214 resultados para Tsuji hydrogenolysis
Resumo:
Les antibiotiques aminoglycosidiques sont des agents bactricides de grande valeur et defficacit large spectre contre les pathognes Gram-positifs et Gram-ngatifs, dont plusieurs membres naturels et semisynthtiques sont importants dans lhistoire clinique depuis 1950. Des travaux crystallographiques sur le ribosome, rcompenss par le prix Nobel, ont dmontr comment leurs diverses structures polyamines sont adaptes pour cibler une hlice dARN dans le centre de codage de la sous-unit 30S du ribosome bactrien. Leur interfrence avec laffinit et la cintique des tapes de slection et vrification des tARN induit la synthse de protines basse fidlit, et linhibition de la translocation, tablissant un cercle vicieux daccumulation dantibiotique et de stress sur la membrane. En rponse ces pressions, les pathognes bactriens ont volu et dissmin une panoplie de mcanismes de rsistance enzymatiques et dexpulsion : tels que les N actyltransfrases, les O phosphotransfrases et les O nucleotidyltransfrases qui ciblent les groupements hydroxyle et amino sur le coeur des aminoglycosides; des mthyl-transfrases, qui ciblent le site de liaison ribosomale; et des pompes dexpulsion actives pour llimination slective des aminoglycosides, qui sont utiliss par les souches Gram-ngatives. Les pathognes les plus problmatiques, qui prsentent aujourdhui une forte rsilience envers la majorit des classes dantibiotiques sur le bord de la pan-rsistance ont t nomms des bactries ESKAPE, une mnmonique pour Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa et Enterobacteriaceae. La distribution globale des souches avec des mcanismes de rsistance envers les standards cliniques aminoglycosides, tels que la tobramycine, lamikacine et la gentamicine, est comprise entre 20 et 60% des isoles cliniques. Ainsi, les aminoglycosides du type 4,6-disubstitus-2-deoxystreptamine sont inadquats comme thrapies anti-infectieuses large spectre. Cependant, la famille des aminoglycosides 4,5-disubstitus, incluant la butirosine, la neomycine et la paromomycine, dont la structure plus complexe, pourrait constituter une alternative. Des collgues dans le groupe Hanessian et collaborateurs dAchaogen Inc. ont dmontr que certains analogues de la paraomomycine et neomycine, modifis par dsoxygnation sur les positions 3 et 4, et par substitution avec la chane N1--hydroxy--aminobutyramide (HABA) provenant de la butirosine, pourrait produire des antibiotiques trs prometteurs. Le Chapitre 4 de cette dissertation prsente la conception et le dveloppement dune stratgie semi-synthtique pour produire des nouveaux aminoglycosides amliors du type 4,5 disubstitus, inspir par des modifications biosynthtiques de la sisomicine, qui frustrent les mcanismes de rsistance bactrienne distribues globalement. Cette voie de synthse dpend dune raction dhydrognolyse de type Tsuji catalyse par palladium, dabord dveloppe sur des modles monosaccharides puis subsquemment applique pour gnrer un ensemble daminoglycosides hybrides entre la neomycine et la sisomicine. Les tudes structure-activit des divers analogues de cette nouvelle classe ont t values sur une gamme de 26 souches bactriennes exprimant des mcanismes de rsistance enzymatique et dexpulsion qui englobe lensemble des pathognes ESKAPE. Deux des antibiotiques hybrides ont une couverture antibacterienne excellente, et cette tude a mis en vidence des candidats prometteurs pour le dveloppement prclinique. La thrapie avec les antibiotiques aminoglycosidiques est toujours associe une probabilit de complications nphrotoxiques. Le potentiel de toxicit de chaque aminoglycoside peut tre largement corrl avec le nombre de groupements amino et de dsoxygnations. Une hypothse de longue date dans le domaine indique que les interactions principales sont effectues par des sels des groupements ammonium, donc lajustement des paramtres de pKa pourrait provoquer une dissociation plus rapide avec leurs cibles, une clairance plus efficace et globalement des analogues moins nphrotoxiques. Le Chapitre 5 de cette dissertation prsente la conception et la synthse asymtrique de chanes N1 HABA substitutes par mono- et bis-fluoration. Des chanes qui possdent des -N pKa dans lintervalle entre 10 et 7.5 ont t appliques sur une neomycine ttra-dsoxygne pour produire des antibiotiques avancs. Malgr la rduction considrable du N pKa, le large spectre bactricide na pas t significativement affect pour les analogues fluors isosteriques. De plus, des tudes structure-toxicit values avec une analyse dapoptose propritaire dAchaogen ont dmontr que la nouvelle chane , difluoro-N1-HABA est moins nocive sur un modle de cellules de rein humain HK2 et elle est