Bicyclic Guanidine Catalyzed Asymmetric Tandem Isomerization Intramolecular-Diels-Alder Reaction: The First Catalytic Enantioselective Total Synthesis of (+)-alpha-Yohimbine.

Science.gov (United States)

Feng, Wei; Jiang, Danfeng; Kee, Choon-Wee; Liu, Hongjun; Tan, Choon-Hong

2016-02-04

Hydroisoquinoline derivatives were prepared in moderate to good enantioselectivities via a bicyclic guanidine-catalyzed tandem isomerization intramolecular-Diels-Alder (IMDA) reaction of alkynes. With this synthetic method, the first enantioselective synthesis of (+)-alpha-yohimbine was completed in 9 steps from the IMDA products. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

An iron/amine-catalyzed cascade process for the enantioselective functionalization of allylic alcohols.

Science.gov (United States)

Quintard, Adrien; Constantieux, Thierry; Rodriguez, Jean

2013-12-02

Three is a lucky number: An enantioselective transformation of allylic alcohols into β-chiral saturated alcohols has been developed by combining two distinct metal- and organocatalyzed catalytic cycles. This waste-free triple cascade process merges an iron-catalyzed borrowing-hydrogen step with an aminocatalyzed nucleophilic addition reaction. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Proton-Switchable Bifunctional Ruthenium Complex That Catalyzes Nitrile Hydroboration.

Science.gov (United States)

Geri, Jacob B; Szymczak, Nathaniel K

2015-10-14

A new bifunctional pincer ligand framework bearing pendent proton-responsive hydroxyl groups was prepared and metalated with Ru(II) and subsequently isolated in four discrete protonation states. Stoichiometric reactions with H2 and HBPin showed facile E-H (E = H or BPin) activation across a Ru(II)-O bond, providing access to unusual Ru-H species with strong interactions with neighboring proton and boron atoms. These complexes were found to promote the catalytic hydroboration of ketones and nitriles under mild conditions, and the activity was highly dependent on the ligand's protonation state. Mechanistic experiments revealed a crucial role of the pendent hydroxyl groups for catalytic activity.

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.

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.

Regio-, Diastereo-, and Enantioselective Nitroso-Diels-Alder Reaction of 1,3-Diene-1-carbamates Catalyzed by Chiral Phosphoric Acids.

Science.gov (United States)

Pous, Jonathan; Courant, Thibaut; Bernadat, Guillaume; Iorga, Bogdan I; Blanchard, Florent; Masson, Géraldine

2015-09-23

Chiral phosphoric acid-catalyzed asymmetric nitroso-Diels-Alder reaction of nitrosoarenes with carbamate-dienes afforded cis-3,6-disubstituted dihydro-1,2-oxazines in high yields with excellent regio-, diastereo-, and enantioselectivities. Interestingly, we observed that the catalyst is able not only to control the enantioselectivity but also to reverse the regioselectivity of the noncatalyzed nitroso-Diels-Alder reaction. The regiochemistry reversal and asynchronous concerted mechanism were confirmed by DFT calculations.

Rhodium-catalyzed chemo-, regio-, and enantioselective addition of 2-pyridones to terminal allenes.

Science.gov (United States)

Li, Changkun; Kähny, Matthias; Breit, Bernhard

2014-12-08

A rhodium-catalyzed chemo-, regio-, and enantioselective addition of 2-pyridones to terminal allenes to give branched N-allyl 2-pyridones is reported. Preliminary mechanistic studies support the hypothesis that the reaction was initiated from the more acidic 2-hydroxypyridine form, and the initial kinetic O-allylation product was finally converted into the thermodynamically more stable N-allyl 2-pyridones. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Science.gov (United States)

Stanley, Levi M.

2010-01-01

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

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.

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

Science.gov (United States)

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

2018-03-07

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

Cu-Catalyzed Asymmetric Allylic Alkylation of Phosphonates and Phosphine Oxides with Grignard Reagents

NARCIS (Netherlands)

Hornillos, Valentin; Perez, Manuel; Fananas-Mastral, Martin; Feringa, Ben L.

An efficient and highly enantioselective copper-catalyzed allylic alkylation of phosphonates and phosphine oxides with Grignard reagents and Taniaphos or phosphoramidites as chiral ligands is reported. Transformation of these products leads to a variety of new phosphorus-containing chiral

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

Science.gov (United States)

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

2001-05-01

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

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.

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

Science.gov (United States)

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

2016-05-04

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

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

Science.gov (United States)

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

2014-02-14

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

A Mechanistic Study of Hydroboration of 1-Octene with 1,3,2 ...

African Journals Online (AJOL)

NJD

... on hydroboration.9,10. Thaisrivongs et al.8 reported hydroboration of a range of alkenes ... low temperature, a good 65 % yield was obtained (Entry 7). Maintaining the ... method, borane-dimethyl sulphide complex reacted with an equimolar ...

Enantioselective Copper-Catalyzed Oxy-Alkynylation of Diazo Compounds.

Science.gov (United States)

Hari, Durga Prasad; Waser, Jerome

2017-06-28

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

Palladium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to Five-, Six-, and Seven-Membered β-Substituted Cyclic Enones: Enantioselective Construction of All-Carbon Quaternary Stereocenters

KAUST Repository

Kikushima, Kotaro; Holder, Jeffrey C.; Gatti, Michele; Stoltz, Brian M.

2011-01-01

The first enantioselective Pd-catalyzed construction of all-carbon quaternary stereocenters via 1,4-addition of arylboronic acids to β-substituted cyclic enones is reported. Reaction of a wide range of arylboronic acids and cyclic enones using a

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.

Copper(II)-catalyzed exo and enantioselective cycloadditions of azomethine imines.

Science.gov (United States)

Sibi, Mukund P; Rane, Digamber; Stanley, Levi M; Soeta, Takahiro

2008-07-17

A strategy for exo and enantioselective 1,3-dipolar cycloaddition of azomethine imines to 2-acryloyl-3-pyrazolidinone is described. The corresponding cycloadducts are isolated with high diastereoselectivities (up to >96:4 exo/endo) and enantioselectivities (up to 98% ee).

Theoretical study on the reaction mechanisms of Michael chirality addition between propionaldehyde and nitroalkene catalyzed by an enantioselective catalyst.

Science.gov (United States)

Zhou, Xinming; Li, Ling; Sun, Xuejun; Wang, Yajun; Du, Dongmei; Fu, Hui

2018-06-01

The asymmetric Michael addition between propionaldehyde and nitroalkene catalyzed by 8-(ethoxycarbonyl)-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylic acid has obtained relatively high yields and excellent enantioselectivities at room temperature. In this study, the molecular structures and optical activity of the most stable conformation I are optimized at B3LYP/6-311++ G(d,p) level. We find that levorotatory conformation I catalyzing the same Michael addition can produce laevo-product A and dextrorotatory conformation I' can obtain the dextral-product A'. These results have guiding significance for further studying on the new chemzymes and the mechanism of the obtained different chiral products. © 2018 Wiley Periodicals, Inc.

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

Science.gov (United States)

Souillart, Laetitia; Cramer, Nicolai

2014-09-01

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

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

Science.gov (United States)

Wang, Chuan; Yamamoto, Hisashi

2015-04-08

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

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.

One-Pot Synthesis of Novel Chiral β-Amino Acid Derivatives by Enantioselective Mannich Reactions Catalyzed by Squaramide Cinchona Alkaloids

Directory of Open Access Journals (Sweden)

Kankan Zhang

2013-05-01

Full Text Available An efficient one-pot synthesis of novel β-amino acid derivatives containing a thiadiazole moiety was developed using a chiral squaramide cinchona alkaloid as organocatalyst. The reactions afforded chiral β-amino acid derivatives in moderate yields and with moderate to excellent enantioselectivities. The present study demonstrated for the first time the use of a Mannich reaction catalyzed by a chiral bifunctional organocatalyst for the one-pot synthesis of novel β-amino acid derivatives bearing a 1,3,4-thiadiazole moiety on nitrogen.

Ruthenium Catalyzed Diastereo- and Enantioselective Coupling of Propargyl Ethers with Alcohols: Siloxy-Crotylation via Hydride Shift Enabled Conversion of Alkynes to π-Allyls.

Science.gov (United States)

Liang, Tao; Zhang, Wandi; Chen, Te-Yu; Nguyen, Khoa D; Krische, Michael J

2015-10-14

The first enantioselective carbonyl crotylations through direct use of alkynes as chiral allylmetal equivalents are described. Chiral ruthenium(II) complexes modified by Josiphos (SL-J009-1) catalyze the C-C coupling of TIPS-protected propargyl ether 1a with primary alcohols 2a-2o to form products of carbonyl siloxy-crotylation 3a-3o, which upon silyl deprotection-reduction deliver 1,4-diols 5a-5o with excellent control of regio-, anti-diastereo-, and enantioselectivity. Structurally related propargyl ethers 1b and 1c bearing ethyl- and phenyl-substituents engage in diastereo- and enantioselective coupling, as illustrated in the formation of adducts 5p and 5q, respectively. Selective mono-tosylation of diols 5a, 5c, 5e, 5f, 5k, and 5m is accompanied by spontaneous cyclization to deliver the trans-2,3-disubstituted furans 6a, 6c, 6e, 6f, 6k, and 6m, respectively. Primary alcohols 2a, 2l, and 2p were converted to the siloxy-crotylation products 3a, 3l, and 3p, which upon silyl deprotection-lactol oxidation were transformed to the trans-4,5-disubstituted γ-butyrolactones 7a, 7l, and 7p. The formation of 7p represents a total synthesis of (+)-trans-whisky lactone. Unlike closely related ruthenium catalyzed alkyne-alcohol C-C couplings, deuterium labeling studies provide clear evidence of a novel 1,2-hydride shift mechanism that converts metal-bound alkynes to π-allyls in the absence of intervening allenes.

Au-Cu core-shell nanocube-catalyzed click reactions for efficient synthesis of diverse triazoles.

Science.gov (United States)

Madasu, Mahesh; Hsia, Chi-Fu; Huang, Michael H

2017-06-01

Au-Cu core-shell nanocubes and octahedra synthesized in aqueous solution were employed to catalyze a 1,3-dipolar cycloaddition reaction between phenylacetylene and benzyl azide in water at 50 °C for 3 h. Interestingly, the nanocubes were far more efficient in catalyzing this reaction, giving 91% yield of a regioselective 1,4-triazole product, while octahedra only recorded 46% yield. The Au-Cu nanocubes were subsequently employed to catalyze the click reaction between benzyl azide and a broad range of aromatic and aliphatic alkynes. The product yields ranged from 78 to 99%. Clearly the Au-Cu cubes exposing {100} surfaces are an excellent and green catalyst for click reactions.

Nickel(0)-catalyzed enantioselective annulations of alkynes and arylenoates enabled by a chiral NHC ligand: efficient access to cyclopentenones.

Science.gov (United States)

Ahlin, Joachim S E; Donets, Pavel A; Cramer, Nicolai

2014-11-24

Cyclopentenones are versatile structural motifs of natural products as well as reactive synthetic intermediates. The nickel-catalyzed reductive [3+2] cycloaddition of α,β-unsaturated aromatic esters and alkynes constitutes an efficient method for their synthesis. Here, nickel(0) catalysts comprising a chiral bulky C1-symmetric N-heterocyclic carbene ligand were shown to enable an efficient asymmetric synthesis of cyclopentenones from mesityl enoates and internal alkynes under mild conditions. The bulky NHC ligand provided the cyclopentenone products in very high enantioselectivity and led to a regioselective incorporation of unsymmetrically substituted alkynes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Supported Single-Site Ti(IV) on a Metal–Organic Framework for the Hydroboration of Carbonyl Compounds

Energy Technology Data Exchange (ETDEWEB)

Huang, Zhiyuan [College; amp, Molecular Sciences, Institute of Advanced Studies, Wuhan University, Wuhan 430072, PR China; Chemical; amp, Engineering Division, Argonne National Laboratory, Lemont, Illinois 60439, United States; Liu, Dong [College; amp, Molecular Sciences, Institute of Advanced Studies, Wuhan University, Wuhan 430072, PR China; Chemical; amp, Engineering Division, Argonne National Laboratory, Lemont, Illinois 60439, United States; Camacho-Bunquin, Jeffrey [Chemical; amp, Engineering Division, Argonne National Laboratory, Lemont, Illinois 60439, United States; Zhang, Guanghui [Department; Yang, Dali [College; amp, Molecular Sciences, Institute of Advanced Studies, Wuhan University, Wuhan 430072, PR China; Chemical; amp, Engineering Division, Argonne National Laboratory, Lemont, Illinois 60439, United States; López-Encarnación, Juan M. [Chemical; amp, Engineering Division, Argonne National Laboratory, Lemont, Illinois 60439, United States; Department; Xu, Yunjie [Department; Ferrandon, Magali S. [Chemical; amp, Engineering Division, Argonne National Laboratory, Lemont, Illinois 60439, United States; Niklas, Jens [Chemical; amp, Engineering Division, Argonne National Laboratory, Lemont, Illinois 60439, United States; Poluektov, Oleg G. [Chemical; amp, Engineering Division, Argonne National Laboratory, Lemont, Illinois 60439, United States; Jellinek, Julius [Chemical; amp, Engineering Division, Argonne National Laboratory, Lemont, Illinois 60439, United States; Lei, Aiwen [College; amp, Molecular Sciences, Institute of Advanced Studies, Wuhan University, Wuhan 430072, PR China; Chemical; amp, Engineering Division, Argonne National Laboratory, Lemont, Illinois 60439, United States; Bunel, Emilio E. [Chemical; amp, Engineering Division, Argonne National Laboratory, Lemont, Illinois 60439, United States; Delferro, Massimiliano [Chemical; amp, Engineering Division, Argonne National Laboratory, Lemont, Illinois 60439, United States

2017-10-10

ABSTRACT: A stable and structurally well-defined titanium alkoxide catalyst supported on a metal-organic-framework (MOF) of UiO-67 topology (ANL1-Ti(OiPr)2) was synthesized and fully characterized by a variety of analytical and spectroscopic techniques, including BET, TGA, PXRD, XAS, DRIFT, SEM, and DFT computations. The Ti-functionalized MOF was demonstrated active for the catalytic hydroboration of a wide range of aldehydes and ketones with HBpin as the boron source. Compared to traditional homogeneous and supported hydroboration catalysts, ANL1-Ti(OiPr)2 is completely recyclable and reusable, making it a promising hydroboration catalyst alternative for green and sustainable chemical synthesis. DFT calculations suggest that the catalytic hydroboration proceeds via a (1) hydride transfer between the active Ti-hydride species and a carbonyl moiety (rate determining step), and (2) alkoxide transfer (intramolecular σ-bond metathesis) to generate the boronate ester product.

Cu(OAc)2 catalyzed Sonogashira cross-coupling reaction in amines

Institute of Scientific and Technical Information of China (English)

Sheng Mei Guo; Chen Liang Deng; Jin Heng Li

2007-01-01

A simple Cu(OAc)2 catalyzed Sonogashira coupling protocol is presented. It was found that the couplings of a variety of aryl halides with terminal alkynes were conducted smoothly to afford the corresponding desired products in moderate to excellent yields, using Cu(OAc)2 as the catalyst and Et3N as the solvent.

Development of Copper-Catalyzed Electrophilic Trifluoromethylation and Exploiting Cu/Cu2O Nanowires with Novel Catalytic Reactivity

KAUST Repository

Li, Huaifeng

2014-06-01

This thesis is based on research in Cu-catalyzed electrophilic trifluoromethylation and exploiting Cu/Cu2O nanowires with novel catalytic reactivity for developing of catalytic and greener synthetic methods. A large number of biological active pharmaceuticals and agrochemicals contain fluorine substituents (-F) or trifluoromethyl groups (-CF3) because these moieties often result in profound changes of their physical, chemical, and biological properties, such as metabolic stability and lipophilicity. For this reason, the introduction of fluorine or trifluoromethyl groups into organic molecules has attracted intensive attention. Among them, transition metal-catalyzed trifluoromethylation reactions has proved to be an efficient and reliable strategy to construct carbon-fluorine (C-F) and carbontrifluoromethyl (C-CF3) bond. We have developed a catalytic process for the first time for trifluoromethylation of terminal alkynes with Togni’s reagent, affording trifluoromethylated acetylenes in good to excellent yields. The reaction is conducted at room temperature and exhibits tolerance to a range of functional groups. Derived from this discovery, the extension of work of copper catalyzed electrophilic trifluoromethylation were investigated which include the electrophilic trifluoromethylation of arylsulfinate salts and electrophilic trifluoromethylation of organotrifluoroborates. Because of growing environmental concern, the development of greener synthetic methods has drawn much attention. Nano-sized catalysts are environment-friendly and an attractive green alternative to the conventional homogeneous catalysts. The nano-sized catalysts can be easily separated from the reaction mixture due to their insolubility and thus they can be used recycled. Notably, because of the high reactivities of nano-sized metal catalysts, the use of ligands can be avoided and the catalysts loadings can be reduced greatly. Moreover, the nano-sized catalysts can increase the exposed surface

The mechanism of transition-metal (Cu or Pd)-catalyzed synthesis of benzimidazoles from amidines: theoretical investigation.

Science.gov (United States)

Li, Juan; Gu, Honghong; Wu, Caihong; Du, Lijuan

2014-11-28

In this study, the Cu(OAc)2- and [PdCl2(PhCN)2]-catalyzed syntheses of benzimidazoles from amidines were theoretically investigated using density functional theory calculations. For the Cu-catalyzed system, our calculations supported a four-step-pathway involving C-H activation of an arene with Cu(II) via concerted metalation-deprotonation (CMD), followed by oxidation of the Cu(II) intermediate and deprotonation of the imino group by Cu(III), and finally reductive elimination from Cu(III). In our calculations, the barriers for the CMD step and the oxidation step are the same. The results are different from the ones reported by Fu et al. in which the whole reaction mechanism includes three steps and the CMD step is rate determining. On the basis of the calculation results for the [PdCl2(PhCN)2]-catalyzed system, C-H bond breaking by CMD occurs first, followed by the rate-determining C-N bond formation and N-H deprotonation. Pd(III) species is not involved in the [PdCl2(PhCN)2]-catalyzed syntheses of benzimidazoles from amidines.

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.

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

Science.gov (United States)

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

2008-01-01

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

Enantioselective rhodium enolate protonations. A new methodology for the synthesis of beta2-amino acids.

Science.gov (United States)

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

2005-06-23

[reaction: see text] Rhodium-catalyzed conjugate addition of an aryl boronic acid to alpha-methylamino acrylates followed by enantioselective protonation of the oxa-pi-allylrhodium intermediate provides access to aryl-substituted beta(2)-amino acids. The impact of the different variables of the reaction on the levels of enantioselectivity has been assessed.

Kinetic mechanism and enantioselectivity of halohydrin dehalogenase from Agrobacterium radiobacter

NARCIS (Netherlands)

Tang, Lixia; Lutje Spelberg, Jeffrey H.; Fraaije, Marco W.; Janssen, DB

2003-01-01

Halohydrin dehalogenase (HheC) from Agrobacterium radiobacter AD1 catalyzes the reversible intramolecular nucleophilic displacement of a halogen by a hydroxyl group in vicinal haloalcohols, producing the corresponding epoxides. The enzyme displays high enantioselectivity toward some aromatic

CO2 as a C1-organic building block: Enantioselective electrocarboxylation of aromatic ketones with CO2catalyzed by cinchona alkaloids under mild conditions

International Nuclear Information System (INIS)

Chen, Bao-Li; Tu, Zhuo-Ying; Zhu, Hong-Wei; Sun, Wen-Wen; Wang, Huan; Lu, Jia-Xing

2014-01-01

Highlights: •Cinchona alkaloids catalysis achieve enantioselective electrocarboxylation of racemic aromatic ketones. •The applications of CO 2 enantioselective electrochemical fixation into optically active hydroxyl carboxylic acids have been expanded. •The applications of alkaloids have been expanded. •The applications of asymmetric synthesis by electrochemical methodology have been expanded. -- Abstract: The enantioselective electrocarboxylation of pro-chiral aromatic ketones (2-acetonaphthone, 1-(6-methoxy-2-naphthyl)ethanone, 1-(4-methoxy-1-naphthyl)ethanone) with atmospheric pressure of CO 2 catalyzed by cinchona alkaloids in the presence of phenol was investigated in an undivided cell for the first time to give optically active 2-hydroxy-2-arylpropionic acid. For the model compound 2-acetonaphthone, the influence of various reaction conditions, such as cathode material, current density, catalyst type, ratio of proton to catalyst and catalyst quantity, on the enantiomeric excesses (ee) and yield has been investigated. Under the optimized conditions of 2-acetonaphthone, all the aromatic ketones examined are converted into corresponding optically active 2-hydroxy-2-arylpropionic acids in moderate yield (32.2% - 41.3%) and ee (48.1% - 48.6%). In addition, the electrochemical behavior of 2-acetonaphthone has been studied by cyclic voltammetry (CV) in the absence and presence of CO 2 . Moreover, the probable reaction pathway was proposed accordingly

Palladium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to Five-, Six-, and Seven-Membered β-Substituted Cyclic Enones: Enantioselective Construction of All-Carbon Quaternary Stereocenters

KAUST Repository

Kikushima, Kotaro

2011-05-11

The first enantioselective Pd-catalyzed construction of all-carbon quaternary stereocenters via 1,4-addition of arylboronic acids to β-substituted cyclic enones is reported. Reaction of a wide range of arylboronic acids and cyclic enones using a catalyst prepared from Pd(OCOCF(3))(2) and a chiral pyridinooxazoline ligand yields enantioenriched products bearing benzylic stereocenters. Notably, this transformation is tolerant to air and moisture, providing a practical and operationally simple method of synthesizing enantioenriched all-carbon quaternary stereocenters.

Enantioselective cycloadditions with alpha,beta-disubstituted acrylimides.

Science.gov (United States)

Sibi, Mukund P; Ma, Zhihua; Itoh, Kennosuke; Prabagaran, Narayanasamy; Jasperse, Craig P

2005-06-09

[reaction: see text] The use of N-H imide templates provides a solution to the problem of rotamer control in Lewis acid catalyzed reactions of alpha,beta-disubstituted acryloyl imides. Reactions proceed through the s-cis rotamer and with improved reactivity because A(1,3) strain is avoided. Enantioselective nitrone, nitrile oxide, and Diels-Alder cycloadditions demonstrate the principle.

CuO-Nanoparticles Catalyzed Synthesis of 1,4-Disubstituted-1,2,3 ...

Indian Academy of Sciences (India)

John Paul Raj

2018-04-13

Apr 13, 2018 ... has been developed for the synthesis of 1,2,3-triazoles. A library of 1 ... Kuang et al., described Cu-catalyzed synthesis of 1H-. 1,2,3-triazoles from 1 ..... Tornøe C W, Christensen C and Meldal M 2002 Peptido- triazoles on solid ... 2015 Copper-catalyzed [3+2] cycloaddition/oxidation reactions between ...

Hydroboration of Graphene Oxide: Towards Stoichiometric Graphol and Hydroxygraphane

Czech Academy of Sciences Publication Activity Database

Poh, H. L.; Sofer, Z.; Šimek, P.; Tomandl, Ivo; Pumera, M.

2015-01-01

Roč. 21, č. 22 (2015), s. 8130-8136 ISSN 0947-6539 R&D Projects: GA ČR(CZ) GA15-09001S; GA MŠk LM2011019 Institutional support: RVO:61389005 Keywords : boranes * electrochemistry * graphene * hydroboration * synthetic methods Subject RIV: CA - Inorganic Chemistry Impact factor: 5.771, year: 2015

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.

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

Science.gov (United States)

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

2016-03-24

Highly enantioselective additions of arylboroxines to simple aryl ketones have been achieved for the first time with a Rh/(R,R,R,R)-WingPhos catalyst, thus providing a range of chiral diaryl alkyl carbinols with excellent ee values and yields. (R,R,R,R)-WingPhos has been proven to be crucial for the high reactivity and enantioselectivity. The method has enabled a new, concise, and enantioselective synthesis of the antidepressant drug escitalopram. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Exploring asymmetric catalytic transformations

NARCIS (Netherlands)

Guduguntla, Sureshbabu

2017-01-01

In Chapter 2, we report a highly enantioselective synthesis of β-alkyl-substituted alcohols through a one-pot Cu- catalyzed asymmetric allylic alkylation with organolithium reagents followed by reductive ozonolysis. The synthesis of γ-alkyl-substituted alcohols was also achieved through Cu-catalyzed

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

Science.gov (United States)

Sharma, Ankit; Hartwig, John F

2013-11-27

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

Enantioselective 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.

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

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).

Highly Enantioselective Construction of Tertiary Thioethers and Alcohols via Phosphine-Catalyzed Asymmetric γ-Addition reactions of 5H-Thiazol-4-ones and 5H-Oxazol-4-ones: Scope and Mechanistic Understandings

KAUST Repository

Wang, Tianli

2015-06-02

Phosphine-catalyzed highly enantioselective γ-additions of 5H-thiazol-4-ones and 5H-oxazol-4-ones to allenoates have been developed for the first time. With the employment of amino-acid derived bifunctional phosphines, a wide range of substituted 5H-thiazol-4-one and 5H-oxazol-4-one derivatives bearing heteroarom (S or O)-containing tertiary chiral centers were constructed in high yields and excellent enantioselectivities. The reported method provides a facile access to enantioenriched tertiary thioether/alcohols. The mechanism of γ-addition reaction was investigated by performing DFT calculations, and the hydrogen bonding interactions between the Brønsted acid moiety of the phosphine catalysts and the “C=O” unit of donor molecules were shown to be crucial in asymmetric induction.

Highly Enantioselective Construction of Tertiary Thioethers and Alcohols via Phosphine-Catalyzed Asymmetric γ-Addition reactions of 5H-Thiazol-4-ones and 5H-Oxazol-4-ones: Scope and Mechanistic Understandings

KAUST Repository

Wang, Tianli; Yu, Zhaoyuan; Hoon, Ding Long; Huang, Kuo-Wei; Lan, Yu; Lu, Yixin

2015-01-01

Phosphine-catalyzed highly enantioselective γ-additions of 5H-thiazol-4-ones and 5H-oxazol-4-ones to allenoates have been developed for the first time. With the employment of amino-acid derived bifunctional phosphines, a wide range of substituted 5H-thiazol-4-one and 5H-oxazol-4-one derivatives bearing heteroarom (S or O)-containing tertiary chiral centers were constructed in high yields and excellent enantioselectivities. The reported method provides a facile access to enantioenriched tertiary thioether/alcohols. The mechanism of γ-addition reaction was investigated by performing DFT calculations, and the hydrogen bonding interactions between the Brønsted acid moiety of the phosphine catalysts and the “C=O” unit of donor molecules were shown to be crucial in asymmetric induction.

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.

Ultrasound-Assisted Enantioselective Esterification of Ibuprofen Catalyzed by a Flower-Like Nanobioreactor

Directory of Open Access Journals (Sweden)

Baiyi An

2016-04-01

Full Text Available A flower-like nanobioreactor was prepared for resolution of ibuprofen in organic solvents. Ultrasound irradiation has been used to improve the enzyme performance of APE1547 (a thermophilic esterase from the archaeon Aeropyrum pernix K1 in the enantioselective esterification. Under optimum reaction conditions (ultrasound power, 225 W; temperature, 45 °C; water activity, 0.21, the immobilized APE1547 showed an excellent catalytic performance (enzyme activity, 13.26 μmol/h/mg; E value, 147.1. After ten repeated reaction batches, the nanobioreactor retained almost 100% of its initial enzyme activity and enantioselectivity. These results indicated that the combination of the immobilization method and ultrasound irradiation can enhance the enzyme performance dramatically.

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.

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.

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

KAUST Repository

Borrmann, Ruediger; Knop, Nils; Rueping, Magnus

2016-01-01

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

Flexible Enantioselectivity of Tryptophanase Attributable to Benzene Ring in Heterocyclic Moiety of D-Tryptophan

Directory of Open Access Journals (Sweden)

Akihiko Shimada

2012-05-01

Full Text Available The invariance principle of enzyme enantioselectivity must be absolute because it is absolutely essential to the homochiral biological world. Most enzymes are strictly enantioselective, and tryptophanase is one of the enzymes with extreme absolute enantioselectivity for L-tryptophan. Contrary to conventional knowledge about the principle, tryptophanase becomes flexible to catalyze D-tryptophan in the presence of diammonium hydrogenphosphate. Since D-amino acids are ordinarily inert or function as inhibitors even though they are bound to the active site, the inhibition behavior of D-tryptophan and several inhibitors involved in this process was examined in terms of kinetics to explain the reason for this flexible enantioselectivity in the presence of diammonium hydrogenphosphate. Diammonium hydrogenphosphate gave tryptophanase a small conformational change so that D-tryptophan could work as a substrate. As opposed to other D-amino acids, D-tryptophan is a very bulky amino acid with a benzene ring in its heterocyclic moiety, and so we suggest that this structural feature makes the catalysis of D-tryptophan degradation possible, consequently leading to the flexible enantioselectivity. The present results not only help to understand the mechanism of enzyme enantioselectivity, but also shed light on the origin of homochirality.

A Mechanistic Study of Hydroboration of 1-Octene with 1,3,2 ...

African Journals Online (AJOL)

dithiaborinane in their ground states have been studied using density functional theory (DFT) at the B3LYP/3-21+G and B3LYP/6-31+G(d) levels. Hydroboration and disproportionation transition states have been determined and activation energies ...

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.

Highly selective cobalt-catalyzed hydrovinylation of styrene

NARCIS (Netherlands)

Grutters, M.M.P.; Müller, C.; Vogt, D.

2006-01-01

The hydrovinylation reaction is a codimerization of a 1,3-diene or vinyl arene and ethene with great potential for fine chemicals and pharmaceuticals. For the first time, enantioselective cobalt-catalyzed hydrovinylations of styrene were achieved with a cobalt-based system bearing a chiral

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).

Preparative and mechanistic studies toward the rational development of catalytic, enantioselective selenoetherification reactions.

Science.gov (United States)

Denmark, Scott E; Kalyani, Dipannita; Collins, William R

2010-11-10

A systematic investigation into the Lewis base catalyzed, asymmetric, intramolecular selenoetherification of olefins is described. A critical challenge for the development of this process was the identification and suppression of racemization pathways available to arylseleniranium ion intermediates. This report details a thorough study of the influences of the steric and electronic modulation of the arylselenenyl group on the configurational stability of enantioenriched seleniranium ions. These studies show that the 2-nitrophenyl group attached to the selenium atom significantly attenuates the racemization of seleniranium ions. A variety of achiral Lewis bases catalyze the intramolecular selenoetherification of alkenes using N-(2-nitrophenylselenenyl)succinimide as the electrophile along with a Brønsted acid. Preliminary mechanistic studies suggest the intermediacy of ionic Lewis base-selenium(II) adducts. Most importantly, a broad survey of chiral Lewis bases revealed that 1,1'-binaphthalene-2,2'-diamine (BINAM)-derived thiophosphoramides catalyze the cyclization of unsaturated alcohols in the presence of N-(2-nitrophenylselenenyl)succinimide and methanesulfonic acid. A variety of cyclic seleno ethers were produced in good chemical yields and in moderate to good enantioselectivities, which constitutes the first catalytic, enantioselective selenofunctionalization of unactivated olefins.

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.

Enantioselective Addition of Allyltin Reagents to Amino Aldehydes Catalyzed with Bis(oxazolinylphenylrhodium(III Aqua Complexes

Directory of Open Access Journals (Sweden)

Hisao Nishiyama

2011-06-01

Full Text Available Bis(oxazolinylphenylrhodium(III aqua complexes, (PheboxRhX2(H2O [X = Cl, Br], were found to be efficient Lewis acid catalysts for the enantioselective addition of allyl- and methallyltributyltin reagents to amino aldehydes. The reactions proceed smoothly in the presence of 5–10 mol % of (PheboxRhX2(H2O complex at ambient temperature to give the corresponding amino alcohols with modest to good enantioselectivity (up to 94% ee.

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

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

KAUST Repository

Yang, Limin; Wang, Fei; Lee, Richmond; Lv, Yunbo; Huang, Kuo-Wei; Zhong, Guofu

2014-01-01

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

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

International Nuclear Information System (INIS)

Kang, Seock Yong; Park, Yong Sun

2016-01-01

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.

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.

A dual Lewis base activation strategy for enantioselective carbene-catalyzed annulations.

Science.gov (United States)

Izquierdo, Javier; Orue, Ane; Scheidt, Karl A

2013-07-24

A dual activation strategy integrating N-heterocyclic carbene (NHC) catalysis and a second Lewis base has been developed. NHC-bound homoenolate equivalents derived from α,β-unsaturated aldehydes combine with transient reactive o-quinone methides in an enantioselective formal [4 + 3] fashion to access 2-benzoxopinones. The overall approach provides a general blueprint for the integration of carbene catalysis with additional Lewis base activation modes.

An efficient synthesis of isocoumarins via a CuI catalyzed cascade reaction process

Institute of Scientific and Technical Information of China (English)

无

2009-01-01

3-Alkyl isocoumarins are provided by CuI/amino acid-catalyzed Sonogashira coupling reaction of o-bromo benzoic acids and terminal alkynes and the subsequent additive cyclization. This cascade process allows synthesis of diverse isocoumarins by varying both coupling partners bearing a wide range of functional groups.

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

Science.gov (United States)

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

2011-01-26

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

Recent Advances in Recoverable Systems for the Copper-Catalyzed Azide-Alkyne Cycloaddition Reaction (CuAAC

Directory of Open Access Journals (Sweden)

Alessandro Mandoli

2016-09-01

Full Text Available The explosively-growing applications of the Cu-catalyzed Huisgen 1,3-dipolar cycloaddition reaction between organic azides and alkynes (CuAAC have stimulated an impressive number of reports, in the last years, focusing on recoverable variants of the homogeneous or quasi-homogeneous catalysts. Recent advances in the field are reviewed, with particular emphasis on systems immobilized onto polymeric organic or inorganic supports.

An enantioselective approach toward 3,4-dihydroisocoumarin through the bromocyclization of styrene-type carboxylic acids.

Science.gov (United States)

Chen, Jie; Zhou, Ling; Tan, Chong Kiat; Yeung, Ying-Yeung

2012-01-20

A facile and enantioselective approach toward 3,4-dihydroisocoumarin was developed. The method involved an amino-thiocarbamate catalyzed enantioselective bromocyclization of styrene-type carboxylic acids, yielding 3-bromo-3,4-dihydroisocoumarins with good yields and ee's. 3-Bromo-3,4-dihydroisocoumarins are versatile building blocks for various dihydroisocoumarin derivatives in which the Br group can readily be modified to achieve biologically important 4-O-type and 4-N-type 3,4-dihydroisocoumarin systems. In addition, studies indicated that, by refining some parameters, the synthetically useful 5-exo phthalide products could be achieved with good yields and ee's.

NHC-Copper(I) Halide-Catalyzed Direct Alkynylation of Trifluoromethyl Ketones on Water

KAUST Repository

Czerwiński, Paweł

2016-05-04

An efficient and easily scalable NHC-copper(I) halide-catalyzed addition of terminal alkynes to 1,1,1-trifluoromethyl ketones, carried out on water for the first time, is reported. A series of addition reactions were performed with as little as 0.1-2.0mol% of [(NHC)CuX] (X=Cl, Br, I, OAc, OTf) complexes, providing tertiary propargylic trifluoromethyl alcohols in high yields and with excellent chemoselectivity from a broad range of aryl- and more challenging alkyl-substituted trifluoromethyl ketones (TFMKs). DFT calculations were performed to rationalize the correlation between the yield of catalytic alkynylation and the sterics of N-heterocyclic carbenes (NHCs), expressed as buried volume (%VBur), indicating that steric effects dominate the yield of the reaction. Additional DFT calculations shed some light on the differential reactivity of [(NHC)CuX] complexes in the alkynylation of TFMKs. The first enantioselective version of a direct alkynylation in the presence of C1-symmetric NHC-copper(I) complexes is also presented. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Asymmetric Chemoenzymatic Reductive Acylation of Ketones by a Combined Iron-Catalyzed Hydrogenation-Racemization and Enzymatic Resolution Cascade

KAUST Repository

El-Sepelgy, Osama

2017-02-28

A general and practical process for the conversion of prochiral ketones into the corresponding chiral acetates has been realized. An iron carbonyl complex is reported to catalyze the hydrogenation-dehydrogenation-hydrogenation of prochiral ketones. By merging the iron-catalyzed redox reactions with enantioselective enzymatic acylations a wide range of benzylic, aliphatic and (hetero)aromatic ketones, as well as diketones, were reductively acylated. The corresponding products were isolated with high yields and enantioselectivities. The use of an iron catalyst together with molecular hydrogen as the hydrogen donor and readily available ethyl acetate as acyl donor make this cascade process highly interesting in terms of both economic value and environmental credentials.

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.

Chiral Cu(II-catalyzed enantioselective β-borylation of α,β-unsaturated nitriles in water

Directory of Open Access Journals (Sweden)

Lei Zhu

2015-10-01

Full Text Available The promising performance of copper(II complexes was demonstrated for asymmetric boron conjugate addition to α,β-unsaturated nitriles in water. The catalyst system, which consisted of Cu(OAc2 and a chiral 2,2′-bipyridine ligand, enabled β-borylation and chiral induction in water. Subsequent protonation, which was accelerated in aqueous medium, led to high activity of this asymmetric catalysis. Both solid and liquid substrates were suitable despite being insoluble in water.

Failure and Redemption of Statistical and Nonstatistical Rate Theories in the Hydroboration of Alkenes.

Science.gov (United States)

Bailey, Johnathan O; Singleton, Daniel A

2017-11-08

Our previous work found that canonical forms of transition state theory incorrectly predict the regioselectivity of the hydroboration of propene with BH 3 in solution. In response, it has been suggested that alternative statistical and nonstatistical rate theories can adequately account for the selectivity. This paper uses a combination of experimental and theoretical studies to critically evaluate the ability of these rate theories, as well as dynamic trajectories and newly developed localized statistical models, to predict quantitative selectivities and qualitative trends in hydroborations on a broader scale. The hydroboration of a series of terminally substituted alkenes with BH 3 was examined experimentally, and a classically unexpected trend is that the selectivity increases as the alkyl chain is lengthened far from the reactive centers. Conventional and variational transition state theories can predict neither the selectivities nor the trends. The canonical competitive nonstatistical model makes somewhat better predictions for some alkenes but fails to predict trends, and it performs poorly with an alkene chosen to test a specific prediction of the model. Added nonstatistical corrections to this model make the predictions worse. Parametrized Rice-Ramsperger-Kassel-Marcus (RRKM)-master equation calculations correctly predict the direction of the trend in selectivity versus alkene size but overpredict its magnitude, and the selectivity with large alkenes remains unpredictable with any parametrization. Trajectory studies in explicit solvent can predict selectivities without parametrization but are impractical for predicting small changes in selectivity. From a lifetime and energy analysis of the trajectories, "localized RRKM-ME" and "competitive localized noncanonical" rate models are suggested as steps toward a general model. These provide the best predictions of the experimental observations and insight into the selectivities.

Palladium-Catalyzed Asymmetric Allylic Alkylation of 4-Substituted Isoxazolidin-5-ones: Straightforward Access to β2,2 -Amino Acids.

Science.gov (United States)

Nascimento de Oliveira, Marllon; Arseniyadis, Stellios; Cossy, Janine

2018-04-03

We report here an unprecedented and highly enantioselective palladium-catalyzed allylic alkylation applied to 4-substituted isoxazolidin-5-ones. Ultimately, the process provides a straightforward access to β 2,2 -amino acids bearing an all-carbon quaternary stereogenic center in great yields and a high degree of enantioselectivity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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.

Enantioselective inhibition of carprofen towards UDP-glucuronosyltransferase (UGT) 2B7.

Science.gov (United States)

Fang, Zhong-Ze; Wang, Haina; Cao, Yun-Feng; Sun, Dong-Xue; Wang, Li-Xuan; Hong, Mo; Huang, Ting; Chen, Jian-Xing; Zeng, Jia

2015-03-01

UDP-glucuronosyltransferases (UGTs)-catalyzed glucuronidation conjugation reaction plays an important role in the elimination of many important clinical drugs and endogenous substances. The present study aims to investigate the enantioselective inhibition of carprofen towards UGT isoforms. In vitro a recombinant UGT isoforms-catalyzed 4-methylumbelliferone (4-MU) glucuronidation incubation mixture was used to screen the inhibition potential of (R)-carprofen and (S)-carprofen towards multiple UGT isoforms. The results showed that (S)-carprofen exhibited stronger inhibition potential than (R)-carprofen towards UGT2B7. However, no significant difference was observed for the inhibition of (R)-carprofen and (S)-carprofen towards other UGT isoforms. Furthermore, the inhibition kinetic behavior was compared for the inhibition of (S)-carprofen and (R)-carprofen towards UGT2B7. A Lineweaver-Burk plot showed that both (S)-carprofen and (R)-carprofen exhibited competitive inhibition towards UGT2B7-catalyzed 4-MU glucuronidation. The inhibition kinetic parameter (Ki ) was calculated to be 7.0 μM and 31.1 μM for (S)-carprofen and (R)-carprofen, respectively. Based on the standard for drug-drug interaction, the threshold for (S)-carprofen and (R)-carprofen to induce a drug-drug interaction is 0.7 μM and 3.1 μM, respectively. In conclusion, enantioselective inhibition of carprofen towards UDP-glucuronosyltransferase (UGT) 2B7 was demonstrated in the present study. Using the in vitro inhibition kinetic parameter, the concentration threshold of (S)-carprofen and (R)-carprofen to possibly induce the drug-drug interaction was obtained. Therefore, clinical monitoring of the plasma concentration of (S)-carprofen is more important than (R)-carprofen to avoid a possible drug-drug interaction between carprofen and the drugs mainly undergoing UGT2B7-catalyzed metabolism. © 2014 Wiley Periodicals, Inc.

Rhodium-catalyzed asymmetric hydroboration of γ,δ-unsaturated amide derivatives: δ-borylated amides.

