 13 : 87). NaBH(4), LiAlH(4), and BH(3) gave lower diastereoselectivities (yields: 76-98%). Fractional crystallization allowed isolation of the cis-diol and the trans-diol (55% and 66% yield, respectively). Borane was used to cleanly give the mono-reduction product. Highly enantioselective CBS reductions afforded the trans-diol (72% yield, 99% ee) and the mono-reduction product (81%, 95% ee). Diastereoselective and enantioselective reductions of the unexplored tetralin-1,4-dione provides a very convenient entry into a number of synthetically highly attractive 1,4-tetralindiols and 4-hydroxy-1-tetralone.

  6. RNA-Cleaving DNA Enzymes with Altered Regio- or Enantioselectivity

    Science.gov (United States)

    Ordoukhanian, Phillip; Joyce, Gerald F.

    2002-01-01

    In vitro evolution methods were used to obtain DNA enzymes that cleave either a 2',5' - phosphodiester following a wibonucleotide or a 3',5' -phosphodiester following an L-ribonucleotide. Both enzymes can operate in an intermolecular reaction format with multiple turnover. The DNA enzyme that cleaves a 2',5' -phosphodiester exhibits a k(sub cat) of approx. 0.01/ min and catalytic efficiency, k(sub cat)/k(sub m) of approx. 10(exp 5)/ M min. The enzyme that cleaves an L-ribonudeotide is about 10-fold slower and has a catalytic efficiency of approx. 4 x 10(exp 5)/ M min. Both enzymes require a divalent metal cation for their activity and have optimal catalytic rate at pH 7-8 and 35-50 C. In a comparison of each enzyme s activity with either its corresponding substrate that contains an unnatural ribonudeotide or a substrate that instead contains a standard ribonucleotide, the 2',5' -phosphodiester-deaving DNA enzyme exhibited a regioselectivity of 6000- fold, while the L-ribonucleotide-cleaving DNA enzyme exhibited an enantioselectivity of 50-fold. These molecules demonstrate how in vitro evolution can be used to obtain regio- and enantioselective catalysts that exhibit specificities for nonnatural analogues of biological compounds.

  7. Rhodium-Catalyzed Enantioselective Cyclopropanation of Olefins with N-Sulfonyl 1,2,3-Triazoles

    Science.gov (United States)

    Chuprakov, Stepan; Kwok, Sen Wai; Zhang, Li; Lercher, Lukas; Fokin, Valery V.

    2009-01-01

    N-Sulfonyl 1,2,3-triazoles readily form rhodium(II) azavinyl carbenes, which react with olefins to produce cyclopropanes with excellent diastereo- and enantioselectivity and in high yield. PMID:19928917

  8. Optimisation of stabilised carboxylesterase NP for enantioselective hydrolysis of naproxen methyl ester

    CSIR Research Space (South Africa)

    Steenkamp, Lucia H

    2008-12-01

    Full Text Available is usually insufficient to warrant commercialisation. However, optimised reactions using heterologously expressed Carboxylesterase NP provided highly enantioselective hydrolysis of racemic naproxen methyl ester. Up to 46.9% conversion was achieved in 5 h...

  9. Correction to: Release of an enantioselective nitrilase from Alcaligenes faecalis MTCC 126: a comparative study.

    Science.gov (United States)

    Singh, Renu; Banerjee, Anirban; Kaul, Praveen; Barse, Brajesh; Banerjee, U C

    2018-02-24

    In the original version of our paper entitled "Release of an enantioselective nitrilase from Alcaligenes faecalis MTCC 126: a comparative study" (2005) 27:415-424, some references to already published articles were inadvertently left out.

  10. Enantioselective synthesis of almorexant via iridium-catalysed intramolecular allylic amidation

    NARCIS (Netherlands)

    Fananas Mastral, Martin; Teichert, Johannes F.; Fernandez-Salas, Jose Antonio; Heijnen, Dorus; Feringa, Ben L.

    2013-01-01

    An enantioselective synthesis of almorexant, a potent antagonist of human orexin receptors, is presented. The chiral tetrahydroisoquinoline core structure was prepared via iridium-catalysed asymmetric intramolecular allylic amidation. Further key catalytic steps of the synthesis include an oxidative

  11. Sensitized enantioselective laser-induced phosphorescence detection in chiral capillary electrophoresis

    NARCIS (Netherlands)

    Lammers, I.; Buijs, J.B.; Ariese, F.; Gooijer, C.

    2010-01-01

    The sensitivity of enantioselective cyclodextrin-induced room-temperature phosphorescence detection of camphorquinone (CQ) is enhanced using sensitization via a donor with a high extinction coefficient. The enantiomeric distinction is based on the different phosphorescence lifetimes of (+)-CQ and

  12. Enantioselective Addition of Organolithium Reagents to Imines Mediated by C2-Symmetric Bis(aziridine) Ligands

    DEFF Research Database (Denmark)

    Johansson, F.; Tanner, David Ackland

    1998-01-01

    The C-2-symmetric bis(aziridine) ligands 1 - 5 have been screened in the enantioselective addition of organolithium reagents to imines. Ligand 1 (used in stoichiometric amounts) was found to be superior in terms of chemical yield and enantioselectivity, the best result being 90% yield and 89% e.......e. in the addition of vinyllithium to imine 6a. Use of ligand 1 in substoichiometric amounts gave poorer yield and lower enantioselectivity. The enantioselectivity of the reaction was investigated as a function of substrate, reagent, stoichiometry and temperature, but no firm mechanistic conclusions could be drawn....... Preliminary results with deuterium-labelled methyllithium indicate complexation/exchange processes involving ligand, reagent and substrate. (C) 1998 Elsevier Science Ltd. All rights reserved....

  13. BIOACCUMULATION AND ENANTIOSELECTIVE BIOTRANSFORMATION OF FIPRONIL BY RAINBOW TROUT (ONCORHYNCHUS MYKISS)

    Science.gov (United States)

    Dietary accumulation and enantioselective biotransformation was determined for rainbow trout (Oncorhynchus mykiss) exposed to fipronil, a widely used chiral pesticide. Measurement of the fish carcass tissue (whole fish minus GI tract and liver) showed a rapid accumulation of fip...

  14. Asymmetric aza-Morita-Baylis-Hillman reactions of chiral N-phosphonyl imines with acrylates via GAP chemistry/technology.

    Science.gov (United States)

    Yang, Bing; Ji, Xiaozhou; Xue, Yunsheng; Zhang, Haowei; Shen, Minxing; Jiang, Bo; Li, Guigen

    2016-07-07

    Chiral N-phosphonyl imines have been proven to be efficient electrophilic acceptors for asymmetric aza-Morita-Baylis-Hillman (aza-MBH) reactions with acrylates under convenient conditions. Thirty examples of β-amino acrylates were generated in high yields (up to 99.4%) and diastereoselectivity (up to >99 : 1 dr) in an atom-economical fashion. The synthesis was proved to follow the GAP (group-assisted purification) chemistry, i.e., the pure products can be obtained simply by washing the crude products with hexane/ethyl acetate (v/v, 10/1) without the use of chromatography or recrystallization. DFT calculations were also conducted to support an asymmetric induction model accounting for high diastereoselectivity.

  15. Synthesis and evaluation of the anti-HIV activity of aza and deaza analogues of isoddA and their phosphates as prodrugs.

    Science.gov (United States)

    Franchetti, P; Cappellacci, L; Grifantini, M; Messini, L; abu Sheikha, G; Loi, A G; Tramontano, E; de Montis, A; Spiga, M G; La Colla, P

    1994-10-14

    Some aza and deaza analogues of the anti-HIV agent 2',3'-dideoxy-3'-oxoadenosine (isoddA) (8-aza-, 8-aza-1-deaza, 8-aza-3-deaza-, 1-deaza-, and 3-deaza-isoddA) were synthesized and found inactive against HIV in vitro. The hypothesis that the inactivity of these isonucleosides might be due to their poor affinity for cellular nucleoside kinases was checked by the synthesis of a series of 5'-[bis(2,2,2-trichloroethyl) phosphate] triesters and 5'-phenyl phosphoramidate derivatives which, acting as membrane soluble prodrugs, could release the free phosphate form inside the cell. The 5'-(phenylmethoxy)alaninyl phosphate derived from 8-aza-isoddA was found active against HIV-1 and HIV-2 with a potency similar to that of isoddA, while the anti-HIV potency of 5'-(phenylmethoxy)alaninyl phosphate of isoddA proved remarkably higher than that of isoddA, in particular against HIV-2, being similar to that of AZT. Further evidence that 8-aza-isoddA could behave as anti-HIV agent, provided that it is activated as phosphate, was obtained by the synthesis of its 5'-triphosphate derivative, which proved to be an active inhibitor of HIV-1 recombinant reverse transcriptase.

  16. Quantum Molecular Interaction Field Models of Substrate Enantioselection in Asymmetric Processes.

    Science.gov (United States)

    Kozlowski, Marisa C; Ianni, James C

    2010-06-01

    Computational models correlating substrate structure to enantioselection with asymmetric catalysts using the QMQSAR program are described. In addition to rapidly providing predictions that could be used to facilitate the screening of catalysts for novel substrates, the QMQSAR program identifies the portions of the substrate that most directly influence the enantioselectivity. The lack underlying relationship between all the substrates in one case, requires two quantitative structure selectivity relationships (QSSR) models to describe all of the experimental results.

  17. Enhancement of Enantioselectivity by Altering Alcohol Concentration for Esterification in Supercritical CO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Jau-yann.; Liang, Ming-tsai

    1999-06-01

    This work used Candida rugosa lipase to resolve racemic Naproxen by esterification with ethanol, n-butanol, n-hexanol, or n-decanol in supercritical CO{sub 2}. It was found that the lipase enantioselectively esterified (S)-Naproxen within all systems. The enantiomeric ratio increased four folds by slightly decreasing the alcohol concentration. The effect of the alcohol concentration on the enantioselectivity was greater than of changing acyl acceptors. (author)

  18. Enhancement of Enantioselectivity by Altering Alcohol Concentration for Esterification in Supercritical CO[sub 2

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Jau-yann.; Liang, Ming-tsai

    1999-06-01

    This work used Candida rugosa lipase to resolve racemic Naproxen by esterification with ethanol, n-butanol, n-hexanol, or n-decanol in supercritical CO[sub 2]. It was found that the lipase enantioselectively esterified (S)-Naproxen within all systems. The enantiomeric ratio increased four folds by slightly decreasing the alcohol concentration. The effect of the alcohol concentration on the enantioselectivity was greater than of changing acyl acceptors. (author)

  19. A New Mn–Salen Micellar Nanoreactor for Enantioselective Epoxidation of Alkenes in Water

    Directory of Open Access Journals (Sweden)

    Francesco P. Ballistreri

    2018-03-01

    Full Text Available A new chiral Mn–salen catalyst, functionalized with a long aliphatic chain and a choline group, able to act as surfactant catalyst for green epoxidation in water, is here described. This catalyst was employed with a commercial surfactant (CTABr leading to a nanoreactor for the enantioselective epoxidation of some selected alkenes in water, using NaClO as oxidant. This is the first example of a nanoreactor for enantioselective epoxidation of non-functionalized alkenes in water.

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

    Science.gov (United States)

    Skucas, Eduardas; MacMillan, David W. C.

    2012-01-01

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

  1. Short Enantioselective Total Synthesis of (-)-Rhazinilam Using a Gold(I)-Catalyzed Cyclization.

    Science.gov (United States)

    Magné, Valentin; Lorton, Charlotte; Marinetti, Angela; Guinchard, Xavier; Voituriez, Arnaud

    2017-09-15

    (R)-(-)-Rhazinilam has been synthesized in nine steps and 20% overall yield. The key steps involve two metal-catalyzed processes: the enantioselective gold(I)-catalyzed cycloisomerization of an allene-functionalized pyrrole and the palladium-catalyzed hydrocarboxylation of a vinyl moiety with formate as a CO surrogate. This novel strategy represents the shortest and highest yielding enantioselective total synthesis of (-)-rhazinilam.

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

    Science.gov (United States)

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

    2015-01-21

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

  3. Asymmetric Synthesis of Optically Active Spirocyclic Indoline Scaffolds through an Enantioselective Reduction of Indoles

    KAUST Repository

    Borrmann, Ruediger

    2016-11-30

    An enantioselective synthesis of spirocyclic indoline scaffolds was achieved by applying an asymmetric iridium-catalyzed hydrogenation of 3H-indoles. Low catalyst loadings and mild reaction conditions provide a broad range of differently substituted products with excellent yields and enantioselectivities. The developed methodology allows an efficient synthesis of this important spirocyclic structural motif, which is present in numerous biologically active molecules and privileged structures in medicinal chemistry.

  4. Immunotherapy for adenoid cystic carcinoma of salivary glands: cancer/testis antigens and 5-aza-2'-deoxycytidine.

    Science.gov (United States)

    Liang, Suxia; Fan, Mingwen

    2009-11-01

    Adenoid cystic carcinoma of salivary glands is the epithelial tumor. There are amount of malignant occurrences of adenoid cystic carcinoma of salivary glands in the head and neck area. Cancer/testis antigens can be found in various malignant tumors, normal adult testis and occasionally placenta, but not in the other normal adult tissues. This characteristic makes Cancer/testis antigens as potential markers to be applied in immunotherapeutic strategies against cancer. It has been shown that in different tumors, the expression of certain Cancer/testis antigens is activated treated with 5-aza-CdR via the demethylation of their promoter CpG islands. It is logical that multiple Cancer/testis antigens may correlate with the clinicopathologic factors of adenoid cystic carcinoma of salivary glands and be the potential markers of prognosis treated with 5-aza-CdR. So the hypothesis will provide the new direction that we can use Cancer/testis antigens as candidate antigens for adenoid cystic carcinoma of salivary glands immunotherapy due to the high expression rate activated with 5-aza-CdR.

  5. Integrative assessment of enantioselectivity in endocrine disruption and immunotoxicity of synthetic pyrethroids

    Energy Technology Data Exchange (ETDEWEB)

    Zhao Meirong [Research Center of Environmental Science, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China); Chen Fang [College of Environmental Science and Engineering, Zhejiang Gongshang University, Hangzhou 310018 (China); Wang Cui; Zhang Quan [Research Center of Environmental Science, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China); Gan Jianying [Department of Environmental Sciences, University of California, Riverside, CA 92521 (United States); Liu Weiping, E-mail: wliu@zjut.edu.c [Research Center of Environmental Science, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China)

    2010-05-15

    The increasing release of chiral chemicals into the environment dictates attention to a better understanding of enantioselectivity in their human and ecotoxicological effects. Although enantioselectivity has been considered in many recent studies, there is little effort for discerning the connection between different processes, and as such, our current knowledge about chiral contaminants is rather scattered and incoherent. In this study, we simultaneously evaluated enantioselectivity of two chiral pesticides, lambda-cyhalothrin (LCT) and (Z)-cis-bifenthrin (cis-BF), in immunotoxicity to macrophage cells (RAW264.7), and endocrine disruption activity in human breast carcinoma cell line MCF-7. Analysis of cell proliferation, cell viability, apoptosis, and receptor gene expression showed significant differences between the enantiomers of LCT or cis-BF in estrogenic potential and immunocytotoxicity. The selectivity in these effects consistently followed the same direction, with (-)-LCT or 1S-cis-BF displaying a greater activity than its counterpart. The consistency was attributed to interplaying mechanisms in the closely interacting immune and endocrine systems. The underlying interplays suggest that other chiral xenobiotics may also show a directional enantioselectivity in immunotoxicity and endocrine toxicity. Given that many biological processes are inter-related, enantioselectivity may follow specific patterns that can be revealed via integrative assessments as demonstrated in this study. - Chiral contaminants should consider multiple effects and relate directions of enantioselectivity to their interplaying processes.

  6. Integrative assessment of enantioselectivity in endocrine disruption and immunotoxicity of synthetic pyrethroids

    International Nuclear Information System (INIS)

    Zhao Meirong; Chen Fang; Wang Cui; Zhang Quan; Gan Jianying; Liu Weiping

    2010-01-01

    The increasing release of chiral chemicals into the environment dictates attention to a better understanding of enantioselectivity in their human and ecotoxicological effects. Although enantioselectivity has been considered in many recent studies, there is little effort for discerning the connection between different processes, and as such, our current knowledge about chiral contaminants is rather scattered and incoherent. In this study, we simultaneously evaluated enantioselectivity of two chiral pesticides, lambda-cyhalothrin (LCT) and (Z)-cis-bifenthrin (cis-BF), in immunotoxicity to macrophage cells (RAW264.7), and endocrine disruption activity in human breast carcinoma cell line MCF-7. Analysis of cell proliferation, cell viability, apoptosis, and receptor gene expression showed significant differences between the enantiomers of LCT or cis-BF in estrogenic potential and immunocytotoxicity. The selectivity in these effects consistently followed the same direction, with (-)-LCT or 1S-cis-BF displaying a greater activity than its counterpart. The consistency was attributed to interplaying mechanisms in the closely interacting immune and endocrine systems. The underlying interplays suggest that other chiral xenobiotics may also show a directional enantioselectivity in immunotoxicity and endocrine toxicity. Given that many biological processes are inter-related, enantioselectivity may follow specific patterns that can be revealed via integrative assessments as demonstrated in this study. - Chiral contaminants should consider multiple effects and relate directions of enantioselectivity to their interplaying processes.

  7. Catalytic Enantioselective Alkylation of β-Keto Esters with Xanthydrol in the Presence of Chiral Palladium Complex

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyu Yeon; Kim, Dae Young [Soonchunhyang Univ., Asan (Korea, Republic of)

    2016-01-15

    Our research interest has been directed toward the development of synthetic methods for the enantioselective construction of stereogenic carbon centers. Recently, we explored the catalytic enantioselective functionalization of active methines in the presence of chiral palladium(II) complexes. In conclusion, we have accomplished the efficient catalytic enantioselective alkylation of β-keto esters 1 with xanthydrol 2 with high yields and excellent enantioselectivity (up to 98% ee). It should be noted that this alkyaltion reaction proceeds well using air- and moisture-stable chiral palladium com- plexes with low loading (1 mol%)

  8. Chemo- and Enantioselective Intramolecular Silver-Catalyzed Aziridinations.

    Science.gov (United States)

    Ju, Minsoo; Weatherly, Cale D; Guzei, Ilia A; Schomaker, Jennifer M

    2017-08-07

    Asymmetric nitrene-transfer reactions are a powerful tool for the preparation of enantioenriched amine building blocks. Reported herein are chemo- and enantioselective silver-catalyzed aminations which transform di- and trisubstituted homoallylic carbamates into [4.1.0]-carbamate-tethered aziridines in good yields and with ee values of up to 92 %. The effects of the substrate, silver counteranion, ligand, solvent, and temperature on both the chemoselectivity and ee value were explored. Stereochemical models were proposed to rationalize the observed absolute stereochemistry of the aziridines, which undergo nucleophilic ring opening to yield enantioenriched amines with no erosion in stereochemical integrity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Enantioselective behaviour of tetraconazole during strawberry wine-making process.

    Science.gov (United States)

    Liu, Na; Pan, Xinglu; Zhang, Shuang; Ji, Mingshan; Zhang, Zhihong

    2018-05-01

    The fate of tetraconazole enantiomers in strawberries during wine-making process was studied. The residues were determined by ultra-performance convergence chromatography tandem triple quadrupole mass spectrometry after each process steps. Results indicated that there was significant enantioselective dissipation of tetraconazole enantiomers during the fermentation process. And (-)-tetraconazole degraded faster than (+)-tetraconazole. The half-lives of (-)-tetraconazole and (+)-tetraconazole were 3.12, 3.76 days with washing procedure and 3.18, 4.05 days without washing procedure. The processing factors of strawberry wine samples after each step were generally less than 1. In particular, the processing factors of the fermentation process were the lowest. The results could help facilitate more accurate risk assessments of tetraconazole during wine-making process. © 2018 Wiley Periodicals, Inc.

  10. 5-Aza-2'-deoxycytidine protects against emphysema in mice via suppressing p16Ink4a expression in lung tissue

    Directory of Open Access Journals (Sweden)

    He ZH

    2017-10-01

    Full Text Available Zhi-Hui He,1 Yan Chen,2 Ping Chen,2 Sheng-Dong He,2 Hui-Hui Zeng,2 Ji-Ru Ye,2 Da Liu,2 Jun Cao3 1Intensive Care Unit, 2Department of Respiratory Medicine, Second Xiangya Hospital, Central South University, Changsha, 3Department of Respiratory Medicine, Hunan Provincial People’s Hospital, Changsha, China Background: There is a growing realization that COPD, or at least emphysema, involves several processes presenting in aging and cellular senescence. Endothelial progenitor cells (EPCs contribute to neovascularization and play an important role in the development of COPD. The gene for p16Ink4a is a major dominant senescence one. The aim of the present study was to observe changes in lung function, histomorphology of lung tissue, and expression of p16Ink4a in lung tissue and bone marrow-derived EPCs in emphysematous mice induced by cigarette-smoke extract (CSE, and further to search for a potential candidate agent protecting against emphysema induced by CSE. Materials and methods: An animal emphysema model was induced by intraperitoneal injection of CSE. 5-Aza-2'-deoxycytidine (5-Aza-CdR was administered to the emphysematous mice. Lung function and histomorphology of lung tissue were measured. The p16Ink4a protein and mRNA in EPCs and lung tissues were detected using Western blotting and quantitative reverse-transcription polymerase chain reaction, respectively. Results: CSE induced emphysema with increased p16Ink4a expression in lung tissue and bone marrow-derived EPCs. 5-Aza-CdR partly protected against emphysema, especially in the lung-morphology profile, and partly protest against the overexpression of p16Ink4a in EPCs and lung tissue induced by CSE. Conclusion: 5-Aza-CdR partly protected against emphysema in mice via suppressing p16Ink4a expression in EPCs and lung tissue. Keywords: 5-Aza-2'-deoxycytidine, cigarette smoke, emphysema, endothelial progenitor cells, p16Ink4a

  11. Enantioselective bioaccumulation of diniconazole in Tenebrio molitor larvae.

    Science.gov (United States)

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

    2013-12-01

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

  12. Enantioselective γ-Alkylation of α,β-Unsaturated Malonates and Ketoesters by a Sequential Ir-Catalyzed Asymmetric Allylic Alkylation/Cope Rearrangement

    OpenAIRE

    Liu, Wen-Bo; Okamoto, Noriko; Alexy, Eric J.; Hong, Allen Y.; Tran, Kristy; Stoltz, Brian M.

    2016-01-01

    A catalytic, enantioselective ? -alkylation of ?,?-unsaturated malonates and ketoesters is reported. This strategy entails a highly regio- and enantioselective iridium-catalyzed ?-alkylation of an extended enolate, and a subsequent translocation of chirality to the ?-position via a Cope rearrangement.

  13. An enantioselective cascade reaction between α,β-unsaturated aldehydes and malonic half-thioesters: a rapid access to chiral δ-lactones.

    Science.gov (United States)

    Ren, Qiao; Sun, Shaofa; Huang, Jiayao; Li, Wenjun; Wu, Minghu; Guo, Haibing; Wang, Jian

    2014-06-11

    We disclose a novel efficient enantioselective organocatalytic cascade reaction for the preparation of δ-lactones in good to excellent yields (69-93%) and with high to excellent enantioselectivities (88-96% ee).

  14. Highly diastereo- and enantioselective [3+2] annulation of isatin-derived Morita-Baylis-Hillman carbonates with trifluoropyruvate catalyzed by tertiary amines.

    Science.gov (United States)

    Zhong, Neng-Jun; Wei, Feng; Xuan, Qing-Qing; Liu, Li; Wang, Dong; Chen, Yong-Jun

    2013-12-07

    An enantioselective [3+2] annulation of Morita-Baylis-Hillman carbonates with trifluoropyruvate catalyzed by modified cinchona alkaloids was developed in good to excellent yields with excellent diastereo- and enantioselectivities.

  15. Effect of DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine on radiosensitivity of the human lung cancer cells in three-dimensional culture

    International Nuclear Information System (INIS)

    Pan Dong; Xue Gang; Li Xiaoman; Chen Yaxiong; Ren Zhenxin; Du Yarong; Hu Burong

    2014-01-01

    5-Aza-CdR is a specific inhibitor of DNMTs which could suppress tumor growth by demethylation of genomic DNA. There have only few studies thus far concerning it as radiosensitizers in three-dimensional (3D) cells. The principal aim of this study is to evaluate the effects of 5-Aza-CdR on the radiosensitivity of A549 cells in monolayer (2D) and 3D cultures in an attempt to find out a new combination treatments with radiotherapy. The cell proliferation was detected by MTT assay after pretreated with different doses of 5-Aza-CdR for 72 h. A549 cells were treated with or without 5-Aza-CdR (2, 5 μmol/L) for 72 h before be exposed to X-rays of 1, 2, 4, 6 Gy, respectively. The DNA damage was evaluated by micronucleus assay and clonogenic assays. Pretreatment with 5-Aza-CdR inhibited the A549 cell proliferation significantly. More micronucleus were observed after irradiation in 3D cells pretreated with 2 and 5 μmol/L concentration of drug than those without treatment. The survival fractions of cells pretreated by both 2 and 5 μmol/L drug reduced significantly in 3D cultures after irradiation. These significances, however, were found in 2D cells pretreated by only 5 μmol/L drug. Our results suggest that 5-Aza-CdR can inhibit the A549 cells proliferation and apparently enhance the radiosensitivity of cells in 3D cultures. Using of the low dose 5-Aza-CdR in clinical radiotherapy may reduce side effects and enhance effectively the cancer target therapy. (authors)

  16. [The potential effects of linalool on enantioselective skin permeation of norgestrel].

    Science.gov (United States)

    Rong, Yi; Yu, Wen-Ying; Guo, Xia; Zeng, Shan-Shan; Shen, Zheng-Rong; Zeng, Su; Ye, Jin-Cui

    2014-08-01

    The purpose of this study is to investigate the enantioselectivity of norgestrel (NG) transdermal permeation and the potential influence of linalool and lipids on the enantioselectivity. In vitro skin permeation studies of NG across the excised rat skins were performed with Valia-Chien diffusion cells, and the permeation samples were analyzed by enantioselective HPLC. The possible enantioselective permeation of NG across intact rat back skin and lipids extracted rat back skin and the influence of linalool were evaluated. The skin permeation rate of dl-NG was two times higher than that of l-NG when donor solutions (EtOH/H2O 2 : 8, v/v) containing l-NG or dl-NG. It may be mainly attributed to the solubility discrepancy between enantiomer and racemate. The enantioselective permeation of dl-NG across intact rat skin was observed when the donor solutions containing dl-linalool. The permeation flux of l-NG was 22% higher than that of d-NG. But interestingly, the enantioselective permeation of dl-NG disappeared under the same experimental condition except that the lipid extracted rat skin was used. Attenuated total reflection-fourier transform infrared spectroscopy analysis of stratum corneum showed that the wave number for asymmetric CH2 stretching vibrations of lipids treated with dl-linalool was greater than that of the control. The results indicated that the enantioselective permeation of NG may be contributed by the interaction between dl-linalool and lipids. More than half of lipids were composed of ceramides. The stereospecific interaction maybe existed among chiral enhancer (linalool), lipids (ceramides) and/or chiral drugs (NG).

  17. Synthesis of macrocyclic bifunctional chelating agents: 1,4,7 - tri(carboxy-methyl) - 10 - (2-amino-ethyl) - 1,4,7,10 - tetra-aza-cyclo-dodecane and 1,4,8 - tri(carboxy-methyl)- 11 - (2-amino-ethyl) - 1,4,8,11 - tetra-aza-cyclo-tetra-decane

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, A.K. [Institute of Nuclear Medicine and Allied Sciences, Dept. of Radiopharmaceuticals, Delhi (India); Chatal, J.F. [Institut National de la Sante et de la Recherche Medicale (INSERM U-463), Lab. d' Interactions Recepteurs Ligands en Immunocancerologie et immunopathologie, 44 - Nantes (France)

    2001-02-01

    The convenient, synthetically useful bifunctional chelating agents, 1,4,7 - tri(carboxy-methyl) - 10 - (2-amino-ethyl) - 1,4,7,10 - tetra-aza-cyclo-dodecane and 1,4,8 - tri(carboxy-methyl) - 11 - (2-amino-ethyl) - 1,4,8,11 - tetra-aza-cyclo-tetra-decane, were obtained by reaction of ethyl bromo-acetate with 1,4,7,10 - tetra-aza-cyclo-dodecane and 1,4,8,11 - tetra-aza-cyclo-tetra-decane, followed by reaction with N-(2-bromo-ethyl)phthalimide. This method is proven to be more efficient to prepare bifunctional chelating agents with aliphatic side arms in high yields, above 53%. (authors)

  18. Synthesis of macrocyclic bifunctional chelating agents: 1,4,7 - tri(carboxy-methyl) - 10 - (2-amino-ethyl) - 1,4,7,10 - tetra-aza-cyclo-dodecane and 1,4,8 - tri(carboxy-methyl)- 11 - (2-amino-ethyl) - 1,4,8,11 - tetra-aza-cyclo-tetra-decane

    International Nuclear Information System (INIS)

    Mishra, A.K.; Chatal, J.F.

    2001-01-01

    The convenient, synthetically useful bifunctional chelating agents, 1,4,7 - tri(carboxy-methyl) - 10 - (2-amino-ethyl) - 1,4,7,10 - tetra-aza-cyclo-dodecane and 1,4,8 - tri(carboxy-methyl) - 11 - (2-amino-ethyl) - 1,4,8,11 - tetra-aza-cyclo-tetra-decane, were obtained by reaction of ethyl bromo-acetate with 1,4,7,10 - tetra-aza-cyclo-dodecane and 1,4,8,11 - tetra-aza-cyclo-tetra-decane, followed by reaction with N-(2-bromo-ethyl)phthalimide. This method is proven to be more efficient to prepare bifunctional chelating agents with aliphatic side arms in high yields, above 53%. (authors)

  19. Enantioselective conjugate addition of diethylzinc to chalcone catalyzed by Co(acac)(2) and chiral amino alcohols

    NARCIS (Netherlands)

    de Vries, A.H.M.; Feringa, B.L.

    1997-01-01

    Co(acac)(2) in the presence of chiral ligands has been employed as catalyst for the enantioselective conjugate addition of diethylzinc to chalcone. With chiral amino alcohols derived from (+)-camphor, enantioselectivities up to 83% were achieved. (C) 1997 Elsevier Science Ltd.

  20. Cu(I)-Catalyzed Enantioselective Friedel-Crafts Alkylation of Indoles with 2-Aryl-N-sulfonylaziridines as Alkylating Agents.

    Science.gov (United States)

    Ge, Chen; Liu, Ren-Rong; Gao, Jian-Rong; Jia, Yi-Xia

    2016-07-01

    A highly enantioselective Friedel-Crafts alkylation of indoles with N-sulfonylaziridines as alkylating agents has been developed by utilizing the complex of Cu(CH3CN)4BF4/(S)-Segphos as a catalyst. A range of optically active tryptamine derivatives are obtained in good to excellent yields and enantioselectivities (up to >99% ee) via a kinetic resolution process.

  1. Hydroxymethylation beyond Carbonylation: Enantioselective Iridium Catalyzed Reductive Coupling of Formaldehyde with Allylic Acetates via Enantiotopic ?-Facial Discrimination

    OpenAIRE

    Garza, Victoria J.; Krische, Michael J.

    2016-01-01

    Chiral iridium complexes modified by SEGPHOS catalyze the 2-propanol mediated reductive coupling of branched allylic acetates 1a?1o with formaldehyde to form primary homoallylic alcohols 2a?2o with excellent control of regio- and enantioselectivity. These processes, which rely on enantiotopic ?-facial discrimination of ?-allyliridium intermediates, represent the first examples of enantioselective formaldehyde C-C coupling beyond aldol addition.

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

    Science.gov (United States)

    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. © 2015 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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. © 2014 Wiley Periodicals, Inc.

  4. New eco-friendly animal bone meal catalysts for preparation of chalcones and aza-Michael adducts

    Directory of Open Access Journals (Sweden)

    Riadi Yassine

    2012-06-01

    Full Text Available Abstract Two efficient reactions were successfully carried out using Animal Bone Meal (ABM and potassium fluoride or sodium nitrate doped ABMs as new heterogeneous catalysts under very mild conditions. After preparation and characterization of the catalysts, we first report their use in a simple and convenient synthesis of various chalcones by Claisen–Schmidt condensation and then in an aza-Michael addition involving several synthesized chalcones with aromatic amines. All the reactions were carried out at room temperature in methanol; the chalcone synthesis was also achieved in water environment under microwave irradiation. Doping ABM enhances the rate and yield at each reaction. Catalytic activities are discussed and the ability to re-use the ABM is demonstrated. Results For Claisen–Schmidt the use of ABM alone, yields never exceeded 17%. In each entry, KF/ABM and NaNO3/ABM (79-97% gave higher yields than using ABM alone under thermic condition. Also the reaction proceeded under microwave irradiation in good yields (72-94% for KF/ABM and 81-97% for NaNO3/ABM and high purity. For aza-Michael addition the use of ABM doped with KF or NaNO3 increased the catalytic activity remarkably. The very high yields could be noted (84-95% for KF/ABM and 81-94% for NaNO3/ABM. Conclusion The present method is an efficient and selective procedure for the synthesis of chalcones an aza-Michael adducts. The ABM and doped ABMs are a new, inexpensive and attractive solid supports which can contribute to the development of catalytic processes and reduced environmental problems.

  5. Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds

    Directory of Open Access Journals (Sweden)

    Alexey M. Starosotnikov

    2017-12-01

    Full Text Available 4-Aza-6-nitrobenzofuroxan (ANBF reacts with 1,3-dicarbonyl compounds and other CH acids to give carbon-bonded 1,4-adducts – 1,4-dihydropyridines fused with furoxan ring. In the case of most acidic β-diketones, which exist mainly in the enol form in polar solvents, the reactions proceed in the absence of any added base emphasizing the highly electrophilic character of ANBF. The resulting compounds combine in one molecule NO-donor furoxan ring along with a pharmacologically important 1,4-dihydropyridine fragment and therefore can be considered as prospective platforms for the design of pharmacology-oriented heterocyclic systems.

  6. Catalytic enantioselective addition of organoboron reagents to fluoroketones controlled by electrostatic interactions

    Science.gov (United States)

    Lee, Kyunga; Silverio, Daniel L.; Torker, Sebastian; Robbins, Daniel W.; Haeffner, Fredrik; van der Mei, Farid W.; Hoveyda, Amir H.

    2016-08-01

    Organofluorine compounds are central to modern chemistry, and broadly applicable transformations that generate them efficiently and enantioselectively are in much demand. Here we introduce efficient catalytic methods for the addition of allyl and allenyl organoboron reagents to fluorine-substituted ketones. These reactions are facilitated by readily and inexpensively available catalysts and deliver versatile and otherwise difficult-to-access tertiary homoallylic alcohols in up to 98% yield and >99:1 enantiomeric ratio. Utility is highlighted by a concise enantioselective approach to the synthesis of the antiparasitic drug fluralaner (Bravecto, presently sold as the racemate). Different forms of ammonium-organofluorine interactions play a key role in the control of enantioselectivity. The greater understanding of various non-bonding interactions afforded by these studies should facilitate the future development of transformations that involve fluoroorganic entities.

  7. Enantioselective Henry reaction catalyzed by "ship in a bottle" complexes.

    Science.gov (United States)

    Bania, Kusum K; Karunakar, Galla V; Goutham, Kommuru; Deka, Ramesh C

    2013-07-15

    Two chiral Schiff-base complexes of copper(II) have been successfully encapsulated inside the cavity of zeolite-NaY via a "ship in a bottle" synthesis method. The presence of the two complexes inside the cages of zeolite-Y has been confirmed based on various spectrochemical and physicochemical techniques, viz. FTIR, UV-vis/DRS, ESR, XPS, CV, EDX, SEM, and TGA. Zeolite-encapsulated chiral copper(II) Schiff-base complexes are found to give a high-enantioselective (84% ee, R conformation) nitro-aldol product at -20 °C. The encapsulated copper complexes are found to show higher catalytic efficiency than their homogeneous counterparts under identical conditions. Density functional theory (DFT) calculation has been implemented to understand the effect of the zeolite matrix on structural, electronic, and reactivity properties of the synthesized complexes. Theoretical calculation predicts that upon encapsulation into the zeolite matrix the Cu center becomes more susceptible to nucleophilic attack, favoring a nitro-aldol reaction. A plausible mechanism is suggested based on the experimental and theoretical results. The structures of reaction intermediates and transition state(s) involved in the catalytic cycle are derived using DFT.

  8. Nanoscopic control and quantification of enantioselective optical forces

    Science.gov (United States)

    Zhao, Yang; Saleh, Amr A. E.; van de Haar, Marie Anne; Baum, Brian; Briggs, Justin A.; Lay, Alice; Reyes-Becerra, Olivia A.; Dionne, Jennifer A.

    2017-11-01

    Circularly polarized light (CPL) exerts a force of different magnitude on left- and right-handed enantiomers, an effect that could be exploited for chiral resolution of chemical compounds as well as controlled assembly of chiral nanostructures. However, enantioselective optical forces are challenging to control and quantify because their magnitude is extremely small (sub-piconewton) and varies in space with sub-micrometre resolution. Here, we report a technique to both strengthen and visualize these forces, using a chiral atomic force microscope probe coupled to a plasmonic optical tweezer. Illumination of the plasmonic tweezer with CPL exerts a force on the microscope tip that depends on the handedness of the light and the tip. In particular, for a left-handed chiral tip, transverse forces are attractive with left-CPL and repulsive with right-CPL. Additionally, total force differences between opposite-handed specimens exceed 10 pN. The microscope tip can map chiral forces with 2 nm lateral resolution, revealing a distinct spatial distribution of forces for each handedness.

  9. Enantioselective degradation of dufulin in four types of soil.

    Science.gov (United States)

    Zhang, Kan-Kan; Hu, De-Yu; Zhu, Hui-Jun; Yang, Jin-Chuan; Song, Bao-An

    2014-02-26

    In this study, enantioselective degradation of dufulin in four types of soil (Guiyang silty loam, Nanning silty clay, Hefei silty clay, and Harbin silty clay) was investigated under sterile and nonsterile conditions. Pesticide residues in soil samples were extracted with acetonitrile. S-(+)-Dufulin and R-(-)-dufulin were separated and determined on an amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak IA) chiral column by normal phase high-performance liquid chromatography (HPLC). The absolute configurations of dufulin enantiomers were determined by obtaining experimental and computed circular dichroism spectra. Dufulin enantiomers were found to be configurationally stable in the selected soils, and no interconversion was observed during the incubation of enantiopure S-(+)- or R-(-)-dufulin under nonsterile conditions. Compared to the half-life (t1/2) of dufulin in sterile soils, the degradation rate was higher in nonsterile soils, which suggests that dufulin degradation can be attributed primarily to microbial activity in soils used for agricultural cultivation. Furthermore, enantiopure S-(+)-dufulin degraded more rapidly than its antipode. This suggests that use of enantiopure S-(+)-dufulin could exert less disturbance to soil bioactivity and contribute less to environmental pollution.

  10. Enantioselective biotransformation of pentoxifylline into lisofylline using wine yeast biocatalysis.

    Science.gov (United States)

    Pekala, Elzbieta; Wójcik, Tomasz

    2007-01-01

    Lisofylline (1-(5-R-hydroxyhexyl)-3,5-dimethylxanthine (LSF)) is a new methylxanthine, a stereospecific isomer which is a metabolite of pentoxifylline (1-(5-oxohexyl)-3,5-dimethylxanthine (PTX)). Alcohol dehydrogenases (E.C. 1.1.X.Y.) are enzymes that catalyze the oxidation and reduction of hydroxyl and carbonyl compounds. They may be employed either as crude or purified enzymes or as components of whole cells. The aim of this study was to explore the stereoselective bioreduction of PTX in the presence of whole cell baker's and wine yeasts, which function as biocatalysts in the production of LSF. The experiments were conducted in water and a number of organic solvents (toluene, hexane, ethyl acetate), and we obtained LSF with different yields and ee values. Our research demonstrated that the highest activity is shown when the KKPU strain is used in an aqueous medium. The biotransformation of PTX into LSF in this case was characterized by high yield and enantioselectivity: 95% and ee = 98%, respectively.

  11. Enantioselective Pharmacokinetics of α-Lipoic Acid in Rats

    Directory of Open Access Journals (Sweden)

    Ryota Uchida

    2015-09-01

    Full Text Available α-Lipoic acid (LA is widely used for nutritional supplements as a racemic mixture, even though the R enantiomer is biologically active. After oral administration of the racemic mixture (R-α-lipoic acid (RLA and S-α-lipoic acid (SLA mixed at the ratio of 50:50 to rats, RLA showed higher plasma concentration than SLA, and its area under the plasma concentration-time curve from time zero to the last (AUC was significantly about 1.26 times higher than that of SLA. However, after intravenous administration of the racemic mixture, the pharmacokinetic profiles, initial concentration (C0, AUC, and half-life (T1/2 of the enantiomers were not significantly different. After oral and intraduodenal administration of the racemic mixture to pyrolus-ligated rats, the AUCs of RLA were significantly about 1.24 and 1.32 times higher than that of SLA, respectively. In addition, after intraportal administration the AUC of RLA was significantly 1.16 times higher than that of SLA. In conclusion, the enantioselective pharmacokinetics of LA in rats arose from the fraction absorbed multiplied by gastrointestinal availability (FaFg and hepatic availability (Fh, and not from the total clearance.

  12. DNA demethylation by 5-aza-2-deoxycytidine treatment abrogates 17 beta-estradiol-induced cell growth and restores expression of DNA repair genes in human breast cancer cells.