prometteuse pour le dveloppement dantibiotiques du type neomycine avec des proprits thrapeutiques amliores. Le chapitre final de cette dissertation prsente la proposition et validation dune synthse biomimtique par assemblage spontan du aminoglycoside 66-40C, un dimre C2 symtrique bis-imine macrocyclique 16 membres. La structure propose du macrocycle a t affine par spectroscopie nuclaire un systme trans,trans-bis-azadine anti-parallle. Des calculs indiquent que leffet anomrique de la liaison glycosidique entre les anneaux A et B fournit la pr-organisation pour le monomre 6 aldhydo sisomicine et favorise le produit macrocyclique observ. Lassemblage spontan dans leau a t tudi par la dimrisation de trois divers analogues et par des expriences dentre croisement qui ont dmontr la gnralit et la stabilit du motif macrocyclique de l'aminoglycoside 66-40C.
Resumo:
The mechanism of the hydrogenation/hydrogenolysis of dinitrodiphenyldisulfides using sulfided NiMo/ gamma Al2O3 catalysts has been examined in detail. Although two routes are possible, the major pathway involves an initial S-S bond cleavage followed by reduction of the nitro group. Importantly, the disulfide hydrogenolysis occurs in the absence of the catalyst with the role of the catalyst thought to be to activate the hydrogen and trap the cleaved intermediate as well as facilitate the reduction of the nitro group. Monitoring the mass balance throughout the reaction demonstrates the difficulty in measuring intrinsic kinetics for gas-liquid-solid reactions. Although the mass balance is restored at the end of the reaction, up to 45% of the substrate/products is found to be adsorbed on the catalyst during the reaction. (c) 2008 Elsevier B.V. All rights reserved.
Resumo:
The palladium-catalyzed hydrogenolysis of aromatic ketones to alkylbenzenes was studied in mixtures of ionic liquids to explore the promotional effect of these reaction media. Choline-based ionic liquids displayed complete miscibility with the aromatic ketone substrate at reaction temperature and a clear phase separation of the derived alkylbenzene product at room temperature. Selected ionic liquids were then assessed as reaction media in the hydrogenolysis of aromatic ketones over palladium catalysts. A binary mixture of choline and betainium bis(trifluoromethylsulfonyl)imide ionic liquids resulted in the highest conversion and selectivity values in the hydrogenolysis of acetophenone. At the end of the reaction, the immiscible alkylbenzene separates from the ionic liquid mixture and the pure product phase can be isolated by simple decantation. After optimization of the reaction conditions, high yields (>90%) of alkylbenzene were obtained in all cases. The catalyst and the ionic liquid could be used at least three times without any loss of activity or selectivity.
Resumo:
<p>For the first time, the hydrogenation/hydrogenolysis of a range of disulfides has been achieved over a supported palladium catalyst using hydrogen under relatively benign conditions. These unexpected results demonstrate that it is possible to avoid the poisoning of the catalyst by either the nitrogen-containing groups or the sulfur species, allowing both efficient reaction and recycling of the catalyst under the proper conditions (e.g., at low temperatures). A slight loss in activity was found on recycling; however, the catalyst activity can be recovered using hydrogen pretreatment. The reaction mechanism for the hydrogenolysis and hydrogenation of ortho-, meta-, and para-dinitrodiphenyldisulfide to the corresponding aminothiophenol has been elucidated. Density functional theory calculations were used to investigate the adsorption mode of the dinitrodiphenyldisulfides; a clear dependence on adsorption geometry was found regarding whether the molecule is cleaved at the S-S bond before the reduction of the nitro group or vice versa. This study demonstrates the versatility of these catalysts for the hydrogenation/hydrogenolysis of sulfur-containing molecules, which normally are considered poisons, and will extend their use to a new family of substrates. (C) 2007 Elsevier Inc. All rights reserved.</p>
Resumo:
Hydrogenolysis of bark from three different species of tree using heterogeneous platinum group metal catalysts produces two major product streams. Aromatic substituted guaiacols are produced from lignin and the lignin-like regions of suberin and a range of saturated fatty acids and alcohols, including a,?-functionalised species, are produced from the polyester regions of suberin. Control experiments demonstrate clear advantages of catalytic hydrogenolysis over base hydrolysis, both in terms of conversion and product selectivity.