Science.gov (United States)

Hoang, G L; Zhang, S; Takacs, J M

2018-05-08

γ,δ-Unsaturated amides in which the alkene moiety bears an aryl or heteroaryl substituent undergo regioselective rhodium-catalyzed δ-borylation by pinacolborane to afford chiral secondary benzylic boronic esters. The results contrast the γ-borylation of γ,δ-unsaturated amides in which the disubstituted alkene moiety bears only alkyl substituents; the reversal in regiochemistry is coupled with a reversal in the sense of π-facial selectivity.

Metal-Free Catalytic Enantioselective C–B Bond Formation: (Pinacolato)boron Conjugate Additions to α,β-Unsaturated Ketones, Esters, Weinreb Amides and Aldehydes Promoted by Chiral N-Heterocyclic Carbenes

Science.gov (United States)

Wu, Hao; Radomkit, Suttipol; O’Brien, Jeannette M.; Hoveyda, Amir H.

2012-01-01

The first broadly applicable metal-free enantioselective method for boron conjugate addition (BCA) to α,β-unsaturated carbonyls is presented. The C–B bond forming reactions are promoted in the presence of 2.5–7.5 mol % of a readily accessible C1-symmetric chiral imidazolinium salt, which is converted, in situ, to the catalytically active diastereo- and enantiomerically pure N-heterocyclic carbene (NHC) by the common organic base 1,8-diazabicyclo[5.4.0]undec-7-ene (dbu). In addition to the commercially available bis(pinacolato)diboron [B2(pin)2], and in contrast to reactions with the less sterically demanding achiral NHCs, the presence of MeOH is required for high efficiency. Acyclic and cyclic α,β-unsaturated ketones, as well as acyclic esters, Weinreb amides and aldehydes can serve as suitable substrates; the desired β-boryl carbonyls are isolated in up to 94% yield and >98:2 enantiomer ratio (er). Transformations are often carried out at ambient temperature. In certain cases, such as when the relatively less reactive unsaturated amides are used, elevated temperatures are required (50–66 °C); nonetheless, reactions remain highly enantioselective. The utility of the NHC-catalyzed method is demonstrated through comparison with the alternative Cu-catalyzed protocols; in cases involving a polyfunctional substrate, unique profiles in chemoselectivity are exhibited by the metal-free approach (e.g., conjugate addition vs reaction with an alkyne, allene or aldehyde). PMID:22559866

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

Science.gov (United States)

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

2014-11-24

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

1,2-Ferrocenediylazaphosphinines 3: a new class of planar chiral ligands for Cu-catalyzed cyclopropanation

Energy Technology Data Exchange (ETDEWEB)

Paek, Seung Hwan; Co, Thanh Thien; Lee, Dong Ho; Park, Yu Chul; Kim, Tae Jeong [Kyungpook National Univ., Daegu (Korea, Republic of)

2002-12-01

The synthesis and catalytic application of a new class of planar chiral ferrocenes, 1,2-ferrocenediylazaphos-phinines (1 and 2) are described. They are powerful ligands for the copper(I)-catalyzed asymmetric cyclopropanation of a range of alkenes with diazo esters to exhibit an exceptionally high degree of diastereoselectivity ({approx}100%) in favor of trans isomers, regardless the structure of the olefins and the diazo compounds. Comparative studies between 1 and 2 reveal that the former works better in terms of diastereocontrol. In contrast, however, enantioselectivity is low with both 1 and 2 as a whole although, in certain cases with a proper combination of the olefin and the diazo ester, high optical yields (up to 100% ee) can be achieved. Other reaction parameters such as the reaction temperature and the structure of the ligand do exhibit some influence, although infinitesimal, on both chemical and optical yields.

1,2-Ferrocenediylazaphosphinines 3: a new class of planar chiral ligands for Cu-catalyzed cyclopropanation

International Nuclear Information System (INIS)

Paek, Seung Hwan; Co, Thanh Thien; Lee, Dong Ho; Park, Yu Chul; Kim, Tae Jeong

2002-01-01

The synthesis and catalytic application of a new class of planar chiral ferrocenes, 1,2-ferrocenediylazaphos-phinines (1 and 2) are described. They are powerful ligands for the copper(I)-catalyzed asymmetric cyclopropanation of a range of alkenes with diazo esters to exhibit an exceptionally high degree of diastereoselectivity (∼100%) in favor of trans isomers, regardless the structure of the olefins and the diazo compounds. Comparative studies between 1 and 2 reveal that the former works better in terms of diastereocontrol. In contrast, however, enantioselectivity is low with both 1 and 2 as a whole although, in certain cases with a proper combination of the olefin and the diazo ester, high optical yields (up to 100% ee) can be achieved. Other reaction parameters such as the reaction temperature and the structure of the ligand do exhibit some influence, although infinitesimal, on both chemical and optical yields

Construction of axial chirality by rhodium-catalyzed asymmetric dehydrogenative Heck coupling of biaryl compounds with alkenes.

Science.gov (United States)

Zheng, Jun; You, Shu-Li

2014-11-24

Enantioselective construction of axially chiral biaryls by direct C-H bond functionalization reactions has been realized. Novel axially chiral biaryls were synthesized by the direct C-H bond olefination of biaryl compounds, using a chiral [Cp*Rh(III)] catalyst, in good to excellent yields and enantioselectivities. The obtained axially chiral biaryls were found as suitable ligands for rhodium-catalyzed asymmetric conjugate additions. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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

Science.gov (United States)

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

2018-04-16

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

Synthesis of E-Alkyl Alkenes from Terminal Alkynes via Ni-Catalyzed Cross-Coupling of Alkyl Halides with B-Alkenyl-9-borabicyclo[3.3.1]nonanes.

Science.gov (United States)

Di Franco, Thomas; Epenoy, Alexandre; Hu, Xile

2015-10-02

The first Ni-catalyzed Suzuki-Miyaura coupling of alkyl halides with alkenyl-(9-BBN) reagents is reported. Both primary and secondary alkyl halides including alkyl chlorides can be coupled. The coupling method can be combined with hydroboration of terminal alkynes, allowing the expedited synthesis of functionalized alkyl alkenes from readily available alkynes with complete (E)-selectivity in one pot. The method was applied to the total synthesis of (±)-Recifeiolide, a natural macrolide.

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.

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.

PipPhos and MorfPhos : Privileged monodentate phosphoramidite ligands for rhodium-catalyzed asymmetric hydrogenation

NARCIS (Netherlands)

Bernsmann, Heiko; van den Berg, M; Hoen, Robert; Minnaard, AJ; Mehler, G; Reetz, MT; De Vries, JG; Feringa, BL

2005-01-01

A library of 20 monodentate phosphoramidite ligands has been prepared and applied in rhodium-catalyzed asymmetric hydrogenation. This resulted in the identification of two ligands, PipPhos and MorfPhos, that afford excellent and in several cases unprecedented enantioselectivities in the

Asymmetric hydrogenation of quinolines catalyzed by iridium complexes of monodentate BINOL-derived phosphoramidites

NARCIS (Netherlands)

Mrsic, Natasa; Lefort, Laurent; Boogers, Jeroen A. F.; Minnaard, Adriaan J.; Feringa, Ben L.; de Vries, Johannes G.; Mršić, Nataša

The monodentate BINOL-derived phosphoramidite PipPhos is used as ligand for the iridium-catalyzed asymmetric hydrogenation of 2- and 2,6-substituted quinolines. If tri-ortho-tolylphosphine and/or chloride salts are used as additives enantioselectivities are strongly enhanced up to 89%. NMR indicates

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....

Cu(II)-catalyzed esterification reaction via aerobic oxidative cleavage of C(CO)-C(alkyl) bonds.

Science.gov (United States)

Ma, Ran; He, Liang-Nian; Liu, An-Hua; Song, Qing-Wen

2016-02-04

A novel Cu(II)-catalyzed aerobic oxidative esterification of simple ketones for the synthesis of esters has been developed with wide functional group tolerance. This process is assumed to go through a tandem sequence consisting of α-oxygenation/esterification/nucleophilic addition/C-C bond cleavage and carbon dioxide is released as the only byproduct.

Continuous-flow enantioselective α-aminoxylation of aldehydes catalyzed by a polystyrene-immobilized hydroxyproline

Directory of Open Access Journals (Sweden)

Xacobe C. Cambeiro

2011-10-01

Full Text Available The application of polystyrene-immobilized proline-based catalysts in packed-bed reactors for the continuous-flow, direct, enantioselective α-aminoxylation of aldehydes is described. The system allows the easy preparation of a series of β-aminoxy alcohols (after a reductive workup with excellent optical purity and with an effective catalyst loading of ca. 2.5% (four-fold reduction compared to the batch process working at residence times of ca. 5 min.

Iridium-Catalyzed Asymmetric Intramolecular Allylic Amidation : Enantioselective Synthesis of Chiral Tetrahydroisoquinolines and Saturated Nitrogen Heterocycles

NARCIS (Netherlands)

Teichert, Johannes F.; Fañanás-Mastral, Martín; Feringa, Bernard

2011-01-01

For the first time iridium catalysis has been used for the synthesis of chiral tetrahydroisoquinolines with excellent yields and high enantioselectivities (see scheme; cod=1,5-cyclooctadiene, DBU=1,8-diazabicyclo[5.4.0]undec-7-ene). These products are important chiral building blocks for the

Asymmetric Chemoenzymatic Reductive Acylation of Ketones by a Combined Iron-Catalyzed Hydrogenation-Racemization and Enzymatic Resolution Cascade

KAUST Repository

El-Sepelgy, Osama; Brzozowska, Aleksandra; Rueping, Magnus

2017-01-01

. By merging the iron-catalyzed redox reactions with enantioselective enzymatic acylations a wide range of benzylic, aliphatic and (hetero)aromatic ketones, as well as diketones, were reductively acylated. The corresponding products were isolated with high

Predictable and Regioselective Insertion of Internal Unsymmetrical Alkynes in Rhodium-Catalyzed Cycloadditions with Alkenyl Isocyanates

Science.gov (United States)

Friedman, Rebecca Keller; Rovis, Tomislav

2009-01-01

A regioselective, rhodium-catalyzed cycloaddition between a variety of internal, unsymmetrical alkynes is described. We document the impact of both steric and electronic properties of the alkyne on reaction course, efficiency and enantioselectivity. The substituent that better stabilizes a positive charge or the larger group, all else being equal, inserts distal to the carbonyl moiety in a predictable and controllable fashion. The reaction scope is broad and the enantioselectivities are high, providing an ‘instruction manual’ for substrate choice when utilizing this reaction as a synthetic tool. PMID:19569692

Cu(I)-catalyzed efficient synthesis of 2′-Triazolo-nucleoside conjugates

DEFF Research Database (Denmark)

Mathur, D.; Rana, N.; Olsen, Carl Erik

2015-01-01

-nucleoside conjugates, which can be evaluated for different biological activity for suitable drug development, were unambiguously identified on the basis of 1H NMR, 13C NMR, IR, and HRMS data analysis. These compounds have been synthesized for the first time and have not been reported in the literature earlier.......A small library of thirty-two 2′-triazolyl uridine and 2′-triazolyl-5-methyluridine has been synthesized by Cu(I)-catalyzed condensation of 2′-azido-2′-deoxyuridine and 2′-azido-2′-deoxy-5-methyluridine with different alkynes and aryl propargyl ethers in almost quantitative yields. Triazolo...

A Mixed-Ligand Chiral Rhodium(II) Catalyst Enables the Enantioselective Total Synthesis of Piperarborenine B.

Science.gov (United States)

Panish, Robert A; Chintala, Srinivasa R; Fox, Joseph M

2016-04-11

A novel, mixed-ligand chiral rhodium(II) catalyst, Rh2(S-NTTL)3(dCPA), has enabled the first enantioselective total synthesis of the natural product piperarborenine B. A crystal structure of Rh2(S-NTTL)3(dCPA) reveals a "chiral crown" conformation with a bulky dicyclohexylphenyl acetate ligand and three N-naphthalimido groups oriented on the same face of the catalyst. The natural product was prepared on large scale using rhodium-catalyzed bicyclobutanation/ copper-catalyzed homoconjugate addition chemistry in the key step. The route proceeds in ten steps with an 8% overall yield and 92% ee. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ru/Me-BIPAM-Catalyzed Asymmetric Addition of Arylboronic Acids to Aliphatic Aldehydes and α-Ketoesters

Directory of Open Access Journals (Sweden)

Momoko Watanabe

2011-06-01

Full Text Available A ruthenium-catalyzed asymmetric arylation of aliphatic aldehydes and α-ketoesters with arylboronic acids has been developed, giving chiral alkyl(arylmethanols and α-hydroxy esters in good yields. The use of a chiral bidentate phosphoramidite ligand (Me-BIPAM achieved excellent enantioselectivities.

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.

Asymmetric Brønsted acid-catalyzed aza-Diels–Alder reaction of cyclic C-acylimines with cyclopentadiene

Directory of Open Access Journals (Sweden)

Magnus Rueping

2012-10-01

Full Text Available A new chiral Brønsted acid-catalyzed aza-Diels–Alder reaction of cyclic C-acylimines with cyclopentadiene has been developed. The reaction provides optically active aza-tetracycles in good yields with high diastereo- and enantioselectivities under mild reaction conditions.

Copper-catalyzed azide–alkyne cycloaddition (CuAAC) and beyond: new reactivity of copper(i) acetylides†

OpenAIRE

Hein, Jason E.; Fokin, Valery V.

2010-01-01

Copper-catalyzed azide–alkyne cycloaddition (CuAAC) is a widely utilized, reliable, and straightforward way for making covalent connections between building blocks containing various functional groups. It has been used in organic synthesis, medicinal chemistry, surface and polymer chemistry, and bioconjugation applications. Despite the apparent simplicity of the reaction, its mechanism involves multiple reversible steps involving coordination complexes of copper(i) acetylides of varying nucle...

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.

Enantioselective Access to Spirocyclic Sultams by Chiral Cp(x) -Rhodium(III)-Catalyzed Annulations.

Science.gov (United States)

Pham, Manh V; Cramer, Nicolai

2016-02-12

Chiral spirocyclic sultams are a valuable compound class in organic and medicinal chemistry. A rapid entry to this structural motif involves a [3+2] annulation of an N-sulfonyl ketimine and an alkyne. Although the directing-group properties of the imino group for C-H activation have been exploited, the developments of related asymmetric variants have remained very challenging. The use of rhodium(III) complexes equipped with a suitable atropchiral cyclopentadienyl ligand, in conjunction with a carboxylic acid additive, enables an enantioselective and high yielding access to such spirocyclic sultams. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Mechanistic studies of copper(I)-catalyzed 1,3-halogen migration.

Science.gov (United States)

Van Hoveln, Ryan; Hudson, Brandi M; Wedler, Henry B; Bates, Desiree M; Le Gros, Gabriel; Tantillo, Dean J; Schomaker, Jennifer M

2015-04-29

An ongoing challenge in modern catalysis is to identify and understand new modes of reactivity promoted by earth-abundant and inexpensive first-row transition metals. Herein, we report a mechanistic study of an unusual copper(I)-catalyzed 1,3-migration of 2-bromostyrenes that reincorporates the bromine activating group into the final product with concomitant borylation of the aryl halide bond. A combination of experimental and computational studies indicated this reaction does not involve any oxidation state changes at copper; rather, migration occurs through a series of formal sigmatropic shifts. Insight provided from these studies will be used to expand the utility of aryl copper species in synthesis and develop new ligands for enantioselective copper-catalyzed halogenation.

Selective coupling reaction between 2,6-diiodoanisoles and terminal alkynes catalyzed by Pd(PPh32Cl2 and CuI

Directory of Open Access Journals (Sweden)

Allan F. C. Rossini

2012-06-01

Full Text Available The cross-coupling reaction between aryl halides and terminal alkynes, catalyzed by palladium complexes and copper (I salts, consists in an efficient synthetic tool for the formation of C-C bonds, resulting in disubstituted acetylenic compounds. Accordingly, in this work we present our preliminary results involving the selective cross-coupling reaction between 2,6-diiodoanisoles and terminal alkynes, catalyzed by Pd(PPh32Cl2 and CuI, in the formation of 2-iodo-alkynylanisoles (scheme 1.

Automated Quantum Mechanical Predictions of Enantioselectivity in a Rhodium-Catalyzed Asymmetric Hydrogenation.

Science.gov (United States)

Guan, Yanfei; Wheeler, Steven E

2017-07-24

A computational toolkit (AARON: An automated reaction optimizer for new catalysts) is described that automates the density functional theory (DFT) based screening of chiral ligands for transition-metal-catalyzed reactions with well-defined reaction mechanisms but multiple stereocontrolling transition states. This is demonstrated for the Rh-catalyzed asymmetric hydrogenation of (E)-β-aryl-N-acetyl enamides, for which a new C 2 -symmetric phosphorus ligand is designed. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cu-catalyzed C(sp³)-H bond activation reaction for direct preparation of cycloallyl esters from cycloalkanes and aromatic aldehydes.

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Zhao, Jincan; Fang, Hong; Han, Jianlin; Pan, Yi

2014-05-02

Cu-catalyzed dehydrogenation-olefination and esterification of C(sp(3))-H bonds of cycloalkanes with TBHP as an oxidant has been developed. The reaction involves four C-H bond activations and gives cycloallyl ester products directly from cycloalkanes and aromatic aldehydes.

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

Science.gov (United States)

Zhou, Yirong; Breit, Bernhard

2017-12-22

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

Excess Substrate is a Spectator Ligand in a Rhodium-Catalyzed Asymmetric [2+2+2] Cycloaddition of Alkenyl Isocyanates with Tolanes

Science.gov (United States)

Oinen, Mark Emil; Yu, Robert T.; Rovis, Tomislav

2009-01-01

Excess substrate has been identified as an unintended spectator ligand affecting enantioselectivity in the [2+2+2] cycloaddition of alkenyl isocyanates with tolanes. Replacement of excess substrate with an exogenous additive affords products with consistent and higher ee’s. The increase in enantioselectivity is the result of a change in composition of a proposed rhodium(III) intermediate on the catalytic cycle. The net result is a rational probe of a short-lived rhodium(III) intermediate, and gives insight that may have applications in many rhodium catalyzed reactions. PMID:19803471

Synthesis of Novel Aliphatic N-sulfonylamidino Thymine Derivatives by Cu(I)-catalyzed Three-component Coupling Reaction

OpenAIRE

Krstulović, Luka; Ismaili, Hamit; Višnjevac, Aleksandar; Glavaš-Obrovac, Ljubica; Žinić, Biserka

2012-01-01

A series of new aliphatic N-sulfonylamidino thymine derivatives containing nucleobase, N-sulfonyl and amidine pharmacophores in the structure were synthesized by Cu(I)-catalyzed threecomponent coupling of 1-propargyl thymine, benzenesulfonyl azides and amines or ammonium salts. Preliminary in vitro antitumor screening (human cervix adenocarcinoma -HeLa and leukemia cells - Jurkat) revealed promising activities of N,N-diethyl- (2) and N-4-cyanobenzyl- (6) derivatives of 4-acetamido...

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.

Ti-Catalyzed Selective Isomerization of Terminal Mono-substituted Olefins

International Nuclear Information System (INIS)

Lee, Hyung Soo; Lee, Gab Yong

2005-01-01

The isomerization of olefins occurs either by a metal hydride addition-elimination or by a π-allyl metal hydride intermediate. HCo(CO) 4 , [(C 2 H 4 ) 2 RhCl] 2 , Ni[P(OEt) 3 ] 4 , and PtCl 2 (PPh 3 ) 2 -SnCl 2 are effective catalysts for isomerization of olefins via a metal hydride addition-elimination mechanism, 3,4 and Fe 3 (CO) 12 catalyzed isomerization of 3-ethyl-1-pentene and isomerization of 1-heptene catalyzed by (PhCN) 2 PdCl 2 occur via a π-allyl metal hydride mechanism. The cis/trans ratio of 2-butene obtained from isomerization of 1-butene by RhH(CO)(PPh 3 ) 3 has also been investigated. The skeletal isomerization of olefins catalyzed by (R 3 P) 2 NiCl 2 is developed such as conversion of cis-1,4-hexadiene to trans-2-methyl-1,3-pentadiene. Titanium complexes serve as an effective catalysts for a variety of reactions such as hydroalumination, hydroboration, and hydrogenation of unsaturated hydrocarbons. We have been interested in the selective reactions of unsaturated hydrocarbons by using titanium and zirconium compounds. The reagent system composed of LiAlH 4 /Cp 2 TiCl 2 ≤ 2 in the molar ratio promotes the isomerization of 1-octene, but the detailed reaction for isomerization of olefins has not been reported. We report here a selective isomerization of olefins with low valent titanium complex generated from Cp 2 TiCl 2 (Cp=cyclopentadienyl) and LiAlH 4

Correction: A binary catalyst system of a cationic Ru-CNC pincer complex with an alkali metal salt for selective hydroboration of carbon dioxide.

Science.gov (United States)

Ng, Chee Koon; Wu, Jie; Hor, T S Andy; Luo, He-Kuan

2016-12-22

Correction for 'A binary catalyst system of a cationic Ru-CNC pincer complex with an alkali metal salt for selective hydroboration of carbon dioxide' by Chee Koon Ng et al., Chem. Commun., 2016, 52, 11842-11845.

Microwave Assisted Expeditious and Green Cu(II-Clay Catalyzed Domino One-Pot Three Component Synthesis of 2H-indazoles

Directory of Open Access Journals (Sweden)

Bashir Ahmad Dar

2018-01-01

How to Cite: Dar, B.A., Safvi, S.W., Rizvi, M.A. (2018. Microwave Assisted Expeditious and Green Cu(II-Clay Catalyzed Domino One-Pot Three Component Synthesis of 2H-indazoles. Bulletin of Chemical Reaction Engineering & Catalysis, 13 (1: 82-88 (doi:10.9767/bcrec.13.1.963.82-88

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

Science.gov (United States)

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

2015-03-01

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

A Tunable and Enantioselective Hetero-Diels-Alder Reaction Provides Access to Distinct Piperidinoyl Spirooxindoles.

Science.gov (United States)

Jayakumar, Samydurai; Louven, Kathrin; Strohmann, Carsten; Kumar, Kamal

2017-12-11

The active complexes of chiral N,N'-dioxide ligands with dysprosium and magnesium salts catalyze the hetero-Diels-Alder reaction between 2-aza-3-silyloxy-butadienes and alkylidene oxindoles to selectively form 3,3'- and 3,4'-piperidinoyl spirooxindoles, respectively, in very high yields and with excellent enantioselectivities. The exo-selective asymmetric cycloaddition successfully regaled the construction of sp 3 -rich and highly substituted natural-product-based spirooxindoles supporting many chiral centers, including contiguous all-carbon quaternary centers. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

(Salen)Ti(Ⅳ)-Catalyzed Asymmetric Ring-opening of meso Epoxides Using Dithiophosphorus Acid as the Nucleophile

Institute of Scientific and Technical Information of China (English)

Zheng Hong ZHOU; Zhao Ming LI; Bing LIU; Kang Ying LI; Li Xin WANG; Guo Feng ZHAO; Qi Lin ZHOU; Chu Chi TANG

2006-01-01

The asymmetric ring-opening of epoxides with dithiophosphorus acids catalyzed by a (salen)Ti(Ⅳ) complex formed in situ from the reaction of Ti(OPr-i)4 and the chiral Schiff base derived from (1R,2R)-(+)-diaminocyclohexane was realized. The resulting products were obtained with low to good enantioselectivity (up to 73% ee).

Insight into the stereospecificity of short-chain thermus thermophilus alcohol dehydrogenase showing pro-S hydride transfer and prelog enantioselectivity.

Science.gov (United States)

Pennacchio, Angela; Giordano, Assunta; Esposito, Luciana; Langella, Emma; Rossi, Mosè; Raia, Carlo A

2010-04-01

The stereochemistry of the hydride transfer in reactions catalyzed by NAD(H)-dependent alcohol dehydrogenase from Thermus thermophilus HB27 was determined by means of (1)H-NMR spectroscopy. The enzyme transfers the pro-S hydrogen of [4R-(2)H]NADH and exhibits Prelog specificity. Enzyme-substrate docking calculations provided structural details about the enantioselectivity of this thermophilic enzyme. These results give additional insights into the diverse active site architectures of the largely versatile short-chain dehydrogenase superfamily enzymes. A feasible protocol for the synthesis of [4R-(2)H]NADH with high yield was also set up by enzymatic oxidation of 2-propanol-d(8) catalyzed by Bacillus stearothermophilus alcohol dehydrogenase.

Catalytic stereoselective synthesis of highly substituted indanones via tandem Nazarov cyclization and electrophilic fluorination trapping.

Science.gov (United States)

Nie, Jing; Zhu, Hong-Wei; Cui, Han-Feng; Hua, Ming-Qing; Ma, Jun-An

2007-08-02

A new catalytic stereoselective tandem transformation via Nazarov cyclization/electrophilic fluorination has been accomplished. This sequence is efficiently catalyzed by a Cu(II) complex to afford fluorine-containing 1-indanone derivatives with two new stereocenters with high diastereoselectivity (trans/cis up to 49/1). Three examples of catalytic enantioselective tandem transformation are presented.

Asymmetric Construction of Benzindoloquinolizidine: Application of An Organocatalytic Enantioselective Conjugate Addition-Cyclization Cascade Reaction

International Nuclear Information System (INIS)

Kim, Cheolwoong; Seo, Seung Woo; Lee, Yona; Kim, Sunggon

2014-01-01

We have developed the synthetic methodology of enantioenriched benzindoloquinolizidines based on the organocatalytic enantioselective conjugate addition-cyclization cascade reaction of o-N-(3-indoleacetyl)amino-cinnamaldehydes with malonates followed by an acid-catalyzed intramolecular Pictet-Spengler type cyclization. The asymmetric reaction using diphenylprolinol TMS ether as an organocatalyst produces the desired products with good to excellent yields and high enantioselectivities (up to 98% ee). The evaluation of the applications of this synthetic methodology for generating enantioenriched benzindolo-quinolizidines and studies on the biological activity of these compounds against human prostate cancer in particular are now in progress. Results of these studies will be presented in due course. Many new types of chemical reactions have been developed to facilitate easier synthesis of complex compounds. Among the strategies, domino reactions, which have been utilized for the efficient and stereoselective construction of complex molecules from simple precursors in a single process, are widely used due to their high synthetic efficiency by reducing both the number of synthetic operation required and the quantities of chemicals and solvents used

CuX2络合物催化甲基丙烯酸甲酯的氧化聚合%CuX2 COMPLEX-CATALYZED OXIDATIVE POLYMERIZATIONS OF METHYL METHACRYLATE

Institute of Scientific and Technical Information of China (English)

孙燕; 孙晋; 宋瑾; 黄文艳; 蒋必彪; 翟光群

2011-01-01

Oxidative polymerizations of methyl methacrylate ( MMA) catalyzed by complexes of transition metal halides in high oxidation states were investigated. First, CuBr2/2, 2'-bipyridine ( bPy)-catalyzed oxidative polymerizations of MMA in the presence of poly (2-( N, iV-dimethylamino) ethyl methacrylate) were performed in different solvents. When cyclohexanone was used as a solvent, only poly ( methyl methacrylate) ( PMMA) was obtained, suggesting redox initiation between CuBr2/bPy and tertiary amines in cyclohexanone is negligible. Second, oxidative polymerizations of MMA catalyzed by different complexes were carried out. Complexes of CuCl2 ,CuBr2 or FeCl3 with bPy,N,N,/V',N",/V"-pentamethyldiethylenetriamine or N,N,N',N'-tetramethylethylenediamine can catalyze oxidative polymerizations of MMA, and polymerization rates increased with the increase of the catalyst concentration. Molecular weight of PMMA increases with monomer conversions initially and maintains constant later. Last,atom transfer radical polymerization ( ATRP) chain extension using PMMA from the oxidative polymerizations at different conversions was performed. The results show the C-X functionality of PMMA chains at low conversion was also 100% ,and it decreased sharply with conversions. Two different mechanisms were conceived to contribute to the oxidative polymerization of MMA: (1) the complexes form ATRP initiators and catalysts with MMA via monomer addition, and then ATRP proceeds to give rise to PMMA chains with C-X terminal groups; (2) the complexes catalyze/initiate conventional free radical polymerizations of MMA.%研究了高氧化态过渡金属卤化物络合物催化甲基丙烯酸甲酯(MMA)的氧化聚合.首先在叔胺类聚合物存在条件下以CuBr2/2,2′-联吡啶(bPy)络合物催化MMA在不同溶剂中的氧化聚合,结果在环己酮中得到PMMA均聚物,CuBr2/bPy同叔胺的氧化还原引发可以忽略.随后在环己酮中分别以不同络合物催化MMA的氧化聚合.结果发现,Cu

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.

Vanadium-Catalyzed Enantioselective Desymmetrization of meso-Secondary Allylic Alcohols and Homoallylic Alcohols

OpenAIRE

Li, Zhi; Zhang, Wei; Hisashi Yamamoto, H.

2008-01-01

Vanadium-catalyzed epoxidation has extended substrate scope. In addition to various bis-allylic alcohols, bis-homoallylic alcohols can also be desymmetrized using our Vanadium-Bis-hydroxamic acid complexes.

Cu-catalyzed aerobic oxidative cyclizations of 3-N-hydroxyamino-1,2-propadienes with alcohols, thiols, and amines to form α-O-, S-, and N-substituted 4-methylquinoline derivatives.

Science.gov (United States)

Sharma, Pankaj; Liu, Rai-Shung

2015-03-16

A one-pot, two-step synthesis of α-O-, S-, and N-substituted 4-methylquinoline derivatives through Cu-catalyzed aerobic oxidations of N-hydroxyaminoallenes with alcohols, thiols, and amines is described. This reaction sequence involves an initial oxidation of N-hydroxyaminoallenes with NuH (Nu = OH, OR, NHR, and SR) to form 3-substituted 2-en-1-ones, followed by Brønsted acid catalyzed intramolecular cyclizations of the resulting products. Our mechanistic analysis suggests that the reactions proceed through a radical-type mechanism rather than a typical nitrone-intermediate route. The utility of this new Cu-catalyzed reaction is shown by its applicability to the synthesis of several 2-amino-4-methylquinoline derivatives, which are known to be key precursors to several bioactive molecules. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

First Novozym 435 lipase-catalyzed Morita-Baylis-Hillman reaction in the presence of amides.

Science.gov (United States)

Tian, Xuemei; Zhang, Suoqin; Zheng, Liangyu

2016-03-01

The first Novozym 435 lipase-catalyzed Morita-Baylis-Hillman (MBH) reaction with amides as co-catalyst was realized. Results showed that neither Novozym 435 nor amide can independently catalyze the reaction. This co-catalytic system that used a catalytic amount of Novozym 435 with a corresponding amount of amide was established and optimized. The MBH reaction strongly depended on the structure of aldehyde substrate, amide co-catalyst, and reaction additives. The optimized reaction yield (43.4%) was achieved in the Novozym 435-catalyzed MBH reaction of 2, 4-dinitrobenzaldehyde and cyclohexenone with isonicotinamide as co-catalyst and β-cyclodextrin as additive only in 2 days. Although enantioselectivity of Novozym 435 was not found, the results were still significant because an MBH reaction using lipase as biocatalyst was realized for the first time. Copyright © 2015 Elsevier Inc. All rights reserved.

Pyridine synthesis by reactions of allyl amines and alkynes proceeding through a Cu(OAc)2 oxidation and Rh(III)-catalyzed N-annulation sequence.

Science.gov (United States)

Kim, Dong-Su; Park, Jung-Woo; Jun, Chul-Ho

2012-11-28

A new methodology has been developed for the synthesis of pyridines from allyl amines and alkynes, which involves sequential Cu(II)-promoted dehydrogenation of the allylamine and Rh(III)-catalyzed N-annulation of the resulting α,β-unsaturated imine and alkyne.

Enantioselective pharmacokinetics of sibutramine in rat.

Science.gov (United States)

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

2010-02-01

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

Cu-catalyzed esterification reaction via aerobic oxygenation and C-C bond cleavage: an approach to α-ketoesters.

Science.gov (United States)

Zhang, Chun; Feng, Peng; Jiao, Ning

2013-10-09

The Cu-catalyzed novel aerobic oxidative esterification reaction of 1,3-diones for the synthesis of α-ketoesters has been developed. This method combines C-C σ-bond cleavage, dioxygen activation and oxidative C-H bond functionalization, as well as provides a practical, neutral, and mild synthetic approach to α-ketoesters which are important units in many biologically active compounds and useful precursors in a variety of functional group transformations. A plausible radical process is proposed on the basis of mechanistic studies.

(E)-α,β-unsaturated amides from tertiary amines, olefins and CO via Pd/Cu-catalyzed aerobic oxidative N-dealkylation.

Science.gov (United States)

Shi, Renyi; Zhang, Hua; Lu, Lijun; Gan, Pei; Sha, Yuchen; Zhang, Heng; Liu, Qiang; Beller, Matthias; Lei, Aiwen

2015-02-21

A novel Pd/Cu-catalyzed chemoselective aerobic oxidative N-dealkylation/carbonylation reaction has been developed. Tertiary amines are utilized as a "reservoir" of "active" secondary amines in this transformation, which inhibits the formation of undesired by-products and the deactivation of the catalysts. This protocol allows for an efficient and straightforward construction of synthetically useful and bioactive (E)-α,β-unsaturated amide derivatives from easily available tertiary amines, olefins and CO.

Multigram Synthesis of a Chiral Substituted Indoline Via Copper-Catalyzed Alkene Aminooxygenation.

Science.gov (United States)

Sequeira, Fatima C; Bovino, Michael T; Chipre, Anthony J; Chemler, Sherry R

2012-05-01

(S)-5-Fluoro-2-(2,2,6,6-tetramethylpiperidin-1-yloxymethyl)-1-tosylindoline, a 2-methyleneoxy-substituted chiral indoline, was synthesized on multigram scale using an efficient copper-catalyzed enantioselective intramolecular alkene aminooxygenation. The synthesis is accomplished in four steps and the indoline is obtained in 89% ee (>98% after one recrystallization). Other highlights include efficient gram-scale synthesis of the (4R,5S)-di-Ph-box ligand and efficient separation of a monoallylaniline from its bis(allyl)aniline by-product by distillation under reduced pressure.

Tin-free enantioselective radical reactions using silanes.

Science.gov (United States)

Sibi, Mukund P; Yang, Yong-Hua; Lee, Sunggi

2008-12-04

Readily available hexyl silane is an excellent choice as a H-atom donor and a chain carrier in Lewis acid mediated enantioselective radical reactions. Conjugate radical additions to alpha,beta-unsaturated imides at room temperature proceed in good yields and excellent enantioselectivities.

A binary catalyst system of a cationic Ru-CNC pincer complex with an alkali metal salt for selective hydroboration of carbon dioxide.

Science.gov (United States)

Ng, Chee Koon; Wu, Jie; Hor, T S Andy; Luo, He-Kuan

2016-09-27

Binary catalyst systems comprising a cationic Ru-CNC pincer complex and an alkali metal salt were developed for selective hydroboration of CO 2 utilizing pinacolborane at r.t. and 1 atm CO 2 , with the combination of [Ru(CNC Bn )(CO) 2 (H)][PF 6 ] and KOCO 2 t Bu producing formoxyborane in 76% yield. A bicyclic catalytic mechanism was proposed and discussed.

Asymmetric synthesis of allylic sulfonic acids: enantio- and regioselective iridium-catalyzed allylations of Na2SO3.

Science.gov (United States)

Liu, Wei; Zhao, Xiao-ming; Zhang, Hong-bo; Zhang, Liang; Zhao, Ming-zhu

2014-12-15

An enantioselective allylation reaction of allylic carbonates with sodium sulfite (Na2 SO3 ) catalyzed by Ir complex was accomplished, providing allylic sulfonic acids in good to excellent yields with a high level of enantio- and regioselectivities. (R)-2-Phenyl-2-sulfoacetic acid, a key intermediate for the synthesis of Cefsulodin and Sulbenicillin, was synthesized as well. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Catalytic Asymmetric Piancatelli Rearrangement: Brønsted Acid Catalyzed 4π Electrocyclization for the Synthesis of Multisubstituted Cyclopentenones

KAUST Repository

Cai, Yunfei

2016-10-13

The first catalytic asymmetric Piancatelli reaction is reported. Catalyzed by a chiral Brønsted acid, the rearrangement of a wide range of furylcarbinols with a series of aniline derivatives provides valuable aminocyclopentenones in high yields as well as excellent enantioselectivities and diastereoselectivities. The high value of the aza-Piancatelli rearrangement was demonstrated by the synthesis of a cyclopentane-based hNK1 antagonist analogue.

The Catalytic Enantioselective Total Synthesis of (+)‐Liphagal

DEFF Research Database (Denmark)

Day, Joshua J.; McFadden, Ryan M.; Virgil, Scott C.

2011-01-01

Ring a ding: The first catalytic enantioselective total synthesis of the meroterpenoid natural product (+)-liphagal is disclosed. The approach showcases a variety of technology including enantioselective enolate alkylation, a photochemical alkyne-alkene [2+2] reaction, microwaveassisted metal...

Candida Rugosa Lipase-catalyzed Kinetic Resolution of 3-(Isobutyryloxy)methyl 4-[2-(Difluoromethoxy)phenyl]-2-methyl-5,5-dioxo-1,4-dihydrobenzothieno[3,2-b]pyridine-3-carboxylate

NARCIS (Netherlands)

Sobolev, A.; Zhalubovskis, R.; Franssen, M.C.R.; Vigante, B.; Chekavichus, B.; Duburs, G.; Groot, de Æ.

2004-01-01

The lipase-catalyzed kinetic resolution of 3-(isobutyryloxy)methyl 4-[2-(difluoromethoxy)phenyl]-2-methyl-5,5-dioxo-1,4-dihydrobenzothieno[3,2-b]pyridine-3-carboxylate has been performed. The most enantioselective reaction (E = 28) was transesterification with n-butanol in water-saturated toluene at

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

Science.gov (United States)

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

2017-09-27

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

Asymmetric Stetter reactions catalyzed by thiamine diphosphate-dependent enzymes.

Science.gov (United States)

Kasparyan, Elena; Richter, Michael; Dresen, Carola; Walter, Lydia S; Fuchs, Georg; Leeper, Finian J; Wacker, Tobias; Andrade, Susana L A; Kolter, Geraldine; Pohl, Martina; Müller, Michael

2014-12-01

The intermolecular asymmetric Stetter reaction is an almost unexplored transformation for biocatalysts. Previously reported thiamine diphosphate (ThDP)-dependent PigD from Serratia marcescens is the first enzyme identified to catalyze the Stetter reaction of α,β-unsaturated ketones (Michael acceptor substrates) and α-keto acids. PigD is involved in the biosynthesis of the potent cytotoxic agent prodigiosin. Here, we describe the investigation of two new ThDP-dependent enzymes, SeAAS from Saccharopolyspora erythraea and HapD from Hahella chejuensis. Both show a high degree of homology to the amino acid sequence of PigD (39 and 51 %, respectively). The new enzymes were heterologously overproduced in Escherichia coli, and the yield of soluble protein was enhanced by co-expression of the chaperone genes groEL/ES. SeAAS and HapD catalyze intermolecular Stetter reactions in vitro with high enantioselectivity. The enzymes possess a characteristic substrate range with respect to Michael acceptor substrates. This provides support for a new type of ThDP-dependent enzymatic activity, which is abundant in various species and not restricted to prodigiosin biosynthesis in different strains. Moreover, PigD, SeAAS, and HapD are also able to catalyze asymmetric carbon-carbon bond formation reactions of aldehydes and α-keto acids, resulting in 2-hydroxy ketones.

Solvent effect on copper-catalyzed azide-alkyne cycloaddition (CuAAC): synthesis of novel triazolyl substituted quinolines as potential anticancer agents.

Science.gov (United States)

Ellanki, Amarender Reddy; Islam, Aminul; Rama, Veera Swamy; Pulipati, Ranga Prasad; Rambabu, D; Krishna, G Rama; Reddy, C Malla; Mukkanti, K; Vanaja, G R; Kalle, Arunasree M; Kumar, K Shiva; Pal, Manojit

2012-05-15

A regioselective route to novel mono triazolyl substituted quinolines has been developed via copper-catalyzed azide-alkyne cycloaddition (CuAAC) of 2,4-diazidoquinoline with terminal alkynes in DMF. The reaction provided bis triazolyl substituted quinolines when performed in water in the presence of Et(3)N. A number of the compounds synthesized showed promising anti-proliferative properties when tested in vitro especially against breast cancer cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

Enantioselective effect of bifenthrin on antioxidant enzyme gene expression and stress protein response in PC12 cells.

Science.gov (United States)

Lu, Xianting

2013-07-01

Enantioselectivity in toxicology and the health risk of chiral xenobiotics have become frontier topics interfacing chemistry and toxicology. Our previous results showed that cis-bifenthrin (cis-BF) induced cytotoxicity and apoptosis in vitro in an enantioselective manner. However, the exact molecular mechanisms of synthetic pyrethroid-induced enantioselective apoptosis and cytotoxicity have so far received limited research attention. In the present study, the expression patterns of different genes encoding heat shock protein and antioxidant enzymes were investigated by real-time quantitative PCR in rat adrenal pheochromocytoma (PC12) cells after exposure to cis-BF and its enantiomers. The results showed that exposure to 1S-cis-BF resulted in increased transcription of HSP90, HSP70, HSP60, Cu-Zn-superoxide dismutase, Mn-superoxide dismutase, catalase and glutathione-s-transferase at a concentration of 5 µm and above, while exposure to 1R-cis-BF and rac-cis-BF exhibited these effects to lesser degrees. In addition, induction of antioxidant enzyme gene expression produced by 1S-cis-BF might occur, at least in part, through activation of p38 mitogen-activated protein kinases (MAPK) and extracellular regulated kinases, while increase in stress protein response produced by 1S-cis-BF might occur through the p38 MAPK signaling pathway. The results not only suggest that enantioselectivity should be considered in evaluating the ecotoxicological effects and health risk of chiral contaminants, but also will improve the understanding of molecular mechanism for chiral chemical-induced cytotoxicity. Copyright © 2012 John Wiley & Sons, Ltd.