    Science.gov (United States)

    Singh, Kamaleshwar P; Treas, Justin; Tyagi, Tulika; Gao, Weimin

    2012-03-01

    Prolonged exposure to elevated levels of estrogen is a risk factor for breast cancer. Though increased cell growth and loss of DNA repair capacity is one of the proposed mechanisms for estrogen-induced cancers, the mechanism through which estrogen induces cell growth and decreases DNA repair capacity is not clear. DNA hypermethylation is known to inactivate DNA repair genes and apoptotic response in cancer cells. Therefore, the objective of this study was to determine the role of DNA hypermethylation in estrogen-induced cell growth and regulation of DNA repair genes expression in breast cancer cells. To achieve this objective, the estrogen-responsive MCF-7 cells either pretreated with 5-aza-2-deoxycytidine (5-aza-dC) or untreated (as control) were exposed to 17 beta-estradiol (E2), and its effect on cell growth and expression of DNA repair genes were measured. The result revealed that 5-aza-dC abrogates the E2-induced growth in MCF-7 cells. An increased expression of OGG1, MSH4, and MLH1 by 5-aza-dC treatment alone, suggest the DNA hypermethylation as a potential cause for decreased expression of these genes in MCF-7 cells. The decreased expression of ERCC1, XPC, OGG1, and MLH1 by E2 alone and its restoration by co-treatment with 5-aza-dC further suggest that E2 reduces the expression of these DNA repair genes potentially through promoter hypermethylation. Reactivation of mismatch repair (MMR) gene MLH1 and abrogation of E2-induced cell growth by 5-aza-dC treatment suggest that estrogen causes increased growth in breast cancer cells potentially through the inhibition of MMR-mediated apoptotic response. In summary, this study suggests that estrogen increases cell growth and decreases the DNA repair capacity in breast cancer cells, at least in part, through epigenetic mechanism. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. Demethylation by 5-aza-2'-deoxycytidine in colorectal cancer cells targets genomic DNA whilst promoter CpG island methylation persists

    Directory of Open Access Journals (Sweden)

    Kim Kyu-Tae

    2010-07-01

    Full Text Available Abstract Background DNA methylation and histone acetylation are epigenetic modifications that act as regulators of gene expression. Aberrant epigenetic gene silencing in tumours is a frequent event, yet the factors which dictate which genes are targeted for inactivation are unknown. DNA methylation and histone acetylation can be modified with the chemical agents 5-aza-2'-deoxycytidine (5-aza-dC and Trichostatin A (TSA respectively. The aim of this study was to analyse de-methylation and re-methylation and its affect on gene expression in colorectal cancer cell lines treated with 5-aza-dC alone and in combination with TSA. We also sought to identify methylation patterns associated with long term reactivation of previously silenced genes. Method Colorectal cancer cell lines were treated with 5-aza-dC, with and without TSA, to analyse global methylation decreases by High Performance Liquid Chromatography (HPLC. Re-methylation was observed with removal of drug treatments. Expression arrays identified silenced genes with differing patterns of expression after treatment, such as short term reactivation or long term reactivation. Sodium bisulfite sequencing was performed on the CpG island associated with these genes and expression was verified with real time PCR. Results Treatment with 5-aza-dC was found to affect genomic methylation and to a lesser extent gene specific methylation. Reactivated genes which remained expressed 10 days post 5-aza-dC treatment featured hypomethylated CpG sites adjacent to the transcription start site (TSS. In contrast, genes with uniformly hypermethylated CpG islands were only temporarily reactivated. Conclusion These results imply that 5-aza-dC induces strong de-methylation of the genome and initiates reactivation of transcriptionally inactive genes, but this does not require gene associated CpG island de-methylation to occur. In addition, for three of our selected genes, hypomethylation at the TSS of an epigenetically

  14. Demethylation by 5-aza-2'-deoxycytidine in colorectal cancer cells targets genomic DNA whilst promoter CpG island methylation persists

    International Nuclear Information System (INIS)

    Mossman, David; Kim, Kyu-Tae; Scott, Rodney J

    2010-01-01

    DNA methylation and histone acetylation are epigenetic modifications that act as regulators of gene expression. Aberrant epigenetic gene silencing in tumours is a frequent event, yet the factors which dictate which genes are targeted for inactivation are unknown. DNA methylation and histone acetylation can be modified with the chemical agents 5-aza-2'-deoxycytidine (5-aza-dC) and Trichostatin A (TSA) respectively. The aim of this study was to analyse de-methylation and re-methylation and its affect on gene expression in colorectal cancer cell lines treated with 5-aza-dC alone and in combination with TSA. We also sought to identify methylation patterns associated with long term reactivation of previously silenced genes. Colorectal cancer cell lines were treated with 5-aza-dC, with and without TSA, to analyse global methylation decreases by High Performance Liquid Chromatography (HPLC). Re-methylation was observed with removal of drug treatments. Expression arrays identified silenced genes with differing patterns of expression after treatment, such as short term reactivation or long term reactivation. Sodium bisulfite sequencing was performed on the CpG island associated with these genes and expression was verified with real time PCR. Treatment with 5-aza-dC was found to affect genomic methylation and to a lesser extent gene specific methylation. Reactivated genes which remained expressed 10 days post 5-aza-dC treatment featured hypomethylated CpG sites adjacent to the transcription start site (TSS). In contrast, genes with uniformly hypermethylated CpG islands were only temporarily reactivated. These results imply that 5-aza-dC induces strong de-methylation of the genome and initiates reactivation of transcriptionally inactive genes, but this does not require gene associated CpG island de-methylation to occur. In addition, for three of our selected genes, hypomethylation at the TSS of an epigenetically silenced gene is associated with the long term reversion of

  15. Direct and enantioselective α-allylation of ketones via singly occupied molecular orbital (SOMO) catalysis

    Science.gov (United States)

    Mastracchio, Anthony; Warkentin, Alexander A.; Walji, Abbas M.; MacMillan, David W. C.

    2010-01-01

    The first enantioselective organocatalytic α-allylation of cyclic ketones has been accomplished via singly occupied molecular orbital catalysis. Geometrically constrained radical cations, forged from the one-electron oxidation of transiently generated enamines, readily undergo allylic alkylation with a variety of commercially available allyl silanes. A reasonable latitude in both the ketone and allyl silane components is readily accommodated in this new transformation. Moreover, three new oxidatively stable imidazolidinone catalysts have been developed that allow cyclic ketones to successfully participate in this transformation. The new catalyst platform has also been exploited in the first catalytic enantioselective α-enolation and α-carbooxidation of ketones. PMID:20921367

  16. Aziridino Alcohols as Catalysts for the Enantioselective Addition of Diethylzinc to Aldehydes

    DEFF Research Database (Denmark)

    Tanner, David Ackland; Kornø, Hanne Tøfting; Guijarro, David

    1998-01-01

    The chiral aziridino alcohols 1 -3 have been prepared either from amino acids (1a from serine; 1b - 1i and 3 from threonine; 2a - 2e from allo-threonine) or via asymmetric synthesis (1j, 1k, 1l and 2f from methyl cinnamate). These easily available ligands act as catalysts for the enantioselective...... addition of diethylzinc to benzaldehyde, with up to 90% stereoselectivity. The absolute configuration of the alcohol product is dependent on the substitution pattern of the aziridine ring, and different transition state models are proposed to explain the observed switch in enantioselectivity. The C-2...

  17. Synthesis of New Phosphahelicene Scaffolds and Development of Gold(I)-Catalyzed Enantioselective Allenene Cyclizations.

    Science.gov (United States)

    Aillard, Paul; Retailleau, Pascal; Voituriez, Arnaud; Marinetti, Angela

    2015-08-17

    This paper reports on the development of an efficient synthesis of enantiopure phospha[6]helicenes through a [2+2+2] alkyne cyclotrimerization reaction. The corresponding gold complexes proved to be highly efficient both in terms of catalytic activity and enantioselectivity in [2+2] and [4+2] cycloaddition reactions. Furthermore, in the presence of an external nucleophile, such as water or alcohols, the tandem cyclization/addition reactions take place in high yields and excellent diastereo- and enantioselectivities. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Highly efficient and enantioselective cyclization of aromatic imines via directed C-H bond activation.

    Science.gov (United States)

    Thalji, Reema K; Ellman, Jonathan A; Bergman, Robert G

    2004-06-16

    The first highly enantioselective catalytic reaction involving aromatic C-H bond activation is communicated. Enantioselective cyclization of aromatic ketimines containing alkenyl groups tethered at the meta position of an imine directing group has been achieved using 5 mol % [RhCl(coe)2]2 and 15 mol % of an (S)-binol-derived phosphoramidite ligand. Selectivities of up to 96% ee and up to quantitative yields were obtained. Moreover, the identified catalyst system enables the intramolecular alkylation reaction to be performed at temperatures 75 degrees C lower than our previously reported achiral system. The reaction can even be performed at room temperature for one of the optimal substrates.

  19. Asymmetric Hydrogenation of Seven-Membered C=N-containing Heterocycles and Rationalization of the Enantioselectivity.

    Science.gov (United States)

    Balakrishna, Bugga; Bauzá, Antonio; Frontera, Antonio; Vidal-Ferran, Anton

    2016-07-18

    Iridium(I) complexes with phosphine-phosphite ligands efficiently catalyze the enantioselective hydrogenation of diverse seven-membered C=N-containing heterocyclic compounds (eleven examples; up to 97 % ee). The P-OP ligand L3, which incorporates an ortho-diphenyl substituted octahydrobinol phosphite fragment, provided the highest enantioselectivities in the hydrogenation of most of the heterocyclic compounds studied. The observed stereoselection was rationalized by means of DFT calculations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Enantioselective Synthesis of β-Hydrazino Alcohols Using Alcohols and N-Boc-Hydrazine as Substrates.

    Science.gov (United States)

    Cui, Zhihao; Du, Da-Ming

    2016-11-04

    An enantioselective approach for the synthesis of α-hydrazino aldehydes is described that utilizes alcohols and N-Boc hydrazine instead of the conventional combination of aldehydes with azodicarboxylates. This protocol is enabled by merging in situ aerobic dual oxidation with asymmetric organocatalysis. This reaction also exhibits a high tolerance for varieties of substituents on the alcohol component. This approach features excellent enantiocontrol, cheap starting materials, operational simplicity, and scalability. The corresponding chiral β-hydrazino alcohols were obtained by sequential reduction with excellent enantioselectivity (up to 98% ee).

  1. Application of Phosphine-Phosphite Ligands in the Iridium Catalyzed Enantioselective Hydrogenation of 2-Methylquinoline

    Directory of Open Access Journals (Sweden)

    Miguel Rubio

    2010-10-01

    Full Text Available The hydrogenation of 2-methylquinoline with Ir catalysts based on chiral phosphine-phosphites has been investigated. It has been observed that the reaction is very sensitive to the nature of the ligand. Optimization of the catalyst, allowed by the highly modular structure of these phosphine-phosphites, has improved the enantioselectivity of the reaction up to 73% ee. The influence of additives in this reaction has also been investigated. Contrary to the beneficial influence observed in related catalytic systems, iodine has a deleterious effect in the present case. Otherwise, aryl phosphoric acids produce a positive impact on catalyst activity without a decrease on enantioselectivity.

  2. Enantioselective Construction of the ABCDE Pentacyclic Core of the Strychnos Alkaloids.

    Science.gov (United States)

    Gammack Yamagata, Adam D; Dixon, Darren J

    2017-04-07

    An efficient enantioselective 12-step synthesis of the ABCDE pentacyclic core of the Strychnos alkaloids is described. A key feature of this approach is an organocatalyzed enantioselective desymmetrization to generate the morphan core in high ee and dr. After palladium-catalyzed installation of the indole moiety, a subsequent 5-exo-trig dearomatizing atom transfer radical cyclization was developed to construct the C-ring. Following a series of functional group interconversions, the pentacyclic amine core was obtained with all the relevant architecture including five stereocenters pertaining to the Strychnos alkaloids.

  3. Enantioselective Alkylation of 2-Oxindoles Catalyzed by a Bifunctional Phase-Transfer Catalyst: Synthesis of (-)-Debromoflustramine B.

    Science.gov (United States)

    Craig, Ryan; Sorrentino, Emiliano; Connon, Stephen J

    2018-03-26

    A new bifunctional phase-transfer catalyst that employs hydrogen bonding as a control element was developed to promote efficient enantioselective S N 2 reactions for the construction all-carbon quaternary stereocenters in high yield and excellent enantioselectivity (up to 97 % ee) utilizing the alkylation of a malleable oxindole substrate. The utility of the methodology was demonstrated through a concise and highly enantioselective synthesis of (-)-debromoflustramine B. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Enantioselective Iridium Catalyzed Carbonyl Allylation from the Alcohol Oxidation Level via Transfer Hydrogenation: Minimizing Pre-Activation for Synthetic Efficiency

    Science.gov (United States)

    Han, Soo Bong; Kim, In Su; Krische, Michael J.

    2010-01-01

    Existing methods for enantioselective carbonyl allylation, crotylation and tert-prenylation require stoichiometric generation of pre-metallated nucleophiles and often employ stoichiometric chiral modifiers. Under the conditions of transfer hydrogenation employing an ortho-cyclometallated iridium C,O-benzoate catalyst, enantioselective carbonyl allylations, crotylations and tert-prenylations are achieved in the absence of stoichiometric metallic reagents or stoichiometric chiral modifiers. Moreover, under transfer hydrogenation conditions, primary alcohols function dually as hydrogen donors and aldehyde precursors, enabling enantioselective carbonyl addition directly from the alcohol oxidation level. PMID:20024203

  5. Asymmetric Synthesis of Diarylmethyl Sulfones by Palladium-Catalyzed Enantioselective Benzylic Substitution: A Remarkable Effect of Water.

    Science.gov (United States)

    Najib, Atifah; Hirano, Koji; Miura, Masahiro

    2018-03-25

    A Pd/(R)-BINAP-catalyzed enantioselective benzylic sulfonation of diarylmethyl carbonates with sodium sulfinates proceeds to deliver the corresponding chiral diarylmethyl sulfones in good yields with high enantioselectivity. The reaction occurs in a dynamic kinetic asymmetric transformation (DYKAT) manner and thus provides convergent access to optically active benzylic sulfones from racemic secondary benzylic carbonates. Additionally, the addition of H 2 O is found to be critical for high enantioselectivity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Palladium-Catalyzed Enantioselective C-H Olefination of Diaryl Sulfoxides through Parallel Kinetic Resolution and Desymmetrization.

    Science.gov (United States)

    Zhu, Yu-Chao; Li, Yan; Zhang, Bo-Chao; Zhang, Feng-Xu; Yang, Yi-Nuo; Wang, Xi-Sheng

    2018-03-07

    The first example of Pd II -catalyzed enantioselective C-H olefination with non-chiral or racemic sulfoxides as directing groups was developed. A variety of chiral diaryl sulfoxides were synthesized with high enantioselectivity (up to 99 %) through both desymmetrization and parallel kinetic resolution (PKR). This is the first report of Pd II -catalyzed enantioselective C(sp 2 )-H functionalization through PKR, and it represents a novel strategy to construct sulfur chiral centers. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Silver-Mediated Base Pairs in DNA Incorporating Purines, 7-Deazapurines, and 8-Aza-7-deazapurines: Impact of Reduced Nucleobase Binding Sites and an Altered Glycosylation Position.

    Science.gov (United States)

    Zhao, Hang; Leonard, Peter; Guo, Xiurong; Yang, Haozhe; Seela, Frank

    2017-04-24

    Formation of silver-mediated DNA was studied with oligonucleotides incorporating 8-aza-7-deazapurine, 7-deazapurine, and purine nucleosides. The investigation was performed on non-self-complementary duplexes with one or two modifications and self-complementary duplexes with an alternating dA-dT motif. Homo base pairs as well as base pair mismatches of dA analogues with dC and Watson-Crick pairs with dT were studied by stoichiometric silver ion titration and T m measurements. N 8 -Glycosylated 8-aza-7-deazaadenine forms silver-ion-mediated base pairs capturing two silver ions (low silver content) whereas regularly glycosylated 8-aza-7-deazapurine, 7-deazapurine (c 7 A d ), and dA do not form comparable structures. Stable silver-mediated "dA-dC" base pair mismatches were detected for all nucleosides. Two silver ions per base pair are bound by 8-aza-7-deazapurine whereas c 7 A d binds only one silver ion. The situation is different when the equivalents of silver ions were increased to the number of total base pairs. Surprisingly, in 12-mer duplexes as well as in related 25-mer duplexes every base pair consumed one silver ion. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Asymmetric Domino Aza-Michael Addition/[3+2] Cycloaddition Reactions as a Versatile Approach to alpha,beta,gamma,-Triamino Acid Derivatives

    Czech Academy of Sciences Publication Activity Database

    Kapras, Vojtěch; Pohl, Radek; Císařová, I.; Jahn, Ullrich

    2014-01-01

    Roč. 16, č. 4 (2014), s. 1088-1091 ISSN 1523-7060 Institutional support: RVO:61388963 Keywords : 1,3-dipolar cycloaddition * lithium amides * aza-Michael addition * amino acids * pyrazoles Subject RIV: CC - Organic Chemistry Impact factor: 6.364, year: 2014

  9. Improvement of enantioselectivity by immobilized imprinting of epoxide hydrolase from Rhodotorula glutinis

    NARCIS (Netherlands)

    Kronenburg, N.A.E.; Bont, de J.A.M.; Fischer, L.

    2001-01-01

    The yeast Rhodotorula glutinis contains an enantioselective, membrane-associated epoxide hydrolase (EH). Partially purified EH was immobilized in a two-step procedure. In the first step, the proteins were derivatized with itaconic anhydride. In the second step, the derivatized proteins were

  10. Enantioselective analysis of proteinogenic amino acids in cerebrospinal fluid by capillary electrophoresis–mass spectrometry

    NARCIS (Netherlands)

    Prior, Amir; Sánchez-Hernández, Laura; Sastre-Toraño, Javier|info:eu-repo/dai/nl/304840424; Marina, Maria Luisa; de Jong, Gerhardus J.|info:eu-repo/dai/nl/080685072; Somsen, Govert W.

    2016-01-01

    d-Amino acids (AAs) are increasingly being recognized as essential molecules in biological systems. Enantioselective analysis of proteinogenic AAs in biological samples was accomplished by CE–MS employing β-CD as chiral selector and ESI via sheath-liquid (SL) interfacing. Prior to analysis, AAs were

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

    Science.gov (United States)

    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).

  12. Efficient and highly enantioselective formation of the all-carbon quaternary stereocentre of lyngbyatoxin A

    DEFF Research Database (Denmark)

    Vital, Paulo J.V.; Tanner, David

    2006-01-01

    Indole 25, an advanced intermediate in a projected enantioselective total synthesis of lyngbyatoxin A 1, was prepared from allylic alcohol 11 in 9 steps and >95% ee, key transformations being the enantiospecific rearrangement of vinyl epoxide 14 and the Hemetsberger-Knittel reaction of azide 24....

  13. Exploiting the enantioselectivity of Baeyer-Villiger monooxygenases via boron oxidation

    NARCIS (Netherlands)

    Brondani, Patricia B.; Dudek, Hanna; Reis, Joel S.; Fraaije, Marco W.; Andrade, Leandro H.

    2012-01-01

    The enantioselective carbon-boron bond oxidation of several chiral boron-containing compounds by Baeyer-Villiger monooxygenases was evaluated. PAMO and M446G PAMO conveniently oxidized 1-phenylethyl boronate into the corresponding 1-(phenyl)ethanol (ee = 82-91%). Cyclopropyl boronic esters were also

  14. Enantioselective transesterification of glycidol catalysed by a novel lipase expressed from Bacillus subtilis.

    Science.gov (United States)

    Wang, Lei; Tai, Jian-Dong; Wang, Ren; Xun, Er-Na; Wei, Xiao-Fei; Wang, Lei; Wang, Zhi

    2010-05-10

    A novel plasmid (pBSR2) was constructed by incorporating a strong lipase promoter and a terminator into the original pBD64. The lipase gene from Bacillus subtilis strain IFFI10210 was cloned into the plasmid pBSR2 and transformed into B. subtilis A.S.1.1655 to obtain an overexpression strain. The recombinant lipase [BSL2 (B. subtilis lipase 2)] has been expressed from the novel constructed strain and used in kinetic resolution of glycidol through enantioselective transesterification. The effects of reaction conditions on the activity as well as enantioselectivity were investigated. BSL2 showed a satisfying enantioselectivity (E>30) under the optimum conditions [acyl donor: vinyl butyrate; the mole ratio of vinyl butyrate to glycidol was 3:1; organic medium: 1,2-dichloroethane with water activity (a(w))=0.33; temperature 40 degrees C]. The remaining (R)-glycidol with a high enantiomeric purity [ee (enantiomeric excess) >99%] could be obtained when the conversion was approx. 60%. The results clearly show a good potential for industrial application of BSL2 in the resolution of glycidol through enantioselective transesterification.

  15. Lipase Catalyzed Enantioselective Transesterification of 5-Acyloxy-2(5H)-Furanones

    NARCIS (Netherlands)

    Deen, Hanneke van der; Hof, Robert P.; Oeveren, Arjan van; Kellogg, Richard M.; Feringa, Bernard

    1994-01-01

    Several lipases catalyse the transesterification of gamma-acyloxyfuranones in organic solvents with high enantioselectivities. This method has been used for the kinetic resolution of 5-acetoxy-2(5H)-furanone, 5-acetoxy-4-methyl-2(5H)-furanone and 5-propionyloxy-2(5H)-furanone, in e.e.'s ranging from

  16. Diversity-Oriented Enantioselective Synthesis of Highly Functionalized Cyclic and Bicyclic Alcohols

    NARCIS (Netherlands)

    Mao, Bin; Fananas Mastral, Martin; Lutz, Martin; Feringa, Ben L.

    The copper-catalyzed hetero-allylic asymmetric alkylation (h-AAA) of functionalized Grignard reagents that contain alkene or alkyne moieties has been achieved with excellent regio-and enantioselectivity. The corresponding alkylation products were further transformed into a variety of highly

  17. Resolution of alpha/beta-amino acids by enantioselective penicillin G acylase from Achromobacter sp

    Czech Academy of Sciences Publication Activity Database

    Grulich, Michal; Brezovský, J.; Štěpánek, Václav; Palyzová, Andrea; Kyslíková, Eva; Kyslík, Pavel

    2015-01-01

    Roč. 122, DEC 2015 (2015), s. 240-247 ISSN 1381-1177 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61388971 Keywords : Penicillin G acylase * Enantioselectivity * Homologous model Subject RIV: CE - Biochemistry Impact factor: 2.189, year: 2015

  18. Enantioselective Evans-Tishchenko Reduction of b-Hydroxyketone Catalyzed by Lithium Binaphtholate

    Directory of Open Access Journals (Sweden)

    Makoto Nakajima

    2011-06-01

    Full Text Available Lithium diphenylbinaphtholate catalyzed the enantioselective Evans-Tishchenko reduction of achiral b-hydroxyketones to afford monoacyl-protected 1,3-diols with high stereoselectivities. In the reaction of racemic b-hydroxyketones, kinetic optical resolution occurred in a highly stereoselective manner.

  19. The Enantioselectivity of Odor Sensation: Some Examples for Undergraduate Chemistry Courses

    Science.gov (United States)

    Kraft, Philip; Mannschreck, Albrecht

    2010-01-01

    This article discusses seven chiral odorants that demonstrate the enantioselectivity of odor sensation: carvone, Celery Ketone, camphor, Florhydral, 3-methyl-3-sulfanylhexan-1-ol, muscone, and methyl jasmonate. After a general introduction of the odorant-receptor interaction and the combinatorial code of olfaction, the olfactory properties of the…

  20. Directed evolution of metagenome-derived epoxide hydrolase for improved enantioselectivity and enantioconvergence

    Czech Academy of Sciences Publication Activity Database

    Kotík, Michael; Zhao, W.; Lacazio, G.; Archelas, A.

    2013-01-01

    Roč. 91, JUL 2013 (2013), s. 44-51 ISSN 1381-1177 R&D Projects: GA ČR GAP207/10/0135 Institutional support: RVO:61388971 Keywords : Regioselectivity * Enantioselectivity * Chiral building block Subject RIV: CE - Biochemistry Impact factor: 2.745, year: 2013

  1. Enantioselective copper catalyzed allylic alkylation using Grignard reagents; Applications in synthesis

    NARCIS (Netherlands)

    Zijl, Anthoni Wouter van

    2009-01-01

    Enantioselective copper catalyzed allylic alkylation is a powerful carbon-carbon bond forming reaction. In this thesis the development of a new catalyst for the use of Grignard reagents in this reaction is described. This catalyst is based on copper and the ligand Taniaphos. The high regio- and

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

    Science.gov (United States)

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

    2017-12-01

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

  3. Simple Aziridino Alcohols as Chiral Ligands. Enantioselective Additions of Diethylzinc to N-Diphenylphosphinoylimines

    DEFF Research Database (Denmark)

    Tanner, David Ackland; Andersson, Pher G.; Guijarro, David

    1996-01-01

    Simple chiral aziridino alcohols 2-5, easily available from L-serine, L-threonine or L-allo-threonine, have been used as ligands to promote the addition of Et(2)Zn to the diphenylphosphinoylimine 1 (Ar=Ph). Enantioselectivities of up to 94% could be obtained by proper choice of the substituents...

  4. Aziridino Alcohols as Catalysts for the Enantioselective Addition of Diethylzinc to Aldehydes

    DEFF Research Database (Denmark)

    Tanner, David Ackland; Kornø, Hanne Tøfting; Guijarro, David

    1998-01-01

    addition of diethylzinc to benzaldehyde, with up to 90% stereoselectivity. The absolute configuration of the alcohol product is dependent on the substitution pattern of the aziridine ring, and different transition state models are proposed to explain the observed switch in enantioselectivity. The C-2...

  5. Enantioselective polymerization of epoxides using biaryl-linked bimetallic cobalt catalysts: A mechanistic study

    KAUST Repository

    Ahmed, Syud M.

    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. © 2013 American Chemical Society.

  6. DNA-based asymmetric catalysis : Sequence-dependent rate acceleration and enantioselectivity

    NARCIS (Netherlands)

    Boersma, Arnold J.; Klijn, Jaap E.; Feringa, Ben L.; Roelfes, Gerard

    2008-01-01

    This study shows that the role of DNA in the DNA-based enantioselective Diels-Alder reaction of azachalcone with cyclopentadiene is not limited to that of a chiral scaffold. DNA in combination with the copper complex of 4,4'-dimethyl-2,2'-bipyridine (Cu-L1) gives rise to a rate acceleration of up to

  7. ENANTIOSELECTIVE CONJUGATE ADDITION OF DIETHYLZINC TO CHALCONES CATALYZED BY CHIRAL NI(II) AMINOALCOHOL COMPLEXES

    NARCIS (Netherlands)

    DEVRIES, AHM; JANSEN, JFGA; FERINGA, BL

    1994-01-01

    Conjugate addition of diethylzinc to chalcones is catalysed by complexes prepared in situ from Ni(acac)(2) and cis-exo-N,N-dialkyl-3-aminoisoborneols or (+)-cis-endo-N,N-dimethyl-3-aminoborneol ((+)- DAB) (13b). The products are obtained with enantioselectivities up to 84 %. When scalemic

  8. Enantioselective Conjugate Addition of Diethylzinc to Chalcones Catalysed by Chiral Ni(II) Aminoalcohol Complexes

    NARCIS (Netherlands)

    Vries, André H.M. de; Jansen, Johan F.G.A.; Feringa, Bernard

    1994-01-01

    Conjugate addition of diethylzinc to chalcones is catalysed by complexes prepared in situ from Ni(acac)2 and cis-exo-N,N-dialkyl-3-aminoisoborneols or (+)-cis-endo-N,N-dimethyl-3-aminoborneol ((+)-DAB) (13b). The products are obtained with enantioselectivities up to 84 %. When scalemic

  9. Pd(II)-Catalyzed Enantioselective C-H Olefination of Diphenylacetic Acids

    Science.gov (United States)

    Shi, Bing-Feng; Zhang, Yang-Hui; Lam, Jonathan K.; Wang, Dong-Hui; Yu, Jin-Quan

    2009-01-01

    Pd(II)-catalyzed enantioselective C-H olefination of diphenylacetic acid substrates has been achieved through the use of mono-protected chiral amino acid ligands. The absolute configuration of the resulting olefinated products is consistent with that of a proposed C-H insertion intermediate. PMID:20017549

  10. A Green, Enantioselective Synthesis of Warfarin for the Undergraduate Organic Laboratory

    Science.gov (United States)

    Wong, Terence C.; Sultana, Camille M.; Vosburg, David A.

    2010-01-01

    The enantioselective synthesis of drugs is of fundamental importance in the pharmaceutical industry. In this experiment, students synthesize either enantiomer of warfarin, a widely used anticoagulant, in a single step from inexpensive starting materials. Stereoselectivity is induced by a commercial organocatalyst, ("R","R")- or…

  11. Screening of commercial enzymes for the enantioselective hydrolysis of R,S-naproxen ester

    CSIR Research Space (South Africa)

    Steenkamp, Lucia H

    2003-03-03

    Full Text Available CN, filtered through cotton wool and analysed by HPLC to determine the percentage m/m and R/S ratio. Eight commercially available enzymes were selected for optimisation of enantioselectivity through statistically designed experiments where the reaction...

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

    Science.gov (United States)

    Hoang, Gia L.

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

  13. Uncovering Key Structural Features of an Enantioselective Peptide-Catalyzed Acylation Utilizing Advanced NMR Techniques

    Czech Academy of Sciences Publication Activity Database

    Procházková, Eliška; Kolmer, A.; Ilgen, J.; Schwab, M.; Kaltschnee, L.; Fredersdorf, M.; Schmidts, V.; Wende, R. C.; Schreiner, P. R.; Thiele, C. M.

    2016-01-01

    Roč. 55, č. 51 (2016), s. 15754-15759 ISSN 1433-7851 Institutional support: RVO:61388963 Keywords : conformational analysis * enantioselective acylations * NMR spectroscopy * pure shift NMR * RDCs Subject RIV: CC - Organic Chemistry Impact factor: 11.994, year: 2016

  14. In-silico driven engineering of enantioselectivity of a penicillin G acylase towards active pharmaceutical ingredients

    Czech Academy of Sciences Publication Activity Database

    Grulich, Michal; Brezovský, J.; Štěpánek, Václav; Palyzová, Andrea; Marešová, Helena; Zahradník, Jiří; Kyslíková, Eva; Kyslík, Pavel

    2016-01-01

    Roč. 133, Supplement 1 (2016), s. 53-59 ISSN 1381-1177 Institutional support: RVO:61388971 Keywords : Docking experiments * Enantioselectivity * Penicillin G acylase Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 2.269, year: 2016

  15. Syntheses of a Flobufen Metabolite and Dapoxetine Based on Enantioselective Allylation of Aromatic Aldehydes

    Czech Academy of Sciences Publication Activity Database

    Hessler, F.; Korotvička, A.; Nečas, D.; Valterová, Irena; Kotora, M.

    2014-01-01

    Roč. 2014, č. 12 (2014), s. 2543-2548 ISSN 1434-193X Grant - others:GA ČR(CZ) GAP207/11/0587 Institutional support: RVO:61388963 Keywords : synthetic methods * asymmetric catalysis * organocatalysis * allylation * aldehydes * enantioselectivity Subject RIV: CC - Organic Chemistry Impact factor: 3.065, year: 2014

  16. An Enantioselective Synthetic Route toward Second-Generation Light-Driven Rotary Molecular Motors

    NARCIS (Netherlands)

    Pijper, Thomas C.; Pijper, Dirk; Pollard, Michael M.; Dumur, Frederic; Davey, Stephen G.; Meetsma, Auke; Feringa, Ben L.

    2010-01-01

    Controlling the unidirectional rotary process of second-gene ration molecular motors demands access to these motors in their enantiomerically Pure form. In this paper, we describe an enantioselective route to three new second-generation light-driven molecular motors. Their synthesis starts with the

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

    Science.gov (United States)

    Guo, Qunsheng; Zhao, John Cong-Gui

    2013-01-01

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

  18. An enantioselective Brønsted acid catalyzed enamine Mannich reaction.

    Science.gov (United States)

    Tillman, A Louise; Dixon, Darren J

    2007-02-21

    An enantioselective Brønsted acid catalyzed Mannich reaction between acetophenone derived enamines and N-Boc imines has been developed. Simple diol (S)-H(8)-BINOL has been identified as the optimal catalyst, to afford versatile beta-amino aryl ketones in good yield and enantiomeric excess.

  19. A Regio- and Enantioselective CuH-Catalyzed Ketone Allylation with Terminal Allenes.

    Science.gov (United States)

    Tsai, Erica Y; Liu, Richard Y; Yang, Yang; Buchwald, Stephen L

    2018-02-14

    We report a method for the highly enantioselective CuH-catalyzed allylation of ketones that employs terminal allenes as allylmetal surrogates. Ketones and allenes bearing diverse and sensitive functional groups are efficiently coupled with high stereoselectivity and exclusive branched regioselectivity. In stoichiometric experiments, each elementary step of the proposed hydrocupration-addition-metathesis mechanism can be followed by NMR spectroscopy.

  20. Enantioselective Synthesis of α-Acetal-β'-Amino Ketone Derivatives by Rhodium-Catalyzed Asymmetric Hydrogenation.

    Science.gov (United States)

    Llopis, Quentin; Guillamot, Gérard; Phansavath, Phannarath; Ratovelomanana-Vidal, Virginie

    2017-12-01

    A range of β-keto-γ-acetal enamides has been synthesized and transformed into the corresponding enantioenriched α-acetal-β'-amino ketones with enantioinductions of up to 99% by using rhodium/QuinoxP*-catalyzed enantioselective hydrogenation under mild conditions. This method also proved to be highly chemoselective toward the reduction of the C-C double bond.

  1. A DFT exploration of the enantioselective rearrangement of cyclohexene oxide to cyclohexenol

    DEFF Research Database (Denmark)

    Brandt, Peter; Norrby, Per-Ola; Andersson, Pher G.

    2003-01-01

    In this paper, we present computational results for the (1S,3R,4R)-3-(pyrrolidinyl)-methyl-2-azabicyclo[2.2.1]heptane mediated rearrangement of cyclohexene oxide. The results nicely explain the differences in enantioselectivities between catalytic and stoichiometric mode between different ligands...

  2. Enantioselective uptake, translocation and degradation of the chiral pesticides tebuconazole and imazalil by Phragmites australis.

    Science.gov (United States)

    Lv, Tao; Carvalho, Pedro N; Casas, Mònica Escolà; Bollmann, Ulla E; Arias, Carlos A; Brix, Hans; Bester, Kai

    2017-10-01

    Phytoremediation of realistic environmental concentrations (10 μg L -1 ) of the chiral pesticides tebuconazole and imazalil by Phragmites australis was investigated. This study focussed on removal dynamics, enantioselective mechanisms and transformation products (TPs) in both hydroponic growth solutions and plant tissues. For the first time, we documented uptake, translocation and metabolisation of these pesticides inside wetland plants, using enantioselective analysis. Tebuconazole and imazalil removal efficiencies from water reached 96.1% and 99.8%, respectively, by the end of the experiment (day 24). Removal from the solutions could be described by first-order removal kinetics with removal rate constants of 0.14 d -1 for tebuconazole and 0.31 d -1 for imazalil. Removal of the pesticides from the hydroponic solution, plant uptake, within plant translocation and degradation occurred simultaneously. Tebuconazole and imazalil concentrations inside Phragmites peaked at day 10 and 5d, respectively, and decreased thereafter. TPs of tebuconazole i.e., (5-(4-Chlorophenyl)-2,2-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)-1,3-pentanediol and 5-(3-((1H-1,2,4-Triazol-1-yl)methyl)-3-hydroxy-4,4-dimethylpentyl)-2-chlorophenol) were quantified in solution, while the imazalil TPs (α-(2,4-Dichlorophenyl)-1H-imidazole-1-ethanol and 3-[1-(2,4-Dichlorophenyl)-2-(1H-imidazol-1-yl)ethoxy]-1,2-propanediol) were quantified in both solution and plant tissue. Pesticide uptake by Phragmites was positively correlated with evapotranspiration. Pesticide removal from the hydroponic solution was not enantioselective. However, tebuconazole was degraded enantioselectively both in the roots and shoots. Imazalil translocation and degradation inside Phragmites were also enantioselective: R-imazalil translocated faster than S-imazalil. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Recyclable Fe3O4 Nanoparticles Catalysts for Aza-Michael Addition of Acryl Amides by Magnetic Field

    Directory of Open Access Journals (Sweden)

    Zhen-Xing Li

    2017-07-01

    Full Text Available A nanostructure-based catalytic system has the advantages of both homogeneous and heterogeneous catalysis. It is of great significance to develop the sustainable and green process of homogeneous catalytic reaction. We report a novel, efficient and recyclable magnetic Fe3O4 nanoparticles-catalyzed aza-Michael addition reaction of acryl amides, and the magnetic nanoparticles catalysts can be recovered by external magnetic field. Both primary amine and secondary amine can react with various acryl amides providing a good output to target products successfully at room temperature. Further experiments reveal that the magnetic Fe3O4 nanoparticles-based catalyst shows excellent yields, which can be recycled 10 times, and, at the same time, it maintains a high catalytically activity. In this catalytic system, the tedious separation procedures are replaced by external magnetic field, which gives us a different direction for choosing a catalyst in a nanostructure-based catalytic system.

  4. Structure-metabolism relationships inhuman-AOX: Chemical insights from a large database of aza-aromatic and amide compounds.

    Science.gov (United States)

    Lepri, Susan; Ceccarelli, Martina; Milani, Nicolò; Tortorella, Sara; Cucco, Andrea; Valeri, Aurora; Goracci, Laura; Brink, Andreas; Cruciani, Gabriele

    2017-04-18

    Aldehyde oxidase (AOX) is a metabolic enzyme catalyzing the oxidation of aldehyde and aza-aromatic compounds and the hydrolysis of amides, moieties frequently shared by the majority of drugs. Despite its key role in human metabolism, to date only fragmentary information about the chemical features responsible for AOX susceptibility are reported and only "very local" structure-metabolism relationships based on a small number of similar compounds have been developed. This study reports a more comprehensive coverage of the chemical space of structures with a high risk of AOX phase I metabolism in humans. More than 270 compounds were studied to identify the site of metabolism and the metabolite(s). Both electronic [supported by density functional theory (DFT) calculations] and exposure effects were considered when rationalizing the structure-metabolism relationship.

  5. Synthesis of N-(2-chloro purin-6-yl) aza-18-crown-6 and its interaction with human serum albumin.

    Science.gov (United States)

    Li, Cui; Cui, Fengling; Mao, Runze; Huo, Ruina; Qu, Guirong

    2012-01-28

    The synthesis of novel purine nucleosides-linked azacrown ethers in the C6 position, N-(2-chloro purin-6-yl) aza-18-crown-6 (NCPAC), was described. This new nucleoside analogue can be prepared from a series of N9-modified nucleosides and the method allows for new and easy modification of the nucleosides. The interaction between NCPAC and human serum albumin (HSA) was studied using molecular docking and fluorescence techniques. Thermodynamics revealed that the interaction was entropy driven with predominantly hydrophobic forces. From the observed Föster's-type fluorescence resonance energy transfer, the donor (Trp 214 in HSA) to acceptor (NCPAC) distance was calculated to be 3.6 nm. The conformational changes of HSA due to the interaction were investigated qualitatively from synchronous fluorescence spectra. Molecular docking studies were performed to obtain information on the possible residues involved in the interaction process.

  6. Crystallization and preliminary X-ray analysis of an enantioselective halohydrin dehalogenase from Agrobacterium radiobacter AD1

    NARCIS (Netherlands)

    Jong, René M. de; Rozeboom, Henriëtte J.; Kalk, Kor H.; Tang, Lixia; Janssen, Dick B.; Dijkstra, Bauke W.

    2002-01-01

    Halohydrin dehalogenases are key enzymes in the bacterial degradation of vicinal halopropanols and structurally related nematocides. Crystals of the enantioselective halohydrin dehalogenase HheC from Agrobacterium radiobacter AD1 have been obtained at room temperature from hanging-drop

  7. Crystallization and preliminary X-ray analysis of an enantioselective halohydrin dehalogenase from Agrobacterium radiobacter AD1

    NARCIS (Netherlands)

    de Jong, RM; Rozeboom, HJ; Kalk, KH; Tang, Lixia; Janssen, DB; Dijkstra, BW

    Halohydrin dehalogenases are key enzymes in the bacterial degradation of vicinal halopropanols and structurally related nematocides. Crystals of the enantioselective halohydrin dehalogenase HheC from Agrobacterium radiobacter AD1 have been obtained at room temperature from hanging-drop

  8. Enantioselective Bio-Hydrolysis of Various Racemic and meso Aromatic Epoxides Using the Recombinant Epoxide Hydrolase Kau2

    Czech Academy of Sciences Publication Activity Database

    Zhao, W.; Kotík, Michael; Iacazio, G.; Archelas, A.

    2015-01-01

    Roč. 357, č. 8 (2015), s. 1895-1908 ISSN 1615-4150 Institutional support: RVO:61388971 Keywords : biotransformations * chiral resolution * enantioselectivity Subject RIV: CE - Biochemistry Impact factor: 6.453, year: 2015

  9. hGH-V gene expression and promoter activity under glucose and 5-azacytidine (5azaC) effects.

    Science.gov (United States)

    de Jesús Romero-Prado, Marina Maria; Barrera-Saldaña, Hugo A; Castrillo-Diez, Jose Luis

    2010-02-15

    The metabolic conditions affecting placental development depend on nutritional state, genetic constitution and other external factors. The secretion of human placental growth hormone (hGH-V) had shown to be dependent of glucose, but the regulatory effects of this metabolite on hGH-V promoter activity and gene expression in presence of 5-azacytidine had not been studied. In this work we compared the hGH-V promoter activity and the endogenous mRNA expression in human placental choriocarcinoma cell line JAR in the presence of glucose and demethylating genome conditions. High glucose concentration in culture medium diminished hGH-V mRNA endogenous levels in JAR cells whereas the expression of hGH-V from transfected PACs was slightly higher; but in the presence of 5azaC a higher hGH-V gene expression from both the endogenous and the transfected ones was obtained. A drastic diminution of promoter analysis was shown when cells had no glucose (J0 cells) or in presence of 5azaC; the placental transcription factors that showed modified binding capacity were HES-2, PPAR-gamma, H4TF-1 and OCT-1. Our results suggest that in vitro suppressive glucose effect dictates a metabolic context to hGH-V gene expression and promoter regulation whereas a genomic methylation-dependent background is necessary to maintain placental transcription factors able to bind and regulate proximal promoter region of hGH-V in placental cells. Crown Copyright 2009. Published by Elsevier B.V. All rights reserved.

  10. Enantioselective gold(i)-catalyzed rearrangement of cyclopropyl-substituted 1,6-enynes into 2-oxocyclobutyl-cyclopentanes.

    Science.gov (United States)

    Wu, Zhiyong; Lebœuf, David; Retailleau, Pascal; Gandon, Vincent; Marinetti, Angela; Voituriez, Arnaud

    2017-07-04

    A gold(i)-catalyzed cycloisomerization/ring expansion sequence allows the highly enantioselective synthesis of 2-oxocyclobutylcyclopentane derivatives from cyclopropyl-substituted enynes. The bimetallic [(R)-MeO-DTBM-BIPHEP-(AuCl) 2 ] complex was found to be the best precatalyst, affording the desired cyclobutanones in high yields and enantioselectivities (up to 99% ee). The usefulness of the method was further demonstrated by preparing the tricyclic core scaffold of russujaponol D.

