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1
Knight, Julian Gary. « Diphenylphosphinoylalkyk isoxazoles and isoxazolines ». Thesis, University of Cambridge, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306451.
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2
Tout, Jaki. « The synthesis and reactions of alkenyl isoxazoles and isoxazolines ». Thesis, University of Edinburgh, 1993. http://hdl.handle.net/1842/14563.
Texte intégralRésumé :
Four vinyl-isoxazoles and -2-isoxazolines have been synthesised as potential monomers for polymerisation studies. 5-Phenyl-3-vinylisoxazole was prepared in 38% overall yield by a sequence involving cycloaddition of ethoxycarbonyl-formonitrile oxide to phenylacetylene and then reduction of the resulting 3-carbethoxyisoxazole to the aldehyde using di-isobutylaluminium hydride. In the final stage Wittig olefination of the formyl-isoxazole afforded the target compound. 5-Phenyl-3-vinylisoxazole (17%) and 5-phenyl-3-vinyl-2-isoxazoline (26%) were synthesised similarily from ethyl propiolate & benzohydroximoyl chloride, and styrene & ethyl chlorooximidoacetate, respectively. 3-Phenyl-5-vinyl-2-isoxazoline (84%) was obtained in one step by cycloaddition of benzonitrile oxide to butadiene. An alternative and more direct approach to 3-vinylisoxazolines has been developed based on the cycloaddition reactions of acrylonitrile oxide (ANO), and α,β-unsaturated nitrile oxide. ANO was generated, under modified Mukaiyama conditions, by the dehydration of 1-nitropropene with phenyl isocyanate in the presence of catalytic quantities of triethylamine. ANO was trapped by a variety of olefinic dipolarophiles as its 1,3-dipolar cycloadducts in yields ranging from 17% to 71%. Under similar conditions phenylacetylene reacted in low yield (12%). The series of α,β-unsaturated nitrile oxides was extended to include methacrylonitrile oxide and but-2-enonitrile oxide. The dipolarophilic reactivity series was determined by competition experiments. Six dipolarophiles were investigated: Styrene, α-methylstyrene, methyl acrylate, methyl vinyl ketone and three substituted styrences (p-OMe, p-CI and m-NO2). 13C and 1H NMR spectroscopy were used to identify the products and determine the adduct ratio. The results indicated methyl acrylate to be the most reactive dipolarophile. The 1,1-disubstitution in α-methylstyrene effectively lowered its reactivity due to steric effects.
3
Lanson, Marc. « Isoxazoles polyalkyles synthèse, étude structurale et comportement en milieu biologique / ». Grenoble 2 : ANRT, 1987. http://catalogue.bnf.fr/ark:/12148/cb376069814.
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Lanson, Marc. « Isoxazoles polyalkyles : synthese, etude structurale et comportement en milieu biologique ». Paris 6, 1987. http://www.theses.fr/1987PA066468.
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5
Duffy, Kevin James. « Studies on the synthesis and reactivity of fused 3,4-isoxazoles ». Thesis, University of Edinburgh, 1993. http://hdl.handle.net/1842/13734.