Chiral amides via copper-catalysed enantioselective conjugate addition

NARCIS (Netherlands)

Schoonen, Anne K.; Fernández-Ibáñez, M. Ángeles; Fañanás-Mastral, Martín; Teichert, Johannes F.; Feringa, Bernard

2014-01-01

A highly enantioselective one pot procedure for the synthesis of beta-substituted amides was developed starting from the corresponding alpha,beta-unsaturated esters. This new methodology is based on the copper-catalysed enantioselective conjugate addition of Grignard reagents to

Theoretical insights into the sites and mechanisms for base catalyzed esterification and aldol condensation reactions over Cu.

Science.gov (United States)

Neurock, Matthew; Tao, Zhiyuan; Chemburkar, Ashwin; Hibbitts, David D; Iglesia, Enrique

2017-04-28

Condensation and esterification are important catalytic routes in the conversion of polyols and oxygenates derived from biomass to fuels and chemical intermediates. Previous experimental studies show that alkanal, alkanol and hydrogen mixtures equilibrate over Cu/SiO 2 and form surface alkoxides and alkanals that subsequently promote condensation and esterification reactions. First-principle density functional theory (DFT) calculations were carried out herein to elucidate the elementary paths and the corresponding energetics for the interconversion of propanal + H 2 to propanol and the subsequent C-C and C-O bond formation paths involved in aldol condensation and esterification of these mixtures over model Cu surfaces. Propanal and hydrogen readily equilibrate with propanol via C-H and O-H addition steps to form surface propoxide intermediates and equilibrated propanal/propanol mixtures. Surface propoxides readily form via low energy paths involving a hydrogen addition to the electrophilic carbon center of the carbonyl of propanal or via a proton transfer from an adsorbed propanol to a vicinal propanal. The resulting propoxide withdraws electron density from the surface and behaves as a base catalyzing the activation of propanal and subsequent esterification and condensation reactions. These basic propoxides can readily abstract the acidic C α -H of propanal to produce the CH 3 CH (-) CH 2 O* enolate, thus initiating aldol condensation. The enolate can subsequently react with a second adsorbed propanal to form a C-C bond and a β-alkoxide alkanal intermediate. The β-alkoxide alkanal can subsequently undergo facile hydride transfer to form the 2-formyl-3-pentanone intermediate that decarbonylates to give the 3-pentanone product. Cu is unique in that it rapidly catalyzes the decarbonylation of the C 2n intermediates to form C 2n-1 3-pentanone as the major product with very small yields of C 2n products. This is likely due to the absence of Brønsted acid sites

The role of achiral pyrazolidinone templates in enantioselective Diels-Alder reactions: scope, limitations, and conformational insights.

Science.gov (United States)

Sibi, Mukund P; Stanley, Levi M; Nie, Xiaoping; Venkatraman, Lakshmanan; Liu, Mei; Jasperse, Craig P

2007-01-17

We have evaluated the role of achiral pyrazolidinone templates in conjunction with chiral Lewis acids in room temperature, enantioselective Diels-Alder cycloadditions. The role of the fluxional N(1) substituent was examined, with the bulky 1-naphthylmethyl group providing enantioselectivities up to 99% ee, while templates with smaller fluxional groups gave lower selectivities. High selectivities were also observed in reactions of 7d with chiral Lewis acids derived from relatively small chiral ligands, suggesting the pyrazolidinone templates are capable of relaying stereochemical information from the ligand to the reaction center. Lewis acids capable of adapting square planar geometries, such as Cu(OTf)2, Cu(ClO4)2, and Pd(ClO4)2, were found to be particularly effective at providing high selectivities. Additionally, substitution at the C-5 position of the pyrazolidinone templates has been shown to be critical for optimal selectivity. Reactions of the optimal pyrazolidinone appended with a number of common dienophiles and various dienes demonstrate the utility of this achiral template. Furthermore, catalytic loadings could be lowered to 2.5 mol % with essentially no loss in selectivity. Pi-Pi interactions were evaluated as a means to explain the unusually high selectivity observed at room temperature. Finally, non-C2-symmetric ligands were employed as a test to determine if chiral relay was operative.

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; Zhong, Fangrui; Zheng, Bin; Meng, Yuezhong; Lu, Yixin; Huang, Kuo-Wei

2013-01-01

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.

Structural Determinants of Alkyne Reactivity in Copper-Catalyzed Azide-Alkyne Cycloadditions

Directory of Open Access Journals (Sweden)

Xiaoguang Zhang

2016-12-01

Full Text Available This work represents our initial effort in identifying azide/alkyne pairs for optimal reactivity in copper-catalyzed azide-alkyne cycloaddition (CuAAC reactions. In previous works, we have identified chelating azides, in particular 2-picolyl azide, as “privileged” azide substrates with high CuAAC reactivity. In the current work, two types of alkynes are shown to undergo rapid CuAAC reactions under both copper(II- (via an induction period and copper(I-catalyzed conditions. The first type of the alkynes bears relatively acidic ethynyl C-H bonds, while the second type contains an N-(triazolylmethylpropargylic moiety that produces a self-accelerating effect. The rankings of reactivity under both copper(II- and copper(I-catalyzed conditions are provided. The observations on how other reaction parameters such as accelerating ligand, reducing agent, or identity of azide alter the relative reactivity of alkynes are described and, to the best of our ability, explained.

A general enantioselective route to the chamigrene natural product family

KAUST Repository

White, David E.; Stewart, Ian C.; Seashore-Ludlow, Brinton A.; Grubbs, Robert H.; Stoltz, Brian M.

2010-01-01

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.

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.

Rhodium-catalyzed Asymmetric Hydrogenation of α-Dehydroamino Ketones: A General Approach to Chiral α-amino Ketones.

Science.gov (United States)

Gao, Wenchao; Wang, Qingli; Xie, Yun; Lv, Hui; Zhang, Xumu

2016-01-01

Rhodium/DuanPhos-catalyzed asymmetric hydrogenation of aliphatic α-dehydroamino ketones has been achieved and afforded chiral α-amino ketones in high yields and excellent enantioselectives (up to 99 % ee), which could be reduced further to chiral β-amino alcohols by LiAlH(tBuO)3 with good yields. This protocol provides a readily accessible route for the synthesis of chiral α-amino ketones and chiral β-amino alcohols. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The use of phosphite-type ligands in the Ir-catalyzed asymmetric hydrogenation of heterocyclic compounds.

Science.gov (United States)

Lyubimov, Sergey E; Ozolin, Dmitry V; Ivanov, Pavel Yu; Melman, Artem; Velezheva, Valeriya S; Davankov, Vadim A

2014-01-01

A series of chiral phosphite-type ligands was tested in asymmetric Ir-catalyzed hydrogenation of quinolines and 2,4,5,6-tetrahydro-1H-pyrazino(3,2,1-j,k)carbazole. Hydrogenation of quinaldine hydrochloride provided superior enantioselectivity up to 65% ee compared to quinaldine free base. The ligands were tested for the first time in the asymmetric Ir-Ircatalyzed hydrogenation of 2,4,5,6-tetrahydro-1H-pyrazino(3,2,1-j,k)carbazole yielding the antidepressant drug, pirlindole. © 2013 Wiley Periodicals, Inc.

Enantioselective addition of nitrones to activated cyclopropanes.

Science.gov (United States)

Sibi, Mukund P; Ma, Zhihua; Jasperse, Craig P

2005-04-27

In this paper, we demonstrate the first examples of chiral Lewis acid catalysis in the formation of tetrahydro-1,2-oxazines with very high enantioselectivity starting with diactivated cyclopropanes and nitrones (>90% yields and ee). Reactions with racemic substituted cyclopropanes provide approximately 1:1 diastereomeric tetrahydro-1,2-oxazine products with high enantioselectivity. Mechanistic information for the formation of the tetrahydro-1,2-oxazines is also detailed.

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

Synthesis of chitosan-PEO hydrogels via mesylation and regioselective Cu(I)-catalyzed cycloaddition.

Science.gov (United States)

Tirino, Pasquale; Laurino, Rosaria; Maglio, Giovanni; Malinconico, Mario; d'Ayala, Giovanna Gomez; Laurienzo, Paola

2014-11-04

In this work, a well-defined hydrogel was developed by coupling chitosan with PEO through "click chemistry". Azide functionalities were introduced onto chitosan, through mesylation of C-6 hydroxyl groups, and reacted with a di-alkyne PEO by a regioselective Cu(I)-catalyzed cycloaddition. This synthetic approach allowed us to obtain a hydrogel with a controlled crosslinking degree. In fact, the extent of coupling is strictly dependent on the amount of azido groups on chitosan, which in turn can be easily modulated. The obtained hydrogel, with a crosslinking degree of around 90%, showed interesting swelling properties. With respect to chitosan hydrogels reported in literature, a considerably higher equilibrium uptake was reached (940%). The possibility to control the crosslinking degree of hydrogel and its capability to rapidly absorb high amounts of water make this material suitable for several applications, such as controlled drug release and wound healing. Copyright © 2014. Published by Elsevier Ltd.

Phosphine-catalyzed cycloadditions of allenic ketones: new substrates for nucleophilic catalysis.

Science.gov (United States)

Wallace, Debra J; Sidda, Rachel L; Reamer, Robert A

2007-02-02

A range of phosphine-catalyzed cycloaddition reactions of allenic ketones have been studied, extending the scope of these processes from the more widely used 2,3-butadienoates to allow access to a number of synthetically useful products. Reaction of allenyl methyl ketone 4 with exo-enones afforded spirocyclic compounds in good regioselectivity and promising enantioselectivity via a [2 + 3] cycloaddtion. Aromatic allenyl ketones undergo a phosphine-promoted dimerization to afford functionalized pyrans, leading to a formal [2 + 4] Diels-Alder product, but did not react in the [2 + 3] cycloaddition. The results from other reactions that had found utility with 2,3-butadienoates are also reported.

Lipase Catalyzed Kinetic Resolution of rac-2-(3-Methoxy-4-methylphenyl) propan-1-ol and rac-2-(3-Hydroxy-4-methylphenyl)propyl propanoate for S-(+)-Xanthorrhizol

International Nuclear Information System (INIS)

Shafioul, Azam Sharif Mohammed; Cheong, Chan Seong

2012-01-01

Xanthorrhizol is a bisabolane type of natural sesquiterpene, the major component of essential oils of Curcuma xanthorrhiza. 2-(3-Methoxy-4-methylphenyl)propan-1-ol and 2-(3-hydroxy-4-methyl phenyl)propan-1-ol could be essential building block for enantioselective synthesis of xanthorrhizol. Enantioselective (c = 53%, E = 80 ± 3) for R-(+)-2-(3-hydroxy-4-methylphenyl) propan-1-ol and (c = 58%, E = 27 ± 1) for R-(+)-2-(3- methoxy-4-methylphenyl) propan-1-ol resolution processes were developed via lipase-catalyzed reaction. We found lipase Aspergillus oryzae (AOL) and Porcine pancreas (PPL) are selective to transesterification and hydrolysis in organic and aqueous phase. Modified demethylated substrate is appropriate for enantioselective hydrolysis reaction without any additives. Enantiopure chiral alcohol was crystallized from ethyl acetate/ n-hexane co-solvent system. Gram scale resolved chiral intermediate will facilitate the synthesis of the unnatural S-(+)-xanthorrhizol, the corresponding isomer of the natural one

Lipase Catalyzed Kinetic Resolution of rac-2-(3-Methoxy-4-methylphenyl) propan-1-ol and rac-2-(3-Hydroxy-4-methylphenyl)propyl propanoate for S-(+)-Xanthorrhizol

Energy Technology Data Exchange (ETDEWEB)

Shafioul, Azam Sharif Mohammed [University of Science and Technology, Daejeon (Korea, Republic of); Cheong, Chan Seong [Korea Institute of Science and Technology, Seoul (Korea, Republic of)

2012-02-15

Xanthorrhizol is a bisabolane type of natural sesquiterpene, the major component of essential oils of Curcuma xanthorrhiza. 2-(3-Methoxy-4-methylphenyl)propan-1-ol and 2-(3-hydroxy-4-methyl phenyl)propan-1-ol could be essential building block for enantioselective synthesis of xanthorrhizol. Enantioselective (c = 53%, E = 80 ± 3) for R-(+)-2-(3-hydroxy-4-methylphenyl) propan-1-ol and (c = 58%, E = 27 ± 1) for R-(+)-2-(3- methoxy-4-methylphenyl) propan-1-ol resolution processes were developed via lipase-catalyzed reaction. We found lipase Aspergillus oryzae (AOL) and Porcine pancreas (PPL) are selective to transesterification and hydrolysis in organic and aqueous phase. Modified demethylated substrate is appropriate for enantioselective hydrolysis reaction without any additives. Enantiopure chiral alcohol was crystallized from ethyl acetate/ n-hexane co-solvent system. Gram scale resolved chiral intermediate will facilitate the synthesis of the unnatural S-(+)-xanthorrhizol, the corresponding isomer of the natural one.

An N-Linked Bidentate Phosphoramidite Ligand (N-Me-BIPAM for Rhodium-Catalyzed Asymmetric 1,4-Addition of Arylboronic Acids to α,β-Unsaturated Ketones

Directory of Open Access Journals (Sweden)

Norio Miyaura

2012-12-01

Full Text Available A new bidentate phosphoramidite (N-Me-BIPAM based on Shibasaki’s N-linked BINOL was synthesized. This ligand appears to be highly effective for rhodium-catalyzed asymmetric conjugated addition of arylboronic acids to α,β-unsaturated enones. The reaction of ortho-substituted arylboronic acid with acyclic and cyclic enones provides the corresponding products in good yields and enantioselectivities.

Large-scale ruthenium- and enzyme-catalyzed dynamic kinetic resolution of (rac-1-phenylethanol

Directory of Open Access Journals (Sweden)

Bäckvall Jan-E

2007-12-01

Full Text Available Abstract The scale-up of the ruthenium- and enzyme-catalyzed dynamic kinetic resolution (DKR of (rac-1-phenylethanol (2 is addressed. The immobilized lipase Candida antarctica lipase B (CALB was employed for the resolution, which shows high enantioselectivity in the transesterification. The ruthenium catalyst used, (η 5-C5Ph5RuCl(CO2 1, was shown to possess very high reactivity in the "in situ" redox racemization of 1-phenylethanol (2 in the presence of the immobilized enzyme, and could be used in 0.05 mol% with high efficiency. Commercially available isopropenyl acetate was employed as acylating agent in the lipase-catalyzed transesterifications, which makes the purification of the product very easy. In a successful large-scale DKR of 2, with 0.05 mol% of 1, (R-1-phenylethanol acetate (3 was obtained in 159 g (97% yield in excellent enantiomeric excess (99.8% ee.

Phosphoramidite accelerated copper(I)-catalyzed [3+2] cycloadditions of azides and alkynes

NARCIS (Netherlands)

Campbell-Verduyn, Lachlan S.; Mirfeizi, Leila; Dierckx, Rudi A.; Elsinga, Philip H.; Feringa, Ben L.

2009-01-01

Monodentate phosphoramidite ligands are used to accelerate the copper(I)-catalyzed 1,3-dipolar cycloaddition of azides and alkynes (CuAAC) rapidly yielding a wide variety of functionalized 1,4-disubstituted-1,2,3-triazoles; Cu(I) and Cu(II) salts both function as the copper source in aqueous

Asymmetric Synthesis of Hydrocarbazoles Catalyzed by an Octahedral Chiral-at-Rhodium Lewis Acid.

Science.gov (United States)

Huang, Yong; Song, Liangliang; Gong, Lei; Meggers, Eric

2015-12-01

A bis-cyclometalated chiral-at-metal rhodium complex catalyzes the Diels-Alder reaction between N-Boc-protected 3-vinylindoles (Boc = tert-butyloxycarbonyl) and β-carboxylic ester-substituted α,β-unsaturated 2-acyl imidazoles with good-to-excellent regioselectivity (up to 99:1) and excellent diastereoselectivity (>50:1 d.r.) as well as enantioselectivity (92-99% ee) under optimized conditions. The rhodium catalyst serves as a chiral Lewis acid to activate the 2-acyl imidazole dienophile by two-point binding and overrules the preferred regioselectivity of the uncatalyzed reaction. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Graphene-based hybrid for enantioselective sensing applications.

Science.gov (United States)

Zor, Erhan; Morales-Narváez, Eden; Alpaydin, Sabri; Bingol, Haluk; Ersoz, Mustafa; Merkoçi, Arben

2017-01-15

Chirality is a major field of research of chemical biology and is essential in pharmacology. Accordingly, approaches for distinguishing between different chiral forms of a compound are of great interest. We report on an efficient and generic enantioselective sensor that is achieved by coupling reduced graphene oxide with γ-cyclodextrin (rGO/γ-CD). The enantioselective sensing capability of the resulting structure was operated in both electrical and optical mode for of tryptophan enantiomers (D-/L-Trp). In this sense, voltammetric and photoluminescence measurements were conducted and the experimental results were compared to molecular docking method. We gain insight into the occurring recognition mechanism with selectivity toward D- and L-Trp as shown in voltammetric, photoluminescence and molecular docking responses. As an enantioselective solid phase on an electrochemical transducer, thanks to the different dimensional interaction of enantiomers with hybrid material, a discrepancy occurs in the Gibbs free energy leading to a difference in oxidation peak potential as observed in electrochemical measurements. The optical sensing principle is based on the energy transfer phenomenon that occurs between photoexcited D-/L-Trp enantiomers and rGO/γ-CD giving rise to an enantioselective photoluminescence quenching due to the tendency of chiral enantiomers to form complexes with γ-CD in different molecular orientations as demonstrated by molecular docking studies. The approach, which is the first demonstration of applicability of molecular docking to show both enantioselective electrochemical and photoluminescence quenching capabilities of a graphene-related hybrid material, is truly new and may have broad interest in combination of experimental and computational methods for enantiosensing of chiral molecules. Copyright © 2016 Elsevier B.V. All rights reserved.

Synthesis of polystyrene with high melting temperature through BDE/CuCl catalyzed polymerization

Institute of Scientific and Technical Information of China (English)

WAN; Xiaolong

2001-01-01

��Lecomte, P., Drapier, I., Dubios, P. et al., Controlled radical polymerization of methyl methacrylate in the presence of palladium acetate, triphenyl phosphine, and carbon tetrachloride, Macromolecules, 1997, 30: 7631.［12］Kotani, Y., Kamigaito, Y., Sawamoto, M., Re(V)-mediated living radical polymerization of styrene: ReO2I(PPh3)2/RI initiating system, Macromolecules, 1999, 32: 2420.［13］Makino, T., Tokunaga, E., Hogen-Esch, T. E., Controlled atom transfer radical polymerizations of methyl methacrylate under micellar conditions, Polym. Prep., 1998, 39(1): 288.［14］Gaynor, S. G., Qiu, J., Matyjaszewski, K., Controlled/"living" radical polymerization applied to water-borne system, Macromolecule, 1998, 31: 5951.［15］Qiu, J., Gaynor, S. G., Matyjaszewski, K., Controlled/"living" radical polymerization of n-butyl methacrylate by reverse atom transfer radical polymerization, Macromolecules, 1999, 32: 2872.［16］Shipp, D. A., McMurtry, G. P., Gaynor, S. G. et al., Water-borne block copolymer synthesis and a simple and effective one-pot synthesis of acrylate-methacrylate block copolymers by atom transfer radical polymerization, Polym. Prep., 1999, 40(2): 448.［17］Nishikawa, T., Kamigaito, M., Sawamoto, M., Living radical polymerization in water and alcohols: suspension polymerization of methyl methacrylate with RuCl2(PPh3)3 complex, Macromolecules, 1999, 32: 2204.［18］Wan, X. L., Ying, S. K., "Living" radical emulsion polymerization of styrene under Cu0/Bpy/CCl4 and CuCl2/Bpy/AIBN system, Chinese J. Polym. Sci., 2000, (1): 27.［19］Wan, X. L., Ying, S. K., Controlled radical polymerization catalyzed by Cu/BDE complex in water medium, 1. Polymerization of styrene and synthesis of poly(St-b-MMA), J. Appl. Polym. Sci., 2000, 75(1): 802.［20］Wan, X. L., Ying, S. K., Synthesis of block copolymers by emulsion "living"/controlled radical polymerization of vinyl monomers in sequence, Polym. Prep., 1999, 40: 1055.［21］Keller, R. N., Wycoff, H. D., The synthesis

Role of keto–enol tautomerization in a chiral phosphoric acid catalyzed asymmetric thiocarboxylysis of meso-epoxide: a DFT study

KAUST Repository

Ajitha, Manjaly John; Huang, Kuo-Wei

2015-01-01

The mechanism of a chiral phosphoric acid catalyzed thiocarboxylysis of meso-epoxide was investigated by density functional theory (DFT) calculations (M06-2X). The nucleophilic ring opening of epoxide by thiobenzoic acid was found to proceed via a concerted termolecular transition state with a simultaneous dual proton transfer to yield the β-hydroxy thioester product. Electrostatic interactions together with the steric environment inside the chiral catalyst play an important role in determining the enantioselectivity of the reaction.

Role of keto–enol tautomerization in a chiral phosphoric acid catalyzed asymmetric thiocarboxylysis of meso-epoxide: a DFT study

KAUST Repository

Ajitha, Manjaly John

2015-09-15

The mechanism of a chiral phosphoric acid catalyzed thiocarboxylysis of meso-epoxide was investigated by density functional theory (DFT) calculations (M06-2X). The nucleophilic ring opening of epoxide by thiobenzoic acid was found to proceed via a concerted termolecular transition state with a simultaneous dual proton transfer to yield the β-hydroxy thioester product. Electrostatic interactions together with the steric environment inside the chiral catalyst play an important role in determining the enantioselectivity of the reaction.

Development of Environment-Friendly Insecticides Based on Enantioselectivity: Bifenthrin as a Case.

Science.gov (United States)

Qian, Yi; Zhou, Peixue; Zhang, Quan

2017-01-01

Chiral insecticides significantly contribute to the environmental pollutions recently. As the development of industry and agriculture, increasing number of chiral insecticides are to be introduced into the market. However, their enantioselective toxicology to ecosystem still remains uncertain. In this review, we embarked on a structured search of bibliographic databases for peer-reviewed articles regarding the enantioselective effects of bifenthrin, a typical chiral insecticide, on both target and non-target species. With this enantioselective property of chiral insecticides, they often exhibit adverse effects on non-target species enantioselectively. Specifically, the enantioselective effects of bifenthrin on target and non-target organisms were discussed. In target species, R-bifenthrin exerts more significant activities in deinsectization, compared with S-bifenthrin. On the other hand, Sbifenthrin is more toxic to non-target species than R-bifenthrin, which suggests that the application of sole enantiomer is more efficient and environment-friendly than that of racemate. This review confirms the choice of environment-friendly insecticides from the perspective of the enantioselectivity of chiral insecticides. To make insecticides more efficient to target species and less toxic to non-target species, further research should be done to investigated the potential effects of targetactive enantiomers on non-target organisms as well as the enantioselective fate of enantiomers in multiple environmental matrix.

Copper(I)-catalyzed olefination of N-sulfonylhydrazones with sulfones.

Science.gov (United States)

Xu, Shuai; Gao, Yunpeng; Chen, Ri; Wang, Kang; Zhang, Yan; Wang, Jianbo

2016-03-25

The Cu(I)-catalyzed olefination of N-sulfonylhydrazones with sulfones via metal carbene intermediates is reported. This reaction uses readily available starting materials and is operationally simple, thus representing a practical method for the construction of carbon-carbon double bonds. Mechanistically, Cu(I) carbene formation and subsequent carbene migratory insertion are proposed as the key steps.

Organocatalysts for enantioselective synthesis of fine chemicals: definitions, trends and developments

Directory of Open Access Journals (Sweden)

Chiara Palumbo

2015-02-01

Full Text Available Organocatalysis, that is the use of small organic molecules to catalyze organic transformations, has been included among the most successful concepts in asymmetric catalysis, and it has been used for the enantioselective construction of C–C, C–N, C–O, C–S, C–P and C–halide bonds. Since the seminal works in early 2000, the scientific community has been paying an ever-growing attention to the use of organocatalysts for the synthesis, with high yields and remarkable stereoselectivities, of optically active fine chemicals of interest for the pharmaceutical industry. A brief overview is here presented about the two main classes of substrate activation by the catalyst: covalent organocatalysis and non-covalent organocatalysis, with a more stringent focus on some recent outcomes in the field of the latter and of hydrogen bond-based catalysis. Finally, some successful examples of heterogenization of organocatalysts are also discussed, in the view of a potential industrial exploitation.

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

Science.gov (United States)

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

2012-09-19

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

CU(II): catalyzed hydrazine reduction of ferric nitrate

International Nuclear Information System (INIS)

Karraker, D.G.

1981-11-01

A method is described for producing ferrous nitrate solutions by the cupric ion-catalyzed reduction of ferric nitrate with hydrazine. The reaction is complete in about 1.5 hours at 40 0 C. Hydrazoic acid is also produced in substantial quantities as a reaction byproduct

The Brønsted Acid-Catalyzed, Enantioselective Aza-Diels-Alder Reaction for the Direct Synthesis of Chiral Piperidones.

Science.gov (United States)

Weilbeer, Claudia; Sickert, Marcel; Naumov, Sergei; Schneider, Christoph

2017-01-12

We disclose herein the first enantioselective aza-Diels-Alder reaction of β-alkyl-substituted vinylketene silyl-O,O-acetals and imines furnishing a broad range of optically highly enriched 4-alkyl-substituted 2-piperidones. As a catalyst for this one-pot reaction we employed a chiral phosphoric acid which effects a vinylogous Mannich reaction directly followed by ring-closure to the lactam. Subsequent fully diastereoselective transformations including hydrogenation, enolate alkylation, and lactam alkylation/reduction processes converted the cycloadducts into various highly substituted piperidines of great utility for the synthesis of natural products and medicinally active compounds. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Luminescent chemical waves in the Cu(II)-catalyzed oscillatory oxidation of SCN- ions with hydrogen peroxide.

Science.gov (United States)

Pekala, Katarzyna; Jurczakowski, Rafał; Lewera, Adam; Orlik, Marek

2007-05-10

The oscillatory oxidation of thiocyanate ions with hydrogen peroxide, catalyzed by Cu2+ ions in alkaline media, was so far observed as occurring simultaneously in the entire space of the batch or flow reactor. We performed this reaction for the first time in the thin-layer reactor and observed the spatiotemporal course of the above process, in the presence of luminol as the chemiluminescent indicator. A series of luminescent patterns periodically starting from the random reaction center and spreading throughout the entire solution layer was reported. For a batch-stirred system, the bursts of luminescence were found to correlate with the steep decreases of the oscillating Pt electrode potential. These novel results open possibilities for further experimental and theoretical investigations of those spatiotemporal patterns, including studies of the mechanism of this chemically complex process.

N,N'-dioxide/nickel(II)-catalyzed asymmetric inverse-electron-demand hetero-diels-alder reaction of β,γ-unsaturated α-ketoesters with enecarbamates.

Science.gov (United States)

Zhou, Yuhang; Zhu, Yin; Lin, Lili; Zhang, Yulong; Zheng, Jianfeng; Liu, Xiaohua; Feng, Xiaoming

2014-12-08

N,N'-Dioxide/nickel(II) complexes have been developed to catalyze the inverse-electron-demand hetero-Diels-Alder reaction of β,γ-unsaturated α-ketoesters with acyclic enecarbamates. After detailed screening of the reaction parameters, mild optimized reaction conditions were established, affording 3,4-dihydro-2H-pyranamines in up to 99 % yield, 99 % ee and more than 95:5 d.r. The catalytic system was also efficient for β-substituted acyclic enecarbamates, affording more challenging 2,3,4-trisubstituted 3,4-dihydro-2H-pyranamine with three contiguous stereogenic centers in excellent yields, diastereoselectivities, and enantioselectivities. The reaction could be scaled up to a gram scale with no deterioration of either enantioselectivity or yield. Based on these experiments and on previous reports, a possible transition state was proposed. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rh-Catalyzed Annulations of N-Methoxybenzamides and Ketenimines: Sterically and Electronically Controlled Synthesis of Isoquinolinones and Isoindolinones.

Science.gov (United States)

Zhou, Xiaorong; Zhang, Zhiyin; Zhao, Hongyang; Lu, Ping; Wang, Yanguang

2017-04-07

Rhodium-catalyzed C-H activation/annulation reactions of ketenimines with N-methoxybenzamides are reported. The outcome of reactions is dependent on the structure of ketenimines. The β-alkyl-substituted ketenimines furnish 3-iminoisoquinolin-1(2H)-ones in a formal [4 + 2] annulation manner, while the β-ester substituted ketenimines afford 3-aminoisoindolin-1-ones in a formal [4 + 1] annulation manner. The synthesized [4 + 2] products undergo an intramolecular Cu-catalyzed C-N coupling to be converted to benzo[4,5]imidazo[1,2-b]isoquinolin-11-ones, which can be directly prepared from ketenimines and N-methoxybenzamides by a one-pot Rh-catalyzed annulation/Cu-catalyzed C-N coupling sequence.

γ-Sultam-cored N,N-ligands in the ruthenium(ii)-catalyzed asymmetric transfer hydrogenation of aryl ketones.

Science.gov (United States)

Rast, Slavko; Modec, Barbara; Stephan, Michel; Mohar, Barbara

2016-02-14

The synthesis of new enantiopure syn- and anti-3-(α-aminobenzyl)-benzo-γ-sultam ligands 6 and their application in the ruthenium(ii)-catalyzed asymmetric transfer hydrogenation (ATH) of ketones using formic acid/triethylamine is described. In particular, benzo-fused cyclic ketones afforded excellent enantioselectivities in reasonable time employing a low loading of the syn ligand-containing catalyst. A never-before-seen dynamic kinetic resolution (DKR) during reduction of a γ-keto carboxylic ester (S7) derivative of 1-indanone is realized leading as well to excellent induction.

Fully recoverable rigid shape memory foam based on copper-catalyzed azide-alkyne cycloaddition (CuAAC) using a salt leaching technique.

Science.gov (United States)

Alzahrani, Abeer A; Saed, Mohand; Yakacki, Christopher M; Song, Han Byul; Sowan, Nancy; Walston, Joshua J; Shah, Parag K; McBride, Matthew K; Stansbury, Jeffrey W; Bowman, Christopher N

2018-01-07

This study is the first to employ the use of the copper-catalyzed azide-alkyne cycloaddition (CuAAC) polymerization to form a tough and stiff, porous material from a well-defined network possessing a high glass transition temperature. The effect of the network linkages formed as a product of the CuAAC reaction, i.e., the triazoles, on the mechanical behavior at high strain was evaluated by comparing the CuAAC foam to an epoxy-amine-based foam, which consisted of monomers with similar backbone structures and mechanical properties (i.e., T g of 115 °C and a rubbery modulus of 1.0 MPa for the CuAAC foam, T g of 125 °C and a rubbery modulus of 1.2 MPa for the epoxy-amine foam). When each foam was compressed uniformly to 80% strain at ambient temperature, the epoxy-amine foam was severely damaged after only reaching 70% strain in the first compression cycle with a toughness of 300 MJ/m 3 . In contrast, the CuAAC foam exhibited pronounced ductile behavior in the glassy state with three times higher toughness of 850 MJ/m 3 after the first cycle of compression to 80% strain. Additionally, when the CuAAC foam was heated above T g after each of five compression cycles to 80% strain at ambient temperature, the foam completely recovered its original shape while exhibiting a gradual decrease in mechanical performance over the multiple compression cycles. The foam demonstrated almost complete shape fixity and recovery ratios even through five successive cycles, indicative of "reversible plasticity", making it highly desirable as a glassy shape memory foams.

Norcoclaurine Synthase: Mechanism of an Enantioselective Pictet-Spengler Catalyzing Enzyme

Directory of Open Access Journals (Sweden)

Alberto Macone

2010-03-01

Full Text Available The use of bifunctional catalysts in organic synthesis finds inspiration in the selectivity of enzymatic catalysis which arises from the specific interactions between basic and acidic amino acid residues and the substrate itself in order to stabilize developing charges in the transition state. Many enzymes act as bifunctional catalysts using amino acid residues at the active site as Lewis acids and Lewis bases to modify the substrate as required for the given transformation. They bear a clear advantage over non-biological methods for their ability to tackle problems related to the synthesis of enantiopure compounds as chiral building blocks for drugs and agrochemicals. Moreover, enzymatic synthesis may offer the advantage of a clean and green synthetic process in the absence of organic solvents and metal catalysts. In this work the reaction mechanism of norcoclaurine synthase is described. This enzyme catalyzes the Pictet-Spengler condensation of dopamine with 4-hydroxyphenylacetaldehyde (4-HPAA to yield the benzylisoquinoline alkaloids central precursor, (S-norcoclaurine. Kinetic and crystallographic data suggest that the reaction mechanism occurs according to a typical bifunctional catalytic process.

Fluxional additives: a second generation control in enantioselective catalysis.

Science.gov (United States)

Sibi, Mukund P; Manyem, Shankar; Palencia, Hector

2006-10-25

The concept of "fluxional additives", additives that can adopt enantiomeric conformations depending on the chiral information in the ligand, is demonstrated in enantioselective Diels-Alder and nitrone cycloaddition reactions. The additive design is modular, and diverse structures are accessible in three steps. Chiral Lewis acids from main group and transition metals show enhancements in enantioselectivity in the presence of these additives.

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.

Cyclopalladated complexes in enantioselective catalysis

Energy Technology Data Exchange (ETDEWEB)

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

2011-01-31

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

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.

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.

Ruthenium Hydride/Brønsted Acid-Catalyzed Tandem Isomerization/N-Acyliminium Cyclization Sequence for the Synthesis of Tetrahydro-β-carbolines

DEFF Research Database (Denmark)

Hansen, Casper Lykke; Clausen, Janie Regitse Waël; Ohm, Ragnhild Gaard

2013-01-01

This paper describes an efficient tandem sequence for the synthesis of 1,2,3,4-tetrahydro-β-carbolines (THBCs) relying on a ruthenium hydride/Brønsted acid- catalyzed isomerization of allylic amides to N-acyliminium ion intermediates which are trapped by a tethered indolenucleophile. The methodol...... the Suzuki cross-coupling reaction to the isomerization/N-acyliminium cyclization sequence. Finally, diastereo- and enantioselective versions of the title reaction have been examined using substrate control (with dr >15: 1) and asymmetric catalysis (ee up to 57%), respectively...

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

Science.gov (United States)

Zhang, Chunlong; Wen, Yuezhong; Liu, Weiping

2012-01-01

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

Enantioselective carbenoid insertion into C(sp3–H bonds

Directory of Open Access Journals (Sweden)

J. V. Santiago

2016-05-01

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

Copper-catalyzed radical carbooxygenation: alkylation and alkoxylation of styrenes.

Science.gov (United States)

Liao, Zhixiong; Yi, Hong; Li, Zheng; Fan, Chao; Zhang, Xu; Liu, Jie; Deng, Zixin; Lei, Aiwen

2015-01-01

A simple copper-catalyzed direct radical carbooxygenation of styrenes is developed utilizing alkyl bromides as radical resources. This catalytic radical difunctionalization accomplishes both alkylation and alkoxylation of styrenes in one pot. A broad range of styrenes and alcohols are well tolerated in this transformation. The EPR experiment shows that alkyl halides could oxidize Cu(I) to Cu(II) in this transformation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of DOTA-conjugated multimeric [Tyr3]octreotide peptides via a combination of Cu(I)-catalyzed "click" cycloaddition and thio acid/sulfonyl azide "sulfo-click" amidation and their in vivo evaluation.

NARCIS (Netherlands)

Yim, C.B.; Dijkgraaf, I.; Merkx, R.; Versluis, C.; Eek, A.; Mulder, G.E.; Rijkers, D.T.; Boerman, O.C.; Liskamp, R.M.

2010-01-01

Herein, we describe the design, synthesis, and biological evaluation of a series of DOTA-conjugated monomeric, dimeric, and tetrameric [Tyr(3)]octreotide-based analogues as a tool for tumor imaging and/or radionuclide therapy. These compounds were synthesized using a Cu(I)-catalyzed 1,3-dipolar

Scalable production of Cu@C composites for cross-coupling catalysis

Energy Technology Data Exchange (ETDEWEB)

Bu, Lijuan [Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081 (China); Ming, Hai, E-mail: lunaticmh@163.com [College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123 (China)

2015-10-15

Highlights: • Cu@C core–shell composite was prepared by reduction of [Cu(NH{sub 3}){sub 4}]{sup 2+} with glucose. • The carbon shell in Cu@C can be tuned to the different degree of carbonization. • The Cu@C composites were utilized to catalyze the C−N cross coupling reaction. • The catalytic ability of Cu@C depends on the degree of shell-carbonization. - Abstract: A novel Cu@C core–shell microstructure was prepared by reduction of [Cu(NH{sub 3}){sub 4}]{sup 2+} with glucose using a mild hydrothermal process. The carbon shell of such Cu@C composite can be tuned to different carbonization degrees just through varying the calcination conditions. The structural properties of as-prepared Cu@C were investigated in detail by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), transmission electron micrographs (TEM) and Raman spectra. In addition, these Cu@C composites were firstly used to catalyze the C−N cross coupling of amines with iodobenzene. Among them, the catalytic ability of Cu@C composites increased as their surface carbon’s carburization degree improved.

Evaluation of achiral templates with fluxional Brønsted basic substituents in enantioselective conjugate additions.

Science.gov (United States)

Adachi, Shinya; Takeda, Norihiko; Sibi, Mukund P

2014-12-19

Enantioselective conjugate addition of malononitrile to pyrazolidinone-derived enoates proceeds in excellent yields and high enantioselectivities. A comparison of fluxional substituents with and without a Brønsted basic site and their impact on selectivity is detailed. Molecular sieves as an additive were found to be essential to achieve high enantioselectivity.

Application of enantioselective radical reactions: synthesis of (+)-ricciocarpins A and B.

Science.gov (United States)

Sibi, Mukund P; He, Liwen

2004-05-27

Enantioselective synthesis of (+)-ricciocarpins A and B has been achieved in 41 and 45% overall yields, respectively, starting from a beta-substituted oxazolidinone. The key steps in the strategy are an enantioselective conjugate radical addition and the addition of a furyl organometallic to a key aldehyde intermediate. [reaction--see text

Synthesis, characterization and catalytic property of CuO and Ag/CuO nanoparticles for the epoxidation of styrene

Energy Technology Data Exchange (ETDEWEB)

Lashanizadegan, Maryam; Erfaninia, Nasrin [Alzahra University, Tehran (Iran, Islamic Republic of)

2013-11-15

CuO nanorodes, CuO nanoplates and Ag/CuO nanoparticles were synthesized in the presence of polyethylene glycol by depositional in alkaline environment. Oxide nanoparticles were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infrared absorption spectra (FT-IR). CuO and Ag/CuO nanoparticles show high catalytic activity for the selective epoxidation of styrene to styrene oxide by TBHP. Under the optimized reaction condition, the oxidation of styrene catalyzed by CuO nanorods gave 100% conversion with 60 and 35% styrene oxide and benzaldehyde, respectively. Ag/CuO gave 99% conversion and styrene oxide (71%) and benzaldehyde (12%) being the major product.

Primary Alcohols from Terminal Olefins: Formal Anti-Markovnikov Hydration via Triple Relay Catalysis

KAUST Repository

Dong, G.

2011-09-15

Alcohol synthesis is critical to the chemical and pharmaceutical industries. The addition of water across olefins to form primary alcohols (anti-Markovnikov olefin hydration) would be a broadly useful reaction but has largely proven elusive; an indirect hydroboration/oxidation sequence requiring stoichiometric borane and oxidant is currently the most practical methodology. Here, we report a more direct approach with the use of a triple relay catalysis system that couples palladium-catalyzed oxidation, acid-catalyzed hydrolysis, and ruthenium-catalyzed reduction cycles. Aryl-substituted terminal olefins are converted to primary alcohols by net reaction with water in good yield and excellent regioselectivity.

Regio- and Enantioselective Sequential Dehalogenation of rac-1,3-Dibromobutane by Haloalkane Dehalogenase LinB.

Science.gov (United States)

Gross, Johannes; Prokop, Zbyněk; Janssen, Dick; Faber, Kurt; Hall, Mélanie

2016-08-03

The hydrolytic dehalogenation of rac-1,3-dibromobutane catalyzed by the haloalkane dehalogenase LinB from Sphingobium japonicum UT26 proceeds in a sequential fashion: initial formation of intermediate haloalcohols followed by a second hydrolytic step to produce the final diol. Detailed investigation of the course of the reaction revealed favored nucleophilic displacement of the sec-halogen in the first hydrolytic event with pronounced R enantioselectivity. The second hydrolysis step proceeded with a regioselectivity switch at the primary position, with preference for the S enantiomer. Because of complex competition between all eight possible reactions, intermediate haloalcohols formed with moderate to good ee ((S)-4-bromobutan-2-ol: up to 87 %). Similarly, (S)-butane-1,3-diol was formed at a maximum ee of 35 % before full hydrolysis furnished the racemic diol product. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective H-atom transfer reaction: a strategy to synthesize formaldehyde aldol products.

Science.gov (United States)

Sibi, Mukund P; Patil, Kalyani

2005-04-14

[reaction: see text] Enantioselective radical alkylation of Baylis-Hillman adducts furnished aldol products in good yield and selectivity. The results illustrate that the selectivity in the hydrogen atom transfer is dependent on the size of the ester substituent, with smaller substituents providing better enantioselectivity.

Synthesis of a novel chemotype via sequential metal-catalyzed cycloisomerizations

Directory of Open Access Journals (Sweden)

Bo Leng

2012-08-01

Full Text Available Sequential cycloisomerizations of diynyl o-benzaldehyde substrates to access novel polycyclic cyclopropanes are reported. The reaction sequence involves initial Cu(I-mediated cycloisomerization/nucleophilic addition to an isochromene followed by diastereoselective Pt(II-catalyzed enyne cycloisomerization.

Enantioselective N-demethylation and hydroxylation of sibutramine in human liver microsomes and recombinant cytochrome p-450 isoforms.

