DNA-based catalytic enantioselective intermolecular oxa-Michael addition reactions

NARCIS (Netherlands)

Megens, Rik P.; Roelfes, Gerard

2012-01-01

Using the DNA-based catalysis concept, a novel Cu(II) catalyzed enantioselective oxa-Michael addition of alcohols to enones is reported. Enantioselectivities of up to 86% were obtained. The presence of water is important for the reactivity, possibly by reverting unwanted side reactions such as

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.

Enantioselective conjugate addition of silylketene acetals to beta-enamidomalonates. Synthesis of beta-amino acid derivatives.

Science.gov (United States)

Sibi, Mukund P; Chen, Jianxie

2002-08-22

[reaction: see text] Conjugate addition of silylketene acetals or enolsilanes to enamidomalonates proceeds with excellent chemical efficiency and good selectivity using Cu(OTf)2 and a chiral bisoxazoline. The effect of the Lewis acid, ligand, the N-acyl substituent, and the nucleophile on yield and selectivity for the addition product have been evaluated.

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.

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 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.

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

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.

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.

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.

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

Science.gov (United States)

Yu, Yue-Na; Xu, Ming-Hua

2013-03-15

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

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.

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.

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...

(+)-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

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.

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.

Isoindolinones as Michael Donors under Phase Transfer Catalysis: Enantioselective Synthesis of Phthalimidines Containing a Tetrasubstituted Carbon Stereocenter

Directory of Open Access Journals (Sweden)

Francesco Scorzelli

2015-05-01

Full Text Available Readily available chiral ammonium salts derived from cinchona alkaloids have proven to be effective phase transfer catalysts in the asymmetric Michael reaction of 3-substituted isoindolinones. This protocol provides a convenient method for the construction of valuable asymmetric 3,3-disubstituted isoindolinones in high yields and  moderate to good enantioselectivity. Diastereoselectivity was also investigated in the construction of contiguous tertiary and quaternary stereocenters. The use of acrolein as Michael acceptor led to an interesting tricyclic derivative, a pyrroloisoindolinone analogue, via a tandem conjugated addition/cyclization reaction.

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

Free-radical-mediated conjugate additions. Enantioselective synthesis of butyrolactone natural products: (-)-enterolactone, (-)-arctigenin, (-)-isoarctigenin, (-)-nephrosteranic acid, and (-)-roccellaric acid.

Science.gov (United States)

Sibi, Mukund P; Liu, Pingrong; Ji, Jianguo; Hajra, Saumen; Chen, Jian-xie

2002-03-22

Lewis acid-mediated conjugate addition of alkyl radicals to a differentially protected fumarate 10 produced the monoalkylated succinates with high chemical efficiency and excellent stereoselectivity. A subsequent alkylation or an aldol reaction furnished the disubstituted succinates with syn configuration. The chiral auxiliary, 4-diphenylmethyl-2-oxazolidinone, controlled the stereoselectivity in both steps. Manipulation of the disubstituted succinates obtained by alkylation furnished the natural products (-)-enterolactone, (-)-arctigenin, and (-)-isoarctigenin. The overall yields for the target natural products were 20-26% over six steps. Selective functionalization of the disubstituted succinates obtained by aldol condensation gave the paraconic acid natural products (-)-nephrosteranic acid (8) and (-)-roccellaric acid (9). The overall yield of the natural products 8 and 9 over four steps was 53% and 42%, respectively.

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.

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...

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.

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 �

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.

Sequential rhodium/palladium catalysis: enantioselective formation of dihydroquinolinones in the presence of achiral and chiral ligands.

Science.gov (United States)

Zhang, Lei; Qureshi, Zafar; Sonaglia, Lorenzo; Lautens, Mark

2014-12-08

Compatible combinations of achiral and chiral ligands can be used in rhodium/palladium catalysis to achieve highly enantioselective domino reactions. The difference in rates of catalysis and minimal effects of ligand interference confer control in the domino sequence. The "all-in-one" 1,4-conjugate arylation and C-N cross-coupling through sequential Rh/Pd catalysis provides access to enantioenriched dihydroquinolinone building blocks. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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.

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.

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.

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.

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 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.

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.

Niobium Pentachloride Activation of Enone Derivatives: Diels-Alder and Conjugate Addition Products

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Gil Valdo José da Silva

2002-05-01

Full Text Available Niobium pentachloride has proven to be a powerful activating agent for Diels-Alder or conjugate addition reactions of cycloenones. The Diels-Alder product was obtained only with an unsubstituted enone (cyclohexenone and the highly reactive diene cyclopentadiene; substituents in the b-position of enones seem to prevent Diels-Alder reaction: oxygenated substituents favor the formation of vinyl chlorides (ethyl ether or dichloromethane as solvents or enol ethers (ethyl acetate as solvent, while a methyl substituent prevents any kind of transformation with NbCl5. Less reactive dienes, furan and 2-methylfuran gave the conjugate addition products of the furan ring to the enone system.

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.

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.

Regioselective 1,4- and 1,6-Conjugate Additions of Grignard Reagent-Derived Organozinc(II)ates to Polyconjugated Esters.

Science.gov (United States)

Hatano, Manabu; Mizuno, Mai; Ishihara, Kazuaki

2016-09-16

Regioselective synthetic methods were developed for 1,4- and 1,6-conjugate additions of Grignard reagent-derived organozinc(II)ates to malonate-derived polyconjugated esters. By taking advantage of the tight ion-pair control of organozinc(II)ates, it was possible to switch between 1,4- and 1,6-conjugate additions by introducing a terminal ethoxy moiety in the conjugation.

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...

Regioselectivity of conjugate additions to monoalkyl-1,4-benzoquinones

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SNEZANA TRIFUNOVIC

2002-09-01

Full Text Available The regioselectivity of the reaction of conjugate addition of thiols, amines, methanol and hydrogen chloride with the monoalkyl-1,4-benzoquinones avarone and 2-tert-butyl-1,4-benzoquinone was investigated. It was shown that the regioselectivity of the reaction is influenced by the electrophilicity of position 5 in unprotonated 2-alkylquinones, the increased electrophilicity of position 6 in acidic medium, and by the acidity of the intermediate hydroquinones.

Rhodium(I)-Complexes Catalyzed 1,4-Conjugate Addition of Arylzinc Chlorides to N-Boc-4-pyridone.

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Guo, Fenghai; McGilvary, Matthew A; Jeffries, Malcolm C; Graves, Briana N; Graham, Shekinah A; Wu, Yuelin

2017-05-01

Rhodium(I)-complexes catalyzed the 1,4-conjugate addition of arylzinc chlorides to N -Boc-4-pyridone in the presence of chlorotrimethylsilane (TMSCl). A combination of [RhCl(C₂H₄)₂]₂ and BINAP was determined to be the most effective catalyst to promote the 1,4-conjugate addition reactions of arylzinc chlorides to N -Boc-4-pyridone. A broad scope of arylzinc reagents with both electron-withdrawing and electron-donating substituents on the aromatic ring successfully underwent 1,4-conjugate addition to N -Boc-4-pyridone to afford versatile 1,4-adducts 2-substituted-2,3-dihydropyridones in good to excellent yields (up to 91%) and excellent ee (up to 96%) when ( S )-BINAP was used as chiral ligand.

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.

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

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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.

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.

THE IMPACT OF CONJUGATED LINOLEIC ACID ADDITION ON PH VALUE OF LONGISSIMUS DORSI MUSCLE

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Przemysław WASILEWSKI

2009-08-01

Full Text Available The subject of research was 60 crossbred gilts, divided into 6 groups, fed the fodder with addition of conjugated linoleic acid (CLA or sunflower oil (SFO in amount: 0.5; 1.0; and 2.0 %, respectively. Animals were slaughtered with the body weight ca. 95 kg. The aim of research was to determine pH value of loin meat tissue (Longissimus dorsi of right half-carcass in 45 minutes, 2, 3, 4, 5, 6 hours and 24 hours after slaughter. Results were statistically elaborated using one-way variance analysis. Longissimus dorsi muscle pH values measured 45 minutes after slaughter in case of all groups of pigs were in range from 6.34 up to 6.47, what shows good meat quality. The lowest pH1 (measured 45 minutes after slaughter had meat of fatteners where addition of 2 % sunflower oil was given into fodder and the highest value of this trait was in group of individuals where also was given sunflower oil in 1 % amount. Statistical significant differences in pH value measured in different time after slaughter i.e. after 45 minutes, 2, 3, 4, 6 and 24 hours between tested groups of pigs were not stated. The exception is the result of pH measurement 5 hours after slaughter. Statistical significant differences were between group of pigs getting 0.5 % addition of conjugated linoleic acid characterized by the highest pH value of meat and group of animals fed the fodder with 1 % addition of conjugated linoleic acid (P≤0.01. On the basis of the results obtained in presented paper may be stated that feeding pigs with addition of conjugated linoleic acid in amounts 0.5; 1.0 and 2.0 % did not impact negatively on meat quality defined by pH value.

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

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.

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.

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 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.

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.

Rhodium(II)-catalyzed enantioselective synthesis of troponoids.

Science.gov (United States)

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

2015-06-22

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

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).

Conjugate addition of diethyl 1-fluoro-1-phenylsulfonylmethanephosphonate to alpha,beta-unsaturated compounds

Czech Academy of Sciences Publication Activity Database

Opekar, Stanislav; Pohl, Radek; Eigner, V.; Beier, Petr

2013-01-01

Roč. 78, č. 9 (2013), s. 4573-4579 ISSN 0022-3263 R&D Projects: GA ČR GP203/08/P310 Institutional support: RVO:61388963 Keywords : fluorine * phosphonate * conjugate addition Subject RIV: CC - Organic Chemistry Impact factor: 4.638, year: 2013

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.

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.

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

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).

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).

Metal-conjugated affinity labels: A new concept to create enantioselective artificial metalloenzymes

KAUST Repository

Reiner, Thomas

2013-02-20

How to train a protein: Metal-conjugated affinity labels were used to selectively position catalytically active metal centers in the binding pocket of proteases. The resulting artificial metalloenzymes achieve up to 82% e.r. in the hydrogenation of ketones. The modular setup enables a rapid generation of artificial metalloenzyme libraries, which can be adapted to a broad range of catalytic conditions. 2013 The Authors.

Metal-conjugated affinity labels: A new concept to create enantioselective artificial metalloenzymes

KAUST Repository

Reiner, Thomas; Jantke, Dominik; Marziale, Alexander N.; Raba, Andreas; Eppinger, Jö rg

2013-01-01

How to train a protein: Metal-conjugated affinity labels were used to selectively position catalytically active metal centers in the binding pocket of proteases. The resulting artificial metalloenzymes achieve up to 82% e.r. in the hydrogenation of ketones. The modular setup enables a rapid generation of artificial metalloenzyme libraries, which can be adapted to a broad range of catalytic conditions. 2013 The Authors.

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.

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.

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.

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.

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.

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.

Cross-conjugated Trienamine Catalysis with α'-Alkylidene 2-Cyclohexenones: Application in β,γ-Regioselective Aza-Diels-Alder Reaction.

Science.gov (United States)

Zhou, Zhi; Wang, Zhou-Xiang; Ouyang, Qin; Xiao, Wei; Du, Wei; Chen, Ying-Chun

2017-02-24

Endo-type cross-conjugated trienamines between highly congested α'-alkylidene 2-cyclohexenones and a chiral primary amine catalyst serve as HOMO-raised dienophiles in inverse-electron-demand aza-Diels-Alder cycloadditions with a number of 1-azadiene substrates. The reactions exhibit exclusive β,γ-regioselectivity, and multifunctional products with high molecular complexity are efficiently constructed in excellent diastereo- and enantioselectivity (>19:1 d.r., up to 99 % ee). © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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.

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.

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.

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%)

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.

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 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.

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.

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.

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 ...

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 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.

Catalytic asymmetric synthesis of the alkaloid (+)-myrtine

NARCIS (Netherlands)

Pizzuti, Maria Gabriefla; Minnaard, Adriaan J.; Feringa, Ben L.

2008-01-01

A new protocol for the asymmetric synthesis of trans-2,6-disubstituted-4-piperidones has been developed using a catalytic enantioselective conjugate addition reaction in combination with a diastereoselective lithiation-substitution sequence; an efficient synthesis of (+)-myrtine has been achieved

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.

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.

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.

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

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

Science.gov (United States)

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

2018-03-07

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

Conjugate additions of a simple monosilylcopper reagent with use of the CuI.DMS complex: stereoselectivities and a dramatic impact by DMS.

Science.gov (United States)

Dambacher, Jesse; Bergdahl, Mikael

2005-01-21

Conjugate additions utilizing the simple monosilylcuprate reagent Li[PhMe2SiCuI] to alpha,beta-unsaturated carbonyl compounds are described. The presence of dimethyl sulfide (DMS), either as a component originating from the (CuI)4(DMS)3 complex or as a solvent added, has an amazing influence on both chemical yield and the level of diastereomeric ratio (dr) of the products. Gilman-type silylcyanocuprates {Li(Ph2MeSi)2Cu/LiCN} have previously been used to guarantee good results in conjugate addition reactions. External additives such as HMPA, tributylphosphine, or dialkylzinc are not necessary in conjunction with the simple Li[PhMe2SiCuI] reagent. It is demonstrated that the monosilylcuprate reagent with DMS as the solvent is very useful with sterically hindered (beta,beta-disubstituted) enones, and provides very high yields of the beta-silylated 1,4-addition products. Since there is no oligomerization problem associated with the simple monosilylcuprate reagent, this reagent should be considered as a very useful 1,4-silyl donor to enals, enones, and enoates in conjugate addition reactions.

Conjugate Addition of Nucleophiles to the Vinyl Function of 2-Chloro-4-vinylpyrimidine Derivatives

Directory of Open Access Journals (Sweden)

Lucjan Strekowski

2010-03-01

Full Text Available Conjugate addition reaction of various nucleophiles across the vinyl group of 2-chloro-4-vinylpyrimidine, 2-chloro-4-(1-phenylvinylpyrimidine and 2-chloro-4-vinylquinazoline provides the corresponding 2-chloro-4-(2-substituted ethylpyrimidines and 2-chloro-4-(2-substituted ethylquinazolines. Treatment of these products, without isolation, with N-methylpiperazine results in nucleophilic displacement of chloride and yields the corresponding 2,4-disubstituted pyrimidines and quinazolines.

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.

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.

BF3·Et2O promoted conjugate addition of ethanethiol to electron-deficient alkynes

Institute of Scientific and Technical Information of China (English)

Qing Fa Zhou; Xue Ping Chu; Shen Zhao; Tao Lu; Wei Fang Tang

2012-01-01

An effective method for the synthesis of vinyl thioethers through the conjugate addition of ethanethiol to electron-deficient alkynes promoted by BF3·Et2O has been developed.Electron-deficient internal alkynes react with ethanethiol in this system to yield mainly Z-isomer of vinyl thioether adducts,while electron-deficient terminal alkynes afford mainly E-isomer of vinyl thioether adducts.

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.

Highly enantio- and diastereoselective reactions of γ-substituted butenolides through direct vinylogous conjugate additions

KAUST Repository

Zhang, Wen; Tan, Davin; Lee, Richmond; Tong, Guanghu; Chen, Wenchao; Qi, Baojian; Huang, Kuo-Wei; Tan, Choonhong; Jiang, Zhiyong

2012-01-01

The strength of the weak: An L-tert-leucine-derived amine-thiourea catalyst (see scheme, green box) promotes the asymmetric vinylogous conjugate addition reaction between γ-aryl- and alkyl-substituted butenolides with the butenamides and enoates shown. Computational studies show the preference for the observed stereochemistry is a result of favourable weak non-bonding interactions, which stabilize the transition state. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Highly enantio- and diastereoselective reactions of γ-substituted butenolides through direct vinylogous conjugate additions

KAUST Repository

Zhang, Wen

2012-09-05

The strength of the weak: An L-tert-leucine-derived amine-thiourea catalyst (see scheme, green box) promotes the asymmetric vinylogous conjugate addition reaction between γ-aryl- and alkyl-substituted butenolides with the butenamides and enoates shown. Computational studies show the preference for the observed stereochemistry is a result of favourable weak non-bonding interactions, which stabilize the transition state. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Stereoselective conjugate radical additions: application of a fluorous oxazolidinone chiral auxiliary for efficient tin removal.

Science.gov (United States)

Hein, Jason E; Zimmerman, Jake; Sibi, Mukund P; Hultin, Philip G

2005-06-23

[reaction: see text] A series of asymmetric free-radical-mediated intermolecular conjugate additions using a fluorous oxazolidinone chiral auxiliary has been completed. The fluorous auxiliary facilitated product isolation using fluorous solid phase extractions (FSPE), effectively removing excess organic and organometallic reagents. Parallel reactions carried out with a similar but nonfluorous norephedrine-derived oxazolidinone demonstrated the superior stereoselectivity and purification obtainable with the fluorous chiral auxiliary.

Investigating the chemical changes of chlorogenic acids during coffee brewing: conjugate addition of water to the olefinic moiety of chlorogenic acids and their quinides.

Science.gov (United States)

Matei, Marius Febi; Jaiswal, Rakesh; Kuhnert, Nikolai

2012-12-12

Coffee is one of the most popular and consumed beverages in the world and is associated with a series of benefits for human health. In this study we focus on the reactivity of chlorogenic acids, the most abundant secondary metabolites in coffee, during the coffee brewing process. We report on the hydroxylation of the chlorogenic acid cinnamoyl substituent by conjugate addition of water to form 3-hydroxydihydrocaffeic acid derivatives using a series of model compounds including monocaffeoyl and dicaffeoylquinic acids and quinic acid lactones. The regiochemistry of conjugate addition was established based on targeted tandem MS experiments. Following conjugate addition of water a reversible water elimination yielding cis-cinnamoyl derivatives accompanied by acyl migration products was observed in model systems. We also report the formation of all of these derivatives during the coffee brewing process.

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.

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

Arenethiolatecopper(I) complexes as homogeneous catalysts for Michael addition reactions

NARCIS (Netherlands)

Koten, G. van; Klaveren, M. van; Lambert, F.; Eijkelkamp, D.J.F.M.; Grove, D.M.

1994-01-01

Arenethiolatocopper(I) complexes are shown to be efficient homogeneous catalysts in Michael addition reactions of several Grignard reagents to acyclic enones; the addition products are formed with excellent chemoselectivity (>99%) and good enantioselectivity (76% e.e.).

Catalytic diastereoselective tandem conjugate addition-elimination reaction of Morita-Baylis-Hillman C adducts by C-C bond cleavage

KAUST Repository

Yang, Wenguo; Tan, Davin; Lee, Richmond; Li, Lixin; Pan, Yuanhang; Huang, Kuo-Wei; Tan, Choonhong; Jiang, Zhiyong

2012-01-01

Through the cleavage of the C-C bond, the first catalytic tandem conjugate addition-elimination reaction of Morita-Baylis-Hillman C adducts has been presented. Various S N2′-like C-, S-, and P-allylic compounds could be obtained with exclusive E

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

Synthesis of purines bearing functionalized C-substituents by the conjugate addition of nucleophiles to 6-vinylpurines and 6-ethynylpurines

Czech Academy of Sciences Publication Activity Database

Kuchař, Martin; Pohl, Radek; Votruba, Ivan; Hocek, Michal

-, č. 22 (2006), s. 5083 -5098 ISSN 1434-193X R&D Projects: GA MŠk(CZ) 1M0508; GA AV ČR(CZ) 1QS400550501 Institutional research plan: CEZ:AV0Z40550506 Keywords : purines * Michael addition * conjugate additions * cross-coupling Subject RIV: CC - Organic Chemistry Impact factor: 2.769, year: 2006

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.

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.

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

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.

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.

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.

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.

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

Hydrogen bond donor–acceptor–donor organocatalysis for conjugate addition of benzylidene barbiturates via complementary DAD– ADA hydrogen bonding

NARCIS (Netherlands)

Leung, King-Chi; Cui, Jian-Fang; Hui, Tsz-Wai; Zhou, Zhong-Yuan; Wong, Man-Kin

2014-01-01

A new class of hydrogen bond donor-acceptor-donor (HB-DAD) organocatalysts has been developed for conjugate addition of benzylidene barbiturates. HB-DAD organocatalyst 1a (featuring para-chloro-pyrimidine as the hydrogen bond acceptor (HBA), N-H as the hydrogen bond donor (HBD) and a trifluoroacetyl

Enantioselective Analytical- and Preparative-Scale Separation of Hexabromocyclododecane Stereoisomers Using Packed Column Supercritical Fluid Chromatography

Directory of Open Access Journals (Sweden)

Nicole Riddell

2016-11-01

Full Text Available 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.

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.

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.

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.

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.

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.

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.

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.

Enantioselective Direct α-Amination of Aldehydes via a Photoredox Mechanism: A Strategy for Asymmetric Amine Fragment Coupling

OpenAIRE

Cecere, Giuseppe; Koenig, Christian M.; Alleva, Jennifer L.; MacMillan, David W. C.

2013-01-01

The direct, asymmetric α-amination of aldehydes has been accomplished via a combination of photoredox and organocatalysis. Photon-generated, nitrogen-centered radicals undergo enantioselective α-addition to catalytically formed chiral enamines to directly produce stable α-amino aldehyde adducts bearing synthetically useful amine substitution patterns. Incorporation of a photolabile group on the amine precursor obviates the need to employ a photoredox catalyst in this transformation. Important...

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 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.

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

KAUST Repository

Zhao, Changgui

2018-02-05

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

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.

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

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

Science.gov (United States)

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

2014-05-02

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

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

Directory of Open Access Journals (Sweden)

Yiyang Liu

2014-10-01

Full Text Available Pd-catalyzed enantioselective alkylation in conjunction with further synthetic elaboration enables the formal total syntheses of a number of “classic” natural product target molecules. This publication highlights recent methods for setting quaternary and tetrasubstituted tertiary carbon stereocenters to address the synthetic hurdles encountered over many decades across multiple compound classes spanning carbohydrate derivatives, terpenes, and alkaloids. These enantioselective methods will impact both academic and industrial settings, where the synthesis of stereogenic quaternary carbons is a continuing challenge.

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.

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.

Preliminary studies towards the preparation of reactive 3-pyrrolin-2-ones in conjugate addition reactions for the syntheses of potentially bioactive 2-pyrrolidinones and pyrrolidines

International Nuclear Information System (INIS)

Alves, Jose C.F.

2007-01-01

Pyrrolin-2-ones and 2-pyrrolidinones are moieties often found in the structure of several biologically active natural products and 3-pyrrolin-2-ones are valuable starting materials in organic synthesis due to their ability to react as acceptors in conjugate addition reactions. In this article we report the initial results about the performed study aiming at the syntheses of reactive 3-pyrrolin-2-ones in conjugate addition reactions and the preparation of a potential precursor for the synthesis of the nootropic (+/-)-nebracetam. (author)

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

Enhanced catalysis and enantioselective resolution of racemic naproxen methyl ester by lipase encapsulated within iron oxide nanoparticles coated with calix[8]arene valeric acid complexes.

Science.gov (United States)

Sayin, Serkan; Akoz, Enise; Yilmaz, Mustafa

2014-09-14

In this study, two types of nanoparticles have been used as additives for the encapsulation of Candida rugosa lipase via the sol-gel method. In one case, the nanoparticles were covalently linked with a new synthesized calix[8]arene octa valeric acid derivative (C[8]-C4-COOH) to produce new calix[8]arene-adorned magnetite nanoparticles (NP-C[8]-C4-COOH), and then NP-C[8]-C4-COOH was used as an additive in the sol-gel encapsulation process. In the other case, iron oxide nanoparticles were directly added into the sol-gel encapsulation process in order to interact electrostatically with both C[8]-C4-COOH and Candida rugosa lipase. The catalytic activities and enantioselectivities of two novel encapsulated lipases (Enc-NP-C[8]-C4-COOH and Enc-C[8]-C4-COOH@Fe3O4) in the hydrolysis reaction of racemic naproxen methyl ester were evaluated. The results showed that the activity and enantioselectivity of the lipase were improved when the lipase was encapsulated in the presence of calixarene-based additives. Indeed, the encapsulated lipases have an excellent rate of enantioselectivity, with E = 371 and 265, respectively, as compared to the free enzyme (E = 137). The lipases encapsulated with C[8]-C4-COOH and iron oxide nanoparticles (Enc-C[8]-C4-COOH@Fe3O4) retained more than 86% of their initial activities after 5 repeated uses and 92% with NP-C[8]-C4-COOH.

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.

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).

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

KAUST Repository

Zhao, Changgui; Guo, Donghui; Munkerup, Kristin; Huang, Kuo-Wei; Li, Fangyi; Wang, Jian

2018-01-01

on the transition-metal-catalyzed transformations. Here, we report the enantioselective NHC-catalyzed (NHC: N-heterocyclic carbenes) atroposelective annulation of cyclic 1,3-diones with ynals. In the presence of NHC precatalyst, base, Lewis acid and oxidant, a

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

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

Science.gov (United States)

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

2016-07-01

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

Enantioselective synthesis of possible diastereomers of heptadeca-1-ene-4,6-diyne-3,8,9,10-tetrol; putative structure of a conjugated diyne natural product isolated from Hydrocotyle leucocephala.

Science.gov (United States)

Prasad, Kavirayani R; Swain, Bandita

2011-04-01

Enantioselective synthesis of possible diastereomers of heptadeca-1-ene-4,6-diyne-3,8,9,10-tetrol, a structure proposed for the natural product isolated from Hydrocotyle leucocephala is accomplished. The reported spectral data of the natural product did not match those of any of the isomers that were synthesized and established that the structure proposed for the natural product is not correct and requires revision.

Using chiral ionic liquid additives to enhance asymmetric induction in a Diels-Alder reaction.

Science.gov (United States)

Goodrich, P; Nimal Gunaratne, H Q; Hall, L; Wang, Y; Jin, L; Muldoon, M J; Ribeiro, A P C; Pombeiro, A J L; Pârvulescu, V I; Davey, P; Hardacre, C

2017-01-31

A bis-oxazoline ligand has been complexed using Cu(ii) and Zn(ii) trifluoromethanesulfonate and a range of chiral ionic liquid (CIL) additives based on natural products were used as a co-catalyst for a Diels-Alder reaction. The catalytic performance of these systems was compared for the asymmetric Diels-Alder reaction between N-acryloyloxazolidinone and cyclopentadiene with and without the presence of a CIL additive. In the absence of the CIL, both catalysts resulted in low enantioselectivities in conventional solvents and ionic liquids. However, whilst only a minor effect of the CIL was observed for the Cu based catalyst, in the case of the Zn based catalyst, significant enhancements in endo enantioselectivity of up to 50% were found on the addition of a CIL.

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.

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.

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.

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

OpenAIRE

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

2016-01-01

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

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

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

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

Science.gov (United States)

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

2009-01-01

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

Hexafluorobenzene: A powerful solvent for a noncovalent stereoselective organocatalytic Michael addition reaction

KAUST Repository

Lattanzi, Alessandra; De Fusco, Claudia; Russo, Alessio; Poater, Albert; Cavallo, Luigi

2012-01-01

A dramatic enhancement of the diastereo- and enantioselectivity in the nitro-Michael addition reaction organocatalysed by a commercially available α,α-l-diaryl prolinol was disclosed when performing the reaction in unconventional hexafluorobenzene

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.

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...

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.

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.

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

Directory of Open Access Journals (Sweden)

Makoto Nakajima

2011-06-01

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

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.

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.

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

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.

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…

Enantioselective Crystallization of Sodium Chlorate in the Presence of Racemic Hydrophobic Amino Acids and Static Magnetic Fields

Directory of Open Access Journals (Sweden)

María-Paz Zorzano

2014-06-01

Full Text Available We study the bias induced by a weak (200 mT external magnetic field on the preferred handedness of sodium chlorate crystals obtained by slow evaporation at ambient conditions of its saturated saline solution with 20 ppm of added racemic (dl hydrophobic amino acids. By applying the Fisher test to pairs of experiments with opposing magnetic field orientation we conclude, with a confidence level of 99.7%, that at the water-air interface of this saline solution there is an enantioselective magnetic interaction that acts upon racemic mixtures of hydrophobic chiral amino acids. This interaction has been observed with the three tested racemic hydrophobic amino acids: dl-Phe, dl-Try and dl-Trp, at ambient conditions and in spite of the ubiquitous chiral organic contamination. This enantioselective magnetic dependence is not observed when there is only one handedness of added chiral amino-acid, if the added amino acid is not chiral or if there is no additive. This effect has been confirmed with a double blind test. This novel experimental observation may have implications for our view of plausible initial prebiotic scenarios and of the roles of the geomagnetic field in homochirality in the biosphere.

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

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...

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.

Direct, enantioselective α-alkylation of aldehydes using simple olefins.

Science.gov (United States)

Capacci, Andrew G; Malinowski, Justin T; McAlpine, Neil J; Kuhne, Jerome; MacMillan, David W C

2017-11-01

Although the α-alkylation of ketones has already been established, the analogous reaction using aldehyde substrates has proven surprisingly elusive. Despite the structural similarities between the two classes of compounds, the sensitivity and unique reactivity of the aldehyde functionality has typically required activated substrates or specialized additives. Here, we show that the synergistic merger of three catalytic processes-photoredox, enamine and hydrogen-atom transfer (HAT) catalysis-enables an enantioselective α-aldehyde alkylation reaction that employs simple olefins as coupling partners. Chiral imidazolidinones or prolinols, in combination with a thiophenol, iridium photoredox catalyst and visible light, have been successfully used in a triple catalytic process that is temporally sequenced to deliver a new hydrogen and electron-borrowing mechanism. This multicatalytic process enables both intra- and intermolecular aldehyde α-methylene coupling with olefins to construct both cyclic and acyclic products, respectively. With respect to atom and step-economy ideals, this stereoselective process allows the production of high-value molecules from feedstock chemicals in one step while consuming only photons.

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 Copper-Catalyzed Carboetherification of Unactivated Alkenes**

Science.gov (United States)

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

2014-01-01

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

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.