Texte intégralRésumé :
This thesis is concerned with the synthesis of various fused, 3,4-isoxazoles by the thermal cyclisation of 2-nitroaryl and 2-nitroheteroaryl acetic acid derivatives and the exploitation of the uses of these compounds in heterocyclic synthesis by their reduction to afford 2-aminoaryl and heteroaryl ketones followed by the annulation of these latter derivatives. Heating solutions of 2-(3-nitropyrid-2-yl)propanedioate esters under reflux in inert solvents afforded isoxazolo[4,3-b]pyridine-3-carboxylate derivatives. The successful application of this novel synthesis on a large scale was crucially dependent on the physical removal of the corresponding alcohol component from the reaction mixture. The thermal cyclisation of various 2-substituted 2-(3-nitropyrid-2-yl)ethanoates was also examined and in the case of cyano derivatives afforded the anticipated isoxazolo[4,3-b]pyridines but was less successful for substrates containing keto groups. 2-(3-Nitropyrid-2-yl)ethanoate failed to cyclise to afford the parent isoxazolo[4,3-b]pyridine. Evidence is presented for the involvement of ketene intermediates in these thermal cyclisation reactions. Reduction of the isoxazol[4,3-b]pyridine-3-carboxylate derivatives gave either 2-(3-aminopyrid-2-yl)-2-hydroxyethanoate or 2-(3-aminopyrid-2-yl)-2-oxoethanoate derivatives depending on the substrate, the former compounds being converted into the latter by oxidation with manganese dioxide. Annulation of the 2-(3-aminopyrid-2-yl)-2-oxoethanoates produced then gave a variety of substituted 1,5-napthyridin-2(1H)-one derivatives. The chemical transformations of these new 1,5-napthyridine derivatives was also briefly examined. 1,7-Napthyridin-2(1H)-one derivatives were also prepared by a similar sequence of reactions commencing with the thermal cyclisation of diethyl 2-(3-nitropyrid-4-yl)propanedioate to give ethyl isoxazolo[3,4-c]pyridine-3-carboxylate followed by reductive ring opening of the latter and subsequent annulation of ethyl 2-(3-aminopyrid-4-yl)-2-oxoethanoate so produced.
6
Duller, Kathryn April Marion. « A cycloaddition route to heterocyclic tricarbonyl natural products ». Thesis, University of Nottingham, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307821.
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7
Khatimi, Nadia. « Synthèse d'hétérocycles substitués par un groupe trifluorométhyle (isoxazoles, aziridines, thiophènes, pyrroles) ». Lyon 1, 1996. http://www.theses.fr/1996LYO10177.
Texte intégralRésumé :
Le memoire presente en vue de l'obtention du diplome de doctorat est consacre a la synthese d'heterocycles possedant un groupe trifluoromethyle. La premiere partie presente une synthese originale de plusieurs trifluoromethylisoxazoles. Ces composes ont ete utilises pour preparer des aziridines substituees par une chaine trifluoroethyle. La synthese proposee est stereoselective. Dans le deuxieme chapitre, une synthese totalement stereoselective d'aziridines substituees par un groupe trifluoromethyle est proposee: les aziridines sont obtenues par addition du trifluoromethylsilane sur des azirines. Le dernier chapitre est essentiellement consacre a la synthese et la reactivite d'enamino enones substituees par un groupe trifluoromethyle. Leur cyclisation en pyrrole a ete effectuee et l'etude de differents facteurs, gouvernant une cyclisation 3 exotrig ou 5 exotrig, a ete realisee. A ce jour, ce travail a donne lieu a deux publications parues dans des revues internationales: 1 c. Felix, n. Khatimi et a. Laurent, j. Org. Chem. , 1995, 60, 3907-12. 2 c. Felix, n. Khatimi et a. Laurent, tetrahedron lett. , 1994, 35, 3303-3304
8
FALCOU, SERGE, et André Pierre Joseph Rassat. « Utilisation des isoxazoles en synthese : approche de la synthese de la phyllanthocine ». Paris 6, 1995. http://www.theses.fr/1995PA066314.
Texte intégralRésumé :
La synthese de la phyllanthocine et en particulier du systeme spirocetal bicyclique 6,5 fait intervenir la condensation aldolique de l'enolate du 3-acetylisoxazole sur un hydroxyaldehyde methyle. Apres la mise au point de la synthese de cet isoxazole inconnu, et suite a la mauvaise reactivite de l'enolate de cet isoxazole, une modification de la strategie de synthese nous a conduit a realiser un umpolung en condensant un alcynure sur le 3-carbomethoxyisoxazole. Cette strategie permet d'acceder au produit d'aldolisation precedemment souhaite par addition conjuguee diastereoselective d'un hemiacetalate sur une enone convenable dans des conditions basiques. La fermeture du cycle a six centres du spirocetal de la phyllanthocine etant realisee, la coupure reductrice de l'isoxazole a permis d'obtenir le precurseur direct du spirocetal
9
Michaud, Thierry. « Synthese d'heterocycles azotes enatiomeriquement purs (aziridines, azetidines, isoxazoles) au depart de monosaccharides ». Clermont-Ferrand 2, 1995. http://www.theses.fr/1995CLF21711.