Science.gov (United States)

Shinde, Dhananjay D; Kim, Min-Jung; Jeong, Eun-Sook; Kim, Yang-Weon; Lee, Ji-Woo; Shin, Jae-Gook; Kim, Dong-Hyun

2014-01-01

The enantioselective metabolism of sibutramine was examined using human liver microsomes (HLM) and recombinant cytochrome P-450 (CYP) isoforms. This drug is metabolized to N-mono-desmethyl- (M1) and N,N-di-desmethylsibutramine (M2), and subsequent hydroxylation results in hydroxyl M1 (HM1) and hydroxyl M2 (HM2). No significant difference was noted in formation of M1from sibutramine between R- and S-sibutramine in HLM. However, S-enantiomers of M1 and M2 were preferentially metabolized to M2, HM1, and HM2compared to R-enantiomers in HLM, and intrinsic clearance (Clint) ratios of S-enantiomers/R-enantiomers were 1.97, 4.83, and 9.94 for M2, HM1, and HM2, respectively. CYP3A4 and CYP3A5 were only involved in the formation of M1, whereas CYP2B6 and CYP2C19 were responsible for all metabolic reactions of sibutramine. CYP2C19 and CYP3A5 displayed catalytic preference for S-sibutramine to S-M1, whereas CYP2B6 and CYP3A4 showed little or no stereoselectivity in metabolism of sibutramine to M1. In the case of M2 formation, CYP2B6 metabolized S-M1 more rapidly than R-M1 with a Clint ratio of 2.14. However, CYP2C19 catalyzed less S-M1 than R-M1 and the Clint ratio of S-M1 to R-M1 was 0.65. The most significant enantioselectivity was observed in formation of HM1 from M1, and HM2 from M2. CYP2B6 and CYP2C19 exhibited preferential catalysis of formation of hydroxyl metabolites from S-enantiomers rather than R-enantiomers. These results indicate that S-sibutramine was more rapidly metabolized by CYP isoforms than R-sibutramine, and that enantioselective metabolism needs to be considered in drug interactions involving sibutramine and co-administered drugs.

Investigation of Radioiodination of Meta-Iodobenzylguanidine Compound with 131I Isotope in Solid Phase Using Cu Catalyzer

International Nuclear Information System (INIS)

Davarpanah, M. R.; Attar Nosrati, S.; Khoshhosn, H.; Kazemi Boudani, M.; Fazlali, M.; Ghannadi Maragheh, M.

2012-01-01

In this study the radioiodination process of meta-iodobenzylguanidine with 131 I isotope in presence of ammonium sulphate and Cu(II) Catalyzer was investigated. In order to optimize the process, the influence of different parameters on labeling yield was studied. The results of experiments showed that the use of oil bath with temperature of 160 d egree C is necessary. After the labeling process, purification step of the final product was carried out using Dowex-1 x 8 resin. The mean labeling yield was 97.2 p ercent . In this method radiolabelling of MIBG with 131 I (185 MBq for diagnostic dose and 3330 MBq for therapeutic dose) is quite simple and it complies with the requirements of routine production of 13 1I-MIBG radiopharmaceutical for diagnostic and therapeutic purposes. This paper is a narration of industrial scale production of 131 I-MIBG radiopharmaceutical.

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.

Atroposelective Synthesis of Axially Chiral Biaryls by Palladium-Catalyzed Asymmetric C-H Olefination Enabled by a Transient Chiral Auxiliary.

Science.gov (United States)

Yao, Qi-Jun; Zhang, Shuo; Zhan, Bei-Bei; Shi, Bing-Feng

2017-06-01

Atroposelective synthesis of axially chiral biaryls by palladium-catalyzed C-H olefination, using tert-leucine as an inexpensive, catalytic, and transient chiral auxiliary, has been realized. This strategy provides a highly efficient and straightforward access to a broad range of enantioenriched biaryls in good yields (up to 98 %) with excellent enantioselectivities (95 to >99 % ee). Kinetic resolution of trisubstituted biaryls bearing sterically more demanding substituents is also operative, thus furnishing the optically active olefinated products with excellent selectivity (95 to >99 % ee, s-factor up to 600). © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Organocatalytic Asymmetric Michael Addition of 4-Hydroxycoumarin to β,γ-Unsaturated α-Keto Esters

Energy Technology Data Exchange (ETDEWEB)

Suh, Chang Won; Han, Tae Hyun; Kim, Dae Young [Soonchunhyang Univ., Asan (Korea, Republic of)

2013-06-15

In conclusion, we have developed organocatalytic enantioselective conjugate addition reaction of 4-hydroxycoumarin (1) to β,γ-unsaturated α-keto esters 2 to afford biologically valuable warfarin derivatives 3. The process is efficiently catalyzed by a binaphthyl-modified thiourea organocatalyst. The coumarin core is present as a characteristic structural motif in a large number of natural products and biologically active molecules.1 Particularly, many of these naturally occurring 4-hydroxycoumarin and their synthetic analogues are important precursors for the synthesis of natural products and pharmaceuticals. Enantioselective organocatalytic conjugate addition of 4-hydroxycoumarin to α,β-unsaturated ketones is a straightforward method to access warfarin which is an effective anticoagulants. Although a number of reactions of α,β-unsaturated ketones as Michael acceptors have been reported, the corresponding β,γ-unsaturated α-keto esters have received relatively little attention as Michael acceptors. Recently, several groups have reported the asymmetric Michael addition of 4-hydroxycoumarin to β,γ-unsaturated α-keto esters catalyzed by Cu(II)-bisoxazoline, N,N'-dioxide-Ni(II) complexes, thiourea catalysts. Although several efficient methods have been achieved by these systems, an effective method for the synthesis of warfarin analogues is still a challenge.

Organocatalytic Asymmetric Michael Addition of 4-Hydroxycoumarin to β,γ-Unsaturated α-Keto Esters

International Nuclear Information System (INIS)

Suh, Chang Won; Han, Tae Hyun; Kim, Dae Young

2013-01-01

In conclusion, we have developed organocatalytic enantioselective conjugate addition reaction of 4-hydroxycoumarin (1) to β,γ-unsaturated α-keto esters 2 to afford biologically valuable warfarin derivatives 3. The process is efficiently catalyzed by a binaphthyl-modified thiourea organocatalyst. The coumarin core is present as a characteristic structural motif in a large number of natural products and biologically active molecules.1 Particularly, many of these naturally occurring 4-hydroxycoumarin and their synthetic analogues are important precursors for the synthesis of natural products and pharmaceuticals. Enantioselective organocatalytic conjugate addition of 4-hydroxycoumarin to α,β-unsaturated ketones is a straightforward method to access warfarin which is an effective anticoagulants. Although a number of reactions of α,β-unsaturated ketones as Michael acceptors have been reported, the corresponding β,γ-unsaturated α-keto esters have received relatively little attention as Michael acceptors. Recently, several groups have reported the asymmetric Michael addition of 4-hydroxycoumarin to β,γ-unsaturated α-keto esters catalyzed by Cu(II)-bisoxazoline, N,N'-dioxide-Ni(II) complexes, thiourea catalysts. Although several efficient methods have been achieved by these systems, an effective method for the synthesis of warfarin analogues is still a challenge

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%)

Vancomycin Molecular Interactions: Antibiotic and Enantioselective Mechanisms

Science.gov (United States)

Ward, Timothy J.; Gilmore, Aprile; Ward, Karen; Vowell, Courtney

Medical studies established that vancomycin and other related macrocyclic antibiotics have an enhanced antimicrobial activity when they are associated as dimers. The carbohydrate units attached to the vancomycin basket have an essential role in the dimerization reaction. Covalently synthesized dimers were found active against vancomycin-resistant bacterial strains. A great similarity between antibiotic potential and enantioselectivity was established. A covalent vancomycin dimer was studied in capillary electrophoresis producing excellent chiral separation of dansyl amino acids. Balhimycin is a macrocyclic glycopeptide structurally similar to vancomycin. The small differences are, however, responsible for drastic differences in enantioselectivity in the same experimental conditions. Contributions from studies examining vancomycin's mechanism for antimicrobial activity have substantially aided our understanding of its mechanism in chiral recognition.

Enantioselective synthesis of tetrafluorinated ribose and fructose.

Science.gov (United States)

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

2009-02-21

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

Determination of the human cytochrome P450 monooxygenase catalyzing the enantioselective oxidation of 2,2',3,5',6-pentachlorobiphenyl (PCB 95) and 2,2',3,4,4',5',6-heptachlorobiphenyl (PCB 183).

Science.gov (United States)

Nagayoshi, Haruna; Kakimoto, Kensaku; Konishi, Yoshimasa; Kajimura, Keiji; Nakano, Takeshi

2017-10-17

2,2',3,5',6-Pentachlorobiphenyl (PCB 95) and 2,2',3,4,4',5',6-heptachlorobiphenyl (PCB 183) possess axial chirality and form the aS and aR enantiomers. The enantiomers of these congeners have been reported to accumulate in the human body enantioselectively via unknown mechanisms. In this study, we determined the cytochrome P450 (CYP) monooxygenase responsible for the enantioselective oxidization of PCB 95 and PCB 183, using a recombinant human CYP monooxygenase. We evaluated 13 CYP monooxygenases, namely CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2E1, CYP2J2, CYP3A4, CYP3A5, CYP4F2, and aromatase (CYP19), and revealed that CYP2A6 preferably oxidizes aS-PCB 95 enantioselectively; however, it did not oxidize PCB 183. The enantiomer composition was elevated from 0.5 (racemate) to 0.54. In addition, following incubation with CYP2A6, the enantiomer fraction (EF) of PCB 95 demonstrated a time-dependent increase.

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 ...

From ketones to esters by a Cu-catalyzed highly selective C(CO)-C(alkyl) bond cleavage: aerobic oxidation and oxygenation with air.

Science.gov (United States)

Huang, Xiaoqiang; Li, Xinyao; Zou, Miancheng; Song, Song; Tang, Conghui; Yuan, Yizhi; Jiao, Ning

2014-10-22

The Cu-catalyzed aerobic oxidative esterification of simple ketones via C-C bond cleavage has been developed. Varieties of common ketones, even inactive aryl long-chain alkyl ketones, are selectively converted into esters. The reaction tolerates a wide range of alcohols, including primary and secondary alcohols, chiral alcohols with retention of the configuration, electron-deficient phenols, as well as various natural alcohols. The usage of inexpensive copper catalyst, broad substrate scope, and neutral and open air conditions make this protocol very practical. (18)O labeling experiments reveal that oxygenation occurs during this transformation. Preliminary mechanism studies indicate that two novel pathways are mainly involved in this process.

Copper-catalyzed azide alkyne cycloaddition polymer networks

Science.gov (United States)

Alzahrani, Abeer Ahmed

The click reaction concept, introduced in 2001, has since spurred the rapid development and reexamination of efficient, high yield reactions which proceed rapidly under mild conditions. Prior to the discovery of facile copper catalysis in 2002, the thermally activated azide-alkyne or Huisgen cycloaddition reaction was largely ignored following its discovery in large part due to its slow kinetics, requirement for elevated temperature and limited selectivity. Now, arguably, the most prolific and capable of the click reactions, the copper-catalyzed azide alkyne cycloaddition (CuAAC) reaction is extremely efficient and affords exquisite control of the reaction. The orthogonally and chemoselectivity of this reaction enable its wide utility across varied scientific fields. Despite numerous inherent advantages and widespread use for small molecule synthesis and solution-based polymer chemistry, it has only recently and rarely been utilized to form polymer networks. This work focuses on the synthesis, mechanisms, and unique attributes of the CuAAC reaction for the fabrication of functional polymer networks. The photo-reduction of a series of copper(II)/amine complexes via ligand metal charge transfer was examined to determine their relative efficiency and selectivity in catalyzing the CuAAC reaction. The aliphatic amine ligands were used as an electron transfer species to reduce Cu(II) upon irradiation with 365 nm light while also functioning as an accelerating agent and as protecting ligands for the Cu(I) that was formed. Among the aliphatic amines studied, tertiary amines such as triethylamine (TEA), tetramethyldiamine (TMDA), N,N,N',N",N"-pentamethyldiethylenetriamine (PMDTA), and hexamethylenetetramine (HMTETA) were found to be the most effective. The reaction kinetics were accelerated by increasing the PMDETA : Cu(II) ratio with a ratio of ligand to Cu(II) of 4:1 yielding the maximum conversion in the shortest time. The sequential and orthogonal nature of the photo-Cu

Enantioselective 1,3-dipolar cycloadditions of diazoacetates with electron-deficient olefins.

Science.gov (United States)

Sibi, Mukund P; Stanley, Levi M; Soeta, Takahiro

2007-04-12

[reaction: see text] A general strategy for highly enantioselective 1,3-dipolar cycloaddition of diazoesters to beta-substituted, alpha-substituted, and alpha,beta-disubstituted alpha,beta-unsaturated pyrazolidinone imides is described. Cycloadditions utilizing less reactive alpha,beta-disubstituted dipolarophiles require elevated reaction temperatures, but still provide the corresponding pyrazolines with excellent enantioselectivities. Finally, an efficient synthesis of (-)-manzacidin A employing this cycloaddition methodology as a key step is illustrated.

Quinine-Promoted, Enantioselective Boron-Tethered Diels-Alder Reaction by Anomeric Control of Transition State Conformation.

Science.gov (United States)

Scholl, Katie; Dillashaw, John; Timpy, Evan; Lam, Yu-Hong; DeRatt, Lindsey; Benton, Tyler R; Powell, Jacqueline P; Houk, Kendall N; Morgan, Jeremy B

2018-05-01

Diels-Alder reactions of tethered vinyl-metal species offer the opportunity to fashion highly functionalized diol intermediates for synthesis. We have developed the first enantioselective boron-tethered Diels-Alder reaction using quinine as a chiral promoter. Quinine recovery, enantioselectivity enhancement, and manipulation of the cyclohexene core are also investigated. DFT modeling calculations confirm the role of quinine as a bidentate ligand enhancing reaction rates. The enantioselectivity of the cycloaddition is proposed to originate from a boron-centered anomeric effect.

Exo selective enantioselective nitrone cycloadditions.

Science.gov (United States)

Sibi, Mukund P; Ma, Zhihua; Jasperse, Craig P

2004-01-28

We have developed a novel method for accessing exo adducts with high enantioselectivity in nitrone cycloadditions to enoates. Pyrazolidinones proved to be effective achiral templates in the cycloadditions, providing exo adducts typically in >15:1 selectivity and 90-98% ee. The use of Lewis acids that form square planar complexes, such as copper triflate, was important for obtaining high exo selectivity.

In vitro enantioselective human liver microsomal metabolism and prediction of in vivo pharmacokinetic parameters of tetrabenazine by DLLME-CE.

Science.gov (United States)

Bocato, Mariana Zuccherato; de Lima Moreira, Fernanda; de Albuquerque, Nayara Cristina Perez; de Gaitani, Cristiane Masetto; de Oliveira, Anderson Rodrigo Moraes

2016-09-05

A new capillary electrophoresis method for the enantioselective analysis of cis- and trans- dihydrotetrabenazine (diHTBZ) after in vitro metabolism by human liver microsomes (HLMs) was developed. The chiral electrophoretic separations were performed by using tris-phosphate buffer (pH 2.5) containing 1% (w/v) carboxymethyl-β-CD as background electrolyte with an applied voltage of +15kV and capillary temperature kept at 15°C. Dispersive liquid-liquid microextraction was employed to extract the analytes from HLMs. Dichloromethane was used as extraction solvent (75μL) and acetone as disperser solvent (150μL). The method was validated according to official guidelines and showed to be linear over the concentration range of 0.29-19.57μmolL(-1) (r=0.9955) for each metabolite enantiomer. Within- and between-day precision and accuracy evaluated by relative standard deviation and relative error were lower than 15% for all enantiomers. The stability assay showed that the analytes kept stable under handling, storage and in metabolism conditions. After method validation, an enantioselective in vitro metabolism and in vivo pharmacokinetic prediction was carried out. This study showed a stereoselective metabolism and the observed kinetic profile indicated a substrate inhibition behavior. DiHTBZ enantiomers were catalyzed mainly by CYP2C19 and the predicted clearance suggests that liver metabolism is the main route for TBZ elimination which supports the literature data. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Regio- and enantioselective synthesis of N-substituted pyrazoles by rhodium-catalyzed asymmetric addition to allenes.

Science.gov (United States)

Haydl, Alexander M; Xu, Kun; Breit, Bernhard

2015-06-08

The rhodium-catalyzed asymmetric N-selective coupling of pyrazole derivatives with terminal allenes gives access to enantioenriched secondary and tertiary allylic pyrazoles, which can be employed for the synthesis of medicinally important targets. The reaction tolerates a large variety of functional groups and labelling experiments gave insights into the reaction mechanism. This new methodology was further applied in a highly efficient synthesis of JAK 1/2 inhibitor (R)-ruxolitinib. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A TEMPO-free copper-catalyzed aerobic oxidation of alcohols.

Science.gov (United States)

Xu, Boran; Lumb, Jean-Philip; Arndtsen, Bruce A

2015-03-27

The copper-catalyzed aerobic oxidation of primary and secondary alcohols without an external N-oxide co-oxidant is described. The catalyst system is composed of a Cu/diamine complex inspired by the enzyme tyrosinase, along with dimethylaminopyridine (DMAP) or N-methylimidazole (NMI). The Cu catalyst system works without 2,2,6,6-tetramethyl-l-piperidinoxyl (TEMPO) at ambient pressure and temperature, and displays activity for un-activated secondary alcohols, which remain a challenging substrate for catalytic aerobic systems. Our work underscores the importance of finding alternative mechanistic pathways for alcohol oxidation, which complement Cu/TEMPO systems, and demonstrate, in this case, a preference for the oxidation of activated secondary over primary alcohols. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Oligomerization of optically active N-(4-hydroxyphenylmandelamide in the presence of β-cyclodextrin and the minor role of chirality

Directory of Open Access Journals (Sweden)

Helmut Ritter

2014-10-01

Full Text Available The oxidative oligomerization of a chiral mandelamide derivative (N-(4-hydroxyphenylmandelamide, 1 was performed in the presence of horseradish peroxidase, laccase and N,N'-bis(salicylideneethylenediamine-iron(II to obtain chiral oligophenols 2. The low enantioselectivity of the enzymatic catalyzed asymmetric enantiomer-differentiating oligomerizations was investigated. In addition, the poor influence of cyclodextrin on the enantioselectivity of enzymatic catalyzed asymmetric enantiomer-differentiating oligomerizations was studied.

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

Science.gov (United States)

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

2015-03-01

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

Aerobic Asymmetric Dehydrogenative Cross-Coupling between Two C(sp3)-H Groups Catalyzed by a Chiral-at-Metal Rhodium Complex.

Science.gov (United States)

Tan, Yuqi; Yuan, Wei; Gong, Lei; Meggers, Eric

2015-10-26

A sustainable C-C bond formation is merged with the catalytic asymmetric generation of one or two stereocenters. The introduced catalytic asymmetric cross-coupling of two C(sp3)-H groups with molecular oxygen as the oxidant profits from the oxidative robustness of a chiral-at-metal rhodium(III) catalyst and exploits an autoxidation mechanism or visible-light photosensitized oxidation. In the latter case, the catalyst serves a dual function, namely as a chiral Lewis acid for catalyzing enantioselective enolate chemistry and at the same time as a visible-light-driven photoredox catalyst. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Catalytic Enantioselective Total Synthesis of (+)-Liphagal

KAUST Repository

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

2011-01-01

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.

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.

Enantioselective ProPhenol-catalyzed addition of 1,3-diynes to aldehydes to generate synthetically versatile building blocks and diyne natural products.

Science.gov (United States)

Trost, Barry M; Chan, Vincent S; Yamamoto, Daisuke

2010-04-14

A highly enantioselective method for the catalytic addition of terminal 1,3-diynes to aldehydes was developed using our dinuclear zinc ProPhenol (1) system. Furthermore, triphenylphosphine oxide was found to interact synergistically with the catalyst to substantially enhance the chiral recognition. The generality of this catalytic transformation was demonstrated with aryl, alpha,beta-unsaturated and saturated aldehydes, of which the latter were previously limited in alkynyl zinc additions. The chiral diynol products are also versatile building blocks that can be readily elaborated; this was illustrated through highly selective trans-hydrosilylations, which enabled the synthesis of a beta-hydroxyketone and enyne. Additionally, the development of this method allowed for the rapid total syntheses of several biologically important diynol-containing natural products.

Facile synthesis of dendritic Cu by electroless reaction of Cu-Al alloys in multiphase solution

Science.gov (United States)

Wang, Ying; Liang, Shuhua; Yang, Qing; Wang, Xianhui

2016-11-01

Two-dimensional nano- or micro-scale fractal dendritic coppers (FDCs) were synthesized by electroless immersing of Cu-Al alloys in hydrochloric acid solution containing copper chloride without any assistance of template or surfactant. The FDC size increases with the increase of Al content in Cu-Al alloys immersed in CuCl2 + HCl solution. Compared to Cu40Al60 and Cu45Al55 alloys, the FDC shows hierarchical distribution and homogeneous structures using Cu17Al83 alloy as the starting alloy. The growth direction of the FDC is , and all angles between the trunks and branches are 60°. Nanoscale Cu2O was found at the edge of FDC. Interestingly, nanoporous copper (NPC) can also be obtained through Cu17Al83 alloy. Studies showed that the formation of FDC depended on two key factors: the potential difference between CuAl2 intermetallic and α-Al phase of dual-phase Cu-Al alloys; a replacement reaction that usually occurs in multiphase solution. The electrochemical experiment further proved that the multi-branch dendritic structure is very beneficial to the proton transfer in the process of catalyzing methanol.

Cu(I)/Diamine-catalyzed Aryl-alkyne Coupling Reactions

Institute of Scientific and Technical Information of China (English)

无

2005-01-01

CuI/ethylene diamine/K2CO3/dioxane is shown to be a useful system for the cross coupling reactions of various aryl iodides and bromides with aryl and alkyl alkynes. Compared to the conventional Sonogashira reactions, the new procedure is free of palladium and phosphines.

Heterocycles by Transition Metals Catalyzed Intramolecular Cyclization of Acetylene Compounds

International Nuclear Information System (INIS)

Vizer, S.A.; Yerzhanov, K.B.; Dedeshko, E.C.

2003-01-01

Review shows the new strategies in the synthesis of heterocycles, having nitrogen, oxygen and sulfur atoms, via transition metals catalyzed intramolecular cyclization of acetylenic compounds on the data published at the last 30 years, Unsaturated heterocyclic compounds (pyrroles and pyrroline, furans, dihydro furans and benzofurans, indoles and iso-indoles, isoquinolines and isoquinolinones, aurones, iso coumarins and oxazolinone, lactams and lactones with various substitutes in heterocycles) are formed by transition metals, those salts [PdCl 2 , Pd(OAc) 2 , HgCl 2 , Hg(OAc) 2 , Hg(OCOCF 3 ) 2 , AuCl 3 ·2H 2 O, NaAuCl 4 ·2H 2 O, CuI, CuCl], oxides (HgO) and complexes [Pd(OAc) 2 (PPh 3 )2, Pd(PPh 3 ) 4 , PdCl 2 (MeCN) 2 , Pd(OAc ) 2 /TPPTS] catalyzed intramolecular cyclization of acetylenic amines, amides, ethers, alcohols, acids, ketones and βdiketones. More complex hetero polycyclic systems typical for natural alkaloids can to obtain similar. Proposed mechanisms of pyrroles, isoquinolines, iso indoles and indoles, benzofurans and iso coumarins, thiazolopyrimidinones formation are considered. (author)

Copper-Catalyzed Oxidative Reaction of β-Keto Sulfones with Alcohols via C-S Bond Cleavage: Reaction Development and Mechanism Study.

Science.gov (United States)

Du, Bingnan; Wang, Wenmin; Wang, Yang; Qi, Zhenghang; Tian, Jiaqi; Zhou, Jie; Wang, Xiaochen; Han, Jianlin; Ma, Jing; Pan, Yi

2018-02-16

A Cu-catalyzed cascade oxidative radical process of β-keto sulfones with alcohols has been achieved by using oxygen as an oxidant. In this reaction, β-keto sulfones were converted into sulfinate esters under the oxidative conditions via cleavage of C-S bond. Experimental and computational studies demonstrate that a new pathway is involved in this reaction, which proceeds through the formation of the key four-coordinated Cu II intermediate, O-O bond homolysis induced C-S bond cleavage and Cu-catalyzed esterification to form the final products. This reaction provides a new strategy to sulfonate esters and enriches the research content of C-S bond cleavage and transformations. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Copper-catalyzed decarboxylative trifluoromethylation of allylic bromodifluoroacetates.

Science.gov (United States)

Ambler, Brett R; Altman, Ryan A

2013-11-01

The development of new synthetic fluorination reactions has important implications in medicinal, agricultural, and materials chemistries. Given the prevalence and accessibility of alcohols, methods to convert alcohols to trifluoromethanes are desirable. However, this transformation typically requires four-step processes, specialty chemicals, and/or stoichiometric metals to access the trifluoromethyl-containing product. A two-step copper-catalyzed decarboxylative protocol for converting allylic alcohols to trifluoromethanes is reported. Preliminary mechanistic studies distinguish this reaction from previously reported Cu-mediated reactions.

Mechanistic Insights into Solvent and Ligand Dependency in Cu(I)-Catalyzed Allylic Alkylation with gem-Diborylalkanes.

Science.gov (United States)

Zhang, Qi; Wang, Bing; Liu, Jia-Qin; Fu, Yao; Wu, Yu-Cheng

2018-01-19

The recent Cu-catalyzed allylic substitution reaction between gem-diboryalkane and allyl electrophiles shows intriguing solvent and ligand-controlled regioselectivity. The α-alkylation product was obtained in DMF solvent, while γ-alkylation product was obtained in dioxane solvent and the dioxane and NHC ligand situation. In the present study, density functional theory calculations have been used to investigate the reaction mechanism and origin of the regioselectivity. For both dioxane and DMF, γ-alkylation undergoes successive oxidative addition (CH 2 Bpin trans to leaving group) and direct Cγ-C reductive elimination. The α-alkylation is found to undergo oxidative addition (CH 2 Bpin trans to leaving group), isomerization, and Cα-C reductive elimination rather than the previously proposed oxidative addition (-CH 2 Bpin cis to the leaving group) and Cα-C reductive elimination. The γ-alkylation and α-alkylation is, respectively, favorable for dioxane and DMF solvent, which is consistent with the γ- and α-selectivity in experiment. The solvent interferes the isomerization step, thereby affects the relative facility of the α- and γ-alkylation. Further investigation shows that η 1 -intermediate formation promoted by solvent is the rate-determining step of the isomerization. The stronger electron-donating ability of DMF than dioxane facilitates the η 1 -intermediate formation and finally results in the easier isomerization in DMF. For dioxane and NHC situation, in the presence of neutral NHC ligand, the -PO 4 Et 2 group tightly coordinates with the Cu center after the oxidative addition, preventing the isomerization process. The regioselectivity is determined by the relative facility of the oxidative addition step. Therefore, the favorable oxidative addition (in which -CH 2 Bpin trans to the leaving group) results in the facility of γ-alkylation.

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.

Enantioselective Epoxide Polymerization Using a Bimetallic Cobalt Catalyst

KAUST Repository

Thomas, Renee M.; Widger, Peter C. B.; Ahmed, Syud M.; Jeske, Ryan C.; Hirahata, Wataru; Lobkovsky, Emil B.; Coates, Geoffrey W.

2010-01-01

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.

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

Science.gov (United States)

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

2015-04-01

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

The Palladium-Catalyzed Aerobic Kinetic Resolution of Secondary Alcohols: Reaction Development, Scope, and Applications

KAUST Repository

Ebner, Davidâ C.; Bagdanoff, Jeffreyâ T.; Ferreira, Ericâ M.; McFadden, Ryanâ M.; Caspi, Danielâ D.; Trend, Raissaâ M.; Stoltz, Brianâ M.

2009-01-01

The first palladium-catalyzed enantioselective oxidation of secondary alcohols has been developed, utilizing the readily available diamine (-)-sparteine as a chiral ligand and molecular oxygen as the stoichiometric oxidant. Mechanistic insights regarding the role of the base and hydrogen-bond donors have resulted in several improvements to the original system. Namely, addition of cesium carbonate and tert-butyl alcohol greatly enhances reaction rates, promoting rapid resolutions. The use of chloroform as solvent allows the use of ambient air as the terminal oxidant at 23 degrees C, resulting in enhanced catalyst selectivity. These improved reaction conditions have permitted the successful kinetic resolution of benzylic, allylic, and cyclopropyl secondary alcohols to high enantiomeric excess with good-to-excellent selectivity factors. This catalyst system has also been applied to the desymmetrization of meso-diols, providing high yields of enantioenriched hydroxyketones.

The Palladium-Catalyzed Aerobic Kinetic Resolution of Secondary Alcohols: Reaction Development, Scope, and Applications

KAUST Repository

Ebner, Davidâ C.

2009-12-07

The first palladium-catalyzed enantioselective oxidation of secondary alcohols has been developed, utilizing the readily available diamine (-)-sparteine as a chiral ligand and molecular oxygen as the stoichiometric oxidant. Mechanistic insights regarding the role of the base and hydrogen-bond donors have resulted in several improvements to the original system. Namely, addition of cesium carbonate and tert-butyl alcohol greatly enhances reaction rates, promoting rapid resolutions. The use of chloroform as solvent allows the use of ambient air as the terminal oxidant at 23 degrees C, resulting in enhanced catalyst selectivity. These improved reaction conditions have permitted the successful kinetic resolution of benzylic, allylic, and cyclopropyl secondary alcohols to high enantiomeric excess with good-to-excellent selectivity factors. This catalyst system has also been applied to the desymmetrization of meso-diols, providing high yields of enantioenriched hydroxyketones.

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

Science.gov (United States)

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

2015-07-24

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

Enantioselective radical addition/trapping reactions with alpha,beta-disubstituted unsaturated imides. Synthesis of anti-propionate aldols.

Science.gov (United States)

Sibi, Mukund P; Petrovic, Goran; Zimmerman, Jake

2005-03-02

This manuscript describes a highly diastereo- and enantioselective intermolecular radical addition/hydrogen atom transfer to alpha,beta-disubstituted enoates. Additionally, we show that anti-propionate aldol-like products can be easily prepared from alpha-methyl-beta-acyloxyenoates in good yields and high diastereo- and enantioselectivities.

Enantioselective properties of induced lipases from Geotrichum

Czech Academy of Sciences Publication Activity Database

Zarevúcka, Marie; Kejík, Z.; Šaman, David; Wimmer, Zdeněk; Demnerová, K.

2005-01-01

Roč. 37, - (2005), s. 481-486 ISSN 0141-0229 R&D Projects: GA MŠk(CZ) OC D30.001; GA MŠk(CZ) OC D13.10 Institutional research plan: CEZ:AV0Z40550506 Keywords : Geotrichum * lipase * enantioselectivity Subject RIV: CC - Organic Chemistry Impact factor: 1.705, year: 2005

Lanthanide Lewis acid-mediated enantioselective conjugate radical additions.

Science.gov (United States)

Sibi, Mukund P; Manyem, Shankar

2002-08-22

[reaction: see text] Lanthanide triflates along with proline-derived ligands have been found to be efficient catalysts for enantioselective conjugate addition of nucleophilic radicals to enoates. N-Acyl oxazolidinones, when used as achiral additives, gave meaningful enhancements in the ees for the product.

Enantioselective Diels-Alder Reaction Using Chiral Mg Complexes Derived from Chiral 2-[2-[(Alkyl- or 2-[2-[(Arylsulfonyl)amino]phenyl]-4-phenyl-1,3-oxazoline.

Science.gov (United States)

Ichiyanagi, Tsuyoshi; Shimizu, Makoto; Fujisawa, Tamotsu

1997-11-14

Magnesium complexes derived from (R)-2-[2-[(alkyl- or (R)-2-[2-[(arylsulfonyl)amino]phenyl]-4-phenyl-1,3-oxazolines and methylmagnesium iodide were found to be efficient Lewis acid catalysts for the Diels-Alder reaction of 3-alkenoyl-1,3-oxazolidin-2-one with cyclopentadiene. Chiral ligands were easily prepared from readily available D-phenylglycinol in good yields. The reaction of 3-acryloyl-1,3-oxazolidin-2-one with cyclopentadiene catalyzed by a stoichiometric amount of the Lewis acid gave exclusively the endo-cycloaddition product in up to 92% ee. The sulfonamide group on the chiral ligand strongly influenced the enantiofacial selectivity: the use of a toluene-, benzene-, 1- or 2-naphthalene-, or methanesulfonamide group in the chiral ligand gave the endo-(2R)-cycloaddition product, while a trifluoromethanesulfonamide group predominantly gave its enantiomer, the endo-(2S)-cycloaddition product, in 65% ee. The scope and limitations of the catalytic effect of chiral Mg(II) complexes on the enantioselectivity of the Diels-Alder reaction were investigated. The reaction mechanism of the Mg(II)-catalyzed reaction is also discussed on the basis of the experimental results.

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.

Relative Performance of Alkynes in Copper-Catalyzed Azide-Alkyne Cycloaddition

Science.gov (United States)

Kislukhin, Alexander A.; Hong, Vu P.; Breitenkamp, Kurt E.; Finn, M.G.

2013-01-01

Copper-catalyzed azide–alkyne cycloaddition (CuAAC) has found numerous applications in a variety of fields. We report here only modest differences in the reactivity of various classes of terminal alkynes under typical bioconjugative and preparative organic conditions. Propargyl compounds represent an excellent combination of azide reactivity, ease of installation, and cost. Electronically activated propiolamides are slightly more reactive, at the expense of increased propensity for Michael addition. Certain alkynes, including tertiary propargyl carbamates, are not suitable for bioconjugation due to copper-induced fragmentation. A fluorogenic probe based on such reactivity is available in one step from rhodamine 110 and can be useful for optimization of CuAAC conditions. PMID:23566039

Asymmetric Diels-Alder Reaction of α,β-Unsaturated Oxazolidin-2-one Derivatives Catalyzed by a Chiral Fe(III)-Bipyridine Diol Complex.

Science.gov (United States)

Li, Mao; Carreras, Virginie; Jalba, Angela; Ollevier, Thierry

2018-02-16

An asymmetric Fe III -bipyridine diol catalyzed Diels-Alder reaction of α,β-unsaturated oxazolidin-2-ones has been developed. Among various Fe II /Fe III salts, Fe(ClO 4 ) 3 ·6H 2 O was selected as the Lewis acid of choice. The use of a low catalyst loading (2 mol % of Fe(ClO 4 ) 3 ·6H 2 O and 2.4 mol % of Bolm's ligand) afforded high yields (up to 99%) and high enantiomeric excesses (up to 98%) of endo-cycloadducts for the Diels-Alder reaction between cyclopentadiene and substituted acryloyloxazolidin-2-ones. Other noncyclic dienes led to decreased enantioselectivities. A proposed model supports the observed stereoinduction.

The rabbit liver microsomal biotransformation of 1,1-dialkylethylenes: enantioface selection of epoxidation and enantioselectivity of epoxide hydrolysis.

Science.gov (United States)

Bellucci, G; Chiappe, C; Cordoni, A; Marioni, F

1994-01-01

The rabbit liver microsomal biotransformation of alpha-methylstyrene (1a), 2-methyl-1-hexene (1b), 2,4,4-trimethyl-1-pentene (1c), and 1,3,3-trimethyl-1-butene (1d) has been investigated with the aim at establishing the enantioface selection of the cytochrome P-450-promoted epoxidation of the double bond and the enantioselectivity of microsomal epoxide hydrolase(mEH)-catalyzed hydrolysis of the resulting epoxides. GLC on a Chiraldex G-TA (ASTEC) column was used to determine the enantiomeric composition of the products. The epoxides 2 first produced in incubations carried out in the presence of an NADPH regenerating system were not detected, being rapidly hydrolyzed by mEH to diols 3. The enantiomeric composition of the latter showed that no enantioface selection occurred in the epoxidation of 1c and 1d, and a very low (8%) ee of the (R)-epoxide was formed from 1b. Incubation of racemic epoxides 2b-d with the microsomal fraction showed that the mEH-catalyzed hydrolysis of 2c and 2d was practically nonenantioselective, while that of 2b exhibited a selectivity E = 4.9 favoring the hydrolysis of the (S)-enantiomer. A comparison of these results with those previously obtained for linear and branched chain alkyl monosubstituted oxiranes shows that the introduction of the second alkyl substituent suppresses the selectivity of the mEH reaction of the latter and reverses that of the former substrates.

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.

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

KAUST Repository

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

2013-01-01

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.

Copper(I)-Catalyzed Asymmetric Desymmetrization through Inverse-Electron-Demand aza-Diels-Alder Reaction: Efficient Access to Tetrahydropyridazines Bearing a Unique α-Chiral Silane Moiety.

Science.gov (United States)

Wei, Liang; Zhou, Yu; Song, Zhi-Min; Tao, Hai-Yan; Lin, Zhenyang; Wang, Chun-Jiang

2017-04-11

An unprecedented copper(I)-catalyzed asymmetric desymmetrization of 5-silylcyclopentadienes with in situ formed azoalkene was realized through an inverse-electron-demand aza-Diels-Alder reaction (IEDDA) pathway, in which 5-silylcyclopentadienes served as efficient enophiles. This new protocol provides a facile access to the biologically important heterocyclic tetrahydropyridazines containing a unique α-chiral silane motif and three adjoining stereogenic centers in generally good yield (up to 92 %) with exclusive regioselectivity, high diastereoselectivity (>20:1 diastereomeric ratio), and excellent enantioselectivity (up to 98 % enantiomeric excess). DFT calculations and control experiments further confirmed the proposed reaction mechanism. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Copper-catalyzed oxidative Heck reactions between alkyltrifluoroborates and vinyl arenes.

Science.gov (United States)

Liwosz, Timothy W; Chemler, Sherry R

2013-06-21

We report herein that potassium alkyltrifluoroborates can be utilized in oxidative Heck-type reactions with vinyl arenes. The reaction is catalyzed by a Cu(OTf)2/1,10-phenanthroline with MnO2 as the stoichiometric oxidant. In addition to the alkyl Heck, amination, esterification, and dimerization reactions of alkyltrifluoroborates are demonstrated under analogous reaction conditions. Evidence for an alkyl radical intermediate is presented.

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.

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

Science.gov (United States)

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

2015-12-01

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

Synthesis of Bioactive 2-(Arylaminothiazolo[5,4-f]-quinazolin-9-ones via the Hügershoff Reaction or Cu- Catalyzed Intramolecular C-S Bond Formation

Directory of Open Access Journals (Sweden)

Damien Hédou

2016-06-01

Full Text Available A library of thirty eight novel thiazolo[5,4-f]quinazolin-9(8H-one derivatives (series 8, 10, 14 and 17 was prepared via the Hügershoff reaction and a Cu catalyzed intramolecular C-S bond formation, helped by microwave-assisted technology when required. The efficient multistep synthesis of the key 6-amino-3-cyclopropylquinazolin-4(3H-one (3 has been reinvestigated and performed on a multigram scale from the starting 5-nitroanthranilic acid. The inhibitory potency of the final products was evaluated against five kinases involved in Alzheimer’s disease and showed that some molecules of the 17 series described in this paper are particularly promising for the development of novel multi-target inhibitors of kinases.

AuCu@Pt Nanoalloys for Catalytic Application in Reduction of 4-Nitrophenol

Directory of Open Access Journals (Sweden)

Sadia Mehmood

2016-01-01

Full Text Available To enhance and optimize nanocatalyst ability for nitrophenol (4-NP reduction reaction we look beyond Au-metal nanoparticles and describe a new class of Au nanoalloys with controlled composition for core of AuCu-metals and Pt-metal shell. The reduction of 4-NP was investigated in aqueous media spectroscopically on 7.8 nm Au nanospheres (AuNSs, 8.3 nm AuCuNSs, and 9.1 nm AuCu@Pt core-shell NSs in diameter. The rate constants of the catalyzed reaction at room temperature, activation energies, and entropies of activation of reactions catalyzed by the AuCu@Pt core-shell NSs are found to have different values to those of the pure metal NSs. The results strongly support the proposal that catalysis by nanoparticles is taking place efficiently on the surface of NSs. These core-shell nanocatalysts exhibited stability throughout the reduction reaction and proved that heterogonous type mechanisms are most likely to be dominant in nanoalloy based catalysis if the surface of the NSs is not defected upon shell incorporation.

Strengths, Weaknesses, Opportunities and Threats: Computational Studies of Mn- and Fe-Catalyzed Epoxidations

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Filipe Teixeira

2016-12-01

Full Text Available The importance of epoxides as synthetic intermediates in a number of highly added-value chemicals, as well as the search for novel and more sustainable chemical processes have brought considerable attention to the catalytic activity of manganese and iron complexes towards the epoxidation of alkenes using non-toxic terminal oxidants. Particular attention has been given to Mn(salen and Fe(porphyrin catalysts. While the former attain remarkable enantioselectivity towards the epoxidation of cis-alkenes, the latter also serve as an important model for the behavior of cytochrome P450, thus allowing the exploration of complex biological processes. In this review, a systematic survey of the bibliographical data for the theoretical studies on Mn- and Fe-catalyzed epoxidations is presented. The most interesting patterns and trends are reported and finally analyzed using an evaluation framework similar to the SWOT (Strengths, Weaknesses, Opportunities and Threats analysis performed in enterprise media, with the ultimate aim to provide an overview of current trends and areas for future exploration.

Copper-Catalyzed Synthesis of Trifluoroethylarenes from Benzylic Bromodifluoroacetates.

Science.gov (United States)

Ambler, Brett R; Zhu, Lingui; Altman, Ryan A

2015-08-21

Trifluoroethylarenes are found in a variety of biologically active molecules, and strategies for accessing this substructure are important for developing therapeutic candidates and biological probes. Trifluoroethylarenes can be directly accessed via nucleophilic trifluoromethylation of benzylic electrophiles; however, current catalytic methods do not effectively transform electron-deficient substrates and heterocycles. To address this gap, we report a Cu-catalyzed decarboxylative trifluoromethylation of benzylic bromodifluoroacetates. To account for the tolerance of sensitive functional groups, we propose an inner-sphere mechanism of decarboxylation.

