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1
Saha, Manik Chandra. „Physico-chemical studies on coordination compounds of imine acids with dioxouranium (VI) and trivalent lanthanide ions“. Thesis, University of North Bengal, 1988. http://hdl.handle.net/123456789/764.
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2
Evans, Caroline. „A novel methodology for the asymmetric synthesis of beta-lactams and beta-amino acids“. Thesis, University of Bath, 2012. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558881.
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3
Baskakova, Alevtina. „Synthesis of branched [alpha]-[alpha-] and [beta]-amino[beta-amino] acids using C-nucleophile additions to imines and nitrones“. Berlin Logos-Verl, 2009. http://d-nb.info/99789301X/04.
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4
Garbay, Guillaume. „Nouvelles voies de synthèse sans métaux d'oligomères et de polymères π-conjugués pour l'électronique organique“. Thesis, Bordeaux, 2016. http://www.theses.fr/2016BORD0240/document.
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Dans cette thèse sont développées les synthèses et caractérisations de nouveaux polymères conjugués pour des applications dans l’électronique organique. Ces polymères ont été synthétisés via des réactions de polymérisation sans utilisation de métaux de transition. Des polyazomethines à base de carbazole ont ainsi été synthétisés par polycondensation entre des carbazole portant des fonctions amine et aldéhyde en positions 2,7 et 3,6. Leurs propriétés optiques et électroniques ont été étudiées en fonction de la position des fonctions imines ainsi formées. Un comonomère de type EDOT a ensuite été intégré dans le polymère et l’impact de ce comonomère sur les propriétés du copolymère ainsi formé a été étudié.Des polymères à base d’acide squarique et croconique ont ensuite été synthétisés. En faisant varierles conditions de synthèse, les propriétés optoélectroniques ont pu être contrôlées, permettant d’obtenir des composés présentant une émission blanche, qui ont ensuite été intégrés en tant que couche active dans des dispositifs de type OLED.Enfin, des polymères plus originaux ont été étudiés, utilisant des réactions de polymérisation originale, permettant par exemple la formation de benzobisthiazole in situ. D’autres polymères ont été synthétisés en intégrant dans leur chaine des monomères originaux, comme la tetrazine ou la divanilline. Les propriétés optoélectroniques de ces composés ont ensuite été étudiées en vue deleur éventuelle intégration dans des dispositifsIn this work, synthesis and characterizations of new conjugated polymers are described.These polymers, developed for their integration into devices, have been synthesized via transitionmetalfree polymerizations. Carbazole based polyazomethines have been synthesized via polycondensation reactions between di-substituted carbazoles, bearing amino and formyl functionsin positions 3,6 or 2,7. Optical and electronical properties of such polymers have been studieddepending of the linkage position. A comonomer EDOT has then been integrated into the polymer chain, and impact of such insertion has been studied. Squaric and croconic acid base polymers have also been synthesized. By varying polymerization conditions, optoelectronic properties have been tuned, leading to the formation of polymers exhibiting a white emission. These polymers have then been integrated into OLED, as the active layer. Finally, more original polymers have been synthesized, using more original reactions or monomers such as by forming in situ benzobisthiazole. Other polymers integrating more originals monomers, such a tetrazine or divanillin, have been synthesized. Optoelectronic properties of such materials have been studied for the purpose of their integration into devices
5
Ward, Simon Edward. „Novel amino-acids from imino Diels-Alder reactions“. Thesis, University of Cambridge, 1997. https://www.repository.cam.ac.uk/handle/1810/283723.
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6
Capra, Julien. „Synthese biomimetique de composes azotes biologiquement actifs“. Thesis, Paris 11, 2011. http://www.theses.fr/2011PA112030.
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Ce travail de thèse est consacré à la synthèse de composés azotés biologiquement actifs s’inspirant notamment d’une réaction biosynthétique. Dans un premier temps, nos travaux avaient pour but de développer une nouvelle voie d’accès aux acides alpha-aminés par une réaction d’isomérisation énantiosélective d’imines. Après différentes études préliminaires, les meilleurs précurseurs d’acides alphaaminés par cette méthode que nous ayons identifiés sont les alpha céto amides. L’isomérisation 1,3 d’une imine formée à partir d’un alpha céto amide et de la diphénylméthanamine à l’aide de différents alcoolates chiraux a été réalisée. L’utilisation de l’alcoolate dérivé de la (+)-N-méthylpseudoéphédrine, employé en quantité sub-stœchiométrique, a permis d’obtenir l’alpha amino amide correspondant avec un excès énantiomérique de 67%. Il reste encore à mettre au point des conditions opératoires satisfaisantes pour la conversion de cet adduit en acide alpha aminé. L’étude de l’isomérisation 1,3 d’imines nous a permis de mettre en évidence une réaction de déshydrogénation 1,4 permettant d’accéder de façon originale à des 2-azadiènes et nécessitant la présence d’oxygène. Ainsi, plusieurs 2-azadiènes non activés ont été préparés par traitement basique d’imines issues de la condensation d’acétophénones et de diphénylméthanamine sous atmosphère d’air. Dans une dernière partie, l’étude de l’addition conjuguée d’une oxazolidinone chirale sur des alkylidènemalonates de dialkyle a été réalisée dans le but de développer une méthode d’accès à des acides alpha aminés. Les conditions opératoires mises au point ont permis d’obtenir une excellente diastéréosélectivité à partir de la plupart des alkylidènemalonates de dialkyleThis thesis work is devoted to the synthesis of biologically active nitrogen-containing compounds, particularly inspired by a biosynthetic reaction. Initially, our work aimed to develop a new pathway to a-amino acids using anenantioselective imine isomerization reaction. After various preliminary studies, the best precursors of a-amino acids that we have identified are a-keto amides. The 1,3isomerization of an imine formed from an a-keto amide and diphenylmethanamine using various chiral alkoxides was then conducted. The alkoxide derived from (+)-N-méthylpseudoéphédrine, employed in sub-stoichiometric quantities, allowed obtaining the corresponding a-amino amide with 67% enantiomeric excess. It still remains to develop satisfactory operating conditions for the conversion of this adduct to an a-amino acid.The study of the 1,3 isomerization of imines allowed us to bring to light a 1,4 dehydrogenation reaction, which allows an original access to 2-azadienes and which requires the presence of oxygen. Thus, several non-activated 2-azadienes have been prepared by basic treatment of imines derived from acetophenones anddiphenylmethanamine, under air atmosphere.In the last part, the study of the conjugate addition of a chiral oxazolidinone on dialkyl alkylidenemalonates was carried out, with the aim to develop a method of access to enantiopure b-amino acids. Reactions conditions developed allowed to obtain an excellent diastereoselectivity from most dialkyl alkylidenemalonates
7
Jones, Catrin A. „The asymmetric synthesis of #alpha#-amino acids from imines“. Thesis, Bangor University, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263167.
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8
Lewis, Kirk Alexander. „Stereoselective synthesis using aminyl radicals derived from α-amino acids“. Thesis, Loughborough University, 1997. https://dspace.lboro.ac.uk/2134/32976.
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Chapter 1 is the introduction to the thesis. It contains an overview of amino acids and aminyl radicals. The amino acids section includes material on their synthesis through traditional methods and asymmetric syntheses, as well as the use of radical reactions in their formation. The aminyl radical section gives a description of the nature of the radical and then proceeds with general techniques for aminyl radical formation. A more detailed account of our own group's use of sulfenamides and imines in aminyl radical formation is ·covered and the chapter is ended with a look at the work of aminyl radicals in amino acid synthesis and my subsequent intentions in this area. The preparation and cyclisation of sulfenamide precursors derived from [alpha]-amino acids is discussed in chapter 2. Both the cyclisations of aminyl and urethanyl (introduction of benzyloxycarbonyl and tosyl protecting groups onto amine) radicals onto suitably placed alkenyl substituents were investigated. 5-Exo-trig cyclisation reactions successfully afforded the cyclic products in moderate yield with reasonable diastereoselectivity. The effects of the [alpha]-CO2R (where R = Me or tBu), the size of the amino acid side chain and placement of alkenyl substituent (N-substituted or sidechain containing alkene) are discussed. The use of imines as aminyl radical precursors is explored in chapter 3. [Alpha]-amino acids and aldehydes were condensed and the cyclisation products isolated. The formation of aminyl radicals by 5-exo-trig cyclisation and subsequent H-atom abstraction gave moderate to good yields of N-cyclopentyl substituted a-amino acids. Preparation of the aldehydes is discussed. Tandem cyclisations involving aspects of chapters 2 and 3 are looked at in chapter 4. The preparation of the unnatural a-amino acids required for tandem cyclisation and subsequent formation of the sulfenamide or imine is reported. 5-Exo, 6-exo cyclisation of the sulfenamide derivative gave the tandem product in low yield and with moderate diastereoselectivity. This was in contrast to the imine derived reaction which proved unsuccessful. The remaining chapters incorporate the detailing of experimental relevant to the discussion and the presentation of references quoted throughout the thesis.
9
Betit, Lyanne. „Derivatization of Azomethine Imines into beta-Aminocarbonyl Motifs“. Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32473.
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β-Aminocarbonyl motifs are a privileged substructures in medicinal chemistry and peptidomimetics. As part of our efforts toward metal free aminations, we developed a method for intermolecular amino-carbonylation of alkenes using hydrazones. This method provides access to cyclic azomethine imines containing a β-aminocarbonyl motif. Conceptually, these dipoles can be derivatized into many bioactive compounds, such as 1,3-diamines, β-amino amides and β-amino acids.
The first part of this thesis will present the results on the derivatization of our aminocarbonylation products into various nitrogen-containing molecules, such as β-amino amides, β-amino acids and pyrazolones. More specifically, a short, chromatography-free derivatization of azomethine imines into N-Boc-β-amino amides will be presented.
Following these results, the next chapter will focus on attempts at develop novel aminocarbonylation reactivity between 1,2-diacylhydrazines and alkenes followed by results from our reductive N-N bond cleavage experiments on our cyclic hydrazides.
10
Hartley, James Holroyd. „Saccharide accelerated hydrolysis of boronic acid imines“. Thesis, University of Birmingham, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.369335.
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11
Rajamäki, Suvi Henna Maria. „Lewis acid mediated cyclisations of methylenecyclopropyl imines“. Thesis, University of Southampton, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.401829.
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12
Wood, Nicholas James. „The role of proline in osmoregulation by a streptomycete“. Thesis, University of Warwick, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.319812.
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13
Muramatsu, Hisashi. „Studies of enzymes useful for production of optically active N-alkyl amino acids and cyclic imino acids“. Kyoto University, 2005. http://hdl.handle.net/2433/145013.