  11. Catalytic Enantioselective Synthesis of 3,4-Unsubstituted Thiochromenes through Sulfa-Michael/Julia-Kocienski Olefination Cascade Reaction.

    Science.gov (United States)

    Simlandy, Amit Kumar; Mukherjee, Santanu

    2017-05-05

    A highly enantioselective cascade sulfa-Michael/Julia-Kocienski olefination reaction between 2-mercaptobenzaldehydes and β-substituted vinyl PT-sulfones has been realized for the synthesis of 3,4-unsubstituted 2H-thiochromenes. This reaction, catalyzed by diphenylprolinol TMS ether, proceeds through an aromatic iminium intermediate and furnishes a wide range of 2-substiuted 2H-thiochromenes with excellent enantioselectivities (up to 99:1 er).

  12. Hydroxymethylation beyond Carbonylation: Enantioselective Iridium-Catalyzed Reductive Coupling of Formaldehyde with Allylic Acetates via Enantiotopic π-Facial Discrimination.

    Science.gov (United States)

    Garza, Victoria J; Krische, Michael J

    2016-03-23

    Chiral iridium complexes modified by SEGPHOS catalyze the 2-propanol-mediated reductive coupling of branched allylic acetates 1a-1o with formaldehyde to form primary homoallylic alcohols 2a-2o with excellent control of regio- and enantioselectivity. These processes, which rely on enantiotopic π-facial discrimination of σ-allyliridium intermediates, represent the first examples of enantioselective formaldehyde C-C coupling beyond aldol addition.

  13. An enantioselective organocatalytic intramolecular Morita-Baylis-Hillman (IMBH) reaction of dienones, and elaboration of the IMBH adducts to fluorenones.

    Science.gov (United States)

    Satpathi, Bishnupada; Wagulde, Siddhant V; Ramasastry, S S V

    2017-07-13

    An enantioselective organocatalytic intramolecular Morita-Baylis-Hillman (IMBH) reaction of dienones is reported for the first time. This has been achieved by incorporating entropy and synergy considerations during the substrate design. The reaction conditions are thoroughly verified for an efficient synthesis of highly functionalised cyclopenta-fused arenes and heteroarenes in excellent yields and enantioselectivities. The synthetic utility of the IMBH-adducts has been demonstrated by transforming them into 3,4-disubstituted fluorenones in a serendipitous manner.

  14. Cyclic aldimines as superior electrophiles for Cu-catalyzed decarboxylative Mannich reaction of β-ketoacids with a broad scope and high enantioselectivity.

    Science.gov (United States)

    Zhang, Heng-Xia; Nie, Jing; Cai, Hua; Ma, Jun-An

    2014-05-02

    A novel Cu-catalyzed enantioselective decarboxylative Mannich reaction of cyclic aldimines with β-ketoacids is described. The cyclic structure of these aldimines, in which the C═N bond is constrained in the Z geometry, appears to be important, allowing Mannich condensation to proceed in high yields with excellent enantioselectivities. A chiral chroman-4-amine was synthesized from the decarboxylative Mannich product in several steps without loss of enantioselectivity.

  15. ALDOL- AND MANNICH-TYPE REACTIONS VIA IN SITU OLEFIN MIGRATION IN IONIC LIQUID. (R828129)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  16. Choline-based biodegradable ionic liquid catalyst for Mannich-type ...

    Indian Academy of Sciences (India)

    aCollege of Chemical Engineering, Nanjing Tech University, Nanjing 210009, People's Republic of China. bSchool of Chemistry & Environmental Engineering, Yancheng Teachers University, Yancheng 224002,. People's Republic of China e-mail: fangdong106@sina.com. MS received 2 February 2016; revised 20 October ...

  17. RUTHENIUM-CATALYZED TANDEM OLEFIN MIGRATION-ALDOL AND MANNICH-TYPE REACTIONS IN IONIC LIQUID.

    Science.gov (United States)

    In the presence of a catalytic amount of RuCl2(PPh3)3, a cross-coupling of 3-buten-2-ol with aldehydes and imines was developed via a tandem olefin migration--aldol--Mannich reaction in bmim[PF6]. With In(OAc)3 as a co-catalyst, a-vinylbenzyl alcohol and aldehydes underwent sim...

  18. Catalytic asymmetric mannich-type reaction of N-alkylidene-α-aminoacetonitrile with ketimines.

    Science.gov (United States)

    Lin, Shaoquan; Kawato, Yuji; Kumagai, Naoya; Shibasaki, Masakatsu

    2015-04-20

    Optically active vicinal diamines are versatile chiral building blocks in organic synthesis. A soft Lewis acid/hard Brønsted base cooperative catalyst allows for an efficient stereoselective coupling of N-alkylidene-α-aminoacetonitrile and ketimines to access this class of compounds bearing consecutive tetra- and trisubstituted stereogenic centers. The strategic use of a soft Lewis basic thiophosphinoyl group for ketimines is the key to promoting the reaction, and aliphatic ketimines serve as suitable substrates with as little as 3 mol % catalyst loading. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Enantioselective Analysis in instruments onboard ROSETTA/PHILAE and ExoMars

    Science.gov (United States)

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

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

  20. Transition-metal-catalyzed enantioselective heteroatom-hydrogen bond insertion reactions.

    Science.gov (United States)

    Zhu, Shou-Fei; Zhou, Qi-Lin

    2012-08-21

    Carbon-heteroatom bonds (C-X) are ubiquitous and are among the most reactive components of organic compounds. Therefore investigations of the construction of C-X bonds are fundamental and vibrant fields in organic chemistry. Transition-metal-catalyzed heteroatom-hydrogen bond (X-H) insertions via a metal carbene or carbenoid intermediate represent one of the most efficient approaches to form C-X bonds. Because of the availability of substrates, neutral and mild reaction conditions, and high reactivity of these transformations, researchers have widely applied transition-metal-catalyzed X-H insertions in organic synthesis. Researchers have developed a variety of rhodium-catalyzed asymmetric C-H insertion reactions with high to excellent enantioselectivities for a wide range of substrates. However, at the time that we launched our research, very few highly enantioselective X-H insertions had been documented primarily because of a lack of efficient chiral catalysts and indistinct insertion mechanisms. In this Account, we describe our recent studies of copper- and iron-catalyzed asymmetric X-H insertion reactions by using chiral spiro-bisoxazoline and diimine ligands. The copper complexes of chiral spiro-bisoxazoline ligands proved to be highly enantioselective catalysts for N-H insertions of α-diazoesters into anilines, O-H insertions of α-diazoesters into phenols and water, O-H insertions of α-diazophosphonates into alcohols, and S-H insertions of α-diazoesters into mercaptans. The iron complexes of chiral spiro-bisoxazoline ligands afforded the O-H insertion of α-diazoesters into alcohols and water with unprecedented enantioselectivities. The copper complexes of chiral spiro-diimine ligands exhibited excellent reactivity and enantioselectivity in the Si-H insertion of α-diazoacetates into a wide range of silanes. These transition-metal-catalyzed X-H insertions have many potential applications in organic synthesis because the insertion products, including chiral

  1. Maleimide as an efficient nucleophilic partner in the aza-Morita-Baylis-Hillman reaction: synthesis of chiral 3-substituted-3-aminooxindoles.

    Science.gov (United States)

    Kumar, Akshay; Sharma, Vivek; Kaur, Jasneet; Kumar, Naveen; Chimni, Swapandeep Singh

    2015-05-28

    A highly enantioselective Morita-Baylis-Hillman reaction of maleimides with isatin derived ketimines has been developed to obtain enantiomerically enriched 3-substituted-3-aminooxindoles using β-isocupreidine as an organocatalyst. Maleimide acting as a nucleophile provides products with up to 99% ee.

  2. Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams

    KAUST Repository

    Behenna, Douglas C.

    2011-12-18

    The enantioselective synthesis of nitrogen-containing heterocycles (N-heterocycles) represents a substantial chemical research effort and resonates across numerous disciplines, including the total synthesis of natural products and medicinal chemistry. In this Article, we describe the highly enantioselective palladium-catalysed decarboxylative allylic alkylation of readily available lactams to form 3,3-disubstituted pyrrolidinones, piperidinones, caprolactams and structurally related lactams. Given the prevalence of quaternary N-heterocycles in biologically active alkaloids and pharmaceutical agents, we envisage that our method will provide a synthetic entry into the de novo asymmetric synthesis of such structures. As an entry for these investigations we demonstrate how the described catalysis affords enantiopure quaternary lactams that intercept synthetic intermediates previously used in the synthesis of the Aspidosperma alkaloids quebrachamine and rhazinilam, but that were previously only available by chiral auxiliary approaches or as racemic mixtures. © 2012 Macmillan Publishers Limited. All rights reserved.

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

    Science.gov (United States)

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

    2015-04-13

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

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

    Science.gov (United States)

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

    2012-01-01

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

  5. Enantioselective [3+3] atroposelective annulation catalyzed by N-heterocyclic carbenes

    KAUST Repository

    Zhao, Changgui

    2018-02-05

    Axially chiral molecules are among the most valuable substrates in organic synthesis. They are typically used as chiral ligands or catalysts in asymmetric reactions. Recent progress for the construction of these chiral molecules is mainly focused on the transition-metal-catalyzed transformations. Here, we report the enantioselective NHC-catalyzed (NHC: N-heterocyclic carbenes) atroposelective annulation of cyclic 1,3-diones with ynals. In the presence of NHC precatalyst, base, Lewis acid and oxidant, a catalytic C–C bond formation occurs, providing axially chiral α-pyrone−aryls in moderate to good yields and with high enantioselectivities. Control experiments indicated that alkynyl acyl azoliums, acting as active intermediates, are employed to atroposelectively assemble chiral biaryls and such a methodology may be creatively applied to other useful NHC-catalyzed asymmetric transformations.

  6. Enantioselective Intramolecular Hydroarylation of Alkenes via Directed C-H Bond Activation

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Hitoshi; Thalji, Reema; Bergman, Robert; Ellman, Jonathan

    2008-05-22

    Highly enantioselective catalytic intramolecular ortho-alkylation of aromatic imines containing alkenyl groups tethered at the meta position relative to the imine directing group has been achieved using [RhCl(coe){sub 2}]{sub 2} and chiral phosphoramidite ligands. Cyclization of substrates containing 1,1- and 1,2-disubstituted as well as trisubstituted alkenes were achieved with enantioselectivities >90% ee for each substrate class. Cyclization of substrates with Z-alkene isomers proceeded much more efficiently than substrates with E-alkene isomers. This further enabled the highly stereoselective intramolecular alkylation of certain substrates containing Z/E-alkene mixtures via a Rh-catalyzed alkene isomerization with preferential cyclization of the Z-isomer.

  7. Enantioselective intramolecular hydroarylation of alkenes via directed C-H bond activation.

    Science.gov (United States)

    Harada, Hitoshi; Thalji, Reema K; Bergman, Robert G; Ellman, Jonathan A

    2008-09-05

    Highly enantioselective catalytic intramolecular ortho-alkylation of aromatic imines containing alkenyl groups tethered at the meta position relative to the imine directing group has been achieved using [RhCl(coe)2]2 and chiral phosphoramidite ligands. Cyclization of substrates containing 1,1- and 1,2-disubstituted as well as trisubstituted alkenes were achieved with enantioselectivities >90% ee for each substrate class. Cyclization of substrates with Z-alkene isomers proceeded much more efficiently than substrates with E-alkene isomers. This further enabled the highly stereoselective intramolecular alkylation of certain substrates containing Z/E-alkene mixtures via a Rh-catalyzed alkene isomerization with preferential cyclization of the Z-isomer.

  8. Enantioselective Intramolecular Hydroarylation of Alkenes via Directed C–H Bond Activation

    Science.gov (United States)

    Harada, Hitoshi; Thalji, Reema K.; Bergman, Robert G.; Ellman, Jonathan A.

    2008-01-01

    Highly enantioselective catalytic intramolecular ortho-alkylation of aromatic imines containing alkenyl groups tethered at the meta position relative to the imine directing group has been achieved using [RhCl(coe)2]2 and chiral phosphoramidite ligands. Cyclization of substrates containing 1,1- and 1,2-disubstituted as well as trisubstituted alkenes were achieved with enantioselectivities >90% ee for each substrate class. Cyclization of substrates with Z-alkene isomers proceeded much more efficiently than substrates with E-alkene isomers. This further enabled the highly stereoselective intramolecular alkylation of certain substrates containing Z/E-alkene mixtures via a Rh-catalyzed alkene isomerization with preferential cyclization of the Z-isomer. PMID:18681407

  9. Multicomponent, Enantioselective Michael-Michael-Aldol-β-Lactonizations Delivering Complex β-Lactones.

    Science.gov (United States)

    Van, Khoi N; Romo, Daniel

    2018-01-19

    Optically active, tertiary amine Lewis bases react with unsaturated acid chlorides to deliver chiral, α,β-unsaturated acylammonium salts. These intermediates participate in a catalytic, enantioselective, three-component process delivering bi- and tricyclic β-lactones through a Michael-Michael-aldol-β-lactonization. In a single operation, the described multicomponent, organocascade process forms complex bi- and tricyclic β-lactones by generating four new bonds, two rings, and up to four contiguous stereocenters. In the racemic series, yields of 22-75% were achieved using 4-pyrrolidinopyridine as Lewis base. In the enantioselective series employing isothiourea catalysts, a kinetic resolution of the initially formed racemic Michael adduct appears operative, providing yields of 46% to quantitative (based on 50% max) with up to 94:6 er. Some evidence for a dynamic kinetic asymmetric transformation for tricyclic-β-lactone 1d was obtained following optimization (yields up to 61%, 94:6 er) through a presumed reversible Michael.

  10. Palladium/PC-Phos-Catalyzed Enantioselective Arylation of General Sulfenate Anions: Scope and Synthetic Applications.

    Science.gov (United States)

    Wang, Lei; Chen, Mingjie; Zhang, Peichao; Li, Wenbo; Zhang, Junliang

    2018-03-07

    Herein we reported an efficient palladium-catalyzed enantioselective arylation of both alkyl and aryl sulfenate anions to deliver various chiral sulfoxides in good yields (up to 98%) with excellent enantioselectivities (up to 99% ee) by the use of our developed chiral O,P-ligands (PC-Phos). PC-Phos are easily prepared in short steps from inexpensive commercially available starting materials. The single-crystal structure of the PC4/PdCl 2 showed that a rarely observed 11-membered ring was formed via the O,P-coordination with the palladium(II) center. The salient features of this method include general substrate scope, ease of scale-up, applicable to the late-stage modification of bioactive compounds, and the synthesis of a marketed medicine Sulindac.

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

    KAUST Repository

    Behenna, Douglas C.

    2011-11-14

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

  12. L-proline-catalyzed enantioselective one-pot cross-Mannich reaction of aldehydes.

    Science.gov (United States)

    Hayashi, Yujiro; Urushima, Tatsuya; Tsuboi, Wataru; Shoji, Mitsuru

    2007-01-01

    This protocol describes a procedure for the synthesis of syn-beta-amino alpha-substituted aldehydes, versatile intermediates in synthetic organic chemistry, via asymmetric, direct, one-pot, three-component, cross-Mannich reaction of two different aldehydes. The reaction consists of two steps; one is the formation of imine by the reaction of aldehyde and p-anisidine in the presence of Pro, and the second step is the enantioselective addition reaction of enamine generated from the other aldehyde and Pro with the imine generated in the first step. As the aldehyde easily racemizes, gamma-amino alcohol was isolated and characterized after reduction. The yield and diastereo- and enantioselectivities are generally excellent. It will take approximately 26 h to complete the protocol: 0.5 h to set up the reaction, 20.5 h for the reaction and 5 h for the isolation and purification.

  13. Enantioselective Light Harvesting with Perylenediimide Guests on Self-Assembled Chiral Naphthalenediimide Nanofibers.

    Science.gov (United States)

    Sethy, Ramarani; Kumar, Jatish; Métivier, Rémi; Louis, Marine; Nakatani, Keitaro; Mecheri, Nila Mohan Thazhe; Subhakumari, Akhila; Thomas, K George; Kawai, Tsuyoshi; Nakashima, Takuya

    2017-11-20

    Self-assembling molecular systems often display amplified chirality compared to the monomeric state, which makes the molecular recognition more sensitive to chiral analytes. Herein, we report the almost absolute enantioselective recognition of a chiral perylenediimide (PDI) molecule by chiral supramolecular nanofibers of a bichromophoric naphthalenediimide (NDI) derivative. The chiral recognition was evaluated through the Förster resonance energy transfer (FRET) from the NDI-based host nanofibers to the guest PDI molecules. The excitation energy was successfully transferred to the guest molecule through efficient energy migration along the host nanofiber, thus demonstrating the light-harvesting capability of these hybrid systems. Furthermore, circularly polarized luminescence (CPL) was enantioselectively sensitized by the guest molecule as the wavelength band and sign of the CPL signal were switched in response to the chiral guest molecule. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Enantioselective analysis of ibuprofen and its biotransformation products in water/sediment systems,

    DEFF Research Database (Denmark)

    Sundström, Maria; Escola, Monica; Radke, Michael

    2015-01-01

    As ibuprofen degrades enantioselectively in activated sludge, the same process is assumed to occur in surface lake-water and in river-water based biofilms. Yet, the effects of the wastewater inflow, containing non-racemic ibuprofen, into natural systems have never been studied. The role...... and oxic) from the Baltic Sea (Tvären and B1) were collected. All systems were spiked with ibuprofen and followed during one month (aerated and in darkness). The enantiomers of ibuprofen, 2-hydroxyibuprofen, 1-hydroxyibuprofen and 3-hydroxyibuprofen as well as carboxyibuprofen, were separated by HPLC...... equipped with an enantioselective HPLC-column. The detection was performed by MS/MS. Single first-order kinetics and Weibull distribution models were fitted to the data. Both models indicated that ibuprofen degraded with half-lives around 4-5 and 5-6 days in Largen and Fyrisån respectively and 3-4 and 5...

  15. Synthesis of 3-fluoro-3-aryl oxindoles: Direct enantioselective α arylation of amides

    KAUST Repository

    Wu, Linglin

    2012-02-06

    Modus operandi: Catalytic access to the title compounds through a new asymmetric α-arylation protocol is reported (see scheme). These products are formed in good yields and excellent enantioselectivities by using a new and easily synthesized chiral N-heterocyclic carbene (NHC) ligand. Advanced DFT calculations reveal the properties of the NHC ligand and the mode of operation of the catalyst. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Biochemical characterization of an enantioselective esterase from Brevundimonas sp. LY-2.

    Science.gov (United States)

    Zhang, Jing; Zhao, Mengjun; Yu, Die; Yin, Jingang; Zhang, Hao; Huang, Xing

    2017-06-19

    Lactofen, a member of the diphenylether herbicides, has high activity and is commonly used to control broadleaf weeds. As a post-emergent herbicide, it is directly released to the environment, and easily caused the pollution. This herbicide is degraded in soil mainly by microbial activity, but the functional enzyme involved in the biodegradation of lactofen is still not clear now. A novel esterase gene lacH, involved in the degradation of lactofen, was cloned from the strain Brevundimonas sp. LY-2. The gene contained an open reading frame of 921 bp, and a putative signal peptide at the N-terminal was identified with the most likely cleavage site between Ala 28 and Ala 29. The encoded protein, LacH, could catalyze the hydrolysis of lactofen to form acifluorfen. Phylogenetic analysis showed that LacH belong to family V of bacterial lipolytic enzymes. Biochemical characterization analysis showed that LacH was a neutral esterase with an optimal pH of 7.0 and an optimal temperature of 40 °C toward lactofen. Besides, the activity of LacH was strongly inhibited by Hg 2+ and Zn 2+ . LacH preferred short chain p-nitrophenyl esters (C 2 -C 6 ), exhibited maximum activity toward p-nitrophenyl acetate. Furthermore, the enantioselectivity of LacH during lactofen hydrolysis was also studied, and the results show that R-(-)-lactofen was degraded faster than S-(+)-lactofen, indicating the occurrence of enantioselectivity in the enzymatic reaction. Our studies characterized a novel esterase involved in the biodegradation of diphenylether herbicide lactofen. The esterase showed enantioselectivity during lactofen degradation, which revealed the occurrence of enzyme-mediated enantioselective degradation of chiral herbicides.

  17. Catalytic Enantioselective Synthesis of Tetrahydocarbazoles and Exocyclic Pictet-Spengler-Type Reactions

    DEFF Research Database (Denmark)

    Hansen, Casper Lykke; Ohm, Ragnhild Gaard; Olsen, Lasse Bohn

    2016-01-01

    A synthetic strategy for the synthesis of chiral tetrahydrocarbazoles (THCAs) has been developed. The strategy relies on two types of 6-exo-trig cyclization of 3-substituted indole substrates. Enantioselective domino Friedel-Crafts-type reactions leading to THCAs can be catalyzed by chiral phosph...... phosphoric acid derivatives (with up to >99% ee), and the first examples of exocyclic Pictet-Spengler reactions to form THCAs are reported....

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

    Science.gov (United States)

    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.

  19. Linking homogeneous and heterogeneous enantioselective catalysis through a self-assembled coordination polymer.

    Science.gov (United States)

    García, José I; López-Sánchez, Beatriz; Mayoral, José A

    2008-11-06

    Combining the advantages of homogeneous and heterogeneous enantioselective catalysis is possible through self-supported copper coordination polymers, based on a new kind of ditopic chiral ligand bearing two azabis(oxazoline) moieties. When the coordination polymer is used to catalyze a cyclopropanation reaction, it becomes soluble in reaction conditions but precipitates after reaction completion, allowing easy recovery and efficient reuse in the same reaction up to 14 times.

  20. Copper(II)/amine synergistically catalyzed enantioselective alkylation of cyclic N-acyl hemiaminals with aldehydes.

    Science.gov (United States)

    Sun, Shutao; Mao, Ying; Lou, Hongxiang; Liu, Lei

    2015-07-07

    The first catalytic asymmetric alkylation of N-acyl quinoliniums with aldehydes has been described. A copper/amine synergistic catalytic system has been developed, allowing the addition of functionalized aldehydes to a wide range of electronically varied N-acyl quinoliniums in good yields with excellent enantiocontrol. The synergistic catalytic system was also effective for N-acyl dihydroisoquinoliniums and β-caboliniums, demonstrating the general applicability of the protocol in the enantioselective alkylation of diverse cyclic N-acyl hemiaminals.

  1. Mo-catalyzed asymmetric olefin metathesis in target-oriented synthesis: Enantioselective synthesis of (+)-africanol

    Science.gov (United States)

    Weatherhead, Gabriel S.; Cortez, G. A.; Schrock, Richard R.; Hoveyda, Amir H.

    2004-01-01

    Catalytic asymmetric ring-opening metathesis (AROM) provides an efficient method for the synthesis of a variety of optically enriched small organic molecules that cannot be easily prepared by alternative methods. The development of Mo-catalyzed AROM transformations that occur in tandem with ring-closing metathesis are described. The utility of the Mo-catalyzed AROM/ring-closing metathesis is demonstrated through an enantioselective approach to the synthesis of (+)-africanol. PMID:15056762

  2. A combined continuous microflow photochemistry and asymmetric organocatalysis approach for the enantioselective synthesis of tetrahydroquinolines

    Directory of Open Access Journals (Sweden)

    Erli Sugiono

    2013-11-01

    Full Text Available A continuous-flow asymmetric organocatalytic photocyclization–transfer hydrogenation cascade reaction has been developed. The new protocol allows the synthesis of tetrahydroquinolines from readily available 2-aminochalcones using a combination of photochemistry and asymmetric Brønsted acid catalysis. The photocylization and subsequent reduction was performed with catalytic amount of chiral BINOL derived phosphoric acid diester and Hantzsch dihydropyridine as hydrogen source providing the desired products in good yields and with excellent enantioselectivities.

  3. Enantioselective synthesis of (S)-2-cyano-2-methylpentanoic acid by nitrilase.

    Science.gov (United States)

    Yoshida, Toyokazu; Mitsukura, Koichi; Mizutani, Takuya; Nakashima, Ryo; Shimizu, Yasuyo; Kawabata, Hiroshi; Nagasawa, Toru

    2013-05-01

    The nitrilase gene of Rhodococcus rhodochrous J1 was expressed in Escherichia coli using the expression vector, pKK223-3. The recombinant E. coli JM109 cells hydrolyzed enantioselectively 2-methyl-2-propylmalononitrile to form (S)-2-cyano-2-methylpentanoic acid (CMPA) with 96 % e.e. Under optimized conditions, 80 g (S)-CMPA l(-1) was produced with a molar yield of 97 % at 30 °C after a 24 h without any by-products.

  4. Diastereo- and Enantioselective Iridium Catalyzed Carbonyl (α-Cyclopropyl)allylation via Transfer Hydrogenation.

    Science.gov (United States)

    Tsutsumi, Ryosuke; Hong, Suckchang; Krische, Michael J

    2015-09-07

    The first examples of diastereo- and enantioselective carbonyl α-(cyclopropyl)allylation are reported. Under the conditions of iridium catalyzed transfer hydrogenation using the chiral precatalyst (R)-Ir-I modified by SEGPHOS, carbonyl α-(cyclopropyl)allylation may be achieved with equal facility from alcohol or aldehyde oxidation levels. This methodology provides a conduit to hitherto inaccessible inaccessible enantiomerically enriched cyclopropane-containing architectures. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Enantioselective synthesis of the novel chiral sulfoxide derivative as a glycogen synthase kinase 3beta inhibitor.

    Science.gov (United States)

    Saitoh, Morihisa; Kunitomo, Jun; Kimura, Eiji; Yamano, Toru; Itoh, Fumio; Kori, Masakuni

    2010-09-01

    Glycogen synthase kinase 3beta (GSK-3beta) inhibitors are expected to be attractive therapeutic agents for the treatment of Alzheimer's disease (AD). Recently we discovered sulfoxides (S)-1 as a novel GSK-3beta inhibitor having in vivo efficacy. We investigated practical asymmetric preparation methods for the scale-up synthesis of (S)-1. The highly enantioselective synthesis of (S)-1 (94% ee) was achieved by titanium-mediated oxidation with D-(-)-diethyl tartrate on gram scale.

  6. Enantioselective cytotoxicity of the insecticide bifenthrin on a human amnion epithelial (FL) cell line

    International Nuclear Information System (INIS)

    Liu Huigang; Zhao Meirong; Zhang Cong; Ma Yun; Liu Weiping

    2008-01-01

    Synthetic pyrethroids (SPs) are used in preference to organochlorines and organophosphates due to their high efficiency, low toxicity to mammals, and ready biodegradability. Previous studies reported that enantioselective toxicity of SPs occurs in aquatic toxicity. Several studies have indicated that SPs could lead to oxidative damage in humans or animals which was associated with their toxic effects. Little is known about the differences in the effects of chronic toxicity induced by individual stereoisomers of chiral SPs. The present study was therefore undertaken to evaluate the enantioselectivity in cytotoxicity, genotoxicity caused by bifenthrin (BF) on human amnion epithelial (FL) cell lines and pesticidal activity on target organism. The cell proliferation and cytoflow analysis indicated that 1S-cis-BF presented more toxic effects than 1R-cis-BF above the concentration of 7.5 mg L -1 (p > 0.05). FL cells incubated with 1S-cis-BF exhibited a dose-dependent accumulation of intracellular reactive oxygen species (ROS). In the comet assay, the number of cells with damaged DNA incubated with 1S-cis-BF was more than that with 1R-cis-BF (p 50 values of enantiomer to the target pest on Pieris rapae L. show that 1R-cis-BF was 300 times more active than 1S-cis-BF. These results indicate that the enantioselective toxicity and activity of BF between non-target organism and target organism was reversal. These implications together suggest that assessment of the environmental safety and new pesticides development with chiral centers should consider enantioselectivity

  7. Catalytic enantioselective Michael addition reactions of alpha-nitroesters to alpha,beta-unsaturated ketones

    NARCIS (Netherlands)

    Keller, E; Veldman, N; Spek, AL; Feringa, BL

    1997-01-01

    Enantioselective Michael additions of alpha-nitroesters 2a-d with alpha,beta-unsaturated ketones were carried out in the presence of a catalytic amount of chiral Al-Li-(R,R')-2,2'-dihydroxy-1,1'-binaphthyl ('AlLiBINOL') complex prepared in situ from LiAlH4 and 2.45 equiv. of (R,R')-BINOL. The

  8. Catalytic enantioselective Michael addition reactions of α-nitroesters to α,β-unsaturated ketones

    NARCIS (Netherlands)

    Keller, Erik; Veldman, Nora; Spek, Anthony L.; Feringa, Bernard

    1997-01-01

    Enantioselective Michael additions of α-nitroesters 2a-d with α,β-unsaturated ketones were carried out in the presence of a catalytic amount of chiral Al-Li-(R,R')-2,2'-dihydroxy-1,1'-binaphthyl (‘AlLiBINOL’) complex prepared in situ from LiAlH4 and 2.45 equiv. of (R,R')-BINOL. The

  9. Enantioselective extraction mediated by a chiral cavitand-salen covalently assembled on a porous silicon surface.

    Science.gov (United States)

    D'Urso, Alessandro; Tudisco, Cristina; Ballistreri, Francesco P; Condorelli, Guglielmo G; Randazzo, Rosalba; Tomaselli, Gaetano A; Toscano, Rosa M; Trusso Sfrazzetto, Giuseppe; Pappalardo, Andrea

    2014-05-21

    A chiral organic-inorganic hybrid material, based on a porous silicon surface functionalized with a chiral cavitand, was designed and synthesized. The affinity of this device in water toward a bromine-marked alkyl-ammonium salt has been evaluated using XPS detection. UV and CD measurements highlight the enantioselective extraction from a racemic mixture in water of the S-enantiomer of the selected guest (ee ≥ 80%).

  10. Lewis base catalyzed enantioselective allylic hydroxylation of Morita-Baylis-Hillman carbonates with water

    KAUST Repository

    Zhu, Bo

    2011-08-19

    A Lewis base catalyzed allylic hydroxylation of Morita-Baylis-Hillman (MBH) carbonates has been developed. Various chiral MBH alcohols can be synthesized in high yields (up to 99%) and excellent enantioselectivities (up to 94% ee). This is the first report using water as a nucleophile in asymmetric organocatalysis. The nucleophilic role of water has been verified using 18O-labeling experiments. © 2011 American Chemical Society.

  11. Catalytic enantioselective vinylogous Mukaiyama-Michael addition of 2-silyloxyfurans to cyclic unsaturated oxo esters.

    Science.gov (United States)

    Jusseau, Xavier; Retailleau, Pascal; Chabaud, Laurent; Guillou, Catherine

    2013-03-15

    The copper-catalyzed asymmetric addition of 2-silyloxyfurans to cyclic unsaturated oxo esters is reported. The reaction proceeds with excellent diastereocontrol (usually dr 99:1) and modest to high enantioselectivity, depending on the nature of the ester group and the substitution of the cyclic oxo ester. We have shown that these substrates can be transformed into a variety of building blocks bearing a γ-butenolide or γ-lactone connected to a cycloalkane or cycoalkene moiety.

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

    Science.gov (United States)

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

    2017-08-01

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

  13. C-5’-Triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides: Synthesis and biological evaluation

    Directory of Open Access Journals (Sweden)

    Roberto Romeo

    2015-03-01

    Full Text Available A novel series of 2’-oxa-3’-aza-4’a-carbanucleosides, featured with a triazole linker at the 5’-position, has been developed by exploiting a click chemistry reaction of 5’-azido-2’-oxa-3’-aza-4’a-carbanucleosides with substituted alkynes. Biological tests indicate an antitumor activity for the synthesized compounds: most of them inhibit cell proliferation of Vero, BS-C-1, HEp-2, MDCK, and HFF cells with a CC50 in the range of 5.0–40 μM. The synthesized compounds do not show any antiviral activity.

  14. Enantioselective Characteristics and Montmorillonite-Mediated Removal Effects of α-Hexachlorocyclohexane in Laying Hens.

    Science.gov (United States)

    Liu, Xueke; Shen, Zhigang; Wang, Peng; Liu, Chang; Yao, Guojun; Zhou, Zhiqiang; Liu, Donghui

    2016-06-07

    α-Hexachlorocyclohexane (α-HCH) is a chiral organochlorine pesticide that is often ubiquitously detected in various environmental matrices and may be absorbed by the human body via food consumption, with serious detriments to human health. In this study, enantioselective degradation kinetics and residues of α-HCH in laying hens were investigated after a single dose of exposure to the pesticide, whereas enantioselectivity and residues of α-HCH in eggs, droppings, and various tissues were investigated after long-term exposure. Meanwhile, montmorillonite (MMT), a feed additive with high capacity of adsorption, was investigated for its ability to remove α-HCH from laying hens. Most non-brain tissues enantioselectively accumulated (-)-α-HCH, while (+)-α-HCH was preferentially accumulated in the brain. The enantiomer fractions (EFs) in most tissues gradually decreased, implying continuous depletion of (+)-α-HCH in laying hens. After 30 days of exposure and 31 days of elimination, the concentration of α-HCH in eggs and tissues of laying hens with MMT-containing feed was lower than that with MMT-free feed, indicating the removal effects of MMT for α-HCH in laying hens. The findings presented herein suggest that modified MMT may potentially be useful in reducing the enrichment of α-HCH in laying hens and eggs, thus lowering the risk of human intake of α-HCH.

  15. Phytotoxicity of chiral herbicide bromacil: Enantioselectivity of photosynthesis in Arabidopsis thaliana

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zunwei; Zou, Yuqin; Wang, Jia [MOE Key Laboratory of Environmental Remediation & Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China); Li, Meichao [Research Center of Analysis and Measurement, Zhejiang University of Technology, Hangzhou 310032 (China); Wen, Yuezhong, E-mail: wenyuezhong@zju.edu.cn [MOE Key Laboratory of Environmental Remediation & Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China)

    2016-04-01

    With the wide application of chiral herbicides and the frequent detection of photosystem II (PSII) herbicides, it is of great importance to assess the direct effects of PSII herbicides on photosynthesis in an enantiomeric level. In the present study, the enantioselective phytotoxicity of bromacil (BRO), typical photosynthesis inhibition herbicide, on Arabidopsis thaliana was investigated. The results showed that S-BRO exhibited a greater inhibition of electron transmission in photosystem I (PSI) of A. thaliana than R-BRO by inhibiting the transcription of fnr 1. S-BRO also changed the chlorophyll fluorescence parameters Y (II), Y (NO), and Y (NPQ) to a greater extent than R-Bro. Transcription of genes psbO2, Lhcb3 and Lhcb6 was down-regulated in an enantioselective rhythm and S-BRO caused more serious influence, indicating that S-BRO did worse damage to the photosystem II (PSII) of A. thaliana than R-BRO. This study suggested that S-BRO disturbed the photosynthesis of plants to a larger extent than R-BRO and provided a new sight to evaluate the phytotoxicity of chiral herbicides. - Highlights: • It is necessary to assess the direct effects of PSII herbicides on photosynthesis. • Phytotoxicity of bromacil is investigated in an enantiomeric level. • Bromacil disturbed enantioselectively the photosystem II of Arabidopsis thaliana. • S-bromacil caused severer damage to photosynthesis of Arabidopsis than R-bromacil. • Photosynthesis should be considered for phytotoxicity assessment of herbicides.

  16. Phytotoxicity of chiral herbicide bromacil: Enantioselectivity of photosynthesis in Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Chen, Zunwei; Zou, Yuqin; Wang, Jia; Li, Meichao; Wen, Yuezhong

    2016-01-01

    With the wide application of chiral herbicides and the frequent detection of photosystem II (PSII) herbicides, it is of great importance to assess the direct effects of PSII herbicides on photosynthesis in an enantiomeric level. In the present study, the enantioselective phytotoxicity of bromacil (BRO), typical photosynthesis inhibition herbicide, on Arabidopsis thaliana was investigated. The results showed that S-BRO exhibited a greater inhibition of electron transmission in photosystem I (PSI) of A. thaliana than R-BRO by inhibiting the transcription of fnr 1. S-BRO also changed the chlorophyll fluorescence parameters Y (II), Y (NO), and Y (NPQ) to a greater extent than R-Bro. Transcription of genes psbO2, Lhcb3 and Lhcb6 was down-regulated in an enantioselective rhythm and S-BRO caused more serious influence, indicating that S-BRO did worse damage to the photosystem II (PSII) of A. thaliana than R-BRO. This study suggested that S-BRO disturbed the photosynthesis of plants to a larger extent than R-BRO and provided a new sight to evaluate the phytotoxicity of chiral herbicides. - Highlights: • It is necessary to assess the direct effects of PSII herbicides on photosynthesis. • Phytotoxicity of bromacil is investigated in an enantiomeric level. • Bromacil disturbed enantioselectively the photosystem II of Arabidopsis thaliana. • S-bromacil caused severer damage to photosynthesis of Arabidopsis than R-bromacil. • Photosynthesis should be considered for phytotoxicity assessment of herbicides.

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

    Science.gov (United States)

    Eibler, Dorothee; Seyfried, Carolin; Vetter, Walter

    2017-09-01

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

  18. Novel N-Doped Carbon Dots/β-Cyclodextrin Nanocomposites for Enantioselective Recognition of Tryptophan Enantiomers

    Directory of Open Access Journals (Sweden)

    Qi Xiao

    2016-11-01

    Full Text Available Based on N-doped carbon dots/β-cyclodextrin nanocomposites modified glassy carbon electrodes (N-CDs/β-CD/GCE, an effective electrochemical sensor for enantioselective recognition of tryptophan (Trp enantiomers was developed by differential pulse voltammograms (DPVs. Fluorescent N-CDs were synthesized through a hydrothermal method and characterized by spectroscopic approaches. The N-CDs/β-CD nanocomposites were efficiently electrodeposited on the surface of GCE through C–N bond formation between N-CDs and electrode. The obtained N-CDs/β-CD/GCE was characterized by multispectroscopic and electrochemical methods. Such N-CDs/β-CD/GCE generated a significantly lower Ip and more negative Ep in the presence of l-Trp in DPVs, which was used for the enantioselective recognition of Trp enantiomers. The N-CDs/β-CD nanocomposites showed different binding constants for tryptophan enantiomers, and they further selectively bonded with l-Trp to form inclusion complexes. This N-CDs/β-CD/GCE combined advantages of N-CDs with strong C–N binding ability and β-CD with specific recognition of Trp enantiomers to fabricate a novel sensing platform for enantioselective recognition of Trp enantiomers. This strategy provided the possibility of using a nanostructured sensor to discriminate the chiral molecules in bio-electroanalytical applications.

  19. Enantioselective bioaccumulation and toxic effects of fipronil in the earthworm Eisenia foetida following soil exposure.

    Science.gov (United States)

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

    2015-04-01

    Enantiomers of chiral pesticides often have different bioactivity, toxicity and environmental behaviours. Fipronil has been used in racemate for agricultural purposes against soil insects, leading to increased inputs into soil environments and complex biota exposures. To understand the potential risk associated with fipronil enantiomer exposure, subchronic toxicity and bioaccumulation tests with earthworms (Eisenia foetida) in fipronil-spiked soils were evaluated under laboratory conditions. Enantioselective toxicity was measured in E. foetida biomass after 28 days of subchronic exposure, with increased toxicity from racemate and S-fipronil compared with R-fipronil. The bioaccumulation of fipronil in earthworm tissues was also enantioselective, with a preferential accumulation of S-fipronil, and the enantiomer fraction was approximately 0.56-0.60. During soil exposure, fipronil was transformed primarily into fipronil sulfide, sulfone and amide, and E. foetida rapidly accumulated fipronil and sulfone. This work demonstrates the enantioselective subchronic toxicity and bioaccumulation of enantiomers of fipronil in E. foetida. The earthworm tissues exhibited a relative enrichment of fipronil and fipronil sulfone, and these compounds might biomagnify (with a biota-to-soil accumulation factor of ≥1.0 kgOCkglip-1), allowing for the possible trophic transfer and/or bioaccumulation of all these chemicals if earthworms were consumed by predator organisms. © 2014 Society of Chemical Industry.

  20. Enantioselective acute toxicity effects and bioaccumulation of furalaxyl in the earthworm (Eisenia foetida).

    Science.gov (United States)

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

    2014-06-01

    The enantioselectivities of individual enantiomers of furalaxyl in acute toxicity and bioaccumulation in the earthworm (Eisenia foetida) were studied. The acute toxicity was tested by filter paper contact test. After 48 h of exposure, the calculated LC50 values of the R-form, rac-form, and S-form were 2.27, 2.08, and 1.22 µg cm(-2), respectively. After 72 h of exposure, the calculated LC50 values were 1.90, 1.54, and 1.00 µg cm(-2), respectively. Therefore, the acute toxicity of furalaxyl enantiomers was enantioselective. During the bioaccumulation experiment, the enantiomer fraction of furalaxyl in earthworm tissue was observed to deviate from 0.50 and maintained a range of 0.55-0.60; in other words, the bioaccumulation of furalaxyl was enantioselective in earthworm tissue with a preferential accumulation of S-furalaxyl. The uptake kinetic of furalaxyl enantiomers fitted the first-order kinetics well and the calculated kinetic parameters were consistent with the low accumulation efficiency. © 2014 Wiley Periodicals, Inc.

  1. Investigation of Enantioselective Membrane Permeability of α-Lipoic Acid in Caco-2 and MDCKII Cell

    Directory of Open Access Journals (Sweden)

    Ryota Uchida

    2016-01-01

    Full Text Available α-Lipoic acid (LA contains a chiral carbon and exists as two enantiomers (R-α-lipoic acid (RLA and S-α-lipoic acid (SLA. We previously demonstrated that oral bioavailability of RLA is better than that of SLA. This difference arose from the fraction absorbed multiplied by gastrointestinal availability (Fa × Fg and hepatic availability (Fh in the absorption phase. However, it remains unclear whether Fa and/or Fg are involved in enantioselectivity. In this study, Caco-2 cells and Madin–Darby canine kidney strain II cells were used to assess the enantioselectivity of membrane permeability. LA was actively transported from the apical side to basal side, regardless of the differences in its steric structure. Permeability rates were proportionally increased in the range of 10–250 µg LA/mL, and the permeability coefficient did not differ significantly between enantiomers. Hence, we conclude that enantioselective pharmacokinetics arose from the metabolism (Fh or Fg × Fh, and definitely not from the membrane permeation (Fa in the absorption phase.

  2. Aza-Peptidyl Michael Acceptor and Epoxide Inhibitors—Potent and Selective Inhibitors of Schistosoma mansoni and Ixodes ricinus Legumains (Asparaginyl Endopeptidases)

    Czech Academy of Sciences Publication Activity Database

    Ovat, A.; Muindi, F.; Fagan, C.; Brouner, M.; Hansell, E.; Dvořák, J.; Sojka, Daniel; Kopáček, Petr; McKerrow, J. H.; Caffrey, C. R.; Powers, J. C.