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…

Organocatalytic conjugate-addition polymerization of linear and cyclic acrylic monomers by N-heterocyclic carbenes: Mechanisms of chain initiation, propagation, and termination

KAUST Repository

Zhang, Yuetao

2013-11-27

This contribution presents a full account of experimental and theoretical/computational investigations into the mechanisms of chain initiation, propagation, and termination of the recently discovered N-heterocyclic carbene (NHC)-mediated organocatalytic conjugate-addition polymerization of acrylic monomers. The current study specifically focuses on three commonly used NHCs of vastly different nucleophilicity, 1,3-di-tert-butylimidazolin-2-ylidene (ItBu), 1,3- dimesitylimidazolin-2-ylidene (IMes), and 1,3,4-triphenyl-4,5-dihydro-1H-1,2,4- triazol-5-ylidene (TPT), and two representative acrylic monomers, the linear methyl methacrylate (MMA) and its cyclic analog, biomass-derived renewable γ-methyl-α-methylene-γ-butyrolactone (MMBL). For MMA, there exhibits an exquisite selectivity of the NHC structure for the three types of reactions it promotes: enamine formation (single-monomer addition) by IMes, dimerization (tail-to-tail) by TPT, and polymerization by ItBu. For MMBL, all three NHCs promote no dimerization but polymerization, with the polymerization activity being highly sensitive to the NHC structure and the solvent polarity. Thus, ItBu is the most active catalyst of the series and converts quantitatively 1000-3000 equiv of MMBL in 1 min or 10 000 equiv in 5 min at room temperature to MMBL-based bioplastics with a narrow range of molecular weights of Mn = 70-85 kg/mol, regardless of the [MMBL]/[ItBu] ratio employed. The ItBu-catalyzed MMBL polymerization reaches an exceptionally high turnover frequency up to 122 s -1 and a high initiator efficiency value up to 1600%. Unique chain-termination mechanisms have been revealed, accounting for the production of relative high-molecular-weight linear polymers and the catalytic nature of this NHC-mediated conjugate-addition polymerization. Computational studies have provided mechanistic insights into reactivity and selectivity between two competing pathways for each NHC-monomer zwitterionic adduct, namely enamine

Organocatalytic conjugate-addition polymerization of linear and cyclic acrylic monomers by N-heterocyclic carbenes: Mechanisms of chain initiation, propagation, and termination

KAUST Repository

Zhang, Yuetao; Schmitt, Meghan L.; Falivene, Laura; Caporaso, Lucia; Cavallo, Luigi; Chen, Eugene You Xian

2013-01-01

This contribution presents a full account of experimental and theoretical/computational investigations into the mechanisms of chain initiation, propagation, and termination of the recently discovered N-heterocyclic carbene (NHC)-mediated organocatalytic conjugate-addition polymerization of acrylic monomers. The current study specifically focuses on three commonly used NHCs of vastly different nucleophilicity, 1,3-di-tert-butylimidazolin-2-ylidene (ItBu), 1,3- dimesitylimidazolin-2-ylidene (IMes), and 1,3,4-triphenyl-4,5-dihydro-1H-1,2,4- triazol-5-ylidene (TPT), and two representative acrylic monomers, the linear methyl methacrylate (MMA) and its cyclic analog, biomass-derived renewable γ-methyl-α-methylene-γ-butyrolactone (MMBL). For MMA, there exhibits an exquisite selectivity of the NHC structure for the three types of reactions it promotes: enamine formation (single-monomer addition) by IMes, dimerization (tail-to-tail) by TPT, and polymerization by ItBu. For MMBL, all three NHCs promote no dimerization but polymerization, with the polymerization activity being highly sensitive to the NHC structure and the solvent polarity. Thus, ItBu is the most active catalyst of the series and converts quantitatively 1000-3000 equiv of MMBL in 1 min or 10 000 equiv in 5 min at room temperature to MMBL-based bioplastics with a narrow range of molecular weights of Mn = 70-85 kg/mol, regardless of the [MMBL]/[ItBu] ratio employed. The ItBu-catalyzed MMBL polymerization reaches an exceptionally high turnover frequency up to 122 s -1 and a high initiator efficiency value up to 1600%. Unique chain-termination mechanisms have been revealed, accounting for the production of relative high-molecular-weight linear polymers and the catalytic nature of this NHC-mediated conjugate-addition polymerization. Computational studies have provided mechanistic insights into reactivity and selectivity between two competing pathways for each NHC-monomer zwitterionic adduct, namely enamine

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.

Protein carriers of conjugate vaccines

Science.gov (United States)

Pichichero, Michael E

2013-01-01

The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products. PMID:23955057

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.

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.

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

Pd(II)/Bipyridine-Catalyzed Conjugate Addition of Arylboronic Acids to α,β-Unsaturated Carboxylic Acids. Synthesis of β-Quaternary Carbons Substituted Carboxylic Acids.

Science.gov (United States)

Liu, Rui; Yang, Zhenyu; Ni, Yuxin; Song, Kaixuan; Shen, Kai; Lin, Shaohui; Pan, Qinmin

2017-08-04

Pd(II)/bipyridine-catalyzed conjugate addition of arylboronic acids to α,β-unsaturated carboxylic acids (including β,β-disubstituted acrylic acids) was developed and optimized, which provided a mild and convenient method for the highly challenging synthesis of β-quaternary carbons substituted carboxylic acids.

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Hou, Feng; Miyakawa, Takuya [Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657 (Japan); Kataoka, Michihiko [Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai 559-8531 (Japan); Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto 606-8502 (Japan); Takeshita, Daijiro [Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657 (Japan); Kumashiro, Shoko [Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto 606-8502 (Japan); Uzura, Atsuko [Research and Development Center, Nagase and Co., Ltd., 2-2-3 Muratani, Nishi-ku, Kobe 651-2241 (Japan); Urano, Nobuyuki [Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai 559-8531 (Japan); Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto 606-8502 (Japan); Nagata, Koji [Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657 (Japan); Shimizu, Sakayu [Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto 606-8502 (Japan); Faculty of Bioenvironmental Science, Kyoto Gakuen University, Sogabe-cho, Kameoka 621-8555 (Japan); Tanokura, Masaru, E-mail: amtanok@mail.ecc.u-tokyo.ac.jp [Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657 (Japan)

2014-04-18

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

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...

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.

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.

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

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.

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.

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.

Design, Synthesis and Biological Activity of Novel Reversible Peptidyl FVIIa Inhibitors Rh-Catalyzed Enantioselective Synthesis of Diaryl Amines

DEFF Research Database (Denmark)

Storgaard, Morten

functional group tolerance. Unfortunately, these -aryl tetramic acids were too unreactive and ring opening toward the synthesis of the building block did not succeed. However, -aryl tetramic acids are still interesting compounds due to their potential biological activity. The building block 3.15 (P1......-catalyzed enantioselective synthesis of diaryl amines, which is an important class of compounds (Chapter 4). For example it is found in the third generation anti-histaminic agent levocetirizine. Development of efficient synthetic routes is therefore of considerably interest. The rhodium-catalyzed enantioselective synthesis...

Preparation, structural analysis and bioactivity of ribonuclease A-albumin conjugate: tetra-conjugation or PEG as the linker.

Science.gov (United States)

Li, Chunju; Lin, Qixun; Wang, Jun; Shen, Lijuan; Ma, Guanghui; Su, Zhiguo; Hu, Tao

2012-12-31

Ribonuclease A (RNase A) is a therapeutic enzyme with cytotoxic action against tumor cells. Its clinical application is limited by the short half-life and insufficient stability. Conjugation of albumin can overcome the limitation, whereas dramatically decrease the enzymatic activity of RNase A. Here, three strategies were proposed to prepare the RNase A-bovine serum albumin (BSA) conjugates. R-SMCC-B (a conjugate of four RNase A attached with one BSA) and R-PEG-B (a mono-conjugate) were prepared using Sulfo-SMCC (a short bifunctional linker) and mal-PEG-NHS (a bifunctional PEG), respectively. Mal-PEG-NHS and hexadecylamine (HDA) were used to prepare the mono-conjugate, R-HDA-B, where HDA was adopted to bind BSA. The PEG linker can elongate the proximity between RNase A and BSA. In contrast, four RNase A were closely located on BSA in R-SMCC-B. R-SMCC-B showed the lowest K(m) and the highest relative enzymatic activity and k(cat)/K(m) in the three conjugates. Presumably, the tetravalent interaction of RNase A in R-SMCC-B can increase the binding affinity to its substrate. In addition, the slow release of BSA from R-HDA-B may increase the enzymatic activity of R-HDA-B. Our study is expected to provide strategies to develop protein-albumin conjugate with high therapeutic potential. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

Formation of primary sperm conjugates in a haplogyne spider (Caponiidae, Araneae) with remarks on the evolution of sperm conjugation in spiders.

Science.gov (United States)

Lipke, Elisabeth; Michalik, Peter

2012-11-01

Sperm conjugation, where two or more sperm are physically united, is a rare but widespread pheno-menon across the animal kingdom. One group well known for its different types of sperm conjugation are spiders. Particularly, haplogyne spiders show a high diversity of sperm traits. Besides individual cleistospermia, primary (synspermia) and secondary (coenospermia, "spermatophore") sperm conjugation occurs. However, the evolution of sperm conjugates and sperm is not understood in this group. Here, we look at how sperm are transferred in Caponiidae (Haplogynae) in pursuit of additional information about the evolution of sperm transfer forms in spiders. Additionally, we investigated the male reproductive system and spermatozoa using light- and transmission electron-microscopy and provide a 3D reconstruction of individual as of well as conjugated spermatozoa. Mature spermatozoa are characterized by an extremely elongated, helical nucleus resulting in the longest spider sperm known to date. At the end of spermiogenesis, synspermia are formed by complete fusion of four spermatids. Thus, synspermia might have evolved early within ecribellate Haplogynae. The fused sperm cells are surrounded by a prominent vesicular area. The function of the vesicular area remains still unknown but might be correlated with the capacitation process inside the female. Further phylogenetic and functional implications of the spermatozoa and sperm conjugation are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemo- and Enantioselective Intramolecular Silver-Catalyzed Aziridinations.

Science.gov (United States)

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

2017-08-07

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

Enantioselective copper-catalyzed carboetherification of unactivated alkenes.

Science.gov (United States)

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

2014-06-16

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

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.

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.

Catalytic diastereoselective tandem conjugate addition-elimination reaction of Morita-Baylis-Hillman C adducts by C-C bond cleavage

KAUST Repository

Yang, Wenguo

2012-02-08

Through the cleavage of the C-C bond, the first catalytic tandem conjugate addition-elimination reaction of Morita-Baylis-Hillman C adducts has been presented. Various S N2′-like C-, S-, and P-allylic compounds could be obtained with exclusive E configuration in good to excellent yields. The Michael product could also be easily prepared by tuning the β-C-substituent group of the α-methylene ester under the same reaction conditions. Calculated relative energies of various transition states by DFT methods strongly support the observed chemoselectivity and diastereoselectivity. © 2012 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

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...

Purification of SUMO conjugating enzymes and kinetic analysis of substrate conjugation

Science.gov (United States)

Yunus, Ali A.; Lima, Christopher D.

2009-01-01

SUMO conjugation to protein substrates requires the concerted action of a dedicated E2 ubiquitin conjugation enzyme (Ubc9) and associated E3 ligases. Although Ubc9 can directly recognize and modify substrate lysine residues that occur within a consensus site for SUMO modification, E3 ligases can redirect specificity and enhance conjugation rates during SUMO conjugation in vitro and in vivo. In this chapter, we will describe methods utilized to purify SUMO conjugating enzymes and model substrates which can be used for analysis of SUMO conjugation in vitro. We will also describe methods to extract kinetic parameters during E3-dependent or E3-independent substrate conjugation. PMID:19107417

Ionic liquids as precatalysts in the highly stereoselective conjugate addition of α,β-unsaturated aldehydes to chalcones.

Science.gov (United States)

Ta, Linda; Axelsson, Anton; Bijl, Joachim; Haukka, Matti; Sundén, Henrik

2014-10-20

Imidazolium-based ionic liquids (ILs) serve both as recyclable reaction media and as precatalysts for the N-heterocyclic carbene-catalyzed conjugate addition of α,β-unsaturated aldehydes to chalcones. The reaction produces a broad scope of 1,6-ketoesters incorporating an anti-diphenyl moiety in high yields and with high stereoselectivity. In recycling experiments, the IL can be reused up to five times with retained reactivity and selectivity. Moreover, the 1,6-ketoesters form self-assembled organogels in aliphatic hydrocarbons. The reaction protocol is robust, easily operated, scalable and highly functionalized compounds can be obtained from inexpensive and readily accessible starting materials. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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

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.

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

Recent Advances in Conjugated Polymers for Light Emitting Devices

Science.gov (United States)

AlSalhi, Mohamad Saleh; Alam, Javed; Dass, Lawrence Arockiasamy; Raja, Mohan

2011-01-01

A recent advance in the field of light emitting polymers has been the discovery of electroluminescent conjugated polymers, that is, kind of fluorescent polymers that emit light when excited by the flow of an electric current. These new generation fluorescent materials may now challenge the domination by inorganic semiconductor materials of the commercial market in light-emitting devices such as light-emitting diodes (LED) and polymer laser devices. This review provides information on unique properties of conjugated polymers and how they have been optimized to generate these properties. The review is organized in three sections focusing on the major advances in light emitting materials, recent literature survey and understanding the desirable properties as well as modern solid state lighting and displays. Recently, developed conjugated polymers are also functioning as roll-up displays for computers and mobile phones, flexible solar panels for power portable equipment as well as organic light emitting diodes in displays, in which television screens, luminous traffic, information signs, and light-emitting wallpaper in homes are also expected to broaden the use of conjugated polymers as light emitting polymers. The purpose of this review paper is to examine conjugated polymers in light emitting diodes (LEDs) in addition to organic solid state laser. Furthermore, since conjugated polymers have been approved as light-emitting organic materials similar to inorganic semiconductors, it is clear to motivate these organic light-emitting devices (OLEDs) and organic lasers for modern lighting in terms of energy saving ability. In addition, future aspects of conjugated polymers in LEDs were also highlighted in this review. PMID:21673938

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

Photodynamic tissue adhesion with chlorin(e6) protein conjugates.

Science.gov (United States)

Khadem, J; Veloso, A A; Tolentino, F; Hasan, T; Hamblin, M R

1999-12-01

To test the hypothesis that a photodynamic laser-activated tissue solder would perform better in sealing scleral incisions when the photosensitizer was covalently linked to the protein than when it was noncovalently mixed. Conjugates and mixtures were prepared between the photosensitizer chlorin(e6) and various proteins (albumin, fibrinogen, and gelatin) in different ratios and used to weld penetrating scleral incisions made in human cadaveric eyes. A blue-green (488-514 nm) argon laser activated the adhesive, and the strength of the closure was measured by increasing the intraocular pressure until the wound showed leakage. Both covalent conjugates and noncovalent mixtures showed a light dose-dependent increase in leaking pressure. A preparation of albumin chlorin(e6) conjugate with additional albumin added (2.5 protein to chlorin(e6) molar ratio) showed significantly higher weld strength than other protein conjugates and mixtures. This is the first report of dye-protein conjugates as tissue solders. These conjugates may have applications in ophthalmology.

Structure Property Relationships in Organic Conjugated Systems

OpenAIRE

O'Neill, Luke; Lynch, Patrick; McNamara, Mary

2005-01-01

A series of π conjugated oligomers were studied by absorption and photoluminescence spectroscopy. A linear relationship between the positioning of the absorption and photoluminescence maxima plotted against inverse conjugation length is observed. The relationships are in good agreement with the simple particle in a box method, one of the earliest descriptions of the properties of one-dimensional organic molecules. In addition to the electronic transition energies, it was observed that the Sto...

Modelling of charge carrier transport in conjugated polymers doped by polar additives

Czech Academy of Sciences Publication Activity Database

Toman, Petr; Nešpůrek, Stanislav; Bartkowiak, W.

2009-01-01

Roč. 27, č. 3 (2009), s. 797-812 ISSN 0137-1339. [International Conference on Electrical and Related Properties of Organic Solids /11./. Piechowice, 13.07.2008-17.07.2008] R&D Projects: GA ČR GA203/06/0285; GA AV ČR KAN400720701; GA MŠk MEB050815 Institutional research plan: CEZ:AV0Z40500505 Keywords : conjugated polymers * charge carrier transport * molecular electronics Subject RIV: CD - Macromolecular Chemistry Impact factor: 0.384, year: 2009

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

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

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.

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.

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....

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.

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.

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.

Chiral phosphites as ligands in asymmetric metal complex catalysis and synthesis of coordination compounds

International Nuclear Information System (INIS)

Gavrilov, Konstantin N; Bondarev, Oleg G; Polosukhin, Aleksei I

2004-01-01

The data published during the last five years on the application of chiral derivatives of phosphorous acid in coordination chemistry and enantioselective catalysis are summarised and discussed. The effect of the nature of these ligands on the structure of metal complexes and on the efficiency of catalytic organic syntheses is shown. Hydroformylation, hydrogenation, allylic substitution and conjugate addition catalysed by transition metal complexes with optically active phosphites and hydrophosphoranes are considered. The prospects for the development of this field of research are demonstrated.

Small angle scattering from protein/sugar conjugates

Science.gov (United States)

Jackson, Andrew; White, John

2006-11-01

The Maillard reaction between free amine groups on proteins and sugars is well known. We have examined the effect of the reaction of the casein group of milk proteins with sugars on their nanoscale structure and aggregation. The small angle neutron scattering from beta casein and sodium caseinate and their sugar conjugates have been studied as a function of solution concentration. At high conjugate concentration (greater than ca. 5 mg/ml) the addition of sugar reduces supra-micellar aggregation of the protein whilst at lower concentration, where the protein is expected to be deaggregated already, little effect is seen. Guinier analysis of the scattering data show a radius of gyration of around 75 A˚ for beta casein in solution and around 80 A˚ for the sucrose conjugate.

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.

Hexafluorobenzene: A powerful solvent for a noncovalent stereoselective organocatalytic Michael addition reaction

KAUST Repository

Lattanzi, Alessandra

2012-01-01

A dramatic enhancement of the diastereo- and enantioselectivity in the nitro-Michael addition reaction organocatalysed by a commercially available α,α-l-diaryl prolinol was disclosed when performing the reaction in unconventional hexafluorobenzene as a medium. DFT calculations were performed to clarify the origin of stereoselectivity and the role of C 6F 6. © The Royal Society of Chemistry 2012.

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.

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.

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

The development of catalytic nucleophilic additions of terminal alkynes in water.

Science.gov (United States)

Li, Chao-Jun

2010-04-20

One of the major research endeavors in synthetic chemistry over the past two decades is the exploration of synthetic methods that work under ambient atmosphere with benign solvents, that maximize atom utilization, and that directly transform natural resources, such as renewable biomass, from their native states into useful chemical products, thus avoiding the need for protecting groups. The nucleophilic addition of terminal alkynes to various unsaturated electrophiles is a classical (textbook) reaction in organic chemistry, allowing the formation of a C-C bond while simultaneously introducing the alkyne functionality. A prerequisite of this classical reaction is the stoichiometric generation of highly reactive metal acetylides. Over the past decade, our laboratory and others have been exploring an alternative, the catalytic and direct nucleophilic addition of terminal alkynes to unsaturated electrophiles in water. We found that various terminal alkynes can react efficiently with a wide range of such electrophiles in water (or organic solvent) in the presence of simple and readily available catalysts, such as copper, silver, gold, iron, palladium, and others. In this Account, we describe the development of these synthetic methods, focusing primarily on results from our laboratory. Our studies include the following: (i) catalytic reaction of terminal alkynes with acid chloride, (ii) catalytic addition of terminal alkynes to aldehydes and ketones, (iii) catalytic addition of alkynes to C=N bonds, and (iv) catalytic conjugate additions. Most importantly, these reactions can tolerate various functional groups and, in many cases, perform better in water than in organic solvents, clearly defying classical reactivities predicated on the relative acidities of water, alcohols, and terminal alkynes. We further discuss multicomponent and enantioselective reactions that were developed. These methods provide an alternative to the traditional requirement of separate steps in

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

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

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.

Small angle scattering from protein/sugar conjugates

International Nuclear Information System (INIS)

Jackson, Andrew; White, John

2006-01-01

The Maillard reaction between free amine groups on proteins and sugars is well known. We have examined the effect of the reaction of the casein group of milk proteins with sugars on their nanoscale structure and aggregation. The small angle neutron scattering from beta casein and sodium caseinate and their sugar conjugates have been studied as a function of solution concentration. At high conjugate concentration (greater than ca. 5mg/ml) the addition of sugar reduces supra-micellar aggregation of the protein whilst at lower concentration, where the protein is expected to be deaggregated already, little effect is seen. Guinier analysis of the scattering data show a radius of gyration of around 75A-bar for beta casein in solution and around 80A-bar for the sucrose conjugate

Small angle scattering from protein/sugar conjugates

Energy Technology Data Exchange (ETDEWEB)

Jackson, Andrew [Research School of Chemistry, Australian National University, Canberra, ACT 0200 (Australia)]. E-mail: ajj@nist.gov; White, John [Research School of Chemistry, Australian National University, Canberra, ACT 0200 (Australia)

2006-11-15

The Maillard reaction between free amine groups on proteins and sugars is well known. We have examined the effect of the reaction of the casein group of milk proteins with sugars on their nanoscale structure and aggregation. The small angle neutron scattering from beta casein and sodium caseinate and their sugar conjugates have been studied as a function of solution concentration. At high conjugate concentration (greater than ca. 5mg/ml) the addition of sugar reduces supra-micellar aggregation of the protein whilst at lower concentration, where the protein is expected to be deaggregated already, little effect is seen. Guinier analysis of the scattering data show a radius of gyration of around 75A-bar for beta casein in solution and around 80A-bar for the sucrose conjugate.

Synthesis, characterization and the release kinetics of antiproliferative agents from polyamidoamine conjugates

CSIR Research Space (South Africa)

Aderibigbe, BA

2015-01-01

Full Text Available Polyamidoamine conjugates containing curcumin and bisphosphonate were synthesized via a one-pot aqueous phase Michael addition reaction. In the design of the conjugate, bisphosphonate formed an integral part of the polymer carrier backbone. Curcumin...

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.

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

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.

Enantioselective Intramolecular CH-Insertions upon Cu-Catalyzed Decomposition of Phenyliodonium Ylides

Directory of Open Access Journals (Sweden)

Christelle Boléa

2001-02-01

Full Text Available The Cu-catalyzed intramolecular CH insertion of phenyliodonium ylide 5b has been investigated at 0° C in the presence of several chiral ligands. Enantioselectivities vary in the range of 38–72 %, and are higher than those resulting from reaction of the diazo compound 5c at 65° C. The results are consistent with a carbenoid mechanism for Cu-catalyzed decomposition of phenyliodonium ylides.

Synthesis and antimicrobial activity of gold nanoparticle conjugates with cefotaxime

Science.gov (United States)

Titanova, Elena O.; Burygin, Gennady L.

2016-04-01

Gold nanoparticles (GNPs) have attracted significant interest as a novel platform for various applications to nanobiotechnology and biomedicine. The conjugates of GNPs with antibiotics and antibodies were also used for selective photothermal killing of protozoa and bacteria. Also the conjugates of some antibiotics with GNPs decreased the number of bacterial growing cells. In this work was made the procedure optimization for conjugation of cefotaxime (a third-generation cephalosporin antibiotic) with GNPs (15 nm) and we examined the antimicrobial properties of this conjugate to bacteria culture of E. coli K-12. Addition of cefotaxime solution to colloidal gold does not change their color and extinction spectrum. For physiologically active concentration of cefotaxime (3 μg/mL), it was shown that the optimum pH for the conjugation was more than 9.5. A partial aggregation of the GNPs in saline medium was observed at pH 6.5-7.5. The optimum concentration of K2CO3 for conjugation cefotaxime with GNPs-15 was 5 mM. The optimum concentration of cefotaxime was at 0.36 μg/mL. We found the inhibition of the growth of E. coli K12 upon application cefotaxime-GNP conjugates.

Enhanced photodynamic efficacy of zinc phthalocyanine by conjugating to heptalysine.

Science.gov (United States)

Li, Linsen; Luo, Zhipu; Chen, Zhuo; Chen, Jincan; Zhou, Shanyong; Xu, Peng; Hu, Ping; Wang, Jundong; Chen, Naisheng; Huang, Jinling; Huang, Mingdong

2012-11-21

Zinc phthalocyanine (ZnPc) is a promising photosensitizer for photodynamic therapy, but faces some challenges: ZnPc is insoluble in water and thus requires either special formulation of ZnPc by, e.g., liposome or Cremophor EL, or chemical modification of Pc ring to enhance its bioavailability and photodynamic efficacy. Here, we conjugated monosubstituted ZnPc-COOH with a series of oligolysine moieties with different numbers of lysine residues (ZnPc-(Lys)(n) (n = 1, 3, 5, 7, 9) to improve the water solubility of the ZnPc conjugates. We measured the photosensitizing efficacies and the cellular uptakes of this series of conjugates on a normal and a cancerous cell line. In addition, we developed a sensitive in situ method to distinguish the difference in photodynamic efficacy among conjugates. Our results showed that ZnPc-(Lys)(7) has the highest photodynamic efficacy compared to the other conjugates investigated.

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...

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.

Improvement of Emulsifying Properties of Wheat Gluten Hydrolysate λ-Carrageenan Conjugates

Directory of Open Access Journals (Sweden)

Jin-Shui Wang

2006-01-01

Full Text Available Gluten hydrolysate was prepared through limited enzymatic hydrolysis of wheat gluten resulting from the byproducts of wheat starch. The enzyme applied in the present study was Protamex. Response surface methodology was used to investigate the effects of pH, gluten hydrolysate (GHPλ-carrageenan (C ratio and reaction time on emulsifying properties of the GHP-C conjugate. The regression model for emulsion activity index (EAI was significant at p=0.001, while reaction time had a significant effect on EAI of the conjugate with regression coefficient of 4.25. The interactions of pH and GHP/ C ratio, and GHP/C ratio and reaction time significantly affected the EAI of the conjugate. Both the emulsifying property and nitrogen solubility index (NSI of GHP-C conjugate prepared under the optimal conditions increased more remarkably, compared to the control. The denaturation temperature of GHP-C conjugate obviously increased compared to wheat gluten. The addition of GHP-C conjugate had different effects on dough characteristics. Moreover, this conjugate can delay the increase in the bread crumb firmness during storage. It demonstrated that this conjugate couldimprove the dough characteristics and had anti-staling properties of bread.

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.

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.

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.

The extended regulatory networks of SXT/R391 integrative and conjugative elements and IncA/C conjugative plasmids.

Science.gov (United States)

Poulin-Laprade, Dominic; Carraro, Nicolas; Burrus, Vincent

2015-01-01

Nowadays, healthcare systems are challenged by a major worldwide drug resistance crisis caused by the massive and rapid dissemination of antibiotic resistance genes and associated emergence of multidrug resistant pathogenic bacteria, in both clinical and environmental settings. Conjugation is the main driving force of gene transfer among microorganisms. This mechanism of horizontal gene transfer mediates the translocation of large DNA fragments between two bacterial cells in direct contact. Integrative and conjugative elements (ICEs) of the SXT/R391 family (SRIs) and IncA/C conjugative plasmids (ACPs) are responsible for the dissemination of a broad spectrum of antibiotic resistance genes among diverse species of Enterobacteriaceae and Vibrionaceae. The biology, diversity, prevalence and distribution of these two families of conjugative elements have been the subject of extensive studies for the past 15 years. Recently, the transcriptional regulators that govern their dissemination through the expression of ICE- or plasmid-encoded transfer genes have been described. Unrelated repressors control the activation of conjugation by preventing the expression of two related master activator complexes in both types of elements, i.e., SetCD in SXT/R391 ICEs and AcaCD in IncA/C plasmids. Finally, in addition to activating ICE- or plasmid-borne genes, these master activators have been shown to specifically activate phylogenetically unrelated mobilizable genomic islands (MGIs) that also disseminate antibiotic resistance genes and other adaptive traits among a plethora of pathogens such as Vibrio cholerae and Salmonella enterica.

The extended regulatory networks of SXT/R391 integrative and conjugative elements and IncA/C conjugative plasmids.

Directory of Open Access Journals (Sweden)

Dominic ePoulin-Laprade

2015-08-01

Full Text Available Nowadays, healthcare systems are challenged by a major worldwide drug resistance crisis caused by the massive and rapid dissemination of antibiotic resistance genes and associated emergence of multidrug resistant pathogenic bacteria, in both clinical and environmental settings. Conjugation is the main driving force of gene transfer among microorganisms. This mechanism of horizontal gene transfer mediates the translocation of large DNA fragments between two bacterial cells in direct contact. Integrative and conjugative elements (ICEs of the SXT/R391 family (SRIs and IncA/C conjugative plasmids (ACPs are responsible for the dissemination of a broad spectrum of antibiotic resistance genes among diverse species of Enterobacteriaceae and Vibrionaceae. The biology, diversity, prevalence and distribution of these two families of conjugative elements have been the subject of extensive studies for the past 15 years. Recently, the transcriptional regulators that govern their dissemination through the expression of ICE- or plasmid-encoded transfer genes have been described. Unrelated repressors control the activation of conjugation by preventing the expression of two related master activator complexes in both types of elements, i.e. SetCD in SXT/R391 ICEs and AcaCD in IncA/C plasmids. Finally, in addition to activating ICE- or plasmid-borne genes, these master activators have been shown to specifically activate phylogenetically unrelated mobilizable genomic islands (MGIs that also disseminate antibiotic resistance genes and other adaptive traits among a plethora of pathogens such as Vibrio cholerae and Salmonella enterica.

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.

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.

Different Effect of the Additional Electron-Withdrawing Cyano Group in Different Conjugation Bridge: The Adjusted Molecular Energy Levels and Largely Improved Photovoltaic Performance.