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Kyoto University (京都大学)0048
新制・課程博士
博士(農学)
甲第11611号
農博第1467号
新制||農||904(附属図書館)
学位論文||H17||N4004(農学部図書室)
23254
UT51-2005-D360
京都大学大学院農学研究科応用生命科学専攻
(主査)教授 江﨑 信芳, 教授 坂田 完三, 教授 渡邊 隆司
学位規則第4条第1項該当
14
Nakatsu, Hiroki. „Studies on Chiral Bronsted Acid-Catalyzed Activation of Imino Functionalities“. 京都大学 (Kyoto University), 2014. http://hdl.handle.net/2433/188505.
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15
Lebée, Clément. „Nouvelles méthodes catalytiques d’accès aux amines α,β-fonctionnalisées“. Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS169.
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Développement de méthodes d'α,β-fonctionnalisation d'amines et formation d'hétérocycles optiquement actifs via l'utilisation de l'organocatalyse et de la catalyse photoredoxDevelopment of methods α,β-functionalization of amines andformation of optically active heterocycles via the use of the organocatalysis and thephotoredox catalysis
16
Yurino, Taiga. „Development and Synthetic Application of N-Boc-Protected Aminals as the Precursors of N-Boc-Protected Imines“. 京都大学 (Kyoto University), 2013. http://hdl.handle.net/2433/179370.
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17
Hubert, Cathy. „Accès à des acides alpha-aminophosphoniques. Effets des ultrasons et mécanisme“. Toulouse 3, 1994. http://www.theses.fr/1994TOU30252.
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Le sujet traite concerne une etude synthetique et theorique d'une reaction a mecanisme complexe donnant acces a des molecules aminophosphore qui sont des aminoacides dans lesquels la fonction carboxylique a ete remplacee par fonction acide phosphonique. Les analogues phosphores des -aminoacides sont connus pour leurs proprietes biologiques (antibacteriennes, antibiotiques) ou phytosanitaires importantes. Nous avons synthetise de nouveaux acides aminophosphoniques, contenant un reste thiophene ou pyrrole, dans le but d'en evaluer leurs proprietes. Ces preparations ont ete effectue par les methodes habituelles: reactions sans solvant par chauffage. Dans un deuxieme temps, il a ete montre que les reactions sont sensibles a l'activation par ultrasons, ce qui a motive une etude du mecanisme. Un processus radicalaire a ete mis en evidence pour certains substrats, alors que d'autres reagissent de maniere ionique. D'une maniere generale on peut dire que la reaction etudiee peut se produire par un continuum de mecanisme, selon la variation des groupes substituants de l'atome de phosphore. Un tel phenomene rare en chimie organique, constit ue certainement un point de depart pour des futures recherches
18
Huguenot, Florent. „Réactivité d'imines et d'oxazolidines fluorées chirales : application à la synthèse d'aminoacides et d'aminoalcools fluorés énantiopurs : thèse pour le doctorat en sciences spécialité Chimie Organique“. Reims, 2004. http://theses.univ-reims.fr/exl-doc/GED00000050.pdf.
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Cette thèse s'inscrit dans le domaine de la chimie organofluorée et de la synthèse asymétrique. Nous avons ainsi étudié diverses méthodologies originales de synthèse de composés di- et trifluorométhylés énantiopurs à partir d'oxazolidines et d'imines fluorées chirales. Les imines et oxazolidines trifluorométhylées sont préparées par réaction du fluoral ou de trifluorométhylcétones avec des amines ou des aminoalcools chiraux. Les analogues difluorométhylés sont obtenus en exploitant les propriétés électrophiles des difluoroénoxysilanes. La réduction des oxazolidines fluorées par les hydrures est complètement stéréosélective, ce qui donne accès à des amines di- et trifluorométhylées énantiopures. Les oxazolidines avec un acide de Lewis forment in situ des ions iminiums, qui donnent accès aux a-aminonitriles, précurseurs des a-aminoacides et des 1,2-diamines énantiopures, aux b-aminoesters et aux b-aminocétones, précurseurs de b-aminoacides et de 1,3-aminoalcools énantiopursThis thesis falls under the field of organofluorinated chemistry and the asymmetrical synthesis. We studied various original methodologies of synthesis of di- and trifluoromethyl enantiopur compounds starting from chiral fluorinated oxazolidines and ketimines. The trifluoromethyl ketimines and oxazolidines are prepared by reaction of the fluoral or trifluorométhyl ketones with chiral amines or aminoalcohols. The difluoromethyl analogues are obtained by exploiting the electrophilic properties of difluoroenoxysilanes. The reduction of fluorinated oxazolidines by the hydrides is completely stereoselective, which gives access to enantiopur di- and trifluoromethyl amines. Oxazolidines with Lewis acid form in situ iminium species, which give access to the a-aminonitriles, precursors of enantiopur a-amino acids and 1,2-diamines, and acces to b-aminoesters and the b-aminoketones, precursors of enantiopur b-amino acids and 1,3-aminoalcohols
19
Coantic, Stéphanie. „Réactivité des N-sulfonyl, N-sulfinyl et N-sulfénylimines dans la réaction de Staudinger : la synthèse de β-lactames N-sulfurés et leur utilisation pour la synthèse de β-aminoacides [alpha]-oxygénés“. Aix-Marseille 3, 2004. http://www.theses.fr/2004AIX30045.
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La synthèse des N-sulfonyl, des N-sulfinyl et des N-sulfénylimines a été réalisée. Ces imines N-sulfurées ont été testées dans la réaction de Staudinger sur des cétènes [alpha]-oxygénés. Cette réaction de cycloaddition [2+2] a été appliquée avec succès à de nombreuses imines N-sulfénylées pour donner des N-sulfényl β-lactames avec de bons rendements et de bonnes sélectivités. Ces azétidinones porteuses d'un groupement électrodonneur sur l'atome d'azote du cycle ont ensuite été engagées dans des réactions d'oxydation de l'atome de soufre pour donner de façon quantitative les produits N-sulfinylés et N-sulfonylés. Ces nouveaux β-lactames, porteurs de groupements électroattracteurs sur l'atome d'azote, ont été utilisés dans des réactions d'ouverture nucléophile avec des amines, des alcools ou des thiols pour donner de nouveaux β-aminoacides [alpha]-oxygénésThe synthesis of N-sulfonyl, N-sulfinyl and N-sulfenylimines has been achieved. These N-thiolated imines were tested in the Staudinger reaction with [alpha]-oxygenated ketenes. The [2+2] cycloaddition reaction was successfully applied to many N-sulfenylimines to give N-sulfenyl β-lactames with good yields and a good selectivity. These azetidinones bearing an electron-donor group on the nitrogen of the cycle were then used in the oxidation reaction of the sulphur to give the N-sulfinylated and N-sulfonylated cycloadducts. The new β-lactames bearing an electron-acceptor group on the nitrogen were used in nucleophilic ring opening reactions with amines, alcohols or thiols to give new [alpha]-oxygenated β-aminoacids
20
Huguenot, Florent Portella Charles Brigaud Thierry. „Réactivité d'imines et d'oxazolidines fluorées chirales“. Reims : S.C.D. de l'Université, 2005. http://scdurca.univ-reims.fr/exl-doc/GED00000050.pdf.
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21
Courant, Thibaut. „Multi-fonctionnalisation d’imines : synthèse de composés aminés α-β-fonctionnalisés par procédé photocatalysé et réactions asymétriques organocatalysées“. Thesis, Paris 11, 2013. http://www.theses.fr/2013PA112308.
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Ce projet scientifique concerne le développement de nouvelles méthodes efficaces de fonctionnalisation d’imines par des procédés organocatalysés et photocatalysésDans un premier temps la réaction photocatalysée d’alkylation d’énamines en conditions douces à été étudiée. L’utilisation de photocatalyseurs sous forme de complexes organométalliques d’Iridium a permis de réaliser la double fonctionnalisation d’ènecarbamates, permettant ainsi d’obtenir des substituts d’imines hautement substitués. Ce procédé permet de s’affranchir de l’utilisation de métaux lourds et ne nécessite qu’une activation par la lumière visible pour fonctionner. Cette transformation radicalaire éco-compatible à par la suite été soumise à une étude mécanistique approfondie. Dans une deuxième partie, la réaction d’aza-Friedel-Crafts organocatalysée par des acides de Brønsted chiraux à été étudiée. Dans cette réaction, la bi-fonctionnalité des acides chiraux dérivés du BINOL a été exploitée. Elle permet l’addition énantiosélective d’une grande variété d’indoles substitués sur des acyl-pyrrolidinones générées in situ. Les composés synthétisés présentent des structures bioactives intéressantes notamment sur le système nerveux central.Enfin, la première réaction de Povarov asymétrique impliquant des amino-hétérocycles comme précurseurs de 2-azadiènes à été décrite. Cette étude s’appuie sur des travaux antérieurs du laboratoire et permet la synthèse des analogues hétérocycliques de tétrahydroquinoléines précédemment décrites. Le procédé met en jeu une séquence multicomposants réduction/Povarov catalysée par des acides phosphoriques chiraux et permet l’accès rapide à une large bibliothèque d’analoguesThe aim of this study is the development of new methodologies for imines functionalization by organocatalysed and photocatalysed processes.First, a photocatalysed alkylation reaction of enecarbamates have been described. The use of organometallic Iridium complexes allowed the double functionalization of enecarbamates leading to highly substituted imines surrogates. This process is a green alternative to the use of heavy metals and only needs visible light as an renewable energy source to proceed. This environment-friendly radical transformation has been submitted to mechanistic study.In a second part, an aza-Friedel-Crafts reaction organocatalysed by chiral Brønsted acid has been studied. The bi-fonctionnality of chiral phosphoric acids has been advantageously used to perform the Friedel-Crafts addition of various substituted indole to in situ generated acyl-iminium ions. The compounds obtained by this methodology are showing interesting biological activities on central nervous system. Finally, the first enantioselective Povarov reaction involving amino-heterocycles as 2-azadienes precursors has been reported. This reaction is based on previous lab reports and the synthesis of tetrahydroquinoline analogues has been described. The multicomponent reduction/Povarov reaction sequence catalyzed by chiral phosphoric acids derived gives a rapid access to a wide library of bioactives analogues
22
Rowland, Gerald B. „Enantioselective Bronsted acid-catalyzed addition of carbon and nitrogen nucleophiles to imines“. [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002618.
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Rowland, Gerald B. Jr. „Enantioselective, Bronsted Acid-Catalyzed Additions of Nitrogen and Carbon Nucleophiles to Imines“. Scholar Commons, 2008. https://scholarcommons.usf.edu/etd/483.
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The development of enantioselective reaction methodology has been at the forefront of research in both academic and industrial research laboratories due to the importance of chiral molecules in biological systems. An emerging area of research in the development of enantioselective reaction methodology has been the development of organocatalytic reactions. Organocatalysis, the use of small, chiral organic molecules as catalysts, has the advantage over traditional Lewis acid catalysis in that the reactions in general produce less toxic by-products. One recent breakthrough in the development of enantioselective methodology has been the development of chiral phosphoric acids as organocatalysts. Chiral phosphoric acids have been shown to be excellent catalysts for a wide variety of reactions. In this thesis chiral phosphoric acid-catalyzed enantioselective reaction methodologies have been developed for the addition of sulfonamides and indoles to imines.