    2009-01-01

    Roč. 52, č. 22 (2009), s. 7192-7210 ISSN 0022-2623 R&D Projects: GA ČR GA206/06/0865; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : legumain * IrAE * aza-peptide Michael acceptors Subject RIV: EC - Immunology Impact factor: 4.802, year: 2009

  3. Synthesis of Dihydrophenanthridines and Oxoimidazolidines from Anilines and Ethylglyoxylate via Aza Diels-Alder Reaction of Arynes and KF-Induced Annulation.

    Science.gov (United States)

    Reddy, R Santhosh; Lagishetti, Chandraiah; Chen, Shuo; Kiran, I N Chaithanya; He, Yun

    2016-09-16

    The transition-metal-free multicomponent coupling of arynes, anilines, and ethylglyoxylate, proceeding via an inverse electron-demand aza Diels-Alder cycloaddition and N-arylation, has been demonstrated. This protocol allows rapid access to N-aryl dihydrophenanthridine derivatives in moderate to high yields at room temperature from readily available starting materials. In addition, an unprecedented fluoride induced annulation of ethyl(arylimino)acetates led to the formation of highly functionalized oxoimidazolidine derivatives in good yields under mild conditions.

  4. A practical and green approach toward synthesis of N3-substituted dihydropyrimidinones: using Aza-Michael addition reaction catalyzed by KF/Al2O3.

    Science.gov (United States)

    Wang, Xicun; Quan, Zhengjun; Wang, Jun-Ke; Zhang, Zhang; Wang, Mangang

    2006-09-01

    A simple and efficient method for the synthesis of N3-substituted 3,4-dihydropyrimidinones by aza-Michael addition reactions of 3,4-dihydropyrimidinones to alpha,beta-ethylenic compounds catalyzed by KF/Al(2)O(3) is described. The advantage of this method is high regioselectivity, high purity, and the use of a cheaper, milder, and efficient catalyst for the hetero-Michael addition reaction.

  5. Automated synthesis of a library of triazolated 1,2,5-thiadiazepane 1,1-dioxides via a double aza-Michael strategy.

    Science.gov (United States)

    Zang, Qin; Javed, Salim; Hill, David; Ullah, Farman; Bi, Danse; Porubsky, Patrick; Neuenswander, Benjamin; Lushington, Gerald H; Santini, Conrad; Organ, Michael G; Hanson, Paul R

    2012-08-13

    The construction of a 96-member library of triazolated 1,2,5-thiadiazepane 1,1-dioxides was performed on a Chemspeed Accelerator (SLT-100) automated parallel synthesis platform, culminating in the successful preparation of 94 out of 96 possible products. The key step, a one-pot, sequential elimination, double-aza-Michael reaction, and [3 + 2] Huisgen cycloaddition pathway has been automated and utilized in the production of two sets of triazolated sultam products.

  6. Alpha anomer of 5-aza-2'-deoxycytidine down-regulates hTERT mRNA expression in human leukemia HL-60 cells

    Czech Academy of Sciences Publication Activity Database

    Hájek, Miroslav; Votruba, Ivan; Holý, Antonín; Krečmerová, Marcela; Tloušťová, Eva

    2008-01-01

    Roč. 75, č. 4 (2008), s. 965-972 ISSN 0006-2952 R&D Projects: GA MŠk 1M0508; GA AV ČR 1QS400550501 Institutional research plan: CEZ:AV0Z40550506 Keywords : alpha-5-aza-2'-deoxycytidine * DNA hypomethylation * hTERT * c- myc Subject RIV: CC - Organic Chemistry Impact factor: 4.838, year: 2008

  7. Optimization of catalyst-solvent system for preparation of alpha-5,6-dihydro-5-aza-2'-deoxy-[6-3H]-cytidine

    Czech Academy of Sciences Publication Activity Database

    Elbert, Tomáš

    2011-01-01

    Roč. 54, č. 5 (2011), s. 285-285 ISSN 0362-4803. [Workshop of the International Isotope Society - Central European Division. The Synthesis and Applications of Isotopes and Isotopically Labelled Compounds /17./. 23.09.2010-24.09.2010, Bad Soden] Institutional research plan: CEZ:AV0Z40550506 Keywords : tritium * labelled compounds * alfa-5,6-dihydro-5-aza-2'-deoxy-cytidine Subject RIV: CC - Organic Chemistry

  8. Brønsted acid catalyzed regioselective aza-Ferrier reaction : A novel synthetic method of α-(N-Boc-2-pyrrolidinyl)aldehydes

    OpenAIRE

    Tayama, Eiji; Otoyama, Seijun; Isaka, Wataru

    2008-01-01

    The 1,4-elimination reaction of (Z)-N-Boc-2-(4-methoxy-2-alkenyloxy)pyrrolidines (1) is shown to proceed with high (1E,3E)-stereoselectivity to afford N-Boc-2-(1,3-dienyloxy)pyrrolidines (2); the Bronsted acid catalyzed aza-Ferrier reaction of the N-Boc-2-(1,3-dienyloxy)pyrrolidines (2) provides a-(N-Boc-2-pyrrolidinyl) aldehydes (3) in excellent yields with high a-regioselectivities.

  9. The influence of anions and kink structure on the enantioselective electro-oxidation of glucose.

    Science.gov (United States)

    Attard, Gary A; Harris, Catherine; Herrero, Enrique; Feliu, Juan

    2002-01-01

    The electro-oxidation of glucose in sulfuric acid using well-defined chiral platinum single crystal electrodes has been demonstrated previously to be an enantioselective reaction with the degree of enantioselectivity being dependent on the surface density of kink sites. The chirality of the surface originates from the microstructure of the kink site whereby the sequence of the three fundamental adsorption sites [111], [100] and [110] constituting the kink may be viewed from the electrolyte phase either in a clockwise (R-enantiomer) or anti-clockwise (S-enantiomer) fashion. In the present study, this work is extended to examine the role of both kink structure and specifically adsorbed anions on the mechanism of chiral discrimination. Kinked surfaces based on [111] terraces (Pt[976],Pt[643] and Pt[531]),[100] terraces (Pt[721]) and [110] terraces (Pt[11,7,1] and Pt[841]) have been investigated and both the magnitude and potential dependence of the enantioselective electro-oxidation of glucose characterised. Additionally, the changes engendered by interchanging the character of the two steps whose confluence form the kink whilst maintaining the symmetry of the terrace has also been examined via a comparison of Pt[643] and Pt[431]. Low energy electron diffraction (LEED) was used to confirm that all surfaces when clean and thermally annealed were in their (1 x 1) state. Cyclic voltammetry (CV) confirmed this finding for flame-annealed electrodes after cooling in hydrogen. Three general points emerge from the electro-oxidation studies: (i) The highest degree of enantioselectivity is exhibited by kink sites adjacent to [111] and [110] terraces in sulfuric acid. (ii) The adsorption of specifically adsorbed anions like bisulfate/sulfate influences strongly the chiral discriminatory behaviour of all surfaces. (iii) No electro-oxidation takes place at [110] sites, as evidenced by complete overlap of the [110] step hydrogen underpotential deposition (UPD) charge in glucose and

  10. Enantioselective Michael Addition of 3-Aryl-Substituted Oxindoles to Methyl Vinyl Ketone Catalyzed by a Binaphthyl-Modified Bifunctional Organocatalyst

    Directory of Open Access Journals (Sweden)

    Saet Byeol Woo

    2012-06-01

    Full Text Available The enantioselective conjugate addition reaction of 3-aryl-substituted oxindoles with methyl vinyl ketone promoted by binaphthyl-modified bifunctional organocatalysts was investigated. The corresponding Michael adducts, containing a quaternary center at the C3-position of the oxindoles, were generally obtained in high yields with excellent enantioselectivities (up to 91% ee.

  11. Synthesis, Biological Profiling and Determination of the Tubulin-Bound Conformation of 12-Aza-Epothilones (Azathilones

    Directory of Open Access Journals (Sweden)

    Andrea Jantsch

    2016-08-01

    Full Text Available 12-Aza-epothilones (azathilones incorporating quinoline side chains and bearing different N12-substituents have been synthesized via highly efficient RCM-based macrocyclizations. Quinoline-based azathilones with the side chain N-atom in the meta-position to the C15 atom in the macrocycle are highly potent inhibitors of cancer cell growth in vitro. In contrast, shifting the quinoline nitrogen to the position para to C15 leads to a ca. 1000-fold loss in potency. Likewise, the desaturation of the C9-C10 bond in the macrocycle to an E double bond produces a substantial reduction in antiproliferative activity. This is in stark contrast to the effect exerted by the same modification in the natural epothilone macrocycle. The conformation of a representative azathilone bound to α/β-tubulin heterodimers was determined based on TR-NOE measurements and a model for the posture of the compound in its binding site on β-tubulin was deduced through a combination of STD measurements and CORCEMA-ST calculations. The tubulin-bound, bioactive conformation of azathilones was found to be overall similar to that of epothilones A and B.

  12. Synthesis of amphiphilic macrocyclic molecules from family of aza-porphyrins and study in Langmuir-Blodgett films

    International Nuclear Information System (INIS)

    Palacin, Serge

    1988-01-01

    The cellular automata, also called formal neurons, directly inspired by the knowledge concerning the nervous system, are able to mimic some basic processes of brain, as shape recognition, connecting memory, information sorting... This work aims to build a molecular structure able to fit the working rules of a bidimensional cellular automata. So, amphiphilic molecules belonging to the aza-porphyrin family are synthesized and organized into a planar paving by the Langmuir-Blodgett technique. The regular structure of the outcoming ultra-thin films is studied by linear dichroism and anisotropic electron spin resonance. The physico-chemical behaviour of the amphiphilic molecules is studied and brings about an explanation of the redox phenomena which are observed on the monomolecular film on the water surface. So are we able to outline the future chemical addressing ways of the bidimensional cellular automata. In the end of this dissertation, different ways likely to insure covalent bindings between the active sites and allow the transfer of information within the cellular network are discussed. (author) [fr

  13. Near-infrared fluorescent aza-BODIPY dye-loaded biodegradable polymeric nanoparticles for optical cancer imaging

    Energy Technology Data Exchange (ETDEWEB)

    Hamon, Casey L.; Dorsey, Christopher L. [Texas State University, Department of Chemistry and Biochemistry (United States); Özel, Tuğba [Texas State University, Materials Science, Engineering, and Commercialization Program (United States); Barnes, Eugenia M.; Hudnall, Todd W.; Betancourt, Tania, E-mail: tb26@txstate.edu [Texas State University, Department of Chemistry and Biochemistry (United States)

    2016-07-15

    Nanoparticles are being readily investigated as carriers for the delivery of imaging and therapeutic agents for the detection, monitoring, and treatment of cancer and other diseases. In the present work, the preparation of biodegradable polymeric nanoparticles loaded with a near-infrared fluorescent aza-boron dipyrromethene (NIR-BODIPY) derivative, and their use as contrast agents for optical imaging in cancer are described. Nanoparticles were prepared by nanoprecipitation of amphiphilic block copolymers of poly(lactic acid) and poly(ethylene glycol). The size, morphology, dye loading, spectral properties, quantum yield, cytocompatibility, and in vitro NIR imaging potential of the nanoparticles in breast and ovarian cancer cells were evaluated. Spherical nanoparticles of 30–70 nm in diameter were loaded with 0.73 w/w% BODIPY derivative. At this loading, the dye presented a fluorescence quantum yield in the same order of magnitude as in solution. Nanoparticle suspensions at concentrations up to 580 μg/mL were cytocompatible to breast (MDA-MB-231) and ovarian (SKOV-3 and Caov-3) cancer cells after a four-hour incubation period. Fluorescence microscopy images demonstrated the ability of the nanoparticles to act as imaging agents in all three cell lines in as little as 1 hour. The results shown indicate the potential of these NIR-BODIPY-loaded nanoparticles as contrast agents for near-infrared optical imaging in cancer.Graphical abstract.

  14. A parametric study on biphasic medium conditions for the enantioselective production of naproxen by Candida rugosa lipase.

    Science.gov (United States)

    Takaç, Serpil; Mutlu, Deniz

    2007-04-01

    A parametric study to increase the enantioselectivity of Candida rugosa lipase (CRL) toward S-Naproxen production by the hydrolysis of racemic Naproxen methyl ester in an aqueous-organic biphasic batch system was carried out. Effects of organic solvent type, aqueous phase/organic solvent volume ratio, agitation rate, concentrations of the substrate and the enzyme, pH of the aqueous phase, and temperature on the enantiomeric excess for the product (eep), on the enantiomeric ratio (E) and on the conversion (x) were evaluated. Employing isooctane as the solvent resulted in higher eep, E, and x than those obtained in hexane, cyclohexane, and toluene. The higher the volume ratio of aqueous phase/organic solvent employed, the higher the conversion and enantioselectivity achieved. The increase in agitation rate increased the hydrolysis rate. Higher concentration of racemic Naproxen methyl ester than 10 mg/mL decreased both the conversion and enantioselectivity. The increase in crude CRL concentration resulted in enhancement of x, but the decrease of eep and E. Acidic pH led to higher conversion and enantioselectivity than the medium and alkaline pH values. A further increase in temperature to over 45 degrees C decreased the conversion and enantioselectivity. The highest enantiomeric ratio achieved in the S-Naproxen production was E = 171.1, with x = 49.8% and eep = 95.7%.

  15. Enantioselective Effects of Metalaxyl Enantiomers on Breast Cancer Cells Metabolic Profiling Using HPLC-QTOF-Based Metabolomics

    Directory of Open Access Journals (Sweden)

    Ping Zhang

    2017-01-01

    Full Text Available In this study, an integrative high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (HPLC-QTOF based metabolomics approach was performed to evaluate the enantioselective metabolic perturbations in MCF-7 cells after treatment with R-metalaxyl and S-metalaxyl, respectively. Untargeted metabolomics profile, multivariate pattern recognition, metabolites identification, and pathway analysis were determined after metalaxyl enantiomer exposure. Principal component analysis (PCA and partitial least-squares discriminant analysis (PLS-DA directly reflected the enantioselective metabolic perturbations induced by metalaxyl enantiomers. On the basis of multivariate statistical results, a total of 49 metabolites including carbohydrates, amino acids, nucleotides, fatty acids, organic acids, phospholipids, indoles, derivatives, etc. were found to be the most significantly changed metabolites and metabolic fluctuations caused by the same concentration of R-metalaxyl and S-metalaxyl were enantioselective. Pathway analysis indicated that R-metalaxyl and S-metalaxyl mainly affected the 7 and 10 pathways in MCF-7 cells, respectively, implying the perturbed pathways induced by metalaxyl enantiomers were also enantioselective. Furthermore, the significantly perturbed metabolic pathways were highly related to energy metabolism, amino acid metabolism, lipid metabolism, and antioxidant defense. Such results provide more specific insights into the enantioselective metabolic effects of chiral pesticides in breast cancer progression, reveal the underlying mechanisms, and provide available data for the health risk assessments of chiral environmental pollutants at the molecular level.

  16. Enantioselective Effects of Metalaxyl Enantiomers on Breast Cancer Cells Metabolic Profiling Using HPLC-QTOF-Based Metabolomics.

    Science.gov (United States)

    Zhang, Ping; Zhu, Wentao; Wang, Dezhen; Yan, Jin; Wang, Yao; He, Lin

    2017-01-12

    In this study, an integrative high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (HPLC-QTOF) based metabolomics approach was performed to evaluate the enantioselective metabolic perturbations in MCF-7 cells after treatment with R -metalaxyl and S -metalaxyl, respectively. Untargeted metabolomics profile, multivariate pattern recognition, metabolites identification, and pathway analysis were determined after metalaxyl enantiomer exposure. Principal component analysis (PCA) and partitial least-squares discriminant analysis (PLS-DA) directly reflected the enantioselective metabolic perturbations induced by metalaxyl enantiomers. On the basis of multivariate statistical results, a total of 49 metabolites including carbohydrates, amino acids, nucleotides, fatty acids, organic acids, phospholipids, indoles, derivatives, etc. were found to be the most significantly changed metabolites and metabolic fluctuations caused by the same concentration of R -metalaxyl and S -metalaxyl were enantioselective. Pathway analysis indicated that R -metalaxyl and S -metalaxyl mainly affected the 7 and 10 pathways in MCF-7 cells, respectively, implying the perturbed pathways induced by metalaxyl enantiomers were also enantioselective. Furthermore, the significantly perturbed metabolic pathways were highly related to energy metabolism, amino acid metabolism, lipid metabolism, and antioxidant defense. Such results provide more specific insights into the enantioselective metabolic effects of chiral pesticides in breast cancer progression, reveal the underlying mechanisms, and provide available data for the health risk assessments of chiral environmental pollutants at the molecular level.

  17. Highly enantioselective [3 + 2]-annulation of isatin-derived morita-baylis-hillman adducts with cyclic sulfonimines.

    Science.gov (United States)

    Wei, Feng; Huang, Hong-Yan; Zhong, Neng-Jun; Gu, Chun-Ling; Wang, Dong; Liu, Li

    2015-04-03

    An organocatalytic [3 + 2]-annulation between isatin-derived Morita-Baylis-Hillman adducts and cyclic sulfonimines has been developed in high yields with excellent enantio- and diastereoselectivities via an allylic nitrogen-ylide intermediate. The reaction provides access to heavily substituted aza-spirooxindole derivatives, which also contain ring fused cyclic sultams.

  18. Increased enantioselectivity and remarkable acceleration of lipase-catalyzed transesterification by using an imidazolium PEG-alkyl sulfate ionic liquid.

    Science.gov (United States)

    Itoh, Toshiyuki; Matsushita, Yuichi; Abe, Yoshikazu; Han, Shi-Hui; Wada, Shohei; Hayase, Shuichi; Kawatsura, Motoi; Takai, Shigeomi; Morimoto, Minoru; Hirose, Yoshihiko

    2006-12-13

    Several types of imidazolium salt ionic liquids were prepared derived from poly(oxyethylene)alkyl sulfate and used as an additive or coating material for lipase-catalyzed transesterification in an organic solvent. A remarkably increased enantioselectivity was obtained when the salt was added at 3-10 mol % versus substrate in the Burkholderia cepacia lipase (lipase PS-C)-catalyzed transesterification of 1-phenylethanol by using vinyl acetate in diisopropyl ether or a hexane solvent system. In particular, a remarkable acceleration was accomplished by the ionic liquid coating with lipase PS in an iPr(2)O solvent system while maintaining excellent enantioselectivity; it reached approximately 500- to 1000-fold acceleration for some substrates with excellent enantioselectivity. A similar acceleration was also observed for IL 1-coated Candida rugosa lipase. MALDI-TOF mass spectrometry experiments of the ionic-liquid-coated lipase PS suggest that ionic liquid binds with lipase protein.

  19. A direct approach to amines with remote stereocentres by enantioselective CuH-catalysed reductive relay hydroamination

    Science.gov (United States)

    Zhu, Shaolin; Niljianskul, Nootaree; Buchwald, Stephen L.

    2016-02-01

    Amines with remote stereocentres (stereocentres that are three or more bonds away from the C-N bond) are important structural elements in many pharmaceutical agents and natural products. However, previously reported methods to prepare these compounds in an enantioselective manner are indirect and require multistep synthesis. Here, we report a copper-hydride-catalysed, enantioselective synthesis of γ- or δ-chiral amines from readily available allylic alcohols, esters and ethers using a reductive relay hydroamination strategy (a net reductive process in which an amino group is installed at a site remote from the original carbon-carbon double bond). The protocol was suitable for substrates containing a wide range of functional groups and provided remote chiral amine products with high levels of regio- and enantioselectivity. Sequential amination of substrates containing several carbon-carbon double bonds could be achieved, demonstrating the high chemoselectivity of this process.

  20. Observation of the Strong Electronic Coupling in Near-Infrared-Absorbing Tetraferrocene aza-Dipyrromethene and aza-BODIPY with Direct Ferrocene-α- and Ferrocene-β-Pyrrole Bonds: Toward Molecular Machinery with Four-Bit Information Storage Capacity.

    Science.gov (United States)

    Zatsikha, Yuriy V; Holstrom, Cole D; Chanawanno, Kullapa; Osinski, Allen J; Ziegler, Christopher J; Nemykin, Victor N

    2017-01-17

    The 1,3,7,9-tetraferrocenylazadipyrromethene (3) and the corresponding 1,3,5,7-tetraferrocene aza-BODIPY (4) were prepared via three and four synthetic steps, respectively, starting from ferrocenecarbaldehyde using the chalcone-type synthetic methodology. The novel tetra-iron compounds have ferrocene groups directly attached to both the α- and the β-pyrrolic positions, and the shortest Fe-Fe distance determined by X-ray crystallography for 3 was found to be ∼6.98 Å. These new compounds were characterized by UV-vis, nuclear magnetic resonance, and high-resolution electrospray ionization mass spectrometry methods, while metal-metal couplings in these systems were probed by electro- and spectroelectrochemistry, chemical oxidations, and Mössbauer spectroscopy. Electrochemical data are suggestive of the well-separated stepwise oxidations of all four ferrocene groups in 3 and 4, while spectroelectrochemical and chemical oxidation experiments allowed for characterization of the mixed-valence forms in the target compounds. Intervalence charge-transfer band analyses indicate that the mixed-valence [3] + and [4] + complexes belong to the weakly coupled class II systems in the Robin-Day classification. This interpretation was further supported by Mössbauer spectroscopy in which two individual doublets for Fe(II) and Fe(III) centers were observed in room-temperature experiments for the mixed-valence [3] n+ and [4] n+ species (n = 1-3). The electronic structure, redox properties, and UV-vis spectra of new systems were correlated with Density Functional Theory (DFT) and time-dependent DFT calculations (TDDFT), which are suggestive of a ferrocene-centered highest occupied molecular orbital and chromophore-centered lowest unoccupied molecular orbital in 3 and 4 as well as predominant spin localization at the ferrocene fragment attached to the α-pyrrolic positions in [3] + and [4] + .

  1. Enantioselective determination of the chiral pesticide isofenphos-methyl in vegetables, fruits, and soil and its enantioselective degradation in pak choi using HPLC with UV detection.

    Science.gov (United States)

    Gao, Beibei; Zhang, Qing; Tian, Mingming; Zhang, Zhaoxian; Wang, Minghua

    2016-09-01

    An enantioselective method for the simultaneous determination of the chiral pesticide isofenphos-methyl in vegetables, fruits, and soil has been established using high-performance liquid chromatography with UV detection. The complete enantioseparation was conducted by reversed-phase liquid chromatography with a cellulose-tris-(4-methylbenzoate) chiral stationary phase (CSP) (Lux Cellulose-3). The effects of different mobile phase compositions, temperatures, and flow rates on enantioseparation were also investigated. The experimental and calculated electronic circular dichroism spectra indicate that the first peak is (S)-(+)-isofenphos-methyl and the second peak is (R)-(-)-isofenphos-methyl. Alumina-A and Florisil solid-phase extraction (SPE) columns were used to clean up for vegetable, fruit, and soil samples. The mean recoveries of the two enantiomers ranged from 83.2 to 110.9 % with intra-day relative standard deviations (RSDs) from 3.2 to 10.8 % and inter-day RSDs from 3.6 to 10 %. Good linearity (≥0.9992) was obtained for the two enantiomers in all matrix-matched calibration curves in the range of 0.25 to 20 mg L(-1). The limit of detection for two enantiomers in six matrices was in the range of 0.008 to 0.011 mg kg(-1), and the limit of quantification was estimated to range from 0.027 to 0.037 mg kg(-1). The results indicated that this method was a convenient and dependable approach for the simultaneous determination of isofenphos-methyl enantiomers in food and environmental samples. The stereoselective degradation of isofenphos-methyl in pak choi has shown that the (R)-(-)-isofenphos-methyl isomer (half-life t 1/2 = 2.2 days) degraded faster than the (S)-(+)-isomer (t 1/2 = 1.9 days). Graphical Abstract The enantioselective determination and enantioselective degradation of the chiral pesticide isofenphos-methyl.

  2. Direct, Intermolecular, Enantioselective, Iridium-Catalyzed Allylation of Carbamates to Form Carbamate-Protected, Branched Allylic Amines

    Science.gov (United States)

    Weix, Daniel J.; Marković, Dean; Ueda, Mitsuhiro; Hartwig, John F.

    2009-01-01

    The direct reaction between carbamates and achiral allylic carbonates to form branched, conveniently protected primary allylic amines with high regioselectivity and enantioselectivity is reported. This process occurs without base or with 0.5 equiv K3PO4 in the presence of a metalacyclic iridium catalyst containing a labile ethylene ligand. The reactions of aryl, heteroaryl and alkyl-substituted allylic carbonates with BocNH2, FmocNH2, CbzNH2, TrocNH2, TeocNH2, and 2-oxazolidinone occur in good yields, with high selectivity for the branched isomer, and high enantioselectivities (98% average ee). PMID:19552468

  3. Enantioselective Alkynylation of Aromatic Aldehydes Catalyzed by a Sterically Highly Demanding Chiral-at-Rhodium Lewis Acid.

    Science.gov (United States)

    Luo, Shipeng; Zhang, Xiao; Zheng, Yu; Harms, Klaus; Zhang, Lilu; Meggers, Eric

    2017-09-01

    The enantioselective catalytic alkynylation of aromatic aldehydes is reported using a sterically highly hindered bis-cyclometalated rhodium-based Lewis acid catalyst featuring the octahedral metal as the only stereogenic center. Yields of 58-98% with 79-98% enantiomeric excess were achieved using 1-2 mol % of catalyst. This work complements previous work from our laboratory on the enantioselective alkynylation of 2-trifluoroacetyl imidazoles (Chem. - Eur. J. 2016, 22, 11977-11981) and trifluoromethyl ketones (J. Am. Chem. Soc. 2017, 139, 4322-4325) using catalysts with octahedral metal-centered chirality.

  4. Pd-catalysed methoxycarbonylation of vinylarenes using chiral monodentate phosphetanes and phospholane as ligands. Effect of substrate substituents on enantioselectivity.

    Science.gov (United States)

    Muñoz, Bianca K; Godard, Cyril; Marinetti, Angela; Ruiz, Aurora; Benet-Buchholz, Jordi; Claver, Carmen

    2007-12-21

    Palladium complexes bearing phospholane 1 and phosphetane 2-4 ligands have been synthesised to be used as catalyst precursors in the asymmetric methoxycarbonylation of vinyl arenes. Single crystals of the complex [PdCl2(2)2] II were obtained from a toluene solution and analysed by X-ray crystallography. Using these complexes, excellent regioselectivity (up to 99%) to the branched esters was obtained. Phosphetane ligands provide higher enantioselectivity than the phospholane under the same reaction conditions and an important influence of the substrate was observed. Enantioselectivity up to 50% was obtained using 4-methoxystyrene.

  5. Rhodium-catalyzed enantioselective intramolecular C-H silylation for the syntheses of planar-chiral metallocene siloles.

    Science.gov (United States)

    Zhang, Qing-Wei; An, Kun; Liu, Li-Chuan; Yue, Yuan; He, Wei

    2015-06-01

    Reported herein is the rhodium-catalyzed enantioselective C-H bond silylation of the cyclopentadiene rings in Fe and Ru metallocenes. Thus, in the presence of (S)-TMS-Segphos, the reactions took place under very mild conditions to afford metallocene-fused siloles in good to excellent yields and with ee values of up to 97%. During this study it was observed that the steric hindrance of chiral ligands had a profound influence on the reactivity and enantioselectivity of the reaction, and might hold the key to accomplishing conventionally challenging asymmetric C-H silylations. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Nickel-catalyzed enantioselective cross-couplings of racemic secondary electrophiles that bear an oxygen leaving group.

    Science.gov (United States)

    Oelke, Alexander J; Sun, Jianwei; Fu, Gregory C

    2012-02-15

    To date, effective nickel-catalyzed enantioselective cross-couplings of alkyl electrophiles that bear oxygen leaving groups have been limited to reactions of allylic alcohol derivatives with Grignard reagents. In this Communication, we establish that, in the presence of a nickel/pybox catalyst, a variety of racemic propargylic carbonates are suitable partners for asymmetric couplings with organozinc reagents. The method is compatible with an array of functional groups and utilizes commercially available catalyst components. The development of a versatile nickel-catalyzed enantioselective cross-coupling process for electrophiles that bear a leaving group other than a halide adds a significant new dimension to the scope of these reactions.

  7. Exploration of Cocatalyst Effects on a Bimetallic Cobalt Catalyst System: Enhanced Activity and Enantioselectivity in Epoxide Polymerization

    KAUST Repository

    Widger, Peter C. B.

    2011-07-26

    Organic ionic compounds were synthesized and investigated as cocatalysts with a bimetallic cobalt complex for enantioselective epoxide polymerization. The identities of both the cation and the anion were systematically varied, and the subsequent reactivity was studied. The nature of the ionic cocatalyst dramatically impacted the rate and enantioselectivity of the catalyst system. The ionic cocatalyst [P(N=P(N(CH2)4)3) 4 +][tBuCO2 -] in combination with a bimetallic cobalt complex produced a catalyst system that exhibited the greatest activity and selectivity for a variety of monosubstituted epoxides. © 2011 American Chemical Society.

  8. Enantioselective Synthesis of Chiral-at-Cage o-Carboranes via Pd-Catalyzed Asymmetric B-H Substitution.

    Science.gov (United States)

    Cheng, Ruofei; Li, Bowen; Wu, Jie; Zhang, Jie; Qiu, Zaozao; Tang, Wenjun; You, Shu-Li; Tang, Yong; Xie, Zuowei

    2018-03-26

    Carborane cage chirality is an outstanding issue of great interest as the icosahedral carboranes have wide applications in medicinal and materials chemistry. The synthesis of optically active carborane derivatives, whose chirality is associated with the substitution patterns on the polyhedron, will open new avenues to carborane chemistry. We report herein an efficient method to achieve chiral-at-cage arylation of o-carboranes with high regio- and enantio-selectivities by a strategy of palladium-catalyzed asymmetric intramolecular B-H arylation and cyclization. This represents the first example of the enantioselective reaction on carboranes, providing an efficient way for the construction of chiral-at-cage compounds with new skeletons.

  9. Combining the catalytic enantioselective reaction of visible-light-generated radicals with a by-product utilization system.

    Science.gov (United States)

    Huang, Xiaoqiang; Luo, Shipeng; Burghaus, Olaf; Webster, Richard D; Harms, Klaus; Meggers, Eric

    2017-10-01

    We report an unusual reaction design in which a chiral bis-cyclometalated rhodium(iii) complex enables the stereocontrolled chemistry of photo-generated carbon-centered radicals and at the same time catalyzes an enantioselective sulfonyl radical addition to an alkene. Specifically, employing inexpensive and readily available Hantzsch esters as the photoredox mediator, Rh-coordinated prochiral radicals generated by a selective photoinduced single electron reduction are trapped by allyl sulfones in a highly stereocontrolled fashion, providing radical allylation products with up to 97% ee. The hereby formed fragmented sulfonyl radicals are utilized via an enantioselective radical addition to form chiral sulfones, which minimizes waste generation.

  10. Enantioselective small molecule synthesis by carbon dioxide fixation using a dual Brønsted acid/base organocatalyst.

    Science.gov (United States)

    Vara, Brandon A; Struble, Thomas J; Wang, Weiwei; Dobish, Mark C; Johnston, Jeffrey N

    2015-06-17

    Carbon dioxide exhibits many of the qualities of an ideal reagent: it is nontoxic, plentiful, and inexpensive. Unlike other gaseous reagents, however, it has found limited use in enantioselective synthesis. Moreover, unprecedented is a tool that merges one of the simplest biological approaches to catalysis-Brønsted acid/base activation-with this abundant reagent. We describe a metal-free small molecule catalyst that achieves the three component reaction between a homoallylic alcohol, carbon dioxide, and an electrophilic source of iodine. Cyclic carbonates are formed enantioselectively.

  11. A DFT study on the mechanisms for the cycloaddition reactions between 1-aza-2-azoniaallene cations and acetylenes.

    Science.gov (United States)

    Wang, Jing-mei; Li, Zhi-ming; Wang, Quan-rui; Tao, Feng-gang

    2013-01-01

    The mechanisms of cycloaddition reactions between 1-aza-2-azoniaallene cations 1 and acetylenes 2 have been investigated using the global electrophilicity and nucleophilicity of the corresponding reactants as global reactivity indexes defined within the conceptual density functional theory. The reactivity and regioselectivity of these reactions were predicted by analysis of the energies, geometries, and electronic nature of the transition state structures. The theoretical results revealed that the reaction features a tandem process: an ionic 1,3-dipolar cycloaddition to produce the cycloadducts 3 H-pyrazolium salts 3 followed by a [1,2]-shift affording the thermodynamically more stable adducts 4 or 5. The mechanism of the cycloaddition reactions can be described as an asynchronous concerted pathway with reverse electron demand. The model reaction has also been investigated at the QCISD/6-31++G(d,p) and CCSD(T)/6-31++G(d,p)//B3LYP/6-31++G(d,p) levels as well as by the DFT. The polarizable continuum model, at the B3LYP/6-31++G(d,p) level of theory, was used to study solvent effects on all the studied reactions. In solvent dichloromethane, all the initial cycloadducts 3 were obtained via direct ionic process as the result of the solvent effect. The consecutive [1,2]-shift reaction, in which intermediates 3 are rearranged to the five-membered heterocycles 4/5, is proved to be a kinetically controlled reaction, and the regioselectivity can be modulated by varying the migrant. The LOL function and RDG function based on localized electron analysis were used to analysis the covalent bond and noncovalent interactions in order to unravel the mechanism of the title reactions.

  12. The epigenetic modifiers 5-aza-2'-deoxycytidine and trichostatin A influence adipocyte differentiation in human mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    J. Zych

    2013-05-01

    Full Text Available Epigenetic mechanisms such as DNA methylation and histone modification are important in stem cell differentiation. Methylation is principally associated with transcriptional repression, and histone acetylation is correlated with an active chromatin state. We determined the effects of these epigenetic mechanisms on adipocyte differentiation in mesenchymal stem cells (MSCs derived from bone marrow (BM-MSCs and adipose tissue (ADSCs using the chromatin-modifying agents trichostatin A (TSA, a histone deacetylase inhibitor, and 5-aza-2′-deoxycytidine (5azadC, a demethylating agent. Subconfluent MSC cultures were treated with 5, 50, or 500 nM TSA or with 1, 10, or 100 µM 5azadC for 2 days before the initiation of adipogenesis. The differentiation was quantified and expression of the adipocyte genes PPARG and FABP4 and of the anti-adipocyte gene GATA2 was evaluated. TSA decreased adipogenesis, except in BM-MSCs treated with 5 nM TSA. Only treatment with 500 nM TSA decreased cell proliferation. 5azadC treatment decreased proliferation and adipocyte differentiation in all conditions evaluated, resulting in the downregulation of PPARG and FABP4 and the upregulation of GATA2. The response to treatment was stronger in ADSCs than in BM-MSCs, suggesting that epigenetic memories may differ between cells of different origins. As epigenetic signatures affect differentiation, it should be possible to direct the use of MSCs in cell therapies to improve process efficiency by considering the various sources available.

  13. Gene expression profiling of the synergy of 5-aza-2′-deoxycytidine and paclitaxel against renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Han Tiandong

    2012-09-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC is one of the most common kidney cancers and is highly resistant to chemotherapy. We previously demonstrated that 5-aza-2′-deoxycytidine (DAC could significantly increase the susceptibility of renal cell carcinoma (RCC cells to paclitaxel (PTX treatment in vitro, and showed the synergy of DAC and PTX against RCC. The purpose of this study is to investigated the gene transcriptional alteration and investigate possible molecular mechanism and pathways implicated in the synergy of DAC and PTX against RCC. Methods cDNA microarray was performed and coupled with real-time PCR to identify critical genes in the synergistic mechanism of both agents against RCC cells. Various patterns of gene expression were observed by cluster analysis. IPA software was used to analyze possible biological pathways and to explore the inter-relationships between interesting network genes. Results We found that lymphoid enhancer-binding factor 1 (LEF1, transforming growth factor β-induced (TGFBI, C-X-C motif ligand 5 (CXCL5 and myelocytomatosis viral related oncogene (c-myc may play a pivotal role in the synergy of DAC and PTX. The PI3K/Akt pathway and other pathways associated with cyclins, DNA replication and cell cycle/mitotic regulation were also associated with the synergy of DAC and PTX against RCC. Conclusion The activation of PI3K/Akt-LEF1/β-catenin pathway could be suppressed synergistically by two agents and that PI3K/Akt-LEF1/β-catenin pathway is participated in the synergy of two agents.

  14. Chiral separations in normal phase liquid chromatography: enantioselectivity of recently commercialized polysaccharide-based selectors. Part I: enantioselectivity under generic screening conditions.

    Science.gov (United States)

    Younes, Ahmed A; Mangelings, Debby; Vander Heyden, Yvan

    2011-06-01

    Four recently commercialized polysaccharide-based chiral stationary phases, Sepapak(®) 1, Sepapak(®) 2, Sepapak(®) 3, and Sepapak(®) 4, now called Lux(®) Cellulose-1, Lux(®) Cellulose-2, Lux(®) Amylose-2 and Lux(®) Cellulose-4, respectively, were examined for their enantioselectivity on a set of 61 racemic compounds by applying the screening conditions of a previously developed chiral screening strategy in normal phase liquid chromatography (NPLC) [N. Matthijs et al., J. Chromatogr. A 1041 (2004) 119-133]. The enantioselectivity on these phases was compared to that on the initial set of polysaccharide-based phases, Chiralpak(®) AD-H, Chiralcel(®) OD-H, and Chiralcel(®) OJ-H, used in the earlier defined strategy. The results showed that 53 compounds out of 61 (86.9%) were resolved on the initial set of chiral stationary phases (CSPs) using two mobile phases per compound, either heptane-ethanol-diethylamine (DEA) or heptane-isopropanol-DEA for testing basic compounds and heptane-ethanol-trifluoroacetic acid (TFA) or heptane-isopropanol-TFA for acidic, bifunctional and neutral compounds. The recently commercialized set of columns gave 54 separations in total (88.5%). Our results indicated that ethanol (EtOH) as polar modifier provides a higher success rate and better resolutions than isopropanol (IPA) on both sets of stationary phases. However, the usefulness of the mobile phase with IPA as polar modifier cannot be neglected for complementarity reasons. It was found that the screening is improved by the introduction of the recently commercialized polysaccharides based CSPs since they provided enantioseparation for compounds that were not resolved by the traditional CSPs. The combination between the initial and the recently commercialized CSPs showed enantioresolution for 55 compounds out of 61 (90%), among which 47 were baseline resolved. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. A new enantioselective CE method for determination of oxcarbazepine and licarbazepine after fungal biotransformation.

    Science.gov (United States)

    Bocato, Mariana Zuccherato; Bortoleto, Marcela Armelim; Pupo, Mônica Tallarico; de Oliveira, Anderson Rodrigo Moraes

    2014-10-01

    The present work describes, for the first time, the simultaneous separation of oxcarbazepine (OXC) and its active metabolite 10-hydroxy-10,11-dihydrocarbamazepine (licarbazepine, Lic) by chiral CE. The developed method was employed to monitor the enantioselective biotransformation of OXC into its active metabolite by fungi. The electrophoretic separations were performed using 10 mmol/L of a Tris-phosphate buffer solution (pH 2.5) containing 1% w/v of β-CD phosphate sodium salt (P-β-CD) as running electrolyte, -20 kV of applied voltage and a 15°C capillary temperature. The method was linear over the concentration range of 1000-30 000 ng/mL for OXC and 75-900 ng/mL for each Lic enantiomer (r ≥ 0.9952). Within-day precision and accuracy evaluated by RSD and relative errors, respectively, were lower than 15% for all analytes. The validated method was used to evaluate the enantioselective biotransformation of OXC, mediated by fungi, into its active metabolite Lic. This study showed that the fungi Glomerella cingulata (VA1) and Beuveria bassiana were able to enantioselectively metabolize the OXC into Lic after 360 h of incubation. Biotransformation by the fungus Beuveria bassiana showed 79% enantiomeric excess for (S)-(+)-Lic, while VA1 gave an enantiomeric excess of 100% for (S)-(+)-Lic. This study opens a new route to the drug (S)-(+)-licarbazepine. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Novel smart chiral magnetic microspheres for enantioselective adsorption of tryptophan enantiomers

    Science.gov (United States)

    Guo, Lian-Di; Song, Ya-Ya; Yu, Hai-Rong; Pan, Li-Ting; Cheng, Chang-Jing

    2017-06-01

    Multifunctional microspheres simultaneously possessing chirality, magnetism and thermosensitivity show great potentials in direct enantiomeric separation. Herein we report a novel type of smart chiral magnetic microspheres with core/shell/shell structures (Fe3O4@SiO2@PNCD) and its application in enantioselective adsorption of tryptophan (Trp) enantiomers. The prepared Fe3O4@SiO2@PNCD are composed of a Fe3O4 nanoparticle core, an acidic-resistant SiO2 middle shell and a thermosensitive microgel functional shell (PNCD). The PNCD plays an important role in the enantioselective adsorption of Trp enantiomers. The β-cyclodextrin (β-CD) molecules on the PNCD act as smart receptors or chiral selectors, and can selectively recognize and bind L-Trp enantiomers into their cavities by forming host-guest inclusion complexes. The poly(N-isopropylacrylamide) (PNIPAM) chains on the PNCD serve as microenvironmental adjustors for the association constants of β-CD/L-Trp complexes. The fabricated Fe3O4@SiO2@PNCD demonstrate fascinating temperature-responsive chiral recognition and adsorption selectivity toward Trp enantiomers. Most importantly, the desorption of Trp enantiomers and the regeneration of the Fe3O4@SiO2@PNCD can be easily achieved via simply changing the operation temperature. Moreover, the regenerated Fe3O4@SiO2@PNCD can be readily recovered from the amino acids enantiomeric solution under an external magnetic field for reuse. The present study provides a novel strategy for the direct enantioselective adsorption and separation of various enantiomeric compounds.