Copper-catalyzed recycling of halogen activating groups via 1,3-halogen migration.

Science.gov (United States)

Grigg, R David; Van Hoveln, Ryan; Schomaker, Jennifer M

2012-10-03

A Cu(I)-catalyzed 1,3-halogen migration reaction effectively recycles an activating group by transferring bromine or iodine from a sp(2) to a benzylic carbon with concomitant borylation of the Ar-X bond. The resulting benzyl halide can be reacted in the same vessel under a variety of conditions to form an additional carbon-heteroatom bond. Cross-over experiments using an isotopically enriched bromide source support intramolecular transfer of Br. The reaction is postulated to proceed via a Markovnikov hydrocupration of the o-halostyrene, oxidative addition of the resulting Cu(I) complex into the Ar-X bond, reductive elimination of the new sp(3) C-X bond, and final borylation of an Ar-Cu(I) species to turn over the catalytic cycle.

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.

Higher-order human telomeric G-quadruplex DNA metalloenzymes enhance enantioselectivity in the Diels-Alder reaction.

Science.gov (United States)

Li, Yinghao; Jia, Guoqing; Wang, Changhao; Cheng, Mingpan; Li, Can

2015-03-02

Short human telomeric (HT) DNA sequences form single G-quadruplex (G4 ) units and exhibit structure-based stereocontrol for a series of reactions. However, for more biologically relevant higher-order HT G4 -DNAs (beyond a single G4 unit), the catalytic performances are unknown. Here, we found that higher-order HT G4 -DNA copper metalloenzymes (two or three G4 units) afford remarkably higher enantioselectivity (>90 % ee) and a five- to sixfold rate increase, compared to a single G4 unit, for the Diels-Alder reaction. Electron paramagnetic resonance (EPR) and enzymatic kinetic studies revealed that the distinct catalytic function between single and higher-order G4 -DNA copper metalloenzymes can be attributed to different Cu(II) coordination environments and substrate specificity. Our finding suggests that, like protein enzymes and ribozymes, higher-order structural organization is crucial for G4 -DNA-based catalysis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselctive Syntheses of Sulfur Analogues of Flavan-3-Ols

Directory of Open Access Journals (Sweden)

Richard Lombardy

2010-08-01

Full Text Available The first enantioselective syntheses of sulfur flavan-3-ol analogues 1–8 have been accomplished, whereby the oxygen atom of the pyran ring has been replaced by a sulfur atom. The key steps were: (a Pd(0 catalyzed introduction of –S t-butyl group, (b Sharpless enantioselective dihydroxylation of the alkene, (c acid catalyzed ring closure to produce the thiopyran ring, and (d removal of benzyl groups using N,N-dimethylaniline and AlCl3. The compounds were isolated in high chemical and optical purity.

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

Science.gov (United States)

2016-01-01

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

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

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

KAUST Repository

Behenna, Douglas C.; Mohr, Justin T.; Sherden, Nathaniel H.; Marinescu, Smaranda C.; Harned, Andrew M.; Tani, Kousuke; Seto, Masaki; Ma, Sandy; Nová k, Zoltá n; 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.

2011-01-01

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 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.

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.

Diastereoselective Au-Catalyzed Allene Cycloisomerizations to Highly Substituted Cyclopentenes.

Science.gov (United States)

Reeves, Ryan D; Phelps, Alicia M; Raimbach, William A T; Schomaker, Jennifer M

2017-07-07

Site- and regiocontrolled Au-catalyzed allene carbocyclizations furnish highly substituted cyclopentenes in >1:1 dr. Significant substitution on the substrate is tolerated, with potential to install five contiguous stereocenters after alkene functionalization. Major challenges include identifying a Au/Cu catalyst that controls both the relative rates of allene epimerization/cyclization and the facial selectivity in addition of a metal enolate to the allene. Experiments to achieve stereodivergent cyclizations and transform key cyclopentenes into useful synthetic building blocks are described.

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

Science.gov (United States)

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

2015-06-15

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

Cu-catalyzed aerobic oxidative esterification of acetophenones with alcohols to α-ketoesters.

Science.gov (United States)

Xu, Xuezhao; Ding, Wen; Lin, Yuanguang; Song, Qiuling

2015-02-06

Copper-catalyzed aerobic oxidative esterification of acetophenones with alcohols using molecular oxygen has been developed to form a broad range of α-ketoesters in good yields. In addition to reporting scope and limitations of our new method, mechanism studies are reported that reveal that the carbonyl oxygen in the ester mainly originated from dioxygen.

Cu(II)-catalyzed oxidation of dopamine in aqueous solutions: mechanism and kinetics.

Science.gov (United States)

Pham, A Ninh; Waite, T David

2014-08-01

Spontaneous oxidation of dopamine (DA) and the resultant formation of free radical species within dopamine neurons of the substantia nigra (SN) is thought to bestow a considerable oxidative load upon these neurons and may contribute to their vulnerability to degeneration in Parkinson's disease (PD). An understanding of DA oxidation under physiological conditions is thus critical to understanding the relatively selective vulnerability of these dopaminergic neurons in PD and may support the development of novel neuro-protective approaches for this disorder. In this study, the oxidation of dopamine (0.2-10μM) was investigated both in the absence and the presence of copper (0.01-0.4μM), a redox active metal that is present at considerable concentrations in the SN, over a range of background chloride concentrations (0.01-0.7M), different oxygen concentrations and at physiological pH7.4. DA was observed to oxidize extremely slowly in the absence of copper and at moderate rates only in the presence of copper but without chloride. The oxidation of DA however was significantly enhanced in the presence of both copper and chloride with the rate of DA oxidation greatest at intermediate chloride concentrations (0.05-0.2M). The variability of the catalytic effect of Cu(II) on DA oxidation at different chloride concentrations can be explained and successfully modeled by appropriate consideration of the reaction of Cu(II) species with DA and the conversion of Cu(I) to Cu(II) through oxygenation. This model suggests that the speciation of Cu(II) and Cu(I) is critically important to the kinetics of DA oxidation and thus the vulnerability to degradation of dopaminergic neuron in the brain milieu. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

Enantioselective resolution of (R,S)-1-phenylethanol catalyzed by lipases immobilized in starch films

International Nuclear Information System (INIS)

Hoffmann, Isabel; Silva, Vanessa D.; Nascimento, Maria da G.

2011-01-01

Lipases from different sources and two mycelium-bound lipases, in a free or immobilized form, in ginger starch film were screened as biocatalysts in the reaction of (R,S)-1-phenylethanol (1) with vinyl acetate and other acylating agents. The effect of various reaction parameters in the resolution of (1) catalyzed by lipase from Burkholderia cepacia (BCL) immobilized in ginger starch film was evaluated (acyl donor type, alcohol:acyl donor molar ratio, temperature and organic solvent). The catalytic efficiency of BCL immobilized in polymeric blends of ginger starch and polyethylene oxide (PEO), in different compositions, was also studied. Vinyl acetate and iso-propenyl acetate furnished the highest conversion (9%) and enantiomeric excess (> 99%) of the (R)-ester. The alcohol:acyl donor molar ratio and temperature optimum were 1:1 and 28 deg respectively. The mixture of n-hexane/glycerol (9:1 v:v) was the most adequate for this reaction (conversion 23%, E > 200). The ginger starch/PEO (7:3 m/m) blend was successfully reused six times consecutively. (author)

Enantioselective resolution of (R,S)-1-phenylethanol catalyzed by lipases immobilized in starch films

Energy Technology Data Exchange (ETDEWEB)

Hoffmann, Isabel; Silva, Vanessa D.; Nascimento, Maria da G., E-mail: graca@qmc.ufsc.b [Universidade Federal de Santa Catarina (UFSC), Florianopolis, SC (Brazil). Dept. de Quimica

2011-07-01

Lipases from different sources and two mycelium-bound lipases, in a free or immobilized form, in ginger starch film were screened as biocatalysts in the reaction of (R,S)-1-phenylethanol (1) with vinyl acetate and other acylating agents. The effect of various reaction parameters in the resolution of (1) catalyzed by lipase from Burkholderia cepacia (BCL) immobilized in ginger starch film was evaluated (acyl donor type, alcohol:acyl donor molar ratio, temperature and organic solvent). The catalytic efficiency of BCL immobilized in polymeric blends of ginger starch and polyethylene oxide (PEO), in different compositions, was also studied. Vinyl acetate and iso-propenyl acetate furnished the highest conversion (9%) and enantiomeric excess (> 99%) of the (R)-ester. The alcohol:acyl donor molar ratio and temperature optimum were 1:1 and 28 deg respectively. The mixture of n-hexane/glycerol (9:1 v:v) was the most adequate for this reaction (conversion 23%, E > 200). The ginger starch/PEO (7:3 m/m) blend was successfully reused six times consecutively. (author)

Enantioselective conjugate radical addition to alpha'-hydroxy enones.

Science.gov (United States)

Lee, Sunggi; Lim, Chae Jo; Kim, Sunggak; Subramaniam, Rajesh; Zimmerman, Jake; Sibi, Mukund P

2006-09-14

Enantioselective conjugate radical addition to alpha'-hydroxy alpha,beta-unsaturated ketones, compounds containing bidentate donors, has been investigated. It has been found that radical additions to alpha'-hydroxy alpha,beta-unsaturated ketones in the presence of Mg(NTf2)2 and bisoxazoline ligand 5a proceeded cleanly, yielding the addition products in high chemical yields and good enantiomeric excesses.

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.

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.

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

Facile synthesis of dendritic Cu by electroless reaction of Cu-Al alloys in multiphase solution

Energy Technology Data Exchange (ETDEWEB)

Wang, Ying; Liang, Shuhua, E-mail: liangxaut@gmail.com; Yang, Qing; Wang, Xianhui

2016-11-30

Highlights: • Nano- or micro-scale fractal dendritic copper (FDC) was synthesized by electroless immersing of Cu-Al alloys in CuCl{sub 2} + HCl. • FDC size increases with the increase of Al content in Cu-Al alloys immersed in CuCl{sub 2} + HCl solution. • Nanoscale Cu{sub 2}O was found at the edge of FDC. Nanoporous copper (NPC) can also be obtained by using Cu{sub 17}Al{sub 83} alloy. • The potential difference between CuAl{sub 2} and α-Al phase and the replacement reaction in multiphase solution are key factors. - Abstract: Two-dimensional nano- or micro-scale fractal dendritic coppers (FDCs) were synthesized by electroless immersing of Cu-Al alloys in hydrochloric acid solution containing copper chloride without any assistance of template or surfactant. The FDC size increases with the increase of Al content in Cu-Al alloys immersed in CuCl{sub 2} + HCl solution. Compared to Cu{sub 40}Al{sub 60} and Cu{sub 45}Al{sub 55} alloys, the FDC shows hierarchical distribution and homogeneous structures using Cu{sub 17}Al{sub 83} alloy as the starting alloy. The growth direction of the FDC is <110>, and all angles between the trunks and branches are 60°. Nanoscale Cu{sub 2}O was found at the edge of FDC. Interestingly, nanoporous copper (NPC) can also be obtained through Cu{sub 17}Al{sub 83} alloy. Studies showed that the formation of FDC depended on two key factors: the potential difference between CuAl{sub 2} intermetallic and α-Al phase of dual-phase Cu-Al alloys; a replacement reaction that usually occurs in multiphase solution. The electrochemical experiment further proved that the multi-branch dendritic structure is very beneficial to the proton transfer in the process of catalyzing methanol.

Beyond benzyl grignards: facile generation of benzyl carbanions from styrenes.

Science.gov (United States)

Grigg, R David; Rigoli, Jared W; Van Hoveln, Ryan; Neale, Samuel; Schomaker, Jennifer M

2012-07-23

Benzylic functionalization is a convenient approach towards the conversion of readily available aromatic hydrocarbon feedstocks into more useful molecules. However, the formation of carbanionic benzyl species from benzyl halides or similar precursors is far from trivial. An alternative approach is the direct reaction of a styrene with a suitable coupling partner, but these reactions often involve the use of precious-metal transition-metal catalysts. Herein, we report the facile and convenient generation of reactive benzyl anionic species from styrenes. A Cu(I)-catalyzed Markovnikov hydroboration of the styrenic double bond by using a bulky pinacol borane source is followed by treatment with KOtBu to facilitate a sterically induced cleavage of the C-B bond to produce a benzylic carbanion. Quenching this intermediate with a variety of electrophiles, including CO(2), CS(2), isocyanates, and isothiocyanates, promotes C-C bond formation at the benzylic carbon atom. The utility of this methodology was demonstrated in a three-step, two-pot synthesis of the nonsteroidal anti-inflammatory drug (±)-flurbiprofen. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterization of two bacterial hydroxynitrile lyases with high similarity to cupin superfamily proteins

NARCIS (Netherlands)

Hussain, Z.; Wiedner, R.; Steiner, K.; Hajek, T.; Avi, M.; Hecher, B.; Sessitsch, A.; Schwab, H.

2012-01-01

Hydroxynitrile lyases (HNLs) catalyze the cleavage of cyanohydrins. In the reverse reaction, they catalyze the formation of carbon-carbon bonds by enantioselective condensation of hydrocyanic acid with carbonyls. In this study, we describe two proteins from endophytic bacteria that display activity

Methane Oxidation to Methanol Catalyzed by Cu-Oxo Clusters Stabilized in NU-1000 Metal-Organic Framework.

Science.gov (United States)

Ikuno, Takaaki; Zheng, Jian; Vjunov, Aleksei; Sanchez-Sanchez, Maricruz; Ortuño, Manuel A; Pahls, Dale R; Fulton, John L; Camaioni, Donald M; Li, Zhanyong; Ray, Debmalya; Mehdi, B Layla; Browning, Nigel D; Farha, Omar K; Hupp, Joseph T; Cramer, Christopher J; Gagliardi, Laura; Lercher, Johannes A

2017-08-02

Copper oxide clusters synthesized via atomic layer deposition on the nodes of the metal-organic framework (MOF) NU-1000 are active for oxidation of methane to methanol under mild reaction conditions. Analysis of chemical reactivity, in situ X-ray absorption spectroscopy, and density functional theory calculations are used to determine structure/activity relations in the Cu-NU-1000 catalytic system. The Cu-loaded MOF contained Cu-oxo clusters of a few Cu atoms. The Cu was present under ambient conditions as a mixture of ∼15% Cu + and ∼85% Cu 2+ . The oxidation of methane on Cu-NU-1000 was accompanied by the reduction of 9% of the Cu in the catalyst from Cu 2+ to Cu + . The products, methanol, dimethyl ether, and CO 2 , were desorbed with the passage of 10% water/He at 135 °C, giving a carbon selectivity for methane to methanol of 45-60%. Cu oxo clusters stabilized in NU-1000 provide an active, first generation MOF-based, selective methane oxidation catalyst.

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

Science.gov (United States)

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

2018-05-04

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

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

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

Copper-catalyzed one-pot synthesis of 1,2,4-triazoles from nitriles and hydroxylamine.

Science.gov (United States)

Xu, Hao; Ma, Shuang; Xu, Yuanqing; Bian, Longxiang; Ding, Tao; Fang, Xiaomin; Zhang, Wenkai; Ren, Yanrong

2015-02-06

A simple and efficient copper-catalyzed one-pot synthesis of substituted 1,2,4-triazoles through reactions of two nitriles with hydroxylamine has been developed. The protocol uses simple and readily available nitriles and hydroxylamine hydrochloride as the starting materials and inexpensive Cu(OAc)2 as the catalyst, and the corresponding 1,2,4-triazole derivatives are obtained in moderate to good yields. The reactions include sequential intermolecular addition of hydroxylamine to one nitrile to provide amidoxime, copper-catalyzed treatment of the amidoxime with another nitrile, and intramolecular dehydration/cyclization. This finding provides a new and useful strategy for synthesis of 1,2,4-triazole derivatives.

Diversification of indoles via microwave-assisted ligand-free copper-catalyzed N-arylation

Energy Technology Data Exchange (ETDEWEB)

Kwon, Jae Kwan; Lee, Jin Hee; Kim, Tae Sung; Yum, Eul Kgun [Dept. of Chemistry, Chu ngnam National University, Daejon (Korea, Republic of); Park, Jee Jung [Western Seoul Center Korea Basic Science Institute, Seoul (Korea, Republic of)

2016-12-15

A simple, efficient Cu{sub 2}O catalyst system under microwave irradiation was developed for N-arylation of various indoles without ligands and additives. Diverse N-heteroarylated indoles were prepared by coupling indoles with various heteroaryl halides within 1 h. The selective reactivity of bromoindole with aryl iodide provided N-aryl bromoindoles, which could be useful intermediates for palladium-catalyzed Heck and Suzuki coupling reactions.

Enhanced bromate formation during chlorination of bromide-containing waters in the presence of CuO: Catalytic disproportionation of hypobromous acid

KAUST Repository

Liu, Chao; von Gunten, Urs; Croue, Jean-Philippe

2012-01-01

of bromide-containing waters in the presence of cupric oxide (CuO). CuO was effective to catalyze hypochlorous acid (HOCl) or hypobromous acid (HOBr) decay (e.g., at least 104 times enhancement for HOBr at pH 8.6 by 0.2 g L-1 CuO). Significant halate

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

Post Modification of Acetylene Functional Poly(oxindole biphenylylene) by Photoinduced CuAAC

KAUST Repository

Arslan, Mustafa; Cem Bicak, Tugrul; Pulido, Bruno; Nunes, Suzana Pereira; Yagci, Yusuf

2018-01-01

A novel strategy to obtain side chain modified poly(oxindole biphenylylene) (POXI) by photoinduced copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction is described. In the first step, an alkyne-functionalized poly(oxindolebiphenylylene) (POXI-alkyne) is synthesized by superacid-catalyzed condensation of isatin with aromatic hydrocarbons. Subsequently, poly(ethylene glycol) methyl ether (Me-PEG), 1-pyrenemethanol (Py-OH) and 1,3-dibromopropane (DBP) are functionalized by azide groups via simple nucleophilic substitution reaction. Visible-light-induced CuAAC reaction between POXI-alkyne and the corresponding azide functionalized click components employing dibenzoyldiethylgermane (DBDEG) as photoactivator resulted in the formation of POXI-PEG, POXI-Py and insoluble network, respectively. Successful modification of POXI was confirmed by the spectral, (1H NMR, FT-IR, Fluorescence), chromatographic (GPC) and thermal (DSC) investigations.

Post Modification of Acetylene Functional Poly(oxindole biphenylylene) by Photoinduced CuAAC

KAUST Repository

Arslan, Mustafa

2018-02-08

A novel strategy to obtain side chain modified poly(oxindole biphenylylene) (POXI) by photoinduced copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction is described. In the first step, an alkyne-functionalized poly(oxindolebiphenylylene) (POXI-alkyne) is synthesized by superacid-catalyzed condensation of isatin with aromatic hydrocarbons. Subsequently, poly(ethylene glycol) methyl ether (Me-PEG), 1-pyrenemethanol (Py-OH) and 1,3-dibromopropane (DBP) are functionalized by azide groups via simple nucleophilic substitution reaction. Visible-light-induced CuAAC reaction between POXI-alkyne and the corresponding azide functionalized click components employing dibenzoyldiethylgermane (DBDEG) as photoactivator resulted in the formation of POXI-PEG, POXI-Py and insoluble network, respectively. Successful modification of POXI was confirmed by the spectral, (1H NMR, FT-IR, Fluorescence), chromatographic (GPC) and thermal (DSC) investigations.

Synthesis of phenanthridines via palladium-catalyzed picolinamide-directed sequential C–H functionalization

Directory of Open Access Journals (Sweden)

Ryan Pearson

2013-05-01

Full Text Available We report a new synthesis of phenanthridines based on palladium-catalyzed picolinamide-directed sequential C–H functionalization reactions starting from readily available benzylamine and aryl iodide precursors. Under the catalysis of Pd(OAc2, the ortho-C–H bond of benzylpicolinamides is first arylated with an aryl iodide. The resulting biaryl compound is then subjected to palladium-catalyzed picolinamide-directed intramolecular dehydrogenative C–H amination with PhI(OAc2 oxidant to form the corresponding cyclized dihydrophenanthridines. The benzylic position of these dihydrophenanthridines could be further oxidized with Cu(OAc2, removing the picolinamide group and providing phenathridine products. The cyclization and oxidation could be carried out in a single step and afford phenathridines in moderate to good yields.

Mechanism insight of pollutant degradation and bromate inhibition by Fe-Cu-MCM-41 catalyzed ozonation.

Science.gov (United States)

Chen, Weirui; Li, Xukai; Tang, Yiming; Zhou, Jialu; Wu, Dan; Wu, Yin; Li, Laisheng

2018-03-15

A flexible catalyst, Fe-Cu-MCM-41, was employed to enhance diclofenac (DCF) mineralization and inhibit bromate formation in catalytic ozonation process. Greater TOC removal was achieved in Fe-Cu-MCM-41/O 3 process (78%) than those in Fe-MCM-41/O 3 (65%), Cu-MCM-41/O 3 (73%) and sole ozonation (42%). But it was interesting that both Cu-MCM-41/O 3 and Fe-MCM-41/O 3 achieved 93% bromate inhibition efficiency, only 71% inhibition efficiency was observed in Fe-Cu-MCM-41/O 3 . Influence of pH, TBA/NaHSO 3 and detection of by-products were conducted to explore the mechanism. By Pyridine adsorption-IR and XPS, a relationship was found among activity of catalysts, Lewis acid sites and electron transfer effect between Fe (II/III) and Cu (I/II). Fe-Cu-MCM-41 promoted ozone decomposition to generate OH, which accounted for enhanced DCF mineralization. The consumption of aqueous O 3 also suppressed the oxidative of Br - and HBrO/Br - . More HBrO/BrO - accumulated in catalytic ozonation process and less bromate generated. Bromate formation in Fe-Cu-MCM-41/O 3 process was sensitive with pH value, the acidic condition was not favor for bromate formation. Both DCF mineralization and bromate inhibition were influenced by surface reaction. Moreover, Fe-Cu-MCM-41 showed excellent catalytic performance in suppressing the accumulation of carboxylic acid, especially for oxalic acid. Nearly no oxalic acid was detected during Fe-Cu-MCM-41/O 3 process. Copyright © 2017 Elsevier B.V. All rights reserved.

Pyrones to pyrans: enantioselective radical additions to acyloxy pyrones.

Science.gov (United States)

Sibi, Mukund P; Zimmerman, Jake

2006-10-18

This paper describes a highly site-, diastereo-, and enantioselective intermolecular radical addition/hydrogen atom transfer to hydroxypyrone pyromeconic and kojic acids. The methodology can be extended to the formation of chiral quaternary centers. The products obtained are densely functionalized pyran moieties. The products contain structural features amenable for the introduction of additional substituents.

(+)-camphor-derived tri- and tetradentate amino alcohols; synthesis and application as ligands in the nickel catalyzed enantioselective conjugate addition of diethylzinc

NARCIS (Netherlands)

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

1997-01-01

Several novel tri- and tetradentate amino alcohol ligands, all derived from (+)-camphor, have been synthesized by using specific N-alkylation procedures. The amino alcohols were employed as chiral ligands in the nickel catalyzed conjugate additions of diethylzine to chalcone and cyclohexenone as

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

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.

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.

Synthesis of the C(18)-C(34) fragment of amphidinolide C and the C(18)-C(29) fragment of amphidinolide F.

Science.gov (United States)

Roy, Sudeshna; Spilling, Christopher D

2010-11-19

A convergent synthesis of the C(18)-C(34) fragment of amphidinolide C and the C(18)-C(29) fragment of amphidinolide F is reported. The approach involves the synthesis of the common intermediate tetrahydrofuranyl-β-ketophosphonate via cross metathesis, Pd(0)-catalyzed cyclization, and hydroboration-oxidation. The β-ketophosphonate was coupled to three side chain aldehydes using a Horner-Wadsworth-Emmons (HWE) olefination reaction to give dienones, which were reduced with l-selectride to give the fragments of amphidinolide C and F.

Synthesis of Imidazopyridines via Copper-Catalyzed, Formal Aza-[3 + 2] Cycloaddition Reaction of Pyridine Derivatives with α-Diazo Oxime Ethers.

Science.gov (United States)

Park, Sangjune; Kim, Hyunseok; Son, Jeong-Yu; Um, Kyusik; Lee, Sooho; Baek, Yonghyeon; Seo, Boram; Lee, Phil Ho

2017-10-06

The Cu-catalyzed, formal aza-[3 + 2] cycloaddition reaction of pyridine derivatives with α-diazo oxime ethers in trifluoroethanol was used to synthesize imidazopyridines via the release of molecular nitrogen and elimination of alcohol. These methods enabled modular synthesis of a wide range of N-heterobicyclic compounds such as imidazopyridazines, imidazopyrimidines, and imidazopyrazines with an α-imino Cu-carbenoid generated from the α-diazo oxime ethers and copper.

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...

PLE CATALYZED HYDROLYZES OF ALPHA-SUBSTITUTED ALPHA-HYDROXY ESTERS - THE INFLUENCE OF THE SUBSTITUENTS

NARCIS (Netherlands)

MOORLAG, H; KELLOGG, RM

1991-01-01

The enzymatic hydrolyses of a variety of alpha-substituted mandelic and lactic esters using pig liver esterase (PLE) have been investigated. High to moderate enantioselectivity was found for various alpha-substituted mandelic esters, whereas PLE showed low to no enantioselectivity for

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

Science.gov (United States)

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

2013-03-15

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

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

Science.gov (United States)

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

2015-02-01

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

A Catalytic, Asymmetric Formal Synthesis of (+)-Hamigeran B

KAUST Repository

Mukherjee, Herschel

2011-03-04

A concise asymmetric, formal synthesis of (+)-hamigeran B is reported. A Pd-catalyzed, decarboxylative allylic alkylation, employing a trifluoromethylated derivative of t-BuPHOX, is utilized as the enantioselective step to form the critical quaternary carbon center in excellent yield and enantioselectivity. The product is converted in three steps to a late-stage intermediate previously used in the synthesis of hamigeran B.

A Catalytic, Asymmetric Formal Synthesis of (+)-Hamigeran B

KAUST Repository

Mukherjee, Herschel; McDougal, Nolan T.; Virgil, Scott C.; Stoltz, Brian M.

2011-01-01

A concise asymmetric, formal synthesis of (+)-hamigeran B is reported. A Pd-catalyzed, decarboxylative allylic alkylation, employing a trifluoromethylated derivative of t-BuPHOX, is utilized as the enantioselective step to form the critical quaternary carbon center in excellent yield and enantioselectivity. The product is converted in three steps to a late-stage intermediate previously used in the synthesis of hamigeran B.

Synthesis of Arylthiopyrimidines by Copper-catalyzed Aerobic Oxidative C-S Cross-coupling

Energy Technology Data Exchange (ETDEWEB)

Lee, Ok Suk; Kim, Hyeji; Sohn, Jeong-Hun [Chungnam National University, Daejeon (Korea, Republic of); Lee, Hee-Seung [KAIST, Daejeon (Korea, Republic of); Shin, Hyunik [Yonsung Fine Chemicals R and D Center, Suwon (Korea, Republic of)

2016-02-15

Copper-catalyzed C–S cross-coupling reactions have been considered as powerful tools in synthetic chemistry and utilized for diverse heterocycle syntheses. In the reactions, the aspects of no need of ligands has been particular advantage over other metal catalysis. We have developed a Cu-catalyzed cascade reaction for the synthesis of fully substituted 2-arylthiopyrimidines from 3,4-dihydropyrimidine-2(1H)-thiones (DHPMs) under aerobic conditions. This cascade reaction of DHPM with aryl iodide proceeds presumably via sequential tautomerization, C–S cross-coupling, and oxidative dehydrogenation (oxidation followed by elimination). Considering that DHPM substrates were easily synthesized by Biginelli three component coupling reaction of aryl aldehyde, β-ketoester, and thiourea, the present method provides a direct access toward diverse 2-arylthiopyrimidines which have been used as a prominent substructure of drug molecules.

NeoPHOX – a structurally tunable ligand system for asymmetric catalysis

Directory of Open Access Journals (Sweden)

Jaroslav Padevět

2016-06-01

Full Text Available A synthesis of new NeoPHOX ligands derived from serine or threonine has been developed. The central intermediate is a NeoPHOX derivative bearing a methoxycarbonyl group at the stereogenic center next to the oxazoline N atom. The addition of methylmagnesium chloride leads to a tertiary alcohol, which can be acylated or silylated to produce NeoPHOX ligands with different sterical demand. The new NeoPHOX ligands were tested in the iridium-catalyzed asymmetric hydrogenation and palladium-catalyzed allylic substitution. In both reactions high enantioselectivities were achieved, that were comparable to the enantioselectivities obtained with the up to now best NeoPHOX ligand derived from expensive tert-leucine.

Mechanism and the origins of stereospecificity in copper-catalyzed ring expansion of vinyl oxiranes: a traceless dual transition-metal-mediated process.

Science.gov (United States)

Mustard, Thomas J L; Mack, Daniel J; Njardarson, Jon T; Cheong, Paul Ha-Yeon

2013-01-30

Density functional theory computations of the Cu-catalyzed ring expansion of vinyloxiranes is mediated by a traceless dual Cu(I)-catalyst mechanism. Overall, the reaction involves a monomeric Cu(I)-catalyst, but a single key step, the Cu migration, requires two Cu(I)-catalysts for the transformation. This dual-Cu step is found to be a true double Cu(I) transition state rather than a single Cu(I) transition state in the presence of an adventitious, spectator Cu(I). Both Cu(I) catalysts are involved in the bond forming and breaking process. The single Cu(I) transition state is not a stationary point on the potential energy surface. Interestingly, the reductive elimination is rate-determining for the major diastereomeric product, while the Cu(I) migration step is rate-determining for the minor. Thus, while the reaction requires dual Cu(I) activation to proceed, kinetically, the presence of the dual-Cu(I) step is untraceable. The diastereospecificity of this reaction is controlled by the Cu migration step. Suprafacial migration is favored over antarafacial migration due to the distorted Cu π-allyl in the latter.

A sensitive fluorescence biosensor for alkaline phosphatase activity based on the Cu(II)-dependent DNAzyme

Energy Technology Data Exchange (ETDEWEB)

Zhao, Mengmeng; Guo, Yajuan; Wang, Lixu [College of Chemistry, Fuzhou University, Fuzhou, Fujian 350116 (China); Luo, Fang, E-mail: luofang0812@163.com [College of Biological Science and Technology, Fuzhou University, Fuzhou, Fujian 350116 (China); Lin, Cuiying, E-mail: lcuiying@fzu.edu.cn [College of Chemistry, Fuzhou University, Fuzhou, Fujian 350116 (China); Lin, Zhenyu; Chen, Guonan [College of Chemistry, Fuzhou University, Fuzhou, Fujian 350116 (China)

2016-12-15

Alkaline phosphatase (ALP) plays an important role in phosphate metabolism processes; deviation from its normal level may indicate different kinds of diseases, so it is highly necessary to develop some simple and sensitive methods to monitor the ALP level. In this study, a simple, high selective, and sensitive fluorescent biosensor has been proposed for ALP activity determination. The Cu(II)-dependent DNAzyme (Cu-Enzyme) are divided into two parts: Cu-Enzyme 1 and Cu-Enzyme 2, and labelled with alkyne and azido groups, respectively. The Cu-substrate (Cu-Sub) is labelled with a FAM fluorophore (6-carboxyfluorescein) at the 3′-end and an additional quencher (BHQ1) at the 5′-end. The 5′-end of Cu-Enzyme 1 is labelled with BHQ1 as well. The hybridization of the Cu-Enzyme 1 and Cu-Enzyme 2 with Cu-Sub strand results in the low background fluorescence signal because the fluorescence from FAM is quenched. The addition of ALP can hydrolyze AA-P into AA, which can reduce Cu(II) into Cu(I) and in turn catalyze the cycloaddition of Cu-Enzyme 1 and Cu-Enzyme 2 to form a modified Cu-Enzyme. Then the modified Cu-Enzyme catalyzes the cleavage of the Cu-Sub strands into two pieces. One piece containing FAM fluorophore can easily diffuse into solution and give off a strong fluorescence signal. The enhanced fluorescent intensity has a linear relationship with the ALP concentration in the range of 0.36–54.55 U L{sup −1} with the detection limit of 0.14 U L{sup −1} (S/N = 3). The proposed biosensor has been successfully applied to detect ALP in serum samples with satisfied results. - Highlights: • We have proposed a simple, high selective and sensitive fluorescent biosensor for ALP. • The biosensor combines the high selectivity and the click reaction and the high sensitivity of the fluorescence detection. • The biosensor has been successfully applied to detect ALP in serum samples with satisfied results.

Enantioselective synthesis of alpha,beta-disubstituted-beta-amino acids.

Science.gov (United States)

Sibi, Mukund P; Prabagaran, Narayanasamy; Ghorpade, Sandeep G; Jasperse, Craig P

2003-10-01

Highly diastereoselective and enantioselective addition of N-benzylhydroxylamine to imides 17 and 20-30 produces alpha,beta-trans-disubstituted N-benzylisoxazolidinones 19 and 31-41. These reactions proceed in 60-96% ee with 93-99% de's using 5 mol % of Mg(NTf2)2 and ligand 18. The product isoxazolidinones can be hydrogenolyzed directly to provide alpha,beta-disubstituted-beta-amino acids.

The natural catalytic function of CuGE glucuronoyl esterase in hydrolysis of genuine lignin-carbohydrate complexes from birch

DEFF Research Database (Denmark)

Mosbech, Caroline; Holck, Jesper; Meyer, Anne S.

2018-01-01

Glucuronoyl esterases belong to carbohydrate esterase family 15 and catalyze de-esterification. Their natural function is presumed to be cleavage of ester linkages in lignin-carbohydrate complexes particularly those linking lignin and glucuronoyl residues in xylans in hardwood. Here, we show...... for the first time a detailed product profile of aldouronic acids released from birchwood lignin by a glucuronoyl esterase from the white-rot fungus Cerrena unicolor (CuGE). CuGE releases substrate for GH10 endo-xylanase which results in significantly increased product release compared to the action of endo......-xylanase alone. CuGE also releases neutral xylo-oligosaccharides that can be ascribed to the enzymes feruloyl esterase side activity as demonstrated by release of ferulic acid from insoluble wheat arabinoxylan. The data verify the enzyme's unique ability to catalyze removal of all glucuronoxylan associated...

A facile copper(I)-catalyzed homocoupling of terminal alkynes to 1,3-diynes with diaziridinone under mild conditions

OpenAIRE

Zhu, Yingguang; Shi, Yian

2013-01-01

A novel and efficient Cu(I)-catalyzed oxidative homocoupling of terminal alkynes with diaziridinone as oxidant is described. Various terminal alkynes can be transformed into the corresponding 1,3-diynes in good yields. The reaction process is base-free, operationally simple, and amenable to gram scale.

Efficient degradation of carbamazepine by easily recyclable microscaled CuFeO_2 mediated heterogeneous activation of peroxymonosulfate

International Nuclear Information System (INIS)

Ding, Yaobin; Tang, Hebin; Zhang, Shenghua; Wang, Songbo; Tang, Heqing

2016-01-01

Highlights: • CuFeO_2 microparticles were prepared by a microwave-assisted hydrothermal method. • CuFeO_2 microparticles efficiently catalyzed the activation of peroxymonosulfate. • Quenching experiments confirmed sulfate radicals as the major reactive radicals. • Carbamazepine was rapidly degraded by micro-CuFeO_2/peroxymonosulfate. • Feasibility of CuFeO_2/peroxymonosulfate was tested for treatment of actual water. - Abstract: Microscaled CuFeO_2 particles (micro-CuFeO_2) were rapidly prepared via a microwave-assisted hydrothermal method and characterized by scanning electron microscopy, X-ray powder diffraction and X-ray photoelectron spectroscopy. It was found that the micro-CuFeO_2 was of pure phase and a rhombohedral structure with size in the range of 2.8 ± 0.6 μm. The micro-CuFeO_2 efficiently catalyzed the activation of peroxymonosulfate (PMS) to generate sulfate radicals (SO_4·−), causing the fast degradation of carbamazepine (CBZ). The catalytic activity of micro-CuFeO_2 was observed to be 6.9 and 25.3 times that of micro-Cu_2O and micro-Fe_2O_3, respectively. The enhanced activity of micro-CuFeO_2 for the activation of PMS was confirmed to be attributed to synergistic effect of surface bonded Cu(I) and Fe(III). Sulfate radical was the primary radical species responsible for the CBZ degradation. As a microscaled catalyst, micro-CuFeO_2 can be easily recovered by gravity settlement and exhibited improved catalytic stability compared with micro-Cu_2O during five successive degradation cycles. Oxidative degradation of CBZ by the couple of PMS/CuFeO_2 was effective in the studied actual aqueous environmental systems.

Catalytic enantioselective alkene aminohalogenation/cyclization involving atom transfer.

Science.gov (United States)

Bovino, Michael T; Chemler, Sherry R

2012-04-16

Problem solved: the title reaction was used for the synthesis of chiral 2-bromo, chloro, and iodomethyl indolines and 2-iodomethyl pyrrolidines. Stereocenter formation is believed to occur by enantioselective cis aminocupration and C-X bond formation is believed to occur by atom transfer. The ultility of the products as versatile synthetic intermediates was demonstrated, as was a radical cascade cyclization sequence. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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…

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 Although the enantioselective kinetic resolution of ester racemates of the non-steroidal antiinflammatory drug naproxen ([2-(6-methoxy-2-naphthyl) propionic acid]) is a common demonstration for biocatalysis, the enantiomeric excess of the reactions...

Synthesis of the C(18)–C(34) Fragment of Amphidinolide C and the C(18)–C(29) Fragment of Amphidinolide F

Science.gov (United States)

Roy, Sudeshna; Spilling, Christopher D.

2010-01-01

A convergent synthesis of the C(18)–C(34) fragment of amphidinolide C and the C(18)–C(29) fragment of amphidinolide F is reported. The approach involves the synthesis of the common intermediate tetrahydrofuranyl-β-ketophosphonate via cross metathesis, Pd(0)-catalyzed cyclization and hydroboration-oxidation. The β-ketophosphonate was coupled to three side chain aldehydes using a Horner-Wadsworth-Emmons (HWE) olefination reaction to give dienones, which were reduced with L-selectride to give the fragments of amphidinolide C and F. PMID:21028791

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

Science.gov (United States)

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

2015-03-27

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

Molecular-level Design of Heterogeneous Chiral Catalysts

Energy Technology Data Exchange (ETDEWEB)

Gellman, Andrew John [Carnegie Mellon University; Sholl, David S. [Georgia Institute of Technology; Tysoe, Wilfred T. [University of Wisconsin - Milwaukee; Zaera, Francisco [University of California at Riverside

2013-04-28

Understanding and controlling selectivity is one of the key challenges in heterogeneous catalysis. Among problems in catalytic selectivity enantioselectivity is perhaps the most the most challenging. The primary goal of the project on “Molecular-level Design of Heterogeneous Chiral Catalysts” is to understand the origins of enantioselectivity on chiral heterogeneous surfaces and catalysts. The efforts of the project team include preparation of chiral surfaces, characterization of chiral surfaces, experimental detection of enantioselectivity on such surfaces and computational modeling of the interactions of chiral probe molecules with chiral surfaces. Over the course of the project period the team of PI’s has made some of the most detailed and insightful studies of enantioselective chemistry on chiral surfaces. This includes the measurement of fundamental interactions and reaction mechanisms of chiral molecules on chiral surfaces and leads all the way to rationale design and synthesis of chiral surfaces and materials for enantioselective surface chemistry. The PI’s have designed and prepared new materials for enantioselective adsorption and catalysis. Naturally Chiral Surfaces • Completion of a systematic study of the enantiospecific desorption kinetics of R-3-methylcyclohexanone (R-3-MCHO) on 9 achiral and 7 enantiomeric pairs of chiral Cu surfaces with orientations that span the stereographic triangle. • Discovery of super-enantioselective tartaric acid (TA) and aspartic acid (Asp) decomposition as a result of a surface explosion mechanism on Cu(643)R&S. Systematic study of super-enantiospecific TA and Asp decomposition on five enantiomeric pairs of chiral Cu surfaces. • Initial observation of the enantiospecific desorption of R- and S-propylene oxide (PO) from Cu(100) imprinted with {3,1,17} facets by L-lysine adsorption. Templated Chiral Surfaces • Initial observation of the enantiospecific desorption of R- and S-PO from Pt(111) and Pd(111

A facile copper(I)-catalyzed homocoupling of terminal alkynes to 1,3-diynes with diaziridinone under mild conditions.

Science.gov (United States)

Zhu, Yingguang; Shi, Yian

2013-11-21

A novel and efficient Cu(I)-catalyzed oxidative homocoupling of terminal alkynes with diaziridinone as an oxidant is described. Various terminal alkynes can be transformed into the corresponding 1,3-diynes in good yields. The reaction process is base-free, operationally simple, and amenable to the gram scale.

Novel Role of Carbon Dioxide as a Selective Agent in Palladium-Catalyzed Cyclotrimerization of Alkynes

Institute of Scientific and Technical Information of China (English)

李金恒; 谢叶香

2004-01-01

Carbon dioxide was found as a selective agent to promote the palladium-catalyzed cyclotrimerization of alkynes in water. Both aryl and alkylacetylenes afforded the corresponding cyclotrimerization products regioselectively in high yields using PdCl2, CuCl2, and CO2 as the catalytic system. However, tert-butylacetylene bearing a bulky group gave a dimerization product. Mechanism of this reaction was also discussed.