The development of Bronsted acid-catalyzed amidation of imines allows for an expedient route for the synthesis of N,N-aminals, which have been incorporated into a wide variety of biologically active compounds. Initial studies were undertaken to determine the practicality of a Bronsted acid-catalyzed method for the addition of amides to N-Boc protected imines. Over 20 achiral Bronsted acids were screened, and it was found that phenylphosphinic acid and trifluoromethanesulfinimide were both excellent catalysts for the addition of amides to a variety of imines giving the respective products in excellent yield. The methodology was extended to the development of an enantioselective method for the addition of sulfonamides to imines. It was found that a chiral phosphoric acid derived from the VAPOL ligand was suitable for this purpose. The developed methodology is capable of tolerating a wide variety of functional groups allowing for the preparation of the N, N-aminal products in excellent yield and enantioselectivities.
An enantioselective phosphoric acid-catalyzed aza-Friedel-Crafts reaction between N-benzylindoles derivatives and N-benzoyl protected imines has been developed. A catalyst derived from the BINOL backbone was found to be the optimum catalyst for the enantioselective transformation. The developed methodology was capable of tolerating a wide variety of functional groups and provides an expedient route for the synthesis of chiral 3-indolylmethanamines.
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Larson, Shawn E. „Enantioselective Brønsted and Lewis Acid-Catalyzed Reaction Methodology: Aziridines as Building Blocks for Catalytic Asymmetric Induction“. Scholar Commons, 2012. http://scholarcommons.usf.edu/etd/4357.
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Chiral molecules as with biological activity are plentiful in nature and the chemical literature; however they represent a smaller portion of the pharmaceutical drug market. As asymmetric methodologies grow more powerful, the tools are becoming available to synthesize chiral molecules in an enantioselective and efficient manner.
Recent breakthroughs in our understanding of phosphoric acid now allow for Lewis acid catalysis via pairing with alkaline earth metals. Using alkaline earth metals with chiral phosphates is an emerging approach to asymmetric methodology, but already has an influential record.
The development of new conditions for the phosphoric acid-catalyzed highly enantioselective ring-opening of meso-aziridines with a series of functionalized aromatic thiol nucleophiles is described in this thesis. This methodology utilizes commercially available aromatic thiols, a series of meso-aziridines, and a catalytic amount of VAPOL calcium phosphate to explore the substrate scope of this highly enantioselective reaction.
Additionally, the development of new conditions for a catalytic asymmetric aza-Darzens aziridine synthesis mediated by a vaulted biphenanthrol (VAPOL) magnesium phosphate salt is described in this thesis. Using simple substrates, this methodology explores the scope and reactivity of a new magnesium catalyst for an aziridination reaction capable of building chirality and complexity simultaneously.
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Lecointe, Lucile. „Synthèse énantiosélective d'alpha-aminoacides hétérocycliques et/ou aromatiques“. Montpellier 2, 1998. http://www.theses.fr/1998MON20038.
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Le but de ce travail est la synthese enantioselective de quatre aminoacides non proteinogeniques biologiquement actifs : l'azatryptophane, l'azatyrosine, la tribromophenylalanine et la trichlorophenylalanine. L'azatrytpophane a ete synthetise pour ses proprietes de standard photochimique. L'azatyrosine possede quant a elle des proprietes biologiques, notamment comme agent anticancereux. Les tribromo et trichlorophenylalanines ont ete synthetisees pour etre incorporees dans une sequence peptidique en vue d'un marquage isotopique apres remplacement des halogenes par des tritiums. Les quatre aminoacides ont ete obtenus enantiomeriquement purs par differentes methodes. Le dedoublement chimique realise grace a une base de schiff issue de l'hydroxypinanone et d'un ester methylique de l'azatryptophane et la resolution enzymatique ont permis d'obtenir l'azatryptophane enantiomeriquement pur. L'azatyrosine, la trichlorophenylalanine et la tribromophenylalanine ont ete synthetisees facilement et ceci avec de bons rendements, elles ont ete obtenues enantiomeriquement pures soit par alkylation diastereoselective d'une base de schiff issue de l'hydroxypinanone et du glycinate de tertiobutyle soit par deracemisation effectuee sur une base de schiff issue de la condensation de l'hydroxypinanone sur l'ester methylique ou tertiobutylique de l'aminoacide respectif. L'alkylation diastereoselective et la deracemisation conduisent apres hydrolyse de l'imine et de l'ester aux memes enantiomeres, si la chiralite de l'hydroxypinanone est la meme.
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Malm, Christian [Verfasser]. „Catalyst Substrate Interaction of Organo Phosphate Brønsted Acid Catalysts with Imines / Christian Malm“. Mainz : Universitätsbibliothek der Johannes Gutenberg-Universität Mainz, 2020. http://d-nb.info/1223379434/34.
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Delle, Chiaie Kayla R. „Exploration of Bis(imino)pyridine Iron Alkoxides for the Synthesis of Novel Degradable Polymers“. Thesis, Boston College, 2018. http://hdl.handle.net/2345/bc-ir:108245.
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Thesis advisor: Jeffery A. ByersThis dissertation discusses the development of a family of iron complexes and their role in the synthesis of degradable polymers. Chapter one will introduce the different areas of redox-switchable polymerization. In chapter two the synthesis of block copolymers containing a polyester and polyether block is presented. The application redox-switchable polymerization to form a copolymer with two fundamentally distinct backbone functionalities and their characterization is discussed. In chapter three the synthesis of a degradable cross-linked polymer through a novel redox-triggered cross linking event is summarized. In chapter four, a detailed mechanistic study of iron-complex catalyzed epoxide polymerization is examined and a unique mechanistic scheme is proposed. Lastly, in chapter five the synthesis and characterization of a formally iron(I) complex is presented. This complex shows remarkable catalytic activity towards ring-opening polymerization
Thesis (PhD) — Boston College, 2018
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
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Laghmari, Mohamed. „Phosphines sulfonées hydrosolubles : étude mécanistique de l'hydrogénation en système biphasique : réduction asymétrique des déhydropeptides et des imines“. Lyon 1, 1993. http://www.theses.fr/1993LYO10099.
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Le premier chapitre est une mise au point bibliographique concernant la synthese de phosphines hydrosolubles et leurs utilisations en catalyse en milieu aqueux ou biphasique. Le second chapitre concerne l'etude du mecanisme de la reaction d'hydrogenation en systeme biphasique. Les effets de sel, d'agent chiraux et d'agent de transfert de phase sur l'enantioselectivite sont abordes. Une incorporation d'un atome de deuterium en des groupements acetamido et ester est mise en evidence lors de la reduction des precurseurs d'aminoacides via les complexes du rhodium associes a des phosphines sulfonees par h#2 dans d#2o. Par contre dans le cas de la reduction d'autres substrats ethyleniques, une incorporation de plusieurs atomes de deuteriums a lieu a la suite d'une serie de reaction de -elimination, ceci en presence ou non d'eau. Le troisieme chapitre aborde d'une part la reduction d'imines, d'autre part la reduction des dehydropeptides. Dans le cas des imines, l'influence du degre de sulfonation de la phosphine sur l'enantioselectivite a ete mise en evidence, des enantioselectivites de 96% ont ete obtenues. La reduction des dehydropeptides en systeme biphasique est possible et suivant la nature de la phosphine sulfonee on peut atteindre des diastereoselectivites de l'ordre de 88%
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Ramaya, Sharn. „Synthetic studies towards C-glycosyl amino acids : Part I, The synthesis of C-glycosyl amino acids using zinc reagents; Part II, Approaches towards the synthesis of C-glycosyl amino acids using an imino ene reaction“. Thesis, University of Bristol, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390646.
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Bauhuber, Sonja [Verfasser], und Achim [Akademischer Betreuer] Göpferich. „Linear poly(ethylene imine)-poly(ethylene glycol) copolymers for nucleic acid delivery - Synthesis and characterization / Sonja Bauhuber. Betreuer: Achim Göpferich“. Regensburg : Universitätsbibliothek Regensburg, 2012. http://d-nb.info/104543356X/34.
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Ko, Kochun. „Bactericidal Mechanisms of Escapin, A Protein in the Ink of a Sea Hare“. Digital Archive @ GSU, 2011. http://digitalarchive.gsu.edu/biology_diss/92.
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A 60 kDa monomeric protein isolated from the defensive purple ink secretion of the sea hare Aplysia californica has broad antimicrobial activity in tryptone peptone rich medium. This protein, which we call ‘escapin’, belongs to an L-amino acid oxidase family. The goals of my project were 1) to determine the products of escapin’s oxidation of its main substrate L-lysine, 2) to characterize the antimicrobial effects of escapin’s products, and 3) determine bactericidal mechanisms of action of these products.
Escapin is a powerful bactericidal agent against several bacteria species including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Vibrio harveyi. Escapin operates through a two-step process: 1) deamination of L-amino acids (especially L-lysine) by enzymatic activity to produce escapin intermediate products of L-lysine (EIP-K), hydrogen peroxide, and ammonia; and 2) EIP-K simultaneously reacts with hydrogen peroxide to generate escapin end products (EEP-K). EIP exists as an equilibrium mixture of the linear a-keto analogue of lysine and its cyclic forms, and the relative amount of the linear form increases with pH decreases. The powerful bactericidal effect of escapin requires the simultaneous presence of hydrogen peroxide and EIP-K in weak acidic conditions, which suggests that linear form of EIP-K with hydrogen peroxide is responsible for the bactericidal effect of escapin. Using E. coli MC4100 as a model, the mechanism of action of escapin was examined. Brief treatment with EIP-K + H2O2, but not EIP-K or H2O2 alone, causes irreversible DNA condensation with a time course similar to the bactericidal effect. A mutant strain resistant to EIP-K + H2O2 was isolated, and a single point mutation was found in the oxidative stress regulator gene (oxyR). Through a complementary assay, it was shown that wild type E. coli is conferred resistance to EIP-K + H2O2 by carrying mutated oxyR plasmid. Furthermore, in this bactericidal effect, heat or cold shock does not substitute for hydrogen peroxide induced oxidative stress. Thus, escapin’s powerful bactericidal effect may be through irreversible DNA condensation mediated through hydrogen peroxide generating an oxidative stress response, but the pathway mediating EIP-K’s synergistic effect is still unclear.
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Tomifuji, Rei. „Studies on Design of 3d Transition Metal Lewis Acid Catalysts for Efficient Activation of Aldehydes and Imines“. Doctoral thesis, Kyoto University, 2020. http://hdl.handle.net/2433/253290.
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京都大学0048
新制・課程博士
博士(工学)
甲第22454号
工博第4715号
新制||工||1736(附属図書館)
京都大学大学院工学研究科材料化学専攻
(主査)教授 松原 誠二郎, 教授 杉野目 道紀, 教授 中尾 佳亮
学位規則第4条第1項該当
Doctor of Philosophy (Engineering)
Kyoto University
DGAM
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Marcotte, Stéphane. „Synthèse de composés gem-difluorés d'intérêt biologique“. Rouen, 2001. http://www.theses.fr/2001ROUES030.