Science.gov (United States)

Li, Huiyang; Fang, Manman; Hou, Yingqin; Tang, Runli; Yang, Yizhou; Zhong, Cheng; Li, Qianqian; Li, Zhen

2016-05-18

Four organic sensitizers (LI-68-LI-71) bearing various conjugated bridges were designed and synthesized, in which the only difference between LI-68 and LI-69 (or LI-70 and LI-71) was the absence/presence of the CN group as the auxiliary electron acceptor. Interestingly, compared to the reference dye of LI-68, LI-69 bearing the additional CN group exhibited the bad performance with the decreased Jsc and Voc values. However, once one thiophene moiety near the anchor group was replaced by pyrrole with the electron-rich property, the resultant LI-71 exhibited a photoelectric conversion efficiency increase by about 3 folds from 2.75% (LI-69) to 7.95% (LI-71), displaying the synergistic effect of the two moieties (CN and pyrrole). Computational analysis disclosed that pyrrole as the auxiliary electron donor (D') in the conjugated bridge can compensate for the lower negative charge in the electron acceptor, which was caused by the CN group as the electron trap, leading to the more efficient electron injection and better photovoltaic performance.

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

Improved synthesis of (S)-N-Boc-5-oxaproline for protein synthesis with the α-ketoacid-hydroxylamine (KAHA) ligation.

Science.gov (United States)

Murar, Claudia E; Harmand, Thibault J; Bode, Jeffrey W

2017-09-15

We describe a new route for the synthesis of (S)-N-Boc-5-oxaproline. This building block is a key element for the chemical synthesis of proteins with the α-ketoacid-hydroxylamine (KAHA) ligation. The new synthetic pathway to the enantiopure oxaproline is based on a chiral amine mediated enantioselective conjugate addition of a hydroxylamine to trans-4-oxo-2-butenoate. This route is practical, scalable and economical and provides decagram amounts of material for protein synthesis and conversion to other protected forms of (S)-oxaproline. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Free and conjugated dopamine in human ventricular fluid

International Nuclear Information System (INIS)

Sharpless, N.S.; Thal, L.J.; Wolfson, L.I.; Tabaddor, K.; Tyce, G.M.; Waltz, J.M.

1981-01-01

Free dopamine and an acid hydrolyzable conjugate of dopamine were measured in human ventricular fluid specimens with a radioenzymatic assay and by high performance liquid chromatography (HPLC) with electrochemical detection. Only trace amounts of free norepinephrine and dopamine were detected in ventricular fluid from patients with movement disorders. When the ventricular fluid was hydrolyzed by heating in HClO 4 or by lyophilization in dilute HClO 4 , however, a substantial amount of free dopamine was released. Values for free plus conjugated dopamine in ventricular fluid from patients who had never taken L-DOPA ranged from 139 to 340 pg/ml when determined by HPLC and from 223 to 428 pg/ml when measured radioenzymatically. The correlation coefficient for values obtained by the two methods in the same sample of CSF was 0.94 (P<0.001). Patients who had been treated with L-DOPA had higher levels of conjugated dopamine in their ventricular CSF which correlated inversely with the time between the last dose of L-DOPA and withdrawal of the ventricular fluid. Additionally, one patient with acute cerebral trauma had elevated levels of free norepinephrine and both free and conjugated dopamine in his ventricular fluid. Conjugation may be an important inactivation pathway for released dopamine in man. (Auth.)

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.

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

Bispecific small molecule-antibody conjugate targeting prostate cancer.

Science.gov (United States)

Kim, Chan Hyuk; Axup, Jun Y; Lawson, Brian R; Yun, Hwayoung; Tardif, Virginie; Choi, Sei Hyun; Zhou, Quan; Dubrovska, Anna; Biroc, Sandra L; Marsden, Robin; Pinstaff, Jason; Smider, Vaughn V; Schultz, Peter G

2013-10-29

Bispecific antibodies, which simultaneously target CD3 on T cells and tumor-associated antigens to recruit cytotoxic T cells to cancer cells, are a promising new approach to the treatment of hormone-refractory prostate cancer. Here we report a site-specific, semisynthetic method for the production of bispecific antibody-like therapeutics in which a derivative of the prostate-specific membrane antigen-binding small molecule DUPA was selectively conjugated to a mutant αCD3 Fab containing the unnatural amino acid, p-acetylphenylalanine, at a defined site. Homogeneous conjugates were generated in excellent yields and had good solubility. The efficacy of the conjugate was optimized by modifying the linker structure, relative binding orientation, and stoichiometry of the ligand. The optimized conjugate showed potent and selective in vitro activity (EC50 ~ 100 pM), good serum half-life, and potent in vivo activity in prophylactic and treatment xenograft mouse models. This semisynthetic approach is likely to be applicable to the generation of additional bispecific agents using drug-like ligands selective for other cell-surface receptors.

Bispecific small molecule–antibody conjugate targeting prostate cancer

Science.gov (United States)

Kim, Chan Hyuk; Axup, Jun Y.; Lawson, Brian R.; Yun, Hwayoung; Tardif, Virginie; Choi, Sei Hyun; Zhou, Quan; Dubrovska, Anna; Biroc, Sandra L.; Marsden, Robin; Pinstaff, Jason; Smider, Vaughn V.; Schultz, Peter G.

2013-01-01

Bispecific antibodies, which simultaneously target CD3 on T cells and tumor-associated antigens to recruit cytotoxic T cells to cancer cells, are a promising new approach to the treatment of hormone-refractory prostate cancer. Here we report a site-specific, semisynthetic method for the production of bispecific antibody-like therapeutics in which a derivative of the prostate-specific membrane antigen-binding small molecule DUPA was selectively conjugated to a mutant αCD3 Fab containing the unnatural amino acid, p-acetylphenylalanine, at a defined site. Homogeneous conjugates were generated in excellent yields and had good solubility. The efficacy of the conjugate was optimized by modifying the linker structure, relative binding orientation, and stoichiometry of the ligand. The optimized conjugate showed potent and selective in vitro activity (EC50 ∼100 pM), good serum half-life, and potent in vivo activity in prophylactic and treatment xenograft mouse models. This semisynthetic approach is likely to be applicable to the generation of additional bispecific agents using drug-like ligands selective for other cell-surface receptors. PMID:24127589

Are conjugated linolenic acid isomers an alternative to conjugated linoleic acid isomers in obesity prevention?

Science.gov (United States)

Miranda, Jonatan; Arias, Noemi; Fernández-Quintela, Alfredo; del Puy Portillo, María

2014-04-01

Despite its benefits, conjugated linoleic acid (CLA) may cause side effects after long-term administration. Because of this and the controversial efficacy of CLA in humans, alternative biomolecules that may be used as functional ingredients have been studied in recent years. Thus, conjugated linolenic acid (CLNA) has been reported to be a potential anti-obesity molecule which may have additional positive effects related to obesity. According to the results reported in obesity, CLNA needs to be given at higher doses than CLA to be effective. However, because of the few studies conducted so far, it is still difficult to reach clear conclusions about the potential use of these CLNAs in obesity and its related changes (insulin resistance, dyslipidemia, or inflammation). Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

Evaluation of iodovinyl antibody conjugates: Comparison with a p-iodobenzoyl conjugate and direct radioiodination

International Nuclear Information System (INIS)

Hadley, S.W.; Wilbur, D.S.

1990-01-01

The preparations and conjugations of 2,3,5,6-tetrafluorophenyl 5-[125I/131I]iodo-4-pentenoate (7a) and 2,3,5,6-tetrafluorophenyl 3,3-dimethyl-5-[125I/131I]iodo-4-pentenoate (7b) to monoclonal antibodies are reported. Reagents 7a and 7b were prepared in high radiochemical yield by iododestannylation of their corresponding 5-tri-n-butylstannyl precursors. Radioiodinated antibody conjugates were prepared by reaction of 7a or 7b with the protein at basic pH. Evaluation of these conjugates by several in vitro procedures demonstrated that the radiolabel was attached to the antibody in a stable manner and that the conjugates maintained immunoreactivity. Comparative dual-isotope biodistribution studies of a monoclonal antibody Fab fragment conjugate of 7a and 7b with the same Fab fragment labeled with N-succinimidyl p-[131I]iodobenzoate (PIB, p-iodobenzoate, 2) or directly radioiodinated have been carried out in tumor-bearing nude mice. Coinjection of the Fab conjugate of 7a with the Fab conjugate of 2 demonstrated that the biodistributions were similar in most organs, except the neck tissue (thyroid-containing) and the stomach, which contained substantially increased levels of the 7a label. Coinjection of the Fab conjugate of 7a with the Fab fragment radioiodinated by using the chloramine-T method demonstrated that the biodistributions were remarkably similar, suggesting roughly equivalent in vivo deiodination of these labeled antibody fragments. Coinjection of the Fab conjugate of 7a with the Fab conjugate of 7b indicated that there was ∼ a 2-fold reduction in the amount of in vivo deiodination of the 7b conjugate as compared to the 7a conjugate

Preparation and biodistribution study of 99Tcm labelled dextran conjugates

International Nuclear Information System (INIS)

Yang Chunhui; Li Hongyu; Liang Jixin; Lu Jia; Luo Hongyi; Zheng Deqiang; Sun Guiquan

2012-01-01

99 Tc m Mannosylated dextran conjugates were prepared through [ 99 Tc m (CO) 3 ] + precursor synthesized by carbonyl Isolink kit. The labelled conjugates were injected sub-dermally into the rear foots of the mice, and the patent blue solution was injected at the same site 10 min before sacrifice. The mice were killed at 1 h and 4 h postinjection, and the samples of different tissues including SLN, 2LN, injection site, liver, spleen, blood were dissected and counted. The uptake in terms was calculated. The results of biodistribution demonstrated that the SLN uptakes of radiopharmaceutical (without mannose in the molecules) were rather low and in vivo excretion of these conjugates were comparatively faster, and the uptake of injection site was also low; on the other hand, the SLN uptakes of radio pharmaceutical (with mannose in their molecules) were much higher than those of their corresponding dextran conjugates without mannose, but the retention in the injection site of these conjugates increased too. The results indicated that the affinity of mannosyl-dextran conjugates to the receptors on the surface of macrophages in the lymph node. In addition, the different relative molecular mass of dextran conjugates also cause different biodistribution results, the major one had higher SLN uptake, the difference was significant (P 99 Tc m (CO) 3 ] + labelled mannosylated dextran conjugates showed promising properties as SLN imaging agent and worth further investigation. (authors)

New heparin–indomethacin conjugate with an ester linkage: Synthesis, self aggregation and drug delivery behavior

Energy Technology Data Exchange (ETDEWEB)

Li, Nan-Nan; Zheng, Bing-Na [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Lin, Jian-Tao [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Guangdong Medical College, Dongguan 523808 (China); Zhang, Li-Ming, E-mail: ceszhlm@mail.sysu.edu.cn [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China)

2014-01-01

New heparin–indomethacin conjugate with an ester linkage was prepared by the carbodiimide-mediated condensation reaction, and then characterized by FTIR and {sup 1}HNMR analyses. Due to its amphiphilic character, such a conjugate could self-aggregate into spherical nanoparticles in aqueous system, as confirmed by fluorescence spectroscopy, dynamic light scattering and transmission electron microscopy. By the in vitro drug release tests, the resultant conjugate nanoparticles were found to have a sustained and esterase-sensitive release behavior for conjugated indomethacin. In addition, the uptake of these conjugate nanoparticles into human nasopharyngeal carcinoma CNE1 cells was confirmed by fluorescence microscopy. - Highlights: • New heparin–indomethacin conjugate with an ester linkage was prepared. • Such a conjugate could self-aggregate into spherical nanoparticles in aqueous system. • The resultant conjugate nanoparticles exhibited an esterase-sensitive drug release behavior. • The resultant conjugate nanoparticles showed the cellular uptake ability in CNE1 cells.

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.

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.

Optimization of condition for conjugation of enrofloxacin to enzymes in chemiluminescence enzyme immunoassay

Science.gov (United States)

Yu, Songcheng; Yu, Fei; Zhang, Hongquan; Qu, Lingbo; Wu, Yongjun

2014-06-01

In this study, in order to find out a proper method for conjugation of enrofloxacin to label enzymes, two methods were compared and carbodiimide condensation was proved to be better. The results showed that the binding ratio of enrofloxacin and alkaline phosphatase (ALP) was 8:1 and that of enrofloxacin and horseradish peroxidase (HRP) was 5:1. This indicated that conjugate synthesized by carbodiimide condensation was fit for chemiluminescence enzyme immunoassay (CLEIA). Furthermore, data revealed that dialysis time was an important parameter for conjugation and 6 days was best. Buffer to dilute conjugate had little effect on CLEIA. The storage condition for conjugates was also studied and it was shown that the conjugate was stable at 4 °C with no additive up to 30 days. These data were valuable for establishing CLEIA to quantify enrofloxacin.

Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

Directory of Open Access Journals (Sweden)

Jacqueline M. Miller

2011-01-01

Full Text Available Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles.

Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

Science.gov (United States)

Miller, Jacqueline M.; Mesaros, Narcisa; Van Der Wielen, Marie; Baine, Yaela

2011-01-01

Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT) designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles. PMID:21991444

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

Nanostructured conjugated polymers in chemical sensors: synthesis, properties and applications.

Science.gov (United States)

Correa, D S; Medeiros, E S; Oliveira, J E; Paterno, L G; Mattoso, Luiz C

2014-09-01

Conjugated polymers are organic materials endowed with a π-electron conjugation along the polymer backbone that present appealing electrical and optical properties for technological applications. By using conjugated polymeric materials in the nanoscale, such properties can be further enhanced. In addition, the use of nanostructured materials makes possible miniaturize devices at the micro/nano scale. The applications of conjugated nanostructured polymers include sensors, actuators, flexible displays, discrete electronic devices, and smart fabric, to name a few. In particular, the use of conjugated polymers in chemical and biological sensors is made feasible owning to their sensitivity to the physicochemical conditions of its surrounding environment, such as chemical composition, pH, dielectric constant, humidity or even temperature. Subtle changes in these conditions bring about variations on the electrical (resistivity and capacitance), optical (absorptivity, luminescence, etc.), and mechanical properties of the conjugated polymer, which can be precisely measured by different experimental methods and ultimately associated with a specific analyte and its concentration. The present review article highlights the main features of conjugated polymers that make them suitable for chemical sensors. An especial emphasis is given to nanostructured sensors systems, which present high sensitivity and selectivity, and find application in beverage and food quality control, pharmaceutical industries, medical diagnosis, environmental monitoring, and homeland security, and other applications as discussed throughout this review.

Nanostructured Conjugated Polymers for Energy-Related Applications beyond Solar Cells.

Science.gov (United States)

Xie, Jian; Zhao, Cui-E; Lin, Zong-Qiong; Gu, Pei-Yang; Zhang, Qichun

2016-05-20

To meet the ever-increasing requirements for the next generation of sustainable and versatile energy-related devices, conjugated polymers, which have potential advantages over small molecules and inorganic materials, are among the most promising types of green candidates. The properties of conjugated polymers can be tuned through modification of the structure and incorporation of different functional moieties. In addition, superior performances can be achieved as a result of the advantages of nanostructures, such as their large surface areas and the shortened pathways for charge transfer. Therefore, nanostructured conjugated polymers with different properties can be obtained to be applied in different energy-related organic devices. This review focuses on the application and performance of the recently reported nanostructured conjugated polymers for high-performance devices, including rechargeable lithium batteries, microbial fuel cells (MFCs), thermoelectric generators, and photocatalytic systems. The design strategies, reaction mechanisms, advantages, and limitations of nanostructured conjugated polymers are further discussed in each section. Finally, possible routes to improve the performances of the current systems are also included in the conclusion. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Co-conjugation vis-à-vis individual conjugation of α-amylase and glucoamylase for hydrolysis of starch.

Science.gov (United States)

Jadhav, Swati B; Singhal, Rekha S

2013-10-15

Two enzymes, α-amylase and glucoamylase have been individually and co-conjugated to pectin by covalent binding. Both the enzyme systems showed better thermal and pH stability over the free enzyme system with the complete retention of original activities. Mixture of individually conjugated enzymes showed lower inactivation rate constant with longer half life than the co-conjugated enzyme system. Individually conjugated enzymes showed an increase of 56.48 kJ/mole and 38.22 kJ/mole in activation energy for denaturation than the free enzymes and co-conjugated enzymes, respectively. Km as well as Vmax of individually and co-conjugated enzymes was found to be higher than the free enzymes. SDS-polyacrylamide gel electrophoresis confirmed the formation of conjugate and co-conjugate as evident by increased molecular weight. Both the enzyme systems were used for starch hydrolysis where individually conjugated enzymes showed highest release of glucose at 60 °C and pH 5.0 as compared to free and co-conjugated enzyme. Copyright © 2013 Elsevier Ltd. All rights reserved.

Lectins as carriers: preparation and purification of a concanavalin A-trypsin conjugate

International Nuclear Information System (INIS)

Shier, W.T.

1985-01-01

The scheme for the preparation and purification of Con A-trypsin demonstrates the presence of Con A in the conjugate by affinity purification and by hemagglutination. The presence of Con A was demonstrated in two additional ways. The conjugate was prepared using trypsin labeled with iodine 125 and unlabeled Con A. The resulting conjugate containing 42,800 cpm/mg protein was used to demonstrate prolonged retention of the conjugated trypsin in mouse footpads. The presence of trypsin was also demonstrated in the conjugate by affinity chromatography and by the esterase activity characteristic of trypsin with tosyl-L-arginine methyl ester as substrate. Con A-trypsin was also assayed for proteolytic activity with a macromolecular substrate azocasein. A comparison of proteolytic activities with these two substrates indicated that 50-80% of the proteolytic activity observed with the small substrate is retained with macromolecular substrates

HER2 specific delivery of methotrexate by dendrimer conjugated anti-HER2 mAb

International Nuclear Information System (INIS)

Shukla, Rameshwer; Thomas, Thommey P; Desai, Ankur M; Kotlyar, Alina; Park, Steve J; Baker, James R Jr

2008-01-01

Herceptin, a humanized monoclonal antibody that binds to human growth factor receptor-2 (HER2), was covalently attached to a fifth-generation (G5) polyamidoamine dendrimer containing the cytotoxic drug methotrexate. The specific binding and internalization of this conjugate labeled with FITC was clearly demonstrated in cell lines overexpressing HER2 by flow cytometry as well as confocal microscopic analysis. In addition, binding and uptake of antibody conjugated dendrimers was completely blocked by excess non-conjugated herceptin. The dendrimer conjugate was also shown to inhibit the dihydrofolate reductase with similar activity to methotrexate. Co-localization experiments with lysotracker red indicate that antibody conjugate, although internalized efficiently into cells, has an unusually long residence time in the lysosome. Somewhat lower cytotoxicity of the conjugate in comparison to free methotrexate was attributed to the slow release of methotrexate from the conjugate and its long retention in the lysosomal pocket

Protein carriers of conjugate vaccines: characteristics, development, and clinical trials.

Science.gov (United States)

Pichichero, Michael E

2013-12-01

The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products.

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.

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

Peptide- and saccharide-conjugated dendrimers for targeted drug delivery: a concise review

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Liu, Jie; Gray, Warren D.; Davis, Michael E.; Luo, Ying

2012-01-01

Dendrimers comprise a category of branched materials with diverse functions that can be constructed with defined architectural and chemical structures. When decorated with bioactive ligands made of peptides and saccharides through peripheral chemical groups, dendrimer conjugates are turned into nanomaterials possessing attractive binding properties with the cognate receptors. At the cellular level, bioactive dendrimer conjugates can interact with cells with avidity and selectivity, and this function has particularly stimulated interests in investigating the targeting potential of dendrimer materials for the design of drug delivery systems. In addition, bioactive dendrimer conjugates have so far been studied for their versatile capabilities to enhance stability, solubility and absorption of various types of therapeutics. This review presents a brief discussion on three aspects of the recent studies to use peptide- and saccharide-conjugated dendrimers for drug delivery: (i) synthesis methods, (ii) cell- and tissue-targeting properties and (iii) applications of conjugated dendrimers in drug delivery nanodevices. With more studies to elucidate the structure–function relationship of ligand–dendrimer conjugates in transporting drugs, the conjugated dendrimers hold promise to facilitate targeted delivery and improve drug efficacy for discovery and development of modern pharmaceutics. PMID:23741608

DNA-templated antibody conjugation for targeted drug delivery to cancer cells

DEFF Research Database (Denmark)

Liu, Tianqiang

2016-01-01

-templated organic synthesis due to the wide existence of the 3-histidine cluster in most wild-type proteins. In this thesis, three projects that relate to targeted drug delivery to cancer cells based on the DTPC method is described. The first project was a delivery system which uses transferrin as the targeting....... The study shows that DNA is a highly useful tool for the assembly of proteins with potential therapeutic applications. The DNA-templated protein conjugation shows a promising application in constructing antibody-toxin conjugates or antibody-drug conjugates. In addition, DNA strands used for antibody...... either antibody engineering or special expression systems and are both time and labor consuming. To avoid the drawbacks caused by conventional chemical modification and recombinant methodologies, an ideal site specific conjugation technique would use natural amino acid residues to the protein by a new...

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

Thermal Stability of siRNA Modulates Aptamer- conjugated siRNA Inhibition

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Alexey Berezhnoy

2012-01-01

Full Text Available Oligonucleotide aptamer-mediated in vivo cell targeting of small interfering RNAs (siRNAs is emerging as a useful approach to enhance the efficacy and reduce the adverse effects resulting from siRNA-mediated genetic interference. A current main impediment in aptamer-mediated siRNA targeting is that the activity of the siRNA is often compromised when conjugated to an aptamer, often requiring labor intensive and time consuming design and testing of multiple configurations to identify a conjugate in which the siRNA activity has not been significantly reduced. Here, we show that the thermal stability of the siRNA is an important parameter of siRNA activity in its conjugated form, and that siRNAs with lower melting temperature (Tm are not or are minimally affected when conjugated to the 3′ end of 2′F-pyrimidine-modified aptamers. In addition, the configuration of the aptamer-siRNA conjugate retains activity comparable with the free siRNA duplex when the passenger strand is co-transcribed with the aptamer and 3′ overhangs on the passenger strand are removed. The approach described in this paper significantly reduces the time and effort necessary to screening siRNA sequences that retain biological activity upon aptamer conjugation, facilitating the process of identifying candidate aptamer-siRNA conjugates suitable for in vivo testing.

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

A nanodiamond-fluorescein conjugate for cell studies

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Pedroso-Santana, Seidy; Fleitas-Salazar, Noralvis; Sarabia-Sainz, Andrei; Silva-Campa, Erika; Burgara-Estrella, Alexel; Angulo-Molina, Aracely; Melendrez, Rodrigo; Pedroza-Montero, Martin; Riera, Raul

2018-03-01

The use of nanodiamonds in studies with living systems generally involves the modification of their surfaces with functional groups. Fluorescent molecules can be attached to these groups, so that one can know the exact position of the particles in each moment of the interaction with the cells. Here we modify the surface of detonation nanodiamonds and nitrogen-vacancy center nanodiamonds using carboxylation and hydroxylation procedures. Subsequent reactions with silicates and cysteine, before addition of fluorescein allow to obtain fluorescent nano-conjugates. We used confocal microscopy to observe the position of nanodiamonds interacting with HeLa cells. At 3 h post-incubation the green fluorescence is localized in extracellular rounded like-vesicles assemblies while at 24 h the conjugates can be observed inside the cells. The measurement of the fluorescence emitted by both conjugates allowed to find an enhanced emission of fluorescein isothiocyanate (FITC) when the nitrogen-vacancy center is present. We propose the existence of a fluorescence enhancement by electron transference process. The procedure described in this work allows the functionalization of nanodiamonds with FITC and other molecules using functional surface groups and small size mediators. Also, as was proved in our work, the nanodiamond-fluorescein conjugates can be used to track nanoparticles position within the cell. Localization studies are particularly important for drug delivery applications of nanodiamonds.

Bacteriophytochromes control conjugation in Agrobacterium fabrum.

Science.gov (United States)

Bai, Yingnan; Rottwinkel, Gregor; Feng, Juan; Liu, Yiyao; Lamparter, Tilman

2016-08-01

Bacterial conjugation, the transfer of single stranded plasmid DNA from donor to recipient cell, is mediated through the type IV secretion system. We performed conjugation assays using a transmissible artificial plasmid as reporter. With this assay, conjugation in Agrobacterium fabrum was modulated by the phytochromes Agp1 and Agp2, photoreceptors that are most sensitive in the red region of visible light. In conjugation studies with wild-type donor cells carrying a pBIN-GUSINT plasmid as reporter that lacked the Ti (tumor inducing) plasmid, no conjugation was observed. When either agp1(-) or agp2(-) knockout donor strains were used, plasmid DNA was delivered to the recipient, indicating that both phytochromes suppress conjugation in the wild type donor. In the recipient strains, the loss of Agp1 or Agp2 led to diminished conjugation. When wild type cells with Ti plasmid and pBIN-GUS reporter plasmid were used as donor, a high rate of conjugation was observed. The DNA transfer was down regulated by red or far-red light by a factor of 3.5. With agp1(-) or agp2(-) knockout donor cells, conjugation in the dark was about 10 times lower than with the wild type donor, and with the double knockout donor no conjugation was observed. These results imply that the phytochrome system has evolved to inhibit conjugation in the light. The decrease of conjugation under different temperature correlated with the decrease of phytochrome autophosphorylation. Copyright © 2015 Elsevier B.V. All rights reserved.

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)).

Polymers for Protein Conjugation

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Gianfranco Pasut

2014-01-01

Full Text Available Polyethylene glycol (PEG at the moment is considered the leading polymer for protein conjugation in view of its unique properties, as well as to its low toxicity in humans, qualities which have been confirmed by its extensive use in clinical practice. Other polymers that are safe, biodegradable and custom-designed have, nevertheless, also been investigated as potential candidates for protein conjugation. This review will focus on natural polymers and synthetic linear polymers that have been used for protein delivery and the results associated with their use. Genetic fusion approaches for the preparation of protein-polypeptide conjugates will be also reviewed and compared with the best known chemical conjugation ones.

Chiral gold(I vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

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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.

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

Effect of guar gum conjugation on functional, antioxidant and antimicrobial activity of egg white lysozyme.

Science.gov (United States)

Hamdani, Afshan Mumtaz; Wani, Idrees Ahmed; Bhat, Naseer Ahmad; Siddiqi, Raushid Ahmad

2018-02-01

This study was undertaken to analyze the effect of conjugation of egg-white lysozyme with guar gum. Lysozyme is an antimicrobial polypeptide that can be used for food preservation. Its antibacterial activity is limited to gram positive bacteria. Conjugation with polysaccharides like guar gum may broaden its activity against gram negatives. Conjugate was developed through Maillard reaction. Assays carried out included sugar estimation, SDS-PAGE, GPC, color, FT-IR, DSC, thermal stability, solubility, emulsifying, foaming and antioxidant activity. In addition, antimicrobial activity of the conjugate was determined against two gram positive (Staphyllococcus aureus and Enterococcus) and two gram negative pathogens (E. coli and Salmonella). Results showed higher functional properties of lysozyme-guar gum conjugate. The antioxidant properties increased from 2.02-35.80% (Inhibition of DPPH) and 1.65-4.93AAE/g (reducing power) upon guar gum conjugation. Conjugate significantly inhibited gram negative bacteria and the antibacterial activity also increased significantly against gram positive pathogens. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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.

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.

Poly(ethylene glycol-Prodrug Conjugates: Concept, Design, and Applications

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Shashwat S. Banerjee

2012-01-01

Full Text Available Poly(ethylene glycol (PEG is the most widely used polymer in delivering anticancer drugs clinically. PEGylation (i.e., the covalent attachment of PEG of peptides proteins, drugs, and bioactives is known to enhance the aqueous solubility of hydrophobic drugs, prolong circulation time, minimize nonspecific uptake, and achieve specific tumor targetability through the enhanced permeability and retention effect. Numerous PEG-based therapeutics have been developed, and several have received market approval. A vast amount of clinical experience has been gained which has helped to design PEG prodrug conjugates with improved therapeutic efficacy and reduced systemic toxicity. However, more efforts in designing PEG-based prodrug conjugates are anticipated. In light of this, the current paper highlights the synthetic advances in PEG prodrug conjugation methodologies with varied bioactive components of clinical relevance. In addition, this paper discusses FDA-approved PEGylated delivery systems, their intended clinical applications, and formulations under clinical trials.

Diclofenac in Arabidopsis cells: Rapid formation of conjugates.

Science.gov (United States)

Fu, Qiuguo; Ye, Qingfu; Zhang, Jianbo; Richards, Jaben; Borchardt, Dan; Gan, Jay

2017-03-01

Pharmaceutical and personal care products (PPCPs) are continuously introduced into the soil-plant system, through practices such as agronomic use of reclaimed water and biosolids containing these trace contaminants. Plants may accumulate PPCPs from soil, serving as a conduit for human exposure. Metabolism likely controls the final accumulation of PPCPs in plants, but is in general poorly understood for emerging contaminants. In this study, we used diclofenac as a model compound, and employed 14 C tracing, and time-of-flight (TOF) and triple quadruple (QqQ) mass spectrometers to unravel its metabolism pathways in Arabidopsis thaliana cells. We further validated the primary metabolites in Arabidopsis seedlings. Diclofenac was quickly taken up into A. thaliana cells. Phase I metabolism involved hydroxylation and successive oxidation and cyclization reactions. However, Phase I metabolites did not accumulate appreciably; they were instead rapidly conjugated with sulfate, glucose, and glutamic acid through Phase II metabolism. In particular, diclofenac parent was directly conjugated with glutamic acid, with acyl-glutamatyl-diclofenac accounting for >70% of the extractable metabolites after 120-h incubation. In addition, at the end of incubation, >40% of the spiked diclofenac was in the non-extractable form, suggesting extensive sequestration into cell matter. The rapid formation of non-extractable residue and dominance of diclofenac-glutamate conjugate uncover previously unknown metabolism pathways for diclofenac. In particular, the rapid conjugation of parent highlights the need to consider conjugates of emerging contaminants in higher plants, and their biological activity and human health implications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Recyclable enantioselective catalysts based on copper(II) complexes of 2-(pyridine-2-yl)imidazolidine-4-thione: their application in asymmetric Henry reactions

Czech Academy of Sciences Publication Activity Database

Nováková, G.; Drabina, P.; Frumarová, Božena; Sedlák, M.