Enhanced bromate formation during chlorination of bromide-containing waters in the presence of CuO: Catalytic disproportionation of hypobromous acid

KAUST Repository

Liu, Chao

2012-10-16

Bromate (BrO3 -) in drinking water is traditionally seen as an ozonation byproduct from the oxidation of bromide (Br-), and its formation during chlorination is usually not significant. This study shows enhanced bromate formation during chlorination of bromide-containing waters in the presence of cupric oxide (CuO). CuO was effective to catalyze hypochlorous acid (HOCl) or hypobromous acid (HOBr) decay (e.g., at least 104 times enhancement for HOBr at pH 8.6 by 0.2 g L-1 CuO). Significant halate concentrations were formed from a CuO-catalyzed hypohalite disproportionation pathway. For example, the chlorate concentration was 2.7 ± 0.2 μM (225.5 ± 16.7 μg L-1) after 90 min for HOCl (Co = 37 μM, 2.6 mg L-1 Cl2) in the presence of 0.2 g L-1 CuO at pH 7.6, and the bromate concentration was 6.6 ± 0.5 μM (844.8 ± 64 μg L -1) after 180 min for HOBr (Co = 35 μM) in the presence of 0.2 g L-1 CuO at pH 8.6. The maximum halate formation was at pHs 7.6 and 8.6 for HOCl or HOBr, respectively, which are close to their corresponding pKa values. In a HOCl-Br--CuO system, BrO3 - formation increases with increasing CuO doses and initial HOCl and Br- concentrations. A molar conversion (Br - to BrO3 -) of up to (90 ± 1)% could be achieved in the HOCl-Br--CuO system because of recycling of Br - to HOBr by HOCl, whereas the maximum BrO3 - yield in HOBr-CuO is only 26%. Bromate formation is initiated by the formation of a complex between CuO and HOBr/OBr-, which then reacts with HOBr to generate bromite. Bromite is further oxidized to BrO3 - by a second CuO-catalyzed process. These novel findings may have implications for bromate formation during chlorination of bromide-containing drinking waters in copper pipes. © 2012 American Chemical Society.

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.

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.

Efficient degradation of carbamazepine by easily recyclable microscaled CuFeO{sub 2} mediated heterogeneous activation of peroxymonosulfate

Energy Technology Data Exchange (ETDEWEB)

Ding, Yaobin, E-mail: yaobinding@mail.scuec.edu.cn [Key Laboratory of Catalysis and Materials Science of the State Ethnic Affairs Commission and Ministry of Education, College of Resources and Environmental Science, South-Central University for Nationalities, Wuhan 430074 (China); Tang, Hebin [College of Pharmacy, South-Central University for Nationalities, Wuhan 430074 (China); Zhang, Shenghua; Wang, Songbo [Key Laboratory of Catalysis and Materials Science of the State Ethnic Affairs Commission and Ministry of Education, College of Resources and Environmental Science, South-Central University for Nationalities, Wuhan 430074 (China); Tang, Heqing, E-mail: tangheqing@mail.scuec.edu.cn [Key Laboratory of Catalysis and Materials Science of the State Ethnic Affairs Commission and Ministry of Education, College of Resources and Environmental Science, South-Central University for Nationalities, Wuhan 430074 (China)

2016-11-05

Highlights: • CuFeO{sub 2} microparticles were prepared by a microwave-assisted hydrothermal method. • CuFeO{sub 2} microparticles efficiently catalyzed the activation of peroxymonosulfate. • Quenching experiments confirmed sulfate radicals as the major reactive radicals. • Carbamazepine was rapidly degraded by micro-CuFeO{sub 2}/peroxymonosulfate. • Feasibility of CuFeO{sub 2}/peroxymonosulfate was tested for treatment of actual water. - Abstract: Microscaled CuFeO{sub 2} particles (micro-CuFeO{sub 2}) were rapidly prepared via a microwave-assisted hydrothermal method and characterized by scanning electron microscopy, X-ray powder diffraction and X-ray photoelectron spectroscopy. It was found that the micro-CuFeO{sub 2} was of pure phase and a rhombohedral structure with size in the range of 2.8 ± 0.6 μm. The micro-CuFeO{sub 2} efficiently catalyzed the activation of peroxymonosulfate (PMS) to generate sulfate radicals (SO{sub 4}·−), causing the fast degradation of carbamazepine (CBZ). The catalytic activity of micro-CuFeO{sub 2} was observed to be 6.9 and 25.3 times that of micro-Cu{sub 2}O and micro-Fe{sub 2}O{sub 3}, respectively. The enhanced activity of micro-CuFeO{sub 2} for the activation of PMS was confirmed to be attributed to synergistic effect of surface bonded Cu(I) and Fe(III). Sulfate radical was the primary radical species responsible for the CBZ degradation. As a microscaled catalyst, micro-CuFeO{sub 2} can be easily recovered by gravity settlement and exhibited improved catalytic stability compared with micro-Cu{sub 2}O during five successive degradation cycles. Oxidative degradation of CBZ by the couple of PMS/CuFeO{sub 2} was effective in the studied actual aqueous environmental systems.

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

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…

Cu/Nitroxyl Catalyzed Aerobic Oxidation of Primary Amines into Nitriles at Room Temperature

OpenAIRE

Kim, Jinho; Stahl, Shannon S.

2013-01-01

An efficient catalytic method has been developed for aerobic oxidation of primary amines to the corresponding nitriles. The reactions proceed at room temperature and employ a catalyst consisting of (4,4′-tBu2bpy)CuI/ABNO (ABNO = 9-azabicyclo[3.3.1]nonan-3-one N-oxyl). The reactions exhibit excellent functional group compatibility and substrate scope, and are effective with benzylic, allylic and aliphatic amines. Preliminary mechanistic studies suggest that aerobic oxidation of the Cu catalyst...

The role of the achiral template in enantioselective transformations. Radical conjugate additions to alpha-methacrylates followed by hydrogen atom transfer.

Science.gov (United States)

Sibi, Mukund P; Sausker, Justin B

2002-02-13

We have evaluated various achiral templates (1a-g, 10, and 16) in conjunction with chiral Lewis acids in the conjugate addition of nucleophilic radicals to alpha-methacrylates followed by enantioselective H-atom transfer. Of these, a novel naphthosultam template (10) gave high enantioselectivity in the H-atom-transfer reactions with ee's up to 90%. A chiral Lewis acid derived from MgBr(2) and bisoxazoline (2) gave the highest selectivity in the enantioselective hydrogen-atom-transfer reactions. Non-C(2) symmetric oxazolines (20-25) have also been examined as ligands, and of these, compound 25 gave optimal results (87% yield and 80% ee). Insights into rotamer control in alpha-substituted acrylates and the critical role of the tetrahedral sulfone moiety in realizing high selectivity are discussed.

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.

CuO and Ag2O/CuO Catalyzed Oxidation of Aldehydes to the Corresponding Carboxylic Acids by Molecular Oxygen

Directory of Open Access Journals (Sweden)

Yaowu Sha

2008-04-01

Full Text Available Furfural was oxidized to furoic acid by molecular oxygen under catalysis by 150nm-sized Ag2O/CuO (92% or simply CuO (86.6%. When 30 nm-size catalyst was used,the main product was a furfural Diels-Alder adduct. Detailed reaction conditions andregeneration of catalysts were investigated. Under optimal conditions, a series of aromaticand aliphatic aldehydes were oxidized to the corresponding acids in good yields.

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.

Toxicity of Aromatic Ketone to Yeast Cell and Improvement of the Asymmetric Reduction of Aromatic Ketone Catalyzed by Yeast Cell with the Introduction of Resin Adsorption

Directory of Open Access Journals (Sweden)

Zhong-Hua Yang

2008-01-01

Full Text Available Asymmetric reduction of the prochiral aromatic ketone catalyzed by yeast cells is one of the most promising routes to produce its corresponding enantiopure aromatic alcohol, but the space-time yield does not meet people’s expectations. Therefore, the toxicity of aromatic ketone and aromatic alcohol to the yeast cell is investigated in this work. It has been found that the aromatic compounds are poisonous to the yeast cell. The activity of yeast cell decreases steeply when the concentration of acetophenone (ACP is higher than 30.0 mmol/L. Asymmetric reduction of acetophenone to chiral S-α-phenylethyl alcohol (PEA catalyzed by the yeast cell was chosen as the model reaction to study in detail the promotion effect of the introduction of the resin adsorption on the asymmetric reduction reaction. The resin acts as the substrate reservoir and product extraction agent in situ. It has been shown that this reaction could be remarkably improved with this technique when the appropriate kind of resin is applied. The enantioselectivity and yield are acceptable even though the initial ACP concentration reaches 72.2 mmol/L.

Cu/Nitroxyl Catalyzed Aerobic Oxidation of Primary Amines into Nitriles at Room Temperature.

Science.gov (United States)

Kim, Jinho; Stahl, Shannon S

2013-07-05

An efficient catalytic method has been developed for aerobic oxidation of primary amines to the corresponding nitriles. The reactions proceed at room temperature and employ a catalyst consisting of (4,4'- t Bu 2 bpy)CuI/ABNO (ABNO = 9-azabicyclo[3.3.1]nonan-3-one N -oxyl). The reactions exhibit excellent functional group compatibility and substrate scope, and are effective with benzylic, allylic and aliphatic amines. Preliminary mechanistic studies suggest that aerobic oxidation of the Cu catalyst is the turnover-limiting step of the reaction.

Purification and characterisation of a novel enantioselective epoxide hydrolase from Aspergillus niger M200

Czech Academy of Sciences Publication Activity Database

Kotík, Michael; Kyslík, Pavel

2006-01-01

Roč. 1760, - (2006), s. 245-252 ISSN 0006-3002 Institutional research plan: CEZ:AV0Z50200510 Keywords : epoxide hydrolase * enantioselectivity * aspergillus niger Subject RIV: EE - Microbiology, Virology

Understanding NOx SCR Mechanism and Activity on Cu/Chabazite Structures throughout the Catalyst Life Cycle

Energy Technology Data Exchange (ETDEWEB)

Ribeiro, Fabio; Delgass, Nick; Gounder, Rajmani; Schneider, William F.; Miller, Jeff; Yezerets, Aleksey; McEwen, Jean-Sabin; Peden, Charles HF; Howden, Ken

2014-12-09

Oxides of nitrogen (NOx) compounds contribute to acid rain and photochemical smog and have been linked to respiratory ailments. NOx emissions regulations continue to tighten, driving the need for high performance, robust control strategies. The goal of this project is to develop a deep, molecular level understanding of the function of Cu-SSZ-13 and Cu-SAPO-34 materials that catalyze the SCR of NOx with NH3.

Synthesis of Donor/Acceptor-Substituted Diazo Compounds in Flow and Their Application in Enantioselective Dirhodium-Catalyzed Cyclopropanation and C-H Functionalization.

Science.gov (United States)

Rackl, Daniel; Yoo, Chun-Jae; Jones, Christopher W; Davies, Huw M L

2017-06-16

A tandem reaction system has been developed for the preparation of donor/acceptor-substituted diazo compounds in continuous flow coupled to dirhodium-catalyzed C-H functionalization or cyclopropanation. Hydrazones were oxidized in flow by solid-supported N-iodo-p-toluenesulfonamide potassium salt (PS-SO 2 NIK) to generate the diazo compounds, which were then purified by passing through a column of molecular sieves/sodium thiosulfate.

Palladium-catalyzed cyclization reactions of 2-vinylthiiranes with heterocumulenes. Regioselective and enantioselective formation of thiazolidine, oxathiolane, and dithiolane derivatives.

Science.gov (United States)

Larksarp, C; Sellier, O; Alper, H

2001-05-18

The first palladium-catalyzed ring-expansion reaction of 2-vinylthiiranes with heterocumulenes to form sulfur-containing five-membered-ring heterocycles is described. This regioselective reaction requires 5 mol % of Pd(2)(dba)(3).CHCl(3) and 10 mol % of bidendate phosphine ligand (dppp, BINAP), at 50-80 degrees C, in THF. The reaction of 2-vinylthiiranes with carbodiimides, isocyanates, and ketenimines affords 1,3-thiazolidine derivatives, whereas the reaction with diphenylketene or isothiocyanates results in the formation of 1,3-oxathiolane or 1,3-dithiolane compounds in good to excellent isolated yields and in up to 78% ee.

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...

Modelling substrate specificity and enantioselectivity for lipases and esterases by substrate-imprinted docking

Directory of Open Access Journals (Sweden)

Tyagi Sadhna

2009-06-01

Full Text Available Abstract Background Previously, ways to adapt docking programs that were developed for modelling inhibitor-receptor interaction have been explored. Two main issues were discussed. First, when trying to model catalysis a reaction intermediate of the substrate is expected to provide more valid information than the ground state of the substrate. Second, the incorporation of protein flexibility is essential for reliable predictions. Results Here we present a predictive and robust method to model substrate specificity and enantioselectivity of lipases and esterases that uses reaction intermediates and incorporates protein flexibility. Substrate-imprinted docking starts with covalent docking of reaction intermediates, followed by geometry optimisation of the resulting enzyme-substrate complex. After a second round of docking the same substrate into the geometry-optimised structures, productive poses are identified by geometric filter criteria and ranked by their docking scores. Substrate-imprinted docking was applied in order to model (i enantioselectivity of Candida antarctica lipase B and a W104A mutant, (ii enantioselectivity and substrate specificity of Candida rugosa lipase and Burkholderia cepacia lipase, and (iii substrate specificity of an acetyl- and a butyrylcholine esterase toward the substrates acetyl- and butyrylcholine. Conclusion The experimentally observed differences in selectivity and specificity of the enzymes were reproduced with an accuracy of 81%. The method was robust toward small differences in initial structures (different crystallisation conditions or a co-crystallised ligand, although large displacements of catalytic residues often resulted in substrate poses that did not pass the geometric filter criteria.

Enantioselective apoptosis induced by individual isomers of bifenthrin in Hep G2 cells.

Science.gov (United States)

Liu, Huigang; Li, Juan

2015-03-01

Bifenthrin (BF) has been used in racemate for agricultural purposes against soil insects, leading to increased inputs into soil environments. However, most of the studies about the toxicology research on BF were performed in its racemic form. The aim of the present study was to evaluate the enantiomer-specific cis-BF-induced apoptosis and intracellular reactive oxygen species (ROS) generation on human hepatocarcinoma cells (Hep G2). The results of cell viability assay and cytoflow assay indicated an obvious enantioselective hepatocyte toxicity of 1S-cis-BF in Hep G2 cells. 1S-cis-BF also induced ROS production, up-regulated Bax protein expression and down-regulated Bcl-2 expression levels. The present study suggested that enantioselective toxicity should be evaluated on currently used chiral pesticides, such as synthetic pyrethroids. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Computer-Assisted Design and Synthetic Applications of Chiral Enol Borinates: Novel, Highly Enantioselective Aldol Reagents

Directory of Open Access Journals (Sweden)

Gennari Cesare

1998-01-01

Full Text Available We have recently described the development of a quantitative transition state model for the prediction of stereoselectivity in the boron-mediated aldol reaction. This model provides qualitative insights into the factors contributing to the stereochemical outcome of a variety of reactions of synthetic importance. The force field model was used to assist the design and preparation of new chiral boron ligands derived from menthone. The chiral boron enolates were employed in various stereoselective processes, including the addition to chiral aldehydes and the reagent-controlled total synthesis of (3S,4S-statine. The chiral enolates derived from alpha-halo and alpha-oxysubstituted thioacetates were added to aldehydes and imines. Addition to imines leads to the enantioselective synthesis of chiral aziridines, a formal total synthesis of (+-thiamphenicol, and a new highly efficient synthesis of the paclitaxel (taxol® C-13 side-chain and taxol semisynthesis from baccatin III. The stereochemical outcome of the addition to imines was rationalised with the aid of computational studies. Enantioselective addition reactions of the chiral boron enolate derived from thioacetate have successfully been applied to solid phase bound aldehydes to give aldol products in comparable yields and enantioselectivities to the usual solution conditions.

Enantioselective Effects of o,p'-DDT on Cell Invasion and Adhesion of Breast Cancer Cells: Chirality in Cancer Development.

Science.gov (United States)

He, Xiangming; Dong, Xiaowu; Zou, Dehong; Yu, Yang; Fang, Qunying; Zhang, Quan; Zhao, Meirong

2015-08-18

The o,p'-dichlorodiphenyltrichloroethane (DDT) with a chiral center possesses enantioselective estrogenic activity, in which R-(-)-o,p'-DDT exerts a more potent estrogenic effect than S-(+)-o,p'-DDT. Although concern regarding DDT exposure and breast cancer has increased in recent decades, the mode of enantioselective action of o,p'-DDT in breast cancer development is still unknown. Herein, we conducted a systematic study of the effect of o,p'-DDT on stereoselective breast tumor cell progression in a widely used in vitro breast tumor cell model, MCF-7 cells. We demonstrated that R-(-)-o,p'-DDT promoted more cancer cell invasion mediated by the human estrogen receptor (ER) by inducing invasion-promoted genes (matrix metalloproteinase-2 and -9 and human telomerase reverse transcriptase) and inhibiting invasion-inhibited genes (tissue inhibitor of metalloproteinase-1 and -4). Molecular docking verified that the binding affinity between R-(-)-o,p'-DDT and human ER was stronger than that of S-(+)-o,p'-DDT. The enantioselective-induced decrease in cell-to-cell adhesion may involve the downregulation of adhesion-promoted genes (E-cadherin and β-catenin). For the first time, these results reveal that estrogenic-like chiral compounds are of significant concern in the progression of human cancers and that human health risk assessment of chiral chemicals should consider enantioselectivity.

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

Science.gov (United States)

Thomas, John Meurig; Raja, Robert

2008-06-01

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

Exploration of Cocatalyst Effects on a Bimetallic Cobalt Catalyst System: Enhanced Activity and Enantioselectivity in Epoxide Polymerization

KAUST Repository

Widger, Peter C. B.; Ahmed, Syud M.; Coates, Geoffrey W.

2011-01-01

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.

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.

Platinum-Catalyzed, Terminal-Selective C(sp(3))-H Oxidation of Aliphatic Amines.

Science.gov (United States)

Lee, Melissa; Sanford, Melanie S

2015-10-14

This Communication describes the terminal-selective, Pt-catalyzed C(sp(3))-H oxidation of aliphatic amines without the requirement for directing groups. CuCl2 is employed as a stoichiometric oxidant, and the reactions proceed in high yield at Pt loadings as low as 1 mol%. These transformations are conducted in the presence of sulfuric acid, which reacts with the amine substrates in situ to form ammonium salts. We propose that protonation of the amine serves at least three important roles: (i) it renders the substrates soluble in the aqueous reaction medium; (ii) it limits binding of the amine nitrogen to Pt or Cu; and (iii) it electronically deactivates the C-H bonds proximal to the nitrogen center. We demonstrate that this strategy is effective for the terminal-selective C(sp(3))-H oxidation of a variety of primary, secondary, and tertiary amines.

Syntheses, structures, and properties of imidazolate-bridged Cu(II)-Cu(II) and Cu(II)-Zn(II) dinuclear complexes of a single macrocyclic ligand with two hydroxyethyl pendants.

Science.gov (United States)

Li, Dongfeng; Li, Shuan; Yang, Dexi; Yu, Jiuhong; Huang, Jin; Li, Yizhi; Tang, Wenxia

2003-09-22

The imidazolate-bridged homodinuclear Cu(II)-Cu(II) complex, [(CuimCu)L]ClO(4).0.5H(2)O (1), and heterodinuclear Cu(II)-Zn(II) complex, [(CuimZnL(-)(2H))(CuimZnL(-)(H))](ClO(4))(3) (2), of a single macrocyclic ligand with two hydroxyethyl pendants, L (L = 3,6,9,16,19,22-hexaaza-6,19-bis(2-hydroxyethyl)tricyclo[22,2,2,2(11,14)]triaconta-1,11,13,24,27,29-hexaene), have been synthesized as possible models for copper-zinc superoxide dismutase (Cu(2),Zn(2)-SOD). Their crystal structures analyzed by X-ray diffraction methods have shown that the structures of the two complexes are markedly different. Complex 1 crystallizes in the orthorhombic system, containing an imidazolate-bridged dicopper(II) [Cu-im-Cu](3+) core, in which the two copper(II) ions are pentacoordinated by virtue of an N4O environment with a Cu.Cu distance of 5.999(2) A, adopting the geometry of distorted trigonal bipyramid and tetragonal pyramid, respectively. Complex 2 crystallizes in the triclinic system, containing two similar Cu-im-Zn cores in the asymmetric unit, in which both the Cu(II) and Zn(II) ions are pentacoordinated in a distorted trigonal bipyramid geometry, with the Cu.Zn distance of 5.950(1)/5.939(1) A, respectively. Interestingly, the macrocyclic ligand with two arms possesses a chairlike (anti) conformation in complex 1, but a boatlike (syn) conformation in complex 2. Magnetic measurements and ESR spectroscopy of complex 1 have revealed the presence of an antiferromagnetic exchange interaction between the two Cu(II) ions. The ESR spectrum of the Cu(II)-Zn(II) heterodinuclear complex 2 displayed a typical signal for mononuclear trigonal bipyramidal Cu(II) complexes. From pH-dependent ESR and electronic spectroscopic studies, the imidazolate bridges in the two complexes have been found to be stable over broad pH ranges. The cyclic voltammograms of the two complexes have been investigated. Both of the two complexes can catalyze the dismutation of superoxide and show rather high activity.

Total Synthesis of (R, R, R)-gamma-Tocopherol through Cu-Catalyzed Asymmetric 1,2-Addition

NARCIS (Netherlands)

Wu, Zhongtao; Harutyunyan, Syuzanna R.; Minnaard, Adriaan J.

2014-01-01

Based on the asymmetric copper-catalyzed 1,2-addition of Grignard reagents to ketones, (R,R,R)--tocopherol has been synthesized in 36% yield over 12 steps (longest linear sequence). The chiral center in the chroman ring was constructed with 73% ee by the 1,2-addition of a phytol-derived Grignard

Kinetics of aggregation growth with competition between catalyzed birth and catalyzed death

International Nuclear Information System (INIS)

Wang Haifeng; Gao Yan; Lin Zhenquan

2008-01-01

An aggregation growth model of three species A, B and C with the competition between catalyzed birth and catalyzed death is proposed. Irreversible aggregation occurs between any two aggregates of the like species with the constant rate kernels I n (n = 1,2,3). Meanwhile, a monomer birth of an A species aggregate of size k occurs under the catalysis of a B species aggregate of size j with the catalyzed birth rate kernel K(k,j) = Kkj v and a monomer death of an A species aggregate of size k occurs under the catalysis of a C species aggregate of size j with the catalyzed death rate kernel L(k,j)=Lkj v , where v is a parameter reflecting the dependence of the catalysis reaction rates of birth and death on the size of catalyst aggregate. The kinetic evolution behaviours of the three species are investigated by the rate equation approach based on the mean-field theory. The form of the aggregate size distribution of A species a k (t) is found to be dependent crucially on the competition between the catalyzed birth and death of A species, as well as the irreversible aggregation processes of the three species: (1) In the v k (t) satisfies the conventional scaling form; (2) In the v ≥ 0 case, the competition between the catalyzed birth and death dominates the process. When the catalyzed birth controls the process, a k (t) takes the conventional or generalized scaling form. While the catalyzed death controls the process, the scaling description of the aggregate size distribution breaks down completely

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.

Chiral separation and enantioselective degradation of vinclozolin in soils.

Science.gov (United States)

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

2014-03-01

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

Simple introduction of anion trapping site to polymer electrolytes through dehydrocoupling or hydroboration reaction using 9-borabicyclo[3.3.1]nonane

International Nuclear Information System (INIS)

Mizumo, Tomonobu; Sakamoto, Kenji; Matsumi, Noriyoshi; Ohno, Hiroyuki

2005-01-01

Organoboron-based anion trapping polymer electrolytes were synthesized through hydroboration or dehydrocoupling reaction between poly(propylene oxide) (PPO) oligomer (M n =400, 1200, 2000 and 4000) and 9-borabicyclo[3.3.1]nonane (9-BBN). Obtained oligomers were added various lithium salts (LiN(CF 3 SO 2 ) 2 , LiSO 3 CF 3 , LiCO 2 CF 3 or LiBr) to analyze the ionic conductivity and lithium ion transference number (t Li + ). The ionic conductivity of the oligomer in the presence of LiN(CF 3 SO 2 ) 2 showed higher ionic conductivity than other systems, however, the t Li + was less than 0.3. When LiSO 3 CF 3 or LiCO 2 CF 3 , was added high t Li + over 0.6 was obtained. Such difference in t Li + can be explained by HSAB principle. Since boron is a hard acid, soft (CF 3 SO 2 ) 2 N - anion can not be trapped effectively. High ionic conductivity of 1.3x10 -6 Scm -1 and high t Li + of 0.73 was obtained when PPO chain length was 2000. These values of facilely prepared polymer electrolytes are comparable to those of the PPOs having covalently bonded salt moieties on the chain ends

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.

Copper-catalyzed transformation of ketones to amides via C(CO)-C(alkyl) bond cleavage directed by picolinamide.

Science.gov (United States)

Ma, Haojie; Zhou, Xiaoqiang; Zhan, Zhenzhen; Wei, Daidong; Shi, Chong; Liu, Xingxing; Huang, Guosheng

2017-09-13

Copper catalyzed chemoselective cleavage of the C(CO)-C(alkyl) bond leading to C-N bond formation with chelation assistance of N-containing directing groups is described. Inexpensive Cu(ii)-acetate serves as a convenient catalyst for this transformation. This method highlights the emerging strategy to transform unactivated alkyl ketones into amides in organic synthesis and provides a new strategy for C-C bond cleavage.

Copper-Catalyzed Chan-Lam Cyclopropylation of Phenols and Azaheterocycles.

Science.gov (United States)

Derosa, Joseph; O'Duill, Miriam L; Holcomb, Matthew; Boulous, Mark N; Patman, Ryan L; Wang, Fen; Tran-Dubé, Michelle; McAlpine, Indrawan; Engle, Keary M

2018-04-06

Small molecules containing cyclopropane-heteroatom linkages are commonly needed in medicinal chemistry campaigns yet are problematic to prepare using existing methods. To address this issue, a scalable Chan-Lam cyclopropylation reaction using potassium cyclopropyl trifluoroborate has been developed. With phenol nucleophiles, the reaction effects O-cyclopropylation, whereas with 2-pyridones, 2-hydroxybenzimidazoles, and 2-aminopyridines the reaction brings about N-cyclopropylation. The transformation is catalyzed by Cu(OAc) 2 and 1,10-phenanthroline and employs 1 atm of O 2 as the terminal oxidant. This method is operationally convenient to perform and provides a simple, strategic disconnection toward the synthesis of cyclopropyl aryl ethers and cyclopropyl amine derivatives bearing an array of functional groups.

Optimisation of the enantioselective biocatalytic hydrolysis of naproxen ethyl ester using ChiroCLEC-CR

CSIR Research Space (South Africa)

Brady, D

2004-03-04

Full Text Available In a biocatalytic reaction the immobilized lipase ChiroCLEC-CR enantioselectively hydrolysed a naproxen ethyl ester racemate, yielding (S)-naproxen with an enantiomeric excess of more than 98%, an enantiomeric ratio (E) of more than 100...

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.

Kinetic Resolution of sec-Thiols by Enantioselective Oxidation with Rationally Engineered 5-(Hydroxymethyl)furfural Oxidase.

Science.gov (United States)

Pickl, Mathias; Swoboda, Alexander; Romero, Elvira; Winkler, Christoph K; Binda, Claudia; Mattevi, Andrea; Faber, Kurt; Fraaije, Marco W

2018-03-05

Various flavoprotein oxidases were recently shown to oxidize primary thiols. Herein, this reactivity is extended to sec-thiols by using structure-guided engineering of 5-(hydroxymethyl)furfural oxidase (HMFO). The variants obtained were employed for the oxidative kinetic resolution of racemic sec-thiols, thus yielding the corresponding thioketones and nonreacted R-configured thiols with excellent enantioselectivities (E≥200). The engineering strategy applied went beyond the classic approach of replacing bulky amino acid residues with smaller ones, as the active site was additionally enlarged by a newly introduced Thr residue. This residue established a hydrogen-bonding interaction with the substrates, as verified in the crystal structure of the variant. These strategies unlocked HMFO variants for the enantioselective oxidation of a range of sec-thiols. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective recognition of mandelic acid by a 3,6-dithiophen-2-yl-9H-carbazole-based chiral fluorescent bisboronic acid sensor.

Science.gov (United States)

Wu, Yubo; Guo, Huimin; James, Tony D; Zhao, Jianzhang

2011-07-15

We have prepared chiral fluorescent bisboronic acid sensors with 3,6-dithiophen-2-yl-9H-carbazole as the fluorophore. The thiophene moiety was used to extend the π-conjugation framework of the fluorophore in order to red-shift the fluorescence emission and, at the same time, to enhance the novel process where the fluorophore serves as the electron donor of the photoinduced electron transfer process (d-PET) of the boronic acid sensors; i.e., the background fluorescence of the sensor 1 at acidic pH is weaker compared to that at neutral or basic pH, in stark contrast to the typical a-PET boronic acid sensors (where the fluorophore serves as the electron acceptor of the photoinduced electron transfer process). The benefit of the d-PET boronic acid sensors is that the recognition of the hydroxylic acids can be achieved at acidic pH. We found that the thiophene moiety is an efficient π-conjugation linker and electron donor; as a result, the d-PET contrast ratio of the sensors upon variation of the pH is improved 10-fold when compared to the previously reported d-PET sensors without the thiophene moiety. Enantioselective recognition of tartaric acid was achieved at acid pH, and the enantioselectivity (total response K(D)I(F)(D)/K(L)I(F)(L)) is 3.3. The fluorescence enhancement (I(F)(Sample)/I(F)(Blank)) of sensor 1 upon binding with tartaric acid is 3.5-fold at pH 3.0. With the fluorescent bisboronic acid sensor 1, enantioselective recognition of mandelic acid was achieved for the first time. To the best of our knowledge, this is the first time that the mandelic acid has been enantioselectively recognized using a chiral fluorescent boronic acid sensor. Chiral monoboronic acid sensor 2 and bisboronic acid sensor 3 without the thiophene moiety failed to enantioselectively recognize mandelic acid. Our findings with the thiophene-incorporated boronic acid sensors will be important for the design of d-PET fluorescent sensors for the enantioselective recognition of �

Material and orientation dependent activity for heterogeneously catalyzed carbon-bromine bond homolysis

Energy Technology Data Exchange (ETDEWEB)

Walch, Hermann; Gutzler, Rico; Sirtl, Thomas; Eder, Georg; Lackinger, Markus [LMU Munich, Section Crystallography (Germany)

2010-07-01

Adsorption of the organic molecule 1,3,5-tris(4-bromophenyl)benzene on different metallic substrates, namely Cu(111), Ag(111) and Ag(110) has been studied by variable temperature Scanning Tunneling Microscopy (STM). Depending on substrate temperature, material and orientation, we observe a surface-catalyzed dehalogenation reaction. Deposition onto the catalytically active substrates Cu(111) and Ag(110) held at room temperature leads to cleavage of the carbon-bromine bonds and subsequent formation of protopolymers, i.e radical metal coordination complexes. However upon deposition on Ag(111) no such reaction has been observed. Instead, various self-assembled ordered structures based on intact molecules could be identified. Also sublimation onto either substrate held at 80 K did not result in any dehalogenation, thereby exemplifying that the dehalogenation reaction is thermally activated. We explain the differences in catalytic activity by charge transfer into unoccupied molecular orbitals and subsequent destabilization of the C-Br bond, whereby enhanced molecule-substrate interaction leads to an increasing magnitude of charge transfer. The interaction strength follows the general reactivity order Cu>Ag>Au for (111) faces and is generally enhanced on higher corrugated surfaces as the (110) facet in case of fcc substrates.

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...

Molecular Design of a Chiral Brønsted Acid with Two Different Acidic Sites: Regio-, Diastereo-, and Enantioselective Hetero-Diels-Alder Reaction of Azopyridinecarboxylate with Amidodienes Catalyzed by Chiral Carboxylic Acid-Monophosphoric Acid.

Science.gov (United States)

Momiyama, Norie; Tabuse, Hideaki; Noda, Hirofumi; Yamanaka, Masahiro; Fujinami, Takeshi; Yamanishi, Katsunori; Izumiseki, Atsuto; Funayama, Kosuke; Egawa, Fuyuki; Okada, Shino; Adachi, Hiroaki; Terada, Masahiro

2016-09-07

A chiral Brønsted acid containing two different acidic sites, chiral carboxylic acid-monophosphoric acid 1a, was designed to be a new and effective concept in catalytic asymmetric hetero-Diels-Alder reactions of azopyridinecarboxylate with amidodienes. The multipoint hydrogen-bonding interactions among the carboxylic acid, monophosphoric acid, azopyridinecarboxylate, and amidodiene achieved high catalytic and chiral efficiency, producing substituted 1,2,3,6-tetrahydropyridazines with excellent stereocontrol in a single step. This constitutes the first example of regio-, diastereo-, and enantioselective azo-hetero-Diels-Alder reactions by chiral Brønsted acid catalysis.

Total syntheses of mitragynine, paynantheine and speciogynine via an enantioselective thiourea-catalysed Pictet-Spengler reaction

NARCIS (Netherlands)

Kerschgens, I. P.; Claveau, E.; Wanner, M.J.; Ingemann, S.; van Maarseveen, J.H.; Hiemstra, H.

2012-01-01

The pharmacologically interesting indole alkaloids (-)-mitragynine, (+)-paynantheine and (+)-speciogynine were synthesised in nine steps from 4-methoxytryptamine by a route featuring (i) an enantioselective thiourea-catalysed Pictet-Spengler reaction, providing the tetrahydro-β-carboline ring and

Kinetics and mechanism of auto- and copper-catalyzed oxidation of 1,4-naphthohydroquinone.

Science.gov (United States)

Yuan, Xiu; Miller, Christopher J; Pham, A Ninh; Waite, T David

2014-06-01

Although quinones represent a class of organic compounds that may exert toxic effects both in vitro and in vivo, the molecular mechanisms involved in quinone species toxicity are still largely unknown, especially in the presence of transition metals, which may both induce the transformation of the various quinone species and result in generation of harmful reactive oxygen species. In this study, the oxidation of 1,4-naphthohydroquinone (NH2Q) in the absence and presence of nanomolar concentrations of Cu(II) in 10 mM NaCl solution over a pH range of 6.5-7.5 has been investigated, with detailed kinetic models developed to describe the predominant mechanisms operative in these systems. In the absence of copper, the apparent oxidation rate of NH2Q increased with increasing pH and initial NH2Q concentration, with concomitant oxygen consumption and peroxide generation. The doubly dissociated species, NQ(2-), has been shown to be the reactive species with regard to the one-electron oxidation by O2 and comproportionation with the quinone species, both generating the semiquinone radical (NSQ(·-)). The oxidation of NSQ(·-) by O2 is shown to be the most important pathway for superoxide (O2(·-)) generation with a high intrinsic rate constant of 1.0×10(8)M(-1)s(-1). Both NSQ(·-) and O2(·-) served as chain-propagating species in the autoxidation of NH2Q. Cu(II) is capable of catalyzing the oxidation of NH2Q in the presence of O2 with the oxidation also accelerated by increasing the pH. Both the uncharged (NH2Q(0)) and the mono-anionic (NHQ(-)) species were found to be the kinetically active forms, reducing Cu(II) with an intrinsic rate constant of 4.0×10(4) and 1.2×10(7)M(-1)s(-1), respectively. The presence of O2 facilitated the catalytic role of Cu(II) by rapidly regenerating Cu(II) via continuous oxidation of Cu(I) and also by efficient removal of NSQ(·-) resulting in the generation of O2(·-). The half-cell reduction potentials of various redox couples at neutral p

Different effects of clopidogrel and clarithromycin on the enantioselective pharmacokinetics of sibutramine and its active metabolites in healthy subjects.

Science.gov (United States)

Shinde, Dhananjay D; Kim, Ho-Sook; Choi, Jae-Seok; Pan, Wei; Bae, Soo Kyung; Yeo, Chang-Woo; Shon, Ji-Hong; Kim, Dong-Hyun; Shin, Jae Gook

2013-05-01

In this study, we assessed the effects of clopidogrel and clarithromycin, known CYP2B6 and CYP3A inhibitors, respectively, on the enantioselective disposition of racemic sibutramine in conjunction with CYP2B6 polymorphisms in humans. Sibutramine showed enantioselective plasma profiles with consistently higher concentrations of R-enantiomers. Clopidogrel and clarithromycin significantly increased the sibutramine plasma concentration, but their effects differed between enantiomers; a 2.2-fold versus 4.1-fold increase in the AUC in S-enantiomer and 1.8-fold versus 2.0-fold for the R-enantiomer, respectively. The AUCs of S- and R-desmethyl metabolites changed significantly during the clopidogrel phase (P sibutramine was higher in subjects with the CYP2B6*6/*6 genotype, but no statistical difference was observed among the CYP2B6 genotypes. These results suggest that the enantioselective disposition of sibutramine and its active metabolites are influenced by the altered genetic and environmental factors of CYP2B6 and CYP3A activity in vivo. © The Author(s) 2013.

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.

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.

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...

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

Stereoselective reactions. XXXII. Enantioselective deprotonation of 4-tert-butylcyclohexanone by fluorine-containing chiral lithium amides derived from 1-phenylethylamine and 1-(1-naphthyl)ethylamine.

Science.gov (United States)

Aoki, K; Koga, K

2000-04-01

Enantioselective deprotonation of 4-tert-butylcyclohexanone was examined using 1-phenylethylamine- and 1-(1-naphthyl)ethylamine-derived chiral lithium amides having an alkyl or a fluoroalkyl substituent at the amide nitrogen. The lithium amides having a 2,2,2-trifluoroethyl group on the amide nitrogen are easily accessible in both enantiomeric forms, and were found to induce good enantioselectivity in the present reaction.

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....

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

NARCIS (Netherlands)

Prior, Amir; Sánchez-Hernández, Laura; Sastre-Toraño, Javier; Marina, Maria Luisa; de Jong, Gerhardus J.; 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

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.

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

New chiral phosphinephosphinite ligands: Application to stereoselective synthesis of a key intermediate of 1{beta}-methyl carbapenems by Rh(I)-catalyzed asymmetric hydroformylation

Energy Technology Data Exchange (ETDEWEB)

Saito, Takao; Yoshida, Akifumi; Matsumura, Kazuhiko [Takasago International Corp., Kanagawa (Japan)] [and others

1995-12-31

Transition metal catalyzed asymmetric hydroformylation is an attractive and highly useful homologation process for organic synthesis. Recently, the authors reported that the Rh(I) complexes of phosphinephosphite BINAPHOS are highly efficient catalysts for enantioselective hydroformylation of a variety of olefins. This time, the authors have designed and synthesized new chiral phosphinephosphinite ligands having binaphthyl backbone, (R)-2-diarylphosphino-2{prime}-diarylphosphinoxy-1,1{prime}-binaphthy1 (hereafter abbreviated (R)-BIPNITE). The Rh(I) complexes of these ligands are effective catalysts for the asymmetric hydroformylation of 4-vinylazetidin-2-one to give the corresponding oxo-aldehyde 3{beta} as the major product in very high diastereoselectivities and in good regioselectivities. Interestingly, modifications of the aryl substituents in phosphine and phosphinite moieties afforded higher selectivities. Aldehyde 3{beta} was easily oxidized with NaClO{sub 2} to 4, a key intermediate of 1{beta}-methyl carbapenems. Thus, the present method provides a new practical route to a versatile key intermediate for the synthesis of carbapenem antibiotics.

Platinum-Catalyzed Terminal-Selective C(sp3)–H Oxidation of Aliphatic Amines

Science.gov (United States)

Lee, Melissa; Sanford, Melanie S.

2016-01-01

This paper describes the terminal-selective Pt-catalyzed C(sp3)–H oxidation of aliphatic amines without the requirement for directing groups. CuCl2 is employed as a stoichiometric oxidant, and the reactions proceed in high yield at Pt loadings as low as 1 mol %. These transformations are conducted in the presence of sulfuric acid, which reacts with the amine substrates in situ to form ammonium salts. We propose that protonation of the amine serves at least three important roles: (i) it renders the substrates soluble in the aqueous reaction medium; (ii) it limits binding of the amine nitrogen to Pt or Cu; and (ii) it electronically deactivates the C–H bonds proximal to the nitrogen center. We demonstrate that this strategy is effective for the terminal-selective C(sp3)–H oxidation of a variety of primary, secondary and tertiary amines. PMID:26439251

The Triple Roles of Glutathione for a DNA-Cleaving DNAzyme and Development of a Fluorescent Glutathione/Cu2+-Dependent DNAzyme Sensor for Detection of Cu2+ in Drinking Water.

Science.gov (United States)

Wang, Shijin; Liu, Chengcheng; Li, Guiying; Sheng, Yongjie; Sun, Yanhong; Rui, Hongyue; Zhang, Jin; Xu, Jiacui; Jiang, Dazhi

2017-03-24

Pistol-like DNAzyme (PLDz) is an oxidative DNA-cleaving catalytic DNA with ascorbic acid as cofactor. Herein, glutathione was induced into the reaction system to maintain reduced ascorbic acid levels for higher efficient cleavage. However, data indicated that glutathione played triple roles in PLDz-catalyzed reactions. Glutathione alone had no effect on PLDz, and showed inhibitory effect on ascorbic acid-induced PLDz catalysis, but exhibited stimulating effect on Cu 2+ -promoted self-cleavage of PLDz. Further analysis of the effect of glutathione/Cu 2+ on PLDz indicated that H 2 O 2 played a key role in PLDz catalysis. Finally, we developed a fluorescent Cu 2+ sensor (PL-Cu 1.0) based on the relationship between glutathione/Cu 2+ and catalytic activity of PLDz. The fluorescent intensity showed a linear response toward the logarithm concentration of Cu 2+ over the range from 80 nM to 30 μM, with a detection limit of 21.1 nM. PL-Cu 1.0 provided only detection of Cu 2+ over other divalent metal ions. Ca 2+ and Mg 2+ could not interfere with Cu 2+ detection even at a 1000-fold concentration. We further applied PL-Cu 1.0 for Cu 2+ detection in tap and bottled water. Water stored in copper taps overnight had relatively high Cu 2+ concentrations, with a maximum 22.3 μM. Trace Cu 2+ (52.2 nM) in deep spring was detected among the tested bottled water. Therefore, PL-Cu 1.0 is feasible to detect Cu 2+ in drinking water, with a practical application.

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

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

Enantioselective organo-photocatalysis mediated by atropisomeric thiourea derivatives.