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195 p.
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How does the image of the future operate upon history, and upon national and individual identities? To what extent are possible futures colonized by the image? What are the un-said futurecratic discourses that underlie the image of the future? Such questions inspired the examination of Japans futures images in this thesis. The theoretical point of departure for this examination is Polaks (1973) seminal research into the theory of the image of the future and seven contemporary Japanese texts which offer various alternative images for Japans futures, selected as representative of a national conversation about the futures of that nation. These seven images of the future are: 1. Report of the Prime Ministers Commission on Japans Goals in the 21st CenturyThe Frontier Within: Individual Empowerment and Better Governance in the New Millennium, compiled by a committee headed by Japans preeminent Jungian psychologist Kawai Hayao (1928-2007); 2. Slow Is Beautifula publication by Tsuji Shinichi, in which he re-images Japan as a culture represented by the metaphor of the sloth, concerned with slow and quality-oriented livingry as a preferred image of the future to Japans current post-bubble cult of speed and economic efficiency; 3. MuRatopia is an image of the future in the form of a microcosmic prototype community and on-going project based on the historically significant island of Awaji, and established by Japanese economist and futures thinker Yamaguchi Kaoru; 4. F.U.C.K, I Love Japan, by author Tanja Yujiro provides this seven text image of the future line-up with a youth oriented sub-culture perspective on that nations futures; 5. IMAGINATION / CREATIONa compilation of round table discussions about Japans futures seen from the point of view of Japans creative vanguard; 6. Visionary People in a Visionless Country: 21 Earth Connecting Human Stories is a collection of twenty one essays compiled by Denmark born Tokyo resident Peter David Pedersen; and, 7. EXODUS to the Land of Hope, authored by Murakami Ryu, one of Japans most prolific and influential writers, this novel suggests a future scenario portraying a massive exodus of Japans youth, who, literate with state-of-the-art information and communication technologies (ICTs) move en masse to Japans northern island of Hokkaido to launch a cyber-revolution from the peripheries. The thesis employs a Futures Triangle Analysis (FTA) as the macro organizing framework and as such examines both pushes of the present and weights from the past before moving to focus on the pulls to the future represented by the seven texts mentioned above. Inayatullahs (1999) Causal Layered Analysis (CLA) is the analytical framework used in examining the texts. Poststructuralist concepts derived primarily from the work of Michel Foucault are a particular (but not exclusive) reference point for the analytical approach it encompasses. The research questions which reflect the triangulated analytic matrix are: 1. What are the pushesin terms of current trendsthat are affecting Japans futures? 2. What are the historical and cultural weights that influence Japans futures? 3. What are the emerging transformative Japanese images of the future discourses, as embodied in actual texts, and what potential do they offer for transformative change in Japan? Research questions one and two are discussed in Chapter five and research question three is discussed in Chapter six. The first two research questions should be considered preliminary. The weights outlined in Chapter five indicate that the forces working against change in Japan are formidable, structurally deep-rooted, wide-spread, and under-recognized as change-adverse. Findings and analyses of the push dimension reveal strong forces towards a potentially very different type of Japan. However it is the seven contemporary Japanese images of the future, from which there is hope for transformative potential, which form the analytical heart of the thesis. In analyzing these texts the thesis establishes the richness of Japans images of the future and, as such, demonstrates the robustness of Japans stance vis--vis the problem of a perceived map-less and model-less future for Japan. Frontier is a useful image of the future, whose hybrid textuality, consisting of government, business, academia, and creative minority perspectives, demonstrates the earnestness of Japans leaders in favour of the creation of innovative futures for that nation. Slow is powerful in its aim to reconceptualize Japans philosophies of temporality, and build a new kind of nation founded on the principles of a human-oriented and expanded vision of economy based around the core metaphor of slowness culture. However its viability in Japan, with its post-Meiji historical pushes to an increasingly speed-obsessed social construction of reality, could render it impotent. MuRatopia is compelling in its creative hybridity indicative of an advanced IT society, set in a modern day utopian space based upon principles