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Dans notre travail, nous décrivons la synthèse de divers composés gem-difluorés d'intérêt biologique. Dans une première partie, nous avons réalisé la synthèse de β-aminoacides-α, α-difluorés et de 3,3-difluoroazétidin-2-ones avec des excès énantiomériques élevés. Ceux-ci sont obtenus par une réaction de Réformatsky sur des imines chirales dérivés d'aminoalcools optiquement purs. Dans une seconde partie, nous avons développé des méthodes d'accès à de nouveaux nucléosides difluorométhylés en position 2' et 3'. De nombreux nucléosides ont ainsi été synthétisés à partir de glycal et leur activité biologique a en partie été évaluée. Enfin, nous avons exploré diverses voies pour l'accès aux gem-difluoro-C-glycosides. En particulier, nous avons obtenu des dérivés du D-galactose et du L-idose comportant un groupe CF2 en position anomérique. Ces composés peuvent être vus comme des précurseurs de glycopeptides difluorés non hydrolisablesIn this work, we describe the synthesis of diverse gem-difluorinated compounds of biological interest. We first performed the synthesis of α,α-difluoro-β-aminoacid and 3,3-difluoroazetidin-2one with high enantiomeric excess. Thèse were obtained via a Reformatsky type reaction on chiral imines derived from optically pure aminoalcohol. Secondly, we developed access to new 2' and 3' difluoromethylnucleosides. Various nucleosides were synthetized starting from furanoid glycal and their biological activity was evaluated. Finally, we explored different routes to gem-difluoro-C-glycosides. We obtained analogs of D-galactose and L-idose having a CF2 on the anomeric position. These compounds can be précursors of non hydrolysable difluorinated glycopeptides
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Nugent, Benjamin M. „Regio- and stereoselective additions to azomethines free radical cyclizations and chiral Bronsted acid catalyzed reactions of imines /“. [Bloomington, Ind.] : Indiana University, 2006. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:3206873.
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Thesis (Ph. D.)--Indiana University, Dept. of Chemistry, 2006.Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0275. Adviser: Jeffrey N. Johnston. "Title from dissertation home page (viewed Feb. 22, 2007)."
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Mouysset-Dognon, Dominique. „Synthèses diastéréosélectives d'[alpha]-amino acides contraints par réactions de cycloaddition impliquant des imines chirales de glyoxylate d'alkyle“. Aix-Marseille 3, 1996. http://www.theses.fr/1996AIX30056.
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Le but de ce travail est de synthetiser des -amino-acides non naturels contraints. Pour cela, nous avons mis en uvre des reactions de cycloaddition avec les synthons -imino-esters. Ainsi par reaction de cycloaddition 3+2, l'ester methylique de l'acide 1--1(4-methoxyphenyl)-ethyl-4-methylene-pyrrolidine-2-carboxylique a ete synthetise, il s'agit d'un analogue exomethylene de la proline, produit de la reaction originale du p-methoxyphenyl-imino-acetate de methyle avec le complexe trimethylene methane du palladium mis au point par b. M. Trost. Cette synthese repousse les limites d'applications de cette reaction. Nous avons aussi principalement travaille a la synthese de cycles a quatre chainons par reaction de staudinger. Plusieurs familles originales de composes -lactamiques ont ainsi ete obtenues. Une serie de composes a ete synthetisee a partir du 1-phenylethyl-imino-acetate de methyle et de differents cetenes fonctionnalises. Nous avons aussi travaille avec le 1-p-methoxyphenylethyl-imino-acetate de methyle. La methode d'obtention de ces produits est simple et rapide. Les rendements sont excellents. Nous avons etudie cette reaction d'un point de vue synthetique et mecanistique. Seuls les isomeres de configuration cis sont obtenus sauf dans le cas du carboethoxy-cetene ou le mecanisme reactionnel implique est different. Les reactions de deprotection des fonctions amide et ester des differents cycloadduits -lactamiques conduisent avec de bons rendements aux -amino-acides cycliques desires. Une synthese a egalement ete realisee avec une imine de glyoxylate derivee de la threonine. Les deux adduits cis sont formes dans un rapport de 70:30. L'isomere majoritaire est isole enantiomeriquement pur. Une analyse au rx a permis de determiner sa configuration et une etude de modelisation moleculaire permet d'expliquer la differenciation faciale observee. Nous avons aussi commence l'etude de l'utilisation de -lactames synthetises a partir de cetenes fonctionnalises par une chaine alkyle a extremite nucleophile ou d'imines fonctionnalisees de la meme facon (cas de la threonine) pour obtenir l'ouverture du -lactame par attaque intramoleculaire et ainsi former des cycles plus grands presentant de l'interet en tant que repartiteurs
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Ingle, Gajendrasingh. „Chiral BINOL Metal Phosphate/Phosphoric Acid Catalyzed Enantioselective Addition of Phosphorus and Sulfur Nucleophiles to Imines and Epoxides“. Scholar Commons, 2012. http://scholarcommons.usf.edu/etd/4339.
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The research presented in this dissertation focuses on chiral BINOL metal phosphatephosphoric acid catalyzed enantioselective additions of phosphorus and sulfur nucleophiles to imines and epoxides. In chapter 2, we reported a new method to synthesize chiral amino phosphine oxides. The reaction combines N-substituted imines and diphenylphosphine oxide catalyzed by chiral magnesium 9-antryl phosphate. A wide variety of aliphatic and aromatic aldimines substituted by electron neutral benzhydryl or dibenzocycloheptene groups were excellent substrates for the addition reaction. The imines protected with dibenzocycloheptene protecting group provided better enantioselectivity than those protected with benzhydryl group, while both imines gave comparable yields. Also, the substituted diphenylphosphine oxides were excellent nucleophiles obtaining chiral α-amino phosphine oxides in good yields and enantioselectivities.
In chapter 3, we reported the first catalytic asymmetric method to prepare enantioenriched N,S-acetals catalyzed TRIP phosphoric acids. The reaction combined N-acyl imines with thiols to generate products in excellent yield and enantioselectivity. Electron-rich and electron-deficient aromatic N-acyl imines were excellent substrate for the addition reaction. A wide range of aliphatic and aromatic thiols obtained the N,S-acetals in excellent yields and enantioselectivities.
The TRIP phosphoric acid was found to be an extremely efficient catalyst for the transformation, resulting in asymmetric induction at extremely low catalyst loading.
In chapter 4, a highly enantioselective method for desymmetrization of meso-epoxides using thiols catalyzed by substituted BINOL lithium phosphate is reported. This is the first example of epoxide activation using metal phosphate is reported. Various five and six membered aliphatic cyclic meso-epoxides were excellent substrates for the desymmetrization reaction; aromatic acyclic epoxides also reacted with excellent yield and asymmetric induction. Similarly electron rich and electron deficient aromatic thiols obtained the β-hydroxyl sulfides in excellent yields and enantioselectivities.
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Vu, Huy-Dinh. „Accès à des hétérocycles azotés énantiopurs par cyclisation d’amino-ynones“. Thesis, Rennes 1, 2014. http://www.theses.fr/2014REN1S098/document.
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La synthèse d’hétérocycles azotés énantiopurs est un enjeu important dans la chimie du vivant et représente l’un des axes de notre laboratoire depuis quelques années. L’ensemble du travail a bénéficié pour cela du « pool chiral » constitué par les acides aminés naturels. Dans la première partie de notre travail, nous avons utilisé l’acide aspartique à partir duquel des exemples variés de β-amino-ynones ont été construits. Leur cyclisation par catalyse à l’or a donné accès à des pyridones, précurseurs de dérivés pipécoliques énantiopurs. Un travail analogue a été entrepris sur des γ-amino-ynones et a donné un résultat moins prévisible : cyclisation à cinq sommets suivie du réarrangement de Meyer-Schuster. Cette synthèse s’est montrée plus efficace en milieu acide méthane sulfonique qu’en présence d’or et représente un nouveau mode d’accès aux vinylogues d’amides de la pyrrolidine, intermédiaires-clé en synthèse totale. Enfin, l’utilisation d’un acide de Lewis, ZnCl₂, sur des γ- et δ-amino-ynones a fourni des imines cycliques, à cinq ou six sommets et portant un alcyne, que nous avons isolées sous forme libre ou complexée par l’acide de LewisThe synthesis of enantiopure nitrogen heterocycles is an important issue in chemistry and has been part our laboratory work for several years. The entire work took advantage of the chiral pool consisting of natural amino acids. In the first part of our work, we used aspartic acid from which various examples of β-amino-ynones were built. Their catalytic cyclization gave access to pyridones that were used as enantiopure pipecolic acid precursors. A similar work was undertaken on γ-amino-ynones and gave a less predictable result: cyclization to a five members ring followed by Meyer-Schuster rearrangement. This synthesis was more effective in a methane sulfonic acid medium than in the presence of gold and represents a new mode of access to pyrrolidine vinylogous amides that are key-intermediate in total synthesis. Finally, the use of a Lewis acid -ZnCl₂- on γ- and δ-amino-ynones provided five and six members cyclic imines, carrying an alkyne, which we isolated in the free form or complexed with the Lewis acid
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Capra, Julien. „Synthèse biomimétique de composés azotés biologiquement actifs“. Phd thesis, Université Paris Sud - Paris XI, 2011. http://tel.archives-ouvertes.fr/tel-00711703.
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Ce travail de thèse est consacré à la synthèse de composés azotés biologiquement actifs s'inspirant notamment d'une réaction biosynthétique. Dans un premier temps, nos travaux avaient pour but de développer une nouvelle voie d'accès aux acides α-aminés par une réaction d'isomérisation énantiosélective d'imines. Après différentes études préliminaires, les meilleurs précurseurs d'acides a-aminés par cette méthode que nous ayons identifiés sont les α-céto amides. L'isomérisation 1,3 d'une imine formée à partir d'un α-céto amide et de la diphénylméthanamine à l'aide de différents alcoolates chiraux a été réalisée. L'utilisation de l'alcoolate dérivé de la (+)-N-méthylpseudoéphédrine, employé en quantité sub-stoechiométrique, a permis d'obtenir l'α-amino amide correspondant avec un excès énantiomérique de 67%. Il reste encore à mettre au point des conditions opératoires satisfaisantes pour la conversion de cet adduit en acide α-aminé. L'étude de l'isomérisation 1,3 d'imines nous a permis de mettre en évidence une réaction de déshydrogénation 1,4 permettant d'accéder de façon originale à des 2-azadiènes et nécessitant la présence d'oxygène. Ainsi, plusieurs 2-azadiènes non activés ont été préparés par traitement basique d'imines issues de la condensation d'acétophénones et de diphénylméthanamine sous atmosphère d'air. Dans une dernière partie, l'étude de l'addition conjuguée d'une oxazolidinone chirale sur des alkylidènemalonates de dialkyle a été réalisée dans le but de développer une méthode d'accès à des acides β-aminés. Les conditions opératoires mises au point ont permis d'obtenir une excellente diastéréosélectivité à partir de la plupart des alkylidènemalonates de dialkyle.