2016-01-01

Roč. 358, č. 15 (2016), s. 2541-2552 ISSN 1615-4150 Institutional support: RVO:61389013 Keywords : asymmetric catalysis * enantioselectivity * heterogeneous catalysis Subject RIV: CC - Organic Chemistry Impact factor: 5.646, year: 2016

Synthesis, characterization, and in vivo efficacy evaluation of PGG–docetaxel conjugate for potential cancer chemotherapy

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Jiang X

2012-02-01

Full Text Available Danbo Yang1, Sang Van2, Yingyi Shu1, Xiaoqing Liu1, Yangfeng Ge1, Xinguo Jiang3, Yi Jin2, Lei Yu1,21Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai, People’s Republic of China; 2Biomedical Group, Nitto Denko Technical Corporation, CA, USA; 3School of Pharmacy, Fudan University, Shanghai, People’s Republic of ChinaAim: This work is intended to develop and evaluate a biopolymeric poly(L-γ-glutamyl-glutamine (PGG–docetaxel (DTX conjugate that can spontaneously self-assemble in aqueous solutions to become nanoparticles.Methods: DTX was covalently attached to hydrophilic PGG by direct esterification, and the conjugate was characterized by proton nuclear magnetic resonance spectroscopy, molecular weight gel permeation chromatography, solubility, size distribution and morphology, and hemolysis. Conjugated DTX was found to have 2000 times improved water solubility compared with free DTX. Dynamic light scattering, transmission electron microscopy, and atomic force microscopy revealed the particle size, distribution and morphology of the PGG–DTX conjugate. In addition, the conjugate was further tested for in vitro cytotoxicity and in vivo antitumor efficacy on the human non-small cell lung cancer cell line NCI-H460.Results: Conjugated DTX was found to have 2000 times improved water solubility compared with free DTX. The conjugate formed nanoparticles with an average diameter of 30 nm in spherical shape and unimodal particle size distribution. The conjugate exhibited about 2% hemolysis at 10 mg/mL, compared with 56% for Tween 80® at 0.4 mg/mL, and 33% for Cremophor EL® at 10 mg/mL. In addition, the conjugate was further tested for in vitro cytotoxicity and in vivo antitumor efficacy on the human non-small cell lung cancer cell line NCI-H460. As expected, conjugated DTX exhibited lower cytotoxicity compared to that of free DTX, in concentration

Enantioselective copper catalysed intramolecular C-H insertion reactions of α-diazo-β-keto sulfones, α-diazo-β-keto phosphine oxides and 2-diazo-1,3-diketones; the influence of the carbene substituent.

Science.gov (United States)

Shiely, Amy E; Slattery, Catherine N; Ford, Alan; Eccles, Kevin S; Lawrence, Simon E; Maguire, Anita R

2017-03-22

Enantioselectivities in C-H insertion reactions, employing the copper-bis(oxazoline)-NaBARF catalyst system, leading to cyclopentanones are highest with sulfonyl substituents on the carbene carbon, and furthermore, the impact is enhanced by increased steric demand on the sulfonyl substituent (up to 91%ee). Enantioselective intramolecular C-H insertion reactions of α-diazo-β-keto phosphine oxides and 2-diazo-1,3-diketones are reported for the first time.

Optical phase conjugation

CERN Document Server

Fisher, Robert A

1983-01-01

This book appears at a time of intense activity in optical phase conjugation. We chose not to await the maturation of the field, but instead to provide this material in time to be useful in its development. We have tried very hard to elucidate and interrelate the various nonlinear phenomena which can be used for optical phase conjugation.

CRISPR-Cas and Restriction-Modification Act Additively against Conjugative Antibiotic Resistance Plasmid Transfer in Enterococcus faecalis

OpenAIRE

Price, Valerie J.; Huo, Wenwen; Sharifi, Ardalan; Palmer, Kelli L.

2016-01-01

ABSTRACT Enterococcus faecalis is an opportunistic pathogen and a leading cause of nosocomial infections. Conjugative pheromone-responsive plasmids are narrow-host-range mobile genetic elements (MGEs) that are rapid disseminators of antibiotic resistance in the faecalis species. Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas and restriction-modification confer acquired and innate immunity, respectively, against MGE acquisition in bacteria. Most multidrug-resistant E.?fa...

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

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Erli Sugiono

2013-11-01

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

A Simple Primary Amine Catalyst for Enantioselective α-Hydroxylations and α-Fluorinations of Branched Aldehydes

OpenAIRE

Witten, Michael R.; Jacobsen, Eric N.

2015-01-01

A new primary amine catalyst for the asymmetric α-hydroxylation and α-fluorination of α-branched aldehydes is described. The products of the title transformations are generated in excellent yields and with high enantioselectivities. Both processes can be performed within short reaction times and on gram scale. The similarity in the results obtained in both reactions, combined with computational evidence, implies a common basis for stereoinduction and the possibility of a general catalytic mec...

Synthesis of New Chiral Benzimidazolylidene–Rh Complexes and Their Application in Asymmetric Addition Reactions of Organoboronic Acids to Aldehydes

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Weiping He

2016-09-01

Full Text Available A series of novel chiral N-heterocyclic carbene rhodium complexes (NHC–Rh based on benzimidazole have been prepared, and all of the NHC–Rh complexes were fully characterized by NMR and mass spectrometry. These complexes could be used as catalysts for the asymmetric 1,2-addition of organoboronic acids to aldehydes, affording chiral diarylmethanols with high yields and moderate enantioselectivities.

Enantioselective column coupled electrophoresis employing large bore capillaries hyphenated with tandem mass spectrometry for ultra-trace determination of chiral compounds in complex real samples.

Science.gov (United States)

Piešťanský, Juraj; Maráková, Katarína; Kovaľ, Marián; Havránek, Emil; Mikuš, Peter

2015-12-01

A new multidimensional analytical approach for the ultra-trace determination of target chiral compounds in unpretreated complex real samples was developed in this work. The proposed analytical system provided high orthogonality due to on-line combination of three different methods (separation mechanisms), i.e. (1) isotachophoresis (ITP), (2) chiral capillary zone electrophoresis (chiral CZE), and (3) triple quadrupole mass spectrometry (QqQ MS). The ITP step, performed in a large bore capillary (800 μm), was utilized for the effective sample pretreatment (preconcentration and matrix clean-up) in a large injection volume (1-10 μL) enabling to obtain as low as ca. 80 pg/mL limits of detection for the target enantiomers in urine matrices. In the chiral CZE step, the different chiral selectors (neutral, ionizable, and permanently charged cyclodextrins) and buffer systems were tested in terms of enantioselectivity and influence on the MS detection response. The performance parameters of the optimized ITP - chiral CZE-QqQ MS method were evaluated according to the FDA guidance for bioanalytical method validation. Successful validation and application (enantioselective monitoring of renally eliminated pheniramine and its metabolite in human urine) highlighted great potential of this chiral approach in advanced enantioselective biomedical applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interspecies differences in the enantioselectivity of epoxide hydrolases in Cryptococcus laurentii (Kufferath) C.E. Skinner and Cryptococcus podzolicus (Bab'jeva & Reshetova) Golubev

CSIR Research Space (South Africa)

Botes, AL

2005-01-01

Full Text Available Isolates representing Cryptococcus laurentii and Cryptococcus podzolicus, originating from soil of a heath land indigenous to South Africa, were screened for the presence of enantioselective epoxide hydrolases for 2, 2-disubstituted epoxides...

Production of carrier-peptide conjugates using chemically reactive unnatural amino acids

Science.gov (United States)

Young, Travis; Schultz, Peter G

2013-12-17

Provided are methods of making carrier polypeptide that include incorporating a first unnatural amino acid into a carrier polypeptide variant, incorporating a second unnatural amino acid into a target polypeptide variant, and reacting the first and second unnatural amino acids to produce the conjugate. Conjugates produced using the provided methods are also provided. In addition, orthogonal translation systems in methylotrophic yeast and methods of using these systems to produce carrier and target polypeptide variants comprising unnatural amino acids are provided.

Qualidade conjugal: mapeando conceitos

Directory of Open Access Journals (Sweden)

Clarisse Mosmann

2006-12-01

Full Text Available Apesar da ampla utilização do conceito de qualidade conjugal, identifica-se falta de clareza conceitual acerca das variáveis que o compõem. Esse artigo apresenta revisão da literatura na área com o objetivo de mapear o conceito de qualidade conjugal. Foram analisadas sete principais teorias sobre o tema: Troca Social, Comportamental, Apego, Teoria da Crise, Interacionismo Simbólico. Pelos postulados propostos nas diferentes teorias, podem-se identificar três grupos de variáveis fundamentais na definição da qualidade conjugal: recursos pessoais dos cônjuges, contexto de inserção do casal e processos adaptativos. Neste sentido, a qualidade conjugal é resultado do processo dinâmico e interativo do casal, razão deste caráter multidimensional.

Properties of acid gels made from sodium caseinate-maltodextrin conjugates prepared by a wet heating method.

Science.gov (United States)

Zhang, Shuwen; Gong, Yuansheng; Khanal, Som; Lu, Yanjie; Lucey, John A

2017-11-01

Covalent attachment of polysaccharides to proteins (conjugation) via the Maillard reaction has been extensively studied. Conjugation can lead to a significant improvement in protein functionality (e.g., solubility, emulsification, and heat stability). Caseins have previously been successfully conjugated with maltodextrin (Md), but the effect on the detailed acid gelation properties has not been examined. We studied the effect of conjugating sodium caseinate (NaCN) with 3 different sized Md samples via the Maillard reaction in aqueous solutions. The Md samples had dextrose equivalents of 4 to 7, 9 to 12, and 20 to 23 for Md40, Md100, and Md200, respectively. The conjugation reaction was performed in mixtures with 5% NaCN and 5% Md, which were heated at 90°C for 10 h. The degree of conjugation was estimated from the reduction in free amino groups as well as color changes. Sodium dodecyl sulfate-PAGE analysis was performed to confirm conjugation by employing staining of both protein and carbohydrate bands. The molar mass of samples was determined by size-exclusion chromatography coupled with multi-angle laser light scattering. After the conjugation reaction, samples were then gelled by the addition of 0.63% (wt/vol) glucono-δ-lactone at 30°C, such that samples reached pH 4.6 after about 13 h. The rheological properties of samples during acidification was monitored by small-strain dynamic oscillatory rheology. The microstructure of acid gels at pH 4.6 was examined by fluorescence microscopy. Conjugation resulted in a loss of 10.8, 8.8, and 11.9% of the available amino groups in the protein for the NaCN-Md40 conjugates (C40), NaCN-Md100 conjugates (C100), and NaCN-Md100 conjugates (C200), respectively. With a decrease in the size of the type of Md, an increase occurred in the molar mass of the resultant conjugate. The weight average molar masses of NaCN-Md samples were 340, 368, and 425 kDa for the conjugates C40, C100, and C200, respectively. Addition of Md to Na

High operational and environmental stability of high-mobility conjugated polymer field-effect transistors through the use of molecular additives

KAUST Repository

Nikolka, Mark; Nasrallah, Iyad; Rose, Bradley Daniel; Ravva, Mahesh Kumar; Broch, Katharina; Sadhanala, Aditya; Harkin, David; Charmet, Jerome; Hurhangee, Michael; Brown, Adam; Illig, Steffen; Too, Patrick; Jongman, Jan; McCulloch, Iain; Bredas, Jean-Luc; Sirringhaus, Henning

2016-01-01

Due to their low-temperature processing properties and inherent mechanical flexibility, conjugated polymer field-effect transistors (FETs) are promising candidates for enabling flexible electronic circuits and displays. Much progress has been made on materials performance; however, there remain significant concerns about operational and environmental stability, particularly in the context of applications that require a very high level of threshold voltage stability, such as active-matrix addressing of organic light-emitting diode displays. Here, we investigate the physical mechanisms behind operational and environmental degradation of high-mobility, p-type polymer FETs and demonstrate an effective route to improve device stability. We show that water incorporated in nanometre-sized voids within the polymer microstructure is the key factor in charge trapping and device degradation. By inserting molecular additives that displace water from these voids, it is possible to increase the stability as well as uniformity to a high level sufficient for demanding industrial applications.

High operational and environmental stability of high-mobility conjugated polymer field-effect transistors through the use of molecular additives

KAUST Repository

Nikolka, Mark

2016-12-12

Due to their low-temperature processing properties and inherent mechanical flexibility, conjugated polymer field-effect transistors (FETs) are promising candidates for enabling flexible electronic circuits and displays. Much progress has been made on materials performance; however, there remain significant concerns about operational and environmental stability, particularly in the context of applications that require a very high level of threshold voltage stability, such as active-matrix addressing of organic light-emitting diode displays. Here, we investigate the physical mechanisms behind operational and environmental degradation of high-mobility, p-type polymer FETs and demonstrate an effective route to improve device stability. We show that water incorporated in nanometre-sized voids within the polymer microstructure is the key factor in charge trapping and device degradation. By inserting molecular additives that displace water from these voids, it is possible to increase the stability as well as uniformity to a high level sufficient for demanding industrial applications.

Synthesis and structural elucidation of glutathione and N-aceyl-cysteine conjugates of 5-aminosalicylic acid

DEFF Research Database (Denmark)

Jensen, J.; Cornett, Claus; Olsen, C. E.

1993-01-01

The ability of 5-aminosalicylic acid (5-ASA) to be oxidized to a quinone monoimine compound capable of conjugating with nucleophilic compounds such as N-acetyl-cysteine (NAC) and glutathione (GSH) has been investigated in vitro. Three isomeric conjugates of 5-ASA and NAC as well as three isomeric...... conjugates of 5-ASA and GSH were found to be formed. 5-ASA was initially oxidized by PbO2 in a solution of TRIS-HCl buffer pH 9.3 followed by the in situ addition of N-acetyl-cysteine or glutathione to the oxidized 5-ASA at pH 7.5. The resulting conjugates were N-acetylated at the aromatic amino group...... to investigate whether such conjugates are excreted in the urine from persons treated with 5-ASA. The N-acetyl-cysteine conjugates could be detected by fluorescense, which resulted in low detection limits ranging from 0.02 mug to 0.06 mug per ml corresponding to the transformation of about 0.003% of the daily...

BCL::EMAS — Enantioselective Molecular Asymmetry Descriptor for 3D-QSAR

Directory of Open Access Journals (Sweden)

Mariusz Butkiewicz

2012-08-01

Full Text Available Stereochemistry is an important determinant of a molecule’s biological activity. Stereoisomers can have different degrees of efficacy or even opposing effects when interacting with a target protein. Stereochemistry is a molecular property difficult to represent in 2D-QSAR as it is an inherently three-dimensional phenomenon. A major drawback of most proposed descriptors for 3D-QSAR that encode stereochemistry is that they require a heuristic for defining all stereocenters and rank-ordering its substituents. Here we propose a novel 3D-QSAR descriptor termed Enantioselective Molecular ASymmetry (EMAS that is capable of distinguishing between enantiomers in the absence of such heuristics. The descriptor aims to measure the deviation from an overall symmetric shape of the molecule. A radial-distribution function (RDF determines a signed volume of tetrahedrons of all triplets of atoms and the molecule center. The descriptor can be enriched with atom-centric properties such as partial charge. This descriptor showed good predictability when tested with a dataset of thirty-one steroids commonly used to benchmark stereochemistry descriptors (r² = 0.89, q² = 0.78. Additionally, EMAS improved enrichment of 4.38 versus 3.94 without EMAS in a simulated virtual high-throughput screening (vHTS for inhibitors and substrates of cytochrome P450 (PUBCHEM AID891.

Oxidative N-Heterocyclic Carbene-Catalyzed γ-Carbon Addition of Enals to Imines: Mechanistic Studies and Access to Antimicrobial Compounds.

Science.gov (United States)

Zheng, Peng-Cheng; Cheng, Jiajia; Su, Shihu; Jin, Zhichao; Wang, Yu-Huang; Yang, Song; Jin, Lin-Hong; Song, Bao-An; Chi, Yonggui Robin

2015-07-06

The reaction mechanism of the γ-carbon addition of enal to imine under oxidative N-heterocyclic carbene catalysis is studied experimentally. The oxidation, γ-carbon deprotonation, and nucleophilic addition of γ-carbon to imine were found to be facile steps. The results of our study also provide highly enantioselective access to tricyclic sulfonyl amides that exhibit interesting antimicrobial activities against X. oryzae, a bacterium that causes bacterial disease in rice growing. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective accumulation, metabolism and phytoremediation of lactofen by aquatic macrophyte Lemna minor.

Science.gov (United States)

Wang, Fang; Yi, Xiaotong; Qu, Han; Chen, Li; Liu, Donghui; Wang, Peng; Zhou, Zhiqiang

2017-09-01

Pesticides are frequently detected in water bodies due to the agricultural application, which may pose impacts on aquatic organisms. The enantioselective bioaccumulation and metabolism of the herbicide lactofen in aquatic floating macrophyte Lemna minor (L. minor) were studied and the potential L. minor phytoremediation was investigated. Ultra-high performance liquid chromatography - tandem mass spectrometry (UHPLC-MS-MS) analysis for lactofen and its two known metabolites in L. minor was performed. The initial concentrations of racemic lactofen, R-lactofen and S-lactofen were all 30μgL -1 in the growth solution. The distribution of lactofen and its metabolites in growth solution and L. minor was determined throughout a 5-d laboratory trial. It was observed that S-lactofen was preferentially taken up and metabolized in L. minor. After rac-lactofen exposure, the accumulation amount of S-lactofen was approximately 3-fold more than that of R-lactofen in L. minor and the metabolism rate of S-lactofen (T 1/2 =0.92 d) was significantly faster than R-lactofen (T 1/2 =1.55 d). L. minor could only slightly accelerate the metabolism and removal of lactofen in the growth solution. As for the metabolites, desethyl lactofen was found to be the major metabolite in L. minor and the growth solution, whereas the metabolite acifluorfene was undetectable. No interconversion of the two enantiomers was observed after individual enantiomer exposure, indicating they were configurationally stable. The findings of this work represented that the accumulation and metabolism of lactofen in L. minor were enantioselective, and L. minor had limited capacity for the removal of lactofen and its metabolite in water. Copyright © 2017. Published by Elsevier Inc.

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.

Enzymatic Kinetic Resolution of 2-Piperidineethanol for the Enantioselective Targeted and Diversity Oriented Synthesis

Directory of Open Access Journals (Sweden)

Dario Perdicchia

2015-12-01

Full Text Available 2-Piperidineethanol (1 and its corresponding N-protected aldehyde (2 were used for the synthesis of several natural and synthetic compounds. The existence of a stereocenter at position 2 of the piperidine skeleton and the presence of an easily-functionalized group, such as the alcohol, set 1 as a valuable starting material for enantioselective synthesis. Herein, are presented both synthetic and enzymatic methods for the resolution of the racemic 1, as well as an overview of synthesized natural products starting from the enantiopure 1.

Cross-Conjugated n-Dopable Aromatic Polyketone

NARCIS (Netherlands)

Voortman, Thomas P.; Bartesaghi, Davide; Koster, L. Jan Anton; Chiechi, Ryan C.

2015-01-01

This paper describes the synthesis and characterization of a high molecular weight cross-conjugated polyketone synthesized via scalable Friedel Crafts chemistry. Cross-conjugated polyketones are precursors to conjugated polyions; they become orders of magnitude more conductive after a two-electron

Conjugated polymers developed from alkynes

Institute of Scientific and Technical Information of China (English)

Yajing Liu; Jacky W.Y.Lam; Ben Zhong Tang

2015-01-01

The numerous merits of conjugated polymers(CPs) have encouraged scientists to develop a variety of synthetic routes to CPs with diverse structures and functionalities. Among the large scope of substrates,alkyne plays an important role in constructing polymers with conjugated backbones. In addition to some well-developed reactions including Glaser–Hay and Sonogashira coupling, azide/thiol-yne click reaction and cyclotrimerization, some novel alkyne-based reactions have also been explored such as oxidative polycoupling, decarbonylative polycoupling and multicomponent tandem polymerizations. his review focuses on the recent progress on the synthetic methodology of CPs in the last ive years using monomers with two or more triple bonds and some of their high-technological applications. Selected examples of materials properties of these CPs are given in this review, such as luorescence response to chemical or physical stimuli, magnetism, white light emission, cell imaging and bioprobing. Finally, a short perspective is raised in regard to the outlook of the preparation methodologies, functionalities as well as potential applications of CPs in the future.

Enantioselective rhodium/ruthenium photoredox catalysis en route to chiral 1,2-aminoalcohols.

Science.gov (United States)

Ma, Jiajia; Harms, Klaus; Meggers, Eric

2016-08-09

A rhodium-based chiral Lewis acid catalyst combined with [Ru(bpy)3](PF6)2 as a photoredox sensitizer allows for the visible-light-activated redox coupling of α-silylamines with 2-acyl imidazoles to afford, after desilylation, 1,2-amino-alcohols in yields of 69-88% and with high enantioselectivity (54-99% ee). The reaction is proposed to proceed via an electron exchange between the α-silylamine (electron donor) and the rhodium-chelated 2-acyl imidazole (electron acceptor), followed by a stereocontrolled radical-radical reaction. Substrate scope and control experiments reveal that the trimethylsilyl group plays a crucial role in this reductive umpolung of the carbonyl group.

Specific Conjugation of the Hinge Region for Homogeneous Preparation of Antibody Fragment-Drug Conjugate: A Case Study for Doxorubicin-PEG-anti-CD20 Fab' Synthesis.

Science.gov (United States)

Zhou, Zhan; Zhang, Jing; Zhang, Yan; Ma, Guanghui; Su, Zhiguo

2016-01-20

Conventional preparation strategies for antibody-drug conjugates (ADCs) result in heterogeneous products with various molecular sizes and species. In this study, we developed a homogeneous preparation strategy by site-specific conjugation of the anticancer drug with an antibody fragment. The model drug doxorubicin (DOX) was coupled to the Fab' fragment of anti-CD20 IgG at its permissive sites through a heterotelechelic PEG linker, generating an antibody fragment-drug conjugate (AFDC). Anti-CD20 IgG was digested and reduced specifically with β-mercaptoethylamine to generate the Fab' fragment with two free mercapto groups in its hinge region. Meanwhile, DOX was conjugated with α-succinimidylsuccinate ω-maleimide polyethylene glycol (NHS-PEG-MAL) to form MAL-PEG-DOX, which was subsequently linked to the free mercapto containing Fab' fragment to form a Fab'-PEG-DOX conjugate. The dual site-specific bioconjugation was achieved through the combination of highly selective reduction of IgG and introduction of heterotelechelic PEG linker. The resulting AFDC provides an utterly homogeneous product, with a definite ratio of one fragment to two drugs. Laser confocal microscopy and cell ELISA revealed that the AFDC could accumulate in the antigen-positive Daudi tumor cell. In addition, the Fab'-PEG-DOX retained appreciable targeting ability and improved antitumor activity, demonstrating an excellent therapeutic effect on the lymphoma mice model for better cure rate and significantly reduced side effects.

Block-conjugate-gradient method

International Nuclear Information System (INIS)

McCarthy, J.F.

1989-01-01

It is shown that by using the block-conjugate-gradient method several, say s, columns of the inverse Kogut-Susskind fermion matrix can be found simultaneously, in less time than it would take to run the standard conjugate-gradient algorithm s times. The method improves in efficiency relative to the standard conjugate-gradient algorithm as the fermion mass is decreased and as the value of the coupling is pushed to its limit before the finite-size effects become important. Thus it is potentially useful for measuring propagators in large lattice-gauge-theory calculations of the particle spectrum

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

Science.gov (United States)

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

2013-01-01

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

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.

Androgen Receptor Antagonism By Divalent Ethisterone Conjugates In Castrate-Resistant Prostate Cancer Cells

Science.gov (United States)

Levine, Paul M.; Lee, Eugine; Greenfield, Alex; Bonneau, Richard; Logan, Susan K.; Garabedian, Michael J.; Kirshenbaum, Kent

2013-01-01

Sustained treatment of prostate cancer with Androgen Receptor (AR) antagonists can evoke drug resistance, leading to castrate-resistant disease. Elevated activity of the AR is often associated with this highly aggressive disease state. Therefore, new therapeutic regimens that target and modulate AR activity could prove beneficial. We previously introduced a versatile chemical platform to generate competitive and non-competitive multivalent peptoid oligomer conjugates that modulate AR activity. In particular, we identified a linear and a cyclic divalent ethisterone conjugate that exhibit potent anti-proliferative properties in LNCaP-abl cells, a model of castrate-resistant prostate cancer. Here, we characterize the mechanism of action of these compounds utilizing confocal microscopy, time-resolved fluorescence resonance energy transfer, chromatin immunoprecipitation, flow cytometry, and microarray analysis. The linear conjugate competitively blocks AR action by inhibiting DNA binding. In addition, the linear conjugate does not promote AR nuclear localization or co-activator binding. In contrast, the cyclic conjugate promotes AR nuclear localization and induces cell-cycle arrest, despite its inability to compete against endogenous ligand for binding to AR in vitro. Genome-wide expression analysis reveals that gene transcripts are differentially affected by treatment with the linear or cyclic conjugate. Although the divalent ethisterone conjugates share extensive chemical similarities, we illustrate that they can antagonize the AR via distinct mechanisms of action, establishing new therapeutic strategies for potential applications in AR pharmacology. PMID:22871957

Ibuprofen-conjugated hyaluronate/polygalacturonic acid hydrogel for the prevention of epidural fibrosis.

Science.gov (United States)

Lin, Cheng-Yi; Peng, Hsiu-Hui; Chen, Mei-Hsiu; Sun, Jui-Sheng; Chang, Chih-Ju; Liu, Tse-Ying; Chen, Ming-Hong

2016-05-01

The formation of fibrous tissue is part of the natural healing response following a laminectomy. Severe scar tissue adhesion, known as epidural fibrosis, is a common cause of failed back surgery syndrome. In this study, by combining the advantages of drug treatment with a physical barrier, an ibuprofen-conjugated crosslinkable polygalacturonic acid and hyaluronic acid hydrogel was developed for epidural fibrosis prevention. Conjugation was confirmed and measured by 1D(1)H NMR spectroscopy.In vitroanalysis showed that the ibuprofen-conjugated polygalacturonic acid-hyaluronic acid hydrogel showed low cytotoxicity. In addition, the conjugated ibuprofen decreased prostaglandin E2production of the lipopolysaccharide-induced RAW264.7 cells. Histological data inin vivostudies indicated that the scar tissue adhesion of laminectomized male adult rats was reduced by the application of our ibuprofen-conjugated polygalacturonic acid-hyaluronic acid hydrogel. Its use also reduced the population of giant cells and collagen deposition of scar tissue without inducing extensive cell recruitment. The results of this study therefore suggest that the local delivery of ibuprofenviaa polygalacturonic acid-hyaluronic acid-based hydrogel reduces the possibility of epidural fibrosis. © The Author(s) 2016.

Micelle-like nanoassemblies based on polymer-drug conjugates as an emerging platform for drug delivery.

Science.gov (United States)

Liu, Zhihong; Wang, Yutao; Zhang, Na

2012-07-01

During the past decades, polymer-drug conjugates are one of the hottest topics in novel drug development fields. Amphiphilic polymer-drug conjugates in aqueous solution could form micelles or micelle-like nanoassemblies. Compared with polymer-drug conjugates and the micelles into which drugs are physically entrapped, micelles or micelle-like nanoassemblies based on polymer-drug conjugates bring several additional advantages, including increased drug-loading capacity, enhanced intracellular uptake, reduced systemic toxicity, and improved therapeutic efficacy. This review focuses on recent progress achieved in the research field of micelles or micelle-like nanoassemblies based on polymer-drug conjugates. Firstly, properties of polymers, drugs, and linkers which could be used to build polymer-drug conjugate micelles or micelle-like nanoassemblies are summarized. Then, the characterization methods are described. Finally, the drug-targeting mechanisms are discussed. Micelles or micelle-like nanoassemblies based on polymer-drug conjugates as an emerging platform have the potential to achieve medical treatments with enhanced therapeutic effect. The application of micelles or micelle-like nanoassemblies based on polymer-drug conjugates may give new life to old active compounds abandoned due to their low solubility problems. For clinical application, there is a need to further optimize the properties of the polymer, drug, and linker.

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.

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.

Conjugated polymer zwitterions and solar cells comprising conjugated polymer zwitterions

Science.gov (United States)

Emrick, Todd; Russell, Thomas; Page, Zachariah; Liu, Yao

2018-06-05

A conjugated polymer zwitterion includes repeating units having structure (I), (II), or a combination thereof ##STR00001## wherein Ar is independently at each occurrence a divalent substituted or unsubstituted C3-30 arylene or heteroarylene group; L is independently at each occurrence a divalent C1-16 alkylene group, C6-30arylene or heteroarylene group, or alkylene oxide group; and R1 is independently at each occurrence a zwitterion. A polymer solar cell including the conjugated polymer zwitterion is also disclosed.

Research study of conjugate materials; Conjugate material no chosa kenkyu

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-03-01

The paper reported an introductory research on possibilities of new glass `conjugate materials.` The report took up the structure and synthetic process of conjugate materials to be researched/developed, classified them according to structural elements on molecular, nanometer and cluster levels, and introduced the structures and functions. Further, as glasses with new functions to be proposed, the paper introduced transparent and high-strength glass used for houses and vehicles, light modulation glass which realizes energy saving and optical data processing, and environmentally functional glass which realizes environmental cleaning or high performance biosensor. An initial survey was also conducted on rights of intellectual property to be taken notice of in Japan and abroad in the present situation. Reports were summed up and introduced of Osaka National Research Institute, Electrotechnical Laboratory, and National Industrial Research Institute of Nagoya which are all carrying out leading studies of conjugate materials. 235 refs., 135 figs., 6 tabs.