Texte intégralRésumé :
Un axe important de la chimie des glucides est leur utilisation comme source de chiralite dans la synthese de molecules a proprietes biologiques potentielles. Notre objectif a ete la synthese d'azetidines polyhydroxylees substituees en 2 et 3, enantiomeriquement pures, au depart de monosaccharides. Des ditosylates en 4,6 ont ete prepares en quatre etapes au depart des d-gluco- et d-mannopyranose par acetalisation, c-alkylation, hydrolyse et tosylation. Dans la serie du d-glucopyranose l'action d'amines primaires (methyl-, benzyl-, et tertbutylamine) sur les derives ditosyles permet d'acceder, par l'intermediaire d'un derive monoamine en 6 et monotosyle en 4, a des azetidines fusionnees en 4,6 a un galactopyranoside. Huit azetidines fusionnees ont ete ainsi preparees. Le deblocage des fonctions alcoolprotegees sous forme d'ethers benzyliques, et l'ouverture du cycle pyranose par l'hydrogene en presence d'hydroxyde de palladium sur charbon active conduit a des azetidines polyhydroxylees optiquement pures possedant quatre centres asymetriques. Dans la serie du d-mannopyranose, l'action de la terbutylamine conduit au seul derive 4,6-didesoxy-4,6diaminod-talopyranoside. Les reactions de cycloaddition dipolaire 1,3 des methyl-et benzonitriloxydes sur la 3-bromolevoglucosenone sont regioselectives et conduisent a des isoxazoles fusionnes et substitues en 5 par le groupe carbonyle
10
Blackburn, Jack. « The synthesis, attempted synthesis and applications of 1,2,4-oxadiazoles and isothiazolo-isoxazoles ». Thesis, University of Huddersfield, 2014. http://eprints.hud.ac.uk/id/eprint/26888/.
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11
Gayon, Eric. « Stratégies pour l'accès rapide à des hétérocycles azotés à partir d'alcools propargyliques ». Thesis, Montpellier, Ecole nationale supérieure de chimie, 2012. http://www.theses.fr/2012ENCM0017/document.
Texte intégralRésumé :
La partie principale de ce manuscrit traite du développement de nouvelles méthodologies utilisant la substitution propargylique catalysée par des sels de fer(III), pour la formation de divers hétérocycles azotés (∆4-isoxazolines, isoxazoles, cis-acylaziridines et pyrimidines). En premier lieu, de nouvelles synthèses monotopes de ∆4-isoxazolines et d'isoxazoles diversement substitués impliquant des réactions de cyclisation catalysées par diverses espèces carbophiles ([Au], [Pd], [I+]) ont été développées. La fragilité de la liaison N-O des ∆4-isoxazolines a pu être ensuite exploitée pour conduire à la formation de cis-acylaziridines. De nouvelles voies d'accès aux (Z)-β-énaminones et aux pyrimidines trisubstituées ont été également développéesThe main part of this manuscript deals with the development of new methodologies using iron(III)-catalyzed propargylic substitution, for the synthesis of various nitrogen-containing heterocycles (Δ4-isoxazolines, isoxazoles, cis-acylaziridines and pyrimidines). Firstly, new one-pot syntheses of variously substituted Δ4-isoxazolines and isoxazoles involving cyclization reactions promoted by various carbophilic species ([Au], [Pd], [I+]) have been developed. The weakness of the Δ4-isoxazoline N-O bond has been then exploited, leading to the formation of cis-acylaziridines. New pathways to (Z)-β-enaminones and trisubstituted pyrimidines have also been developed
12
Dawson, Claire E. « A cycloaddition route to heterocyclic triones ». Thesis, University of Nottingham, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243698.
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13
Kivrak, Arif. « Development Of New Methods For The Synthesis Of Pyrazoles, 4-iodopyrazoles, Isoxazoles And 1,2,4-oxadiazoles ». Phd thesis, METU, 2011. http://etd.lib.metu.edu.tr/upload/12612945/index.pdf.