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Almeida, Luciana Yamamoto de 1985. „Avaliação do efeito do tratamento com Orlistat sobre a resposta imune contra melanomas experimentais“. [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/290690.
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Orientador: Edgard GranerDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: A enzima ácido graxo sintase (FASN), responsável pela síntese endógena de ácidos graxos, está presente em grande quantidade em diversas neoplasias malignas e lesões pré-malignas. Sua inibição farmacológica parece estar relacionada com a morte celular seletiva de células tumorais. Orlistat (Xenical®), uma droga anti-obesidade, que possui também propriedades anti-neoplásicas por inibir irreversivelmente FASN, sendo estes efeitos claramente demonstrados em cânceres de mama, próstata, estômago e melanoma. Embora as propriedades antitumorais do Orlistat ocorram devido a um efeito direto sobre as células malignas, até o momento, possíveis mecanismos indiretos sobre o sistema imunológico não foram estudados. Células imunes, como linfócitos T CD8+ (LTCD8+), células natural killer (NK) e células dendríticas (CD), estão envolvidas no processo de defesa antitumoral, por promover a morte de células neoplásicas. Como não há informações na literatura sobre uma possível relação entre FASN e o sistema imunológico, nosso trabalho teve como objetivo principal estudar o efeito da inibição da enzima FASN com Orlistat sobre o fenótipo e porcentagem de LTCD8+, células NK e CDs presentes nos tumores primários e suas respectivas metástases para linfonodos mediastínicos, em modelo de melanoma murino (B16-F10 / C57/Bl6). Adicionalmente, avaliou-se o estado de ativação das CDs CD11c+ presentes nos linfonodos mediastínicos metastáticos, através da expressão de MHC I (complexo maior de histocompatibilidade de classe I) e das moléculas co-estimulatórias CD80 e CD86 na superfície destas células. Através de citometria de fluxo, foram analisadas as porcentagem de LTs CD3+CD8+, células NK CD3-CD49b+ e CDs CD11c+ nos tumores e metástases. A ativação dos LTCD8+ e células NK foi avaliada pela expressão de granzima b e perforina em RNA total obtido dos linfonodos mediastínicos metastáticos, através da reação em cadeia da polimerase em tempo real (qRT-PCR). Além disso, as células NK presentes nas metástases linfonodais também foram avaliadas quanto à expressão do receptor inibitório Ly49A, através de citometria de fluxo. Após o tratamento com Orlistat, houve redução de cerca de 30 % na quantidade de metástases, em comparação com os grupos controle. Os tumores primários do grupo controle apresentaram um baixo percentual de LTs CD3+CD8+ (0,36%) e de células NK CD3-CD49b+ (0,27%). No grupo tratado, não foi possível detectar a presença destas células na massa tumoral, sugerindo uma supressão desta população pelo Orlistat. Além disso, CDs CD11c+ não puderam ser avaliadas nestes tumores. Nos linfonodos mediastínicos metastáticos, houve um discreto aumento de CDs CD11c+, acompanhado de menor expressão das proteínas de superfície MHC I, CD80 e CD86, além de uma redução percentual das células T CD3+CD8+ e NK CD3-CD49b+. A expressão de RNAs mensageiros para granzima b e perforina também foi menor no grupo de camundongos tratados. Finalmente, em relação a Ly49A, sua expressão foi maior nas NKs dos linfonodos metastáticos de animais tratados. Em conjunto, nossos resultados indicam que a inibição de FASN com Orlistat interfere no fenótipo, porcentagem e estado de ativação das células imunológicas intratumorais e dos linfonodos metastáticos, sugerindo possível atividade imunossupressora
Abstract: Fatty acid synthase (FASN), the enzyme responsible for the endogenous synthesis of fatty acids, is highly expressed in several malignant neoplasms and premalignant lesions. Its pharmacological inhibition promotes apoptosis in tumor cells. Orlistat (Xenical ®), an anti-obesity drug, has anti-neoplastic properties by irreversibly inhibiting FASN, which were demonstrated in malignant neoplasms from breast, prostate and stomach and melanoma. Although the known antitumor properties of Orlistat are consequence of a direct effect on malignant cells, indirect mechanisms on the immune system were not described. Immune cells, such as CD8+ T lymphocytes (CD8+ TL), natural killer (NK) and dendritic cells (DC) are involved in the defense against cancer cells. Since there is no information in literature about a relationship between FASN activity and the immune system, our work aimed to study the effect of Orlistat on the phenotype and percentage of CD8+TL, NK and DC present in the primary tumors and their metastases to mediastinal lymph nodes in a experimental model of spontaneous melanoma metastasis (B16-F10 / C57/Bl6). Additionally, we evaluated the activation of CD11c+ DCs present in the metastatic mediastinal lymph nodes, through the expression of MHC I (major histocompatibility complex class I) and costimulatory molecules CD80 and CD86 on cell surface. By using flow cytometry, we analysed the effects of Orlistat on the percentage of CD3+CD8+ TLs, CD3-CD49b+ NK cells, and CD11c+ DCs in primary tumors and lymph node metastases. Activation of CD8+ TLs and NK cells was evaluated through the expression of granzyme b and perforin in the metastatic mediastinal lymph nodes by quantitative RT-PCR. In addition, NK cells present in lymph node metastases were also evaluated regarding the expression of Ly49A by flow cytometry. Orlistat was able to reduce in aproximately 30% the number of metastatic lymph nodes. Control primary tumors had a low percentage of CD3+CD8+ TLs (0.36%) and CD3-CD49b+ (0.27%), which were not detected in the treated tumors, suggesting a supression of this population. In addition, CD11c+ DCs could not be assessed in both treated and control tumors. Regarding metastatic lymph nodes, there was a slight increase of CD11c+ DCs, associated with a lower expression of the surface proteins MHC I, CD80 and CD86. CD3+CD8+ TLs and CD3-CD49b+ NK cells were reduced in the metastases from the treated animals. Moreover, the expression of granzyme b and perforin was lower in the metastases of treated mice. Finally, the expression of of Ly49A on NK cells was higher in metastatic lymph nodes of treated animals. Taken together, our results indicate that inhibition of FASN with Orlistat changes the phenotype, percentage and activation state of intratumoral and lymph node immune cells, suggesting a immunosuppressive activity
Mestrado
Estomatologia
Mestre em Estomatopatologia
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Denhez, Clément. „Nouvelles méthodes de génération et d'activation de complexes zirconocènes : Synthèse de composés azotés“. Reims, 2006. http://theses.univ-reims.fr/exl-doc/GED00000440.pdf.
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Ce mémoire concerne le développement de nouvelles méthodes d’activation de complexes zirconocènes reposant sur une coopération bimétallique. Cette démarche a été appliquée à la synthèse de composés azotés. La première partie de ce travail est consacrée au développement d’une réaction hautement chimiosélective de carboalumination d’aldimines sous catalyse au zirconium. Cette réaction met en jeu des alanes en tant que source de groupements alkyls et procède via l’établissement d’un complexe bimétallique. Dans le cas des imines dérivées de l’aniline une réaction d’acylation régiosélective en position ortho, également catalysée par le zirconium, peut être mise en oeuvre. Dans la deuxième partie, nous avons développé une synthèse diastéréosélective de pyrrolidines substituées en position 2- et 2,5-. Celles-ci sont obtenues à partir de Nallyloxazolidines optiquement pures selon une séquence d’hydrozirconation / cyclisation activée par un acide de Lewis. Au cours du troisième chapitre, nous avons développé une méthode de préparation stéréosélective de γ-lactames via une réaction de couplage intramoléculaire de carbamates homoallyliques impliquant la chimie du zirconium(II). Enfin, la dernière partie de cette thèse a été consacrée au développement d’un nouveau réactif, équivalent synthétique du zirconocène(II). Celui-ci est obtenu par réduction du dichlorure de zirconocène par un alliage de lanthanides, le mischmetall. Ce nouveau réactif a montré un fort potentiel synthétique dans de nombreux couplages et a notamment permis d’utiliser, pour la première fois, des alcynes vrais et de réaliser la première trimérisation d’alcynes catalysée par le zirconiumThis memory deals with the development of new methods for activation of zirconocene complexes through a bimetallic co-operation. New syntheses of nitrogencontaining compounds have been developed on this basis. The first part of this work is devoted to the highly chemoselective carboalumination of aldimines under zirconium catalysis. This reaction involves alanes as alkyl promotors and proceeds through metallacycles involving a bimetallic polarisation. In the case of imines derived from aniline, a zirconium-catalyzed regioselective acylation at the ortho position can be carried out. In the second part, we developed a new diastereoselective synthesis of 2- and 2,5- substituted pyrrolidines starting from optically pure N-allyloxazolidines, according to a hydrozirconation/ Lewis acid-catalyzed cyclization sequence. The third chapter presents a stereoselective synthesis of γ-lactams from N-homoallylcarbamates, by using a zirconium (II)-mediated intramolecular coupling reaction. Finally, the last part of this thesis was devoted to the development of a new reagent, synthetic equivalent of zirconocene(II). This reagent is obtained by reduction of dichlorozirconocene with a lanthanide alloy, the mischmetall. This new reagent possesses an important synthetic potential in many couplings. In particular, the first coupling involving 1- alkynes and the first zirconium catalyzed trimerisation of alkynes have been carried out
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BRÁS, Daniela Cristina de Henriques. „Mechanisms of inhibition of Plasmodium liver infection by amino acid supplementation“. Master's thesis, Instituto de Higiene e Medicina Tropical, 2018. http://hdl.handle.net/10362/52857.
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A malária é uma das doenças infeciosas mais prevalentes no mundo1. É causada por parasitas protozoários do género Plasmodium, os quais são transmitidos aos seus hospedeiros mamíferos através da picada de um mosquito Anopheles fêmea infetado1,2. A primeira fase da infeção, obrigatória e assintomática, ocorre no fígado e é iniciada quando os esporozoítos injetados invadem os hepatócitos do hospedeiro2,3. Aí, os parasitas diferenciam-se e desenvolvem-se até se formarem merozoitos, que são libertados na corrente sanguínea, infetando ciclicamente os eritrócitos e causando os sintomas da malária2,3.
A multiplicação dos parasitas durante a fase hepática da infeção é sustentada pela obtenção de nutrientes a partir do seu hospedeiro. Um desses nutrientes é a arginina (Arg), cujo metabolismo é crucial para o desenvolvimento intra-hepático do parasita4.