Enantioselective aminocatalysis: Michael addition of unactivated ...

Indian Academy of Sciences (India)

KHIANGTE VANLALDINPUIA

2017-09-25

Sep 25, 2017 ... the case of acetone) were stirred at room temperature for. 30 min. Nitroolefin (1 ..... Kaprzak A and Gawronski J 2001 Review on the use of cinchona ... 2006 Functionalized chiral ionic liquids as highly effi- cient asymmetric ...

Hydroxychloroquine-conjugated gold nanoparticles for improved siRNA activity.

Science.gov (United States)

Perche, F; Yi, Y; Hespel, L; Mi, P; Dirisala, A; Cabral, H; Miyata, K; Kataoka, K

2016-06-01

Current technology of siRNA delivery relies on pharmaceutical dosage forms to route maximal doses of siRNA to the tumor. However, this rationale does not address intracellular bottlenecks governing silencing activity. Here, we tested the impact of hydroxychloroquine conjugation on the intracellular fate and silencing activity of siRNA conjugated PEGylated gold nanoparticles. Addition of hydroxychloroquine improved endosomal escape and increased siRNA guide strand distribution to the RNA induced silencing complex (RISC), both crucial obstacles to the potency of siRNA. This modification significantly improved gene downregulation in cellulo. Altogether, our data suggest the benefit of this modification for the design of improved siRNA delivery systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

Transglutaminase-treated conjugation of sodium caseinate and corn fiber gum hydrolysate: Interfacial and dilatational properties.

Science.gov (United States)

Liu, Yan; Selig, Michael J; Yadav, Madhav P; Yin, Lijun; Abbaspourrad, Alireza

2018-05-01

This study compliments previous work where peroxidase was successfully used to crosslink corn fiber gum (CFG) with bovine serum albumin and improve CFG's emulsifying properties. Herein, an alternative type of enzyme, transglutaminase, was used to prepare conjugates of CFG and sodium caseinate. Additionally, the CFG was partially hydrolyzed by sulfuric acid and its crosslinking pattern with caseinate was evaluated. The interfacial crosslinking degree between caseinate and CFG increased after hydrolysis according to high performance size exclusion chromatography. The equilibrium interfacial tension of CFG hydrolysate-caseinate conjugate was lower than that of CFG-caseinate conjugate as the rearrangement rate of the CFG hydrolysate-caseinate conjugate was higher. The dilatational modulus of CFG hydrolysate decreased from that of CFG. Copyright © 2018 Elsevier Ltd. All rights reserved.

Enantioselective Synthesis of Aminodiols by Sequential Rhodium-Catalysed Oxyamination/Kinetic Resolution: Expanding the Substrate Scope of Amidine-Based Catalysis.

Science.gov (United States)

Guasch, Joan; Giménez-Nueno, Irene; Funes-Ardoiz, Ignacio; Bernús, Miguel; Matheu, M Isabel; Maseras, Feliu; Castillón, Sergio; Díaz, Yolanda

2018-03-26

Regio- and stereoselective oxyamination of dienes through a tandem rhodium-catalysed aziridination-nucleophilic opening affords racemic oxazolidinone derivatives, which undergo a kinetic resolution acylation process with amidine-based catalysts (ABCs) to achieve s values of up to 117. This protocol was applied to the enantioselective synthesis of sphingosine. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Self-Adjuvanting Glycopeptide Conjugate Vaccine against Disseminated Candidiasis

Science.gov (United States)

Xin, Hong; Cartmell, Jonathan; Bailey, Justin J.; Dziadek, Sebastian; Bundle, David R.; Cutler, Jim E.

2012-01-01

Our research on pathogenesis of disseminated candidiasis led to the discovery that antibodies specific for Candida albicans cell surface β-1, 2–mannotriose [β-(Man)3] protect mice. A 14 mer peptide Fba, which derived from the N-terminal portion of the C. albicans cytosolic/cell surface protein fructose-bisphosphate aldolase, was used as the glycan carrier and resulted in a novel synthetic glycopeptide vaccine β-(Man)3-Fba. By a dendritic cell-based immunization approach, this conjugate induced protective antibody responses against both the glycan and peptide parts of the vaccine. In this report, we modified the β-(Man)3-Fba conjugate by coupling it to tetanus toxoid (TT) in order to improve immunogenicity and allow for use of an adjuvant suitable for human use. By new immunization procedures entirely compatible with human use, the modified β-(Man)3-Fba-TT was administered either alone or as a mixture made with alum or monophosphoryl lipid A (MPL) adjuvants and given to mice by a subcutaneous (s.c.) route. Mice vaccinated with or, surprisingly, without adjuvant responded well by making robust antibody responses. The immunized groups showed a high degree of protection against a lethal challenge with C. albicans as evidenced by increased survival times and reduced kidney fungal burden as compared to control groups that received only adjuvant or DPBS buffer prior to challenge. To confirm that induced antibodies were protective, sera from mice immunized against the β-(Man)3-Fba-TT conjugate transferred protection against disseminated candidiasis to naïve mice, whereas C. albicans-absorbed immune sera did not. Similar antibody responses and protection induced by the β-(Man)3-Fba-TT vaccine was observed in inbred BALB/c and outbred Swiss Webster mice. We conclude that addition of TT to the glycopeptide conjugate results in a self-adjuvanting vaccine that promotes robust antibody responses without the need for additional adjuvant, which is novel and represents a

Misonidazole-glutathione conjugates in CHO cells

International Nuclear Information System (INIS)

Varghese, A.J.; Whitmore, G.F.

1984-01-01

Misonidazole, after reduction to the hydroxylamine derivative, reacts with glutathione (GSH) under physiological conditions. The reaction product has been identified as a mixture of two isomeric conjugates. When water soluble extracts of CHO cells exposed to misonidazole under hypoxic conditions are subjected to HPLC analysis, misonidazole derivatives, having the same chromatographic properties as the GSH-MISO conjugates, were detected. When CHO cells were incubated with misonidazole in the presence of added GSH, a substantial increase in the amount of the conjugate was detected. When extracts of CHO cells exposed to misonidazole under hypoxia were subsequently exposed to GSH, an increased formation of the conjugate was observed. A rearrangement product of the hydroxylamine derivative of misonidazole is postulated as the reactive intermediate responsible for the formation of the conjugate

Modelling conjugation with stochastic differential equations

DEFF Research Database (Denmark)

Philipsen, Kirsten Riber; Christiansen, Lasse Engbo; Hasman, Henrik

2010-01-01

Enterococcus faecium strains in a rich exhaustible media. The model contains a new expression for a substrate dependent conjugation rate. A maximum likelihood based method is used to estimate the model parameters. Different models including different noise structure for the system and observations are compared......Conjugation is an important mechanism involved in the transfer of resistance between bacteria. In this article a stochastic differential equation based model consisting of a continuous time state equation and a discrete time measurement equation is introduced to model growth and conjugation of two...... using a likelihood-ratio test and Akaike's information criterion. Experiments indicating conjugation on the agar plates selecting for transconjugants motivates the introduction of an extended model, for which conjugation on the agar plate is described in the measurement equation. This model is compared...

Enantioselective Effect of Flurbiprofen on Lithium Disposition in Rats.

Science.gov (United States)

Uwai, Yuichi; Matsumoto, Masashi; Kawasaki, Tatsuya; Nabekura, Tomohiro

2017-01-01

Lithium is administered for treating bipolar disorders and is mainly excreted into urine. Nonsteroidal anti-inflammatory drugs inhibit this process. In this study, we examined the enantioselective effect of flurbiprofen on the disposition of lithium in rats. Pharmacokinetic experiments with lithium were performed. Until 60 min after the intravenous administration of lithium chloride at 30 mg/kg as a bolus, 17.8% of lithium injected was recovered into the urine. Its renal clearance was calculated to be 1.62 mL/min/kg. Neither creatinine clearance (Ccr) nor pharmacokinetics of lithium was affected by the simultaneous injection of (R)-flurbiprofen at 20 mg/kg. (S)-flurbiprofen impaired the renal function and interfered with the urinary excretion of lithium. The ratio of renal clearance of lithium to Ccr was decreased by the (S)-enantiomer. This study clarified that the (S)-flurbiprofen but not (R)-flurbiprofen inhibited the renal excretion of lithium in rats. © 2017 S. Karger AG, Basel.

Poly(2-oxazoline)-Antibiotic Conjugates with Penicillins.

Science.gov (United States)

Schmidt, Martin; Bast, Livia K; Lanfer, Franziska; Richter, Lena; Hennes, Elisabeth; Seymen, Rana; Krumm, Christian; Tiller, Joerg C

2017-09-20

The conjugation of antibiotics with polymers is rarely done, but it might be a promising alternative to low-molecular-weight derivatization. The two penicillins penicillin G (PenG) and penicillin V (PenV) were attached to the end groups of different water-soluble poly(2-oxazoline)s (POx) via their carboxylic acid function. This ester group was shown to be more stable against hydrolysis than the β-lactam ring of the penicillins. The conjugates are still antimicrobially active and up to 20 times more stable against penicillinase catalyzed hydrolysis. The antibiotic activity of the conjugates against Staphylococcus aureus in the presence of penicillinase is up to 350 times higher compared with the free antibiotics. Conjugates with a second antimicrobial function, a dodecyltrimethylammonium group (DDA-X), at the starting end of the PenG and PenV POx conjugates are more antimicrobially active than the conjugates without DDA-X and show high activity in the presence of penicillinase. For example, the conjugates DDA-X-PEtOx-PenG and DDA-X-PEtOx-PenV are 200 to 350 times more active against S. aureus in the presence of penicillinase and almost as effective as the penicillinase stable cloxacollin (Clox) under these conditions. These conjugates show even greater activity compared to cloxacollin without this enzyme present. Further, both conjugates kill Escherichia coli more effectively than PenG and Clox.

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

Science.gov (United States)

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

2010-09-01

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

Enantioselective skin permeation of ibuprofen enantiomers: mechanistic insights from ATR-FTIR and CLSM studies based on synthetic enantiomers as naphthalimide fluorescent probes.

Science.gov (United States)

Che, Qi-en; Quan, Peng; Mu, Mao; Zhang, Xinfu; Zhao, Hanqing; Zhang, Yu; You, Song; Xiao, Yi; Fang, Liang

2014-10-01

The aim of this study was to investigate the mechanisms of different skin permeability of ibuprofen racemate and enantiomers. The percutaneous permeation of ibuprofen racemate and enantiomers through rabbit normal skin and damaged skin (without stratum corneum [SC]) was investigated in vitro using side-by-side diffusion cells. With the melting temperature-membrane transport model, the flux ratio of enantiomer/racemate was calculated from their thermodynamic properties obtained by differential scanning calorimetry. Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) study was performed to evaluate the interaction between the enantiomers and the SC. New fluorescent probes were designed and utilized in confocal laser scanning microscopy (CLSM) study for visualization of the enantioselective permeation of the enantiomers through the intact rabbit skin. The flux of (S)-ibuprofen through normal skin was significantly higher than that of (RS)-ibuprofen and (R)-ibuprofen (p skin, there was no significant difference (p > 0.05). The predicted flux ratio of (S)-ibuprofen/(RS)-ibuprofen (2.50) was in close agreement with the experimentally determined ratio (2.48). These results were supported by ATR-FTIR and CLSM studies that indicated that a chiral environment of the skin led to the enantioselective permeation of enantiomers. The chiral nature of the SC and the different physicochemical properties of the enantiomers should be taken into account in the assessment of different skin permeability of the racemate and enantiomers. The synthetic fluorescent probes used in this study could visualize the enantioselective permeation of the chiral compounds across the skin.

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

Approximate error conjugation gradient minimization methods

Science.gov (United States)

Kallman, Jeffrey S

2013-05-21

In one embodiment, a method includes selecting a subset of rays from a set of all rays to use in an error calculation for a constrained conjugate gradient minimization problem, calculating an approximate error using the subset of rays, and calculating a minimum in a conjugate gradient direction based on the approximate error. In another embodiment, a system includes a processor for executing logic, logic for selecting a subset of rays from a set of all rays to use in an error calculation for a constrained conjugate gradient minimization problem, logic for calculating an approximate error using the subset of rays, and logic for calculating a minimum in a conjugate gradient direction based on the approximate error. In other embodiments, computer program products, methods, and systems are described capable of using approximate error in constrained conjugate gradient minimization problems.

Aptamer-conjugated and drug-loaded acoustic droplets for ultrasound theranosis.

Science.gov (United States)

Wang, Chung-Hsin; Kang, Shih-Tsung; Lee, Ya-Hsuan; Luo, Yun-Ling; Huang, Yu-Fen; Yeh, Chih-Kuang

2012-02-01

Tumor therapy requires multi-functional treatment strategies with specific targeting of therapeutics to reduce general toxicity and increase efficacy. In this study we fabricated and functionally tested aptamer-conjugated and doxorubicin (DOX)-loaded acoustic droplets comprising cores of liquid perfluoropentane compound and lipid-based shell materials. Conjugation of sgc8c aptamers provided the ability to specifically target CCRF-CEM cells for both imaging and therapy. High-intensity focused ultrasound (HIFU) was introduced to trigger targeted acoustic droplet vaporization (ADV) which resulted in both mechanical cancer cell destruction by inertial cavitation and chemical treatment through localized drug release. HIFU insonation showed a 56.8% decrease in cell viability with aptamer-conjugated droplets, representing a 4.5-fold increase in comparison to non-conjugated droplets. In addition, the fully-vaporized droplets resulted in the highest DOX uptake by cancer cells, compared to non-vaporized or partially vaporized droplets. Optical studies clearly illustrated the transient changes that occurred upon ADV of droplet-targeted CEM cells, and B-mode ultrasound imaging revealed contrast enhancement by ADV in ultrasound images. In conclusion, our fabricated droplets functioned as a hybrid chemical and mechanical strategy for the specific destruction of cancer cells upon ultrasound-mediated ADV, while simultaneously providing ultrasound imaging capability. Copyright © 2011 Elsevier Ltd. All rights reserved.

Enhancement of anti-tumor activity of hybrid peptide in conjugation with carboxymethyl dextran via disulfide linkers.

Science.gov (United States)

Gaowa, Arong; Horibe, Tomohisa; Kohno, Masayuki; Tabata, Yasuhiko; Harada, Hiroshi; Hiraoka, Masahiro; Kawakami, Koji

2015-05-01

To improve the anti-tumor activity of EGFR2R-lytic hybrid peptide, we prepared peptide-modified dextran conjugates with the disulfide bonds between thiolated carboxymethyl dextran (CMD-Cys) and cysteine-conjugated peptide (EGFR2R-lytic-Cys). In vitro release studies showed that the peptide was released from the CMD-s-s-peptide conjugate in a concentration-dependent manner in the presence of glutathione (GSH, 2μM-2mM). The CMD-s-s-peptide conjugate exhibited a similar cytotoxic activity with free peptide alone against human pancreatic cancer BxPC-3 cells in vitro. Furthermore, it was shown that the CMD-s-s-peptide conjugates were highly accumulated in tumor tissue in a mouse xenograft model using BxPC-3 cells, and the anti-tumor activity of the conjugate was more effective than that of the free peptide. In addition, the plasma concentrations of peptide were moderately increased and the elimination half-life of the peptide was prolonged after intravenous injection of CMD-s-s-peptide conjugates. These results demonstrated that the conjugate based on thiolated CMD polymer would be potentially useful carriers for the sustained release of the hybrid peptide in vivo. Copyright © 2015 Elsevier B.V. All rights reserved.

Controlled gas-liquid interfacial plasmas for synthesis of nano-bio-carbon conjugate materials

Science.gov (United States)

Kaneko, Toshiro; Hatakeyama, Rikizo

2018-01-01

Plasmas generated in contact with a liquid have been recognized to be a novel reactive field in nano-bio-carbon conjugate creation because several new chemical reactions have been yielded at the gas-liquid interface, which were induced by the physical dynamics of non-equilibrium plasmas. One is the ion irradiation to a liquid, which caused the spatially selective dissociation of the liquid and the generation of additive reducing and oxidizing agents, resulting in the spatially controlled synthesis of nanostructures. The other is the electron irradiation to a liquid, which directly enhanced the reduction action at the plasma-liquid interface, resulting in temporally controlled nanomaterial synthesis. Using this novel reaction field, gold nanoparticles with controlled interparticle distance were synthesized using carbon nanotubes as a template. Furthermore, nanoparticle-biomolecule conjugates and nanocarbon-biomolecule conjugates were successfully synthesized by an aqueous-solution contact plasma and an electrolyte plasma, respectively, which were rapid and low-damage processes suitable for nano-bio-carbon conjugate materials.

Formation of Conjugated Double Bonds to Induce Polystyrene Conductivity by using Different Concentrations of Methoxo-Oxo Bis (8-Quinolyloxo Vanadium (V

Directory of Open Access Journals (Sweden)

Basim Mohamad Hasan

2017-02-01

Full Text Available The effect of different concentrations of additive compound methoxo–oxo bis (8-quinolyloxo vanadium (v on formation of conjugated double bonds as part of photo transformation of polystyrene has been investigated. The UV-Vis spectrophotometery has been used in this work. The results are show that additive concentrations applied increase the formation of conjugated double bond as compared with polystyrene. In this study methoxo – oxo bis (8-quinolyloxo vanadium (v indicates great activity to enhance the conductivity of polystyrene by formation of conjugated double bonds.

Enantioselective biotransformation of propranolol to the active metabolite 4-hydroxypropranolol by endophytic fungi

Directory of Open Access Journals (Sweden)

Keyller Bastos Borges

2011-01-01

Full Text Available The enantioselective biotransformation of propranolol (Prop by the endophytic fungi Phomopsis sp., Glomerella cingulata, Penicillium crustosum, Chaetomium globosum and Aspergillus fumigatus was investigated by studying the kinetics of the aromatic hydroxylation reaction with the formation of 4-hydroxypropranolol (4-OH-Prop. Both Prop enantiomers were consumed by the fungi in the biotransformation process, but the 4-hydroxylation reaction yielded preferentially (--(S-4-OH-Prop. The quantity of metabolites biosynthesized varied slightly among the evaluated endophytic fungi. These results show that all investigated endophytic fungi could be used as biosynthetic tools in biotransformation processes to obtain the enantiomers of 4-OH-Prop.

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.

Zero-energy modes, charge conjugation, and fermion number

International Nuclear Information System (INIS)

Sudarshan, E.C.G.; Yajnik, U.A.

1986-01-01

States with a half-integer fermion number occur when a fermionic field coupled to a soliton possesses a zero mode. This paper spells out the circumstances under which one can retain an integer fermion number as also a charge-conjugation-invariant ground state. It is necessary to make the representation reducible but it is kept irreducible by introducing an additional operator

Synthesis of Novel C-2- or C-15-Labeled BODIPY—Estrone Conjugates

Directory of Open Access Journals (Sweden)

Ildikó Bacsa

2018-04-01

Full Text Available Novel BODIPY–estrone conjugates were synthesized via Cu(I-catalyzed azide–alkyne cycloaddition (CuAAC. Estrone-alkynes or an estrone-azide as starting compounds were synthesized via Michael addition or Sonogashira reaction as key steps. Fluorescent dyes based on BODIPY-core were provided by azide or alkyne functional groups. Fluorescent labeling of estrone was efficiently achieved at the C-2 or C-15 position. The newly-elaborated coupling procedures might have a broad applicability in the synthesis of fluorescent-labeled estrone conjugates suitable for biological assays.

Chemical de-conjugation for investigating the stability of small molecule drugs in antibody-drug conjugates.

Science.gov (United States)

Chen, Tao; Su, Dian; Gruenhagen, Jason; Gu, Christine; Li, Yi; Yehl, Peter; Chetwyn, Nik P; Medley, Colin D

2016-01-05

Antibody-drug conjugates (ADCs) offer new therapeutic options for advanced cancer patients through precision killing with fewer side effects. The stability and efficacy of ADCs are closely related, emphasizing the urgency and importance of gaining a comprehensive understanding of ADC stability. In this work, a chemical de-conjugation approach was developed to investigate the in-situ stability of the small molecule drug while it is conjugated to the antibody. This method involves chemical-mediated release of the small molecule drug from the ADC and subsequent characterization of the released small molecule drug by HPLC. The feasibility of this technique was demonstrated utilizing a model ADC containing a disulfide linker that is sensitive to the reducing environment within cancer cells. Five reducing agents were screened for use in de-conjugation; tris(2-carboxyethyl) phosphine (TCEP) was selected for further optimization due to its high efficiency and clean impurity profile. The optimized de-conjugation assay was shown to have excellent specificity and precision. More importantly, it was shown to be stability indicating, enabling the identification and quantification of the small molecule drug and its degradation products under different formulation pHs and storage temperatures. In summary, the chemical de-conjugation strategy demonstrated here offers a powerful tool to assess the in-situ stability of small molecule drugs on ADCs and the resulting information will shed light on ADC formulation/process development and storage condition selection. Copyright © 2015 Elsevier B.V. All rights reserved.

Conjugative Plasmid Transfer in Xylella fastidiosa Is Dependent on tra and trb Operon Functions

OpenAIRE

Burbank, Lindsey P.; Van Horn, Christopher R.

2017-01-01

The insect-transmitted plant pathogen Xylella fastidiosa is capable of efficient horizontal gene transfer (HGT) and recombination. Natural transformation occurs at high rates in X. fastidiosa, but there also is evidence that certain strains of X. fastidiosa carry native plasmids equipped with transfer and mobilization genes, suggesting conjugation as an additional mechanism of HGT in some instances. Two operons, tra and trb, putatively encoding a conjugative type IV secretion system, are foun...

Photoluminescence in conjugated polymers

International Nuclear Information System (INIS)

Furst, J.E.; Laugesen, R.; Dastoor, P.; McNeill, C.

2002-01-01

Full text: Conjugated polymers combine the electronic and optical properties of semiconductors with the processability of polymers. They contain a sequence of alternate single and double carbon bonds so that the overlap of unhybridised p z orbitals creates a delocalised ρ system which gives semiconducting properties with p-bonding (valence) and p* -antibonding (conduction) bands. Photoluminesence (PL) in conjugated polymers results from the radiative decay of singlet excitons confined to a single chain. The present work is the first in a series of studies in our laboratory that will characterize the optical properties of conjugated polymers. The experiment involves the illumination of thin films of conjugated polymer with UV light (I=360 nm) and observing the subsequent fluorescence using a custom-built, fluorescence spectrometer. Photoluminesence spectra provide basic information about the structure of the polymer film. A typical spectrum is shown in the accompanying figure. The position of the first peak is related to the polymer chain length and resolved multiple vibronic peaks are an indication of film structure and morphology. We will also present results related to the optical degradation of these materials when exposed to air and UV light

Bio-Conjugates for Nanoscale Applications

DEFF Research Database (Denmark)

Villadsen, Klaus

Bio-conjugates for Nanoscale Applications is the title of this thesis, which covers three different projects in chemical bio-conjugation research, namely synthesis and applications of: Lipidated fluorescent peptides, carbohydrate oxime-azide linkers and N-aryl O-R2 oxyamine derivatives. Lipidated...

Fluorescent nanodiamond-bacteriophage conjugates maintain host specificity.

Science.gov (United States)

Trinh, Jimmy T; Alkahtani, Masfer H; Rampersaud, Isaac; Rampersaud, Arfaan; Scully, Marlan; Young, Ryland F; Hemmer, Philip; Zeng, Lanying

2018-06-01

Rapid identification of specific bacterial strains within clinical, environmental, and food samples can facilitate the prevention and treatment of disease. Fluorescent nanodiamonds (FNDs) are being developed as biomarkers in biology and medicine, due to their excellent imaging properties, ability to accept surface modifications, and lack of toxicity. Bacteriophages, the viruses of bacteria, can have exquisite specificity for certain hosts. We propose to exploit the properties of FNDs and phages to develop phages conjugated with FNDs as long-lived fluorescent diagnostic reagents. In this study, we develop a simple procedure to create such fluorescent probes by functionalizing the FNDs and phages with streptavidin and biotin, respectively. We find that the FND-phage conjugates retain the favorable characteristics of the individual components and can discern their proper host within a mixture. This technology may be further explored using different phage/bacteria systems, different FND color centers and alternate chemical labeling schemes for additional means of bacterial identification and new single-cell/virus studies. © 2018 Wiley Periodicals, Inc.

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.

Interplay of alternative conjugated pathways and steric interactions on the electronic and optical properties of donor-acceptor conjugated polymers

KAUST Repository

Lima, Igo T.; Risko, Chad; Aziz, Saadullah Gary; Da Silva Filho, Demé trio A Da Silva; Bredas, Jean-Luc

2014-01-01

Donor-acceptor π-conjugated copolymers are of interest for a wide range of electronic applications, including field-effect transistors and solar cells. Here, we present a density functional theory (DFT) study of the impact of varying the conjugation pathway on the geometric, electronic, and optical properties of donor-acceptor systems. We consider both linear ("in series"), traditional conjugation among the donor-acceptor moieties versus structures where the acceptor units are appended orthogonally to the linear, donor-only conjugated backbone. Long-range-corrected hybrid functionals are used in the investigation with the values of the tuned long-range separation parameters providing an estimate of the extent of conjugation as a function of the oligomer architecture. Considerable differences in the electronic and optical properties are determined as a function of the nature of the conjugation pathway, features that should be taken into account in the design of donor-acceptor copolymers.

Novel Luminescent Multilayer Films Containing π-Conjugated Anionic Polymer with Electronic Microenvironment

Directory of Open Access Journals (Sweden)

Tianlei Wang

2016-09-01

Full Text Available Layered double hydroxides (LDHs, luminescent π-conjugated anionic polymer and montmorillonite (MMT were orderly assembled into luminescent multilayer films via layer-by-layer self-assembly method. The electronic microenvironment (EME, the structure of which is like a traditional capacitor, can be constructed by exfoliated LDHs or MMT nanosheets. In addition, the rigid inorganic laminated configuration can offer stable surroundings between the interlayers. As a result, we conclude that EME can extend the luminescent lifespans of multilayer films substantially, due to affecting relaxation times of π-conjugated anionic polymer. Consequently, because of the remarkable impact on better photoemission behaviors of luminescent π-conjugated anionic polymer, EME assembled by LDHs or MMT nanosheets have had high hopes attached to them. They are expected to have the potential for designing, constructing, and investigating novel light-emitting thin films.

Spin-Center Shift-Enabled Direct Enantioselective α-Benzylation of Aldehydes with Alcohols.

Science.gov (United States)

Nacsa, Eric D; MacMillan, David W C

2018-03-07

Nature routinely engages alcohols as leaving groups, as DNA biosynthesis relies on the removal of water from ribonucleoside diphosphates by a radical-mediated "spin-center shift" (SCS) mechanism. Alcohols, however, remain underused as alkylating agents in synthetic chemistry due to their low reactivity in two-electron pathways. We report herein an enantioselective α-benzylation of aldehydes using alcohols as alkylating agents based on the mechanistic principle of spin-center shift. This strategy harnesses the dual activation modes of photoredox and organocatalysis, engaging the alcohol by SCS and capturing the resulting benzylic radical with a catalytically generated enamine. Mechanistic studies provide evidence for SCS as a key elementary step, identify the origins of competing reactions, and enable improvements in chemoselectivity by rational photocatalyst design.

A pH-responsive carboxymethyl dextran-based conjugate as a carrier of docetaxel for cancer therapy.

Science.gov (United States)

Han, Hwa Seung; Lee, Minchang; An, Jae Yoon; Son, Soyoung; Ko, Hyewon; Lee, Hansang; Chae, Yee Soo; Kang, Young Mo; Park, Jae Hyung

2016-05-01

Although docetaxel is available for the treatment of various cancers, its clinical applications are limited by its poor water solubility and toxicity to normal cells, resulting in severe adverse effects. In this study, we synthesized a polymeric conjugate with an acid-labile ester linkage, consisting of carboxymethyl dextran (CMD) and docetaxel (DTX), as a potential anticancer drug delivery system. The conjugate exhibited sustained release of DTX in physiological buffer (pH 7.4), whereas its release rate increased remarkably under mildly acidic conditions (pH < 6.5), mimicking the intracellular environment. Cytotoxicity tests conducted in vitro demonstrated that the conjugate exhibited much higher toxicity to cancer cells under mildly acidic conditions than at physiological buffer (pH 7.4). These results implied that the ester linkage in the conjugate allowed for selective release of biologically active DTX under mildly acidic conditions. The in vivo biodistribution of a Cy5.5-labeled conjugate was observed using the noninvasive optical imaging technique after its systemic administration into tumor-bearing mice. The conjugate was effectively accumulated into the tumor site, which may have been because of an enhanced permeability and retention effect. In addition, in vivo antitumor efficacy of the conjugate was significantly higher than that of free DTX. Overall, the CMD-based conjugate might have promising potential as a carrier of DTX for cancer therapy. © 2015 Wiley Periodicals, Inc.