  17. 3D chiral nanoplasmonics: fabrication, chiroptic engineering, mechanism, and application in enantioselection (Presentation Recording)

    Science.gov (United States)

    Huang, Zhifeng

    2015-09-01

    Chirality does naturally exist, and the building blocks of life (e.g. DNA, proteins, peptides and sugars) are usually chiral. Chirality inherently imposes chemical/biological selectivity on functional molecules; hence the discrimination in molecular chirality from an enantiomer to the other mirror image (i.e. enantioselection) has fundamental and application significance. Enantiomers interact with left and right handed circularly polarized light in a different manner with respect to optical extinction; hence, electronic circular dichroism (ECD) has been widely used for enantioselection. However, enantiomers usually have remarkably low ECD intensity, mainly owing to the small electric transition dipole moment induced by molecular sizes compared to the ECD-active wavelength in the UV-visible-near IR region. To enhance ECD magnitude, recently it has being developed 3D chiral nanoplasmonic structures having a helical path, and the dimensions are comparable to the ECD wavelength. However, it is still ambiguous the origin of 3D chiroplasmonics, and there is a lack of studying the interaction of 3D chiroplasmoncs with enantiomers for the application of enantioselection. Herein, we will present a one-step fabrication of 3D silver nanospirals (AgNSs) via low-substrate-temperature glancing angle deposition. AgNSs can be deposited on a wide range of substrates (including transparent and flexible substrates), in an area on the order of cm2. A set of spiral dimensions (such as spiral pitches, number of turns and handedness) have been easily engineered to tune the chiroptic properties, leading to studying the chiroplasmonic principles together with finite element simulation and the LC model. At the end, it will be demonstrated that 3D chiroplasmonics can differentiate molecular chirality of enantiomers with dramatic enhancement in the anisotropy g factor. This study opens a door to sensitively discriminate enantiomer chirality.

  18. All-trans retinoic acid combined with 5-Aza-2′-deoxycitidine induces C/EBPα expression and growth inhibition in MLL-AF9-positive leukemic cells

    International Nuclear Information System (INIS)

    Fujiki, Atsushi; Imamura, Toshihiko; Sakamoto, Kenichi; Kawashima, Sachiko; Yoshida, Hideki; Hirashima, Yoshifumi; Miyachi, Mitsuru; Yagyu, Shigeki; Nakatani, Takuya; Sugita, Kanji; Hosoi, Hajime

    2012-01-01

    Highlights: ► We tested whether ATRA and 5-Aza affect AML cell differentiation and growth. ► Cell differentiation and growth arrest were induced in MLL-AF9-expressing cells. ► Increased expression of C/EBPα, C/EBPε, and PU.1 were also observed. ► MLL-AF4/AF5q31-expressing cells are less sensitive to ATRA and 5-Aza. ► Different MLL fusion has distinct epigenetic properties related to RA pathway. -- Abstract: The present study tested whether all-trans retinoic acid (ATRA) and 5-Aza-2′-deoxycitidine (5-Aza) affect AML cell differentiation and growth in vitro by acting on the CCAAT/enhancer binding protein α (C/EBPα) and c-Myc axis. After exposure to a combination of these agents, cell differentiation and growth arrest were significantly higher in human and murine MLL-AF9-expressing cells than in MLL-AF4/AF5q31-expressing cells, which were partly associated with increased expression of C/EBPα, C/EBPε, and PU.1, and decreased expression of c-Myc. These findings indicate that MLL-AF9-expressing cells are more sensitive to ATRA and 5-Aza, indicating that different MLL fusion proteins possess different epigenetic properties associated with retinoic acid pathway inactivation.

  19. All-trans retinoic acid combined with 5-Aza-2 Prime -deoxycitidine induces C/EBP{alpha} expression and growth inhibition in MLL-AF9-positive leukemic cells

    Energy Technology Data Exchange (ETDEWEB)

    Fujiki, Atsushi [Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Imamura, Toshihiko, E-mail: imamura@koto.kpu-m.ac.jp [Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Sakamoto, Kenichi; Kawashima, Sachiko; Yoshida, Hideki; Hirashima, Yoshifumi; Miyachi, Mitsuru; Yagyu, Shigeki; Nakatani, Takuya [Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Sugita, Kanji [Department of Pediatrics, University of Yamanashi, Yamanashi (Japan); Hosoi, Hajime [Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer We tested whether ATRA and 5-Aza affect AML cell differentiation and growth. Black-Right-Pointing-Pointer Cell differentiation and growth arrest were induced in MLL-AF9-expressing cells. Black-Right-Pointing-Pointer Increased expression of C/EBP{alpha}, C/EBP{epsilon}, and PU.1 were also observed. Black-Right-Pointing-Pointer MLL-AF4/AF5q31-expressing cells are less sensitive to ATRA and 5-Aza. Black-Right-Pointing-Pointer Different MLL fusion has distinct epigenetic properties related to RA pathway. -- Abstract: The present study tested whether all-trans retinoic acid (ATRA) and 5-Aza-2 Prime -deoxycitidine (5-Aza) affect AML cell differentiation and growth in vitro by acting on the CCAAT/enhancer binding protein {alpha} (C/EBP{alpha}) and c-Myc axis. After exposure to a combination of these agents, cell differentiation and growth arrest were significantly higher in human and murine MLL-AF9-expressing cells than in MLL-AF4/AF5q31-expressing cells, which were partly associated with increased expression of C/EBP{alpha}, C/EBP{epsilon}, and PU.1, and decreased expression of c-Myc. These findings indicate that MLL-AF9-expressing cells are more sensitive to ATRA and 5-Aza, indicating that different MLL fusion proteins possess different epigenetic properties associated with retinoic acid pathway inactivation.

  20. Improved Enantioselectivity of Subtilisin Carlsberg towards Secondary Alcohols by Protein Engineering

    DEFF Research Database (Denmark)

    Dorau, Robin; Görbe, Tamas; Svedendahl Humble, Maria

    2017-01-01

    for mutagenesis were found by combining available literature data with molecular modeling. SC variants were created by site-directed mutagenesis and were evaluated for a model transacylation reaction containing 1-phenylethanol in THF. Variants showing high E values (>100) were found. However, the conversions were...... still low. A second mutation was made, and both the E values and conversions were increased. Relative to that shown by the wild type, the most successful variant, G165L/M221F, showed increased conversion (up to 36%), enantioselectivity (E values up to 400), substrate scope, and stability in THF....

  1. Enzymatic Kinetic Resolution of 2-Piperidineethanol for the Enantioselective Targeted and Diversity Oriented Synthesis

    Directory of Open Access Journals (Sweden)

    Dario Perdicchia

    2015-12-01

    Full Text Available 2-Piperidineethanol (1 and its corresponding N-protected aldehyde (2 were used for the synthesis of several natural and synthetic compounds. The existence of a stereocenter at position 2 of the piperidine skeleton and the presence of an easily-functionalized group, such as the alcohol, set 1 as a valuable starting material for enantioselective synthesis. Herein, are presented both synthetic and enzymatic methods for the resolution of the racemic 1, as well as an overview of synthesized natural products starting from the enantiopure 1.

  2. Enantioselective biotransformation of propranolol to the active metabolite 4-hydroxypropranolol by endophytic fungi

    Directory of Open Access Journals (Sweden)

    Keyller Bastos Borges

    2011-01-01

    Full Text Available The enantioselective biotransformation of propranolol (Prop by the endophytic fungi Phomopsis sp., Glomerella cingulata, Penicillium crustosum, Chaetomium globosum and Aspergillus fumigatus was investigated by studying the kinetics of the aromatic hydroxylation reaction with the formation of 4-hydroxypropranolol (4-OH-Prop. Both Prop enantiomers were consumed by the fungi in the biotransformation process, but the 4-hydroxylation reaction yielded preferentially (--(S-4-OH-Prop. The quantity of metabolites biosynthesized varied slightly among the evaluated endophytic fungi. These results show that all investigated endophytic fungi could be used as biosynthetic tools in biotransformation processes to obtain the enantiomers of 4-OH-Prop.

  3. Zirconium(IV)- and hafnium(IV)-catalyzed highly enantioselective epoxidation of homoallylic and bishomoallylic alcohols.

    Science.gov (United States)

    Li, Zhi; Yamamoto, Hisashi

    2010-06-16

    In this report, zirconium(IV)- and hafnium(IV)-bishydroxamic acid complexes were utilized in the highly enantioselective epoxidation of homoallylic alcohols and bishomoallylic alcohols, which used to be quite difficult substrates for other types of asymmetric epoxidation reactions. The performance of the catalyst was improved by adding polar additive and molecular sieves. For homoallylic alcohols, the reaction could provide epoxy alcohols in up to 83% yield and up to 98% ee, while, for bishomoallylic alcohols, up to 79% yield and 99% ee of epoxy alcohols rather than cyclized tetrahydrofuran compounds could be obtained in most cases.

  4. Zirconium(IV) and Hafnium(IV)-Catalyzed Highly Enantioselective Epoxidation of Homoallylic and Bishomoallylic Alcohols

    Science.gov (United States)

    Li, Zhi; Yamamoto, Hisashi

    2010-01-01

    In this report, zirconium(IV) and hafnium(IV)-bishydroxamic acid complexes were utilized in the highly enantioselective epoxidation of homoallylic alcohols and bishomoallylic alcohols, which used to be quite difficult substrates for other types of asymmetric epoxidation reactions. The performance of the catalyst was improved by adding polar additive and molecular sieves. For homoallylic alcohols, the reaction could provide epoxy alcohols in up to 81% yield and up to 98% ee, while for bishomoallylic alcohols, up to 75% yield and 99% ee of epoxy alcohols rather than cyclize compounds could be obtained in most cases. PMID:20481541

  5. Enantioselective Synthesis of Caprolactam and Enone Precursors to the Heterocyclic DEFG Ring System of Zoanthenol.

    Science.gov (United States)

    Bagdanoff, Jeffrey T; Behenna, Douglas C; Stockdill, Jennifer L; Stoltz, Brian M

    2016-04-01

    The enantioselective synthesis of both caprolactam and enone synthons for the DEFG ring system of zoanthenol are described. The evolution of this synthetic approach proceeds first through a synthesis using the chiral pool as a starting point. Challenges in protecting group strategy led to the modification of this approach beginning with (±)-glycidol. Ultimately, an efficient approach was developed by employing an asymmetric hetero-Diels-Alder reaction. The caprolactam building block can be converted by an interesting selective Grignard addition to the corresponding enone synthon. Addition of a model alkyne provides support for the late-stage addition of a hindered alkyne into the caprolactam building block.

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

    Science.gov (United States)

    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

  7. Organocatalytic Enantioselective Allylic Etherification of Morita-Baylis-Hillman Carbonates and Silanols.

    Science.gov (United States)

    Liu, Hui-Li; Xie, Ming-Sheng; Qu, Gui-Rong; Guo, Hai-Ming

    2016-10-21

    The organocatalytic asymmetric allylic etherification reaction of Morita-Baylis-Hillman carbonates and silanols was reported for the first time. With modified cinchona alkaloid (DHQD) 2 PYR as the catalyst, a series of aromatic, heterocyclic, or aliphatic Morita-Baylis-Hillman carbonates (25 examples) worked well with triphenylsilanol, affording the corresponding products in moderate to good yields (up to 98%), high regioselectivities (>20:1), and good enantioselectivities (up to 92%). When dimethylphenylsilanol was used as the nucleophile, the product was obtained in 60% yield and 87% ee.

  8. Enantioselective developmental toxicity and immunotoxicity of pyraclofos toward zebrafish (Danio rerio)

    Energy Technology Data Exchange (ETDEWEB)

    Zhuang, Shulin, E-mail: shulin@zju.edu.cn [Institute of Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China); Zhejiang Provincial Key Laboratory of Organic Pollution Process and Control, Hangzhou 310058 (China); Zhang, Zhisheng [Institute of Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China); Zhang, Wenjing; Bao, Lingling [Institute of Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China); Zhejiang Provincial Key Laboratory of Organic Pollution Process and Control, Hangzhou 310058 (China); Xu, Chao, E-mail: chaoxu@zjut.edu.cn [Research Center of Environmental Science, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China); Zhang, Hu [Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 210021 (China)

    2015-02-15

    Highlights: • Pyraclofos has significant enantioselective aquatic toxicities to zebrafish. • Pyraclofos induces time- and concentration-dependent developmental toxicity and immunotoxicity. • The mRNA level of IL-1β gene was significantly up-regulated by pyraclofos. • Pyraclofos binds potently to IL-1β, potentially affecting IL-1β-dependent proinflammatory signal transduction. • Our in vitro and in silico studies help to understand the molecular basis for aquatic toxicity of pyraclofos. - Abstract: Pyraclofos, a relatively new organophosphorus pesticide, has shown potential ecotoxicities, however, its aquatic toxicity, especially enantioselective aquatic toxicity, remains largely unknown. Using zebrafish (Danio rerio) as a preeminent vertebrate aquatic model, the enantioselective differences in the developmental toxicity and immunotoxicity of pyraclofos were evaluated. Following 96-h exposure, pyraclofos enantiomers exhibited acute toxicity and showed lethal concentration 50 of 2.23 and 3.99 mg/L for (R)-Pyraclofos and (S)-Pyraclofos, respectively. Exposure to pyraclofos caused time- and concentration-dependent malformations such as pericardial edema, yolk sac edema, crooked bodies and hatching during the embryonic development, with markedly higher percentages of malformation at higher concentrations. The concentration-dependent immunotoxicity to zebrafish embryo exposed to low level pyraclofos was induced with significant up-regulation of mRNA levels of immune-related interleukin-1β (IL-1β) gene. (R)-Pyraclofos was consistently more toxic than (S)-Pyraclofos for the acute toxicity, developmental toxicity and immunotoxicity to zebrafish. Molecular dynamics simulations revealed that at the atomic level, (R)-Pyraclofos binds more potently to IL-1β protein than (S)-Pyraclofos. This enantioselective binding is mainly contributed by the distinct binding mode of pyraclofos enantiomers and their electrostatic interactions with IL-1β, which potentially

  9. Enantioselective developmental toxicity and immunotoxicity of pyraclofos toward zebrafish (Danio rerio)

    International Nuclear Information System (INIS)

    Zhuang, Shulin; Zhang, Zhisheng; Zhang, Wenjing; Bao, Lingling; Xu, Chao; Zhang, Hu

    2015-01-01

    Highlights: • Pyraclofos has significant enantioselective aquatic toxicities to zebrafish. • Pyraclofos induces time- and concentration-dependent developmental toxicity and immunotoxicity. • The mRNA level of IL-1β gene was significantly up-regulated by pyraclofos. • Pyraclofos binds potently to IL-1β, potentially affecting IL-1β-dependent proinflammatory signal transduction. • Our in vitro and in silico studies help to understand the molecular basis for aquatic toxicity of pyraclofos. - Abstract: Pyraclofos, a relatively new organophosphorus pesticide, has shown potential ecotoxicities, however, its aquatic toxicity, especially enantioselective aquatic toxicity, remains largely unknown. Using zebrafish (Danio rerio) as a preeminent vertebrate aquatic model, the enantioselective differences in the developmental toxicity and immunotoxicity of pyraclofos were evaluated. Following 96-h exposure, pyraclofos enantiomers exhibited acute toxicity and showed lethal concentration 50 of 2.23 and 3.99 mg/L for (R)-Pyraclofos and (S)-Pyraclofos, respectively. Exposure to pyraclofos caused time- and concentration-dependent malformations such as pericardial edema, yolk sac edema, crooked bodies and hatching during the embryonic development, with markedly higher percentages of malformation at higher concentrations. The concentration-dependent immunotoxicity to zebrafish embryo exposed to low level pyraclofos was induced with significant up-regulation of mRNA levels of immune-related interleukin-1β (IL-1β) gene. (R)-Pyraclofos was consistently more toxic than (S)-Pyraclofos for the acute toxicity, developmental toxicity and immunotoxicity to zebrafish. Molecular dynamics simulations revealed that at the atomic level, (R)-Pyraclofos binds more potently to IL-1β protein than (S)-Pyraclofos. This enantioselective binding is mainly contributed by the distinct binding mode of pyraclofos enantiomers and their electrostatic interactions with IL-1β, which potentially

  10. Nano-organocatalyst: magnetically retrievable ferrite-anchored glutathione for microwave-assisted Paal–Knorr reaction, aza-Michael addition, and pyrazole synthesis

    KAUST Repository

    Polshettiwar, Vivek

    2010-01-01

    Postsynthetic Surface modification of magnetic nanoparticles by glutathione imparts desirable chemical functionality and enables the generation of catalytic sites on the surfaces of ensuing organocatalysts. In this article, we discuss the developments, unique activity, and high selectivity of nano-organocatalysts for microwave-assisted Paal-Knorr reaction, aza-Michael addition, and pyrazole synthesis. Their insoluble character Coupled with paramagnetic nature enables easy separation of these nano-catalysts from the reaction mixture using external magnet, which eliminates the requirement of catalyst filtration. Published by Elsevier Ltd.

  11. Aza-peptidyl Michael acceptors. A new class of potent and selective inhibitors of asparaginyl endopeptidases (legumains) from evolutionarily diverse pathogens

    Czech Academy of Sciences Publication Activity Database

    Götz, M. G.; James, K. E.; Hansell, E.; Dvořák, J.; Seshaadri, A.; Sojka, Daniel; Kopáček, Petr; McKerrow, J. H.; Caffrey, C. R.; Powers, J. C.

    2008-01-01

    Roč. 51, č. 9 (2008), s. 2816-2832 ISSN 0022-2623 R&D Projects: GA MŠk(CZ) LC06009; GA ČR GA206/06/0865 Grant - others:The National Institute of Allergy and Infectious Diseases(US) AI053247; National Institute of General Medical Sciences(US) GM54404; National Institute of General Medical Sciences(US) GM61964 Institutional research plan: CEZ:AV0Z60220518 Keywords : legumain * IrAE * aza-peptide Michael acceptors Subject RIV: ED - Physiology Impact factor: 4.898, year: 2008

  12. Enantioselective copper-catalysed propargylic substitution: synthetic scope study and application in formal total syntheses of (+)-anisomycin and (-)-cytoxazone

    NARCIS (Netherlands)

    Detz, R.J.; Abiri, Z.; le Griel, R.; Hiemstra, H.; van Maarseveen, J.H.

    2011-01-01

    A copper catalyst with a chiral pyridine-2,6-bisoxazoline (pybox) ligand was used to convert a variety of propargylic esters with different side chains (R=Ar, Bn, alkyl) into their amine counterparts in very high yields and with good enantioselectivities (up to 90 % enantiomeric excess (ee)).

  13. Synthesis of optically active bifunctional building blocks through enantioselective copper-catalyzed allylic alkylation using Grignard reagents

    NARCIS (Netherlands)

    van Zijl, Anthoni W.; Lopez, Fernando; Minnaard, Adriaan J.; Feringa, Ben L.

    2007-01-01

    Enantioselective copper-catalyzed allylic alkylations were performed on allylic bromides with a protected hydroxyl or amine functional group using several Grignard reagents and Taniaphos L1 as a ligand. The terminal olefin moiety in the products was transformed into various functional groups without

  14. DNA-Accelerated Copper Catalysis of Friedel-Crafts Conjugate Addition/Enantioselective Protonation Reactions in Water

    NARCIS (Netherlands)

    García-Fernández, Almudena; Megens, Rik P.; Villarino, Lara; Roelfes, Gerard

    2016-01-01

    DNA-induced rate acceleration has been identified as one of the key elements for the success of the DNA-based catalysis concept. Here we report on a novel DNA-based catalytic Friedel-Crafts conjugate addition/enantioselective protonation reaction in water, which represents the first example of a

  15. Enantioselective synthesis of benzofurans and benzoxazines via an olefin cross-metathesis-intramolecular oxo-Michael reaction.

    Science.gov (United States)

    Zhang, Jun-Wei; Cai, Quan; Gu, Qing; Shi, Xiao-Xin; You, Shu-Li

    2013-09-11

    Chiral phosphoric acid and Hoveyda-Grubbs II were found to catalyze an olefin cross-metathesis-intramolecular oxo-Michael cascade reaction of the ortho-allylphenols and enones to provide a variety of benzofuran and benzoxazine derivatives in moderate to good yields and enantioselectivity.

  16. Enantioselective α-Alkenylation of Aldehydes with Boronic Acids via the Synergistic Combination of Copper(II) and Amine Catalysis

    Science.gov (United States)

    Stevens, Jason M.

    2013-01-01

    The enantioselective α-alkenylation of aldehydes has been accomplished using boronic acids via the synergistic combination of copper and chiral amine catalysis. The merger of two highly utilized and robust catalytic systems has allowed for the development of a mild and operationally trivial protocol for the direct formation of α-formyl olefins employing common building blocks for organic synthesis. PMID:23889497

  17. The Use of N-Type Ligands in the Enantioselective Liquid–Liquid Extraction of Underivatized Amino Acids

    NARCIS (Netherlands)

    Verkuijl, Bastiaan J.V.; Schoonen, Anne K.; Minnaard, Adriaan J.; Vries, Johannes G. de; Feringa, Bernard

    The first palladium based extraction system using chiral N-based ligands in the enantioselective liquid–liquid extraction (ELLE) of underivatized amino acids, is presented. The system shows the highest selectivity for the ELLE of methionine with metal complexes as hosts reported to date.

  18. Enantioselective Pd(II)-Pd(IV) catalysis utilizing a SPRIX ligand: efficient construction of chiral 3-oxy-tetrahydrofurans.

    Science.gov (United States)

    Takenaka, Kazuhiro; Dhage, Yogesh D; Sasai, Hiroaki

    2013-12-11

    Novel enantioselective catalysis involving a Pd(II)-Pd(IV) cycle was developed by utilizing a SPRIX ligand. Treatment of alkenyl alcohols with a catalytic amount of Pd-SPRIX and TfOH in the presence of PhI(OAc)2 gave optically active 3-oxy-tetrahydrofuran derivatives in good yields.

  19. Platinum(II) catalysts for highly enantioselective 1,6-enyne cycloisomerizations. synthetic, structural, and catalytic studies.

    Science.gov (United States)

    Brissy, Delphine; Skander, Myriem; Jullien, Hélène; Retailleau, Pascal; Marinetti, Angela

    2009-05-21

    A new family of cyclometalated (N-heterocyclic carbene)-Pt(II) complexes bearing monodentate phosphines as ancillary ligands has been designed for use as precatalysts in 1,6-enyne cycloisomerization reactions. Highly enantioselective skeletal rearrangements of allylpropargyl-tosylamide derivatives have been developed by using (S)-Ph-Binepine as the chiral auxiliary. Enantiomeric excesses up to 97% have been obtained.

  20. Synthesis of l-threitol-based crown ethers and their application as enantioselective phase transfer catalyst in Michael additions.

    Science.gov (United States)

    Rapi, Zsolt; Nemcsok, Tamás; Pálvölgyi, Ádám; Keglevich, György; Grün, Alajos; Bakó, Péter

    2017-06-01

    A few new l-threitol-based lariat ethers incorporating a monoaza-15-crown-5 unit were synthesized starting from diethyl l-tartrate. These macrocycles were used as phase transfer catalysts in asymmetric Michael addition reactions under mild conditions to afford the adducts in a few cases in good to excellent enantioselectivities. The addition of 2-nitropropane to trans-chalcone, and the reaction of diethyl acetamidomalonate with β-nitrostyrene resulted in the chiral Michael adducts in good enantioselectivities (90% and 95%, respectively). The substituents of chalcone had a significant impact on the yield and enantioselectivity in the reaction of diethyl acetoxymalonate. The highest enantiomeric excess (ee) values (99% ee) were measured in the case of 4-chloro- and 4-methoxychalcone. The phase transfer catalyzed cyclopropanation reaction of chalcone and benzylidene-malononitriles using diethyl bromomalonate as the nucleophile (MIRC reaction) was also developed. The corresponding chiral cyclopropane diesters were obtained in moderate to good (up to 99%) enantioselectivities in the presence of the threitol-based crown ethers. © 2017 Wiley Periodicals, Inc.

  1. Palladium-Catalyzed Enantioselective C-H Activation of Aliphatic Amines Using Chiral Anionic BINOL-Phosphoric Acid Ligands.

    Science.gov (United States)

    Smalley, Adam P; Cuthbertson, James D; Gaunt, Matthew J

    2017-02-01

    The design of an enantioselective Pd(II)-catalyzed C-H amination reaction is described. The use of a chiral BINOL phosphoric acid ligand enables the conversion of readily available amines into synthetically valuable aziridines in high enantiomeric ratios. The aziridines can be derivatized to afford a range of chiral amine building blocks incorporating motifs readily encountered in pharmaceutically relevant molecules.

  2. Enantioselective Reduction by Crude Plant Parts: Reduction of Benzofuran-2-yl Methyl Ketone with Carrot ("Daucus carota") Bits

    Science.gov (United States)

    Ravia, Silvana; Gamenara, Daniela; Schapiro, Valeria; Bellomo, Ana; Adum, Jorge; Seoane, Gustavo; Gonzalez, David

    2006-01-01

    The use of biocatalysis and biotransformations are important tools in green chemistry. The enantioselective reduction of a ketone by crude plant parts, using carrot ("Daucus carota") as the reducing agent is presented. The experiment introduces an example of a green chemistry procedure that can be tailored to fit in a regular laboratory session.…

  3. Lewis acid-Lewis base catalyzed enantioselective hetero-Diels-Alder reaction for direct access to delta-lactones.

    Science.gov (United States)

    Tiseni, Paolo S; Peters, René

    2008-05-15

    A complex formed in situ from Er(OTf)3 and a simple commercially available norephedrine ligand promotes an unprecedented [4 + 2] cycloaddition of alpha,beta-unsaturated acid chlorides with a broad range of aromatic and heteroaromatic aldehydes by a cooperative bifunctional Lewis acid-Lewis base catalytic mode of action providing valuable delta-lactone building blocks with excellent enantioselectivity.

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

    Science.gov (United States)

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

    2014-04-21

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

  5. Conjugate-base-stabilized Brønsted acids: catalytic enantioselective Pictet-Spengler reactions with unmodified tryptamine.

    Science.gov (United States)

    Mittal, Nisha; Sun, Diana X; Seidel, Daniel

    2014-02-07

    A conjugate-base-stabilized Brønsted acid facilitates catalytic enantioselective Pictet-Spengler reactions with unmodified tryptamine. The chiral carboxylic acid catalyst is readily assembled in just two steps and enables the formation of β-carbolines with up to 92% ee. Achiral acid additives or in situ Boc-protection facilitate catalyst turnover.

  6. Influence of gasoline inhalation on the enantioselective pharmacokinetics of fluoxetine in rats.

    Science.gov (United States)

    Cardoso, Juciane Lauren Cavalcanti; Lanchote, Vera Lucia; Pereira, Maria Paula Marques; Capela, Jorge Manuel Vieira; Lepera, José Salvador

    2013-03-01

    Fluoxetine is used clinically as a racemic mixture of (+)-(S) and (-)-(R) enantiomers for the treatment of depression. CYP2D6 catalyzes the metabolism of both fluoxetine enantiomers. We aimed to evaluate whether exposure to gasoline results in CYP2D inhibition. Male Wistar rats exposed to filtered air (n = 36; control group) or to 600 ppm of gasoline (n = 36) in a nose-only inhalation exposure chamber for 6 weeks (6 h/day, 5 days/week) received a single oral 10-mg/kg dose of racemic fluoxetine. Fluoxetine enantiomers in plasma samples were analyzed by a validated analytical method using LC-MS/MS. The separation of fluoxetine enantiomers was performed in a Chirobiotic V column using as the mobile phase a mixture of ethanol:ammonium acetate 15 mM. Higher plasma concentrations of the (+)-(S)-fluoxetine enantiomer were found in the control group (enantiomeric ratio AUC((+)-(S)/(-)-(R)) = 1.68). In animals exposed to gasoline, we observed an increase in AUC(0-∞) for both enantiomers, with a sharper increase seen for the (-)-(R)-fluoxetine enantiomer (enantiomeric ratio AUC((+)-(S)/(-)-(R)) = 1.07), resulting in a loss of enantioselectivity. Exposure to gasoline was found to result in the loss of enantioselectivity of fluoxetine, with the predominant reduction occurring in the clearance of the (-)-(R)-fluoxetine enantiomer (55% vs. 30%). Copyright © 2013 Wiley Periodicals, Inc.

  7. A catalytic reactor for the organocatalyzed enantioselective continuous flow alkylation of aldehydes.

    Science.gov (United States)

    Porta, Riccardo; Benaglia, Maurizio; Puglisi, Alessandra; Mandoli, Alessandro; Gualandi, Andrea; Cozzi, Pier Giorgio

    2014-12-01

    The use of immobilized metal-free catalysts offers the unique possibility to develop sustainable processes in flow mode. The challenging intermolecular organocatalyzed enantioselective alkylation of aldehydes was performed for the first time under continuous flow conditions. By using a packed-bed reactor filled with readily available supported enantiopure imidazolidinone, different aldehydes were treated with three distinct cationic electrophiles. In the organocatalyzed α-alkylation of aldehydes with 1,3-benzodithiolylium tetrafluoroborate, excellent enantioselectivities, in some cases even better than those obtained in the flask process (up to 95% ee at 25 °C), and high productivity (more than 3800 h(-1) ) were obtained, which thus shows that a catalytic reactor may continuously produce enantiomerically enriched compounds. Treatment of the alkylated products with Raney-nickel furnished enantiomerically enriched α-methyl derivatives, key intermediates for active pharmaceutical ingredients and natural products. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Poly(propylene carbonate): Insight into the Microstructure and Enantioselective Ring-Opening Mechanism

    KAUST Repository

    Salmeia, Khalifah A.

    2012-11-13

    Different poly(propylene carbonate) (PPC) microstructures have been synthesized from the alternating copolymerization of CO 2 with both racemic propylene oxide (PO) and various mixtures of PO enantiomers using chiral salen catalysts. The microstructures of the obtained copolymers as a function of polymerization time have been analyzed by a combination of chiral GC and high-resolution NMR spectroscopy. The 13C NMR spectra of selected poly(propylene carbonate) samples were recorded using a 900 MHz ( 1H) spectrometer, showing a previously unreported fine splitting of the carbonate resonances. This allowed a detailed assignment of signals for various copolymer microstructures taking into account the specifics in their stereo- and regioirregularities. For example, the enantioselectivity preference of the (R,R-salen)Co catalyst for (S)-PO at the beginning of the copolymerization leads predominantly to (S)-PO insertion, with any (R)-PO misinsertion being followed by incorporation of (S)-PO, so that the microstructure features isolated stereoerrors. K rel calculations for the copolymerization showed around 5-fold enantioselectivity for (S)-PO over (R)-PO at short reaction time. Analysis of the copolymer microstructures obtained under various reaction conditions appears to be an additional approach to differentiate the occurrence of bimetallic and bifunctional copolymerization mechanisms that are widely discussed in the literature. © 2012 American Chemical Society.

  9. Characterization of an enantioselective odorant receptor in the yellow fever mosquito Aedes aegypti.

    Directory of Open Access Journals (Sweden)

    Jonathan D Bohbot

    2009-09-01

    Full Text Available Enantiomers differ only in the left or right handedness (chirality of their orientations and exhibit identical chemical and physical properties. In chemical communication systems, enantiomers can be differentially active at the physiological and behavioral levels. Only recently were enantioselective odorant receptors demonstrated in mammals while their existence in insects has remained hypothetical. Using the two-microelectrode voltage clamp of Xenopus oocytes, we show that the yellow fever mosquito, Aedes aegypti, odorant receptor 8 (AaOR8 acts as a chiral selective receptor for the (R-(--enantiomer of 1-octen-3-ol, which in the presence of other kairomones is an attractant used by blood-sucking insects to locate their hosts. In addition to steric constraints, chain length and degree of unsaturation play important roles in this recognition process. This is the first characterization of an enantioselective odorant receptor in insects and the results demonstrate that an OR alone, without helper proteins, can account for chiral specificity exhibited by olfactory sensory neurons (OSNs.

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

    Science.gov (United States)

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

    2015-02-04

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Denmark, Scott E; Heemstra, John R

    2007-07-20

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

  13. Enantioselective Transamination in Continuous Flow Mode with Transaminase Immobilized in a Macrocellular Silica Monolith

    Directory of Open Access Journals (Sweden)

    Ludivine van den Biggelaar

    2017-02-01

    Full Text Available ω-Transaminases have been immobilized on macrocellular silica monoliths and used as heterogeneous biocatalysts in a continuous flow mode enantioselective transamination reaction. The support was prepared by a sol-gel method based on emulsion templating. The enzyme was immobilized on the structured silica monoliths both by adsorption, and by covalent grafting using amino-functionalized silica monoliths and glutaraldehyde as a coupling agent. A simple reactor set-up based on the use of a heat-shrinkable Teflon tube is presented and successfully used for the continuous flow kinetic resolution of a chiral amine, 4-bromo-α-methylbenzylamine. The porous structure of the supports ensures effective mass transfer and the reactor works in the plug flow regime without preferential flow paths. When immobilized in the monolith and used in the flow reactor, transaminases retain their activity and their enantioselectivity. The solid biocatalyst is also shown to be stable both on stream and during storage. These essential features pave the way to the successful development of an environmentally friendly process for chiral amines production.

  14. Importance of dose-schedule of 5-aza-2'-deoxycytidine for epigenetic therapy of cancer

    International Nuclear Information System (INIS)

    Lemaire, Maryse; Chabot, Guy G; Raynal, Noël JM; Momparler, Louise F; Hurtubise, Annie; Bernstein, Mark L; Momparler, Richard L

    2008-01-01

    The inactivation of tumor suppressor genes (TSGs) by aberrant DNA methylation plays an important role in the development of malignancy. Since this epigenetic change is reversible, it is a potential target for chemotherapeutic intervention using an inhibitor of DNA methylation, such as 5-aza-2'-deoxycytidine (DAC). Although clinical studies show that DAC has activity against hematological malignancies, the optimal dose-schedule of this epigenetic agent still needs to be established. Clonogenic assays were performed on leukemic and tumor cell lines to evaluate the in vitro antineoplastic activity of DAC. The reactivation of TSGs and inhibition of DNA methylation by DAC were investigated by reverse transcriptase-PCR and Line-1 assays. The in vivo antineoplastic activity of DAC administered as an i.v. infusion was evaluated in mice with murine L1210 leukemia by measurement of survival time, and in mice bearing murine EMT6 mammary tumor by excision of tumor after chemotherapy for an in vitro clonogenic assay. Increasing the DAC concentration and duration of exposure produced a greater loss of clonogenicity for both human leukemic and tumor cell lines. The reactivation of the TSGs (p57KIP2 in HL-60 leukemic cells and p16CDKN2A in Calu-6 lung carcinoma cells) and the inhibition of global DNA methylation in HL-60 leukemic cells increased with DAC concentration. In mice with L1210 leukemia and in mice bearing EMT6 tumors, the antineoplastic action of DAC also increased with the dose. The plasma level of DAC that produced a very potent antineoplastic effect in mice with leukemia or solid tumors was > 200 ng/ml (> 1 μM). We have shown that intensification of the DAC dose markedly increased its antineoplastic activity in mouse models of cancer. Our data also show that there is a good correlation between the concentrations of DAC that reduce in vitro clonogenicity, reactivate TSGs and inhibit DNA methylation. These results suggest that the antineoplastic action of DAC is

  15. Enantioselection on Heterogeneous Noble Metal Catalyst: Proline-Induced Asymmetry in the Hydrogenation of Isophorone on Pd Catalyst.

    Science.gov (United States)

    Rodríguez-García, Laura; Hungerbühler, Konrad; Baiker, Alfons; Meemken, Fabian

    2015-09-23

    In the (S)-proline-mediated asymmetric hydrogenation of isophorone (IP) on supported Pd catalyst, excellent enantioselectivity is achieved, with an enantiomeric excess of up to 99%. The role of the heterogeneous catalyst has been the subject of a controversial debate, and the current mechanistic understanding cannot explain the observed enantioselectivity of this catalytic system. The lack of in situ information about the role of the heterogeneous catalyst has prompted us to investigate the surface processes occurring at the methanol-Pd catalyst interface using attenuated total reflection infrared spectroscopy. Time-resolved monitoring of the homogeneous solution and of the catalytic solid-liquid interface coupled with catalytic data provides crucial information on the catalytically relevant enantiodifferentiating processes. While the condensation of IP and the corresponding chiral product 3,3,5-trimethylcyclohexanone with the chiral amine is connected to the enantiodifferentiation, it was found that the crucial enantioselectivity-controlling steps take place on the metal surface, and the reaction has to be classified as heterogeneous asymmetric hydrogenation. The presented spectroscopic and catalytic results provide strong evidence for the existence of two competing enantioselective processes leading to opposing enantioselection. Depending on surface coverage of the Pd catalyst, the reaction is controlled either by kinetic resolution ((S)-pathway) or by chiral catalysis ((R)-pathway). Steering the hydrogenation on the (R)-reaction pathway requires sufficient concentration of IP-(S)-proline condensate, as this chiral reactive intermediate becomes the most abundant surface species, inhibiting the competing kinetic resolution. The unraveled (R)-reaction pathway emphasizes an intriguing strategy for inducing chirality in heterogeneous asymmetric catalysis.

  16. Toward a small molecule, biomimetic carbonic anhydrase model: theoretical and experimental investigations of a panel of zinc(II) aza-macrocyclic catalysts.

    Science.gov (United States)

    Koziol, Lucas; Valdez, Carlos A; Baker, Sarah E; Lau, Edmond Y; Floyd, William C; Wong, Sergio E; Satcher, Joe H; Lightstone, Felice C; Aines, Roger D

    2012-06-18

    A panel of five zinc-chelated aza-macrocycle ligands and their ability to catalyze the hydration of carbon dioxide to bicarbonate, H(2)O + CO(2) → H(+) + HCO(3)(–), was investigated using quantum-mechanical methods and stopped-flow experiments. The key intermediates in the reaction coordinate were optimized using the M06-2X density functional with aug-cc-pVTZ basis set. Activation energies for the first step in the catalytic cycle, nucleophilic CO(2) addition, were calculated from gas-phase optimized transition-state geometries. The computationally derived trend in activation energies was found to not correspond with the experimentally observed rates. However, activation energies for the second, bicarbonate release step, which were estimated using calculated bond dissociation energies, provided good agreement with the observed trend in rate constants. Thus, the joint theoretical and experimental results provide evidence that bicarbonate release, not CO(2) addition, may be the rate-limiting step in CO(2) hydration by zinc complexes of aza-macrocyclic ligands. pH-independent rate constants were found to increase with decreasing Lewis acidity of the ligand-Zn complex, and the trend in rate constants was correlated with molecular properties of the ligands. It is suggested that tuning catalytic efficiency through the first coordination shell of Zn(2+) ligands is predominantly a balance between increasing charge-donating character of the ligand and maintaining the catalytically relevant pK(a) below the operating pH.

  17. Characterization of isolated 1-aza-adamantan-4-one (C9H13NO) from microwave, millimeter-wave and infrared spectroscopy supported by electronic structure calculations

    Science.gov (United States)

    Pirali, O.; Goubet, M.; Boudon, V.; D'Accolti, L.; Fusco, C.; Annese, C.

    2017-08-01

    We have synthesized 1-aza-adamantan-4-one (C9H13NO) starting from commercial 1,4-cyclohexanedionemonoethylene acetal and tosylmethylisocianide, following a procedure already described in the literature. The high degree of sample purity was demonstrated by gas chromatography and mass spectrometric measurements and its structure evidenced by 1H and 13C NMR spectroscopy. Among numerous interests in physical chemistry, this target molecule is of high relevance for mechanistic evaluation and the synthesis of novel pharmaceutical compounds. We present a thorough spectroscopic study of this molecule by gas phase vibrational and rotational spectroscopy. Accurate vibrational frequencies have been determined from infrared and far-infrared spectra. The pure rotational spectrum of the molecule has been recorded both by cavity-based Fourier transform microwave spectroscopy in the 2-20 GHz region by supersonically expanding the vapor pressure of the warm sample and by room-temperature absorption spectroscopy in the 140-220 GHz range. Accurate sets of rotational and centrifugal distortion parameters of 1-aza-adamantan-4-one in its ground state and in five vibrationally excited states have been derived from these measurements and compared to accurate quantum chemical calculations. The hyperfine parameters have been discussed in terms of molecular structure around the nitrogen quadrupole nucleus.

  18. Catalytic asymmetric aza-Morita-Baylis-Hillman reaction of methyl acrylate: role of a bifunctional La(O-iPr)3/linked-BINOL complex.

    Science.gov (United States)

    Yukawa, Takafumi; Seelig, Bianca; Xu, Yingjie; Morimoto, Hiroyuki; Matsunaga, Shigeki; Berkessel, Albrecht; Shibasaki, Masakatsu

    2010-09-01

    The catalytic asymmetric aza-Morita-Baylis-Hillman reaction using unactivated methyl acrylate is described. A simple Lewis acidic metal catalyst, such as La(OTf)(3), was not suitable for the reaction, but rare earth metal alkoxide/linked-BINOL complexes possessing bifunctional Lewis acid and Brønsted base properties efficiently promoted the reaction in combination with an achiral nucleophilic organocatalyst. The combined use of a La(O-iPr)(3)/(S,S)-TMS-linked-BINOL complex with a catalytic amount of DABCO promoted the aza-Morita-Baylis-Hillman reaction of a broad range of N-diphenylphosphinoyl imines. Products from aryl, heteroaryl, and alkenyl imines were obtained in 67-99% yield and 81-95% ee. It is noteworthy that isomerizable alkyl imines could be employed as well, giving products in 78-89% yield and 94-98% ee. Initial rate kinetic studies as well as kinetic isotope effect experiments using alpha-deuterio-methyl acrylate support the importance of both the nucleophilicity of La-enolate and the Brønsted basicity of a La-catalyst for promoting the reaction.

  19. Recyclable enantioselective catalysts based on copper(II) complexes of 2-(pyridine-2-yl)imidazolidine-4-thione: their application in asymmetric Henry reactions

    Czech Academy of Sciences Publication Activity Database

    Nováková, G.; Drabina, P.; Frumarová, Božena; Sedlák, M.

    2016-01-01

    Roč. 358, č. 15 (2016), s. 2541-2552 ISSN 1615-4150 Institutional support: RVO:61389013 Keywords : asymmetric catalysis * enantioselectivity * heterogeneous catalysis Subject RIV: CC - Organic Chemistry Impact factor: 5.646, year: 2016

  20. Interspecies differences in the enantioselectivity of epoxide hydrolases in Cryptococcus laurentii (Kufferath) C.E. Skinner and Cryptococcus podzolicus (Bab'jeva & Reshetova) Golubev

    CSIR Research Space (South Africa)

    Botes, AL

    2005-01-01

    Full Text Available Isolates representing Cryptococcus laurentii and Cryptococcus podzolicus, originating from soil of a heath land indigenous to South Africa, were screened for the presence of enantioselective epoxide hydrolases for 2, 2-disubstituted epoxides...

  1. Highly enantioselective aerobic oxidation of alpha-hydroxyphosphonates catalyzed by chiral vanadyl(V) methoxides bearing N-salicylidene-alpha-aminocarboxylates.

    Science.gov (United States)

    Pawar, Vijay D; Bettigeri, Sampada; Weng, Shiue-Shien; Kao, Jun-Qi; Chen, Chien-Tien

    2006-05-17

    An unprecedented vanadyl(V) methoxide complex 4 derived from 3,5-dibromo-N-salicylidene-l-tert-leucinate enables highly enantioselective aerobic oxidations of alpha-hydroxyphosphonates at ambient temperature with selectivity factors ranging from 3 to >99.