Science.gov (United States)

Vallavoju, Nandini; Selvakumar, Sermadurai; Jockusch, Steffen; Sibi, Mukund P; Sivaguru, Jayaraman

2014-05-26

Can photocatalysis be performed without electron or energy transfer? To address this, organo-photocatalysts that are based on atropisomeric thioureas and display lower excited-state energies than the reactive substrates have been developed. These photocatalysts were found to be efficient in promoting the [2+2] photocycloaddition of 4-alkenyl-substituted coumarins, which led to the corresponding products with high enantioselectivity (77-96% ee) at low catalyst loading (1-10 mol%). The photocatalytic cycle proceeds by energy sharing via the formation of both static and dynamic complexes (exciplex formation), which is aided by hydrogen bonding. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Metabolism of styrene in the human liver in vitro: interindividual variation and enantioselectivity

NARCIS (Netherlands)

Wenker, M. A.; Kezić, S.; Monster, A. C.; de Wolff, F. A.

2001-01-01

1. The interindividual variation and enantioselectivity of the in vitro styrene oxidation by cytochrome P450 have been investigated in 20 human microsomal liver samples. Liver samples were genotyped for the CYP2E1*6 and CYP2E1*5B alleles. 2. Kinetic analysis indicated the presence of at least two

One pot 'click' reactions : tandem enantioselective biocatalytic epoxide ring opening and [3+2] azide alkyne cycloaddition

NARCIS (Netherlands)

Campbell-Verduyn, Lachlan S.; Szymanski, Wiktor; Postema, Christiaan P.; Dierckx, Rudi A.; Elsinga, Philip H.; Janssen, Dick B.; Feringa, Ben L.

2010-01-01

Halohydrin dehalogenase (HheC) can perform enantioselective azidolysis of aromatic epoxides to 1,2-azido alcohols which are subsequently ligated to alkynes producing chiral hydroxy triazoles in a one-pot procedure with excellent enantiomeric excess.

High Pressure Diels Alder Reactions of 1-Vinyl-2,2,6-trimethylcyclohexene Catalyzed by Chiral Lewis Acids; An Enantioselective Route to a Drimane Sesquiterpene Precursor.

NARCIS (Netherlands)

Knol, Joop; Meetsma, Auke; Feringa, Bernard

1995-01-01

The Diels Alder reaction of 1-vinyl-2,2,6-trimethylcyclohexene and 3-((E)-3-(methoxycarbonyl)propenoyl)-1,3-oxazolidin-2-one under high pressure, catalyzed by a chiral bis-imine copper(II) complex, yields a drimane sesquiterpene precursor in a highly regio- and diastereoselective manner with

Diazo compounds and N-tosylhydrazones: novel cross-coupling partners in transition-metal-catalyzed reactions.

Science.gov (United States)

Xiao, Qing; Zhang, Yan; Wang, Jianbo

2013-02-19

Transition-metal-catalyzed carbene transformations and cross-couplings represent two major reaction types in organometallic chemistry and organic synthesis. However, for a long period of time, these two important areas have evolved separately, with essentially no overlap or integration. Thus, an intriguing question has emerged: can cross-coupling and metal carbene transformations be merged into a single reaction cycle? Such a combination could facilitate the development of novel carbon-carbon bond-forming methodologies. Although this concept was first explored about 10 years ago, rapid developments inthis area have been achieved recently. Palladium catalysts can be used to couple diazo compounds with a wide variety of organic halides. Under oxidative coupling conditions, diazo compounds can also react with arylboronic acids and terminal alkynes. Both of these coupling reactions form carbon-carbon double bonds. As the key step in these catalytic processes, Pd carbene migratory insertion plays a vital role in merging the elementary steps of Pd intermediates, leading to novel carbon-carbon bond formations. Because the diazo substrates can be generated in situ from N-tosylhydrazones in the presence of base, the N-tosylhydrazones can be used as reaction partners, making this type of cross-coupling reaction practical in organic synthesis. N-Tosylhydrazones are easily derived from the corresponding aldehydes or ketones. The Pd-catalyzed cross-coupling of N-tosylhydrazones is considered a complementary reaction to the classic Shapiro reaction for converting carbonyl functionalities into carbon-carbon double bonds. It can also serve as an alternative approach for the Pd-catalyzed cross-coupling of carbonyl compounds, which is usually achieved via triflates. The combination of carbene formation and cross-coupling in a single catalytic cycle is not limited to Pd-catalyzed reactions. Recent studies of Cu-, Rh-, Ni-, and Co-catalyzed cross-coupling reactions with diazo

Solvent-free copper-catalyzed click chemistry for the synthesis of N-heterocyclic hybrids based on quinoline and 1,2,3-triazole

Directory of Open Access Journals (Sweden)

Martina Tireli

2017-11-01

Full Text Available Copper-catalyzed mechanochemical click reactions using Cu(II, Cu(I and Cu(0 catalysts have been successfully implemented to provide novel 6-phenyl-2-(trifluoromethylquinolines with a phenyl-1,2,3-triazole moiety at O-4 of the quinoline core. Milling procedures proved to be significantly more efficient than the corresponding solution reactions, with up to a 15-fold gain in yield. Efficiency of both solution and milling procedures depended on the p-substituent in the azide reactant, resulting in H < Cl < Br < I reactivity bias. Solid-state catalysis using Cu(II and Cu(I catalysts entailed the direct involvement of the copper species in the reaction and generation of highly luminescent compounds which hindered in situ monitoring by Raman spectroscopy. However, in situ monitoring of the milling processes was enabled by using Cu(0 catalysts in the form of brass milling media which offered a direct insight into the reaction pathway of mechanochemical CuAAC reactions, indicating that the catalysis is most likely conducted on the surface of milling balls. Electron spin resonance spectroscopy was used to determine the oxidation and spin states of the respective copper catalysts in bulk products obtained by milling procedures.

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.

The catalytic cycle of nitrous oxide reductase - The enzyme that catalyzes the last step of denitrification.

Science.gov (United States)

Carreira, Cíntia; Pauleta, Sofia R; Moura, Isabel

2017-12-01

The reduction of the potent greenhouse gas nitrous oxide requires a catalyst to overcome the large activation energy barrier of this reaction. Its biological decomposition to the inert dinitrogen can be accomplished by denitrifiers through nitrous oxide reductase, the enzyme that catalyzes the last step of the denitrification, a pathway of the biogeochemical nitrogen cycle. Nitrous oxide reductase is a multicopper enzyme containing a mixed valence CuA center that can accept electrons from small electron shuttle proteins, triggering electron flow to the catalytic sulfide-bridged tetranuclear copper "CuZ center". This enzyme has been isolated with its catalytic center in two forms, CuZ*(4Cu1S) and CuZ(4Cu2S), proven to be spectroscopic and structurally different. In the last decades, it has been a challenge to characterize the properties of this complex enzyme, due to the different oxidation states observed for each of its centers and the heterogeneity of its preparations. The substrate binding site in those two "CuZ center" forms and which is the active form of the enzyme is still a matter of debate. However, in the last years the application of different spectroscopies, together with theoretical calculations have been useful in answering these questions and in identifying intermediate species of the catalytic cycle. An overview of the spectroscopic, kinetics and structural properties of the two forms of the catalytic "CuZ center" is given here, together with the current knowledge on nitrous oxide reduction mechanism by nitrous oxide reductase and its intermediate species. Copyright © 2017 Elsevier Inc. All rights reserved.

Fabrication, characterization and sensing properties of Cu(II) ion imprinted sol–gel thin film on QCM

International Nuclear Information System (INIS)

Su, Pi-Guey; Hung, Fang-Chieh; Lin, Po-Hung

2012-01-01

Cu(II)-molecularly imprinted sol–gel films (Cu(II)-MISGF), coated on a quartz crystal microbalance (QCM) chip, were fabricated using a sol–gel procedure. Co-hydrolysis and co-condensation of Cu(II) (templates), 3-aminopropyltrimethoxysilane (APTS, functional monomer) and tetraethoxysilane (TEOS, cross-linking agent) were performed with acid and base catalysis. The properties of the Cu(II)-MISGF were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and the electrochemical methods of cyclic voltammetry (CV). Microstructural observations revealed that the acid-catalyzed system yielded more mechanically stable thin films. A combined Cu(II)-MISGF-QCM with flow injection analysis (FIA) method was utilized to investigate the sensing performance of the Cu(II)-MISGF, with special emphasis on the most important properties of sensitivity, selectivity and response time. The Cu(II)-MISGF-QCM sensor, at a TEOS/APTS molar ratio of 10, exhibited excellent selectivity and rapidly responded to Cu(II) ions. - Highlights: ► A Cu(II)-molecularly imprinted sol–gel thin film on chip was fabricated. ► The thin film had mechanical stability using acidic catalyst. ► The thin film had good selectivity and response time for Cu(II) ions.

Dissipation and enantioselective degradation of plant growth retardants paclobutrazol and uniconazole in open field, greenhouse, and laboratory soils.

Science.gov (United States)

Wu, Chengwang; Sun, Jianqiang; Zhang, Anping; Liu, Weiping

2013-01-15

Greenhouses are increasingly important in human food supply. Pesticides used in greenhouses play important roles in horticulture; however, little is known about their behavior in greenhouse environments. This work investigates the dissipation and enantioselctive degradation of plant growth retardants including paclobutrazol and uniconazole in soils under three conditions (i.e., open field, greenhouse, and laboratory). The dissipation and enantioselective degradation of paclobutrazol and uniconazole in greenhouse were different from those in open field; they were more persistent in greenhouse than in open field soil. Leaching produced by rainfall is responsible for the difference in dissipation. Thus, local environmental impacts may occur more easily inside greenhouses, while groundwater may be more contaminated in open field. Spike concentrations of 5, 10, and 20 times the concentrations of native residues were tested for the enantioselective dissipation of the two pesticides; the most potent enantioselective degradation of paclobutrazol and uniconazole occurred at the 10 times that of the native residues in the greenhouse environments and at 20 times native residues in open field environments. The higher soil activity in greenhouses than in open fields was thought to be responsible for such a difference. The environmental risk and regulation of paclobutrazol and uniconazole should be considered at the enantiomeric level.

An entry to a chiral dihydropyrazole scaffold: enantioselective [3 + 2] cycloaddition of nitrile imines.

Science.gov (United States)

Sibi, Mukund P; Stanley, Levi M; Jasperse, Craig P

2005-06-15

We have developed a versatile strategy to access dihydropyrazoles in highly enantioenriched form. Dipolar cycloaddition of electron-deficient acceptors and in situ-generated nitrile imines proceeds with high regio- and enantioselectivity using 10 mol % chiral Lewis acid catalyst. A variety of dihydropyrazoles that incorporate functionality for further manipulation have been prepared.

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

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

One-Pot Catalytic Enantio- and Diastereoselective Syntheses of anti-, syn-cis-Disubstituted, and syn-Vinyl Cyclopropyl Alcohols

Science.gov (United States)

Kim, Hun Young; Salvi, Luca; Carroll, Patrick J.; Walsh, Patrick J.

2009-01-01

Highly enantio- and diastereoselective methods for the synthesis of a variety of cyclopropyl alcohols are reported. These methods represent the first one-pot approaches to syn-vinyl cyclopropyl alcohols, syn-cis-disubstituted cyclopropyl alcohols, and anti-cyclopropyl alcohols from achiral precursors. The methods begin with enantioselective C–C bond formations promoted by a MIB-based zinc catalyst to generate allylic alkoxide intermediates. The intermediates are then subjected to in situ alkoxide-directed cyclopropanation to provide cyclopropyl alcohols. In the synthesis of vinyl cyclopropyl alcohols, hydroboration of enynes is followed by transmetalation of the resulting dienylborane to zinc to provide dienylzinc reagents. Enantioselective addition to aldehydes generates the requisite dienyl zinc alkoxides, which are then subjected to in situ cyclopropanation to furnish vinyl cyclopropyl alcohols. Cyclopropanation occurs at the double bond allylic to the alkoxide. Using this method, syn-vinylcyclopropyl alcohols are obtained in 65–85% yield, 76–93% ee, and >19:1 dr. To prepare anti-cyclopropanols, enantioselective addition of alkylzinc reagents to conjugated enals provides allylic zinc alkoxides. Because direct cyclopropanation provides syn-cyclopropyl alcohols, the intermediate allylic alkoxides were treated with TMSCl/Et3N to generate intermediate silyl ethers. In situ cyclopropanation of the allylic silyl ether resulted in cyclopropanation to form the anti-cyclopropyl silyl ether. Workup with TBAF affords the anti-cyclopropyl alcohols in one-pot in 60–82% yield, 89–99% ee, and ≥10:1 dr. For the synthesis of cis-disubstituted cyclopropyl alcohols, in situ generated (Z)-vinyl zinc reagents were employed in asymmetric addition to aldehydes to generate (Z)-allylic zinc alkoxides. In situ cyclopropanation provides syn-cis-disubstituted cyclopropyl alcohols in 42–70% yield, 88–97% ee, and >19:1 dr. These one-pot procedures enable the synthesis of a

Cofactor engineering of Lactobacillus brevis alcohol dehydrogenase by computational design

NARCIS (Netherlands)

Machielsen, M.P.; Looger, L.L.; Raedts, J.G.J.; Dijkhuizen, S.; Hummel, W.; Henneman, H.G.; Daussmann, T.; Oost, van der J.

2009-01-01

The R-specific alcohol dehydrogenase from Lactobacillus brevis (Lb-ADH) catalyzes the enantioselective reduction of prochiral ketones to the corresponding secondary alcohols. It is stable and has broad substrate specificity. These features make this enzyme an attractive candidate for

Asymmetric Hydrogenation of Quinoxalines Catalyzed by Iridium/PipPhos

NARCIS (Netherlands)

Mrsic, Natasa; Jerphagnon, Thomas; Minnaard, Adriaan J.; Feringa, Ben L.; de Vries, Johannes G.

2009-01-01

A catalyst made in situ from the (cyclooctadiene)iridium chloride dimer, [Ir(COD)Cl](2), and the monodentate phosphoramidite ligand (S)-PipPhos was used in the enantioselective hydrogenation of 2- and 2,6-substituted quinoxalines. In the presence of piperidine hydrochloride as additive full

Synthesis of Fluorinated Amphiphilic Block Copolymers Based on PEGMA, HEMA, and MMA via ATRP and CuAAC Click Chemistry

OpenAIRE

Erol, Fatime Eren; Sinirlioglu, Deniz; Cosgun, Sedat; Muftuoglu, Ali Ekrem

2014-01-01

Synthesis of fluorinated amphiphilic block copolymers via atom transfer radical polymerization (ATRP) and Cu(I) catalyzed Huisgen 1,3-dipolar cycloaddition (CuAAC) was demonstrated. First, a PEGMA and MMA based block copolymer carrying multiple side-chain acetylene moieties on the hydrophobic segment for postfunctionalization was carried out. This involves the synthesis of a series of P(HEMA-co-MMA) random copolymers to be employed as macroinitiators in the controlled synthesis of P(HEMA-co-M...

The Role of Solvent Polarity on Low-Temperature Methanol Synthesis Catalyzed by Cu Nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Ahoba-Sam, Christian [Department of Process, Energy and Environmental Technology, University College of Southeast Norway, Porsgrunn (Norway); Olsbye, Unni [Department of Chemistry, University of Oslo, Oslo (Norway); Jens, Klaus-Joachim, E-mail: Klaus.J.Jens@usn.no [Department of Process, Energy and Environmental Technology, University College of Southeast Norway, Porsgrunn (Norway)

2017-07-14

Methanol syntheses at low temperature in a liquid medium present an opportunity for full syngas conversion per pass. The aim of this work was to study the role of solvents polarity on low-temperature methanol synthesis reaction using eight different aprotic polar solvents. A “once through” catalytic system, which is composed of Cu nanoparticles and sodium methoxide, was used for methanol synthesis at 100°C and 20 bar syngas pressure. Solvent polarity rather than the 7–10 nm Cu (and 30 nm Cu on SiO{sub 2}) catalyst used dictated trend of syngas conversion. Diglyme with a dielectric constant (ε) = 7.2 gave the highest syngas conversion among the eight different solvents used. Methanol formation decreased with either increasing or decreasing solvent ε value of diglyme (ε = 7.2). To probe the observed trend, possible side reactions of methyl formate (MF), the main intermediate in the process, were studied. MF was observed to undergo two main reactions; (i) decarbonylation to form CO and MeOH and (ii) a nucleophilic substitution to form dimethyl ether and sodium formate. Decreasing polarity favored the decarbonylation side reaction while increasing polarity favored the nucleophilic substitution reaction. In conclusion, our results show that moderate polarity solvents, e.g., diglyme, favor MF hydrogenolysis and, hence, methanol formation, by retarding the other two possible side reactions.

Organocatalytic Enantioselective Pictet-Spengler Approach to Biologically Relevant 1-Benzyl-1,2,3,4-Tetrahydroisoquinoline Alkaloids

NARCIS (Netherlands)

Ruiz-Olalla, A.; Würdemann, M.A.; Wanner, M.J.; Ingemann, S.; van Maarseveen, J.H.; Hiemstra, H.

2015-01-01

A general procedure for the synthesis of 1-benzyl-1,2,3,4-tetrahydroisoquinolines was developed, based on organocatalytic, regio- and enantioselective Pictet-Spengler reactions (86-92% ee) of N-(o-nitrophenylsulfenyl)-2-arylethyl-amines with arylacetaldehydes. The presence of the

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

Science.gov (United States)

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

2018-06-04

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

Mechanistic Studies on the Copper-Catalyzed N-Arylation of Amides

Science.gov (United States)

Strieter, Eric R.; Bhayana, Brijesh; Buchwald, Stephen L.

2009-01-01

The copper-catalyzed N-arylation of amides, i.e., the Goldberg reaction, is an efficient method for the construction of products relevant to both industry and academic settings. Herein, we present mechanistic details concerning the catalytic and stoichiometric N-arylation of amides. In the context of the catalytic reaction, our findings reveal the importance of chelating diamine ligands in controlling the concentration of the active catalytic species. The consistency between the catalytic and stoichiometric results suggest that the activation of aryl halides occurs through a 1,2-diamine-ligated copper(I) amidate complex. Kinetic studies on the stoichiometric N-arylation of aryl iodides using 1,2-diamine ligated Cu(I) amidates also provide insights into the mechanism of aryl halide activation. PMID:19072233

Copper-vapor-catalyzed chemical vapor deposition of graphene on dielectric substrates

Science.gov (United States)

Yang, Chao; Wu, Tianru; Wang, Haomin; Zhang, Xuefu; Shi, Zhiyuan; Xie, Xiaoming

2017-07-01

Direct synthesis of high-quality graphene on dielectric substrates is important for its application in electronics. In this work, we report the process of copper-vapor-catalyzed chemical vapor deposition of high-quality and large graphene domains on various dielectric substrates. The copper vapor plays a vital role on the growth of transfer-free graphene. Both single-crystal domains that are much larger than previous reports and high-coverage graphene films can be obtained by adjusting the growth duration. The quality of the obtained graphene was verified to be comparable with that of graphene grown on Cu foil. The progress reported in this work will aid the development of the application of transfer-free graphene in the future.

Enantioselective epoxidation with chiral MN(III)(salen) catalysts: kinetic resolution of aryl-substituted allylic alcohols.

Science.gov (United States)

Adam, W; Humpf, H U; Roschmann, K J; Saha-Möller, C R

2001-08-24

A set of aryl-substituted allylic alcohols rac-2 has been epoxidized by chiral Mn(salen*) complexes 1 as the catalyst and iodosyl benzene (PhIO) as the oxygen source. Whereas one enantiomer of the allylic alcohol 2 is preferentially epoxidized to give the threo- or cis-epoxy alcohol 3 (up to 80% ee) as the main product (dr up to >95:5), the other enantiomer of 2 is enriched (up to 53% ee). In the case of 1,1-dimethyl-1,2-dihydronaphthalen-2-ol (2c), the CH oxidation to the enone 4c proceeds enantioselectively and competes with the epoxidation. The absolute configurations of the allylic alcohols 2 and their epoxides 3 have been determined by chemical correlation or CD spectroscopy. The observed diastereo- and enantioselectivities in the epoxidation reactions are rationalized in terms of a beneficial interplay between the hydroxy-directing effect and the attack along the Katsuki trajectory.

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.

High-Throughput Screening of the Asymmetric Decarboxylative Alkylation Reaction of Enolate-Stabilized Enol Carbonates

KAUST Repository

Stoltz, Brian

2010-06-14

The use of high-throughput screening allowed for the optimization of reaction conditions for the palladium-catalyzed asymmetric decarboxylative alkylation reaction of enolate-stabilized enol carbonates. Changing to a non-polar reaction solvent and to an electron-deficient PHOX derivative as ligand from our standard reaction conditions improved the enantioselectivity for the alkylation of a ketal-protected,1,3-diketone-derived enol carbonate from 28% ee to 84% ee. Similar improvements in enantioselectivity were seen for a β-keto-ester derived- and an α-phenyl cyclohexanone-derived enol carbonate.

High-Throughput Screening of the Asymmetric Decarboxylative Alkylation Reaction of Enolate-Stabilized Enol Carbonates

KAUST Repository

Stoltz, Brian; McDougal, Nolan; Virgil, Scott

2010-01-01

The use of high-throughput screening allowed for the optimization of reaction conditions for the palladium-catalyzed asymmetric decarboxylative alkylation reaction of enolate-stabilized enol carbonates. Changing to a non-polar reaction solvent and to an electron-deficient PHOX derivative as ligand from our standard reaction conditions improved the enantioselectivity for the alkylation of a ketal-protected,1,3-diketone-derived enol carbonate from 28% ee to 84% ee. Similar improvements in enantioselectivity were seen for a β-keto-ester derived- and an α-phenyl cyclohexanone-derived enol carbonate.

Capped CuInS2 quantum dots for H2 evolution from water under visible light illumination

International Nuclear Information System (INIS)

Li, Tzung-Luen; Cai, Cheng-Da; Yeh, Te-Fu; Teng, Hsisheng

2013-01-01

Highlights: ► Dispersed CuInS 2 quantum dots showed remarkable photosynthetic activity using visible light. ► Photogenerated electrons in CuInS 2 were effective in H 2 production from aqueous solution. ► The bifunctional capping reagent effectively transported photogenerated electrons for reaction. ► Ru-loaded CuInS 2 quantum dots showed a quantum efficiency of 4.7% in H 2 evolution. ► Attaching CuInS 2 to TiO 2 with CdS passivation achieved a quantum efficiency of 41%. - Abstract: This study demonstrates H 2 evolution from water decomposition catalyzed by capped CuInS 2 quantum dots (QDs) that are highly dispersed in a polysulfide aqueous solution. The CuInS 2 QDs, which are obtained from solvothermal synthesis, have a size of 4.3 nm and a band gap of 1.97 eV. For photosynthetic H 2 evolution in the aqueous solution, the QDs are capped with a multidentate ligand (3-mercaptopropionic acid), which has a thiol end for attaching the QDs and a hydrophilic carboxylic end for dispersion in water. The capped QDs exhibit low activity in catalyzing H 2 evolution under visible illumination. After photodepositing 0.5 wt.% Ru, the capped QDs are active in producing H 2 with illumination. This demonstrates that the photogenerated electrons travel through the capping reagent to generate deposited Ru, which subsequently serves as an electron trap for H 2 evolution. A heterostructure formed by attaching the capped QDs on TiO 2 nanoparticles, followed by coating CdS with photodeposition, exhibits a high quantum efficiency of 41% for H 2 evolution from the polysulfide solution. These results demonstrate the potential for photosynthesis and phototherapy in biologic in vivo or microfluidic systems based on this capped QD material.

Asymmetric Brønsted Acid Catalyzed Substitution of Diaryl Methanols with Thiols and Alcohols for the Synthesis of Chiral Thioethers and Ethers

KAUST Repository

Chatupheeraphat, Adisak; Liao, Hsuan-Hung; Mader, Steffen; Sako, Makoto; Sasai, Hiroaki; Atodiresei, Iuliana; Rueping, Magnus

2016-01-01

An enantioselective addition of thiols and alcohols to aza-ortho-quinone methides, starting from diaryl methanols, was developed. The asymmetric additions occur under mild reaction conditions in the presence of chiral phosphoric acids and furnish the corresponding adducts with excellent yields and enantioselectivities.

Asymmetric Brønsted Acid Catalyzed Substitution of Diaryl Methanols with Thiols and Alcohols for the Synthesis of Chiral Thioethers and Ethers

KAUST Repository

Chatupheeraphat, Adisak

2016-03-08

An enantioselective addition of thiols and alcohols to aza-ortho-quinone methides, starting from diaryl methanols, was developed. The asymmetric additions occur under mild reaction conditions in the presence of chiral phosphoric acids and furnish the corresponding adducts with excellent yields and enantioselectivities.

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.

Poly(propylene carbonate): Insight into the Microstructure and Enantioselective Ring-Opening Mechanism

KAUST Repository

Salmeia, Khalifah A.; Vagin, Sergei; Anderson, Carly E.; Rieger, Bernhard

2012-01-01

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.

Chiral separation of substituted phenylalanine analogues using chiral palladium phosphine complexes with enantioselective liquid-liquid extraction

NARCIS (Netherlands)

Verkuijl, B.J.V.; Schuur, B.; Minnaard, A.J.; Vries, de J.G.; Feringa, B.L.

2010-01-01

Chiral palladium phosphine complexes have been employed in the chiral separation of amino acids and phenylalanine analogues in particular. The use of (S)-xylyl-BINAP as a ligand for the palladium complex in enantioselective liquid–liquid extraction allowed the separation of the phenylalanine

Equilibrium Studies on Enantioselective Liquid-Liquid Amino Acid Extraction Using a Cinchona Alkaloid Extractant

NARCIS (Netherlands)

Schuur, Boelo; Winkelman, Jozef G. M.; Heeres, Hero J.

2008-01-01

The enantioselective extraction of aqueous 3,5-dinitrobenzoyl-R,S-leucine (A(R,S)) by a cinchona alkaloid extractant (C) in 1,2-dichloroethane was studied at room temperature (294 K) in a batch system for a range of intake concentrations (10(-4)-10(-3) mol/L) and pH values (3.8-6.6). The

Enantioselective analysis of drugs: contributions of high-performance liquid chromatography and capillary electrophoresis

OpenAIRE

Bonato, Pierina Sueli; Jabor, Valquíria Aparecida Polisel; Gaitani, Cristiane Masetto de

2005-01-01

The demand for analytical methods suitable for accurate and reproducible determination of drug enantiomers has increased significantly in the last years. High-performance liquid chromatography (HPLC) using chiral stationary phases and capillary electrophoresis (CE) are the most important techniques used for this purpose. In this paper, the fundamental aspects of chiral separations using both techniques are presented. Some important aspects for the development of enantioselective methods, part...

Rhodium(II)-Catalyzed Asymmetric Sulfur(VI) Reduction of Diazo Sulfonylamidines

OpenAIRE

Selander, Nicklas; Fokin, Valery V.

2012-01-01

Diazo sulfonylamidines readily undergo enantioselective oxygen transfer from sulfur to carbon atom in the presence of chiral rhodium(II) carboxylates resulting in chiral sulfinylamidines. This unusual asymmetric atom transfer “reduction” occurs rapidly under mild conditions, and sulfinylamidines are obtained in excellent yield.

Synthesis of CNTs/CuO and its catalytic performance on the thermal decomposition of ammonium perchlorate

Directory of Open Access Journals (Sweden)

Ping Cui

2016-05-01

Full Text Available Copper oxide (CuO nanoparticles were successfully deposited on carbon nanotubes’ (CNTs surface via complex-precipitation method, the nanocomposite was characterized by transmission electron microscopy (TEM, scanning electron microscopy (SEM, X-ray photoelectron spectroscopy (XPS, X-ray powder diffraction (XRD, Raman spectroscopy, Fourier transform infrared (FT-IR and Brunauer–Emmett–Teller (BET. The catalytic performance of CNTs/CuO on ammonium perchlorate (AP decomposition was analyzed by differential thermal analyzer (DTA, the DTA results showed its excellent catalytic effect on AP decomposition, as 8 wt.% CNTs/CuO was added in AP, the second exothermic peak temperature decreased by 158 °C. Such composite may be a promising candidate for catalyzing the AP thermal decomposition.

Influence of CuO nanoparticle on palm oil based alkyd resin preparation and its antimicrobial activity

Science.gov (United States)

Ruey Ong, Huei; Maksudur Rahman Khan, Md.; Ramli, Ridzuan; Shein Hong, Chi; Yunus, Rosli Mohd

2018-03-01

An alkyd resin has been synthesized from palm oil that reacted with glycerol and phthalic anhydride by alcoholysis-polyesterification process and co-catalyzed by CuO nanoparticle. The CuO nanoparticle was pre-prepared in the glycerol via sol gel method, which creates a new reaction condition for resin preparation. The resins were characterized by fourier transform infrared spectroscopy (FTIR), where a new ester linkage bond (C-O-C) was noticed for resin sample. The antimicrobial activity and the curing behaviour of the resin were determined by Kirby-Bauer and differential scanning calorimeter technique. It was found that, the addition of CuO speeded up the reaction rate and played antimicrobial role. Moreover, it shortens the reaction time of alcoholysis and polyesterification process.

Enantioselective Synthesis of α-Mercapto-β-amino Esters via Rh(II)/Chiral Phosphoric Acid-Cocatalyzed Three-Component Reaction of Diazo Compounds, Thiols, and Imines.

Science.gov (United States)

Xiao, Guolan; Ma, Chaoqun; Xing, Dong; Hu, Wenhao

2016-12-02

An enantioselective method for the synthesis of α-mercapto-β-amino esters has been developed via a rhodium(II)/chiral phosphoric acid-cocatalyzed three-component reaction of diazo compounds, thiols, and imines. This transformation is proposed to proceed through enantioselective trapping of the sulfonium ylide intermediate generated in situ from the diazo compound and thiol by the phosphoric acid-activated imine. With this method, a series of α-mercapto-β-amino esters were obtained in good yields with moderate to good stereoselectivities.

Photoinduced, copper-catalyzed alkylation of amides with unactivated secondary alkyl halides at room temperature.

Science.gov (United States)

Do, Hien-Quang; Bachman, Shoshana; Bissember, Alex C; Peters, Jonas C; Fu, Gregory C

2014-02-05

The development of a mild and general method for the alkylation of amides with relatively unreactive alkyl halides (i.e., poor substrates for SN2 reactions) is an ongoing challenge in organic synthesis. We describe herein a versatile transition-metal-catalyzed approach: in particular, a photoinduced, copper-catalyzed monoalkylation of primary amides. A broad array of alkyl and aryl amides (as well as a lactam and a 2-oxazolidinone) couple with unactivated secondary (and hindered primary) alkyl bromides and iodides using a single set of comparatively simple and mild conditions: inexpensive CuI as the catalyst, no separate added ligand, and C-N bond formation at room temperature. The method is compatible with a variety of functional groups, such as an olefin, a carbamate, a thiophene, and a pyridine, and it has been applied to the synthesis of an opioid receptor antagonist. A range of mechanistic observations, including reactivity and stereochemical studies, are consistent with a coupling pathway that includes photoexcitation of a copper-amidate complex, followed by electron transfer to form an alkyl radical.

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

Science.gov (United States)

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

2017-07-07

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

cis-chlorobenzene dihydrodiol dehydrogenase (TcbB) from Pseudomonas sp. strain P51, expressed in Escherichia coli DH5alpha(pTCB149), catalyzes enantioselective dehydrogenase reactions.

Science.gov (United States)

Raschke, H; Fleischmann, T; Van Der Meer, J R; Kohler, H P

1999-12-01

cis-Chlorobenzene dihydrodiol dehydrogenase (CDD) from Pseudomonas sp. strain P51, cloned into Escherichia coli DH5alpha(pTCB149) was able to oxidize cis-dihydrodihydroxy derivatives (cis-dihydrodiols) of dihydronaphthalene, indene, and four para-substituted toluenes to the corresponding catechols. During the incubation of a nonracemic mixture of cis-1,2-indandiol, only the (+)-cis-(1R,2S) enantiomer was oxidized; the (-)-cis-(S,2R) enantiomer remained unchanged. CDD oxidized both enantiomers of cis-1,2-dihydroxy-1,2,3, 4-tetrahydronaphthalene, but oxidation of the (+)-cis-(1S,2R) enantiomer was delayed until the (-)-cis-(1R,2S) enantiomer was completely depleted. When incubated with nonracemic mixtures of para-substituted cis-toluene dihydrodiols, CDD always oxidized the major enantiomer at a higher rate than the minor enantiomer. When incubated with racemic 1-indanol, CDD enantioselectively transformed the (+)-(1S) enantiomer to 1-indanone. This stereoselective transformation shows that CDD also acted as an alcohol dehydrogenase. Additionally, CDD was able to oxidize (+)-cis-(1R,2S)-dihydroxy-1, 2-dihydronaphthalene, (+)-cis-monochlorobiphenyl dihydrodiols, and (+)-cis-toluene dihydrodiol to the corresponding catechols.

cis-Chlorobenzene Dihydrodiol Dehydrogenase (TcbB) from Pseudomonas sp. Strain P51, Expressed in Escherichia coli DH5α(pTCB149), Catalyzes Enantioselective Dehydrogenase Reactions

Science.gov (United States)

Raschke, Henning; Fleischmann, Thomas; Van Der Meer, Jan Roelof; Kohler, Hans-Peter E.

1999-01-01

cis-Chlorobenzene dihydrodiol dehydrogenase (CDD) from Pseudomonas sp. strain P51, cloned into Escherichia coli DH5α(pTCB149) was able to oxidize cis-dihydrodihydroxy derivatives (cis-dihydrodiols) of dihydronaphthalene, indene, and four para-substituted toluenes to the corresponding catechols. During the incubation of a nonracemic mixture of cis-1,2-indandiol, only the (+)-cis-(1R,2S) enantiomer was oxidized; the (−)-cis-(S,2R) enantiomer remained unchanged. CDD oxidized both enantiomers of cis-1,2-dihydroxy-1,2,3,4-tetrahydronaphthalene, but oxidation of the (+)-cis-(1S,2R) enantiomer was delayed until the (−)-cis-(1R,2S) enantiomer was completely depleted. When incubated with nonracemic mixtures of para-substituted cis-toluene dihydrodiols, CDD always oxidized the major enantiomer at a higher rate than the minor enantiomer. When incubated with racemic 1-indanol, CDD enantioselectively transformed the (+)-(1S) enantiomer to 1-indanone. This stereoselective transformation shows that CDD also acted as an alcohol dehydrogenase. Additionally, CDD was able to oxidize (+)-cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene, (+)-cis-monochlorobiphenyl dihydrodiols, and (+)-cis-toluene dihydrodiol to the corresponding catechols. PMID:10583971

Cis-Chlorobenzene dihydrodiol dehydrogenase (TcbB) from Pseudomonas sp. strain P51, expressed in Escherichia coli DH5{alpha}(pTCB149), catalyzes enantioselective dehydrogenase reactions

Energy Technology Data Exchange (ETDEWEB)

Raschke, H.; Fleischmann, T.; Meer, J.R. van der; Kohler, H.P.E.

1999-12-01

cis-Chlorobenzene dihydrodiol dehydrogenase (CDD) from Pseudomonas sp. strain P51, cloned into Escherichia coli DH5{alpha}(pTCB149) was able to oxidize cis-dihydrodihydroxy derivatives (cis-dihydrodiols) of dihydronaphthalene, indene, and four para-substituted toluenes to the corresponding catechols. During the incubation of a nonracemic mixture of cis-1,2-indandiol, only the (+)-cis-(1R,2S) enantiomer was oxidized; the (-)-cis-(S,2R) enantiomer remained unchanged, CDD oxidized both enantiomers of cis-1,2-dihydroxy-1,2,3,4-tetrahydronaphthalene, but oxidation of the (+)-cis-(1S,2R) enantiomer was delayed until the (-)-cis-(1R,2S) enantiomer was completely depleted. When incubated with nonracemic mixtures of para-substituted cis-toluene dihydrodiols, CDD always oxidized the major enantiomer at a higher rate than the minor enantiomer. When incubated with racemic 1-indanol, CDD enantioselectively transformed the (+)-(1S) enatiomer to 1-indanone. This stereoselective transformation shows that CDD also acted as an alcohol dehydrogenase. Additionally, CDD was able to oxidize (+)-cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene, (+)-cis-monochlorobiphenyl dihydrodiols, and (+)-cis-toluene dihydrodiol to the corresponding catechols.

CATALYTIC KINETIC RESOLUTION OF 5-ALKOXY-2(5H)-FURANONES

NARCIS (Netherlands)

FABER, WS; Kok, Johan C; DELANGE, B; FERINGA, BL; Faber, Wijnand S.; Lange, Ben de; Feringa, Bernard

1994-01-01

The kinetic resolution of racemic 5-alkoxy-2(5H)-furanones, using a chiral aminoalcohol catalyzed 1-4-addition of arylthiols, was examined. Using various butenolides it was shown that a gamma-alkoxy substituent appears to be essential to reach high enantioselectivities whereas electron-donating

Enantioselective Degradation and Chiral Stability of Metalaxyl-M in Tomato Fruits.

Science.gov (United States)

Jing, Xu; Yao, Guojun; Wang, Peng; Liu, Donghui; Qi, Yanli; Zhou, Zhiqiang

2016-05-01

Metalaxyl is an important chiral acetanilide fungicide, and the activity almost entirely originates from the R-enantiomer. Racemic metalaxyl has been gradually replaced by the enantiopure R-enantiomer (metalaxyl-M). In this study a chiral residue analysis method for metalaxyl and the metabolite metalaxyl acid was set up based on high-performance liquid chromatography tandem mass spectroscopy (HPLC-MS/MS). The enantioselective degradation and chiral stability of metalaxyl-M in tomato fruits in two geographically distinct regions of China (Heilongjiang and Hunan Province) were evaluated and the enantioselectivity of metalaxyl acid was also investigated. Tomato plants grew under field conditions with a one-time spray application of metalaxyl-M wettable powder. It was found that R-metalaxyl was not chirally stable and the inactive S-metalaxyl was detected in tomato fruits. At day 40, S-metalaxyl derived from R-metalaxyl accounted for 32% and 26% of the total amount of metalaxyl, respectively. The metabolites R-metalaxyl acid and S-metalaxyl acid were both observed in tomato, and the ratio of S-metalaxyl acid to the sum of S- and R-metalaxyl acid was 36% and 28% at day 40, respectively. For both metalaxyl and metalaxyl acid, the half-life of the S-enantiomer was longer than the R-enantiomer. The results indicated that the enantiomeric conversion should be considered in the bioactivity evaluation and environmental pollution assessment. Chirality 28:382-386, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Enatioselective[2+2+2] Cycloaddition as A Synthetic Tool

Institute of Scientific and Technical Information of China (English)

T.Shibata; S.Yoshida; M.Otsuka; Y.Arai; K.Endo

2007-01-01

1 Results Transition metal-catalyzed [2+2+2] cycloaddition is one of the most efficient protocols for the construction of six-membered ring system.Our group has comprehensively studied various types of highly enantioselective [2+2+2] cycloaddition for the synthesis of chiral cycloadducts; we already reported an iridium-catalyzed intermolecular [2+2+2] cycloaddition between α,ω-diynes,having various tethers and substituents on the alkyne termini,and monoalkynes,possessing oxygen or/and nitrogen functiona...

Paralogous gene analysis reveals a highly enantioselective 1,2-O-isopropylideneglycerol caprylate esterase of Bacillus subtilis

NARCIS (Netherlands)

Droge, MJ; Bos, R; Quax, WJ

Carboxylesterase NP of Bacillus subtilis Thai 1-8, characterized in 1992 as a very enantioselective (S)-naproxen esterase, was found to show no enantiopreference towards (S)-1,2-O-isopropylideneglycerol (IPG) esters. The ybfK gene was identified by the B. subtilis genome project as an unknown gene

Hydrothermal synthesis, crystal structures, and enantioselective adsorption property of bis(L-histidinato)nickel(II) monohydrate

Science.gov (United States)

Ramos, Christian Paul L.; Conato, Marlon T.

2018-05-01

Despite the numerous researches in metal-organic frameworks (MOFs), there are only few reports on biologically important amino acids, histidine in particular, on its use as bridging ligand in the construction of open-framework architectures. In this work, hydrothermal synthesis was used to prepare a compound based on Ni2+ and histidine. The coordination assembly of imidazole side chain of histidine with divalent nickel ions in aqueous condition yielded purple prismatic solids. Single crystal X-ray diffraction (XRD) analysis of the product revealed structure for Ni(C6H8N3O2)2 • H2O that has a monoclinic (C2) structure with lattice parameters, a = 29.41, b = 8.27, c = 6.31 Å, β = 90.01 ˚. Circular dichroism - optical rotatory dispersion (CD-ORD), Powder X-ray diffraction (PXRD) and Fourier transform - infrared spectroscopy (FT-IR) analyses are conducted to further characterize the crystals. Enantioselective adsorption analysis using racemic mixture of 2-butanol confirmed bis(L-histidinato)nickel(II) monohydrate MOF crystal's enantioselective property preferentially favoring the adsorption of (S)-2-butanol isomer.

Formation of bromate and halogenated disinfection byproducts during chlorination of bromide-containing waters in the presence of dissolved organic matter and CuO

KAUST Repository

Liu, Chao; Croue, Jean-Philippe

2015-01-01

Previous studies showed that significant bromate (BrO3-) can be formed via the CuO-catalyzed disproportionation of hypobromous acid (HOBr) pathway. In this study, the influence of CuO on the formation of BrO3- and halogenated disinfection byproducts (DBPs) (e.g., trihalomethanes, THMs and haloacetic acids, HAAs) during chlorination of six dissolved organic matter (DOM) isolates was investigated. Only in the presence of slow reacting DOM (from treated Colorado River water, i.e., CRW-BF-HPO), significant BrO3- formation is observed, which competes with bromination of DOM (i.e., THM and HAA formation). Reactions between HOBr and 12 model compounds in the presence of CuO indicates that CuO-catalyzed HOBr disproportionation is completely inhibited by fast reacting phenols, while it predominates in the presence of practically unreactive compounds (acetone, butanol, propionic, and butyric acids). In the presence of slow reacting di- and tri-carboxylic acids (oxalic, malonic, succinic, and citric acids), BrO3- formation varies, depending on its competition with bromoform and dibromoacetic acid formation (i.e., bromination pathway). The latter pathway can be enhanced by CuO due to the activation of HOBr. Therefore, increasing CuO dose (0-0.2 g L-1) in a reaction system containing chlorine, bromide, and CRW-BF-HPO enhances the formation of BrO3-, total THMs and HAAs. Factors including pH and initial reactant concentrations influence the DBP formation. These novel findings have implications for elevated DBP formation during transportation of chlorinated waters in copper-containing distribution systems.