A Arg tem-se tornado cada vez mais popular na suplementação nutricional dada a sua capacidade de estimular o sistema imunitário5, sendo a única suplementação baseada em aminoácidos avaliada no contexto da malária. No entanto, embora a suplementação com Arg possa aumentar a produção de óxido nítrico (NO), diminuir a parasitemia, e melhorar a sobrevivência em modelos animais de infeção por Plasmodium, os resultados obtidos na clínica têm sido inconclusivos 6,7,8.
Resultados preliminares do laboratório de acolhimento demonstraram que a suplementação de murganhos C57Bl/6 com RKV, em que a administração de Arg (R) é combinada com a de Lisina (K) e Valina (V), dois aminoácidos descritos como inibidores da arginase, leva a uma diminuição acentuada da infeção hepática, sobretudo através da redução do número de hepatócitos infetados, sugerindo uma eliminação dos parasitas. No entanto, permanece por esclarecer se este fenótipo é recapitulado noutras estirpes de murganhos. Assim, o primeiro objetivo desta tese foi caracterizar a infeção hepática por Plasmodium em murganhos BALB/c após suplementação com Arg e RKV. Demonstrámos que a suplementação com Arg é suficiente para inibir a infeção hepática por Plasmodium em murganhos BALB/c, enquanto a suplementação com RKV pode levar tanto ao aumento como à diminuição da infeção hepática, em ambos os casos afetando principalmente o número de hepatócitos infetados. A razão desses resultados contraditórios permanece desconhecida.
O segundo objetivo desta tese foi elucidar o mecanismo de eliminação hepática do parasita em murganhos C57Bl/6 suplementados com RKV. Demonstrámos que a eliminação do parasita pela suplementação com RKV não depende nem da produção de NO, nem da estimulação da resposta de interferão tipo-I (IFN), anteriormente relatadas como cruciais para o controlo da infeção hepática9,10. Utilizando murganhos knockout e eliminando populações de células imunes específicas, identificámos as Células Linfóides Inatas (ILCs) como potenciais células imunes efetoras envolvidas na eliminação do parasita dependente de RKV. Adicionalmente, a sinalização através de MyD88 parece ser essencial para a eliminação hepática do parasita após suplementação com RKV, embora as células envolvidas nessa sinalização permaneçam desconhecidas.
Este projeto irá melhorar o nosso conhecimento quanto aos aspetos fundamentais da biologia de Plasmodium e quanto à resposta do hospedeiro face à infeção, abrindo caminho para o desenvolvimento de potenciais novas estratégias que possam vir a ser usadas para controlar a infeção por Plasmodium.Malaria is an acute febrile illness and one of the most prevalent infectious diseases in the world1. It is caused by protozoan parasites of the genus Plasmodium that enter their mammalian host in the form of sporozoites, via the bite of an infected female Anopheles mosquito1,2. The first, obligatory and asymptomatic phase of infection occurs in the liver and is initiated when injected sporozoites invade their host’s hepatocytes2,3. There, parasites differentiate and develop until merozoites are formed and released into the bloodstream, cyclically infecting red blood cells and causing the malaria symptoms2,3. During the liver-stage of infection, Plasmodium parasites scavenge host nutrients to support their multiplication. One of these nutrients is arginine (Arg), whose metabolism is crucial for the parasite’s intrahepatic development4. Arg is becoming increasingly popular in nutritional supplementation for its ability to boost the immune system5. Arg is so far the only amino acid-based supplementation evaluated in the context of malaria. However, although Arg supplementation can enhance nitric oxide (NO) production, decrease parasitaemia and improve survival in animal models of Plasmodium infection, unclear results have been obtained in the clinic6,7,8. Preliminary results from the host laboratory have shown that supplementation of C57Bl/6 mice with RKV, which combines Arg (R) with Lysine (K) and Valine (V), two amino acids described as arginase inhibitors, but not Arg alone, leads to a striking decrease of hepatic infection, mostly by reducing the number of infected hepatocytes, suggesting that parasites are being eliminated. However, whether this phenotype was also recapitulated in other mouse strains remained unclarified. Thus, the first aim of this thesis was to characterize Plasmodium liver infection in BALB/c mice upon Arg and RKV supplementation. We found that Arg supplementation is sufficient to impair Plasmodium liver infection in BALB/c mice and, on the contrary, RKV supplementation can lead to either an increase or a decrease in Plasmodium hepatic infection, in both cases mostly by affecting the number of infected hepatocytes. The reason for these contradictory results remains unknown. The second aim of this thesis was to elucidate the mechanism of hepatic parasite elimination in C57Bl/6 mice upon RKV supplementation. We found that parasite elimination by RKV supplementation does not rely on NO production nor on a boost of the type-I interferon (IFN) response, previously reported as crucial to control liver-stage infection9,10. Employing knockout mice and depleting specific immune cell populations, we identified Innate Lymphoid Cells (ILCs) as potential effector immune cells involved in RKV-dependent parasite elimination. Additionally, signalling via MyD88, seems to be essential for hepatic parasite’s elimination upon RKV supplementation, although the cells in which this signalling occurs remain unidentified. This project will enhance our knowledge of fundamental aspects of Plasmodium biology and of the host’s response to infection, paving the way to the development of potential new strategies that may ultimately be employed to control Plasmodium infection.
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Blackmore, Ian John. „The reactivity of the bis(imino)pyridine ligand towards alkylating agents and the role of acid in ligand exchange reactions“. Thesis, Imperial College London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.412026.
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Zidirich, Victor Eustáquio Tostes. „Efeitos do ácido linoléico conjugado (CLA) cis-9 trans-11 na resposta imune à ovalbumina“. Universidade Federal de Juiz de Fora, 2011. https://repositorio.ufjf.br/jspui/handle/ufjf/2093.
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O ácido linoléico conjugado, do inglês “Conjugated Linoleic Acid” (CLA) é uma mistura de isômeros de posição e geométricos do ácido linoléico (C18:2 n-6), comumente encontrado em maiores concentrações na carne bovina e em produtos lácteos de ruminantes. Numerosas atividades biológicas têm sido atribuídas aos isômeros C18:2 cis-9, trans-11(c9t11) e ao C18:2 trans-10, cis-12 (t10c12) dentre as quais destacam-se: propriedades anticarcinogênica, antiaterogênica, antiobesogênica, incluindo aumento da massa magra em animais, retardo do aparecimento de diabetes tipo II e também nas respostas imunes humoral e celular. O presente trabalho focou na utilização do c9t11 na dieta em camundongos da linhagem BALB/c, avaliando efeitos na resposta imune humoral como a produção anticorpos específicos para ovalbumina (OVA), bem como a síntese de citocinas e respostas à hipersensibilidade tardia (HTT). O trabalho mostrou que o CLA na dieta reduziu efeitos nas respostas de HTT em 24 horas nos animais e estes apresentaram altos níveis de Ac anti- IgG1 e supressão no perfil Th1 de citocinas como IFN-γ e TNF-α. Com base nesses resultados foi possível perceber que o CLA foi um importante fator no controle do processo inflamatório do modelo e que seu uso poderia ser considerado como uma importante intervenção profilática para muitas doenças de natureza inflamatória.
Conjugated Linoleic Acid (CLA) is a mixture of positional and geometrical isomers of linoleic acid (C18:2 n-6), commonly found in high concentrations in bovine meat and lacteous products from ruminants. Numerous biological activities have been attributed to C18:2 cis-9, trans-11(c9t11) and C18:2 trans-10, cis-12 (t10c12) isomers, among which anti-carcinogenic, anti-aterogenic, anti-obesity properties must be highlighted, including increase of thin mass in animals, delay in type II diabetes emergence and also in humoral and cellular immune responses. This work focused on the use of c9t11 in the diet of BALB/c mice, evaluating effects on humoral immune response by means of production of ovalbumin (OVA) specific antibodies, cytokine production and responses to delayed type hypersensitivity (DTH). The results showed that using CLA in the diet of BALB/c mice decreased effects on DTH responses in a 24h period after animals had been challenged. They exhibited high levels of Ab anti-IgG1 and suppression of Th1 profile cytokines such as IFN-γ and TNF-α. Based on these results, it was possible to say that CLA was an important factor of control in the inflammatory process of the model and that its use could be considered as an important prophylactic intervention for many diseases of inflammatory nature.
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Giungi, Alessandro. „Synergistic catalysis in asymmetric synthesis of polysubstituted pyrrolidines“. Master's thesis, Alma Mater Studiorum - Università di Bologna, 2018. http://amslaurea.unibo.it/16157/.
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This thesis deals with the feasibility of synthesizing stereodefined polysubstituted pyrrolidines in a formal [3+2] cycloaddition, starting with vinylciclopropanes (also called VCP) with two geminal electron-withdrawing groups (EWG), employed to make formal 1,3-dipole, and imines, used as dipolarophiles. This synthesis is based on the so called synergistic catalysis, that could be described as the combination of two catalytic species, each one able to activate one reaction partner. The former catalyst is a palladium complex, capable of activating the VCP by forming the aforementioned 1,3-dipole via oxidative addition. The latter, instead, is a chiral Brønsted acid, like a BINOL-derived phosphoric acid or triflamide, which not only makes the imine more electrophilic, but can also induce the preferential formation of a diastereoisomer over the other one and even enantiomeric excess within the diastereomeric couples, thanks to its axial chirality.
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Maciel, Bruna Leal Lima. „Estado nutricional e efeito da vitamina A na resposta imune frente ? infec??o por Leishmania Infantum“. Universidade Federal do Rio Grande do Norte, 2013. http://repositorio.ufrn.br:8080/jspui/handle/123456789/12575.