  2. Enantioselective organocatalyzed Oxa-Michael-Aldol cascade reactions: Construction of chiral 4H-chromenes with a trifluoromethylated tetrasubstituted carbon stereocenter

    KAUST Repository

    Zhang, Jing

    2015-03-13

    The first organocatalytic asymmetric synthesis of 4H-chromenes bearing a trifluoromethylated tetrasubstituted carbon center is presented. Chiral secondary amines promote the oxa-Michael-aldol cascade reaction between alkynals and 2-trifluoroacetylphenols via iminium-allenamine activation to produce pharmaceutically important heterocycles with excellent enantioselectivities. The proposed reaction can be scaled-up easily with maintenance of the excellent enantioselectivity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Phosphine-catalyzed highly enantioselective [3 + 3] cycloaddition of Morita-Baylis-Hillman carbonates with C,N-cyclic azomethine imines.

    Science.gov (United States)

    Zhang, Lei; Liu, Honglei; Qiao, Guanyu; Hou, Zhanfeng; Liu, Yang; Xiao, Yumei; Guo, Hongchao

    2015-04-08

    The first phosphine-catalyzed highly enantioselective [3 + 3] cycloaddition of Morita-Baylis-Hillman carbonates with C,N-cyclic azomethine imines is described. Using a spirocyclic chiral phosphine as the catalyst, a novel class of pharmaceutically interesting 4,6,7,11b-tetrahydro-1H-pyridazino[6,1-a]iso-quinoline derivatives were obtained in high yields with good to excellent diastereoselectivities and extremely excellent enantioselectivities (98->99% ee).

  4. Engineering chiral porous metal-organic frameworks for enantioselective adsorption and separation

    Science.gov (United States)

    Peng, Yongwu; Gong, Tengfei; Zhang, Kang; Lin, Xiaochao; Liu, Yan; Jiang, Jianwen; Cui, Yong

    2014-07-01

    The separation of racemic molecules is of substantial significance not only for basic science but also for technical applications, such as fine chemicals and drug development. Here we report two isostructural chiral metal-organic frameworks decorated with chiral dihydroxy or -methoxy auxiliares from enantiopure tetracarboxylate-bridging ligands of 1,1‧-biphenol and a manganese carboxylate chain. The framework bearing dihydroxy groups functions as a solid-state host capable of adsorbing and separating mixtures of a range of chiral aromatic and aliphatic amines, with high enantioselectivity. The host material can be readily recycled and reused without any apparent loss of performance. The utility of the present adsorption separation is demonstrated in the large-scale resolution of racemic 1-phenylethylamine. Control experiments and molecular simulations suggest that the chiral recognition and separation are attributed to the different orientations and specific binding energies of the enantiomers in the microenvironment of the framework.

  5. Enantioanalysis of S-deprenyl using enantioselective, potentiometric membrane electrodes based on C60 derivatives

    International Nuclear Information System (INIS)

    Stefan-van Staden, Raluca-Ioana

    2010-01-01

    Enantioselective, potentiometric membrane electrodes based on (1,2-methanofullerene C 60 )-61-carboxylic acid, diethyl (1,2-methanofullerene C 60 )-61-61-dicarboxylate and tert-butyl (1,2-methanofullerene C 60 )-61-carboxylic acid were proposed for the enantioanalysis of S-deprenyl in pharmaceutical compounds. Molecular modeling calculations were performed to prove the reliability of the proposed electrodes. The different characteristics involved in this analysis were explained, namely (i) the stability of each molecule using total energy, hardness and dipole moment, and (ii) the explanation of the mechanism of interaction using intermolecular forces (moderate hydrogen bond interactions), atomic charges and electrostatic potential. Electronic structures as well as molecular interaction have been investigated using Hartree-Fock theory, 3-21G(*) basis set. Stability and feasibility of all the generated structures were supported by their respective energy minima and fundamental frequencies.

  6. Photochemically Immobilized 4-Methylbenzoyl Cellulose as a Powerful Chiral Stationary Phase for Enantioselective Chromatography

    Directory of Open Access Journals (Sweden)

    Eric Francotte

    2016-12-01

    Full Text Available A process to immobilize para-methylbenzoyl cellulose (PMBC on silica gel has been developed and applied to prepare chiral stationary phases (CSPs for enantioselective chromatography. The immobilization was achieved by simple irradiation of the polysaccharide derivative with ultraviolet light after coating on a silica gel support. The influence of parameters such as irradiation time and solvent on immobilization effectiveness were investigated. The performance of the prepared immobilized phases were evaluated by injection of a series of racemic compounds onto the packed columns and determination of their chiral recognition ability. By contrast to the classical coated phase, the immobilized CSP can be used under various chromatographic conditions without limitation of organic solvent types as the mobile phase. This extended applicability permits to improve selectivity and to resolve chiral compounds which are not or only poorly soluble in the mobile phases which are compatible with the non-immobilized PMBC stationary phase.

  7. Enantioselective disposition of omeprazole, pantoprazole, and lansoprazole in a same Brazilian subjects group.

    Science.gov (United States)

    Cassiano, Neila M; Oliveira, Regina V; Bernasconi, Gilberto C R; Cass, Quezia B

    2012-04-01

    This work reports the result of the enantioselective disposition of pantoprazole, omeprazole, and lansoprazole in a same group of Brazilian health subjects. Ten nongenotyped healthy subjects were used for this study. Each subject received a single oral dose of 80 mg of pantoprazole, 40 mg of omeprazole, and 30 mg of lansoprazole, and the plasma concentrations of the enantiomers were measured for 8 h postdose. For pantoprazole and omeprazole, among the 10 volunteers investigated, only one volunteer (Subject # 4) presented higher plasma concentrations of the (+)-enantiomer than those of (-)-enantiomer. Nevertheless, the area under the concentration-time curve of the (+)-lansoprazole was higher than those the (-)-lansoprazole for all subjects. The comparison of proton pump inhibitors' enantiomers disposition from a single group volunteer demonstrated that pantoprazole and omeprazole can be used to differentiate extensive from poor CYP2C19 metabolizer while lansoprazole cannot do it. Copyright © 2011 Wiley Periodicals, Inc.

  8. Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel–Crafts alkylations

    Directory of Open Access Journals (Sweden)

    Tommaso Pecchioli

    2015-05-01

    Full Text Available The first immobilization of a MacMillan’s first generation organocatalyst onto dendritic support is described. A modified tyrosine-based imidazolidin-4-one was grafted to a soluble high-loading hyperbranched polyglycerol via a copper-catalyzed alkyne–azide cycloaddition (CuAAC reaction and readily purified by dialysis. The efficiency of differently functionalized multivalent organocatalysts 4a–c was tested in the asymmetric Friedel–Crafts alkylation of N-methylpyrrole with α,β-unsaturated aldehydes. A variety of substituted enals was investigated to explore the activity of the catalytic system which was also compared with monovalent analogues. The catalyst 4b showed excellent turnover rates and no loss of activity due to immobilization, albeit moderate enantioselectivities were observed. Moreover, easy recovery by selective precipitation allowed the reuse of the catalyst for three cycles.

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

    Science.gov (United States)

    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.

  10. 3,3'-Diaryl-BINOL phosphoric acids as enantioselective extractants of benzylic primary amines.

    Science.gov (United States)

    Verkuijl, Bastiaan J V; de Vries, Johannes G; Feringa, Ben L

    2011-01-01

    We report that 3,3'-diaryl-BINOL phosphoric acids are effective enantioselective extractants in chiral separation methods based on reactive liquid-liquid extraction. These new extractants are capable of separating racemic benzylic primary amine substrates. The effect of the nature of the substituents at the 3,3'-positions of the host were examined as well as the structure of the substrate, together with important parameters such as the organic solvent, the pH of the aqueous phase, and the host stoichiometry. Titration of the substrate with the host was monitored by FTIR, NMR, UV-Vis, and CD spectroscopy, which provided insight into the structure of the host-guest complex involved in extraction. Copyright © 2010 Wiley-Liss, Inc.

  11. Treatment with MAPKAP2 (MK2) inhibitor and DNA methylation inhibitor, 5-aza dC, synergistically triggers apoptosis in hepatocellular carcinoma (HCC) via tristetraprolin (TTP).

    Science.gov (United States)

    Tran, Doan Duy Hai; Koch, Alexandra; Allister, Aldrige; Saran, Shashank; Ewald, Florian; Koch, Martina; Nashan, Björn; Tamura, Teruko

    2016-12-01

    Over 100 putative driver genes that are associated with multiple recurrently altered pathways were detected in hepatocellular carcinoma (HCC), suggesting that multiple pathways will need to be inhibited for any therapeutic method to be effective. In this context, functional modification of the RNA regulating protein, tristetraprolin (TTP) that regulates approximately 2500 genes represents a promising strategy in HCC therapy. Since overexpression of TTP induces cell death in all cell types, it would be useful to target the regulator of TTP. In this study, we applied an inhibitor to MAPKAP2 (MK2) that suppresses TTP function. Importantly, cBIOportal for HCC genomics shows that expression level of the MK2 gene correlates with clinical outcome of HCC. We show that upon treatment with MK2 inhibitor, all 5 HCC cell lines, namely HepG2, Huh7, Hep3B, HLE and HLF, reduced cell growth, especially HepG2 and Hep3B cells underwent apoptosis. Simultaneously, TTP target genes such as c-Myc, IER3 or AKT-1 were downregulated. Depletion of the TTP gene rescued cells from apoptosis and restored the TTP-target mRNA expression in the presence of MK2 inhibitor. Furthermore, MK2 was activated in primary HCC that express TTP at high level. The TTP gene was induced upon treatment with DNA methylation inhibitor, 5-aza dC or interferon in three other cell lines, Huh7, HLE or HLF. Upon treatment with MK2 inhibitor and 5-aza dC or interferon these cells underwent apoptosis. The depletion of TTP in these cells partially rescued them from apoptosis, suggesting that the MK2/TTP pathway plays a role in proliferation and maintenance of HCCs. Notably, under the same conditions human hepatocyte cells (THLE-2) did not undergo apoptosis. These data also suggest that MK2 inhibitor with 5-aza dC or interferon may be a useful tool for therapy against HCC. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Enantioselective Determination of Polycyclic Musks in River and Wastewater by GC/MS/MS

    Directory of Open Access Journals (Sweden)

    Injung Lee

    2016-03-01

    Full Text Available The separation of chiral compounds is an interesting and challenging topic in analytical chemistry, especially in environmental fields. Enantioselective degradation or bioaccumulation has been observed for several chiral pollutants. Polycyclic musks are chiral and are widely used as fragrances in a variety of personal care products such as soaps, shampoos, cosmetics and perfumes. In this study, the gas chromatographic separation of chiral polycyclic musks, 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclo-penta-γ-2-benzopyrane (HHCB, 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetra-hydronaphthalene (AHTN, 6-acetyl-1,1,2,3,3,5-hexamethylindane (AHDI, 5-acetyl-1,1,2,6-tetramethyl-3-iso-propylindane (ATII, and 6,7-dihydro-1,1,2,3,3-pentamethyl-4(5H-indanone (DPMI was achieved on modified cyclodextrin stationary phase (heptakis (2,3-di-O-methyl-6-O-tert-butyl-dimethylsilyl-β-CD in DV-1701. Separation techniques are coupled to tandem mass spectrometry (MS-MS, as it provides the sensitivity and selectivity needed. River and wastewaters (influents and effluents of wastewater treatment plants (WWTPs in the Nakdong River were investigated with regard to the concentrations and the enantiomeric ratios of polycyclic musks. HHCB was most frequently detected in river and wastewaters, and an enantiomeric enrichment was observed in the effluents of one of the investigated wastewater treatment plants (WWTPs. We reported the contamination of river and wastewaters in Korea by chiral polycyclic musks. The results of this investigation suggest that enantioselective transformation may occur during wastewater treatment.

  13. Efficient reductive amination process for enantioselective synthesis of L-phosphinothricin applying engineered glutamate dehydrogenase.

    Science.gov (United States)

    Yin, Xinjian; Wu, Jianping; Yang, Lirong

    2018-03-16

    The objective of this study was to identify and exploit a robust biocatalyst that can be applied in reductive amination for enantioselective synthesis of the competitive herbicide L-phosphinothricin. Applying a genome mining-based library construction strategy, eight NADPH-specific glutamate dehydrogenases (GluDHs) were identified for reductively aminating 2-oxo-4-[(hydroxy)(methyl)phosphinoyl]butyric acid (PPO) to L-phosphinothricin. Among them, the glutamate dehydrogenase cloned from Pseudomonas putida (PpGluDH) exhibited relatively high catalytic activity and favorable soluble expression. This enzyme was purified to homogeneity for further characterization. The specific activity of PpGluDH was 296.1 U/g-protein, which is significantly higher than the reported value for a GluDH. To the best of our knowledge, there has not been any report on protein engineering of GluDH for PPO-oriented activity. Taking full advantage of the available information and the diverse characteristics of the enzymes in the enzyme library, PpGluDH was engineered by site-directed mutation based on multiple sequence alignment. The mutant I170M, which had 2.1-fold enhanced activity, was successfully produced. When the I170M mutant was applied in the batch production of L-phosphinothricin, it showed markedly improved catalytic efficiency compared with the wild type enzyme. The conversion reached 99% (0.1 M PPO) with an L-phosphinothricin productivity of 1.35 g/h·L, which far surpassed the previously reported level. These results show that PpGluDH I170M is a promising biocatalyst for highly enantioselective synthesis of L-phosphinothricin by reductive amination.

  14. Enantioselective assay for therapeutic drug monitoring of eslicarbazepine acetate: no interference with carbamazepine and its metabolites.

    Science.gov (United States)

    Alves, Gilberto; Fortuna, Ana; Sousa, Joana; Direito, Rosa; Almeida, Anabela; Rocha, Marília; Falcão, Amílcar; Soares-da-Silva, Patrício

    2010-08-01

    As add-on therapy, phase III clinical trials of eslicarbazepine acetate (ESL) conducted in patients with refractory partial-onset seizures have shown good efficacy, safety, and tolerability, even in patients taking carbamazepine (CBZ) at baseline (approximately 60% of the enrolled patients). Thus, considering the pharmacological disadvantages of CBZ and the similar efficacy spectrum of CBZ and ESL, switching to ESL may be successful in many patients. As ESL is a prodrug almost instantaneously converted to S-licarbazepine (S-Lic; approximately 95%), an interest in therapeutic drug monitoring (TDM) of S-Lic is likely to develop in the future. This study investigated the plasma concentrations of S-Lic and R-licarbazepine (R-Lic) enantiomers in patients under CBZ long-term treatment to assess the potential interference of CBZ or its metabolites in the enantioselective TDM of ESL (using S-Lic concentrations). A chiral high-performance liquid chromatography assay with ultraviolet detection (HPLC-UV) previously developed and validated by our research group was used. Twenty-four patients admitted to the Coimbra University Hospital and supposedly receiving CBZ long-term treatment were identified. Blood samples were collected from patients and serum CBZ concentrations were measured by the usual TDM protocol. Aliquots of plasma from such patients were also submitted to a chiral HPLC-UV analysis. The bioanalytical data indicated that S-Lic and R-Lic were not present at detectable concentrations in plasma samples of the CBZ-treated patients. The chromatograms generated by the analysis of patient plasma samples, when compared with those obtained from blank plasma samples spiked with S-Lic and R-Lic, clearly showed the absence of interferences at the retention times of both Lic enantiomers. These data support the usefulness of the chiral HPLC-UV method used for the enantioselective TDM of ESL (using S-Lic) for programs in which switching from CBZ to ESL is implemented.

  15. Enantioselective toxicities of chiral ionic liquids 1-alkyl-3-methyl imidazolium tartrate on Scenedesmus obliquus.

    Science.gov (United States)

    Liu, Huijun; Zhang, Xiaoqiang; Dong, Ying; Chen, Caidong; Zhu, Shimin; Ma, Xiangjuan

    2015-12-01

    Ionic liquids (ILs) are being used in various industries during the last few decades, while the good solubility and high stability of ILs may pose a potential threat to the aquatic environment. Effect of chiral ionic liquids (CILs) 1-alkyl-3-methyl imidazolium tartrate (RMIM T) on Scenedesmus obliquus (S.obliquus) was studied. The growth rate inhibition and cell membrane permeability increased with increasing RMIM T concentration and increasing alkyl chain lengths. The IC50 values of D-(-)-tartrate 1-hexyl-3-methyl imidazolium (D-(-)-HMIM T) were 28.30, 12.23,10.15 and 14.41 mg/L, respectively, at 24, 48, 72 and 96h. While that of L-(+)-tartrate 1-hexyl-3-methyl imidazolium (L-(+)-HMIM T) were 15.97, 7.91, 9.43 and 12.04 mg/L respectively. The concentration of chl a, chl b and chl (a+b) decreased with increasing RMIM T concentration. The chlorophyll fluorescence parameters (F0, Fv/Fm, Fv/F0, Y(II), ETR and NPQ) were affected by RMIM T, indicating that the RMIM T will damage the PSII, inhibit the transmission of excitation energy, decrease the efficiency of photosynthesis. The results showed that there were enantioselective toxicity of RMIM T to algae, and the toxicity of L-(+)-RMIM T was greater than that of D-(-)-RMIM T, but the enantioselective difference becomes smaller with increasing exposure time, and with the increasing carbon chain length of cation, indicating that cation properties may have a larger effect on toxicity than anion properties. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Structure, mechanism, and enantioselectivity shifting of lipase LipK107 with a simple way.

    Science.gov (United States)

    Zhang, Lujia; Gao, Bei; Yuan, Zuanning; He, Xiao; Yuan, Y Adam; Zhang, John Z H; Wei, Dongzhi

    2014-07-01

    Because of the complex mechanisms of enzymatic reactions, no precise and simple method of understanding and controlling the chiral selectivity of enzymes has been developed. However, structure-based rational design is a powerful approach to engineering enzymes with desired catalytic activities. In this work, a simple, structure-based, large-scale in silico design and virtual screening strategy was developed and successfully applied to enzyme engineering. We first performed protein crystallization and X-ray diffraction to determine the structure of lipase LipK107, which is a novel family I.1 lipase displaying activity for both R and S isomers in chiral resolution reactions. The catalytic mechanism of family I.1, which includes LipK107, was ascertained first through comparisons of the sequences and structures of lipases from other families. The binding states of LipK107, including the energy and the conformation of complexes with the R and S enantiomers, have been evaluated by careful biocomputation to figure out the reason for the higher S selectivity. Based on this study, a simple strategy for manipulating the chiral selectivity by modulating a crucial distance in the enzyme-substrate complex and judging virtual mutations in silico is recommended. Then, a novel electrostatic interaction analysis protocol was used to design LipK107 mutants to validate our strategy. Both positive and negative mutations determined using this theoretical protocol have been implemented in wet experiments and were proved to produce the desired enantioselectivity, showing a 176% increase or 50% decrease in enantioselectivity as desired. Because of its accuracy and versatility, the strategy is promising for practical applications. Copyright © 2014. Published by Elsevier B.V.

  17. The in vitro and in vivo effects of re-expressing methylated von Hippel-Lindau tumor suppressor gene in clear cell renal carcinoma with 5-aza-2'-deoxycytidine.

    Science.gov (United States)

    Alleman, Wade G; Tabios, Ray L; Chandramouli, Gadisetti V R; Aprelikova, Olga N; Torres-Cabala, Carlos; Mendoza, Arnulfo; Rogers, Craig; Rodgers, Craig; Sopko, Nikolai A; Linehan, W Marston; Vasselli, James R

    2004-10-15

    Clear cell renal carcinoma (ccRCC) is strongly associated with loss of the von Hippel-Lindau (VHL) tumor suppressor gene. The VHL gene is functionally lost through hypermethylation in up to 19% of sporadic ccRCC cases. We theorized that re-expressing VHL silenced by methylation in ccRCC cells, using a hypo-methylating agent, may be an approach to treatment in patients with this type of cancer. We test the ability of two hypo-methylating agents to re-express VHL in cell culture and in mice bearing human ccRCC and evaluate the effects of re-expressed VHL in these models. Real-time reverse transcription-PCR was used to evaluate the ability of zebularine and 5-aza-2'-deoxycytidine (5-aza-dCyd) to re-express VHL in four ccRCC cell lines with documented VHL gene silencing through hypermethylation. We evaluated if the VHL re-expressed after hypo-methylating agent treatment could recreate similar phenotypic changes in ccRCC cells observed when the VHL gene is re-expressed via transfection in cell culture and in a xenograft mouse model. Finally we evaluate global gene expression changes occurring in our cells, using microarray analysis. 5-Aza-dCyd was able to re-express VHL in our cell lines both in culture and in xenografted murine tumors. Well described phenotypic changes of VHL expression including decreased invasiveness into Matrigel, and decreased vascular endothelial growth factor and glucose transporter-1 expression were observed in the treated lines. VHL methylated ccRCC xenografted tumors were significantly reduced in size in mice treated with 5-aza-dCyd. Mice bearing nonmethylated but VHL-mutated tumors showed no tumor shrinkage with 5-aza-dCyd treatment. Hypo-methylating agents may be useful in the treatment of patients having ccRCC tumors consisting of cells with methylated VHL.

  18. Combined experimental and theoretical study of the mechanism and enantioselectivity of palladium-catalyzed intermolecular Heck coupling

    DEFF Research Database (Denmark)

    Henriksen, Signe Teuber; Norrby, Per-Ola; Kaukoranta, Päivi

    2008-01-01

    . The steric interactions in this transition state fully account for the enantioselectivity observed with the ligands studied. The calculations also predict relative reactivity and nonlinear mixing effects for the investigated ligands; these predictions are fully validated by experimental testing. Finally......The asymmetric Heck reaction using P,N-ligands has been studied by a combination of theoretical and experimental methods. The reaction follows Halpern-style selectivity; that is, the major isomer is produced from the least favored form of the pre-insertion intermediate. The initially formed Ph......, the low conversion observed with some catalysts was found to be caused by inactivation due to weak binding of the ligand to Pd(0). Adding monodentate PPh3 alleviated the precipitation problem without deteriorating the enantioselectivity and led to one of the most effective catalytic systems to date....

  19. The Significance of Degenerate Processes to Enantioselective Olefin Metathesis Reactions Promoted by Stereogenic-at-Mo Complexes

    Science.gov (United States)

    Meek, Simon J.; Malcolmson, Steven J.; Li, Bo; Schrock, Richard R.; Hoveyda, Amir H.

    2009-01-01

    The present study provides spectroscopic and experimental evidence demonstrating that degenerate metathesis is critical to the effectiveness of this emerging class of chiral catalysts. Isolation and characterization (X-ray) of both diastereomeric complexes, as well as examination of the reactivity and enantioselectivity patterns exhibited by such initiating neophylidenes in promoting RCM processes, are disclosed. Only when sufficient amounts of ethylene are generated and inversion at Mo through degenerate processes occurs at a sufficiently rapid rate, is high enantioselectivity achieved, irrespective of the stereochemical identity of the initiating alkylidene (Curtin-Hammett kinetics). With diastereomeric metal complexes that undergo rapid interconversion, stereomutation at the metal center becomes inconsequential and stereoselective synthesis of a chiral catalyst is not required. PMID:19842640

  20. Expanding the scope of enantioselective ferroPHANE-promoted [3+2] annulations with alpha,beta-unsaturated ketones.

    Science.gov (United States)

    Pinto, Nathalie; Neel, Mathilde; Panossian, Armen; Retailleau, Pascal; Frison, Gilles; Voituriez, Arnaud; Marinetti, Angela

    2010-01-18

    The planar chiral 2-phospha[3]ferrocenophane I has been shown to be the first efficient nucleophilic organocatalyst for the enantioselective synthesis of cyclopentenylphosphonates, through [3+2] cyclizations between diethyl allenylphosphonate and alpha,beta-unsaturated ketones. The same catalyst has also been applied to the highly enantioselective [3+2] cyclizations of allenic esters with dibenzylideneacetone and analogous bis-enones, leading to functionalised cyclopentenes with either monocyclic or spirocyclic structures (ee 84-95 %). It has been shown that the residual enone functions in the resulting cyclopentenes can be involved in subsequent cyclization steps to afford unprecedented C(2)-symmetric bis-cyclopentenylketones. In order to provide insight into the behaviour of FerroPHANE I as a chiral catalyst in [3+2] cyclisations, the energetically most favoured isomers of the key phosphine-allene adduct have been calculated by DFT methods. Factors likely to control the chiral induction process are highlighted.

  1. A Readily Accessible Class of Chiral Cp Ligands and their Application in RuII -Catalyzed Enantioselective Syntheses of Dihydrobenzoindoles.

    Science.gov (United States)

    Wang, Shou-Guo; Park, Sung Hwan; Cramer, Nicolai

    2018-05-04

    Chiral cyclopentadienyl (Cp x ) ligands have a large application potential in enantioselective transition-metal catalysis. However, the development of concise and practical routes to such ligands remains in its infancy. We present a convenient and efficient two-step synthesis of a novel class of chiral Cp x ligands with tunable steric properties that can be readily used for complexation, giving Cp x Rh I , Cp x Ir I , and Cp x Ru II complexes. The potential of this ligand class is demonstrated with the latter in the enantioselective cyclization of azabenzonorbornadienes with alkynes, affording dihydrobenzoindoles in up to 98:2 e.r., significantly outperforming existing binaphthyl-derived Cp x ligands. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Multiscale analysis of enantioselectivity in enzyme-catalysed ‘lethal synthesis’ using projector-based embedding

    Science.gov (United States)

    Bennie, Simon J.; van der Kamp, Marc W.; Manby, Frederick R.; Mulholland, Adrian J.

    2018-01-01

    The action of fluoroacetate as a broad-spectrum mammalian pesticide depends on the ‘lethal synthesis’ of fluorocitrate by citrate synthase, through a subtle enantioselective enolization of fluoroacetyl-coenzyme A. In this work, we demonstrate how a projection-based embedding method can be applied to calculate coupled cluster (CCSD(T)) reaction profiles from quantum mechanics/molecular mechanics optimized pathways for this enzyme reaction. Comparison of pro-R and pro-S proton abstraction in citrate synthase at the CCSD(T)-in-DFT//MM level yields the correct enantioselectivity. We thus demonstrate the potential of projection-based embedding for determining stereoselectivity in enzymatic systems. We further show that the method is simple to apply, eliminates variability due to the choice of density functional theory functional and allows the efficient calculation of CCSD(T) quality enzyme reaction barriers. PMID:29515856

  3. Discovery and selectivity-profiling of 4-benzylamino 1-aza-9-oxafluorene derivatives as lead structures for IGF-1R inhibitors.

    Science.gov (United States)

    Krug, Martin; Erlenkamp, German; Sippl, Wolfgang; Schächtele, Christoph; Totzke, Frank; Hilgeroth, Andreas

    2010-12-01

    Recently the insuline-like growth factor receptor (IGF-1R) emerged as a promising target structure for the development of novel anti-cancer agents. IGF-1R plays a central role in both tumour progression and resistance development against anti-cancer drugs. We discovered 1-aza-9-oxafluorene derivatives as novel lead structures with submicromolar activities against IGF-1R. Structure-activity relationships (SARs) on a series of related receptor tyrosine kinases (RTKs) are discussed in the context of available crystal structures. A preliminary selectivity-profiling is demonstrated for the first compound series. Antiproliferative tumour cell line screening studies yielded one candidate as a promising cytostatic agent without significant toxic effects. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Facile Synthesis of N-Tosyl Aza-Baylis-Hillman Adducts of Acrylamide via a Pd-Catalyzed Hydration of Nitrile to Amide

    International Nuclear Information System (INIS)

    Kim, Eun Sun; Kim, Yu Mi; Kim, Jae Nyoung

    2010-01-01

    We developed an efficient palladium-catalyzed two-step protocol for the synthesis of N-tosyl aza-Baylis-Hillman adducts of acrylamide. The method involved the preparation of the corresponding Baylis-Hillman adducts of acrylonitrile and the following Pd-catalyzed hydration of nitrile with acetaldoxime. The Baylis-Hillman reaction, which involves the coupling of activated vinyl compounds with electrophiles under the catalytic influence of a tertiary amine, gives rise to adducts, so called Baylis-Hillman adducts, with a new stereocenter and has proven to be a very useful carbon-carbon bond-forming method in the synthesis of highly functionalized molecules. As the activated vinyl compounds, various compounds have been used in the Baylis-Hillman reaction including acrylates, acrylonitrile, vinyl ketones, vinyl sulfones and acrylamides. However, among the activated vinyl compounds acrylamide has not been used much for the synthesis of the corresponding Baylis-Hillman adducts due to its sluggish reactivity

  5. Structure–metabolism relationships in human-AOX: Chemical insights from a large database of aza-aromatic and amide compounds

    Science.gov (United States)

    Ceccarelli, Martina; Milani, Nicolò; Tortorella, Sara; Cucco, Andrea; Goracci, Laura; Brink, Andreas; Cruciani, Gabriele

    2017-01-01

    Aldehyde oxidase (AOX) is a metabolic enzyme catalyzing the oxidation of aldehyde and aza-aromatic compounds and the hydrolysis of amides, moieties frequently shared by the majority of drugs. Despite its key role in human metabolism, to date only fragmentary information about the chemical features responsible for AOX susceptibility are reported and only “very local” structure–metabolism relationships based on a small number of similar compounds have been developed. This study reports a more comprehensive coverage of the chemical space of structures with a high risk of AOX phase I metabolism in humans. More than 270 compounds were studied to identify the site of metabolism and the metabolite(s). Both electronic [supported by density functional theory (DFT) calculations] and exposure effects were considered when rationalizing the structure–metabolism relationship. PMID:28373537

  6. Efficacy and safety of azelaic acid (AzA) gel 15% in the treatment of post-inflammatory hyperpigmentation and acne: a 16-week, baseline-controlled study.

    Science.gov (United States)

    Kircik, Leon H

    2011-06-01

    Although there are few differences in the incidence and pathophysiology of acne across various races and ethnicities, there is some evidence that black patients may have larger sebaceous glands and increased sebum production. Of greater clinical relevance, patients with darker skin types are at increased risk for the development of post-inflammatory hyperpigmentation (PIH), which some find as or more troubling than acne itself. This common and bothersome sequelum of acne can be difficult to manage in this population. Topical azelaic acid gel is recognized to have anti-tyrosinase activity, suggesting it may be a suitable treatment option for mild-to-moderate acne with associated moderate-to-severe PIH. This pilot study demonstrates the efficacy of topical AzA gel 15% when applied twice daily for the reduction of both acne and PIH. J

  7. Facile Synthesis of N-Tosyl Aza-Baylis-Hillman Adducts of Acrylamide via a Pd-Catalyzed Hydration of Nitrile to Amide

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Sun; Kim, Yu Mi; Kim, Jae Nyoung [Chonnam National Univ., Gwangju (Korea, Republic of)

    2010-03-15

    We developed an efficient palladium-catalyzed two-step protocol for the synthesis of N-tosyl aza-Baylis-Hillman adducts of acrylamide. The method involved the preparation of the corresponding Baylis-Hillman adducts of acrylonitrile and the following Pd-catalyzed hydration of nitrile with acetaldoxime. The Baylis-Hillman reaction, which involves the coupling of activated vinyl compounds with electrophiles under the catalytic influence of a tertiary amine, gives rise to adducts, so called Baylis-Hillman adducts, with a new stereocenter and has proven to be a very useful carbon-carbon bond-forming method in the synthesis of highly functionalized molecules. As the activated vinyl compounds, various compounds have been used in the Baylis-Hillman reaction including acrylates, acrylonitrile, vinyl ketones, vinyl sulfones and acrylamides. However, among the activated vinyl compounds acrylamide has not been used much for the synthesis of the corresponding Baylis-Hillman adducts due to its sluggish reactivity.

  8. Synthesis Characterization and Antimicrobial Activity of Metal Chelates of 1, 7-Di (2-hydroxyphenyl 1, 7 di (N-methyl aza-1, 3, 5 heptarine-3-ol hydrochloride

    Directory of Open Access Journals (Sweden)

    Nalin P. Patani

    2010-01-01

    Full Text Available The Schiff base complexes derived from 2-furancarboxaldehyde and N-methyl-2-amino phenol have been prepared and characterized using several physical techniques, like elemental analysis, thermogravimetric analysis, magnetic moment measurements, infrared and resonance spectra. N-Methyl-2-amino phenol was condensed stoichiometrically with 2-furancarboxaldehyde in presence of methanol. The resulting 1,7-di(2-hydroxyphenyl 1,7 di(N-methyl aza-1,3,5 heptarine-3-ol hydrochloride was characterized by elemental analysis and spectral studies. The transition metal complexes of Cu2+, Zn2+, Ni2+, Co2+ and Mn2+ of the synthesized complexes were prepared. Metal ligand (M:L ratio, IR, reflectance spectral studies, magnetic properties and antimicrobial activity of the synthesized complexes and its metal complexes were carried out.

  9. El jardín de los frailes de Azaña en la novelística de internados religiosos

    Directory of Open Access Journals (Sweden)

    Ezpeleta Aguilar, Fermín

    2012-12-01

    Full Text Available El jardín de los frailes by Manuel Azaña absorbs the best literary moral values of a genre, the autobiographical novel of boarding religious schools, grown with profusion by the «novecentista » generation. On the one hand, there is flexible treatment of the model of novel of formation, with derivation toward «artist». There is, besides, conformation of a pedagogic body like the novel of instruction. And even, a picture of types and anecdotes. Everything is under the narrative responsibility of a first person that investigates, more than novels of the series, in the cultural keys of the country.El jardín de los frailes, de Manuel Azaña, absorbe los mejores valores literarios de un subgénero, como es el de la novela autobiográfica de colegio, cultivado con profusión por la generación novecentista. Por un lado, hay tratamiento flexible del modelo de novela de formación, con derivación hacia la de artista. Hay además conformación de un cuerpo pedagógico al modo del tratado o de la novela de instrucción. E, incluso, pintura de tipos y anécdotas colegiales. Todo ello bajo la responsabilidad narrativa de un «yo» que indaga, más que en otras novelas de la serie, en las claves culturales del país.

  10. The Chromatin Assembly Factor Complex 1 (CAF1) and 5-Azacytidine (5-AzaC) Affect Cell Motility in Src-transformed Human Epithelial Cells.

    Science.gov (United States)

    Endo, Akinori; Ly, Tony; Pippa, Raffaella; Bensaddek, Dalila; Nicolas, Armel; Lamond, Angus I

    2017-01-06

    Tumor invasion into surrounding stromal tissue is a hallmark of high grade, metastatic cancers. Oncogenic transformation of human epithelial cells in culture can be triggered by activation of v-Src kinase, resulting in increased cell motility, invasiveness, and tumorigenicity and provides a valuable model for studying how changes in gene expression cause cancer phenotypes. Here, we show that epithelial cells transformed by activated Src show increased levels of DNA methylation and that the methylation inhibitor 5-azacytidine (5-AzaC) potently blocks the increased cell motility and invasiveness induced by Src activation. A proteomic screen for chromatin regulators acting downstream of activated Src identified the replication-dependent histone chaperone CAF1 as an important factor for Src-mediated increased cell motility and invasion. We show that Src causes a 5-AzaC-sensitive decrease in both mRNA and protein levels of the p150 (CHAF1A) and p60 (CHAF1B), subunits of CAF1. Depletion of CAF1 in untransformed epithelial cells using siRNA was sufficient to recapitulate the increased motility and invasive phenotypes characteristic of transformed cells without activation of Src. Maintaining high levels of CAF1 by exogenous expression suppressed the increased cell motility and invasiveness phenotypes when Src was activated. These data identify a critical role of CAF1 in the dysregulation of cell invasion and motility phenotypes seen in transformed cells and also highlight an important role for epigenetic remodeling through DNA methylation for Src-mediated induction of cancer phenotypes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. The Chromatin Assembly Factor Complex 1 (CAF1) and 5-Azacytidine (5-AzaC) Affect Cell Motility in Src-transformed Human Epithelial Cells*

    Science.gov (United States)

    Endo, Akinori; Ly, Tony; Pippa, Raffaella; Bensaddek, Dalila; Nicolas, Armel; Lamond, Angus I.

    2017-01-01

    Tumor invasion into surrounding stromal tissue is a hallmark of high grade, metastatic cancers. Oncogenic transformation of human epithelial cells in culture can be triggered by activation of v-Src kinase, resulting in increased cell motility, invasiveness, and tumorigenicity and provides a valuable model for studying how changes in gene expression cause cancer phenotypes. Here, we show that epithelial cells transformed by activated Src show increased levels of DNA methylation and that the methylation inhibitor 5-azacytidine (5-AzaC) potently blocks the increased cell motility and invasiveness induced by Src activation. A proteomic screen for chromatin regulators acting downstream of activated Src identified the replication-dependent histone chaperone CAF1 as an important factor for Src-mediated increased cell motility and invasion. We show that Src causes a 5-AzaC-sensitive decrease in both mRNA and protein levels of the p150 (CHAF1A) and p60 (CHAF1B), subunits of CAF1. Depletion of CAF1 in untransformed epithelial cells using siRNA was sufficient to recapitulate the increased motility and invasive phenotypes characteristic of transformed cells without activation of Src. Maintaining high levels of CAF1 by exogenous expression suppressed the increased cell motility and invasiveness phenotypes when Src was activated. These data identify a critical role of CAF1 in the dysregulation of cell invasion and motility phenotypes seen in transformed cells and also highlight an important role for epigenetic remodeling through DNA methylation for Src-mediated induction of cancer phenotypes. PMID:27872192

  12. Chiral Pincer Carbodicarbene Ligands for Enantioselective Rhodium-Catalyzed Hydroarylation of Terminal and Internal 1,3-Dienes with Indoles.

    Science.gov (United States)

    Marcum, Justin S; Roberts, Courtney C; Manan, Rajith S; Cervarich, Tia N; Meek, Simon J

    2017-11-08

    Catalytic enantioselective addition of N-heteroarenes to terminal and internal 1,3-dienes is reported. Reactions are promoted by 5 mol % of Rh catalyst supported by a new chiral pincer carbodicarbene ligand that delivers allylic substituted arenes in up to 95% yield and up to 98:2 er. Mechanistic and X-ray evidence is presented that supports that the reaction proceeds via a Rh(III)-η 3 -allyl.

  13. Diastereo- and enantioselective iridium-catalyzed allylation of cyclic ketone enolates: synergetic effect of ligands and barium enolates.

    Science.gov (United States)

    Chen, Wenyong; Chen, Ming; Hartwig, John F

    2014-11-12

    We report asymmetric allylic alkylation of barium enolates of cyclic ketones catalyzed by a metallacyclic iridium complex containing a phosphoramidite ligand derived from (R)-1-(2-naphthyl)ethylamine. The reaction products contain adjacent quaternary and tertiary stereocenters. This process demonstrates that unstabilized cyclic ketone enolates can undergo diastereo- and enantioselective Ir-catalyzed allylic substitution reactions with the proper choice of enolate countercation. The products of these reactions can be conveniently transformed to various useful polycarbocyclic structures.

  14. Heterogeneous and homogeneous chiral Cu(II) catalysis in water: enantioselective boron conjugate additions to dienones and dienoesters.

    Science.gov (United States)

    Kitanosono, Taku; Xu, Pengyu; Kobayashi, Shū

    2013-09-25

    It was proved that a judicious choice of counteranion played a prominent role in Cu(II) catalysis for enantioselective boron conjugate additions in water; the use of Cu(OH)2 renders heterogeneous catalysis, whereas Cu(OAc)2 renders homogeneous catalysis; cyclic dienones underwent a remarkable switch of regioselectivity between 1,4- and 1,6-modes of the additions through these catalyses.

  15. Enantioselective Collision-Activated Dissociation of Gas-Phase Tryptophan Induced by Chiral Recognition of Protonated l-Alanine Peptides

    Science.gov (United States)

    Fujihara, Akimasa; Matsuyama, Hiroki; Tajiri, Michiko; Wada, Yoshinao; Hayakawa, Shigeo

    2017-06-01

    Enantioselective dissociation in the gas phase is important for enantiomeric enrichment and chiral transmission processes in molecular clouds regarding the origin of homochirality in biomolecules. Enantioselective collision-activated dissociation (CAD) of tryptophan (Trp) and the chiral recognition ability of l-alanine peptides ( l-Ala n ; n = 2-4) were examined using a linear ion trap mass spectrometer. CAD spectra of gas-phase heterochiral H+( d-Trp)( l-Ala n ) and homochiral H+( l-Trp)( l-Ala n ) noncovalent complexes were obtained as a function of the peptide size n. The H2O-elimination product was observed in CAD spectra of both heterochiral and homochiral complexes for n = 2 and 4, and in homochiral H+( l-Trp)( l-Ala3), indicating that the proton is attached to the l-alanine peptide, and H2O loss occurs from H+( l-Ala n ) in the noncovalent complexes. H2O loss did not occur in heterochiral H+( d-Trp)( l-Ala3), where NH3 loss and (H2O + CO) loss were the primary dissociation pathways. In heterochiral H+( d-Trp)( l-Ala3), the protonation site is the amino group of d-Trp, and NH3 loss and (H2O + CO) loss occur from H+( d-Trp). l-Ala peptides recognize d-Trp through protonation of the amino group for peptide size n = 3. NH3 loss and (H2O + CO) loss from H+( d-Trp) proceeds via enantioselective CAD in gas-phase heterochiral H+( d-Trp)( l-Ala3) at room temperature, whereas l-Trp dissociation was not observed in homochiral H+( l-Trp)( l-Ala3). These results suggest that enantioselective dissociation induced by chiral recognition of l-Ala peptides through protonation could play an important role in enantiomeric enrichment and chiral transmission processes of amino acids.

  16. Sequential rhodium/palladium catalysis: enantioselective formation of dihydroquinolinones in the presence of achiral and chiral ligands.

    Science.gov (United States)

    Zhang, Lei; Qureshi, Zafar; Sonaglia, Lorenzo; Lautens, Mark

    2014-12-08

    Compatible combinations of achiral and chiral ligands can be used in rhodium/palladium catalysis to achieve highly enantioselective domino reactions. The difference in rates of catalysis and minimal effects of ligand interference confer control in the domino sequence. The "all-in-one" 1,4-conjugate arylation and C-N cross-coupling through sequential Rh/Pd catalysis provides access to enantioenriched dihydroquinolinone building blocks. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Enantioselective Cu-Catalyzed Arylation of Secondary Phosphine Oxides with Diaryliodonium Salts toward the Synthesis of P-Chiral Phosphines.