of a high communicative social paradigm, and sustainability. IMAGINATION / CREATION is less the plan than the platform for a new discussion on Japans transformation from an econo-centric social framework to a new Creative Age. It accords with emerging discourses from the Creative Industries, which would re-conceive of Japan as a leading maker of meaning, rather than as the so-called guzu, a term referred to in the book meaning laggard. In total, Love Japan is still the most idiosyncratic of all the images of the future discussed. Its communication style, which appeals to Japans youth cohort, establishes it as a potentially formidable change agent in a competitive market of futures images. Visionary People is a compelling image for its revolutionary and subversive stance against Japans vision-less political leadership, showing that it is the people, not the futures-making elite or aristocracy who must take the lead and create a new vanguard for the nation. Finally, Murakamis Exodus cannot be ruled out as a compelling image of the future. Sharing the appeal of Tanjas Love Japan to an increasingly disenfranchised youth, Exodus portrays a near-term future that is achievable in the here and now, by Japans teenagers, using information and communications technologies (ICTs) to subvert leadership, and create utopianist communities based on alternative social principles. The principal contribution from this investigation in terms of theory belongs to that of developing the Japanese image of the future. In this respect, the literature reviews represent a significant compilation, specifically about Japanese futures thinking, the Japanese image of the future, and the Japanese utopia. Though not exhaustive, this compilation will hopefully serve as a useful starting point for future research, not only for the Japanese image of the future, but also for all image of the future research. Many of the sources are in Japanese and their English summations are an added reason to respect this achievement. Secondly, the seven images of the future analysed in Chapter six represent the first time that Japanese image of the future texts have been systematically organized and analysed. Their translation from Japanese to English can be claimed as a significant secondary contribution. What is more, they have been analysed according to current futures methodologies that reveal a layeredness, depth, and overall richness existing in Japanese futures images. Revealing this image-richness has been one of the most significant findings of this investigation, suggesting that there is fertile research to be found from this still under-explored field, whose implications go beyond domestic Japanese concerns, and may offer fertile material for futures thinkers and researchers, Japanologists, social planners, and policy makers.
Resumo:
Simple and convenient methods for introducing deuterium label at C-3 and C-6 position of N-acetyl-D-galactosamine and D-galactose, respectively, are described. For the synthesis of 2-acetamido-2-deoxy-D-3-[2H] galactopyranose, benzyl 2-acetamido-2-deoxy-4,6-O-benzylidene-agr-D-galactopyranoside was oxidized with dimethyl sulfoxide- acetic anhydride and the product was reduced with sodium borodeuteride to introduce the deuterium at C-3. After benzylidene reduction, the mixture was subjected to hydrogenolysis and purified by column chromatography. 1,2:3,4-di-O-isopropylidene-agr-D-galactopyranoside was oxidized followed by reduction with sodium borodeuteride and deprotection to yield D-6-[2H] galactose.
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A novel sonication-promoted Barbier reaction putatively generated the titled species from the corresponding naphthotriazinylmethyl chloride and magnesium in THF: its formal addition to a variety of carbonyl compounds in situ occurred in excellent yields. Subsequent catalytic hydrogenolysis of the triazine moiety demasked the amine, thus defining a route to various phenylethylamines (including the alkaloid 'mescaline'), or ethanolamines (in two cases), in excellent overall yields. (C) 2000 Elsevier Science Ltd. All rights reserved.
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A new method is described for measuring intracellular free calcium concentrations, [(Ca2+)(i)], in the cells of Dictyostelium discoideum transformed with apoaequorin cDNA of the jellyfish, Aequorea victoria. Aequorin, a calcium-specific indicator, was regenerated in vivo from apoaequorin produced in the cells by incubation with coelenterazine. The results showed that [(Ca2+)(i)] in developing cells markedly increases at the aggregation stage and again at the culmination stage after a temporary drop at the migration stage. Except for the vegetative stage, the cells al all stages of development exhibit a sharp transient increase in [(Ca2+)(i)] upon stimulation with a cAMP (50 nM) pulse, high responses being observed at the migration and culmination stages. Separated prestalk cells of migrating slugs contain more than twice as much [(Ca2+)(i)] and show three times as large a response to cAMP stimulation as prespore cells.