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Nutritional status is an important determinant to the response against Leishmania infection, although few studies have characterized the molecular basis for the association found between malnutrition and the disease. Vitamin A supplementation has long been used in developing countries to prevent mortality by diarrheal and respiratory diseases, but there are no studies on the role of vitamin A in Leishmania infection, although we and others have found vitamin A deficiency in visceral Leishmaniasis (VL). Regulatory T cells are induced in vitro by vitamin A metabolites and are considered important cells implicated T CD4+ cell suppression in human VL. This work aimed to examine the correlation of nutritional status and the effect of vitamin A in the response against Leishmania infantum infection. A total of 179 children were studied: 31 had active VL, 33 VL history, 44 were DTH+ and 71 were DTH- and had negative antibody to Leishmania (DTH-/Ac-). Peripheral blood monuclear cells were isolated in a subgroup of 10 active VL and 16 DTH-/Ac- children and cultivated for 20h under 5 different conditions: 1) Medium, 2) Soluble promastigote L. infantum antigens (SLA), 3) All-trans retinoic acid (ATRA), 4) SLA + ATRA and 5) Concanavalin A. T CD4+CD25highFoxp3+, T CD4+CD25-Foxp3- and CD14+ monocytes were stained and studied by flow cytometry for IL-10, TGF-β and IL-17 production. Nutritional status was compromised in VL children, which presented lower BMI/Age and retinol concentrations when compared to healthy controls. We found a negative correlation between nutritional status (measured by BMI/Age and serum retinol) and anti-Leishmania antibodies and acute phase proteins. There was no correlation between nutritional status and parasite load. ATRA presented a dual effect in Treg cells and monocytes: In healthy children (DTH-/Ac-), it induced a regulatory response, increasing IL-10 and TGF-β production; in VL children it modulated the immune response, preventing increased IL-10 production after SLA stimulation. Furthermore, we found a positive correlation between BMI/Age and IL-17 production and negative correlation between serum retinol and IL-10 and TGF-β production in T CD4+CD25highFoxp3+ cells after SLA stimulus. Our results show a potential dual role of vitamin A in the immune system: improvement of regulatory profile during homeostasis and down modulation of IL-10 in Treg cells and monocytes during symptomatic VL. Therefore, the use of vitamin A concomitant to VL therapy might improve recovery from disease status in Leishmania infantum infection
O estado nutricional ? importante determinante da resposta ? infec??o por Leishmania. No entanto, s?o poucos os trabalhos que caracterizem as bases moleculares das associa??es encontradas entre a desnutri??o e a doen?a. A suplementa??o de vitamina A ? utilizada em pa?ses em desenvolvimento para reduzir a mortalidade por diarreia e doen?as respirat?rias. Apesar disso, n?o existem estudos sobre o papel da vitamina A na infec??o por Leishmania apesar de nosso grupo e outros terem demonstrando a defici?ncia de vitamina A durante a leishmaniose visceral (LV). As c?lulas T regulat?rias s?o consideradas c?lulas supressoras durante a LV e s?o induzidas por metab?litos de vitamina A. Este trabalho teve como objetivo verificar a correla??o do estado nutricional e o efeito da vitamina A na resposta frente ? infec??o por Leishmania infantum. Foram estudadas 179 crian?as, sendo 31 casos de LV ativa, 33 com hist?ria pregressa de LV, 44 DTH+ e 71 DTH- e Anticorpo anti-Leishmania negativo (DTH-/Ac-). C?lulas mononucleadas de sangue perif?rico foram isoladas em um subgrupo de 10 crian?as com LV e 16 DTH-/Ac-, sendo cultivadas por 20h sob as seguintes condi??es: 1) Meio, 2) Ant?genos sol?veis de promastigotas de L. infantum (SLA), 3) ?cido all-trans retin?ico (ATRA), 4) SLA + ATRA e 5) Concanavalina A. As c?lulas T CD4+CD25highFoxp3+, T CD4+CD25-Foxp3- e mon?citos CD14+ foram marcadas e estudadas por citometria de fluxo quanto ? produ??o de IL-10, TGF-β e IL-17. O estado nutricional apresentou-se comprometido nas crian?as com LV, que apresentaram menor IMC/idade e baixas concentra??es de retinol s?rico quando comparadas aos controles sadios. Observou-se correla??o negativa entre o estado nutricional (medido por ?ndice de Massa Corporal/Idade e retinol s?rico) e anticorpos anti-Leishmania e prote?nas de fase aguda. N?o foi encontrada correla??o entre o estado nutricional e a carga parasit?ria. O ATRA apresentou efeito distinto nas c?lulas Treg e mon?citos: Em crian?as saud?veis (DTH-/Ac-), induziu resposta regulat?ria, com aumento na produ??o de IL-10 e TGF-β; e, em crian?as com LV, modulou a resposta imune, diminuindo a produ??o de IL-10 ap?s o est?mulo com SLA. Foi encontrada correla??o positiva entre o IMC/Idade e a produ??o de IL-17 e correla??o negativa entre o retinol s?rico e a produ??o de IL-10 e TGF-β nas c?luas T CD4+CD25highFoxp3+ ap?s est?mulo com SLA. Os dados deste estudo permitem concluir que o estado nutricional comprometido durante a LV ? correlacionado com a resposta imune e inflamat?ria frente ? Leishmania. Al?m disso, possivelmente, a vitamina A apresenta duplo efeito na resposta imune: em crian?as sadias, promove resposta regulat?ria; durante a LV, reduz a produ??o de IL-10 em c?lulas Treg e mon?citos. Dessa forma, o uso de vitamina A durante a LV pode promover a recupera??o de pacientes em tratamento para a doen?a
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Bejan, Dana [Verfasser]. „The strong N–H acid bis[bis(pentafluoroethyl)phosphinyl]imide, H[(C2F5)2P(O)}2N] Salts and ionic liquids / Dana Bejan“. Wuppertal : Universitätsbibliothek Wuppertal, 2011. http://d-nb.info/101829824X/34.
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Genoni, A. „EXPLORING NOVEL ORGANOCATALYTIC METHODOLOGIES FOR CARBON-NITROGEN DOUBLE BOND REDUCTION“. Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/229551.
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The development of novel methodologies for the preparation of enantiomerically pure compounds is a topic of great interest for several fields. In particular, it must be mentioned that chiral amines are finding applications in an ever-increasing number of fields, so the possibility of developing an organocatalytic approach has gained much attention.
During my work, the enantioselective organocatalytic reduction of fluorinated ketimines was successfully realized by using trichlorosilane as reducing agent in the presence of catalytic amounts of an inexpensive and readily available picolinamide derived from ephedrine. The methodology allowed to reduce imines derived both from aryl and alkyl trifluoromethyl ketones in very good yields and high enantioselectivities, typically of 90% e.e. and up to 98% e.e.. With a ACE (Asymmetric Catalyst Efficiency) value of about 44, the ephedrine-derived picolinamidic catalyst established itself as one of the most efficient and versatile catalyst for the reduction of a wide range of fluorinated imines, favourably comparing both with chiral phosphoric acids and even with organometallic catalysts. The well documented possibility to easily remove the N-PMP residue or the benzyl group makes the present method a viable and attractive synthesis also for highly enantiomerically enriched fluorinated primary amines.
Moreover, the straight forward synthesis of a novel class of cinchona-based chiral Lewis bases was developed. A series of enantiomerically pure Lewis bases were obtained by performing a Mitsunobu reaction on the commercially available alkaloids followed by simple condensation with picolinic acid. Under the optimized reaction conditions, such compounds were shown to promote the enantioselective reduction of ketimines with trichlorosilane with nearly quantitative chemical yield and high enantioselectivity. Even more interestingly, these high levels of yields and enantioselectivity remained constant when the reaction was carried out with only a 1 mol % catalyst loading. Further modification of these compounds allowed to raise the enantioselectivity of the process, leading to the quantitative formation of the corresponding amine with up to 88% e.e..
These catalyst were successfully employed also in the organocatalytic reduction of alpha-imino and beta-enamino esters with trichlorosilane, obtaining the corresponding products with high chemical yield and good enantiomeric excess. Moreover, the combination of this low cost, easy to make metal-free catalyst and an inexpensive chiral auxiliary allowed to obtain chiral beta-amino esters with nearly total control of the stereoselectivity.
In the field of catalytic methods for carbon nitrogen double bond reduction, I’ve also studied a very novel catalytic approach to realize the activation and utilization of H2: the concept of frustrated Lewis pair (FLP) recently introduced by the Stephan’s research group. Once performed a screening of several additives to find an efficient catalytic pair, the FLP catalyzed diastereoselective hydrogenation of a chiral ketimine was accomplished with 67% yield and 82:18 d.r. without the necessity to perform the reaction in glovebox.
Finally, taking into account the excellent enantioselectivities obtained in the reduction of C-N double-bonds with phosphoric acid catalysis, we decided to explore the performance of these systems employing HSiCl3 as reducing agent. After an optimization of the stoichiometry of the reaction, we were able to achieve up to 29% e.e. using 10 mol % unsubstituted BINOL-derived phosphoric acid, which could be raised up to 60% e.e. using a stoichiometric amount of the acid.
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Bowens, Andrea Demetrius. „Synthesis and Characterization of Poly(siloxane imide) Block Copolymers and End-Functional Polyimides for Interphase Applications“. Diss., Virginia Tech, 1999. http://hdl.handle.net/10919/29985.
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End-functional poly(ether amic acid)s and poly(siloxane imide) multiblock copolymers, comprised of 2,2'-Bis[4-(3,4-dicarboxyphenoxy)phenyl]propane dianhydride (BPADA) / meta-phenylene diamine (MPDA) and hexafluoroisopropylidene-2-bis(phthalic acid anhydride) (6FDA) / meta-phenylene diamine (MPDA) polyimide segments, have been prepared and characterized to explore possibilities for controlling interface properties. Incorporation of polydimethylsiloxane (PDMS) components into polyimide backbone structures can yield advantageous properties such as low energy surfaces and low stress interfaces.
End-functional BPDA/MPDA poly(amic acid) salts and poly(siloxane amic acid) salts were prepared in methanolic or aqueous tripropylamine solutions. The polymeric salts formed stable water solutions (or dispersions) and imidized in less than 10 minutes at 260°C. The water solubility and rapid imidization times are ideal for on-line processing. Thus, these materials can be used as sizing and interface toughening agents for fiber reinforced composite manufacturing. Epoxy-polyimide networks prepared from the amine functionalized polyimide with DER 331 epoxy resin and diamino diphenylsulfone showed microphase separation (100-300 nm inclusions) by transmission electron microscopy. Slight toughening of the cured epoxy with 9 weight % imide was observed with the imide as the included phase. Epoxy bilayer films of polyimide (amine end-functional and commercial Ultem⠢) and poly(siloxane imide) multiblock copolymers were prepared to evaluate the polymer-matrix interphase region. Atomic force microscopy (AFM) analysis of the bilayer films showed diffusion at the interphase for the bilayers prepared with the polyimides and the BPADA/MPDA block copolymers containing polyimide continuous phases.
Poly(siloxane imide) multiblock copolymers comprised of 6FDA/MPDA polyimide structures are ideal candidates for controlling interfacial properties between silicon substrates layered with thin films for microelectronic applications. These high Tg materials offer an approach for obtaining reduced moisture absorption and low stress interfaces. Evaluation of the refractive indices of the block copolymer films showed a decrease with increasing siloxane content thus suggesting the possibility of lower dielectric constants. The polymer-metal interfacial properties were investigated for films cast on titanium and tantalum substrates. The results suggested a correlation between the surface hydroxyl concentration of the metal oxide layer with the interfacial properties of the cast poly(siloxane imide) block copolymer films. The surface hydroxyls were thought to hydrogen bond with the PDMS component of the block copolymer. Since the titanium substrate has a higher surface hydroxyl concentration than the tantalum, higher silicon concentrations were observed.
The melt imidized end-functional polyimides and poly(siloxane imide) block copolymers produced thermally stable materials with 5% weight loss temperatures well above 400°C. However, the block copolymers showed slightly lower 5% weight loss temperatures as a function of siloxane content with a significant increase in char formation. Correlation of the upper glass transition temperatures with the imide segment length was consistent with findings noted for other phase separated randomly segmented block copolymers.