    Science.gov (United States)

    Beaud, Rodolphe; Phipps, Robert J; Gaunt, Matthew J

    2016-10-12

    Catalytic synthesis of nonracemic P-chiral phosphine derivatives remains a significant challenge. Here we report Cu-catalyzed enantioselective arylation of secondary phosphine oxides with diaryliodonium salts for the synthesis of tertiary phosphine oxides with high enantiomeric excess. The new process is demonstrated on a wide range of substrates and leads to products that are well-established P-chiral catalysts and ligands.

  18. The Mannich Reaction of Malonates with Simple Imines Catalyzed by Bifunctional Cinchona Alkaloids: Enantioselective Synthesis of β-Amino Acids

    Science.gov (United States)

    Song, Jun; Wang, Yi; Deng, Li

    2011-01-01

    We describe the first efficient, direct asymmetric Mannich reactions with malonates and N-Boc aryl and alkyl imines by cooperative hydrogen bonding catalysis with a cinchona alkaloid bearing a thiourea functionality. We have also extended the scope of this reaction to β-ketoesters. The synthetic value of this new reaction is demonstrated in the establishment of a convergent enantioselective route toward the biologically important β-amino acids under mild and air- and moisture-tolerant conditions. PMID:16669669

  19. Enantioselective toxicokinetics study of the bioaccumulation and elimination of α-hexachlorocyclohexane in loaches (Misgurnus anguillicaudatus) and its environmental implications.

    Science.gov (United States)

    Ma, Rui-xue; Liu, Dong-hui; Qu, Han; Zhou, Gao-xin; Zhou, Zhi-qiang; Wang, Peng

    2013-02-01

    The enantioselective bioaccumulation and elimination of α-hexachlorocyclohexane (α-HCH) in loaches (Misgurnus anguillicaudatus) were studied for the first time. Valid chiral residue analysis methods for α-HCH enantiomers in water and loach samples were established using gas chromatography coupled with electron capture detector and a BGB-172 chiral column. A rapid accumulation process was found during the 39-d bioaccumulation experiment. The α-HCH in loaches reached its maximum on the fourth day, after which it fluctuated slightly, reflecting a balance between elimination and reuptake. The maximum bioaccumulation factor was 728 at the 10 μg L(-1) exposure level. The enantiomeric fraction (EF) values showed that the bioaccumulation was enantioselective with enantioenrichment of (+)-α-HCH in the loaches. The elimination experiment indicated that the degradation kinetics of α-HCH fitted a typical first-order kinetics model, and the half-life was about 5 d. Significant enantioselectivity was observed during the elimination process, with the EFs declining from higher than 0.5-0.39, suggesting (+)-α-HCH is preferentially biotransformed than (-)-α-HCH in loaches. The results reveal a high capacity for α-HCH bioconcentration by loaches and that biotransformation is the main route of decontamination. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Enantioseparation and determination of the chiral phenylpyrazole insecticide ethiprole in agricultural and environmental samples and its enantioselective degradation in soil

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qing; Shi, Haiyan; Gao, Beibei; Tian, Mingming; Hua, Xiude; Wang, Minghua, E-mail: wangmha@njau.edu.cn

    2016-01-15

    An effective method for the enantioselective determination of ethiprole enantiomers in agricultural and environmental samples was developed. The effects of solvent extraction, mobile phase and thermodynamic parameters for chiral recognition were fully investigated. Complete enantioseparation of the ethiprole enantiomers was achieved on a Lux Cellulose-2 column. The stereochemical structures of ethiprole enantiomers were also determined, and (R)-(+)-ethiprole was first eluted. The average recoveries were 82.7–104.9% with intra-day RSD of 1.7–8.2% in soil, cucumber, spinach, tomato, apple and peach under optimal conditions. Good linearity (R{sup 2} ≥ 0.9991) was obtained for all the matrix calibration curves within a range of 0.1 to 10 mg L{sup −1}. The limits of detection for both enantiomers were estimated to be 0.008 mg kg{sup −1} in soil, cucumber, spinach and tomato and 0.012 mg kg{sup −1} in apple and peach, which were lower than the maximum residue levels established in Japan. The results indicate that the proposed method is convenient and reliable for the enantioselective detection of ethiprole in agricultural and environmental samples. The behavior of ethiprole in soil was studied under field conditions and the enantioselective degradation was observed with enantiomer fraction values varying from 0.494 to 0.884 during the experiment. The (R)-(+)-ethiprole (t{sub 1/2} = 11.6 d) degraded faster than (S)-(−)-ethiprole (t{sub 1/2} = 34.7 d). This report is the first describe a chiral analytical method and enantioselective behavior of ethiprole, and these results should be extremely useful for the risk evaluation of ethiprole in food and environmental safety. - Highlights: • The ethiprole enantiomers were completely separated. • A novel method for enantioselective determination of ethiprole was developed. • The absolute configurations of ethiprole enantiomers were firstly determined. • The (R)-(+)-ethiprole was preferentially degraded in

  1. Assessing the suitability of 1,2,3-triazole linkers for covalent immobilization of chiral ligands: application to enantioselective phenylation of aldehydes.

    Science.gov (United States)

    Bastero, Amaia; Font, Daniel; Pericàs, Miquel A

    2007-03-30

    Alkynyl-functionalized amino alcohols have been covalently supported on azidomethylpolystyrene resins with different levels of functionalization through Cu(I)-catalyzed 1,3-dipolar cycloadditions ("click chemistry"). The resulting 1,2,3-triazole-substituted resins, characterized by different levels of ligand loading and, depending on the nature of the alkynyl-functionalized amino alcohol, the presence of a one-carbon, four-carbon, or eight-carbon linear spacer, have been tested as catalysts in the enantioselective phenyl transfer from zinc to aldehydes. High catalytic activities and enantioselectivities (up to 82% ee) have been recorded. The influence of structural characteristics of the resin on enantioselectivity are discussed, and the limitations in enantiocontrol inherent to the use of a 1,2,3-triazole linker have been rationalized with the help of DFT calculations on model systems.

  2. Cooperative catalysis: combining an achiral metal catalyst with a chiral Brønsted acid enables highly enantioselective hydrogenation of imines.

    Science.gov (United States)

    Tang, Weijun; Johnston, Steven; Li, Chaoqun; Iggo, Jonathan A; Bacsa, John; Xiao, Jianliang

    2013-10-11

    Asymmetric hydrogenation of imines leads directly to chiral amines, one of the most important structural units in chemical products, from pharmaceuticals to materials. However, highly effective catalysts are rare. This article reveals that combining an achiral pentamethylcyclopentadienyl (Cp*)-iridium complex with a chiral phosphoric acid affords a catalyst that allows for highly enantioselective hydrogenation of imines derived from aryl ketones, as well as those derived from aliphatic ones, with ee values varying from 81 to 98 %. A range of achiral iridium complexes containing diamine ligands were examined, for which the ligands were shown to have a profound effect on the reaction rate, enantioselectivity and catalyst deactivation. The chiral phosphoric acid is no less important, inducing enantioselection in the hydrogenation. The induction occurs, however, at the expense of the reaction rate. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Enantioselectively controlled release of chiral drug (metoprolol) using chiral mesoporous silica materials

    Energy Technology Data Exchange (ETDEWEB)

    Guo Zhen; Liu Xianbin; Ng, Siu-Choon; Chen Yuan; Yang Yanhui [School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459 (Singapore); Du Yu, E-mail: du_yu@jlu.edu.cn, E-mail: yhyang@ntu.edu.sg [College of Electronic Science and Engineering, Jilin University, Changchun 130012 (China)

    2010-04-23

    Chiral porous materials have attracted burgeoning attention on account of their potential applications in many areas, such as enantioseparation, chiral catalysis, chemical sensors and drug delivery. In this report, chiral mesoporous silica (CMS) materials with various pore sizes and structures were prepared using conventional achiral templates (other than chiral surfactant) and a chiral cobalt complex as co-template. The synthesized CMS materials were characterized by x-ray diffraction, nitrogen physisorption, scanning electron microscope and transmission electron microscope. These CMS materials, as carriers, were demonstrated to be able to control the enantioselective release of a representative chiral drug (metoprolol). The release kinetics, as modeled by the power law equation, suggested that the release profiles of metoprolol were remarkably dependent on the pore diameter and pore structure of CMS materials. More importantly, R- and S-enantiomers of metoprolol exhibited different release kinetics on CMS compared to the corresponding achiral mesoporous silica (ACMS), attributable to the existence of local chirality on the pore wall surface of CMS materials. The chirality of CMS materials on a molecular level was further substantiated by vibrational circular dichroism measurements.

  4. Enantioselective Synthesis of Various Cyanohydrins Using Covalently Immobilized Preparations of Hydroxynitrile Lyase from Prunus dulcis.

    Science.gov (United States)

    Alagöz, Dilek; Tükel, S Seyhan; Yildirim, Deniz

    2015-11-01

    The carrier-based and carrier-free (cross-linked enzyme aggregate) covalent immobilizations of Prunus dulcis hydroxynitrile lyase were investigated. The immobilized preparations were tested for enantioselective carbon-carbon bond formation activity in the biphasic medium. Of the tested preparations, only cross-linked enzyme aggregate of P. dulcis hydroxynitrile lyase (PdHNL-CLEA) achieved the synthesis of (R)-mandelonitrile with 93% yield and 99% enantiopurity. PdHNL-CLEA was also used in the synthesis of various (R)-cyanohydrins from corresponding aldehydes/ketones and hydrocyanic acid. When 4-methoxybenzaldehyde, 4-methyl benzaldehyde, and 4-hydroxybenzaldehyde were used as substrates, the yield-enantiomeric excess of corresponding (R)-cyanohydrins were obtained as 95-95, 85-79, and 2-25%, respectively, after 96 h at pH 4.0 and 5 °C. For acetophenone, 4-fluoroacetophenone, 4-chloroacetophenone, 4-bromoacetophenone, and 4-iodoacetophenone, the yield-enantiomeric excess of corresponding (R)-cyanohydrins were 1-99, 20-84, 11-95, 5-99, and 3-24%, respectively at the same conditions. The results demonstrate PdHNL-CLEA can be effectively used in the synthesis of (R)-mandelonitrile.

  5. Catalytic enantioselective synthesis of atropisomeric biaryls by a cation-directed O-alkylation

    Science.gov (United States)

    Jolliffe, John D.; Armstrong, Roly J.; Smith, Martin D.

    2017-06-01

    Axially chiral biaryls, as exemplified by 1,1‧-bi-2-naphthol (BINOL), are key components of catalysts, natural products and medicines. These materials are synthesized conventionally in enantioenriched form through metal-mediated cross coupling, de novo construction of an aromatic ring, point-to-axial chirality transfer or an atropselective transformation of an existing biaryl. Here, we report a highly enantioselective organocatalytic method for the synthesis of atropisomeric biaryls by a cation-directed O-alkylation. Treatment of racemic 1-aryl-2-tetralones with a chiral quinidine-derived ammonium salt under basic conditions in the presence of an alkylating agent leads to atropselective O-alkylation with e.r. up to 98:2. Oxidation with DDQ gives access to C2-symmetric and non-symmetric BINOL derivatives without compromising e.r. We propose that the chiral ammonium counterion differentiates between rapidly equilibrating atropisomeric enolates, leading to highly atropselective O-alkylation. This dynamic kinetic resolution process offers a general approach to the synthesis of enantioenriched atropisomeric materials.

  6. Optimization of lipase-catalyzed enantioselective production of 1-phenyl 1-propanol using response surface methodology.

    Science.gov (United States)

    Soyer, Asli; Bayraktar, Emine; Mehmetoglu, Ulku

    2010-01-01

    Optically active 1-phenyl 1-propanol is used as a chiral building block and synthetic intermediate in the pharmaceutical industries. In this study, the enantioselective production of 1-phenyl 1-propanol was investigated systematically using response surface methodology (RSM). Before RSM was applied, the effects of the enzyme source, the type of acyl donor, and the type of solvent on the kinetic resolution of 1-phenyl 1-propanol were studied. The best results were obtained with Candida antartica lipase (commercially available as Novozym 435), vinyl laurate as the acyl donor, and isooctane as the solvent. In the RSM, substrate concentration, molar ratio of acyl donor to the substrate, amount of enzyme, temperature, and stirring rate were chosen as independent variables. The predicted optimum conditions for a higher enantiomeric excess (ee) were as follows: substrate concentration, 233 mM; molar ratio of acyl donor to substrate, 1.5; enzyme amount, 116 mg; temperature, 47 °C; and stirring rate, 161 rpm. A verification experiment conducted at these optimized conditions for maximum ee yielded 91% for 3 hr, which is higher than the predicted value of 83%. The effect of microwave on the ee was also investigated and ee reached 87% at only 5 min.

  7. The fate and enantioselective behavior of zoxamide during wine-making process.

    Science.gov (United States)

    Pan, Xinglu; Dong, Fengshou; Liu, Na; Cheng, Youpu; Xu, Jun; Liu, Xingang; Wu, Xiaohu; Chen, Zenglong; Zheng, Yongquan

    2018-05-15

    The fate of zoxamide and its enantiomers were evaluated in detail during wine-making process. The enantiomers of zoxamide were separated and determined by ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) after each processing procedure including washing, peeling, fermentation and clarification. Significant enantioselectivity was observed in all three treatments with the half-lives of R-zoxamide and S-zoxamide estimated to be 45.6 and 52.9 h in Group A, 45.0 and 52.1 h in Group B, 56.8 and 70.7 h in Group C, respectively. The results indicated that R-zoxamide degraded faster than S-zoxamide during the fermentation process. The processing factors (PFs) of each procedure were generally less than 1, and the PF of the overall process ranged from 0.019 to 0.051, which indicated that the whole process can reduce the zoxamide residue in red and white wine obviously. The results could help facilitate more accurate risk assessments of zoxamide during wine-making process. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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

  9. Enantioselective kappa opioid binding sites on the macrophage cell line, P388d sub 1

    Energy Technology Data Exchange (ETDEWEB)

    Carr, D.J.J.; Blalock, J.E. (Univ. of Alabama, Birmingham (USA)); DeCosta, B.R.; Jacobson, A.E.; Rice, K.C. (NIDDK, NIH, Bethesda, MD (USA))

    1991-01-01

    A kappa opioid binding site has been characterized on the macrophage cell line, P388d{sub 1}, using the kappa selective affinity ligand, ({sup 3H}(1S,2S)-(-)-trans-2-isothiocyanato-N-methyl-N-(2-(1-phrrolidinyl) cyclohexyl) benzeneacetamide ((-)BD166). The kappa site has a relative molecular mass (Mr) of 38,000 under nonreducing conditions and 42,000 under reducing conditions. Moreover, it exhibits enantioselectivity in that 1S,2S-(-)-trans-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl)cyclohexyl) benzeneacetamide ((-)-U-50,488) blocks ({sup 3}H)95{alpha},7{alpha},8{beta})-(-)-N-methyl-N-(7-(1- pyrrolidinyl)-1-oxaspiro-(4,5)-dec-8-yl)benzeneacetamide (U-69,593) binding to P388d{sub 1} cells with an IC{sub 50} = 7.0 nM whereas 1R,2R-(+)-trans-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl)cyclohexyl) benzeneacetamide ((+)U-50,488) blocks ({sup 3}H)U-69,593 binding to P388d{sub 1} cells with an IC{sub 50} = 700 nM.

  10. Release of an enantioselective nitrilase from Alcaligenes faecalis MTCC 126: a comparative study.

    Science.gov (United States)

    Singh, Renu; Banerjee, Anirban; Kaul, Praveen; Barse, Brajesh; Banerjee, U C

    2005-10-01

    Nitrilases constitute an important class of hydrolases, however, cheap and ready availability of enzyme sources limit their practical synthetic applications. The present investigation was directed to compare the applicability of various physical cell disintegration methods namely, solid shear, liquid shear and sonication, for the release of an enantioselective nitrilase from Alcaligenes faecalis MTCC 126. Different parameters associated with each method were optimized in order to ensure maximal release of active nitrilase. The methods were also compared under optimal conditions for their efficiency of nitrilase release and extent of cell disruption, and enzyme release were visualized under a differential interference contrast microscope (DIC) and SDS-PAGE, respectively. Maximum release of the enzyme protein from the cells was observed in case of liquid shear method employing high-pressure homogenization, however, the specific activity of nitrilase was highest in cell-free extract (CFE) generated by sonication. Both the solid shear and liquid shear proved to be equally effective for maximum release of intracellular enzymes, however, from the specific activity point of view, sonication was found to be a better one compared to other two methodologies. The generated cell-free extract can be further employed for the production of enantiopure chiral carboxylic acids, which are important chiral building blocks.

  11. Enantioselective nitrilase from Pseudomonas putida: cloning, heterologous expression, and bioreactor studies.

    Science.gov (United States)

    Banerjee, Anirban; Dubey, Sachin; Kaul, Praveen; Barse, Brajesh; Piotrowski, Markus; Banerjee, U C

    2009-01-01

    Nitrilases have attracted tremendous attention for the preparation of optically pure carboxylic acids. This article aims to address the production and utilization of a highly enantioselective nitrilase from Pseudomonas putida MTCC 5110 for the hydrolysis of racemic mandelonitrile to (R)-mandelic acid. The nitrilase gene from P. putida was cloned in pET 21b(+) and over-expressed as histidine-tagged protein in Escherichia coli. The histidine-tagged enzyme was purified from crude cell extracts of IPTG-induced cells of E. coli BL21 (DE3). Inducer replacement studies led to the identification of lactose as a suitable and cheap alternative to the costly IPTG. Effects of medium components, various physico-chemical, and process parameters (pH, temperature, aeration, and agitation) for the production of nitrilase by engineered E. coli were optimized and scaled up to a laboratory scale bioreactor (6.6 l). Finally, the recombinant E. coli whole-cells were utilized for the production of (R)-(-)-mandelic acid.

  12. Enantioselective absorption and transformation of a novel chiral neonicotinoid [(14)C]-cycloxaprid in rats.

    Science.gov (United States)

    Wu, Chengchen; Huang, Lei; Tang, Shenghua; Li, Zhong; Ye, Qingfu

    2016-06-01

    Neonicotinoid pesticides caused hazardous effects on pollinators and aquatic ecosystem. The new developed chiral cis-neonicotinoid cycloxaprid(CYC) is a highly potent substitute for low toxicity to bees and high efficiency on target-insects, but little is known about the metabolic dynamics of racemic CYC and its 2 enantiomers(SR and RS) in animal models. In this study, chiral separation of (14)C-labeled racemic CYC was performed in high-performance liquid chromatography under optimal conditions. For the first time that the stereoselectivity of the chiral neonicotinoid insecticide CYC was exhibited in rats after single dose oral administration using (14)C-labeled isotope trace technique. Enantioselective behaviors of racemic CYC, SR and RS were observed in blood metabolism, tissue distribution and excretion. The major deposition of (14)C were found in liver, lung, kidney and heart. After 24 h, skin and fat showed a strong bioaccumulation effect, and total excreted urine and feces of CYC, SR and RS were 50.4%, 59.7% and 74.5%, respectively. Enantiomer RS had the fastest absorption and elimination rates, and it was least bioaccumulated in rats. The results provide scientific basis and practical techniques for environmental risk assessment of chiral pesticides, especially neonicotinoids. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Simple organic molecules as catalysts for enantioselective synthesis of amines and alcohols.

    Science.gov (United States)

    Silverio, Daniel L; Torker, Sebastian; Pilyugina, Tatiana; Vieira, Erika M; Snapper, Marc L; Haeffner, Fredrik; Hoveyda, Amir H

    2013-02-14

    The discovery of catalysts that can be used to synthesize complex organic compounds by enantioselective transformations is central to advances in the life sciences; for this reason, many chemists aim to discover catalysts that allow for preparation of chiral molecules as predominantly one mirror-image isomer. The ideal catalyst should not contain precious elements and should bring reactions to completion in a few hours through operationally simple procedures. Here we introduce a set of small organic molecules that can catalyse reactions of unsaturated organoboron reagents with imines and carbonyls; the products of the reactions are enantiomerically pure amines and alcohols, which might serve as intermediates in the preparation of biologically active molecules. A distinguishing feature of this catalyst class is the presence of a 'key' proton embedded within their structure. Catalysts are derived from the abundant amino acid valine and are prepared in large quantities in four steps with inexpensive reagents. Reactions are scalable, do not demand stringent conditions, and can be performed with as little as 0.25 mole per cent catalyst in less than six hours at room temperature to generate products in more than 85 per cent yield and ≥97:3 enantiomeric ratio. The efficiency, selectivity and operational simplicity of the transformations and the range of boron-based reagents are expected to render this advance important for future progress in syntheses of amines and alcohols, which are useful in chemistry, biology and medicine.

  14. Enantioselective analysis of fluoxetine in pharmaceutical formulations by capillary zone electrophoresis

    Directory of Open Access Journals (Sweden)

    Melania Cârcu-Dobrin

    2017-03-01

    Full Text Available Fluoxetine is an antidepressant, a selective serotonin reuptake inhibitor (SSRI used primarily in the treatment of major depression, panic disorder and obsessive compulsive disorder. Chiral separation of racemic fluoxetine is necessary due to its enantioselective metabolism. In order to develop a suitable method for chiral separation of fluoxetine, cyclodextrin (CD modified capillary electrophoresis (CE was employed. A large number of native and derivatized, neutral and ionized CD derivatives were screened to find the optimal chiral selector. As a result of this process, heptakis(2,3,6-tri-O-methyl-β-CD (TRIMEB was selected for enantiomeric discrimination. A factorial analysis study was performed by orthogonal experimental design in which several factors are varied at the same time to optimize the separation method. The optimized method (50 mM phosphate buffer, pH = 5.0, 10 mM TRIMEB, 15 °C, + 20 kV, 50 mbar/1 s, detection at 230 nm was successful for baseline separation of fluoxetine enantiomers within 5 min. Our method was validated according to ICH guidelines and proved to be sensitive, linear, accurate and precise for the chiral separation of fluoxetine.

  15. Enantioselective silyl protection of alcohols promoted by a combination of chiral and achiral Lewis basic catalysts

    Science.gov (United States)

    Manville, Nathan; Alite, Hekla; Haeffner, Fredrik; Hoveyda, Amir H.; Snapper, Marc L.

    2013-09-01

    Catalytic enantioselective monosilylations of diols and polyols furnish valuable alcohol-containing molecules in high enantiomeric purity. These transformations, however, require high catalyst loadings (20-30 mol%) and long reaction times (2-5 days). Here, we report that a counterintuitive strategy involving the use of an achiral co-catalyst structurally similar to the chiral catalyst provides an effective solution to this problem. A combination of seemingly competitive Lewis basic molecules can function in concert such that one serves as an achiral nucleophilic promoter and the other performs as a chiral Brønsted base. On the addition of 7.5-20 mol% of a commercially available N-heterocycle (5-ethylthiotetrazole), reactions typically proceed within one hour, and deliver the desired products in high yields and enantiomeric ratios. In some instances, there is no reaction in the absence of the achiral base, yet the presence of the achiral co-catalyst gives rise to facile formation of products in high enantiomeric purity.

  16. Efficacy of topical azelaic acid (AzA) gel 15% plus oral doxycycline 40 mg versus metronidazole gel 1% plus oral doxycycline 40 mg in mild-to-moderate papulopustular rosacea.

    Science.gov (United States)

    Del Rosso, James Q; Bruce, Suzanne; Jarratt, Michael; Menter, Alan; Staedtler, Gerald

    2010-06-01

    Rosacea is a leading reason why people seek the care of a dermatologist, accounting for nearly 7 million office visits annually. Pharmacologic treatments include both topical and oral medications, which are increasingly being used in combination, especially at the outset of therapy. This exploratory study assesses the safety, effectiveness and speed of onset of two common topical agents for the treatment of rosacea--azelaic acid gel (AzA) 15% and metronidazole gel 1%--used in conjunction with anti-inflammatory dose doxycycline (40 mg once daily). Men and women (n = 207) with mild-to-moderate papulopustular rosacea were enrolled and randomized to receive either AzA gel 15% twice daily plus doxycycline 40 mg once daily (AzA group) or metronidazole gel 1% once daily plus doxycycline 40 mg once daily (Metro group) for 12 weeks. Both regimens were safe, efficacious and well tolerated. Efficacy parameters revealed a possible trend toward greater and earlier benefit with the AzA-based regimen than with the metronidazole-based regimen. These findings warrant further investigation in a sufficiently powered study.

  17. Charge Tags for Most Comprehensive ESI-MS Monitoring of Morita-Baylis-Hillman (MBH)/aza-MBH Reactions: Solid Mechanistic View and the Dualistic Role of the Charge Tagged Acrylate.

    Science.gov (United States)

    Galaverna, Renan; Camilo, Nilton S; Godoi, Marla N; Coelho, Fernando; Eberlin, Marcos N

    2016-02-05

    Neutral and charge tagged reagents were used to investigate the mechanism of the classical Morita-Baylis-Hillman (MBH) reaction as well as its aza-version using mass spectrometry with electrospray ionization (ESI-MS). The use of an acrylate (activated alkene) with a methylimidazolium ion as a charge tag eliminates the requirement for adding acids as ESI(+) additives, which are normally used to favor protonation and therefore detection of reaction partners (reagents, intermediates, and products) by ESI(+)-MS. For both charge tagged reactions (MBH/aza-MBH), most reactants, intermediates, and the final adducts were efficiently detected in the form of abundant doubly and singly charged ions. Characterization of the reactions partners was performed via both tandem mass spectrometry (ESI(+)-MS/MS) and accurate m/z measurements. The charge tagged reactions also showed faster conversion rates when compare to the neutral reaction, indicating a dualistic role for the charge tagged acrylate. It acts as both the reagent and a cocatalyst due to the inherent ionic-coordination nature of the methylimidazolium ion, which stabilizes the zwitterionic intermediates and reagents through different types of coordination ion pairs. Hemiacetal intermediates for the rate-limiting proton transfer step were also intercepted and characterized for both classical and aza-MBH charge tagged reactions.

  18. Covalently immobilized lipase on aminoalkyl-, carboxy- and hydroxy-multi-wall carbon nanotubes in the enantioselective synthesis of Solketal esters.

    Science.gov (United States)

    Zniszczoł, Aurelia; Herman, Artur P; Szymańska, Katarzyna; Mrowiec-Białoń, Julita; Walczak, Krzysztof Z; Jarzębski, Andrzej; Boncel, Sławomir

    2016-06-01

    Aiming at the preparation of efficient, stable on storage and recyclable nanobiocatalysts for enantioselective transesterification, alkaline lipase from Pseudomonas fluorescens was covalently immobilized (up to 8.5wt.%) on functionalized multi-wall carbon nanotubes (f-MWCNTs). f-MWCNTs were synthesized via: (a) (2+1)-cycloaddition of a nitrene to the C-sp(2) nanotube walls (3.2mmolg(-1), a novel synthetic approach) and, (b) oxidative treatments, i.e. Fenton reagent (3.5mmolg(-1)) and nitrating mixture (2.5mmolg(-1)), yielding aminoalkyl-, hydroxyl- and carboxyl-MWCNTs, respectively. Amino- and epoxy- functionalized mesoporous silica (f-SBA-15) were used as the reference supports. Transesterification of vinyl n-butyrate by racemic Solketal with a chromatographically (GC) traced kinetics was selected as the model reaction. The studies revealed that different chemical functionalization of morphologically identical nanotube supports led to various enzyme loadings, catalytic activities and enantioselectivities. MWCNT-NH2-based nanobiocatalyst was found to be the most active composite among all of the tested systems (yield 20%, t=0.5h, 1321Ug(-1)), i.e. 12 times more active than the native enzyme. In turn, lipase immobilized on MWCNT-COOH emerged as the most enantioselective system (ex aequo with SBA-NH2) (eeR=74%, t=0.5h at yield of 3-5%). The activity of the MWCNT-NH2-based nanobiocatalyst after 8 cycles of transesterification dropped to 60% of its initial value, whereas for SBA-NH2-based composite remained unchanged. Importantly, stability on storage was fully maintained for all MWCNT-based nanobiocatalysts or even 'extra-enhanced' for MWCNT-OH. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Amphiphilic Polymer-Based Fluorescent Probe for Enantioselective Recognition of Amino Acids in Immiscible Water and Organic Phases.

    Science.gov (United States)

    Nian, Shifeng; Pu, Lin

    2017-12-19

    Atom transfer radical polymerization (ATRP) of N-isopropylacrylamide was conducted in the presence of a 3,3'-diformyl-1,1'-BINOL-based diinitiator (BINOL=1,1'-bi-2-naphthol) to give polymer (S)-7, which was soluble in both water and common organic solvents. Polymer (S)-7 in combination with Zn 2+ in aqueous solution (BICINE buffer at pH 8.80) showed highly enantioselective fluorescence enhancement in the presence of a number of amino acids. It was found that chloroform can be used to extract the aqueous polymer-Zn 2+ -amino acid solution and the resulting chloroform extract maintained the highly enantioselective fluorescence response. Thus, the enantiomeric composition of a chiral amino acid can be determined in the two immiscible solvents of water and chloroform. The aqueous polymer-Zn 2+ -amino acid solution showed a lower critical solution temperature (LCST) at 34 °C, above which the polymer-Zn 2+ -amino acid adduct precipitated out. Measuring the fluorescence of the precipitate redissolved in the aqueous buffer solution showed the retention of the high enantioselectivity. Both the chloroform extraction and the thermo-induced precipitation have allowed the fluorescence response of the sensor toward amino acids to be measured away from the original substrate solution. These two strategies should minimize the interference by other reaction components on the fluorescence measurement when the sensor is applied to analyze the asymmetric reaction screening experiments. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Enantioselective changes in oxidative stress and toxin release in Microcystis aeruginosa exposed to chiral herbicide diclofop acid

    International Nuclear Information System (INIS)

    Ye, Jing; Zhang, Ying; Chen, Shengwen; Liu, Chaonan; Zhu, Yongqiang; Liu, Weiping

    2014-01-01

    Highlights: •The first study on enantioselective oxidative stress and toxin release from Microcystis aeruginosa. •Provide information for the R-enantiomer poses more oxidative stress than the S-enantiomer. •Lifecycle analysis of chiral pollutants needs more attention in environmental assessment. -- Abstract: Enantioselective oxidative stress and toxin release from Microcystis aeruginosa after exposure to the chiral herbicide diclofop acid were investigated. Racemic diclofop acid, R-diclofop acid and S-diclofop acid induced reactive oxygen species (ROS) generation, increased the concentration of malondialdehyde (MDA), enhanced the activity of superoxide dismutase (SOD) and triggered toxin release in M. aeruginosa to varying degrees. The increase in MDA concentration and SOD activity in M. aeruginosa occurred sooner after exposure to diclofop acid than when the cyanobacteria was exposed to either the R- and the S-enantiomer. In addition, enantioselective toxicity of the enantiomers was observed. The R-enantiomer trigged more ROS generation, more SOD activity and more toxin synthesis and release in M. aeruginosa cells than the S-enantiomer. Diclofop acid and its R-enantiomer may collapse the transmembrane proton gradient and destroy the cell membrane through lipid peroxidation and free radical oxidation, whereas the S-enantiomer did not demonstrate such action. R-diclofop acid inhibits the growth of M. aeruginosa in the early stage, but ultimately induced greater toxin release, which has a deleterious effect on the water column. These results indicate that more comprehensive study is needed to determine the environmental safety of the enantiomers, and application of chiral pesticides requires more direct supervision and training. Additionally, lifecycle analysis of chiral pollutants in aquatic system needs more attention to aide in the environmental assessment of chiral pesticides

  1. Isoindolinones as Michael Donors under Phase Transfer Catalysis: Enantioselective Synthesis of Phthalimidines Containing a Tetrasubstituted Carbon Stereocenter

    Directory of Open Access Journals (Sweden)

    Francesco Scorzelli

    2015-05-01

    Full Text Available Readily available chiral ammonium salts derived from cinchona alkaloids have proven to be effective phase transfer catalysts in the asymmetric Michael reaction of 3-substituted isoindolinones. This protocol provides a convenient method for the construction of valuable asymmetric 3,3-disubstituted isoindolinones in high yields and  moderate to good enantioselectivity. Diastereoselectivity was also investigated in the construction of contiguous tertiary and quaternary stereocenters. The use of acrolein as Michael acceptor led to an interesting tricyclic derivative, a pyrroloisoindolinone analogue, via a tandem conjugated addition/cyclization reaction.

  2. 2,2',3,3',6,6'-Hexachlorobiphenyl (PCB 136) is Enantioselectively Oxidized to Hydroxylated Metabolites by Rat Liver Microsomes

    Science.gov (United States)

    Wu, Xianai; Pramanik, Ananya; Duffel, Michael W.; Hrycay, Eugene G.; Bandiera, Stelvio M.; Lehmler, Hans-Joachim; Kania-Korwel, Izabela

    2011-01-01

    Developmental exposure to multiple-ortho substituted polychlorinated biphenyls (PCBs) causes adverse neurodevelopmental outcomes in laboratory animals and humans by mechanisms involving the sensitization of Ryanodine receptors (RyRs). In the case of PCB 136, the sensitization of RyR is enantiospecific, with only (-)-PCB 136 being active. However, the role of enantioselective metabolism in the developmental neurotoxicity of PCB 136 is poorly understood. The present study employed hepatic microsomes from phenobarbital (PB-), dexamethasone (DEX-) and corn oil (VEH-)treated male Sprague-Dawley rats to investigate the hypothesis that PCB 136 atropisomers are enantioselectively metabolized by P450 enzymes to potentially neurotoxic, hydroxylated PCB 136 metabolites. The results demonstrated the time- and isoform-dependent formation of three metabolites, with 5-OH-PCB 136 (2,2',3,3',6,6'-hexachlorobiphenyl-5-ol) being the major metabolite. The formation of 5-OH-PCB 136 increased with the activity of P450 2B enzymes in the microsomal preparation, which is consistent with PCB 136 metabolism by rat P450 2B1. The minor metabolite 4-OH-PCB 136 (2,2',3,3',6,6'-hexachlorobiphenyl-4-ol) was produced by a currently unidentified P450 enzymes. An enantiomeric enrichment of (-)-PCB 136 was observed in microsomal incubations due to the preferential metabolism of (+)-PCB 136 to the corresponding 5-OH-PCB 136 (2,2',3,3',6,6'-hexachlorobiphenyl-5-ol) atropisomer. 4-OH-PCB 136 displayed an enrichment of the atropisomer formed from (-)-PCB 136; however, the enrichment of this metabolite atropisomer didn't affect the enantiomeric enrichment of the parent PCB because 4-OH-PCB 136 is only a minor metabolite. Although the formation of 5- and 4-OH-PCB 136 atropisomers increased with time, the enantioselective formation of the OH-PCB metabolites resulted in constant enantiomeric enrichment, especially at later incubation times. These observations not only demonstrate that the chiral signatures of

  3. Enantioselective semi-preparative HPLC separation of PCB metabolites and their absolute structures determined by electronic and vibrational circular dichroism

    Energy Technology Data Exchange (ETDEWEB)

    Tuan, H.P.; Larsson, C.; Huehnerfuss, H. [Hamburg Univ. (Germany). Inst. fuer Organische Chemie; Hoffmann, F.; Froeba, M. [Giessen Univ. (Germany). Inst. fuer Anorganische und Analytische Chemie; Bergmann, Aa. [Stockholm Univ. (Sweden). Dept. of Environmental Chemistry

    2004-09-15

    The present paper represents a first result of an ongoing systematic study of atropisomeric methylsulfonyl, methylthionyl, hydroxy, and methoxy metabolites of environmentally most relevant PCBs. This involves semi-preparative enantioselective HPLC separation to obtain pure atropisomers from synthesized PCB metabolite standards, their configuration estimation using the electronic circular dichroism (UV-CD) method and the determination / confirmation of these absolute configurations applying the combined vibrational circular dichroism (VCD) / ab initio approach. The following substances have been investigated: 4-HO-, 4-MeO-, 4-MeS-, 4-MeSO2-, 3-MeS- and 3-MeSO{sub 2}-CB149.

  4. P(O)R2-Directed Enantioselective C-H Olefination toward Chiral Atropoisomeric Phosphine-Olefin Compounds.

    Science.gov (United States)

    Li, Shi-Xia; Ma, Yan-Na; Yang, Shang-Dong

    2017-04-07

    An effective synthesis of chiral atropoisomeric biaryl phosphine-olefin compounds via palladium-catalyzed enantioselective C-H olefination has been developed for the first time. The reactions are operationally simple, tolerate wide functional groups, and have a good ee value. Notably, P(O)R 2 not only acts as the directing group to direct C-H activation in order to make a useful ligand but also serves to facilitate composition of the product in a useful manner in this transformation.

  5. Enantioselective sulfonation of enones with sulfonyl imines by cooperative N-heterocyclic-carbene/thiourea/tertiary-amine multicatalysis.

    Science.gov (United States)

    Jin, Zhichao; Xu, Jianfeng; Yang, Song; Song, Bao-An; Chi, Yonggui Robin

    2013-11-18

    Many hands make light work: In an organocatalytic asymmetric sulfonation of enones, the activation of a sulfonyl imine by an N-heterocyclic carbene (NHC) catalyst led to the release of a sulfinic anion, which underwent nucleophilic addition to the enone. The enantioselectivity of the process was controlled by a chiral thiourea/amine co-catalyst through anion recognition and hydrogen-bonding interactions. Tol=p-tolyl. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Rational molecular design towards Vis/NIR absorption and fluorescence by using pyrrolopyrrole aza-BODIPY and its highly conjugated structures for organic photovoltaics.

    Science.gov (United States)

    Shimizu, Soji; Iino, Taku; Saeki, Akinori; Seki, Shu; Kobayashi, Nagao

    2015-02-09

    Pyrrolopyrrole aza-BODIPY (PPAB) developed in our recent study from diketopyrrolopyrrole by titanium tetrachloride-mediated Schiff-base formation reaction with heteroaromatic amines is a highly potential chromophore due to its intense absorption and fluorescence in the visible region and high fluorescence quantum yield, which is greater than 0.8. To control the absorption and fluorescence of PPAB, particularly in the near-infrared (NIR) region, further molecular design was performed using DFT calculations. This results in the postulation that the HOMO-LUMO gap of PPAB is perturbed by the heteroaromatic moieties and the aryl-substituents. Based on this molecular design, a series of new PPAB molecules was synthesized, in which the largest redshifts of the absorption and fluorescence maxima up to 803 and 850 nm, respectively, were achieved for a PPAB consisting of benzothiazole rings and terthienyl substituents. In contrast to the sharp absorption of PPAB, a PPAB dimer, which was prepared by a cross-coupling reaction of PPAB monomers, exhibited panchromatic absorption across the UV/Vis/NIR regions. With this series of PPAB chromophores in hand, a potential application of PPAB as an optoelectronic material was investigated. After identifying a suitable PPAB molecule for application in organic photovoltaic cells based on evaluation using time-resolved microwave conductivity measurements, a maximized power conversion efficiency of 1.27 % was achieved. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Synthesis and Properties of Endohedral Aza[60]fullerenes: H₂O@C₅₉N and H₂@C₅₉N as Their Dimers and Monomers.

    Science.gov (United States)

    Hashikawa, Yoshifumi; Murata, Michihisa; Wakamiya, Atsushi; Murata, Yasujiro

    2016-03-30

    The macroscopic-scale syntheses of the first endohedral aza[60]fullerenes X@C59N (X = H2O, H2) were achieved in two different ways: (1) synthesis from endohedral fullerene H2O@C60 as a starting material and (2) molecular surgical synthesis from a C59N precursor having a considerably small opening. In the neutral state of H2O@C59N, we expected the H-bonding interaction or repulsive N-O interaction between entrapped H2O and a nitrogen atom on the C59N cage. However, an attractive electrostatic N-O interaction was suggested from the results of variable temperature NMR, nuclear magnetic relaxation times (T1, T2), and density functional theory (DFT) calculations. Upon the reaction with acetone via cationic intermediate C59N(+), we found a difference in reaction rates between H2O@C59N and H2@C59N dimers (observed reaction rates: k'(H2O)/k'(H2) = 1.74 ± 0.16). The DFT calculations showed thermal stabilization of C59N(+) by entrapped H2O through the electrostatic interaction.

  8. Theoretical molecular structure, vibrational frequencies and NMR investigations of 2-[(1E-2-aza-2-(5-methyl(2-pyridylethenyl]-4-bromobenzen-1-ol

    Directory of Open Access Journals (Sweden)

    Cemal Parlak

    2012-08-01

    Full Text Available The normal mode frequencies and corresponding vibrational assignments, 1H and 13C NMR chemical shifts and structural parameters (bond lengths, bond and dihedral angles of 2-[(1E-2-aza-2-(5-methyl(2-pyridylethenyl]-4-bromobenzen-1-ol (2mpe-4bb Schiff base compound have been theoretically examined by means of Hartree-Fock (HF and Becke-3-Lee-Yang-Parr (B3LYP density functional methods with 6-31G(d and 6-311++G(d,p basis sets. Furthermore, reliable vibrational assignments have made on the basis of potential energy distribution (PED calculated and the thermodynamics functions, highest occupied and lowest unoccupied molecular orbitals (HOMO and LUMO of 2mpe-4bb have been predicted. Theoretical results have been successfully compared with available experimental data in the literature. Regarding the calculations, 2mpe-4bb prefers enol-imine form and DFT method is superior to HF approach except for predicting bond lengths.DOI: http://dx.doi.org/10.4314/bcse.v26i2.11

  9. Treatment of Donor Cells and Reconstructed Embryos with a Combination of Trichostatin-A and 5-aza-2'-Deoxycytidine Improves the Developmental Competence and Quality of Buffalo Embryos Produced by Handmade Cloning and Alters Their Epigenetic Status and Gene Expression.

    Science.gov (United States)

    Saini, Monika; Selokar, Naresh L; Agrawal, Himanshu; Singla, Suresh Kumar; Chauhan, Manmohan Singh; Manik, Radheysham S; Palta, Prabhat

    2017-06-01

    The application of cloning technology on a large scale is limited by very low offspring rate primarily due to aberrant or incomplete epigenetic reprogramming. Trichostatin A (TSA), a histone deacetylase inhibitor, and 5-aza-2'-deoxycytidine (5-aza-dC), an inhibitor of DNA methyltransferases, are widely used for altering the epigenetic status of cloned embryos. We optimized the doses of these epigenetic modifiers for production of buffalo embryos by handmade cloning and examined whether combined treatment with these epigenetic modifiers offered any advantage over treatment with the individual epigenetic modifier. Irrespective of whether donor cells or reconstructed embryos or both were treated with 50 nM TSA +7.5 nM 5-aza-dC, (1) the blastocyst rate was significantly higher (71.6 ± 3.5, 68.3 ± 2.6, and 71.8 ± 2.4, respectively, vs. 43.1 ± 3.4 for controls, p < 0.05); (2) the apoptotic index was lower (5.4 ± 1.1, 9.5 ± 1.0, and 7.4 ± 1.3, respectively, vs. 19.5 ± 2.1 for controls, p < 0.05) and was similar to that of in vitro fertilization blastocysts (6.0 ± 0.8); (3) the global level of H3K18ac was higher (p < 0.01) and that of H3K27me3 lower (p < 0.05) than in controls and was similar among all treatment groups; and (4) the expression level of epigenetic-(HDAC1, DNMT1, and DNMT3a), pluripotency-(OCT4 and NANOG), and development-related (FGF4) genes, but not that of SOX2 and CDX2, was similar among all treatment groups. These results demonstrate that similar levels of beneficial effects can be obtained following treatment of either donor cells or reconstructed embryos or both with the combination of TSA +5-aza-dC. Therefore, there is no advantage in treating both donor cells and reconstructed embryos when the combination of TSA and 5-aza-dC is used.