Texte intégralRésumé :
Synthesis of five-membered heteroaromatic compounds such as pyrazoles, isoxazoles and 1,2,4-oxadiazoles are important for pharmaceutical industry and material science due to their applications. Although there are many methods to prepare such compounds, new variants continue to appear since they exhibit a wide range of biological and medicinal activities.
In this thesis, new methods were developed for the synthesis of 4-iodopyrazoles, pyrazoles, isoxazoles, 1,2,4-oxadiazoles and/or 1,2,4-oxadiazepines. In the first part of the study, electrophilic cyclization of &alpha,&beta
-alkynic hydrazones by molecular iodine and copper iodide were investigated as new ways for the synthesis of 4-iodopyrazoles and pyrazoles, respectively. Initially, &alpha
,&beta
-alkynic hydrazones were prepared by the reactions of propargyl aldehydes and ketones with hydrazines. Then &alpha
,&beta
-alkynic hydrazones were treated with molecular iodine in the presence of NaHCO3, which afforded 4-iodopyrazoles in good to excellent yields. Subsequently, the same reactions were carried out with CuI in the presence of NEt3, which furnished corresponding pyrazoles in good yields. Moreover, ferrocenyl-substituted 4-iodopyrazoles and pyrazole derivatives were synthesized from corresponding
14
Perez, Vincent. « Synthèses sélectives d’isoxazolines et isoxazoles phosphonates : compétition de C- vs. O-alkylation et cycloadditions d’ynamido-phosphonates ». Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS363.
Texte intégralRésumé :
En raison de la vaste gamme d'activités biologiques qu'ils possèdent, les aminophosphonates cycliques ont attiré l’attention des chimistes et des biologistes. La synthèse d’hétérocycles substitués par un atome de phosphore a largement été rapportée dans la littérature. Dans ce contexte, le premier défi a été de proposer une nouvelle voie d'accès au motif 5-phosphono-isoxazoline. Une méthodologie a été développée, reposant sur la formation de N-oxydes d’isoxazolines par réaction de O-alkylation d’un ion nitronate sur un composé α-substitué vinylphosphonate, suivie d’une réduction pour former les composés attendus. La réaction de O-alkylation a notamment fait l’objet d’une étude approfondie pour donner de manière exclusive le N-oxyde d’isoxazoline. Bien que les ynamides aient été largement décrits dans la littérature, la synthèse et la réactivité des ynamido-phosphonates ont quant à elles très peu été étudiées. Le deuxième défi a consisté à trouver une nouvelle approche de formation des ynamido-phosphonates par couplage cupro-catalysé à partir d’un bromoalcynylphosphonate préalablement synthétisé. Ensuite, la réactivité de ces ynamido-phosphonates a été étudiée dans le but de former des isoxazoles substitués par un atome de phosphore et d’azote. Des réactions de cycloaddition [1,3]-dipolaire sur ces ynamides ont été entreprises. Enfin, l’oxydation de ces ynamides a permis d’accéder à de nouveaux motifs phosphonospirodiénones lactamesDue to the wide range of biological activities that they show, cyclic aminophosphonates have attracted attention of the chemists and biologists. Hence, the synthesis of heterocycles substituted with a phosphorus atom has been reported in the literature. In this context, our first challenge was to propose a new route to access the 5-phosphono isoxazoline motif. A methodology was developed based on the formation of isoxazoline N-oxide through an O-alkylation reaction of a nitronate anion to α-substituted vinylphosphonate, followed by a reduction to form the expected product. The O-alkylation reaction was investigated to give exclusively the isoxazoline N-oxide. Although the chemistry of ynamides has been widely reported in the literature, the synthesis and reactivity of ynamido-phosphonates is less documented. Our second challenge consisted to find a new approach to synthesize ynamido-phosphonates using a copper catalyzed coupling reaction with a bromoalkynylphospnates previously formed. Next, the reactivity of these compounds was studied. In order to form isoxazoles substituted with a phosphorus and nitrogen atom, [1,3]-dipolar cycloaddition reactions have been studied with these ynamido-phosphonates. Finally, the oxidation of these ynamido-phosphonates was studied and it gave us access to new phosphonospirodienone lactams
15
Thenna, Hewa Kosala R. S. « Applications Focused Synthetic Modification on Photoremovable Protecting Groups (PRPG) & ; Photochemical Analysis on Organic Azides and Isoxazoles ». University of Cincinnati / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1511858669354976.