Micro-Raman and micro-photoluminescence study of bio-conjugated core–shell CdSe/ZnS nanocrystals

Energy Technology Data Exchange (ETDEWEB)

Borkovska, L., E-mail: bork@isp.kiev.ua [V. Lashkaryov Institute of Semiconductor Physics of NASU, pr. Nauky 41, 03028 Kyiv (Ukraine); Korsunska, N.; Stara, T.; Kolomys, O.; Strelchuk, V. [V. Lashkaryov Institute of Semiconductor Physics of NASU, pr. Nauky 41, 03028 Kyiv (Ukraine); Rachkov, O. [The Institute of Molecular Biology and Genetics of NASU, Zabolotnogo Str. 150, 03680 Kyiv (Ukraine); Kryvko, A. [Instituto Politécnico Nacional – ESIME, Av. IPN, Ed. Z4, U.P.A.L.M., 07738 Mexico D.F. (Mexico)

2014-11-15

The micro-Raman and micro-photoluminescence spectra of non-conjugated and conjugated with antibody against S6K2 commercial CdSe/ZnS quantum dots (QDs) were investigated under different excitation wavelengths and at different temperatures. In the photoluminescence (PL) spectra, the additional PL band shifted on 0.6–0.65 eV to higher energies from the CdSe/ZnS QD exciton PL band is revealed. The relative intensity of this band is found to be several times larger in bio-conjugated QDs, than in the non-conjugated ones. The characteristics of both PL bands (the PL intensity, spectral position and half-width of the PL band) vary similarly under continuous laser light irradiation, storage of the QD samples in the atmospheric ambience as well as during the temperature change. In the Raman spectra recorded under excitation resonant with the high-energy PL band, the additional Raman peaks at about 300 cm{sup −1} and 600 cm{sup −1}, which are close to the frequency of LO and 2LO phonons of bulk CdS, are found. It is proposed that alloyed QDs with chemical composition close to CdS are responsible for the additional high-energy PL band. The possible reasons for the formation of the alloyed QDs are discussed.

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.

Organometallic B12-DNA conjugate

DEFF Research Database (Denmark)

Hunger, Miriam; Mutti, Elena; Rieder, Alexander

2014-01-01

Design, synthesis, and structural characterization of a B12-octadecanucleotide are presented herein, a new organometallic B12-DNA conjugate. In such covalent conjugates, the natural B12 moiety may be a versatile vector for controlled in vivo delivery of oligonucleotides to cellular targets in hum...

The Conjugate Acid-Base Chart.

Science.gov (United States)

Treptow, Richard S.

1986-01-01

Discusses the difficulties that beginning chemistry students have in understanding acid-base chemistry. Describes the use of conjugate acid-base charts in helping students visualize the conjugate relationship. Addresses chart construction, metal ions, buffers and pH titrations, and the organic functional groups and nonaqueous solvents. (TW)

Chiral Pyridinium Phosphoramide as a Dual Brønsted Acid Catalyst for Enantioselective Diels-Alder Reaction.

Science.gov (United States)

Nishikawa, Yasuhiro; Nakano, Saki; Tahira, Yuu; Terazawa, Kanako; Yamazaki, Ken; Kitamura, Chitoshi; Hara, Osamu

2016-05-06

Chiral pyridinium phosphoramide 1·HX was designed to be a new class of chiral Brønsted acid catalyst in which both the pyridinium proton and the adjacent imide-like proton activated by the electron-withdrawing pyridinium moiety could work cooperatively as strong dual proton donors. The potential of 1·HX was shown in the enantioselective Diels-Alder reactions of 1-amino dienes with various dienophiles including N-unsubstituted maleimide, which has yet to be successfully used in an asymmetric Diels-Alder reaction.

Radioiodinated iodobenzoyl conjugates of a monoclonal antibody Fab fragment. In vivo comparisons with chloramine-T-labeled Fab

International Nuclear Information System (INIS)

Wilbur, D.S.; Hadley, S.W.; Grant, L.M.; Hylarides, M.D.

1991-01-01

A comparative investigation of the biodistributions of radioiodinated p- and m-iodobenzoyl conjugates of a monoclonal antibody Fab fragment, NR-LU-10 Fab, and the same antibody Fab fragment radioiodinated by the chloramine-T (ChT) method has been carried out in mice. Coinjected, dual-isotope studies in athymic mice with tumor xenografts have demonstrated that there are only minor differences in the in vivo distributions of the iodobenzoyl-labeled Fabs, except in the excretory organs, kidneys, and intestines, where major differences were observed. Similarly, coinjection of either the p-iodobenzoyl or m-iodobenzoyl conjugate of NR-LU-10 Fab with the Fab radioiodinated with ChT/radioiodide into BALB/c mice provided additional data that indicated that the two iodobenzoyl conjugates distributed similar in a number of selected tissues. The tissue-distribution differences of the regioisomeric iodobenzoyl conjugates in relation to the ChT-radioiodinated Fab were large for the stomach and neck, consistent with previous studies. The most notable difference between the two iodobenzoyl conjugates was the kidney activity, where the m-iodobenzoyl conjugate was similar to the directly labeled Fab, but the p-iodobenzoyl-conjugated Fab was higher by nearly a factor of 2

REVIEW ARTICLE Conjugated Hyperbilirubinaemia in Early Infancy ...

African Journals Online (AJOL)

REVIEW ARTICLE Conjugated Hyperbilirubinaemia in Early Infancy. AOK Johnson. Abstract. Conjugated hyperbilirubinaemia exists when the conjugated serum bilirubin level is more than 2 mg/dl or more than 20 per cent of the total serum bilirubin. It is always pathological in early infancy. The causes are many and diverse ...

Surface conjugation of poly (dimethyl siloxane) with itaconic acid-based materials for antibacterial effects

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Birajdar, Mallinath S.; Cho, Hyunjoo; Seo, Youngmin; Choi, Jonghoon; Park, Hansoo

2018-04-01

Poly (dimethyl siloxane) (PDMS) is widely used in various biomedical applications. However, the PDMS surface is known to cause bacterial adhesion and protein absorption issues due to its high hydrophobicity. Therefore, the development of antibacterial and anti-protein products is necessary to prevent these problems. In this study, to improve its antibacterial property and prevent protein adsorption, PDMS surfaces were conjugated with itaconic acid (IA) and poly (itaconic acid) (PIA) via a chemical method. Additionally, IA and PIA were physically blended with PDMS to compare the antibacterial properties of these materials with those of the chemically conjugated PDMS surfaces. The successful synthesis of the PIA polymer structure was confirmed by proton nuclear magnetic resonance (1H NMR) spectroscopy. The successful conjugation of IA and PIA on PDMS was confirmed by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), water contact angle measurements, and microbicinchoninic acid (BCA) protein assay analyses. The PDMS surfaces functionalized with IA and PIA by the conjugation method better prevented protein adsorption than the bare PDMS. Therefore, these surface-conjugated PDMS can be used in various biomedical applications.

3,3'-Diaryl-BINOL phosphoric acids as enantioselective extractants of benzylic primary amines.

Science.gov (United States)

Verkuijl, Bastiaan J V; de Vries, Johannes G; Feringa, Ben L

2011-01-01

We report that 3,3'-diaryl-BINOL phosphoric acids are effective enantioselective extractants in chiral separation methods based on reactive liquid-liquid extraction. These new extractants are capable of separating racemic benzylic primary amine substrates. The effect of the nature of the substituents at the 3,3'-positions of the host were examined as well as the structure of the substrate, together with important parameters such as the organic solvent, the pH of the aqueous phase, and the host stoichiometry. Titration of the substrate with the host was monitored by FTIR, NMR, UV-Vis, and CD spectroscopy, which provided insight into the structure of the host-guest complex involved in extraction. Copyright © 2010 Wiley-Liss, Inc.

Application of optical phase conjugation to plasma diagnostics (invited)

International Nuclear Information System (INIS)

Jahoda, F.C.; Anderson, B.T.; Forman, P.R.; Weber, P.G.

1985-01-01

Several possibilities for plasma diagnostics provided by optical phase conjugation and, in particular, self-pumped phase conjugation in barium titanate (BaTiO 3 ) are discussed. These include placing a plasma within a dye laser cavity equipped with a phase conjugate mirror for intracavity absorption measurements, time differential refractometry with high spatial resolution, and simplified real-time holographic interferometry. The principles of phase conjugation with particular reference to photorefractive media and the special advantages of self-pumped phase conjugation are reviewed prior to the discussion of the applications. Distinctions are made in the applications between those for which photorefractive conjugators are essential and those for which they only offer experimental simplification relative to other types of phase conjugators

Enantioselective toxicities of chiral ionic liquids 1-alkyl-3-methyl imidazolium tartrate on Scenedesmus obliquus.

Science.gov (United States)

Liu, Huijun; Zhang, Xiaoqiang; Dong, Ying; Chen, Caidong; Zhu, Shimin; Ma, Xiangjuan

2015-12-01

Ionic liquids (ILs) are being used in various industries during the last few decades, while the good solubility and high stability of ILs may pose a potential threat to the aquatic environment. Effect of chiral ionic liquids (CILs) 1-alkyl-3-methyl imidazolium tartrate (RMIM T) on Scenedesmus obliquus (S.obliquus) was studied. The growth rate inhibition and cell membrane permeability increased with increasing RMIM T concentration and increasing alkyl chain lengths. The IC50 values of D-(-)-tartrate 1-hexyl-3-methyl imidazolium (D-(-)-HMIM T) were 28.30, 12.23,10.15 and 14.41 mg/L, respectively, at 24, 48, 72 and 96h. While that of L-(+)-tartrate 1-hexyl-3-methyl imidazolium (L-(+)-HMIM T) were 15.97, 7.91, 9.43 and 12.04 mg/L respectively. The concentration of chl a, chl b and chl (a+b) decreased with increasing RMIM T concentration. The chlorophyll fluorescence parameters (F0, Fv/Fm, Fv/F0, Y(II), ETR and NPQ) were affected by RMIM T, indicating that the RMIM T will damage the PSII, inhibit the transmission of excitation energy, decrease the efficiency of photosynthesis. The results showed that there were enantioselective toxicity of RMIM T to algae, and the toxicity of L-(+)-RMIM T was greater than that of D-(-)-RMIM T, but the enantioselective difference becomes smaller with increasing exposure time, and with the increasing carbon chain length of cation, indicating that cation properties may have a larger effect on toxicity than anion properties. Copyright © 2015 Elsevier B.V. All rights reserved.

Molecularly imprinted polymer-matrix nanocomposite for enantioselective electrochemical sensing of D- and L-aspartic acid

International Nuclear Information System (INIS)

Prasad, Bhim Bali; Srivastava, Amrita; Tiwari, Mahavir Prasad

2013-01-01

A new molecularly imprinted polymer-matrix (titanium dioxide nanoparticle/multiwalled carbon nanotubes) nanocomposite was developed for the modification of pencil graphite electrode as an enantioselective sensing probe for aspartic acid isomers, prevalent at ultra trace level in aqueous and real samples. The nanocomposite having many shape complementary cavities was synthesized adopting surface initiated-activators regenerated by electron transfer for atom transfer radical polymerization. The proposed sensor has high stability, nanocomposite uniformity, good reproducibility, and enhanced electrocatalytic activity to respond oxidative peak current of L-aspartic acid quantitatively by differential pulse anodic stripping voltammetry, without any cross-reactivity in real samples. Under the optimized operating conditions, the L-aspartic acid imprinted modified electrode showed a wide linear response for L-aspartic acid within the concentration range 9.98–532.72 ng mL −1 , with the minimum detection limit of 1.73–1.79 ng mL −1 (S/N = 3) in aqueous and real samples. Almost similar stringent limit (1.79 ng mL −1 ) was obtained with cerebrospinal fluid which is typical for the primitive diagnosis of neurological disorders, caused by an acute depletion of L-aspartic acid biomarker, in clinical settings. Highlights: • We have adopted surface initiated-activators regenerated by electron transfer for atom transfer radical polymerization. • This approach takes advantage of the nanostructured ultrathin imprinted film. • Successful enantioselective sensing and ultratrace analysis of D- and L-aspartic acid. • Stringent detection limit without any non-specific false-positive contribution

Molecularly imprinted polymer-matrix nanocomposite for enantioselective electrochemical sensing of D- and L-aspartic acid

Energy Technology Data Exchange (ETDEWEB)

Prasad, Bhim Bali, E-mail: prof.bbpd@yahoo.com; Srivastava, Amrita; Tiwari, Mahavir Prasad

2013-10-15

A new molecularly imprinted polymer-matrix (titanium dioxide nanoparticle/multiwalled carbon nanotubes) nanocomposite was developed for the modification of pencil graphite electrode as an enantioselective sensing probe for aspartic acid isomers, prevalent at ultra trace level in aqueous and real samples. The nanocomposite having many shape complementary cavities was synthesized adopting surface initiated-activators regenerated by electron transfer for atom transfer radical polymerization. The proposed sensor has high stability, nanocomposite uniformity, good reproducibility, and enhanced electrocatalytic activity to respond oxidative peak current of L-aspartic acid quantitatively by differential pulse anodic stripping voltammetry, without any cross-reactivity in real samples. Under the optimized operating conditions, the L-aspartic acid imprinted modified electrode showed a wide linear response for L-aspartic acid within the concentration range 9.98–532.72 ng mL{sup −1}, with the minimum detection limit of 1.73–1.79 ng mL{sup −1} (S/N = 3) in aqueous and real samples. Almost similar stringent limit (1.79 ng mL{sup −1}) was obtained with cerebrospinal fluid which is typical for the primitive diagnosis of neurological disorders, caused by an acute depletion of L-aspartic acid biomarker, in clinical settings. Highlights: • We have adopted surface initiated-activators regenerated by electron transfer for atom transfer radical polymerization. • This approach takes advantage of the nanostructured ultrathin imprinted film. • Successful enantioselective sensing and ultratrace analysis of D- and L-aspartic acid. • Stringent detection limit without any non-specific false-positive contribution.

Molecular design toward highly efficient photovoltaic polymers based on two-dimensional conjugated benzodithiophene.

Science.gov (United States)

Ye, Long; Zhang, Shaoqing; Huo, Lijun; Zhang, Maojie; Hou, Jianhui

2014-05-20

As researchers continue to develop new organic materials for solar cells, benzo[1,2-b:4,5-b']dithiophene (BDT)-based polymers have come to the fore. To improve the photovoltaic properties of BDT-based polymers, researchers have developed and applied various strategies leading to the successful molecular design of highly efficient photovoltaic polymers. Novel polymer materials composed of two-dimensional conjugated BDT (2D-conjugated BDT) have boosted the power conversion efficiency of polymer solar cells (PSCs) to levels that exceed 9%. In this Account, we summarize recent progress related to the design and synthesis of 2D-conjugated BDT-based polymers and discuss their applications in highly efficient photovoltaic devices. We introduce the basic considerations for the construction of 2D-conjugated BDT-based polymers and systematic molecular design guidelines. For example, simply modifying an alkoxyl-substituted BDT to form an alkylthienyl-substituted BDT can improve the polymer hole mobilities substantially with little effect on their molecular energy level. Secondly, the addition of a variety of chemical moieties to the polymer can produce a 2D-conjugated BDT unit with more functions. For example, the introduction of a conjugated side chain with electron deficient groups (such as para-alkyl-phenyl, meta-alkoxyl-phenyl, and 2-alkyl-3-fluoro-thienyl) allowed us to modulate the molecular energy levels of 2D-conjugated BDT-based polymers. Through the rational design of BDT analogues such as dithienobenzodithiophene (DTBDT) or the insertion of larger π bridges, we can tune the backbone conformations of these polymers and modulate their photovoltaic properties. We also discuss the influence of 2D-conjugated BDT on polymer morphology and the blends of these polymers with phenyl-C61 (or C71)-butyric acid methyl ester (PCBM). Finally, we summarize the various applications of the 2D-conjugated BDT-based polymers in highly efficient PSC devices. Overall, this Account

The effect of high concentration additive on chiral separations in supercritical fluid chromatography.

Science.gov (United States)

Speybrouck, David; Doublet, Charline; Cardinael, Pascal; Fiol-Petit, Catherine; Corens, David

2017-08-11

Supercritical Fluid Chromatography is frequently used to efficiently handle separations of enantiomers. The separation of basic analytes usually requires the addition of a basic additive in the mobile phase to improve the peak shape or even to elute the compounds. The effect of increasing the concentration of 2-propylamine as additive on the elution of a series of basic compounds on a Chiralpak-AD stationary phase was studied. In this study, unusual additive concentrations ranging from 0.3% to 10% of 2-propylamine 2-propylaminein the modifier were explored and the effect on retention, peak shape, selectivity and resolution was evaluated. The addition of a large quantity of additive allowed to drastically improve the selectivity and the resolution, and even enantiomers elution order reversal was observed by changing the concentration of basic additive. The role of the ratio additive/modifier appeared a key to tune the enantioselectivity. Finally, the impact of these drastic conditions on the column material was evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

The studies on the preparation of hapten conjugates for extension of the applicability of radioligandassay

International Nuclear Information System (INIS)

Kim, J.

1979-01-01

The stability of T 4 - 125 I has been secured by addition of a small amount of cysteine in the T 4 - 125 I solution. Various methods for the preparation of thyroid hormone-BSA conjugates were reviewed and an efficient preparation method as well as a qualitative and quantitative analysis procedures for the conjugates has been established. The results of analysis of the prepared hapten conjugates indicated that the mole ratios of BSA: T 3 (acid form) and BSA: T 4 (ethyl ester form) are 1:12 and 1:10, respectively, and the binding % of T 3 (acid form) and T 4 (ethyl ester form) to BSA molecule are 25% and 20%, respectively. (author)

A stereo-controlled route to conjugated E-enediynes

Institute of Scientific and Technical Information of China (English)

ZHOU Lei; JIANG Huanfeng

2007-01-01

3-Ene-1,5-diynes are important components of many enediyne antitumor agents and luminescent materials.A stereo-controlled approach to the synthesis of E-enediynes was developed,and it consists of the following two steps:(1)a mild and economical synthesis of dihalo vinyl derivatives via addition of CuBr2 to alkynes;(2) the Sonogashira coupling reaction of the dihalo vinyl derivatives with terminal alkynes to form conjugated enediynes.

The Gas-Phase Photophysics of Eosin Y and its Maleimide Conjugate.

Science.gov (United States)

Daly, Steven; Kulesza, Alexander; Knight, Geoffrey; MacAleese, Luke; Antoine, Rodolphe; Dugourd, Philippe

2016-05-26

The use of the xanthene family of dyes as fluorescent probes in a wide range of applications has provided impetus for the studying of their photophysical properties. In particular, recent advances in gas-phase techniques such as FRET that utilize such chromophores have placed a greater importance on the characterization of these properties in the gas phase. Additionally, the use of synthetic linker chains to graft the chromophores in a site-specific manner to their target system is ubiquitous. There is, however, often limited information on how the addition of such a linker chain may affect the photophysical properties of the chromophores, which is of fundamental importance for interpretation of experimental data reliant on grafted chromophores. Here, we present data on the optical spectroscopy of different protonation states of Eosin Y, a fluorescein derivative. We compare the photophysics of Eosin Y to its maleimide conjugate, and to the thioether product of the reaction of this conjugate with cysteamine. Comparison of the mass spectra following laser irradiation shows that very different relaxation takes place upon addition of the maleimide moiety but that the photophysics of the bare chromophore are restored upon addition of cysteamine. This radical change in the photophysics is interpreted in terms of charge-transfer states, whose energy relative to the S1 ← S0 transition of the chromophore is dependent on the conjugation of the maleimide moiety. We also show that the shape of the absorption band is unchanged in the gas-phase as compared to the solution-phase, showing a maximum with a shoulder toward the blue, and examination of isotope distributions of the isolated ions show that this shoulder cannot be due to the presence of dimers. Consideration of the fluorescence emission spectrum allows a tentative assignment of the shoulder to be due to a vibrational progression with a high Franck-Condon factor.

Methotrexate and epirubicin conjugates as potential antitumor drugs

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Szymon Wojciech Kmiecik

2017-07-01

Full Text Available Introduction: The use of hybrid molecules has become one of the most significant approaches in new cytotoxic drug design. This study describes synthesis and characterization of conjugates consisting of two well-known and characterized chemotherapeutic agents: methotrexate (MTX and epirubicin (EPR. The synthesized conjugates combine two significant anticancer strategies: combinatory therapy and targeted therapy. These two drugs were chosen because they have different mechanisms of action, which can increase the anticancer effect of the obtained conjugates. MTX, which is a folic acid analog, has high cytotoxic properties and can serve as a targeting moiety that can reach folate receptors (FRs overexpresing tumor cells. Combination of nonselective drugs such as EPR with MTX can increase the selectivity of the obtained conjugates, while maintaining the high cytotoxic properties.Materials and methods: Conjugates were purified by RP-HPLC and the structure was investigated by MS and MS/MS methods. The effect of the conjugates on proliferation of LoVo, LoVo/Dx, MCF-7 and MV-4-11 human cancer cell lines was determined by SRB or MTT assay.Results: The conjugation reaction results in the formation of monosubstituted (α, γ and disubstituted MTX derivatives. In vitro proliferation data demonstrate that the conjugates synthesized in our study show lower cytotoxic properties than both chemotherapeutics used alone.Discussion: Epirubicin cytotoxicity was not observed in obtained conjugates. Effective drugs release after internalization needs further investigation.

Analysis of anabolic androgenic steroids as sulfate conjugates using high performance liquid chromatography coupled to tandem mass spectrometry.

Science.gov (United States)

Rzeppa, S; Heinrich, G; Hemmersbach, P

2015-01-01

Improvements in doping analysis can be effected by speeding up analysis time and extending the detection time. Therefore, direct detection of phase II conjugates of doping agents, especially anabolic androgenic steroids (AAS), is proposed. Besides direct detection of conjugates with glucuronic acid, the analysis of sulfate conjugates, which are usually not part of the routine doping control analysis, can be of high interest. Sulfate conjugates of methandienone and methyltestosterone metabolites have already been identified as long-term metabolites. This study presents the synthesis of sulfate conjugates of six commonly used AAS and their metabolites: trenbolone, nandrolone, boldenone, methenolone, mesterolone, and drostanolone. In the following these sulfate conjugates were used for development of a fast and easy analysis method based on sample preparation using solid phase extraction with a mixed-mode sorbent and detection by high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Validation demonstrated the suitability of the method with regard to the criteria given by the technical documents of the World Anti-Doping Agency (WADA). In addition, suitability has been proven by successful detection of the synthesized sulfate conjugates in excretion urines and routine doping control samples. Copyright © 2015 John Wiley & Sons, Ltd.

Inhibition of bacterial conjugation by phage M13 and its protein g3p: quantitative analysis and model.

Directory of Open Access Journals (Sweden)

Abraham Lin

Full Text Available Conjugation is the main mode of horizontal gene transfer that spreads antibiotic resistance among bacteria. Strategies for inhibiting conjugation may be useful for preserving the effectiveness of antibiotics and preventing the emergence of bacterial strains with multiple resistances. Filamentous bacteriophages were first observed to inhibit conjugation several decades ago. Here we investigate the mechanism of inhibition and find that the primary effect on conjugation is occlusion of the conjugative pilus by phage particles. This interaction is mediated primarily by phage coat protein g3p, and exogenous addition of the soluble fragment of g3p inhibited conjugation at low nanomolar concentrations. Our data are quantitatively consistent with a simple model in which association between the pili and phage particles or g3p prevents transmission of an F plasmid encoding tetracycline resistance. We also observe a decrease in the donor ability of infected cells, which is quantitatively consistent with a reduction in pili elaboration. Since many antibiotic-resistance factors confer susceptibility to phage infection through expression of conjugative pili (the receptor for filamentous phage, these results suggest that phage may be a source of soluble proteins that slow the spread of antibiotic resistance genes.

Growth hormone-releasing peptide-biotin conjugate stimulates myocytes differentiation through insulin-like growth factor-1 and collagen type I.

Science.gov (United States)

Lim, Chae Jin; Jeon, Jung Eun; Jeong, Se Kyoo; Yoon, Seok Jeong; Kwon, Seon Deok; Lim, Jina; Park, Keedon; Kim, Dae Yong; Ahn, Jeong Keun; Kim, Bong-Woo

2015-09-01

Based on the potential beneficial effects of growth hormone releasing peptide (GHRP)-6 on muscle functions, a newly synthesized GHRP-6-biotin conjugate was tested on cultured myoblast cells. Increased expression of myogenic marker proteins was observed in GHRP-6-biotin conjugate-treated cells. Additionally, increased expression levels of insulin-like growth factor-1 and collagen type I were observed. Furthermore, GHRP-6-biotin conjugate-treated cells showed increased metabolic activity, as indicated by increased concentrations of energy metabolites, such as ATP and lactate, and increased enzymatic activity of lactate dehydrogenase and creatine kinase. Finally, binding protein analysis suggested few candidate proteins, including desmin, actin, and zinc finger protein 691 as potential targets for GHRP6-biotin conjugate action. These results suggest that the newly synthesized GHRP-6-biotin conjugate has myogenic stimulating activity through, at least in part, by stimulating collagen type I synthesis and several key proteins. Practical applications of the GHRP-6-biotin conjugate could include improving muscle condition.

The Bacillus subtilis Conjugative Plasmid pLS20 Encodes Two Ribbon-Helix-Helix Type Auxiliary Relaxosome Proteins That Are Essential for Conjugation

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Andrés Miguel-Arribas

2017-11-01

Full Text Available Bacterial conjugation is the process by which a conjugative element (CE is transferred horizontally from a donor to a recipient cell via a connecting pore. One of the first steps in the conjugation process is the formation of a nucleoprotein complex at the origin of transfer (oriT, where one of the components of the nucleoprotein complex, the relaxase, introduces a site- and strand specific nick to initiate the transfer of a single DNA strand into the recipient cell. In most cases, the nucleoprotein complex involves, besides the relaxase, one or more additional proteins, named auxiliary proteins, which are encoded by the CE and/or the host. The conjugative plasmid pLS20 replicates in the Gram-positive Firmicute bacterium Bacillus subtilis. We have recently identified the relaxase gene and the oriT of pLS20, which are separated by a region of almost 1 kb. Here we show that this region contains two auxiliary genes that we name aux1LS20 and aux2LS20, and which we show are essential for conjugation. Both Aux1LS20 and Aux2LS20 are predicted to contain a Ribbon-Helix-Helix DNA binding motif near their N-terminus. Analyses of the purified proteins show that Aux1LS20 and Aux2LS20 form tetramers and hexamers in solution, respectively, and that they both bind preferentially to oriTLS20, although with different characteristics and specificities. In silico analyses revealed that genes encoding homologs of Aux1LS20 and/or Aux2LS20 are located upstream of almost 400 relaxase genes of the RelLS20 family (MOBL of relaxases. Thus, Aux1LS20 and Aux2LS20 of pLS20 constitute the founding member of the first two families of auxiliary proteins described for CEs of Gram-positive origin.

The Bacillus subtilis Conjugative Plasmid pLS20 Encodes Two Ribbon-Helix-Helix Type Auxiliary Relaxosome Proteins That Are Essential for Conjugation.

Science.gov (United States)

Miguel-Arribas, Andrés; Hao, Jian-An; Luque-Ortega, Juan R; Ramachandran, Gayetri; Val-Calvo, Jorge; Gago-Córdoba, César; González-Álvarez, Daniel; Abia, David; Alfonso, Carlos; Wu, Ling J; Meijer, Wilfried J J

2017-01-01

Bacterial conjugation is the process by which a conjugative element (CE) is transferred horizontally from a donor to a recipient cell via a connecting pore. One of the first steps in the conjugation process is the formation of a nucleoprotein complex at the origin of transfer ( oriT ), where one of the components of the nucleoprotein complex, the relaxase, introduces a site- and strand specific nick to initiate the transfer of a single DNA strand into the recipient cell. In most cases, the nucleoprotein complex involves, besides the relaxase, one or more additional proteins, named auxiliary proteins, which are encoded by the CE and/or the host. The conjugative plasmid pLS20 replicates in the Gram-positive Firmicute bacterium Bacillus subtilis . We have recently identified the relaxase gene and the oriT of pLS20, which are separated by a region of almost 1 kb. Here we show that this region contains two auxiliary genes that we name aux1 LS20 and aux2 LS20 , and which we show are essential for conjugation. Both Aux1 LS20 and Aux2 LS20 are predicted to contain a Ribbon-Helix-Helix DNA binding motif near their N-terminus. Analyses of the purified proteins show that Aux1 LS20 and Aux2 LS20 form tetramers and hexamers in solution, respectively, and that they both bind preferentially to oriT LS20 , although with different characteristics and specificities. In silico analyses revealed that genes encoding homologs of Aux1 LS20 and/or Aux2 LS20 are located upstream of almost 400 relaxase genes of the Rel LS20 family (MOB L ) of relaxases. Thus, Aux1 LS20 and Aux2 LS20 of pLS20 constitute the founding member of the first two families of auxiliary proteins described for CEs of Gram-positive origin.

Effect of Maillard Conjugates on the Physical Stability of Zein Nanoparticles Prepared by Liquid Antisolvent Coprecipitation.

Science.gov (United States)

Davidov-Pardo, Gabriel; Joye, Iris J; Espinal-Ruiz, Mauricio; McClements, David Julian

2015-09-30

Protein nanoparticles are often not very stable in a complex food matrix because they are primarily stabilized by electrostatic repulsion. In this study, we envisaged the stabilization of zein nanoparticles through Maillard conjugation reactions with polysaccharides of different molecular mass. Zein nanoparticles (0.5% w/v) containing resveratrol (0.025% w/v grape skin extract) were produced by liquid antisolvent precipitation and coated with Maillard conjugates (MC) of sodium caseinate and different molecular mass carbohydrates during particle production. Zein nanoparticles coated with conjugated polysaccharides of 2.8, 37, and 150 kDa had diameters of 198 ± 5, 176 ± 6, and 180 ± 3 nm, respectively. The encapsulation efficiency (∼83%) was not affected by conjugation, but the conjugates significantly improved particle stability against changes in pH (2.0-9.0), CaCl2 addition (up to 100 mM), and heat treatment (30-90 °C, 30 min). Zein nanoparticles coated by MC may therefore be suitable delivery systems for hydrophobic bioactive molecules in a wide range of commercial products.

Outer membrane protein complex of Meningococcus enhances the antipolysaccharide antibody response to pneumococcal polysaccharide-CRM₁₉₇ conjugate vaccine.