  10. Enantioselective transesterification by Candida antarctica Lipase B immobilized on fumed silica.

    Science.gov (United States)

    Kramer, Martin; Cruz, Juan C; Pfromm, Peter H; Rezac, Mary E; Czermak, Peter

    2010-10-01

    Enzymatic catalysis to produce molecules such as perfumes, flavors, and fragrances has the advantage of allowing the products to be labeled "natural" for marketing in the U.S., in addition to the exquisite selectivity and stereoselectivity of enzymes that can be an advantage over chemical catalysis. Enzymatic catalysis in organic solvents is attractive if solubility issues of reactants or products, or thermodynamic issues (water as a product in esterification) complicate or prevent aqueous enzymatic catalysis. Immobilization of the enzyme on a solid support can address the generally poor solubility of enzymes in most solvents. We have recently reported on a novel immobilization method for Candida antarctica Lipase B on fumed silica to improve the enzymatic activity in hexane. This research is extended here to study the enantioselective transesterification of (RS)-1-phenylethanol with vinyl acetate. The maximum catalytic activity for this preparation exceeded the activity (on an equal enzyme amount basis) of the commercial Novozyme 435(®) significantly. The steady-state conversion for (R)-1-phenylethanol was about 75% as confirmed via forward and reverse reaction. The catalytic activity steeply increases with increasing nominal surface coverage of the support until a maximum is reached at a nominal surface coverage of 230%. We hypothesize that the physical state of the enzyme molecules at a low surface coverage is dominated in this case by detrimental strong enzyme-substrate interactions. Enzyme-enzyme interactions may stabilize the active form of the enzyme as surface coverage increases while diffusion limitations reduce the apparent catalytic performance again at multi-layer coverage. The temperature-, solvent-, and long-term stability for CALB/fumed silica preparations showed that these preparations can tolerate temperatures up to 70°C, continuous exposure to solvents, and long-term storage. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. Evaluating the robustness of the enantioselective stationary phases on the Rosetta mission against space vacuum vaporization

    Science.gov (United States)

    Meierhenrich, Uwe J.; Cason, Julie R. L.; Szopa, Cyril; Sternberg, Robert; Raulin, François; Thiemann, Wolfram H.-P.; Goesmann, Fred

    2013-12-01

    The European Space Agency's Rosetta mission was launched in March 2004 in order to reach comet 67P/Churyumov-Gerasimenko by August 2014. The Cometary Sampling and Composition experiment (COSAC) onboard the Rosetta mission's lander "Philae" has been designed for the cometary in situ detection and quantification of organic molecules using gas chromatography coupled to mass spectrometry (GC-MS). The GC unit of COSAC is equipped with eight capillary columns that will each provide a specific stationary phase for molecular separation. Three of these stationary phases will be used to chromatographically resolve enantiomers, as they are composed of liquid polymers of polydimethylsiloxane (PDMS) to which chiral valine or cyclodextrin units are attached. Throughout the ten years of Rosetta's journey through space to reach comet 67P, these liquid stationary phases have been exposed to space vacuum, as the capillary columns within the COSAC unit were not sealed or filled with carrier gas. Long term exposures to space vacuum can cause damage to such liquid stationary phases as key monomers, volatiles, and chiral selectors can be vaporized and lost in transit. We have therefore exposed identical spare units of COSAC's chiral stationary phases over eight years to vacuum conditions mimicking those experienced in space and we have now investigated their resolution capabilities towards different enantiomers both before and after exposure to space vacuum environments. We have observed that enantiomeric resolution capabilities of these chiral liquid enantioselective stationary phases has not been affected by exposure to space vacuum conditions. Thus we conclude that the three chiral stationary phases of the COSAC experiment onboard the Rosetta mission lander "Philae" can be considered to have maintained their resolution capacities throughout their journey prior to cometary landing in November 2014.

  12. Enantioselective determination of arotinolol in human plasma by HPLC using teicoplanin chiral stationary phase.

    Science.gov (United States)

    Aboul-Enein, Hassan Y; Hefnawy, Mohamed M

    2003-10-01

    A sensitive enantioselective high-performance liquid chromatography (HPLC) method was developed and validated to determine S-(+)- and R-(-)-arotinolol in human plasma. Baseline resolution was achieved by using teicoplanin macrocyclic antibiotic chiral stationary phase (CSP) known as Chirobiotic T with a polar organic mobile phase consisting of methanol:glacial acetic acid:triethylamine, 100:0.1:0.1, (v/v/v) at a fl ow rate of 0.8 mL/min and UV detection set at 317 nm. Human plasma was spiked with stock solution of arotinolol enantiomers and labetalol as the internal standard. The assay involved the use of liquid-liquid extraction procedure with ethyl ether under alkaline condition for human plasma sample prior to HPLC analysis. Recoveries for S-(+)- and R-(-)-arotinolol enantiomers were in the range 93-103% at 200-1400 ng/mL level. Intra-day and inter-day precision calculated as %RSD was in the ranges 1.3-3.4 and 1.9-4.5% for both enantiomers, respectively. Intra-day and inter-day accuracies calculated as percentage error were in the ranges 1.2-3.5 and 1.5-6.2% for both enantiomers, respectively. Linear calibration curves in the concentration range 100-1500 ng/mL for each enantiomer showed a correlation coefficient (r) of 0.9998. The limit of quantitation (LOQ) and limit of detection (LOD) for each enantiomer in human plasma were 100 and 50 ng/mL (S/N = 3), respectively. Copyright 2003 John Wiley & Sons, Ltd.

  13. Enantiomerization and enantioselective bioaccumulation of benalaxyl in Tenebrio molitor larvae from wheat bran.

    Science.gov (United States)

    Gao, Yongxin; Chen, Jinhui; Wang, Huili; Liu, Chen; Lv, Xiaotian; Li, Jianzhong; Guo, Baoyuan

    2013-09-25

    The enantiomerization and enatioselecive bioaccumulation of benalaxyl by dietary exposure to Tenebrio molitor larvae under laboratory conditions were studied by HPLC-MS/MS. Exposure of enantiopure R-benalaxyl and S-benalaxyl in T. molitor larvae revealed significant enantiomerization with formation of the R enantiomers from the S enantiomers, and vice versa. Enantiomerization was not observed in wheat bran during the period of 21 days. For the bioaccumulation experiment, the enantiomer fraction in T. molitor larvae was maintained approximately at 0.6, whereas the enantiomer fraction in wheat bran was maintained at 0.5; in other words, the bioaccumulation of benalaxyl was enantioselective in T. molitor larvae. Mathematical models for a process of uptake, degradation, and enantiomerization were developed, and the rates of uptake, degradation, and enantiomerization of R-benealaxyl and S-benealaxyl were estimated, respectively. The results were that the rate of uptake of R-benalaxyl (kRa = 0.052 h(-1)) was slightly lower than that of S-benalaxyl (kSa = 0.061 h(-1)) from wheat bran; the rate of degradation of R-benalaxyl (kRd = 0.285 h(-1)) was higher than that of S-benalaxyl (kSd = 0.114 h(-1)); and the rate of enantiomerization of R-benalaxyl (kRS = 0.126 h(-1)) was higher than that of S-benalaxyl (kSR = 0.116 h(-1)). It was suggested that enantioselectivtiy was caused not only by actual degradation and metabolism but also by enantiomerization, which was an important process in the environmental fate and behavior of chiral pesticides.

  14. Enantioselective analysis of chiral anteiso fatty acids in the polar and neutral lipids of food.

    Science.gov (United States)

    Hauff, Simone; Hottinger, Georg; Vetter, Walter

    2010-04-01

    Anteiso fatty acids (aFA) are substituted with a methyl group on the antepenultimate carbon of the straight acyl chain. This feature leads to a stereogenic center. The 12-methyltetradecanoic acid (a15:0) and the 14-methylhexadecanoic acid (a17:0) are the most common aFA found in food, although they occur only in very small quantities. In this study we used gas chromatography in combination with a chiral stationary phase to determine the enantiomeric distribution of both a15:0 and a17:0 in the neutral and polar lipids of aquatic food samples and cheese. The best suited column was selected out of four custom-made combinations of heptakis(6-O-tert-butyldimethylsilyl-2,3-di-O-methyl)-beta-cyclodextrin (beta-TBDM) with different amount and polarity of an achiral polysiloxane. After separation of polar and neutral lipids of the food samples by solid phase extraction, fatty acid methyl esters were prepared and the fatty acid methyl esters were fractionated by reversed phase high performance liquid chromatography. Measurements of fractions high in aFA by enantioselective GC/MS in the selected ion monitoring mode verified the dominance of the (S)-enantiomers of a15:0 and a17:0 in both lipid fractions. However (R)-enantiomers were detectable in all samples. The relative proportion of the (R)-enantiomers was up to fivefold higher in the polar lipids than in the neutral lipids. The higher proportions in the polar lipids indicate that microorganisms might be involved in the formation of (R)-aFA.

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

    Science.gov (United States)

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

    2009-03-01

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

  16. Lipase AKG mediated resolutions of alpha,alpha-disubstituted 1,2-diols in organic solvents; Remarkably high regio- and enantio-selectivity

    NARCIS (Netherlands)

    Hof, RP; Kellogg, RM

    1996-01-01

    Diols 1, which contain adjacent tertiary and primary hydroxy groups, can be selectively mono-acylated at the primary hydroxy group by many lipases in organic solvents, Since the reaction does not take place at the chiral tertiary centre itself, observed enantioselectivities are usually low. Only the

  17. Formal synthesis of solanoeclepin A: enantioselective allene diboration and intramolecular [2+2] photocycloaddition for the construction of the tricyclic core

    NARCIS (Netherlands)

    Kleinnijenhuis, R.A.; Timmer, B.J.J.; Lutteke, G.; Smits, J.M.M.; de Gelder, R.; van Maarseveen, J.H.; Hiemstra, H.

    2016-01-01

    An enantioselective synthesis of an intermediate in the Tanino total synthesis of solanoeclepin A has been developed. The key step was an intramolecular [2+2] photocycloaddition, which led to the tricyclo[5.2.1.0(1,6)]decane core in six steps. The first photosubstrate, prepared through an

  18. Influence of degree of sulfonation of BDPP upon enantioselectivity in rhodium-BDPP catalyzed hydrogenation reactions in a two phase system

    NARCIS (Netherlands)

    Lensink, Cornelis; Rijnberg, Evelien; Vries, Johannes G. de

    1997-01-01

    Asymmetric hydrogenation experiments were carried out with catalysts prepared in situ from [Rh(COD)Cl]2 and 2 eq. of a sulfonated (2S,4S)-bis-2,4-(diphenylphosphino)pentane carrying 0-4 sulfonate groups, in a two phase aqueous organic system. The effect of degree of sulfonation on enantioselectivity

  19. Development of tartaric acid derived chiral guanidines and their application to catalytic enantioselective α-hydroxylation of β-dicarbonyl compounds.

    Science.gov (United States)

    Zou, Liwei; Wang, Baomin; Mu, Hongfang; Zhang, Huanrui; Song, Yuming; Qu, Jingping

    2013-06-21

    A novel library of chiral guanidines featuring a tartaric acid skeleton was developed from diethyl l-tartrate. These guanidines are easily accessed with tunable steric and electronic properties. The utilities of the guanidines were highlighted by their ability to catalyze the α-hydroxylation of β-ketoesters and β-diketones with remarkable efficiency and excellent enantioselectivity.

  20. Co(salen)-mediated enantioselective radiofluorination of epoxides. Radiosynthesis of enantiomerically enriched [18F]F-MISO via kinetic resolution

    DEFF Research Database (Denmark)

    Revunov, Evgeny V.; Zhuravlev, Fedor

    2013-01-01

    The first example of transition metal mediated enantioselective radiofluorination of epoxides is reported. The procedure utilizes gaseous [18F]HF in a combination with (−)tetramisole and (R,R)-Co(salen), giving the corresponding (S,S)-18F-fluorohydrines in 78–93% radiochemical yield (RCY) and 20–...

  1. Continuous enantioselective esterification of trans-2-phenyl-1-cyclohexanol using a new Candida rugosa lipase in a packed bed bioreactor.

    Science.gov (United States)

    Sánchez, A; del Río, J L; Valero, F; Lafuente, J; Faus, I; Solà, C

    2001-11-17

    Enantioselective resolution of trans-2-phenyl-1-cyclohexanol (TPCH) by a Candida rugosa lipase, obtained by fermentation in the laboratory, and immobilised on EP100 polypropylene powder has been carried out using isooctane as solvent and propionic acid as esterifying agent. The study have included the utilisation of this biocatalyst in a batch process and the optimisation of the esterification conditions by means of a Box-Hunter-based experimental design. The main variables controlling the process, concentration of acid and alcohol, have been numerically optimised using initial esterification rate as objective function. The optimal concentrations for the batch process were 50 mM for the alcohol and 71 mM for the acid. This esterification reaction kinetics corresponded to a reversible Michaelis-Menten kinetic law for the optimal conditions, which has permitted to select a plug-flow packed bed bioreactor as the most appropriate configuration to minimise the residence time and to avoid shear stress effect on the biocatalyst. The behaviour of the continuous packed bed bioreactor at two different residence times (302 and 582 min) was in accordance with predictions from batch experiments, with slightly deviations (less than 10%). Continuous experiments maintained high values of enantioselectivity (enantiomeric factor was practically 1) and conversion near equilibrium value (35%) when long-time operation was carried out. Besides, long-time stability of biocatalyst has permitted to scale-up the production of enantioenriched (1R,2S)-TPCH propionate to yield gram quantities.

  2. Potencial de biocatálise enantiosseletiva de lipases microbianas Potential of enantioselective biocatalysis by microbial lipases

    Directory of Open Access Journals (Sweden)

    Patrícia de O. Carvalho

    2005-08-01

    Full Text Available Microbial lipases have a great potential for commercial applications due to their stability, selectivity and broad substrate specificity because many non-natural acids, alcohols or amines can be used as the substrate. Three microbial lipases isolated from Brazilian soil samples (Aspergillus niger; Geotrichum candidum; Penicillium solitum were compared in terms of their stability and as biocatalysts in the enantioselective esterification using racemic substrates in organic medium. The lipase from Aspergillus niger showed the highest activity (18.2 U/mL and was highly thermostable, retaining 90% and 60% activity at 50 ºC and 60 ºC after 1 hour, respectively. In organic medium, this lipase provided the best results in terms of enantiomeric excess of the (S-active acid (ee = 6.1% and conversion value (c = 20% in the esterification of (R,S-ibuprofen with 1-propanol in isooctane. The esterification reaction of the racemic mixture of (R,S-2-octanol with decanoic acid proceeded with high enantioselectivity when lipase from Aspergillus niger (E = 13.2 and commercial lipase from Candida antarctica (E = 20 were employed.

  3. Crosslinked aggregates of Rhizopus oryzae lipase as industrial biocatalysts: preparation, optimization, characterization, and application for enantioselective resolution reactions.

    Science.gov (United States)

    Kartal, Funda; Kilinc, Ali

    2012-07-01

    Lipase from Rhizopus oryzae (ROL) was immobilized as crosslinked enzyme aggregate (CLEA) via precipitation with ammonium sulfate and simultaneous crosslinking with glutaraldehyde. The optimum conditions of the immobilization process were determined. Lipase CLEAs showed a twofold increase in activity when Tween 80-pretreated lipase was used for CLEA preparation. CLEAs were shown to have several advantages compared to free lipase. CLEAs were more stable at 50°C and 60°C as well as for a wide range of pH. After incubation at 50°C, CLEA showed 74% of initial activity whereas free enzyme was totally inactivated. Reduction of Schiff bases has been performed for the first time in the CLEA preparation process significantly improving the chemically modified CLEAs' reusability, thus providing an enzyme with high potential for recycling even under aqueous reaction conditions where enzyme leakage is, in general, one of the major problems. The CLEA retained 91% activity after 10 cycles in aqueous medium. The immobilized enzyme was used for kinetic resolution reactions. Results showed that immobilization had an enhancing effect on the conversion (c) as well as on the enantiomeric ratio (E). ROL CLEA displayed five times higher enantioselectivity for the hydrolysis of (R,S)-1-phenylethyl acetate and likewise 1.5 times higher enantioselectivity for the transesterification of racemic (R-S)-1-phenylethanol with vinylacetate. Copyright © 2012 American Institute of Chemical Engineers (AIChE).

  4. Identification of new metabolic pathways in the enantioselective fungicide tebuconazole biodegradation by Bacillus sp. 3B6.

    Science.gov (United States)

    Youness, Mohamed; Sancelme, Martine; Combourieu, Bruno; Besse-Hoggan, Pascale

    2018-02-24

    The use of triazole fungicides in various fields ranging from agriculture to therapy, can cause long-term undesirable effects on different organisms from various environmental compartments and lead to resistance phenomena (even in humans) due to their extensive use and persistence. Their occurrence in various water bodies has increased and tebuconazole, in particular, is often detected, sometimes in high concentration. Only a few bacterial and fungal strains have been isolated and found to biotransform this fungicide, described as not easily biodegradable. Nevertheless, the knowledge of efficient degrading-strains and metabolites potentially formed could improve bioremediation process and global overview of risk assessment. Therefore, a broad screening of microorganisms, isolated from various environmental compartments or from commercially-available strain collections, allowed us to find six bacterial strains able to biotransform tebuconazole. The most efficient one was studied further: this environmental strain Bacillus sp. 3B6 biotransforms the fungicide enantioselectively (ee = 18%) into two hydroxylated metabolites, one of them being transformed in its turn to alkene by a biotic dehydration reaction. This original enantioselective pathway shows that racemic pesticides should be treated by the environmental risk assessment authorities as a mixture of two compounds because persistence, biodegradation, bioaccumulation and toxicity often show chiral dependence. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Heterogeneous versus homogeneous copper(II) catalysis in enantioselective conjugate-addition reactions of boron in water.

    Science.gov (United States)

    Kitanosono, Taku; Xu, Pengyu; Kobayashi, Shū

    2014-01-01

    We have developed Cu(II)-catalyzed enantioselective conjugate-addition reactions of boron to α,β-unsaturated carbonyl compounds and α,β,γ,δ-unsaturated carbonyl compounds in water. In contrast to the previously reported Cu(I) catalysis that required organic solvents, chiral Cu(II) catalysis was found to proceed efficiently in water. Three catalyst systems have been exploited: cat. 1: Cu(OH)2 with chiral ligand L1; cat. 2: Cu(OH)2 and acetic acid with ligand L1; and cat. 3: Cu(OAc)2 with ligand L1. Whereas cat. 1 is a heterogeneous system, cat. 2 and cat. 3 are homogeneous systems. We tested 27 α,β-unsaturated carbonyl compounds and an α,β-unsaturated nitrile compound, including acyclic and cyclic α,β-unsaturated ketones, acyclic and cyclic β,β-disubstituted enones, acyclic and cyclic α,β-unsaturated esters (including their β,β-disubstituted forms), and acyclic α,β-unsaturated amides (including their β,β-disubstituted forms). We found that cat. 2 and cat. 3 showed high yields and enantioselectivities for almost all substrates. Notably, no catalysts that can tolerate all of these substrates with high yields and high enantioselectivities have been reported for the conjugate addition of boron. Heterogeneous cat. 1 also gave high yields and enantioselectivities with some substrates and also gave the highest TOF (43,200 h(-1) ) for an asymmetric conjugate-addition reaction of boron. In addition, the catalyst systems were also applicable to the conjugate addition of boron to α,β,γ,δ-unsaturated carbonyl compounds, although such reactions have previously been very limited in the literature, even in organic solvents. 1,4-Addition products were obtained in high yields and enantioselectivities in the reactions of acyclic α,β,γ,δ-unsaturated carbonyl compounds with diboron 2 by using cat. 1, cat. 2, or cat. 3. On the other hand, in the reactions of cyclic α,β,γ,δ-unsaturated carbonyl compounds with compound 2, whereas 1,4-addition products

  6. Protein engineering of a nitrilase from Burkholderia cenocepacia J2315 for efficient and enantioselective production of (R)-o-chloromandelic acid.

    Science.gov (United States)

    Wang, Hualei; Gao, Wenyuan; Sun, Huihui; Chen, Lifeng; Zhang, Lujia; Wang, Xuedong; Wei, Dongzhi

    2015-12-01

    The nitrilase-mediated pathway has significant advantages in the production of optically pure aromatic α-hydroxy carboxylic acids. However, low enantioselectivity and activity are observed on hydrolyzing o-chloromandelonitrile to produce optically pure (R)-o-chloromandelic acid. In the present study, a protein engineering approach was successfully used to enhance the performance of nitrilase obtained from Burkholderia cenocepacia strain J2315 (BCJ2315) in hydrolyzing o-chloromandelonitrile. Four hot spots (T49, I113, Y199, and T310) responsible for the enantioselectivity and activity of BCJ2315 were identified by random mutagenesis. An effective double mutant (I113M/Y199G [encoding the replacement of I with M at position 113 and Y with G at position 199]), which demonstrated remarkably enhanced enantioselectivity (99.1% enantiomeric excess [ee] compared to 89.2% ee for the wild type) and relative activity (360% of the wild type), was created by two rounds of site saturation mutagenesis, first at each of the four hot spots and subsequently at position 199 for combination with the selected beneficial mutation I113M. Notably, this mutant also demonstrated dramatically enhanced enantioselectivity and activity toward other mandelonitrile derivatives and, thus, broadened the substrate scope of this nitrilase. Using an ethyl acetate-water (1:9) biphasic system, o-chloromandelonitrile (500 mM) was completely hydrolyzed in 3 h by this mutant with a small amount of biocatalyst (10 g/liter wet cells), resulting in a high concentration of (R)-o-chloromandelic acid with 98.7% ee, to our knowledge the highest ever reported. This result highlights a promising method for industrial production of optically pure (R)-o-chloromandelic acid. Insight into the source of enantioselectivity and activity was gained by homology modeling and molecular docking experiments. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. Treatment with 5-Aza-2'-Deoxycytidine Induces Expression of NY-ESO-1 and Facilitates Cytotoxic T Lymphocyte-Mediated Tumor Cell Killing.

    Science.gov (United States)

    Klar, Agnes S; Gopinadh, Jakka; Kleber, Sascha; Wadle, Andreas; Renner, Christoph

    2015-01-01

    NY-ESO-1 belongs to the cancer/testis antigen (CTA) family and represents an attractive target for cancer immunotherapy. Its expression is induced in a variety of solid tumors via DNA demethylation of the promoter of CpG islands. However, NY-ESO-1 expression is usually very low or absent in some tumors such as breast cancer or multiple myeloma. Therefore, we established an optimized in vitro treatment protocol for up-regulation of NY-ESO-1 expression by tumor cells using the hypomethylating agent 5-aza-2'-deoxycytidine (DAC). We demonstrated de novo induction of NY-ESO-1 in MCF7 breast cancer cells and significantly increased expression in U266 multiple myeloma cells. This effect was time- and dose-dependent with the highest expression of NY-ESO-1 mRNA achieved by the incubation of 10 μM DAC for 72 hours. NY-ESO-1 activation was also confirmed at the protein level as shown by Western blot, flow cytometry, and immunofluorescence staining. The detection and quantification of single NY-ESO-1 peptides presented at the tumor cell surface in the context of HLA-A*0201 molecules revealed an increase of 100% and 50% for MCF7 and U266 cells, respectively. Moreover, the enhanced expression of NY-ESO-1 derived peptides at the cell surface was accompanied by an increased specific lysis of MCF7 and U266 cells by HLA-A*0201/NY-ESO-1(157-165) peptide specific chimeric antigen receptor (CAR) CD8+ T cells. In addition, the killing activity of CAR T cells correlated with the secretion of higher IFN-gamma levels. These results indicate that NY-ESO-1 directed immunotherapy with specific CAR T cells might benefit from concomitant DAC treatment.

  8. Synthesis and antituberculosis activity of cycloalkylidenehydrazide and 4-aza-1-thiaspiro[4.5]decan-3-one derivatives of imidazo[2,1-b]thiazole.

    Science.gov (United States)

    Ulusoy, Nuray

    2002-01-01

    New N2-cycloalkylidene-(6-phenyl/4-chlorophenylimidazo[2,1-b]thiazol-3-yl) acetic acid hydrazides (2a-h and 3a-b) were synthesized by reacting (6-phenyl/4-chlorophenylimidazo[2,1-b]thiazol-3-yl)acetic acid hydrazides with cyclohexanones or cyclopentanone. Furthermore, 2a-h were refluxed with thioglycolic or thiolactic acid to give 4-[[(6-phenyl/4-chlorophenylimidazo[2,1-b]thiazol-3-yl) acetyl]amino]-4-aza-1-thiaspiro[4.5]decan-3-ones (4a-h and 5a-h). The structures of the title compounds were established by spectral data (IR, 1H-NMR, 13C-NMR and EIMS (Electron Impact Mass Spectrometry)) and elemental analysis. The synthesized compounds were evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv (ATCC 27294). The compounds exhibited varying degrees of inhibition in the in vitro primary screening that was conducted at a concentration of 6.25 micrograms/ml against M. tuberculosis H37Rv (ATCC 27294) in Bactec 12B medium using the Bactec 460 radiometric system or a broth microdilution assay, the Microplate Alamar Blue Assay (MABA). Compounds 2f, 2h, 3b, 4a, 4c, 4d, 5a-e and 5h demonstrating at 1-east 90% inhibition in the primary screen were re-tested at lower concentrations against M. tuberculosis H37Rv (ATCC 27294) to determine the actual minimum inhibitory concentration (MIC) using MABA. The most active compounds were found to be 4d and 5c. The structure-activity relationships of the derivatives were investigated.

  9. Treatment with 5-Aza-2'-Deoxycytidine Induces Expression of NY-ESO-1 and Facilitates Cytotoxic T Lymphocyte-Mediated Tumor Cell Killing.

    Directory of Open Access Journals (Sweden)

    Agnes S Klar

    Full Text Available NY-ESO-1 belongs to the cancer/testis antigen (CTA family and represents an attractive target for cancer immunotherapy. Its expression is induced in a variety of solid tumors via DNA demethylation of the promoter of CpG islands. However, NY-ESO-1 expression is usually very low or absent in some tumors such as breast cancer or multiple myeloma. Therefore, we established an optimized in vitro treatment protocol for up-regulation of NY-ESO-1 expression by tumor cells using the hypomethylating agent 5-aza-2'-deoxycytidine (DAC.We demonstrated de novo induction of NY-ESO-1 in MCF7 breast cancer cells and significantly increased expression in U266 multiple myeloma cells. This effect was time- and dose-dependent with the highest expression of NY-ESO-1 mRNA achieved by the incubation of 10 μM DAC for 72 hours. NY-ESO-1 activation was also confirmed at the protein level as shown by Western blot, flow cytometry, and immunofluorescence staining. The detection and quantification of single NY-ESO-1 peptides presented at the tumor cell surface in the context of HLA-A*0201 molecules revealed an increase of 100% and 50% for MCF7 and U266 cells, respectively. Moreover, the enhanced expression of NY-ESO-1 derived peptides at the cell surface was accompanied by an increased specific lysis of MCF7 and U266 cells by HLA-A*0201/NY-ESO-1(157-165 peptide specific chimeric antigen receptor (CAR CD8+ T cells. In addition, the killing activity of CAR T cells correlated with the secretion of higher IFN-gamma levels.These results indicate that NY-ESO-1 directed immunotherapy with specific CAR T cells might benefit from concomitant DAC treatment.

  10. Immobilization and Characterization of a New Regioselective and Enantioselective Lipase Obtained from a Metagenomic Library

    Science.gov (United States)

    Alnoch, Robson Carlos; Martini, Viviane Paula; Glogauer, Arnaldo; Costa, Allen Carolina dos Santos; Piovan, Leandro; Muller-Santos, Marcelo; de Souza, Emanuel Maltempi; de Oliveira Pedrosa, Fábio; Mitchell, David Alexander; Krieger, Nadia

    2015-01-01

    In previous work, a new lipase and its cognate foldase were identified and isolated from a metagenomic library constructed from soil samples contaminated with fat. This new lipase, called LipG9, is a true lipase that shows specific activities that are comparable to those of well-known industrially-used lipases with high activity against long-chain triglycerides. In the present work, LipG9 was co-expressed and co-immobilized with its foldase, on an inert hydrophobic support (Accurel MP1000). We studied the performance of this immobilized LipG9 (Im-LipG9) in organic media, in order to evaluate its potential for use in biocatalysis. Im-LipG9 showed good stability, maintaining a residual activity of more than 70% at 50°C after incubation in n-heptane (log P 4.0) for 8 h. It was also stable in polar organic solvents such as ethanol (log P -0.23) and acetone (log P -0.31), maintaining more than 80% of its original activity after 8 h incubation at 30°C. The synthesis of ethyl esters was tested with fatty acids of different chain lengths in n-heptane at 30 °C. The best conversions (90% in 3 h) were obtained for medium and long chain saturated fatty acids (C8, C14 and C16), with the maximum specific activity, 29 U per gram of immobilized preparation, being obtained with palmitic acid (C16). Im-LipG9 was sn-1,3-specific. In the transesterification of the alcohol (R,S)-1-phenylethanol with vinyl acetate and the hydrolysis of the analogous ester, (R,S)-1-phenylethyl acetate, Im-LipG9 showed excellent enantioselectivity for the R-isomer of both substrates (E> 200), giving an enantiomeric excess (ee) of higher than 95% for the products at 49% conversion. The results obtained in this work provide the basis for the development of applications of LipG9 in biocatalysis. PMID:25706996

  11. Immobilization and characterization of a new regioselective and enantioselective lipase obtained from a metagenomic library.

    Directory of Open Access Journals (Sweden)

    Robson Carlos Alnoch

    Full Text Available In previous work, a new lipase and its cognate foldase were identified and isolated from a metagenomic library constructed from soil samples contaminated with fat. This new lipase, called LipG9, is a true lipase that shows specific activities that are comparable to those of well-known industrially-used lipases with high activity against long-chain triglycerides. In the present work, LipG9 was co-expressed and co-immobilized with its foldase, on an inert hydrophobic support (Accurel MP1000. We studied the performance of this immobilized LipG9 (Im-LipG9 in organic media, in order to evaluate its potential for use in biocatalysis. Im-LipG9 showed good stability, maintaining a residual activity of more than 70% at 50 °C after incubation in n-heptane (log P 4.0 for 8 h. It was also stable in polar organic solvents such as ethanol (log P -0.23 and acetone (log P -0.31, maintaining more than 80% of its original activity after 8 h incubation at 30 °C. The synthesis of ethyl esters was tested with fatty acids of different chain lengths in n-heptane at 30 °C. The best conversions (90% in 3 h were obtained for medium and long chain saturated fatty acids (C8, C14 and C16, with the maximum specific activity, 29 U per gram of immobilized preparation, being obtained with palmitic acid (C16. Im-LipG9 was sn-1,3-specific. In the transesterification of the alcohol (R,S-1-phenylethanol with vinyl acetate and the hydrolysis of the analogous ester, (R,S-1-phenylethyl acetate, Im-LipG9 showed excellent enantioselectivity for the R-isomer of both substrates (E> 200, giving an enantiomeric excess (ee of higher than 95% for the products at 49% conversion. The results obtained in this work provide the basis for the development of applications of LipG9 in biocatalysis.

  12. Enantioselective degradation of alpha-cypermethrin and detection of its metabolites in bullfrog (rana catesbeiana).

    Science.gov (United States)

    Yao, Guojun; Jing, Xu; Liu, Chang; Wang, Peng; Liu, Xueke; Hou, Yinzhu; Zhou, ZhiQiang; Liu, Donghui

    2017-07-01

    Bullfrog, as a kind of amphibians, can be easily exposed to varied pollutants in the environment for the reason of its habitats and highly permeable skin. We investigated the degradation kinetics and residues of α-cypermethrin in bullfrog by two different methods of administration for the environmental monitoring the behavior of one of the most used pesticides in the amphibians. The oral administration and water exposure of α-cypermethrin on bullfrog was studied in this work. α-Cypermethrin and its main metabolites of cis-3-(2',2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA) and 3-phenoxybenzoic acid (3-PBA), which have been determined that having correlation with a number of epidemic diseases, were detected simultaneously. The method for residue analysis in the bullfrog's organs was validated. The average recoveries for α-cypermethrin were ranged from 71.7% to 100.3% and the limit of quantification was 0.005mg/kg. The average recoveries of its metabolites at levels between 0.002 and 0.5mg/kg ranged between 77.9% and 102.4% with a limit of quantification of 0.002mg/kg. Furthermore, the enantiomers of α-cypermethrin were separated on gas chromatograph (GC) equipped with a chiral column of BGB-172 and the metabolites were detected by gas chromatography (GC) after derivatization. After exposure of α-cypermethrin on bullfrog, the enantioselective degradation behavior was observed and its metabolites were detected in bullfrog tissues. The dynamic trends of α-cypermethrin and its metabolites were fitted to a two-compartment model except 3-PBA fitting to one-compartment model in skin. Concentration of α-cypermethrin and its metabolites in bullfrog's organs increased and reached an equilibrium state during water exposure of α-cypermethrin. Liver and kidney were the major organs for α-cypermethrin and its metabolites retention in both experiments. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Improvement for enantioselectivity of esterification by the change of alcohol concentration in supercritical CO{sub 2}; Arukoru nodo henka ni yoru chorinkai CO{sub 2} nai esuteruka hanno kyozotai sentakusei no kojo

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Tau-yann; Liang, Ming-tsai

    1999-07-05

    This work used Candid rugosa lipase to resolve racemic Naproxen by esterification with ethanol, n-butanol, n-hexanol, or n-decanol in supercritical CO{sub 2}. It was found that the lipase enantioselectively esterified S-Naproxen within all systems. The enantiomeric ratio increased four folds by slightly decreasing the alcohol concentration. The effect of the alcohol concentration on the enantioselectivity was greater than that of changing acyl acceptors. (author)

  14. Enantioselective syntheses of sulfoxides in octahedral ruthenium(II) complexes via a chiral-at-metal strategy.

    Science.gov (United States)

    Li, Zheng-Zheng; Wen, A-Hao; Yao, Su-Yang; Ye, Bao-Hui

    2015-03-16

    The preparation of chiral 2-(alkylsulfinyl)phenol compounds by enantioselective coordination-oxidation of the thioether ruthenium complexes with a chiral-at-metal strategy has been developed. The enantiomerically pure sulfoxide complexes Δ-[Ru(bpy)2{(R)-LO-R}](PF6) (bpy is 2,2'-bipyridine, HLO-R is 2-(alkylsulfinyl)phenol, R = Me (Δ-1a), Et (Δ-2a), iPr (Δ-3a), Bn (Δ-4a), and Nap (Δ-5a)) and Λ-[Ru(bpy)2{(S)-LO-R}](PF6) (R = Me (Λ-1a), Et (Λ-2a), iPr (Λ-3a), Bn (Λ-4a), and Nap (Λ-5a)) have been synthesized by the reaction of Δ-[Ru(bpy)2(py)2](2+) or Λ-[Ru(bpy)2(py)2](2+) with the prochiral thioether ligands 2-(alkylthio)phenol (HL-R), followed by enantioselective oxidation with m-CPBA as oxidant. The X-ray crystallography was used to verify the stereochemistry of ruthenium complexes and sulfur atoms. The configurations of the ruthenium complexes are stable during the coordination and oxidation reactions. Moreover, the chiral sulfoxide ligands are enantioselectively generated by controlling of the configuration of ruthenium centers in the course of oxidation reaction. That is, the Λ configuration at the ruthenium center generates the S sulfoxide ligand; on the contrary, the Δ configuration of the ruthenium complex originates the R sulfoxide ligand. Acidolysis of Λ-[Ru(bpy)2{(R)-LO-R}](PF6) and Δ-[Ru(bpy)2{(S)-LO-R}](PF6) complexes in the presence of TFA-MeCN afforded the chiral ligands (R)-HLO-R and (S)-HLO-R in 96-99% ee values, respectively. Importantly, the chiral ruthenium complexes can be recycled as Δ/Λ-[Ru(bpy)2(MeCN)2](PF6)2 and reused in a next reaction cycle with complete retention of the configurations at ruthenium centers.

  15. Aza-Riley Oxidation of Ugi-Azide and Ugi-3CR Products toward Vicinal Tricarbonyl Amides: Two-Step MCR-Oxidation Methodology Accessing Functionalized α,β-Diketoamides and α,β-Diketotetrazoles.

    Science.gov (United States)

    Foley, Christopher; Shaw, Arthur; Hulme, Christopher

    2018-03-02

    Direct oxidative deamination of glyoxal-derived Ugi-azide and Ugi three-component reaction products readily affords vicinal tricarbonyls (α,β-diketoamides) and α,β-diketotetrazoles with two diversity elements. This significant extension of our previously described multicomponent reaction-oxidative deamination methodology is proposed to proceed through a mechanistically distinct SeO 2 -mediated C-N oxidation derived from an active enol of α-amino-β-ketone systems, effectively an aza-Riley oxidation. This methodology accesses diverse VTC systems from prototypical amines, glyoxaldehydes, and isocyanide building blocks in a mere two steps.

  16. Effects of supercritical fluid chromatography conditions on enantioselectivity and performance of polyproline-derived chiral stationary phases.

    Science.gov (United States)

    Novell, Arnau; Méndez, Alberto; Minguillón, Cristina

    2015-07-17

    The chromatographic behaviour and performance of four polyproline-derived chiral stationary phases (CSPs) were tested using supercritical fluid chromatography (SFC). A series of structurally related racemic compounds, whose enantioseparation was proved to be sensitive to the type of mobile phase used in NP-HPLC, were chosen to be tested in the SFC conditions. Good enantioselection ability was shown by the CSPs for the analytes tested in the new conditions. Resolution, efficiency and analysis time, were considerably improved with respect to NP-HPLC when CO2/alcohol mobile phases were used. Monolithic columns clearly show enhanced chromatographic parameters and improved performance respect to their bead-based counterparts. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Enantioselective endocrine disrupting effects of omeprazole studied in the H295R cell assay and by molecular modeling

    DEFF Research Database (Denmark)

    Sørensen, Amalie Møller; Hansen, Cecilie Hurup; Bonomo, Silvia

    2016-01-01

    -OME) and R-omeprazole (R-OME) in CYP17A1, CYP19A1 and CYP21A2 were carried out. Exposing H295R cells to OME and its enantiomers resulted in an increase of progesterone (PRO) and 17α-hydroxy-progesterone (OH-PRO) levels. At the same time, a decrease in the corticosteroid and androgen synthesis was observed...... of the heme for S-OME in CYP17A1 and S- and R-OME in CYP21A2. However, density functional theory calculations suggest that the direct N-Fe interaction is weak. The study demonstrates enantioselective differences in the endocrine disrupting potential of chiral drugs such as omeprazole. These findings may have...

  18. Barbier-type anti-Diastereo- and Enantioselective Synthesis of β-Trimethylsilyl, Fluorinated Methyl, Phenylthio Homoallylic Alcohols.

    Science.gov (United States)

    Guo, Rui; Yang, Qin; Tian, Qinshan; Zhang, Guozhu

    2017-07-07

    Catalytic Asymmetric allylation of aldehydes with functionalized allylic reagents represents an important process in synthetic organic chemistry because the resulting chiral homoallylic alcohols are valuable building blocks in diverse research fields. Despite the obvious advantages of allyl halides as allylation reagent under Barbier-type conditions, catalytic asymmetric version using functionalized allyl halides remains largely underdeveloped. Here, we addressed this issue by employing a chromium-catalysis system. The use of readily available allyl bromides with γ substitutions including trimethylsilyl, fluorinated methyl and phenylthio groups provided an efficient and convenient method to introduce those privileged functionalities into homoallylic alcohols. Good yields, high anti-diastereo- and excellent enantioselectivities were achieved under mild reaction conditions.

  19. Enantioselective cascade reactions of stable sulfur ylides and nitroolefins through an axial-to-central chirality transfer strategy.

    Science.gov (United States)

    Lu, Liang-Qiu; Ming, Zhi-Hui; An, Jing; Li, Chao; Chen, Jia-Rong; Xiao, Wen-Jing

    2012-01-20

    An enantioselective [4 + 1] annulation/rearrangement cascade of stable sulfur ylides and nitroolefins has been developed through an efficient axial-to-central chirality transfer with the use of a chiral BINOL-derived sulfide as a reliable stereocontroller. It can provide pharmaceutically and synthetically important oxazolidinones in high stereoselectivities (up to 96:4 e.r. and >95:5 d.r.). Moreover, this strategy was also successfully applied to the asymmetric [4 + 1]/[3 + 2] cycloaddition cascade of sulfur ylides with alkene-tethered nitroolefins, and the corresponding enantioenriched fused heterocycles (up to 87:13 e.r. and >95:5 d.r.) were obtained in good to excellent yields (54-95% yields).

  20. Regio- and Enantioselective Photodimerization within the Confined Space of a Homochiral Ruthenium/Palladium Heterometallic Coordination Cage.

    Science.gov (United States)

    Guo, Jing; Xu, Yao-Wei; Li, Kang; Xiao, Li-Min; Chen, Sha; Wu, Kai; Chen, Xu-Dong; Fan, Yan-Zhong; Liu, Jun-Min; Su, Cheng-Yong

    2017-03-27

    The photoinduced regio- and enantioselective coupling of naphthols and derivatives thereof is achieved in the confined chiral coordination space of a Ru II metalloligand based cage. The racemic or enantiopure cages encapsulate naphthol guests, which then undergo a regiospecific 1,4-coupling, rather than the normal 1,1-coupling, to form 4-(2-hydroxy-1-naphthyl)-1,2-napthoquinones; moderate stereochemical control is achieved with homochiral cages. The photoreactions proceed under both aerobic and anaerobic conditions but through distinct pathways that nevertheless involve the same radical intermediates. This unusual dimerization constitutes a very rare example of asymmetric induction in biaryl coupling by making use of coordination cages with dual functionality-photoredox reactivity and stereoselectivity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.