Incorporating PDMS into the polyimide backbone structure has an effect on the bulk and surface properties. The bulk properties of the poly(siloxane imide) block copolymers were characterized using TEM. The morphologies were consistent with classical block copolymers. Surface properties of the block copolymer films as a function of PDMS content were investigated using angular dependent X-ray photoelectron spectroscopy at take-off angles of 15, 30, and 45°. Surface enrichment of PDMS content over that of the bulk was observed at all three sampling depths. Further evidence of this siloxane enrichment in the surface was demonstrated with water contact angle analyses. With as little as 5 weight % PDMS (Ph. D.
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Meyer, Luc. „Auxiliaires chiraux à centre d'aiguillage : nouveaux outils en synthèse asymétrique. Application à la synthèse d'α-aminoacides de configuration (R) ou (S)“. Rouen, 1997. http://www.theses.fr/1997ROUES063.
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De nouveaux outils pour la synthèse asymétrique sont proposés : des auxiliaires chiraux à centre d'aiguillage (R,S). Le passage du (1R,2S,5R)-2-diméthylphénylméthyl-5-méthylcyclohexyl carbaldéhyde à l'imine correspondante du glycinate de méthyle, suivi de la déprotonation (diisopropylamidure de lithium), puis de l'alkylation par des halogénures d'alkyles conduit après hydrolyse à des α-aminoacides de configuration (R) avec des e. E. >98%. Il a été montré que pour obtenir les α-aminoacides de configuration (S), il n'était pas nécessaire d'inverser la totalité des centres stéréogéniques de l'aldéhyde initial, l'inversion d'un seul centre étant suffisante. Ainsi, à partir de l'aldéhyde (1S,2S,5R), des α-aminoacides de configuration (S) ont été obtenus avec des e. E. >98%. La méthode a été généralisée à la synthèse d'un α-aminoacide à centre quaternaire la (R)-methyldopa avec un e. E. >98%. Les aldéhydes (1R,2S,5R) et (1S,2S,5R) sont aisément obtenus à partir de la (R)-(+)-pulégone et transformés facilement l'un en l'autre par épimérisation. L'aldéhyde utilisé est donc un auxiliaire chiral à centre d'aiguillage (R,S).
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Gardinal, Rodrigo. „Efeito da suplementação prolongada de grão de soja cru e integral no pré-parto sobre o desempenho produtivo, qualidade oocitária e embrionária, e função imune de vacas leiteiras“. Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/10/10135/tde-24052016-093948/.
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Objetivou-se avaliar o efeito da suplementação prolongada de grão de soja cru e integral (GSI) como fonte de ácido graxo Ω6 sobre o desempenho produtivo, perfil metabólico, qualidade oocitária e embrionária e função imune de vacas leiteiras no período de transição e início de lactação. Foram selecionadas 44 vacas da raça Holandesa, multíparas e gestantes, com parto previsto para 90 dias após o início da avaliação e fornecimento das dietas experimentais, porém em razão da ocorrência de enfermidades metabólicas ou infecciosas (3 abortos; 3 deslocamentos de abomaso; 3 enfermidades podais; 4 distocias) 13 animais foram retirados do experimento. As vacas foram distribuídas aleatoriamente em quatro grupos experimentais diferindo entre eles o início do fornecimento de grão de soja cru e integral (GSI) durante o pré-parto. A dieta era baseada na inclusão de 12% de GSI %MS, com aproximadamente 5,1% de extrato etéreo (EE) o início de seu fornecimento foi conforme descrito a seguir: Grupo 0: Animais não receberam dieta contendo GSI no pré-parto; Grupo 30: Início do fornecimento de dieta com GSI nos 30 dias finais da gestação; Grupo 60: Início do fornecimento de dieta com GSI nos 60 dias finais da gestação; Grupo 90: Início do fornecimento de dieta com GSI nos 90 dias finais da gestação. Após o parto, todas as vacas receberam dieta única com 5,1% de EE, baseada na inclusão de 12% de GSI %MS até 90 dias de lactação. Os animais foram arraçoados de acordo com o consumo de matéria seca no dia anterior, de forma a ser mantido porcentual de sobras das dietas, diariamente, entre 5 e 10%. As amostras dos alimentos e sobras foram coletadas diariamente e armazenadas a -20ºC. Semanalmente as amostras coletadas diariamente foram misturadas e foi retirada uma amostra composta referente a um período de uma semana, a fim de mensurar o consumo de matéria seca e nutrientes. Amostras de fezes foram coletadas nos dias -56, -21, 21, 56 e 84 dias em relação ao parto, com o propósito de mensurar a digestibilidade da matéria seca e nutrientes. A produção de leite foi mensurada diariamente e para a composição dos teores de gordura, proteína, lactose e perfil de ácidos graxos amostras foram coletadas semanalmente. As amostras de sangue para análise dos metabólitos sanguíneos foram coletadas semanalmente. Amostras de sangue para mensurar a atividade do sistema imune foram coletadas na semanas -8, -4, -2, -1 em relação ao parto, parto, +1, +2, +4 e +8 semanas no período pós-parto. Nos dias 21, 42, 63 e 84 do período pós-parto foram realizadas aspirações foliculares, com posterior fertilização in vitro dos oócitos. Todas as variáveis mensuradas foram analisadas pelo procedimento PROC MIXED do SAS 9.4 através de regressão polinomial, utilizando efeito fixo de tratamento, semana, interação tratamento*semana e efeito de animal dentro de tratamento como aleatório. Utilizou nível de 5% de significância. Foi observado efeito (P<0,05) linear crescente para CEE no pré-parto. Não foi observado diferenças no CMS e nutrientes no pós-parto. Não houve alteração da digestibilidade nos períodos pré e pós-parto. Não houve alteração no balanço de energia e nitrogênio nos periodos pré e pós-parto. Não foi observado diferença na produção, composição e teor dos componentes totais do leite. No perfil de ácidos graxos do leite houve efeito (P<0,05) linear descrescente para as concentrações de C16:1cis, C18:1 cis, total de C:18 insaturado, total de AG monoinsaturados, insaturados e a relação do total de AGS:AGI. Foi observado efeito linear (P<0,05) crescente para o total de AG aturado e efeito (P<0,05) quadrático para C18:2, CLAcis9-trans11, e total de AGPI. Foi observado efeito linear crescente (P<0,05) para colesterol total, LDL no préparto e linear decrescente (P<0,05) para GGT nos períodos pré e pós-parto. Foi observado efeito quadrático (P<0,05) para HDL no pré-parto e AST no pós-parto. Em relação a atividade do sistema imune foi observado efeito linear (P<0,05) crescente para o percentual de CD3+ ativos no pós-parto, para o percentual de monócitos que produziram espécie reativa de oxigênio (ERO) no pós-parto quando foram estimulados por S.aureus e E.coli e para a intensidade de imunofluorescência de ERO para ganulócitos no pós-parto quando estimulados por S.aureus. Foi observado efeito (P<0,05) quadrático para o percentual de granulócitos, mononucleares, CD8+ ativos no pós-parto e para o percentual de granulócitos que produziram ERO no pós-parto quando estimulados por E.coli. A suplementação prolongada com GSI no pré-parto melhora a atividade do sistema imune, não melhora a qualidade oocitária e embrionária bem como não influencia negativamente os parametros produtivos de vacas leiteiras no período de transição e início de lactaçãoThe objective was to evaluate the effect of prolonged supplementation with whole soybean grain (WSG) as a source of Ω6 fatty acid on the productive performance, metabolic profile, oocyte and embryo quality, and immune function of dairy cows during the transition period and early lactation. Forty-four multiparous, pregnant Holstein cows, with calving predicted to 90 days after the beginning of the evaluation and supply of the experimental diets were selected. However, due to the occurrence of metabolic or infectious disorders (3 abortions, 3 displaced abomasums, 3 foot disorders, 4 dystocias), 13 animals were removed from the experiment. Cows were randomly assigned to one of four experimental groups, which differed in period of supply of whole soybean grains during the prepartum. The diet was based on 12% of WSG (%DM) and had approximately 5.1% of ether extract (EE). Diet supply was as follows: Group 0) control diet not containing WSG; Group 30) WSG supply starting 30 days before predicted calving date; Group 60) WSG supply starting 60 days before predicted calving; Group 90) WSG supply starting 90 days before predicted calving date. After calving, all cows received a single diet with 5.1% EE, based on inclusion of 12% WSG (%DM) until 90 days of lactation. Animals were fed ad libitum to ensure between 5 and 10% orts daily. Dry matter and nutrients intake were evaluated. Samples of feeds and orts were collected daily and stored at -20°C. Samples were composited weekly and analyzed for chemical and bromatological characteristics. Feces samples were collected on days -56, -21, 21, 56, 84 (related to the predicted calving), in order to measure the digestibility of dry matter and nutrients. Milk yield was measured daily and milk samples were collected weekly for evaluation of fat, protein and lactose percentages, and fatty acids profile. Blood samples were taken weekly for analysis of blood metabolites. To measure the activity of the immune system, blood samples were collected at weeks -8, -4, -2, -1 prepartum, at calving, and at weeks +1, +2, +4, +8 postpartum. On days 21, 42, 63 and 84 postpartum, follicular aspirations were performed, with subsequent in-vitro fertilization of the oocytes. All measured variables were analyzed using PROC MIXED of SAS 9.4 through polynomial regression, considering as fixed effects the dietary treatment, week and interaction treatment*week, and animal as random effect. The 5% level of significance was considered. A crescent linear effect was observed (P <0.05) for prepartum ether extract intake. There was no difference in dry matter and nutrients intake during the postpartum period. There were no differences in digestibility pre and postpartum. No difference in energy and nitrogen balance during pre and postpartum periods was observed. Milk production and composition did not differ among dietary treatments. When evaluating the milk fatty acids profile, a decreasing linear effect was noted (P<0.05) for the concentrations of C16:1 cis, C18:1 cis, total unsaturated C18, total monounsaturated fatty acids, total unsaturated fatty acids and total SFA:UFA ratio. There was an increasing linear effect (P<0.05) for the total of saturated fatty acids and a quadratic effect (P<0.05) for C18:2, CLAcis9-trans11, and total PUFA. It was observed increasing linear effect (P<0.05) for total cholesterol and LDL in the prepartum period, and decreasing linear effect (P<0.05) for GGT in the pre and postpartum. We observed a quadratic effect (P<0.05) for HDL in prepartum and for AST during the postpartum. Regarding the activity of the immune system, there was a crescent linear effect (P<0.05) for the percentage of active CD3+ in the postpartum period, for the percentage of monocytes producing reactive oxygen species (ROS) during postpartum period when stimulated by S. aureus and E. coli, and for granulocytes ROS immunofluorescence intensity during postpartum when stimulated by S. aureus. Quadratic effect was observed (P<0.05) for the percentage of granulocytes, mononuclear cells, active CD8+ in the postpartum period and the percentage of granulocytes that produced ROS when stimulated by E. coli. Prolonged supplementation with RWS in the prepartum improves the activity of the immune system, however it does not improve oocyte and embryo quality and does not adversely affect the production performance of dairy cows during the transition period and early lactation