Science.gov (United States)

Lai, Zengzu; Schreiber, John R

2011-05-01

Bacterial polysaccharides (PS) are T cell-independent antigens that do not induce immunologic memory and are poor immunogens in infants. Conjugate vaccines in which the PS is covalently linked to a carrier protein have enhanced immunogenicity that resembles that of T cell-dependent antigens. The Haemophilus influenzae type b (Hib) conjugate vaccine, which uses the outer membrane protein complex (OMPC) from meningococcus as a carrier protein, elicits protective levels of anti-capsular PS antibody (Ab) after a single dose, in contrast to other conjugate vaccines, which require multiple doses. We have previously shown that OMPC robustly engages Toll-like receptor 2 (TLR2) and enhances the early anti-Hib PS Ab titer associated with an increase in TLR2-mediated induction of cytokines. We now show that the addition of OMPC to the 7-valent pneumococcal PS-CRM₁₉₇ conjugate vaccine during immunization significantly increases the anti-PS IgG and IgM responses to most serotypes of pneumococcus contained in the vaccine. The addition of OMPC also increased the likelihood of anti-PS IgG3 production against serotypes 4, 6B, 9V, 18C, 19F, and 23F. Splenocytes from mice who had received OMPC with the pneumococcal conjugate vaccine produced significantly more interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) than splenocytes from mice who received phosphate-buffered saline (PBS) plus the conjugate vaccine. We conclude that OMPC enhances the anti-PS Ab response to pneumococcal PS-CRM₁₉₇ conjugate vaccine, an effect associated with a distinct change in cytokine profile. It may be possible to reduce the number of conjugate vaccine doses required to achieve protective Ab levels by priming with adjuvants that are TLR2 ligands.

pH-responsive polymer–drug conjugates as multifunctional micelles for cancer-drug delivery

International Nuclear Information System (INIS)

Kang, Yang; Ha, Wei; Ma, Yuan; Ding, Li-Sheng; Li, Bang-Jing; Liu, Ying-Qian; Fan, Min-Min; Zhang, Sheng

2014-01-01

We developed a novel linear pH-sensitive conjugate methoxy poly(ethylene glycol)-4β-aminopodophyllotoxin (mPEG-NPOD-I) by a covalently linked 4β-aminopodophyllotoxin (NPOD) and PEG via imine bond, which was amphiphilic and self-assembled to micelles in an aqueous solution. The mPEG-NPOD-I micelles simultaneously served as an anticancer drug conjugate and as drug carriers. As a drug conjugate, mPEG-NPOD-I showed a significantly faster NPOD release at a mildly acidic pH of 5.0 and 4.0 than a physiological pH of 7.4. Notably, it was confirmed that this drug conjugate could efficiently deliver NPOD to the nuclei of the tumor cells and led to much more cytotoxic effects to A549, Hela, and HepG2 cancer cells than the parent NPOD. The half maximal inhibitory concentration (IC 50 ) of mPEG-NPOD-I was about one order magnitude lower than that of the NPOD. In vivo, mPEG-NPOD-I reduced the size of the tumors significantly, and the biodistribution studies indicated that this drug conjugate could selectively accumulate in tumor tissues. As drug carriers, the mPEG-NPOD-I micelles encapsulated hydrophobic PTX with drug-loading efficiencies of 57% and drug-loading content of 16%. The loaded PTX also showed pH-triggered fast release behavior, and good additive cytotoxicity effect was observed for the PEG-NPOD-I/PTX. We are convinced that these multifunctional drug conjugate micelles have tremendous potential for targeted cancer therapy. (paper)

Brain-targeted delivery of trans-activating transcriptor-conjugated magnetic PLGA/lipid nanoparticles.

Directory of Open Access Journals (Sweden)

Xiangru Wen

Full Text Available Magnetic poly (D,L-lactide-co-glycolide (PLGA/lipid nanoparticles (MPLs were fabricated from PLGA, L-α-phosphatidylethanolamine (DOPE, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-amino (polyethylene glycol (DSPE-PEG-NH2, and magnetic nanoparticles (NPs, and then conjugated to trans-activating transcriptor (TAT peptide. The TAT-MPLs were designed to target the brain by magnetic guidance and TAT conjugation. The drugs hesperidin (HES, naringin (NAR, and glutathione (GSH were encapsulated in MPLs with drug loading capacity (>10% and drug encapsulation efficiency (>90%. The therapeutic efficacy of the drug-loaded TAT-MPLs in bEnd.3 cells was compared with that of drug-loaded MPLs. The cells accumulated higher levels of TAT-MPLs than MPLs. In addition, the accumulation of QD-loaded fluorescein isothiocyanate (FITC-labeled TAT-MPLs in bEnd.3 cells was dose and time dependent. Our results show that TAT-conjugated MPLs may function as an effective drug delivery system that crosses the blood brain barrier to the brain.

Multivalent peptidic linker enables identification of preferred sites of conjugation for a potent thialanstatin antibody drug conjugate.

Directory of Open Access Journals (Sweden)

Sujiet Puthenveetil

Full Text Available Antibody drug conjugates (ADCs are no longer an unknown entity in the field of cancer therapy with the success of marketed ADCs like ADCETRIS and KADCYLA and numerous others advancing through clinical trials. The pursuit of novel cytotoxic payloads beyond the mictotubule inhibitors and DNA damaging agents has led us to the recent discovery of an mRNA splicing inhibitor, thailanstatin, as a potent ADC payload. In our previous work, we observed that the potency of this payload was uniquely tied to the method of conjugation, with lysine conjugates showing much superior potency as compared to cysteine conjugates. However, the ADC field is rapidly shifting towards site-specific ADCs due to their advantages in manufacturability, characterization and safety. In this work we report the identification of a highly efficacious site-specific thailanstatin ADC. The site of conjugation played a critical role on both the in vitro and in vivo potency of these ADCs. During the course of this study, we developed a novel methodology of loading a single site with multiple payloads using an in situ generated multi-drug carrying peptidic linker that allowed us to rapidly screen for optimal conjugation sites. Using this methodology, we were able to identify a double-cysteine mutant ADC delivering four-loaded thailanstatin that was very efficacious in a gastric cancer xenograft model at 3mg/kg and was also shown to be efficacious against T-DM1 resistant and MDR1 overexpressing tumor cell lines.

Multivalent peptidic linker enables identification of preferred sites of conjugation for a potent thialanstatin antibody drug conjugate.

Science.gov (United States)

Puthenveetil, Sujiet; He, Haiyin; Loganzo, Frank; Musto, Sylvia; Teske, Jesse; Green, Michael; Tan, Xingzhi; Hosselet, Christine; Lucas, Judy; Tumey, L Nathan; Sapra, Puja; Subramanyam, Chakrapani; O'Donnell, Christopher J; Graziani, Edmund I

2017-01-01

Antibody drug conjugates (ADCs) are no longer an unknown entity in the field of cancer therapy with the success of marketed ADCs like ADCETRIS and KADCYLA and numerous others advancing through clinical trials. The pursuit of novel cytotoxic payloads beyond the mictotubule inhibitors and DNA damaging agents has led us to the recent discovery of an mRNA splicing inhibitor, thailanstatin, as a potent ADC payload. In our previous work, we observed that the potency of this payload was uniquely tied to the method of conjugation, with lysine conjugates showing much superior potency as compared to cysteine conjugates. However, the ADC field is rapidly shifting towards site-specific ADCs due to their advantages in manufacturability, characterization and safety. In this work we report the identification of a highly efficacious site-specific thailanstatin ADC. The site of conjugation played a critical role on both the in vitro and in vivo potency of these ADCs. During the course of this study, we developed a novel methodology of loading a single site with multiple payloads using an in situ generated multi-drug carrying peptidic linker that allowed us to rapidly screen for optimal conjugation sites. Using this methodology, we were able to identify a double-cysteine mutant ADC delivering four-loaded thailanstatin that was very efficacious in a gastric cancer xenograft model at 3mg/kg and was also shown to be efficacious against T-DM1 resistant and MDR1 overexpressing tumor cell lines.

Comparison of genetic algorithms with conjugate gradient methods

Science.gov (United States)

Bosworth, J. L.; Foo, N. Y.; Zeigler, B. P.

1972-01-01

Genetic algorithms for mathematical function optimization are modeled on search strategies employed in natural adaptation. Comparisons of genetic algorithms with conjugate gradient methods, which were made on an IBM 1800 digital computer, show that genetic algorithms display superior performance over gradient methods for functions which are poorly behaved mathematically, for multimodal functions, and for functions obscured by additive random noise. Genetic methods offer performance comparable to gradient methods for many of the standard functions.

A Spectral Conjugate Gradient Method for Unconstrained Optimization

International Nuclear Information System (INIS)

Birgin, E. G.; Martinez, J. M.

2001-01-01

A family of scaled conjugate gradient algorithms for large-scale unconstrained minimization is defined. The Perry, the Polak-Ribiere and the Fletcher-Reeves formulae are compared using a spectral scaling derived from Raydan's spectral gradient optimization method. The best combination of formula, scaling and initial choice of step-length is compared against well known algorithms using a classical set of problems. An additional comparison involving an ill-conditioned estimation problem in Optics is presented

Degenerate four-wave mixing and phase conjugation in a collisional plasma

International Nuclear Information System (INIS)

Federici, J.F.; Mansfield, D.K.

1986-06-01

Although degenerate four-wave mixing (DFWM) has many practical applications in the visible regime, no successful attempt has been made to study or demonstrate DFWM for wavelengths longer than 10μm. Recently, Steel and Lam established plasma as a viable DFWM and phase conjugation (PC) medium for infrared, far-infrared, and microwaves. However, their analysis is incomplete since collisional effects were not included. Using a fluid description, our results demonstrate that when collisional absorption is small and the collisional mean-free path is shorter than the nonlinear density grating scale length, collisional heating generates a thermal force which substantially enhances the phase conjugate reflectivity. When the collisional attenuation length becomes comparable to the length of the plasma, the dominant effect is collisional absorption of the pump waves. Numerical estimates of the phase conjugate reflectivity indicate that for modest power levels, gains greater than or equal to1 are possible in the submillimeter to centimeter wavelength range. This suggests that a plasma is a viable PC medium at those long wavelengths. In addition, doubly DFWM is discussed

Relationships for electron-vibrational coupling in conjugated π organic systems

Science.gov (United States)

O'Neill, L.; Lynch, P.; McNamara, M.; Byrne, H. J.

2005-06-01

A series of π conjugated systems were studied by absorption, photoluminescence and vibrational spectroscopy. As is common for these systems, a linear relationship between the positioning of the absorption and photoluminescence maxima plotted against inverse conjugation length is observed. The relationships are in good agreement with the simple particle in a box method, one of the earliest descriptions of the properties of one-dimensional organic molecules. In addition to the electronic transition energies, it was observed that the Stokes shift also exhibited a well-defined relationship with increasing conjugation length, implying a correlation between the electron-vibrational coupling and chain length. This correlation is further examined using Raman spectroscopy, whereby the integrated Raman scattering is seen to behave superlinearly with chain length. There is a clear indication that the vibrational activity and thus nonradiative decay processes are controllable through molecular structure. The correlations between the Stokes energies and the vibrational structure are also observed in a selection of PPV based polymers and a clear trend of increasing luminescence efficiency with decreasing vibrational activity and Stokes shift is observable. The implications of such structure property relationships in terms of materials design are discussed.

Meeting the challenge: prevention of pneumococcal disease with conjugate vaccines

Directory of Open Access Journals (Sweden)

Echániz-Avilés Irma Gabriela

2001-01-01

Full Text Available Streptococcus pneumoniae is one of the leading causes of both invasive and noninvasive diseases in the pediatric population and continues to represent a significant public health burden worldwide. The increasing incidence of antibioticresistant strains of the pathogen has complicated treatment and management of the various pneumococcal disease manifestations. Thus, the best management strategy may be the prevention of pneumococcal diseases through vaccination. Although several pneumococcal conjugate vaccines have been clinically studied in infants and children, only a 7-valent conjugate vaccine (PNCRM7; Prevnar®/Prevenar® is currently approved for the prevention of invasive disease. Vaccination with PNCRM7 is safe and effective in infants and young children. Routine vaccination with the conjugate vaccine could improve outcomes by safeguarding against the development of antibiotic-resistant strains of S. pneumoniae, thus simplifying the management of pneumococcal disease. Additionally, the overall costs associated with the treatment of pneumococcal diseases could be substantially reduced, particularly in developing countries. The time has come for fully applying this new advancement against S. pneumoniae, to benefit the children of the world. The Spanish version of this paper is available at: http://www.insp.mx/salud/index.html

Direct Cytoplasmic Delivery and Nuclear Targeting Delivery of HPMA-MT Conjugates in a Microtubules Dependent Fashion.

Science.gov (United States)

Zhong, Jiaju; Zhu, Xi; Luo, Kui; Li, Lian; Tang, Manlin; Liu, Yanxi; Zhou, Zhou; Huang, Yuan

2016-09-06

As the hearts of tumor cells, the nucleus is the ultimate target of many chemotherapeutic agents and genes. However, nuclear drug delivery is always hampered by multiple intracellular obstacles, such as low efficiency of lysosome escape and insufficient nuclear trafficking. Herein, an N-(2-hydroxypropyl) methacrylamide (HPMA) polymer-based drug delivery system was designed, which could achieve direct cytoplasmic delivery by a nonendocytic pathway and transport into the nucleus in a microtubules dependent fashion. A special targeting peptide (MT), derived from an endogenic parathyroid hormone-related protein, was conjugated to the polymer backbone, which could accumulate into the nucleus a by microtubule-mediated pathway. The in vitro studies found that low temperature and NaN3 could not influence the cell internalization of the conjugates. Besides, no obvious overlay of the conjugates with lysosome demonstrated that the polymer conjugates could enter the tumor cell cytoplasm by a nonendocytic pathway, thus avoiding the drug degradation in the lysosome. Furthermore, after suppression of the microtubule dynamics with microtubule stabilizing docetaxel (DTX) and destabilizing nocodazole (Noc), the nuclear accumulation of polymeric conjugates was significantly inhibited. Living cells fluorescence recovery after photobleaching study found that the nuclear import rate of conjugates was 2-fold faster compared with the DTX and Noc treated groups. These results demonstrated that the conjugates transported into the nucleus in a microtubules dependent way. Therefore, in addition to direct cytoplasmic delivery, our peptide conjugated polymeric platform could simultaneously mediate nuclear drug accumulation, which may open a new path for further intracellular genes/peptides delivery.

In Vitro Evaluation of Third Generation PAMAM Dendrimer Conjugates

Directory of Open Access Journals (Sweden)

Mohammad Najlah

2017-10-01

Full Text Available The present study compares the use of high generation G3 and low generation G0 Polyamidoamine (PAMAM dendrimers as drug carriers of naproxen (NAP, a poorly water soluble drug. Naproxen was conjugated to G3 in different ratios and to G0 in a 1:1 ratio via a diethylene glycol linker. A lauroyl chain (L, a lipophilic permeability enhancer, was attached to G3 and G0 prodrugs. The G3 and G0 conjugates were more hydrophilic than naproxen as evaluated by the measurement of partitioning between 1-octanol and a phosphate buffer at pH 7.4 and pH 1.2. The unmodified surface PAMAM-NAP conjugates showed significant solubility enhancements of NAP at pH 1.2; however, with the number of NAP conjugated to G3, this was limited to 10 molecules. The lactate dehydrogenase (LDH assay indicated that the G3 dendrimer conjugates had a concentration dependent toxicity towards Caco-2 cells. Attaching naproxen to the surface of the dendrimer increased the IC50 of the resulting prodrugs towards Caco-2 cells. The lauroyl G3 conjugates showed the highest toxicity amongst the PAMAM dendrimer conjugates investigated and were significantly more toxic than the lauroyl-G0-naproxen conjugates. The permeability of naproxen across monolayers of Caco-2 cells was significantly increased by its conjugation to either G3 or G0 PAMAM dendrimers. Lauroyl-G0 conjugates displayed considerably lower cytotoxicity than G3 conjugates and may be preferable for use as a drug carrier for low soluble drugs such as naproxen.

Enantioselective analysis of propranolol and 4-hydroxypropranolol by CE with application to biotransformation studies employing endophytic fungi.

Science.gov (United States)

Borges, Keyller Bastos; Pupo, Mônica Tallarico; Bonato, Pierina Sueli

2009-11-01

A CE method is described for the enantioselective analysis of propranolol (Prop) and 4-hydroxypropranolol (4-OH-Prop) in liquid Czapek medium with application in the study of the enantioselective biotransformation of Prop by endophytic fungi. The electrophoretic conditions previously optimized were as follows: an uncoated fused-silica capillary, 4% w/v carboxymethyl-beta-CD in 25 mmol/L triethylamine/phosphoric acid (H(3)PO(4)) buffer at pH 9 as running electrolyte and 17 kV of voltage. UV detection was carried out at 208 nm. Liquid-liquid extraction using diethyl ether: ethyl acetate (1:1 v/v) as extractor solvent was employed for sample preparation. The calibration curves were linear over the concentration range of 0.25-10.0 microg/mL for each 4-OH-Prop enantiomer and 0.10-10.0 microg/mL for each Prop enantiomer (r>or=0.995). Within-day and between-day relative standard deviations and relative errors for precision and accuracy were lower than 15% for all the enantiomers. Finally, the validated method was used to evaluate Prop biotransformation in its mammalian metabolite 4-OH-Prop by some selected endophytic fungi. The screening of five strains of endophytic fungi was performed and all of them could biotransform Prop to some extent. Specifically, Glomerella cingulata (VA1) biotransformed 47.8% of (-)-(S)-Prop to (-)-(S)-4-OH-Prop with no formation of (+)-(R)-4-OH-Prop in 72 h of incubation.

CONJUGATED BLOCK-COPOLYMERS FOR ELECTROLUMINESCENT DIODES

NARCIS (Netherlands)

Hilberer, A; Gill, R.E; Herrema, J.K; Malliaras, G.G; Wildeman, J.; Hadziioannou, G

In this article we review results obtained in our laboratory on the design and study of new light-emitting polymers. We are interested in the synthesis and characterisation of block copolymers with regularly alternating conjugated and non conjugated sequences. The blocks giving rise to luminescence

Tetrafullerene conjugates for all-organic photovoltaics

NARCIS (Netherlands)

Fernández, G.; Sánchez, L.; Veldman, D.; Wienk, M.M.; Atienza, C.M.; Guldi, D.M.; Janssen, R.A.J.; Martin, N.

2008-01-01

The synthesis of two new tetrafullerene nanoconjugates in which four C60 units are covalently connected through different -conjugated oligomers (oligo(p-phenylene ethynylene) and oligo(p-phenylene vinylene)) is described. The photovoltaic (PV) response of these C60-based conjugates was evaluated by

Novel Aflatoxin Derivatives and Protein Conjugates

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Reinhard Niessner

2007-03-01

Full Text Available Aflatoxins, a group of structurally related mycotoxins, are well known for their toxic and carcinogenic effects in humans and animals. Aflatoxin derivatives and protein conjugates are needed for diverse analytical applications. This work describes a reliable and fast synthesis of novel aflatoxin derivatives, purification by preparative HPLC and characterisation by ESI-MS and one- and two-dimensional NMR. Novel aflatoxin bovine serum albumin conjugates were prepared and characterised by UV absorption and MALDI-MS. These aflatoxin protein conjugates are potentially interesting as immunogens for the generation of aflatoxin selective antibodies with novel specificities.

Comparison of liquid and supercritical fluid chromatography mobile phases for enantioselective separations on polysaccharide stationary phases.

Science.gov (United States)

Khater, Syame; Lozac'h, Marie-Anne; Adam, Isabelle; Francotte, Eric; West, Caroline

2016-10-07

Analysis and production of enantiomerically pure compounds is a major topic of interest when active pharmaceutical ingredients are concerned. Enantioselective chromatography has become a favourite both at the analytical and preparative scales. High-performance liquid chromatography (HPLC) and supercritical fluid chromatography (SFC) are dominating the scene and are often seen as complementary techniques. Nowadays, for economic and ecologic reasons, SFC may be preferred over normal-phase HPLC (NPLC) as it allows significant reductions in solvent consumption. However, the transfer of NPLC methods to SFC is not always straightforward. In this study, we compare the retention of achiral molecules and separation of enantiomers under supercritical fluid (carbon dioxide with ethanol or isopropanol) and liquid normal-phase (heptane with ethanol or isopropanol) elution modes with polysaccharide stationary phases in order to explore the differences between the retention and enantioseparation properties between the two modes. Chemometric methods (namely quantitative structure-retention relationships and discriminant analysis) are employed to compare the results obtained on a large set of analytes (171 achiral probes and 97 racemates) and gain some understanding on the retention and separation mechanisms. The results indicate that, contrary to popular belief, carbon dioxide - solvent SFC mobile phases are often weaker eluents than liquid mobile phases. It appears that SFC and NPLC elution modes provide different retention mechanisms. While some enantioseparations are unaffected, facilitating the transfer between the two elution modes, other enantioseparations may be drastically different due to different types and strength of interactions contributing to enantioselectivity. Copyright © 2016 Elsevier B.V. All rights reserved.

Structure Property Relationships in Organic Conjugated Systems

OpenAIRE

O'Neill, Luke

2008-01-01

A series of pi(п) conjugated oligomers containing 1 to 6 monomer units were studied by absorption and photoluminescence spectroscopies. The results are discussed and examined with regard to the variation of the optical properties with the increase of effective conjugation length. It was found that there was a linear relationship between the positioning of the absorption and photoluminescence maxima plotted against inverse conjugation length. The relationships are in good agreement with the si...

Sources and Bioactive Properties of Conjugated Dietary Fatty Acids.

Science.gov (United States)

Hennessy, Alan A; Ross, Paul R; Fitzgerald, Gerald F; Stanton, Catherine

2016-04-01

The group of conjugated fatty acids known as conjugated linoleic acid (CLA) isomers have been extensively studied with regard to their bioactive potential in treating some of the most prominent human health malignancies. However, CLA isomers are not the only group of potentially bioactive conjugated fatty acids currently undergoing study. In this regard, isomers of conjugated α-linolenic acid, conjugated nonadecadienoic acid and conjugated eicosapentaenoic acid, to name but a few, have undergone experimental assessment. These studies have indicated many of these conjugated fatty acid isomers commonly possess anti-carcinogenic, anti-adipogenic, anti-inflammatory and immune modulating properties, a number of which will be discussed in this review. The mechanisms through which these bioactivities are mediated have not yet been fully elucidated. However, existing evidence indicates that these fatty acids may play a role in modulating the expression of several oncogenes, cell cycle regulators, and genes associated with energy metabolism. Despite such bioactive potential, interest in these conjugated fatty acids has remained low relative to the CLA isomers. This may be partly attributed to the relatively recent emergence of these fatty acids as bioactives, but also due to a lack of awareness regarding sources from which they can be produced. In this review, we will also highlight the common sources of these conjugated fatty acids, including plants, algae, microbes and chemosynthesis.

Preparation and immunological properties of procaine-protein conjugates

International Nuclear Information System (INIS)

Liakopoulou, A.

1981-01-01

Procaine was conjugated to BSA and rat and rabbit Gf using the carbodiimide method and 14 C-procaine as tracer. The composition of the conjugates could be varied depending on the time of incubation and the concentration of procaine in the reaction mixtures. Procaine-BSA conjugates were soluble in water or saline. However, procaine conjugates to rat or rabbit Gf were not readily soluble in saline. These conjugates were good for immunization purposes, but it was cumbersome to work with them when clear solutions were needed, as in the immunochemical procedures used in this study. The immunological properties of the conjugates were studied in rats and rabbits. Rats responded with production of IgGa and precipitating antibodies to the procaine group, but IgE antibodies to the immunogen could not be detected. Furthermore, precipitating antibodies towards the procaine group were raised in rabbits. When BSA was the protein carrier, antibodies to the carrier molecule were also detected in both rats and rabbits. The conjugates of procaine to rat or rabbit Gf did not elicit antibody response to the carrier molecule when used in the homologous species. Hapten inhibition studies suggested that, in the rabbit, antibodies were also produced with specificity directed towards the molecular configuration of the hapten-carrier bond. (author)

IRDye78 Conjugates for Near-Infrared Fluorescence Imaging

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Atif Zaheer

2002-10-01

Full Text Available The detection of human malignancies by near-infrared (NIR fluorescence will require the conjugation of cancer-specific ligands to NIR fluorophores that have optimal photoproperties and pharmacokinetics. IRDye78, a tetra-sulfonated heptamethine indocyanine NIR fluorophore, meets most of the criteria for an in vivo imaging agent, and is available as an N-hydroxysuccinimide ester for conjugation to low-molecular-weight ligands. However, IRDye78 has a high charge-to-mass ratio, complicating purification of conjugates. It also has a potentially labile linkage between fluorophore and ligand. We have developed an ion-pairing purification strategy for IRDye78 that can be performed with a standard C18 column under neutral conditions, thus preserving the stability of fluorophore, ligand, and conjugate. By employing parallel evaporative light scatter and absorbance detectors, all reactants and products are identified, and conjugate purity is maximized. We describe reversible and irreversible conversions of IRDye78 that can occur during sample purification, and describe methods for preserving conjugate stability. Using seven ligands, spanning several classes of small molecules and peptides (neutral, charged, and/or hydrophobic, we illustrate the robustness of these methods, and confirm that IRDye78 conjugates so purified retain bioactivity and permit NIR fluorescence imaging of specific targets.

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

DEFF Research Database (Denmark)

Sundström, Maria; Escola, Monica; Radke, Michael

2015-01-01

of the sediments in the aquatic systems has neither been taken in account previously. In this study, four water-sediment systems were chosen according to anthropogenic exposure and sediment conditions. A low anthropogenic impact lake (Largen), a river receiving wastewater (Fyrisån) and two sediments (anoxic......As ibuprofen degrades enantioselectively in activated sludge, the same process is assumed to occur in surface lake-water and in river-water based biofilms. Yet, the effects of the wastewater inflow, containing non-racemic ibuprofen, into natural systems have never been studied. The role......-7 days in Tvären and B1 respectively. Largen sediments, not impacted by wastewater, degraded ibuprofen faster than Fyrisån sediments did. Yet, these two sediments sediments showed no significant difference with respect to the degradation rates of the ibuprofen enantiomers. A connection between wastewater...

Catalytic enantioselective addition of organometallic reagents to N-formylimines using monodentate phosphoramidite ligands

NARCIS (Netherlands)

Pizzuti, Maria Gabriella; Minnaard, Adriaan J.; Feringa, Ben L.

2008-01-01

[GRAPHICS] The asymmetric synthesis of protected amines via the copper/phosphoramidite-catalyzed addition of organozine and organoaluminum reagents to N-acylimines, generated in situ from aromatic and aliphatic alpha-amidosulfones, is reported. High yields of optically active N-formyl-protected

Catalytic Enantioselective Addition of Organometallic Reagents to N-Formylimines Using Monodentate Phosphoramidite Ligands

NARCIS (Netherlands)

Pizzuti, Maria Gabriella; Minnaard, Adriaan J.; Feringa, Bernard

2008-01-01

The asymmetric synthesis of protected amines via the copper/phosphoramidite-catalyzed addition of organozinc and organoaluminum reagents to N-acylimines, generated in situ from aromatic and aliphatic α-amidosulfones, is reported. High yields of optically active N-formyl-protected amines and

Incorporation of conjugated linoleic acid (CLA and α-linolenic acid (LNA in pacu fillets

Directory of Open Access Journals (Sweden)

Deoclécio José Barilli

2014-03-01

Full Text Available The objective of this study was to evaluate the incorporation of conjugated linoleic acid and α-linolenic acid in fillets of pacu fish raised in net cages and fed diets enriched with these acids. The fish were fed for 49 days, and at the end of this period the fatty acid content in the fillets was determined by gas chromatography. Concentrations of α-linolenic acid, eicosapentaenoic acid, and the total omega-3 (n-3 fatty acid in the fillets increased, improving the n-6/n-3 ratio. In addition, the incorporation of conjugated linoleic acid in the fish fillets proved well established. This study showed that the use of diets enriched with conjugated linoleic acid and α-linolenic acid results in the incorporation of these acids in the of pacu fish fillets, improving their nutritional quality.

Preconditioning the modified conjugate gradient method ...

African Journals Online (AJOL)

In this paper, the convergence analysis of the conventional conjugate Gradient method was reviewed. And the convergence analysis of the modified conjugate Gradient method was analysed with our extension on preconditioning the algorithm. Convergence of the algorithm is a function of the condition number of M-1A.

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

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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.

Superoxide dismutase and catalase conjugated to polyethylene glycol increases endothelial enzyme activity and oxidant resistance

International Nuclear Information System (INIS)

Beckman, J.S.; Minor, R.L. Jr.; White, C.W.; Repine, J.E.; Rosen, G.M.; Freeman, B.A.

1988-01-01

Covalent conjugation of superoxide dismutase and catalase with polyethylene glycol (PEG) increases the circulatory half-lives of these enzymes from 125 I-PEG-catalase or 125 I-PEG-superoxide dismutase produced a linear, concentration-dependent increase in cellular enzyme activity and radioactivity. Fluorescently labeled PEG-superoxide dismutase incubated with endothelial cells showed a vesicular localization. Mechanical injury to cell monolayers, which is known to stimulate endocytosis, further increased the uptake of fluorescent PEG-superoxide dismutase. Addition of PEG and PEG-conjugated enzymes perturbed the spin-label binding environment, indicative of producing an increase in plasma membrane fluidity. Thus, PEG conjugation to superoxide dismutase and catalase enhances cell association of these enzymes in a manner which increases cellular enzyme activities and provides prolonged protection from partially reduced oxygen species

Doxorubicin conjugated to D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS): conjugation chemistry, characterization, in vitro and in vivo evaluation.