Formation of bromate and halogenated disinfection byproducts during chlorination of bromide-containing waters in the presence of dissolved organic matter and CuO

KAUST Repository

Liu, Chao

2015-12-02

Previous studies showed that significant bromate (BrO3-) can be formed via the CuO-catalyzed disproportionation of hypobromous acid (HOBr) pathway. In this study, the influence of CuO on the formation of BrO3- and halogenated disinfection byproducts (DBPs) (e.g., trihalomethanes, THMs and haloacetic acids, HAAs) during chlorination of six dissolved organic matter (DOM) isolates was investigated. Only in the presence of slow reacting DOM (from treated Colorado River water, i.e., CRW-BF-HPO), significant BrO3- formation is observed, which competes with bromination of DOM (i.e., THM and HAA formation). Reactions between HOBr and 12 model compounds in the presence of CuO indicates that CuO-catalyzed HOBr disproportionation is completely inhibited by fast reacting phenols, while it predominates in the presence of practically unreactive compounds (acetone, butanol, propionic, and butyric acids). In the presence of slow reacting di- and tri-carboxylic acids (oxalic, malonic, succinic, and citric acids), BrO3- formation varies, depending on its competition with bromoform and dibromoacetic acid formation (i.e., bromination pathway). The latter pathway can be enhanced by CuO due to the activation of HOBr. Therefore, increasing CuO dose (0-0.2 g L-1) in a reaction system containing chlorine, bromide, and CRW-BF-HPO enhances the formation of BrO3-, total THMs and HAAs. Factors including pH and initial reactant concentrations influence the DBP formation. These novel findings have implications for elevated DBP formation during transportation of chlorinated waters in copper-containing distribution systems.

Enantioselective potential of polysaccharide-based chiral stationary phases in supercritical fluid chromatography.

Science.gov (United States)

Kucerova, Gabriela; Kalikova, Kveta; Tesarova, Eva

2017-06-01

The enantioselective potential of two polysaccharide-based chiral stationary phases for analysis of chiral structurally diverse biologically active compounds was evaluated in supercritical fluid chromatography using a set of 52 analytes. The chiral selectors immobilized on 2.5 μm silica particles were tris-(3,5-dimethylphenylcarmabate) derivatives of cellulose or amylose. The influence of the polysaccharide backbone, different organic modifiers, and different mobile phase additives on retention and enantioseparation was monitored. Conditions for fast baseline enantioseparation were found for the majority of the compounds. The success rate of baseline and partial enantioseparation with cellulose-based chiral stationary phase was 51.9% and 15.4%, respectively. Using amylose-based chiral stationary phase we obtained 76.9% of baseline enantioseparations and 9.6% of partial enantioseparations of the tested compounds. The best results on cellulose-based chiral stationary phase were achieved particularly with propane-2-ol and a mixture of isopropylamine and trifluoroacetic acid as organic modifier and additive to CO 2 , respectively. Methanol and basic additive isopropylamine were preferred on amylose-based chiral stationary phase. The complementary enantioselectivity of the cellulose- and amylose-based chiral stationary phases allows separation of the majority of the tested structurally different compounds. Separation systems were found to be directly applicable for analyses of biologically active compounds of interest. © 2017 Wiley Periodicals, Inc.

Oxidative kinetic resolution of racemic alcohols catalyzed by chiral ferrocenyloxazolinylphosphine-ruthenium complexes.

Science.gov (United States)

Nishibayashi, Yoshiaki; Yamauchi, Akiyoshi; Onodera, Gen; Uemura, Sakae

2003-07-25

Oxidative kinetic resolution of racemic secondary alcohols by using acetone as a hydrogen acceptor in the presence of a catalytic amount of [RuCl(2)(PPh(3))(ferrocenyloxazolinylphosphine)] (2) proceeds effectively to recover the corresponding alcohols in high yields with an excellent enantioselectivity. When 1-indanol is employed as a racemic alcohol, the oxidation proceeds quite smoothly even in the presence of 0.0025 mol % of the catalyst 2 to give an optically active 1-indanol in good yield with high enantioselectivity (up to 94% ee), where turnover frequency (TOF) exceeds 80,000 h(-1). From a practical viewpoint, the kinetic resolution is investigated in a large scale, optically pure (S)-1-indanol (75 g, 56% yield, >99% ee) being obtained from racemic 1-indanol (134 g) by employing this kinetic resolution method twice.

Improved performance of Yarrowia lipolytica lipase-catalyzed kinetic resolution of (R,S)-2-octanol by an integrated strategy of interfacial activation, bioimprinting and immobilization.

Science.gov (United States)

Liu, Ying; Guo, Chen; Sun, Xi-Tong; Liu, Chun-Zhao

2013-08-01

Yarrowia lipolytica lipase (YLL) demonstrated an (R)-enantiopreference for efficient resolution of (R,S)-2-octanol. The activity, enantioselectivity, the ratio of substrate to enzyme, acetaldehyde tolerance, and operational stability of YLL were improved by an integrated strategy of interfacial activation, bioimprinting, and immobilization. In comparison with the control, both the enzymatic activity and enantioselectivity increased by a factor of 8.85 and 2.75 by the integrated strategy, respectively. Fifty-one percentage of conversion with 220 of enantioselectivity was obtained using the immobilized YLL prepared by the integrated strategy at a ratio of 104 of substrate to enzyme loaded. The immobilized YLL retained 97% of its initial activity without a decrease in enantioselectivity after 10 successive reuse cycles. Together these results will result in a promising strategy with the YYL for efficient resolution of (R,S)-2-octanol in practice. Copyright © 2013 Elsevier Ltd. All rights reserved.

Chlorination of iodide-containing waters in the presence of CuO: Formation of periodate

KAUST Repository

Liu, Chao; Salhi, Elisabeth; Croue, Jean-Philippe; von Gunten, Urs

2014-01-01

It has been shown previously that the disproportionation of halogen-containing oxidants (e.g., HOCl, HOBr, and ClO2) is enhanced by a CuO-catalyzed process. In this study, the transformation of iodine during chlorination in the presence of CuO was investigated. There is no significant enhancement of the disproportionation of hypoiodous acid (HOI) in the presence of CuO. The formation rate of iodate (IO3 -) in the CuO-HOCl-I- system significantly increased when compared to homogeneous solutions, which was ascribed to the activation of HOCl by CuO enhancing its reactivity toward HOI. In this reaction system, iodate formation rates increase with increasing CuO (0-0.5 g L-1) and bromide (0-2 μM) doses and with decreasing pH (9.6-6.6). Iodate does not adsorb to the CuO surfaces used in this study. Nevertheless, iodate concentrations decreased after a maximum was reached in the CuO-HOCl-I-(-Br-) systems. Similarly, the iodate concentrations decrease as a function of time in the CuO-HOCl-IO3 - or CuO-HOBr-IO3 - system, and the rates increase with decreasing pH (9.6-6.6) due to the enhanced reactivity of HOCl or HOBr in the presence of CuO. It could be demonstrated that iodate is oxidized to periodate by a CuO-activated hypohalous acid, which is adsorbed on the CuO surface. No periodate could be measured in filtered solutions because it was mainly adsorbed to CuO. The adsorbed periodate was identified by scanning electron microscopy plus energy dispersive spectroscopy and X-ray photoelectron spectroscopy.

Chlorination of iodide-containing waters in the presence of CuO: Formation of periodate

KAUST Repository

Liu, Chao

2014-11-18

It has been shown previously that the disproportionation of halogen-containing oxidants (e.g., HOCl, HOBr, and ClO2) is enhanced by a CuO-catalyzed process. In this study, the transformation of iodine during chlorination in the presence of CuO was investigated. There is no significant enhancement of the disproportionation of hypoiodous acid (HOI) in the presence of CuO. The formation rate of iodate (IO3 -) in the CuO-HOCl-I- system significantly increased when compared to homogeneous solutions, which was ascribed to the activation of HOCl by CuO enhancing its reactivity toward HOI. In this reaction system, iodate formation rates increase with increasing CuO (0-0.5 g L-1) and bromide (0-2 μM) doses and with decreasing pH (9.6-6.6). Iodate does not adsorb to the CuO surfaces used in this study. Nevertheless, iodate concentrations decreased after a maximum was reached in the CuO-HOCl-I-(-Br-) systems. Similarly, the iodate concentrations decrease as a function of time in the CuO-HOCl-IO3 - or CuO-HOBr-IO3 - system, and the rates increase with decreasing pH (9.6-6.6) due to the enhanced reactivity of HOCl or HOBr in the presence of CuO. It could be demonstrated that iodate is oxidized to periodate by a CuO-activated hypohalous acid, which is adsorbed on the CuO surface. No periodate could be measured in filtered solutions because it was mainly adsorbed to CuO. The adsorbed periodate was identified by scanning electron microscopy plus energy dispersive spectroscopy and X-ray photoelectron spectroscopy.

Site-specific bioconjugation of a murine dihydrofolate reductase enzyme by copper(I-catalyzed azide-alkyne cycloaddition with retained activity.

Directory of Open Access Journals (Sweden)

Sung In Lim

Full Text Available Cu(I-catalyzed azide-alkyne cycloaddition (CuAAC is an efficient reaction linking an azido and an alkynyl group in the presence of copper catalyst. Incorporation of a non-natural amino acid (NAA containing either an azido or an alkynyl group into a protein allows site-specific bioconjugation in mild conditions via CuAAC. Despite its great potential, bioconjugation of an enzyme has been hampered by several issues including low yield, poor solubility of a ligand, and protein structural/functional perturbation by CuAAC components. In the present study, we incorporated an alkyne-bearing NAA into an enzyme, murine dihydrofolate reductase (mDHFR, in high cell density cultivation of Escherichia coli, and performed CuAAC conjugation with fluorescent azide dyes to evaluate enzyme compatibility of various CuAAC conditions comprising combination of commercially available Cu(I-chelating ligands and reductants. The condensed culture improves the protein yield 19-fold based on the same amount of non-natural amino acid, and the enzyme incubation under the optimized reaction condition did not lead to any activity loss but allowed a fast and high-yield bioconjugation. Using the established conditions, a biotin-azide spacer was efficiently conjugated to mDHFR with retained activity leading to the site-specific immobilization of the biotin-conjugated mDHFR on a streptavidin-coated plate. These results demonstrate that the combination of reactive non-natural amino acid incorporation and the optimized CuAAC can be used to bioconjugate enzymes with retained enzymatic activity.

Primary amine/CSA ion pair: A powerful catalytic system for the asymmetric enamine catalysis

KAUST Repository

Liu, Chen; Zhu, Qiang; Huang, Kuo-Wei; Lu, Yixin

2011-01-01

A novel ion pair catalyst containing a chiral counteranion can be readily derived by simply mixing cinchona alkaloid-derived diamine with chiral camphorsulfonic acid (CSA). A mixture of 9-amino(9-deoxy)epi-quinine 8 and (-)-CSA was found to be the best catalyst with matching chirality, enabling the direct amination of α-branched aldehydes to proceed in quantitative yields and with nearly perfect enantioselectivities. A 0.5 mol % catalyst loading was sufficient to catalyze the reaction, and a gram scale enantioselective synthesis of biologically important α-methyl phenylglycine has been successfully demonstrated. © 2011 American Chemical Society.

Primary amine/CSA ion pair: A powerful catalytic system for the asymmetric enamine catalysis

KAUST Repository

Liu, Chen

2011-05-20

A novel ion pair catalyst containing a chiral counteranion can be readily derived by simply mixing cinchona alkaloid-derived diamine with chiral camphorsulfonic acid (CSA). A mixture of 9-amino(9-deoxy)epi-quinine 8 and (-)-CSA was found to be the best catalyst with matching chirality, enabling the direct amination of α-branched aldehydes to proceed in quantitative yields and with nearly perfect enantioselectivities. A 0.5 mol % catalyst loading was sufficient to catalyze the reaction, and a gram scale enantioselective synthesis of biologically important α-methyl phenylglycine has been successfully demonstrated. © 2011 American Chemical Society.

Evaluation of (+)-sparteine-like diamines for asymmetric synthesis.

Science.gov (United States)

Dearden, Michael J; McGrath, Matthew J; O'Brien, Peter

2004-08-20

Three new (+)-sparteine-like diamines were prepared from (-)-cytisine and evaluated as sparteine surrogates in the alpha-lithiation rearrangement of cyclooctene oxide and the palladium(II)/diamine catalyzed oxidative kinetic resolution of 1-indanol. The new diamines exhibited opposite enantioselectivity to that observed with (-)-sparteine but increasing the steric hindrance of the N-alkyl group beyond N-Et had a detrimental effect on enantioselectivity. The optimal N-Me diamine was evaluated with much success in five other (-)-sparteine-mediated processes involving different metals (lithium, magnesium, and copper) and different types of reaction mechanisms. Copyright 2004 American Chemical Society

Organocatalytic asymmetric selenofunctionalization of tryptamine for the synthesis of hexahydropyrrolo[2,3-b]indole derivatives

Directory of Open Access Journals (Sweden)

Qiang Wei

2013-08-01

Full Text Available A chiral phosphoric acid-catalyzed selenofunctionalization of tryptamine derivatives provides access to 3a-(phenylselenyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole derivatives in high yields and with synthetically useful levels of enantioselectivity (up to 89% ee.

An investigation of nitrile transforming enzymes in the chemo-enzymatic synthesis of the taxol sidechain

Czech Academy of Sciences Publication Activity Database

Wilding, B.; Veselá, Alicja Barbara; Perry, J.B.J.; Black, W.G.; Zhang, M.; Martínková, Ludmila; Klempier, N.

2015-01-01

Roč. 13, č. 28 (2015), s. 7803-7812 ISSN 1477-0520 R&D Projects: GA ČR(CZ) GAP504/11/0394 Institutional support: RVO:61388971 Keywords : LIPASE -CATALYZED TRANSESTERIFICATION * HIGHLY ENANTIOSELECTIVE SYNTHESIS * BIOLOGICAL EVALUATION Subject RIV: CC - Organic Chemistry Impact factor: 3.559, year: 2015

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

KAUST Repository

Wu, Linglin; Falivene, Laura; Drinkel, Emma E.; Grant, Sharday; Linden, Anthony; Cavallo, Luigi; Dorta, Reto

2012-01-01

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.

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.

A Convergent Enantioselective Total Synthesis of (-)-Perhydrohistrionicotoxin with an Intramolecular Imino Ene-type Reaction as a Key Step

DEFF Research Database (Denmark)

Tanner, David Ackland; Hagberg, Lars

1998-01-01

A convergent enantioselective total synthesis of the neurotoxic spirocyclic alkaloid (-)-perhydrohistrionicotoxin (2) is described. A Lewis acid-mediated intramolecular imine ene-type reaction was used for the key spirocyclisation step (14 to 3, with 3 being obtained as a single diastereoisomer...

Separation of racemic mixture by ultrafiltration of enantioselective micelles. 1 Effect of pH on separation and regeneration

NARCIS (Netherlands)

Overdevest, P.E.M.; Bruin, de T.J.M.; Riet, van 't K.; Keurentjes, J.T.F.; Padt, van der A.

2001-01-01

Many enantiomer separation systems are studied to meet the increasing demand for enantiopure compounds. One way to obtain pure enantiomers is to apply enantioselective micelles in ultrafiltration systems. We have studied the separation of phenylalanine (Phe) enantiomers by the ultrafiltration of

Pd2+ and Cu2+ catalyzed oxidative cross-coupling of mercaptoacetylenes and arylboronic acids

Czech Academy of Sciences Publication Activity Database

Henke, Adam; Šrogl, Jiří

2011-01-01

Roč. 47, č. 14 (2011), s. 4282-4284 ISSN 1359-7345 R&D Projects: GA ČR GA203/08/1318 Grant - others:AV ČR(CZ) M200550908 Institutional research plan: CEZ:AV0Z40550506 Keywords : mercaptoacetylenes * oxidative cross - coupling * Cu/Pd catalysis Subject RIV: CC - Organic Chemistry Impact factor: 6.169, year: 2011

Thermodynamics of Enzyme-Catalyzed Reactions Database

Science.gov (United States)

SRD 74 Thermodynamics of Enzyme-Catalyzed Reactions Database (Web, free access)   The Thermodynamics of Enzyme-Catalyzed Reactions Database contains thermodynamic data on enzyme-catalyzed reactions that have been recently published in the Journal of Physical and Chemical Reference Data (JPCRD). For each reaction the following information is provided: the reference for the data, the reaction studied, the name of the enzyme used and its Enzyme Commission number, the method of measurement, the data and an evaluation thereof.

Enantioselective radical reactions. Evaluation of nitrogen protecting groups in the synthesis of beta-amino acids.

Science.gov (United States)

Sibi, Mukund P; Patil, Kalyani

2006-02-20

We have investigated the effect of nitrogen protecting groups in radical addition trapping experiments leading to beta(2)-amino acids. Of the three N-protecting groups examined, the phthalimido group was optimal with respect to both yields and enantioselectivity. Additionally, radical additions to more complex acrylates were also investigated, which provided access to functionalized beta(2)-amino acids in modest selectivity.

MICROWAVE-ASSISTED CU (I) CATALYZED SOLVENT-FREE THREE COMPONENT COUPLING OF ALDEHYDE, ALKYNE AND AMINE

Science.gov (United States)

Direct Grignard type addition of terminal alkynes to in situ generated imines, from aldehydes and amines, occurs under microwave irradiation using CuBr alone in a one-pot operation. This solventless approach provides ready access to propargylamines and is applicable both...

Enhancing the muon-catalyzed fusion yield

International Nuclear Information System (INIS)

Jones, S.E.

1987-01-01

Much has been learned about muon-catalyzed fusion since the last conference on emerging nuclear energy systems. Here the authors consider what they have learned about enhancing the muon-catalyzed fusion energy yield

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.

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.

Enantioselective changes in oxidative stress and toxin release in Microcystis aeruginosa exposed to chiral herbicide diclofop acid

Energy Technology Data Exchange (ETDEWEB)

Ye, Jing [School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418 (China); MOE Key Lab of Environmental Remediation and Ecosystem Health, College of Natural Research and Environmental Sciences, Zhejiang University, Hangzhou 310058 (China); Zhang, Ying [Department of Environmental Science, East China Normal University, Shanghai 200241 (China); Chen, Shengwen [School of Urban Development and Environment Engineering, Shanghai Second Polytechnic University, Shanghai 201209 (China); Liu, Chaonan; Zhu, Yongqiang [School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418 (China); Liu, Weiping, E-mail: wliu@zju.edu.cn [MOE Key Lab of Environmental Remediation and Ecosystem Health, College of Natural Research and Environmental Sciences, Zhejiang University, Hangzhou 310058 (China)

2014-01-15

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.

OMS-2-Supported Cu Hydroxide-Catalyzed Benzoxazoles Synthesis from Catechols and Amines via Domino Oxidation Process at Room Temperature.

Science.gov (United States)

Meng, Xu; Wang, Yanmin; Wang, Yuanguang; Chen, Baohua; Jing, Zhenqiang; Chen, Gexin; Zhao, Peiqing

2017-07-07

In the presence of manganese oxide octahedral molecular sieve (OMS-2) supported copper hydroxide Cu(OH) x /OMS-2, aerobic synthesis of benzoxazoles from catechols and amines via domino oxidation/cyclization at room temperature is achieved. This heterogeneous benzoxazoles synthesis initiated by the efficient oxidation of catechols over Cu(OH) x /OMS-2 tolerates a variety of substrates, especially amines containing sensitive groups (hydroxyl, cyano, amino, vinyl, ethynyl, ester, and even acetyl groups) and heterocycles, which affords functionalized benzoxazoles in good to excellent yields by employing low catalyst loading (2 mol % Cu). The characterization and plausible catalytic mechanism of Cu(OH) x /OMS-2 are described. The notable features of our catalytic protocol such as the use of air as the benign oxidant and EtOH as the solvent, mild conditions, ease of product separation, being scalable up to the gram level, and superior reusability of catalyst (up to 10 cycles) make it more practical and environmentally friendly for organic synthesis.

Predicting CYP2C19 Catalytic Parameters for Enantioselective Oxidations Using Artificial Neural Networks and a Chirality Code

Science.gov (United States)

Hartman, Jessica H.; Cothren, Steven D.; Park, Sun-Ha; Yun, Chul-Ho; Darsey, Jerry A.; Miller, Grover P.

2013-01-01

Cytochromes P450 (CYP for isoforms) play a central role in biological processes especially metabolism of chiral molecules; thus, development of computational methods to predict parameters for chiral reactions is important for advancing this field. In this study, we identified the most optimal artificial neural networks using conformation-independent chirality codes to predict CYP2C19 catalytic parameters for enantioselective reactions. Optimization of the neural networks required identifying the most suitable representation of structure among a diverse array of training substrates, normalizing distribution of the corresponding catalytic parameters (kcat, Km, and kcat/Km), and determining the best topology for networks to make predictions. Among different structural descriptors, the use of partial atomic charges according to the CHelpG scheme and inclusion of hydrogens yielded the most optimal artificial neural networks. Their training also required resolution of poorly distributed output catalytic parameters using a Box-Cox transformation. End point leave-one-out cross correlations of the best neural networks revealed that predictions for individual catalytic parameters (kcat and Km) were more consistent with experimental values than those for catalytic efficiency (kcat/Km). Lastly, neural networks predicted correctly enantioselectivity and comparable catalytic parameters measured in this study for previously uncharacterized CYP2C19 substrates, R- and S-propranolol. Taken together, these seminal computational studies for CYP2C19 are the first to predict all catalytic parameters for enantioselective reactions using artificial neural networks and thus provide a foundation for expanding the prediction of cytochrome P450 reactions to chiral drugs, pollutants, and other biologically active compounds. PMID:23673224

Copper-catalyzed asymmetric ring opening of oxabicyclic alkenes with organolithium reagents

NARCIS (Netherlands)

Bos, Pieter H.; Rudolph, Alena; Pérez, Manuel; Fañanás-Mastral, Martín; Harutyunyan, Syuzanna R.; Feringa, Bernard

2012-01-01

A highly efficient method is reported for the asymmetric ring opening of oxabicyclic alkenes with organolithium reagents. Using a copper/chiral phosphoramidite complex together with a Lewis acid (BF3·OEt2), full selectivity for the anti isomer and excellent enantioselectivities were obtained for the

Solid state green synthesis and catalytic activity of CuO nanorods in thermal decomposition of potassium periodate

Science.gov (United States)

Patel, Vinay Kumar; Bhattacharya, Shantanu

2017-09-01

The present study reports a facile solid state green synthesis process using the leaf extracts of Hibiscus rosa-sinensis to synthesize CuO nanorods with average diameters of 15-20 nm and lengths up to 100 nm. The as-synthesized CuO nanorods were characterized by x-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy and selected area electron diffraction. The formation mechanism of CuO nanorods has been explained by involving the individual role of amide I (amino groups) and carboxylate groups under excess hydroxyl ions released from NaOH. The catalytic activity of CuO nanorods in thermal decomposition of potassium periodate microparticles (µ-KIO4) microparticles was studied by thermo gravimetric analysis measurement. The original size (~100 µm) of commercially procured potassium periodate was reduced to microscale length scale to about one-tenth by PEG200 assisted emulsion process. The CuO nanorods prepared by solid state green route were found to catalyze the thermal decomposition of µ-KIO4 with a reduction of 18 °C in the final thermal decomposition temperature of potassium periodate.

Enantioselective Analytical- and Preparative-Scale Separation of Hexabromocyclododecane Stereoisomers Using Packed Column Supercritical Fluid Chromatography.

Science.gov (United States)

Riddell, Nicole; Mullin, Lauren Gayle; van Bavel, Bert; Ericson Jogsten, Ingrid; McAlees, Alan; Brazeau, Allison; Synnott, Scott; Lough, Alan; McCrindle, Robert; Chittim, Brock

2016-11-10

Hexabromocyclododecane (HBCDD) is an additive brominated flame retardant which has been listed in Annex A of the Stockholm Convention for elimination of production and use. It has been reported to persist in the environment and has the potential for enantiomer-specific degradation, accumulation, or both, making enantioselective analyses increasingly important. The six main stereoisomers of technical HBCDD (i.e., the (+) and (-) enantiomers of α-, β-, and γ-HBCDD) were separated and isolated for the first time using enantioselective packed column supercritical fluid chromatography (pSFC) separation methods on a preparative scale. Characterization was completed using published chiral liquid chromatography (LC) methods and elution profiles, as well as X-ray crystallography, and the isolated fractions were definitively identified. Additionally, the resolution of the enantiomers, along with two minor components of the technical product (δ- and ε-HBCDD), was investigated on an analytical scale using both LC and pSFC separation techniques, and changes in elution order were highlighted. Baseline separation of all HBCDD enantiomers was achieved by pSFC on an analytical scale using a cellulose-based column. The described method emphasizes the potential associated with pSFC as a green method of isolating and analyzing environmental contaminants of concern.

Kinetics and mechanics of photo-polymerized triazole-containing thermosetting composites via the copper(I)-catalyzed azide-alkyne cycloaddition.

Science.gov (United States)

Song, Han Byul; Wang, Xiance; Patton, James R; Stansbury, Jeffrey W; Bowman, Christopher N

2017-06-01

Several features necessary for polymer composite materials in practical applications such as dental restorative materials were investigated in photo-curable CuAAC (copper(I)-catalyzed azide-alkyne cycloaddition) thermosetting resin-based composites with varying filler loadings and compared to a conventional BisGMA/TEGDMA based composite. Tri-functional alkyne and di-functional azide monomers were synthesized for CuAAC resins and incorporated with alkyne-functionalized glass microfillers for CuAAC composites. Polymerization kinetics, in situ temperature change, and shrinkage stress were monitored simultaneously with a tensometer coupled with FTIR spectroscopy and a data-logging thermocouple. The glass transition temperature was analyzed by dynamic mechanical analysis. Flexural modulus/strength and flexural toughness were characterized in three-point bending on a universal testing machine. The photo-CuAAC polymerization of composites containing between 0 and 60wt% microfiller achieved ∼99% conversion with a dramatic reduction in the maximum heat of reaction (∼20°C decrease) for the 60wt% filled CuAAC composites as compared with the unfilled CuAAC resin. CuAAC composites with 60wt% microfiller generated more than twice lower shrinkage stress of 0.43±0.01MPa, equivalent flexural modulus of 6.1±0.7GPa, equivalent flexural strength of 107±9MPa, and more than 10 times higher energy absorption of 10±1MJm -3 when strained to 11% relative to BisGMA-based composites at equivalent filler loadings. Mechanically robust and highly tough, photo-polymerized CuAAC composites with reduced shrinkage stress and a modest reaction exotherm were generated and resulted in essentially complete conversion. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Rhodium catalyzed regioselective arene homologation of aryl urea via double C-H bond activation and migratory insertion of alkyne

Institute of Scientific and Technical Information of China (English)

Yan Wang; Hao Zhou; Ke Xu; Mei-Hua Shen; Hua-Dong Xu

2017-01-01

A convenient rhodium catalyzed oxidative arene homologation of aniline derivatives with symmetrical or unsymmetrical alkynes using Cu(OAc)2 as oxidant is described.Urea group is shown to be effective as a directing group for initial ortho C-H activation.Two migratory insertion events of alkyne into Rh-C bond occur successively,both with complete regioselectivity.This method is particularly useful for synthesis of polyarenes with different substituents,which has not been reported with conventional protocol.A mechanism has been proposed to explain the observed data.

High-yield conversion of (R)-2-octanol from the corresponding racemate by stereoinversion using Candida rugosa.

Science.gov (United States)

Nie, Yao; Xu, Yan; Qing Mu, Xiao; Tang, Yan; Jiang, Juan; Hao Sun, Zhi

2005-01-01

Whole cells of Candida rugosa catalyzed the conversion of (R)-2-octanol from the corresponding racemate with the optical purity of 97% e.e. and yield of 92% in 10 h. The product was formed through a stereoinversion involving enantioselective oxidation and asymmetric reduction with 2-octanone as the intermediate.

Rh-catalyzed linear hydroformylation of styrene

NARCIS (Netherlands)

Boymans, E.H.; Janssen, M.C.C.; Mueller, C.; Lutz, M.; Vogt, D.

2012-01-01

Usually the Rh-catalyzed hydroformylation of styrene predominantly yields the branched, chiral aldehyde. An inversion of regioselectivity can be achieved using strong p-acceptor ligands. Binaphthol-based diphosphite and bis(dipyrrolyl-phosphorodiamidite) ligands were applied in the Rh-catalyzed

Activation of lipase from .I.Geotrichum candidum./I. and its enantioselectivity towards xenobiotic substrates

Czech Academy of Sciences Publication Activity Database

Kejík, Z.; Zarevúcka, Marie; Demnerová, K.

2003-01-01

Roč. 97, č. 5 (2003), s. 293-294 ISSN 0009-2770. [Sigma-Aldrich konference mladých chemiků, biochemiků a molekulárních biologů /3./. 04.06.2003-07.06.2003, Devět skal - Žďárské vrchy] R&D Projects: GA MŠk OC D13.10 Institutional research plan: CEZ:AV0Z4055905 Keywords : lipase * enantioselectivity Subject RIV: CC - Organic Chemistry

Combining the [2,3] Sigmatropic Rearrangement and Ring-Closing Metathesis Strategies for the Synthesis of Spirocyclic Alkaloids. A Short and Efficient Route to (+/-)-Perhydrohistrionicotoxin

DEFF Research Database (Denmark)

Tanner, David Ackland; Hagberg, Lars; Poulsen, Anders

1999-01-01

This paper describes the use of selenium-based [2,3] sigmatropic rearrangement in combination with ruthenium-catalyzed ring-closing metathesis (RCM) for the synthesis of azaspiro ring systems, as exemplified by the reactions of model substrates 5 and 6. The methodology has been applied to a short...... is potentially enantioselective, and key steps were the [2,3] sigmatropic rearrangement of 11 to 12 via the corresponding allylic selenide (86% yield) and ruthenium-catalyzed RCM of 13 to 14 (80%). (C) 1999 Elsevier Science Ltd. All rights reserved....

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

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)).

Enantioselective radical reactions. Evaluation of nitrogen protecting groups in the synthesis of β2-amino acids

Science.gov (United States)

Sibi, Mukund P.; Patil, Kalyani

2006-01-01

We have investigated the effect of nitrogen protecting groups in radical addition trapping experiments leading to β2-amino acids. Of the three N-protecting groups examined, the phthalimido group was optimal with respect to both yields and enantioselectivity. Additionally, radical additions to more complex acrylates were also investigated, which provided access to functionalized β2-amino acids in modest selectivity. PMID:16799704

CLC in packed beds using syngas and CuO/Al2O3: Model description and experimental validation

International Nuclear Information System (INIS)

Hamers, H.P.; Gallucci, F.; Cobden, P.D.; Kimball, E.; Sint Annaland, M. van

2014-01-01

Highlights: • CLC with CuO/Al 2 O 3 and syngas and air has been demonstrated experimentally. • Model predicts accurately only if kinetics describe the complete solid reduction. • CuO/Al 2 O 3 is proven to catalyze the reversed water gas shift reaction. • H 2 O is more effective to suppress carbon deposition on CuO/Al 2 O 3 than CO 2 . • The OC reaction rate is not permanently affected by exposure to H 2 S. - Abstract: The objective of this work is to study the performance of the oxygen carrier in a packed bed with periodic switching between oxidizing and reducing conditions. In this paper the performance of CuO/Al 2 O 3 as the oxygen carrier in a packed bed reactor with syngas as the fuel are investigated, while also studying the (possible) carbon deposition and the effect of sulphur impurities on the stability of the carrier. Both experiments and simulations are used in this work. Cyclic experiments (oxidation with air and reduction with syngas) have been carried out in a lab scale packed bed reactor with 13 wt% CuO/Al 2 O 3 . The experimental results were well described by a 1D reactor model, provided that critical attention was given to the reaction rate for the complete reduction reaction, including a dramatic decrease in reaction rate at high solid conversions. Feeding syngas (p H2 = p CO = 0.1 bar) resulted in 1.1% carbon deposition of the feed. Steam was proven to be more effective in reducing carbon deposition than CO 2 . Moreover, it has been found that CuO/Al 2 O 3 catalyzed the water gas shift reaction and the reaction rate was not permanently affected by exposure to H 2 S, two key factors for CLC operation. The results of this work imply that CuO/Al 2 O 3 is an effective oxygen carrier as the first packed bed reactor in a TSCLC process and that the developed model is able to describe the performance at larger scales accurately

Chiral gold(I vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

Directory of Open Access Journals (Sweden)

María Martín-Rodríguez

2011-07-01

Full Text Available The synthesis of a GSK 2nd generation inhibitor of the hepatitis C virus, by enantioselective 1,3-dipolar cycloaddition between a leucine derived iminoester and tert-butyl acrylate, was studied. The comparison between silver(I and gold(I catalysts in this reaction was established by working with chiral phosphoramidites or with chiral BINAP. The best reaction conditions were used for the total synthesis of the hepatitis C virus inhibitor by a four step procedure affording this product in 99% ee and in 63% overall yield. The origin of the enantioselectivity of the chiral gold(I catalyst was justified according to DFT calculations, the stabilizing coulombic interaction between the nitrogen atom of the thiazole moiety and one of the gold atoms being crucial.

Hydroxynitrile Lyases with α/β-Hydrolase Fold: Two Enzymes with Almost Identical 3D Structures but Opposite Enantioselectivities and Different Reaction Mechanisms

Science.gov (United States)

Andexer, Jennifer N; Staunig, Nicole; Eggert, Thorsten; Kratky, Christoph; Pohl, Martina; Gruber, Karl

2012-01-01

Hydroxynitrile lyases (HNLs) catalyze the cleavage of cyanohydrins to yield hydrocyanic acid (HCN) and the respective carbonyl compound and are key enzymes in the process of cyanogenesis in plants. In organic syntheses, HNLs are used as biocatalysts for the formation of enantiopure cyanohydrins. We determined the structure of the recently identified, R-selective HNL from Arabidopsis thaliana (AtHNL) at a crystallographic resolution of 2.5 Å. The structure exhibits an α/β-hydrolase fold, very similar to the homologous, but S-selective, HNL from Hevea brasiliensis (HbHNL). The similarities also extend to the active sites of these enzymes, with a Ser-His-Asp catalytic triad present in all three cases. In order to elucidate the mode of substrate binding and to understand the unexpected opposite enantioselectivity of AtHNL, complexes of the enzyme with both (R)- and (S)-mandelonitrile were modeled using molecular docking simulations. Compared to the complex of HbHNL with (S)-mandelonitrile, the calculations produced an approximate mirror image binding mode of the substrate with the phenyl rings located at very similar positions, but with the cyano groups pointing in opposite directions. A catalytic mechanism for AtHNL is proposed, in which His236 from the catalytic triad acts as a general base and the emerging negative charge on the cyano group is stabilized by main-chain amide groups and an α-helix dipole very similar to α/β-hydrolases. This mechanistic proposal is additionally supported by mutagenesis studies. PMID:22851196

Organocatalytic asymmetric allylic amination of Morita–Baylis–Hillman carbonates of isatins

Directory of Open Access Journals (Sweden)

Hang Zhang

2012-08-01

Full Text Available The investigation of a Lewis base catalyzed asymmetric allylic amination of Morita–Baylis–Hillman carbonates derived from isatins afforded an electrophilic pathway to access multifunctional oxindoles bearing a C3-quaternary stereocenter, provided with good to excellent enantioselectivity (up to 94% ee and in high yields (up to 97%.

Organocatalytic Michael and Friedel–Crafts reactions in enantioselective synthesis of biologically active compounds

International Nuclear Information System (INIS)

Maltsev, O V; Beletskaya, Irina P; Zlotin, Sergei G

2011-01-01

Recent applications of organocatalytic Michael and Friedel–Crafts reactions in enantioselective synthesis of biologically active compounds: natural products, pharmaceutical agents and plant protection agents are reviewed. The key mechanisms of stereoinduction, types of organocatalysts and reagents used in these reactions are considered. The material is classified according to the type of newly formed bonds incorporating the asymmetric carbon atom, and the information for the most numerous C–C coupling reactions is systematized according to the natures of the electrophile and the nucleophile. The bibliography includes 433 references.

Proof of concept for continuous enantioselective liquid-liquid extraction in capillary microreactors using 1-octanol as a sustainable solvent

NARCIS (Netherlands)

Susanti, S.; Meinds, Tim G.; Pinxterhuis, Erik B.; Schuur, Boelo; De Vries, Johannes G.; Feringa, Ben L.; Winkelman, Jozef G.M.; Yue, Jun; Heeres, Hero J.

2017-01-01

The use of capillary microreactors for enantioselective liquid-liquid extraction (ELLE) was successfully demonstrated using a model system consisting of a buffered aqueous amino acid derivative (3,5-dinitrobenzoyl-(R,S)-leucine) solution (phosphate buffer, pH 6.58) and a chiral cinchona alkaloid

Muon catalyzed fusion under compressive conditions

International Nuclear Information System (INIS)

Cripps, G.; Goel, B.; Harms, A.A.

1991-01-01

The viability of a symbiotic combination of Muon Catalyzed Fusion (μCF) and high density generation processes has been investigated. The muon catalyzed fusion reaction rates are formulated in the temperature and density range found under moderate compressive conditions. Simplified energy gain and power balance calculations indicate that significant energy gain occurs only if standard type deuterium-tritium (dt) fusion is ignited. A computer simulation of the hydrodynamics and fusion kinetics of a spherical deuterium-tritium pellet implosion including muons is performed. Using the muon catalyzed fusion reaction rates formulated and under ideal conditions, the pellet ignites (and thus has a significant energy gain) only if the initial muon concentration is approximately 10 17 cm -3 . The muons need to be delivered to the pellet within a very short-time (≅ 1 ns). The muon pulse required in order to make the high density and temperature muon catalyzed fusion scheme viable is beyond the present technology for muon production. (orig.) [de

Enantioselective [2+2+2] cycloisomerisation of alkynes in the synthesis of helicenes: the search for effective chiral ligands

Czech Academy of Sciences Publication Activity Database

Stará, Irena G.; Andronova, Angelina; Kollárovič, Adrian; Vyskočil, Š.; Jugé, S.; Lloyd-Jones, G. C.; Guiry, P. J.; Starý, Ivo

2011-01-01

Roč. 76, č. 12 (2011), s. 2005-2022 ISSN 0010-0765 R&D Projects: GA ČR GA203/09/1766; GA MŠk LC512 Institutional research plan: CEZ:AV0Z40550506 Keywords : helicenes * enantioselectivity * cycloisomerisation Subject RIV: CC - Organic Chemistry Impact factor: 1.283, year: 2011

Catalyzed deuterium fueled tokamak reactors

International Nuclear Information System (INIS)

Southworth, F.H.

1977-01-01

Catalyzed deuterium fuel presents several advantages relative to D-T. These are, freedom from tritium breeding, high charged particle power fraction and lowered neutron energy deposition in the blanket. Higher temperature operation, lower power densities and increased confinement are simultaneously required. However, the present study has developed designs which have capitalized upon the advantages of catalyzed deuterium to overcome the difficulties associated with the fuel while obtaining high efficiency

Bioaccumulation and enantioselectivity of type I and type II pyrethroid pesticides in earthworm.

Science.gov (United States)

Chang, Jing; Wang, Yinghuan; Wang, Huili; Li, Jianzhong; Xu, Peng

2016-02-01

In this study, the bioavailability and enantioselectivity differences between bifenthrin (BF, typeⅠpyrethroid) and lambad-cyhalothrin (LCT, type Ⅱ pyrethroid) in earthworm (Eisenia fetida) were investigated. The bio-soil accumulation factors (BSAFs) of BF was about 4 times greater than that of LCT. LCT was degraded faster than BF in soil while eliminated lower in earthworm samples. Compound sorption plays an important role on bioavailability in earthworm, and the soil-adsorption coefficient (K(oc)) of BF and LCT were 22 442 and 42 578, respectively. Metabolic capacity of earthworm to LCT was further studied as no significant difference in the accumulation of LCT between the high and low dose experiment was found. 3-phenoxybenzoic acid (PBCOOH), a metabolite of LCT produced by earthworm was detected in soil. The concentration of PBCOOH at high dose exposure was about 4.7 times greater than that of in low dose level at the fifth day. The bioaccumulation of BF and LCT were both enantioselective in earthworm. The enantiomer factors of BF and LCT in earthworm were approximately 0.12 and 0.65, respectively. The more toxic enantiomers ((+)-BF and (-)-LCT) had a preferential degradation in earthworm and leaded to less toxicity on earthworm for racemate exposure. In combination with other studies, a liner relationship between Log BSAF(S) and Log K(ow) was observed, and the Log BSAF(S) decreased with the increase of Log K(ow). Copyright © 2015 Elsevier Ltd. All rights reserved.

Sonogashira Reaction of Aryl and Heteroaryl Halides with Terminal Alkynes Catalyzed by a Highly Efficient and Recyclable Nanosized MCM-41 Anchored Palladium Bipyridyl Complex

Directory of Open Access Journals (Sweden)

Chung-Yuan Mou

2010-12-01

Full Text Available A heterogeneous catalyst, nanosized MCM-41-Pd, was used to catalyze the Sonogashira coupling of aryl and heteroaryl halides with terminal alkynes in the presence of CuI and triphenylphosphine. The coupling products were obtained in high yields using low Pd loadings to 0.01 mol%, and the nanosized MCM-41-Pd catalyst was recovered by centrifugation of the reaction solution and re-used in further runs without significant loss of reactivity.