Science.gov (United States)

Cao, Na; Feng, Si-Shen

2008-10-01

To develop a polymer-anticancer drug conjugate, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was employed as a carrier of doxorubicin (DOX) to enhance its therapeutic effects and reduce its side effects. Doxorubicin was chemically conjugated to TPGS. The molecular structure, drug loading efficiency, drug release kinetics and stability of the conjugate were characterized. The cellular uptake, intracellular distribution, and cytotoxicity were accessed by using MCF-7 breast cancer cells and C6 glioma cells as in vitro cell model. The conjugate showed higher cellular uptake efficiency and broader distribution within the cells. Judged by IC(50), the conjugate was found 31.8, 69.6, 84.1% more effective with MCF-7 cells and 43.9, 87.7, 42.2% more effective with C6 cells than the parent drug after 24, 48, 72 h culture, respectively. The in vivo pharmacokinetics and biodistribution were investigated after an i.v. administration at 5 mg DOX/kg body weight in rats. Promisingly, 4.5-fold increase in the half-life and 24-fold increase in the area-under-the-curve (AUC) of DOX were achieved for the TPGS-DOX conjugate compared with the free DOX. The drug level in heart, gastric and intestine was significantly reduced, which is an indication of reduced side effects. Our TPGS-DOX conjugate showed great potential to be a prodrug of higher therapeutic effects and fewer side effects than DOX itself.

Antibody-Conjugated Nanoparticles for Biomedical Applications

Directory of Open Access Journals (Sweden)

Manuel Arruebo

2009-01-01

Full Text Available Nanoscience and Nanotechnology have found their way into the fields of Biotechnology and Medicine. Nanoparticles by themselves offer specific physicochemical properties that they do not exhibit in bulk form, where materials show constant physical properties regardless of size. Antibodies are nanosize biological products that are part of the specific immune system. In addition to their own properties as pathogens or toxin neutralizers, as well as in the recruitment of immune elements (complement, improving phagocytosis, cytotoxicity antibody dependent by natural killer cells, etc., they could carry several elements (toxins, drugs, fluorochroms, or even nanoparticles, etc. and be used in several diagnostic procedures, or even in therapy to destroy a specific target. The conjugation of antibodies to nanoparticles can generate a product that combines the properties of both. For example, they can combine the small size of nanoparticles and their special thermal, imaging, drug carrier, or magnetic characteristics with the abilities of antibodies, such as specific and selective recognition. The hybrid product will show versatility and specificity. In this review, we analyse both antibodies and nanoparticles, focusing especially on the recent developments for antibody-conjugated nanoparticles, offering the researcher an overview of the different applications and possibilities of these hybrid carriers.

A clinical trial examining the effect of increased total CRM(197) carrier protein dose on the antibody response to Haemophilus influenzae type b CRM(197) conjugate vaccine.

Science.gov (United States)

Usonis, Vytautas; Bakasenas, Vytautas; Lockhart, Stephen; Baker, Sherryl; Gruber, William; Laudat, France

2008-08-18

CRM(197) is a carrier protein in certain conjugate vaccines. When multiple conjugate vaccines with the same carrier protein are administered simultaneously, reduced response to vaccines and/or antigens related to the carrier protein may occur. This study examined responses of infants who, in addition to diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine (DTaP) received either diphtheria CRM(197)-based Haemophilus influenzae type b conjugate vaccine (HbOC) or HbOC and a diphtheria CRM(197)-based combination 9-valent pneumococcal conjugate vaccine/meningococcal group C conjugate vaccine. Administration of conjugate vaccines with CRM(197) carrier protein load >50 microg did not reduce response to CRM(197) conjugate vaccines or immunogenicity to immunologically cross-reactive diphtheria toxoid.

Novel two-step synthesis of gold nanoparticles capped with bile acid conjugates

International Nuclear Information System (INIS)

Noponen, Virpi; Bhat, Shreedhar; Sievaenen, Elina; Kolehmainen, Erkki

2008-01-01

Bile acids and their conjugates are physiologically important molecules. Syntheses and structure elucidation combined with investigation of properties and applications of bile acids and their derivatives are of academic interest. The concept of using bile acids and their conjugates in nanoscience is a novel idea, which opens up fascinating prospects. In this article, an easy and simple route for obtaining N-lithocholyl-L-(cysteine ethyl ester) (3), capable of effectively capping and stabilizing metal nanoparticles, is described. The whole synthetic route needs only two steps giving a moderate to good yield. The gold NPs are characterized by elemental analysis, UV spectroscopy, and TEM. Additionally, 13 C CP/MAS NMR studies for different ligand/Au ratios have been performed

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.

Enantioselective synthesis of no-carrier added (NCA) 6-[18F]Fluoro-L-Dopa

International Nuclear Information System (INIS)

Duanzhi Yin; Lan Zhang; Yongxian Wang; Ganghua Tang; First Military Medical Univ., Guangzhou; Xiaolan Tang

2003-01-01

6-[ 18 F]Fluoro-L-Dopa (6-FDOPA) is the analogue of L-Dopa, the biosynthesis precursor for dopamine. As a PET tracer, it was widely applied for the presynaptic dopamine function studies in human brain. The application of a chiral phase-transfer-catalyst (PTC) in enantioselective synthesis of N.C.A. 6-[ 18 F]Fluoro-L-Dopa has been developed recently. An improved procedure was described. The labeling precursor (6-Trimethylammoniumveratraldehyde Triflate) and PTC (O-Allyl-N-(9)-anthracenylcinchonidinium Bromide) were synthesized. A successful synthesis route was developed for the preparation of 6-[ 18 F]Fluoro-L-Dopa with high radiochemical yields (4-9%, decay uncorrected) and short synthesis time(80min). The radiochemical purity was over 99% and no D-isomer was detected by HPLC analysis using a chiral mobile phase. (author)

Vibrational Coupling in Conjugated π Systems with a view to Optimization of Fluorescence Yield through Phonon Confinement

OpenAIRE

O'Neill, Luke; Lynch, Patrick; McNamara, Mary; Byrne, Hugh J.

2005-01-01

A series of π conjugated systems were studied by absorption, photoluminescence and vibrational spectroscopy. As is common for these systems, a linear relationship between the positioning of the absorption and photoluminescence maxima plotted against inverse conjugation length is observed. The relationships are in good agreement with the simple particle in a box method, one of the earliest descriptions of the properties of one-dimensional organic molecules. In addition to the electronic transi...

Bis-polymer lipid-peptide conjugates and nanoparticles thereof

Energy Technology Data Exchange (ETDEWEB)

Xu, Ting; Dong, He; Shu, Jessica; Dube, Nikhil

2018-04-24

The present invention provides bis-polymer lipid-peptide conjugates containing a hydrophobic block and headgroup containing a helical peptide and two polymer blocks. The conjugates can self-assemble to form helix bundle subunits, which in turn assemble to provide micellar nanocarriers for drug cargos and other agents. Particles containing the conjugates and methods for forming the particles are also disclosed.

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 %.

Conjugated polymer nanoparticles, methods of using, and methods of making

KAUST Repository

Habuchi, Satoshi; Piwonski, Hubert Marek; Michinobu, Tsuyoshi

2017-01-01

Embodiments of the present disclosure provide for conjugated polymer nanoparticle, method of making conjugated polymer nanoparticles, method of using conjugated polymer nanoparticle, polymers, and the like.

Conjugated polymer nanoparticles, methods of using, and methods of making

KAUST Repository

Habuchi, Satoshi

2017-03-16

Embodiments of the present disclosure provide for conjugated polymer nanoparticle, method of making conjugated polymer nanoparticles, method of using conjugated polymer nanoparticle, polymers, and the like.

Inhibition effects of protein-conjugated amorphous zinc sulfide nanoparticles on tumor cells growth

International Nuclear Information System (INIS)

Cao Ying; Wang Huajie; Cao Cui; Sun Yuanyuan; Yang Lin; Wang Baoqing; Zhou Jianguo

2011-01-01

In this article, a facile and environmentally friendly method was applied to fabricate BSA-conjugated amorphous zinc sulfide (ZnS) nanoparticles using bovine serum albumin (BSA) as the matrix. Transmission electron microscopy analysis indicated that the stable and well-dispersed nanoparticles with the diameter of 15.9 ± 2.1 nm were successfully prepared. The energy dispersive X-ray, X-ray powder diffraction, Fourier transform infrared spectrograph, high resolution transmission electron microscope, and selected area electron diffraction measurements showed that the obtained nanoparticles had the amorphous structure and the coordination occurred between zinc sulfide surfaces and BSA in the nanoparticles. In addition, the inhibition effects of BSA-conjugated amorphous zinc sulfide nanoparticles on tumor cells growth were described in detail by cell viability analysis, optical and electron microscopy methods. The results showed that BSA-conjugated amorphous zinc sulfide nanoparticles could inhibit the metabolism and proliferation of human hepatocellular carcinoma cells, and the inhibition was dose dependent. The half maximal inhibitory concentration (IC50) was 0.36 mg/mL. Overall, this study suggested that BSA-conjugated amorphous zinc sulfide nanoparticles had the application potential as cytostatic agents and BSA in the nanoparticles could provide the modifiable site for the nanoparticles to improve their bioactivity or to endow them with the target function.

Nonlinear conjugate gradient methods in micromagnetics

Directory of Open Access Journals (Sweden)

J. Fischbacher

2017-04-01

Full Text Available Conjugate gradient methods for energy minimization in micromagnetics are compared. The comparison of analytic results with numerical simulation shows that standard conjugate gradient method may fail to produce correct results. A method that restricts the step length in the line search is introduced, in order to avoid this problem. When the step length in the line search is controlled, conjugate gradient techniques are a fast and reliable way to compute the hysteresis properties of permanent magnets. The method is applied to investigate demagnetizing effects in NdFe12 based permanent magnets. The reduction of the coercive field by demagnetizing effects is μ0ΔH = 1.4 T at 450 K.

Human glutathione S-transferase-mediated glutathione conjugation of curcumin and efflux of these conjugates in Caco-2 cells

NARCIS (Netherlands)

Usta, M.; Wortelboer, H.M.; Vervoort, J.J.M.; Boersma, M.G.; Rietjens, I.M.C.M.; Bladeren, van P.J.; Cnubben, N.H.P.

2007-01-01

Curcumin, an alpha,beta-unsaturated carbonyl compound, reacts with glutathione, leading to the formation of two monoglutathionyl curcumin conjugates. In the present study, the structures of both glutathione conjugates of curcumin were identified by LC-MS and one- and two-dimensional H-1 NMR

Chiral recognition with enantioselective ion exchangers based on carbamoylated cinchonan derivatives as chiral selectors for the HPLC enantioseparation

International Nuclear Information System (INIS)

Laemmerhofer, M.

1996-11-01

The high-performance liquid chromatographic (HPLC) separation of enantiomers is preferentially performed using chiral stationary phases (CSPs). If the chiral auxiliary (selector, SO) contains charged or ionizable groups one gets ion exchanger type CSPs which may bind and retain oppositely charged analytes (selectands, SAs). We prepared anion exchanger type CSPs with various quinine and quinidine carbarnates as chiral SOs immobilized either on porous or non-porous silica. These CSPs are able to resolve the enantiomers of a wide spectrum of chiral carboxylic, sulfonic, phosphonic, phosphoric acids and of many other chiral acidic solutes (e.g. N-derivatized alpha-, beta- , gamma-amino acids as 2,4-dinitrophenyl, 3,5-dinitrobenzoyl, benzoyl, acetyl, formyl, t.-butoxycarbonyl, benzyloxycarbonyl, 9-fluorenylmethoxycarbonyl, dansyl amino acids and peptides, alpha-arylalkylcarboxylic acids as profens, alpha-aryloxyalkylcarboxylic acids, alpha-arylthioalkylcarboxylic acids and acidic drugs like etodolac, proglumide, acenocournarol, leucovorin, omeprazole, pantoprazole) employing buffered aqueous mobile phases or non-aqueous mobile phases with buffer dissolved in the organic solvent. The influence of mobile phase parameters and other experimental conditions on retention and enantioselectivity has been evaluated for isocratic and gradient elution techniques, aided by the commercial method development computer software DryLab. Several 'Quantitative Structure-Retention Relationships' (QSRR) have been derived, which allowed prediction of enantioselectivity of new analytes and moreover the optimization of the SO-structure. Spectroscopic investigations as H-NMR, FTIR of certain SO-SA-complexes have been exerted to unveil the mechanism of chiral recognition. (author)

Selective Covalent Conjugation of Phosphorothioate DNA Oligonucleotides with Streptavidin

Directory of Open Access Journals (Sweden)

Christof M. Niemeyer

2011-08-01

Full Text Available Protein-DNA conjugates have found numerous applications in the field of diagnostics and nanobiotechnology, however, their intrinsic susceptibility to DNA degradation by nucleases represents a major obstacle for many applications. We here report the selective covalent conjugation of the protein streptavidin (STV with phosphorothioate oligonucleotides (psDNA containing a terminal alkylthiolgroup as the chemically addressable linking unit, using a heterobifunctional NHS-/maleimide crosslinker. The psDNA-STV conjugates were synthesized in about 10% isolated yields. We demonstrate that the terminal alkylthiol group selectively reacts with the maleimide while the backbone sulfur atoms are not engaged in chemical conjugation. The novel psDNA-STV conjugates retain their binding capabilities for both biotinylated macromolecules and the complementary nucleic acid. Moreover, the psDNA-STV conjugate retained its binding capacity for complementary oligomers even after a nuclease digestion step, which effectively degrades deoxyribonucleotide oligomers and thus the binding capability of regular DNA-STV conjugates. The psDNA-STV therefore hold particular promise for applications e.g. in proteome research and novel biosensing devices, where interfering endogenous nucleic acids need to be removed from analytes by nuclease digestion.

Multifunctional chemical additives for hetero chain polymers; Khimikati-dobavki mnogofunkstional'nogo deystviya dlya geterostepnikh polimerov

Energy Technology Data Exchange (ETDEWEB)

Niyazi, F. F.; Kalontarov, I. Ya.; Chayko, Yu. V.; Kasimova, E. I. [V.I. Nikitin Institute of Chemistry, Academy of Sciences of the Republic of Tajikistan, Dushanbe, (Tajikistan)

1994-07-01

Indane and carbazole derivatives, poly conjugated azomethine, bis-benzimidazole were studied as chemical additives. Photo stabilizing effect was studied as well. It was found that photo stabilizing effect doesn't depend on nature of functional groups of substituent in aromatic nucleus and specified by length and efficiency of conjugation chains.

Dye linked conjugated homopolymers: using conjugated polymer electroluminescence to optically pump porphyrin-dye emission

DEFF Research Database (Denmark)

Nielsen, K.T.; Spanggaard, H.; Krebs, Frederik C

2004-01-01

. Electroluminescent devices of the homopolymer itself and of the zinc-porphyrin containing polymer were prepared and the nature of the electroluminescence was characterized. The homopolymer segments were found to optically pump the emission of the zinc-porphyrin dye moities. The homopolymer exhibits blue......Zinc-porphyrin dye molecules were incorporated into the backbone of a conjugated polymer material by a method, which allowed for the incorporation of only one zinc-porphyrin dye molecule into the backbone of each conjugated polymer molecule. The electronic properties of the homopolymer were...

Lipid-peptide-polymer conjugates and nanoparticles thereof

Science.gov (United States)

Xu, Ting; Dong, He; Shu, Jessica

2015-06-02

The present invention provides a conjugate having a peptide with from about 10 to about 100 amino acids, wherein the peptide adopts a helical structure. The conjugate also includes a first polymer covalently linked to the peptide, and a hydrophobic moiety covalently linked to the N-terminus of the peptide, wherein the hydrophobic moiety comprises a second polymer or a lipid moiety. The present invention also provides helix bundles form by self-assembling the conjugates, and particles formed by self-assembling the helix bundles. Methods of preparing the helix bundles and particles are also provided.

Novel β-cyclodextrin-eosin conjugates.

Science.gov (United States)

Benkovics, Gábor; Afonso, Damien; Darcsi, András; Béni, Szabolcs; Conoci, Sabrina; Fenyvesi, Éva; Szente, Lajos; Malanga, Milo; Sortino, Salvatore

2017-01-01

Eosin B (EoB) and eosin Y (EoY), two xanthene dye derivatives with photosensitizing ability were prepared in high purity through an improved synthetic route. The dyes were grafted to a 6-monoamino-β-cyclodextrin scaffold under mild reaction conditions through a stable amide linkage using the coupling agent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride. The molecular conjugates, well soluble in aqueous medium, were extensively characterized by 1D and 2D NMR spectroscopy and mass spectrometry. Preliminary spectroscopic investigations showed that the β-cyclodextrin-EoY conjugate retains both the fluorescence properties and the capability to photogenerate singlet oxygen of the unbound chromophore. In contrast, the corresponding β-cyclodextrin-EoB conjugate did not show either relevant emission or photosensitizing activity probably due to aggregation in aqueous medium, which precludes any response to light excitation.

Novel β-cyclodextrin–eosin conjugates

Directory of Open Access Journals (Sweden)

Gábor Benkovics

2017-03-01

Full Text Available Eosin B (EoB and eosin Y (EoY, two xanthene dye derivatives with photosensitizing ability were prepared in high purity through an improved synthetic route. The dyes were grafted to a 6-monoamino-β-cyclodextrin scaffold under mild reaction conditions through a stable amide linkage using the coupling agent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl-4-methylmorpholinium chloride. The molecular conjugates, well soluble in aqueous medium, were extensively characterized by 1D and 2D NMR spectroscopy and mass spectrometry. Preliminary spectroscopic investigations showed that the β-cyclodextrin–EoY conjugate retains both the fluorescence properties and the capability to photogenerate singlet oxygen of the unbound chromophore. In contrast, the corresponding β-cyclodextrin–EoB conjugate did not show either relevant emission or photosensitizing activity probably due to aggregation in aqueous medium, which precludes any response to light excitation.

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.

NIR photoregulated chemo- and photodynamic cancer therapy based on conjugated polyelectrolyte-drug conjugate encapsulated upconversion nanoparticles

Science.gov (United States)

Yuan, Youyong; Min, Yuanzeng; Hu, Qinglian; Xing, Bengang; Liu, Bin

2014-09-01

The design of nanoplatforms with target recognition and near-infrared (NIR) laser photoregulated chemo- and photodynamic therapy is highly desirable but remains challenging. In this work, we have developed such a system by taking advantage of a conjugated polyelectrolyte (CPE)-drug conjugate and upconversion nanoparticles (UCNPs). The poly(ethylene glycol) (PEG) grafted CPE not only serves as a polymer matrix for UCNP encapsulation, but also as a fluorescent imaging agent, a photosensitizer as well as a carrier for chemotherapeutic drug doxorubicin (DOX) through a UV-cleavable ortho-nitrobenzyl (NB) linker. Upon 980 nm laser irradiation, the UCNPs emit UV and visible light. The up-converted UV light is utilized for controlled drug release through the photocleavage of the ortho-nitrobenzyl linker, while the up-converted visible light is used to initiate the polymer photosensitizer to produce reactive oxygen species (ROS) for photodynamic therapy. The NIR photo-regulated UCNP@CPE-DOX showed high efficiency of ROS generation and controlled drug release in cancer cells upon single laser irradiation. In addition, the combination therapy showed enhanced inhibition of U87-MG cell growth as compared to sole treatments. As two light sources with different wavelengths are always needed for traditional photodynamic therapy and photoregulated drug release, the adoption of UCNPs as an NIR light switch is highly beneficial to combined chemo- and photodynamic therapy with enhanced therapeutic effects.

Human glutathione S-transferase-mediated glutathione conjugation of curcumin and efflux of these conjugates in caco-2 cells

NARCIS (Netherlands)

Usta, M.; Wortelboer, H.M.; Vervoort, J.; Boersma, M.G.; Rietjens, I.M.C.M.; Bladeren, P.J. van; Cnubben, N.H.P.

2007-01-01

Curcumin, an α,β-unsaturated carbonyl compound, reacts with glutathione, leading to the formation of two monoglutathionyl curcumin conjugates. In the present study, the structures of both glutathione conjugates of curcumin were identified by LC-MS and one- and two-dimensional 1H NMR analysis, and

DENDRIMER CONJUGATES FOR SELECTIVE OF PROTEIN AGGREGATES

DEFF Research Database (Denmark)

2004-01-01

Dendrimer conjugates are presented, which are formed between a dendrimer and a protein solubilising substance. Such dendrimer conjugates are effective in the treatment of protein aggregate-related diseases (e.g. prion-related diseases). The protein solubilising substance and the dendrimer together...

A conserved helicase processivity factor is needed for conjugation and replication of an integrative and conjugative element.

Directory of Open Access Journals (Sweden)

Jacob Thomas

Full Text Available Integrative and conjugative elements (ICEs are agents of horizontal gene transfer and have major roles in evolution and acquisition of new traits, including antibiotic resistances. ICEs are found integrated in a host chromosome and can excise and transfer to recipient bacteria via conjugation. Conjugation involves nicking of the ICE origin of transfer (oriT by the ICE-encoded relaxase and transfer of the nicked single strand of ICE DNA. For ICEBs1 of Bacillus subtilis, nicking of oriT by the ICEBs1 relaxase NicK also initiates rolling circle replication. This autonomous replication of ICEBs1 is critical for stability of the excised element in growing cells. We found a conserved and previously uncharacterized ICE gene that is required for conjugation and replication of ICEBs1. Our results indicate that this gene, helP (formerly ydcP, encodes a helicase processivity factor that enables the host-encoded helicase PcrA to unwind the double-stranded ICEBs1 DNA. HelP was required for both conjugation and replication of ICEBs1, and HelP and NicK were the only ICEBs1 proteins needed for replication from ICEBs1 oriT. Using chromatin immunoprecipitation, we measured association of HelP, NicK, PcrA, and the host-encoded single-strand DNA binding protein Ssb with ICEBs1. We found that NicK was required for association of HelP and PcrA with ICEBs1 DNA. HelP was required for association of PcrA and Ssb with ICEBs1 regions distal, but not proximal, to oriT, indicating that PcrA needs HelP to progress beyond nicked oriT and unwind ICEBs1. In vitro, HelP directly stimulated the helicase activity of the PcrA homologue UvrD. Our findings demonstrate that HelP is a helicase processivity factor needed for efficient unwinding of ICEBs1 for conjugation and replication. Homologues of HelP and PcrA-type helicases are encoded on many known and putative ICEs. We propose that these factors are essential for ICE conjugation, replication, and genetic stability.

Conjugate Gaze Palsies

Science.gov (United States)

... version Home Brain, Spinal Cord, and Nerve Disorders Cranial Nerve Disorders Conjugate Gaze Palsies Horizontal gaze palsy Vertical ... Version. DOCTORS: Click here for the Professional Version Cranial Nerve Disorders Overview of the Cranial Nerves Internuclear Ophthalmoplegia ...

Tailor-made starch-based conjugates containing well-defined poly(vinyl acetate and its derivative poly(vinyl alcohol

Directory of Open Access Journals (Sweden)

2011-06-01

Full Text Available Reversible addition-fragmentation chain transfer (RAFT polymerization was adopted to synthesize starch-based conjugates that possessed controllable architecture and properties. Starch-based xanthate agent was prepared and applied as chain transfer agent to conduct the living/controlled polymerization (LCP of vinyl acetate, which generated tailor-made conjugates of starch and well-defined poly(vinyl acetate (SVAc. The relevant derivatives, conjugates of starch and chain length-controlled poly(vinyl alcohol (SVA, were obtained subsequently. Various characterizations such as Fourier transform infrared spectra (FTIR, ultraviolet-visible spectroscopy (UV, proton nuclear magnetic resonance (1H NMR, gel permeation chromatography (GPC, X-ray diffraction (XRD, Thermogravimetric analysis (TGA, and dynamic mechanical thermal analysis (DMTA were performed to examine the structure of intermediates and the starch-based conjugates. Static contact angle measurements revealed that the hydrophilic character of starch-based conjugates was tunable. Well-defined SVAc was amphiphilic and it was able to self-assemble into size controllable micelles, which was verified by contact angles, transmission electron microscopy (TEM and dynamic light scattering (DLS tests. SVA exhibited much higher capability to form physically cross-linked hydrogel than starch did. Both the characteristic of SVAc and SVA were chain length-dependent.

Purification, characterisation and expression in Saccharomyces cerevisiae of LipG7 an enantioselective, cold-adapted lipase from the Antarctic filamentous fungus Geomyces sp. P7 with unusual thermostability characteristics.

Science.gov (United States)

Florczak, Tomasz; Daroch, Maurycy; Wilkinson, Mark Charles; Białkowska, Aneta; Bates, Andrew Derek; Turkiewicz, Marianna; Iwanejko, Lesley Ann

2013-06-10

A lipase, LipG7, has been purified from the Antarctic filamentous fungus Geomyces sp. P7 which was found to be cold-adapted and able to retain/regain its activity after heat denaturation. The LipG7 exhibits 100% residual activity following 1h incubation at 100°C whilst simultaneously showing kinetic adaptations to cold temperatures. LipG7 was also found to have industrial potential as an enantioselective biocatalyst as it is able to effectively catalyse the enantioselective transesterification of a secondary alcohol. The LipG7 coding sequence has been identified and cloned using 454 pyrosequencing of the transcriptome and inverse PCR. The LipG7 protein has been heterologously expressed in Saccharomyces cerevisiae BJ5465 and shown to exhibit the same characteristics as the native protein. Copyright © 2013 Elsevier Inc. All rights reserved.

Synthesis of Mikto-Arm Star Peptide Conjugates.

Science.gov (United States)

Koo, Jin Mo; Su, Hao; Lin, Yi-An; Cui, Honggang

2018-01-01

Mikto-arm star peptide conjugates are an emerging class of self-assembling peptide-based structural units that contain three or more auxiliary segments of different chemical compositions and/or functionalities. This group of molecules exhibit interesting self-assembly behavior in solution due to their chemically asymmetric topology. Here we describe the detailed procedure for synthesis of an ABC Mikto-arm star peptide conjugate in which two immiscible entities (a saturated hydrocarbon and a hydrophobic and lipophobic fluorocarbon) are conjugated onto a short β-sheet forming peptide sequence, GNNQQNY, derived from the Sup35 prion, through a lysine junction. Automated and manual Fmoc-solid phase synthesis techniques are used to synthesize the Mikto-arm star peptide conjugates, followed by HPLC purification. We envision that this set of protocols can afford a versatile platform to synthesize a new class of peptidic building units for diverse applications.

Fullerene-biomolecule conjugates and their biomedicinal applications.

Science.gov (United States)

Yang, Xinlin; Ebrahimi, Ali; Li, Jie; Cui, Quanjun

2014-01-01

Fullerenes are among the strongest antioxidants and are characterized as "radical sponges." The research on biomedicinal applications of fullerenes has achieved significant progress since the landmark publication by Friedman et al in 1993. Fullerene-biomolecule conjugates have become an important area of research during the past 2 decades. By a thorough literature search, we attempt to update the information about the synthesis of different types of fullerene-biomolecule conjugates, including fullerene-containing amino acids and peptides, oligonucleotides, sugars, and esters. Moreover, we also discuss in this review recently reported data on the biological and pharmaceutical utilities of these compounds and some other fullerene derivatives of biomedical importance. While within the fullerene-biomolecule conjugates, in which fullerene may act as both an antioxidant and a carrier, specific targeting biomolecules conjugated to fullerene will undoubtedly strengthen the delivery of functional fullerenes to sites of clinical interest.

Gold Nanoparticle Conjugation Enhances the Antiacanthamoebic Effects of Chlorhexidine

Science.gov (United States)

Aqeel, Yousuf; Siddiqui, Ruqaiyyah; Anwar, Ayaz; Shah, Muhammad Raza

2015-01-01

Acanthamoeba keratitis is a serious infection with blinding consequences and often associated with contact lens wear. Early diagnosis, followed by aggressive topical application of drugs, is a prerequisite in successful treatment, but even then prognosis remains poor. Several drugs have shown promise, including chlorhexidine gluconate; however, host cell toxicity at physiologically relevant concentrations remains a challenge. Nanoparticles, subcolloidal structures ranging in size from 10 to 100 nm, are effective drug carriers for enhancing drug potency. The overall aim of the present study was to determine whether conjugation with gold nanoparticles enhances the antiacanthamoebic potential of chlorhexidine. Gold-conjugated chlorhexidine nanoparticles were synthesized. Briefly, gold solution was mixed with chlorhexidine and reduced by adding sodium borohydride, resulting in an intense deep red color, indicative of colloidal gold-conjugated chlorhexidine nanoparticles. The synthesis was confirmed using UV-visible spectrophotometry that shows a plasmon resonance peak of 500 to 550 nm, indicative of gold nanoparticles. Further characterization using matrix-assisted laser desorption ionization-mass spectrometry showed a gold-conjugated chlorhexidine complex at m/z 699 ranging in size from 20 to 100 nm, as determined using atomic force microscopy. To determine the amoebicidal and amoebistatic effects, amoebae were incubated with gold-conjugated chlorhexidine nanoparticles. For controls, amoebae also were incubated with gold and silver nanoparticles alone, chlorhexidine alone, neomycin-conjugated nanoparticles, and neomycin alone. The findings showed that gold-conjugated chlorhexidine nanoparticles exhibited significant amoebicidal and amoebistatic effects at 5 μM. Amoebicidal effects were observed by parasite viability testing using a Trypan blue exclusion assay and flow-cytometric analysis using propidium iodide, while amoebistatic effects were observed using growth

Analytical characterization of polymer-drug conjugates

International Nuclear Information System (INIS)

Rizzo, V.; Gigli, M.; Pinciroli, V.

1998-01-01

A few polymeric conjugates of antitumor drugs have been recently developed in view of possible therapeutic advantages: solubilization of sparingly soluble drugs in water, improvement of therapeutic index, organ targeting through a second chemical species bound to the same polymeric chain. In this article it's described the analytical approach used in the characterization of the conjugates for chemical identity, purity and strength of the contained active ingredient. The techniques are: high field NMR and size exclusion chromatography with non-aqueous mobile phase for identity; selective hydrolysis and HPLC for strength and purity. A complete and reliable picture is thus obtained both for qualitative and for quantitative aspects. This is an important step forward in the direction of further development and marketing of polymer-drug conjugates [it