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ARICHI, JAOUAD. « Extraction liquide-liquide de terres rares par des 4-acyl-5-hydroxy-pyrazoles et -isoxazoles equilibres et cinetique de transfert. Synergies ». Université Louis Pasteur (Strasbourg) (1971-2008), 1998. http://www.theses.fr/1998STR13007.
Texte intégralRésumé :
L'extraction liquide-liquide de terres rares trivalentes (ln#3#+) a partir du milieu nitrate par des 4-acyl-5-hydroxy-pyrazoles, -ceto-enols notes ha, a ete etudiee. L'extraction croit avec le numero atomique croissant de ln et avec l'acidite croissante de ha, mais aux depens de la selectivite. La presence d'un agent de solvatation, s, associe a ha, de type o-donneur tel l'ether-couronne dibenzo-18-couronne-6 ou de type n-donneur comme la 2,4,6-tri(2-pyridyl)-1,3,5-triazine (tpytz) provoque un effet synergique important, avec l'extraction de complexes lna#3s, selon l'ordre db18c6 << tpytz. Par contre la selectivite d'extraction est reduite particulierement pour les terres rares les plus lourdes. Cependant, pour les systemes impliquant les 4-acyl-5-hydroxy-isoxazoles et la tpytz, l'ordre de la selectivite d'extraction est celle de la complexation des terres rares par la tpytz. Ce resultat est prometteur pour une separation intergroupe lanthanides (iii)/actinides (iii) contenus dans les combustibles nucleaires, les actinides (iii) etant mieux complexes par la tpytz. Le transport de cuivre et des terres rares par des 4-acyl-5-hydroxy-pyrazoles ou isoxazoles a travers une membrane liquide epaisse a ete realisee. Celui-ci est assure par le gradient de ph etabli entre les phases aqueuses d'entree et de sortie de la membrane. A forte vitesse d'agitation, un regime mixte diffusionnel-cinetique est observe. L'etape cinetique lente, pour laquelle differentes lois de vitesse apparentes ont ete etablies et discutees, est localisee a l'interface d'entree de la membrane. Le flux de sortie est toujours limite par la diffusion des especes cua#2 et lna#3 a travers la couche organique non agitee de l'interface de sortie.
17
Piovesan, Luciana Almeida. « Avaliação da atividade antimicrobiana de derivados isoxazóis ». Universidade Federal de Santa Maria, 2005. http://repositorio.ufsm.br/handle/1/10395.
Texte intégralRésumé :
Conselho Nacional de Desenvolvimento Científico e TecnológicoIsoxazoles compounds have been showing a great variety of pharmacological activities. Such activities might be increased by the presence of halomethyl-substitute groups in isoxazoles. This work shows the synthesis of the series of 5-trichloromethyl-5-hydroxi-4,5- dihydroisoxazoles 2a-o, 5-carboxy-isoxazoles 3a-o e 3-aryl-5- trichloro(fluoro)methylisoxazoles, 4j, 4p-t, 5j, 5p-t compounds, and further evaluation of the antimicrobial activity, by using the broth dillution technique, considering a bank of catalogued strains, represented by Gram-positive bacteria (Staphylococcus aureus), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and yeast (Candida spp and Cryptococcus neoformans). All of the tested isoxazoles have presented antimicrobial activity at the tested concentrations, and the yeast species were more vulnerable than the bacteria species, being the values of minimum inhibitory concentration between 0,019 mg/mL and 1,25 mg/mL.
Sabendo que compostos isoxazolínicos têm demonstrado grande variedade de atividades farmacológicas e que essas atividades poderiam ser acentuadas pela presença de grupos halometil-substituintes no ciclo isoxazolínico este trabalho mostra a síntese das séries de 5-triclorometil-5-hidroxi-4,5-diidroisoxazóis 2a-o, 5-carboxilisoxazóis 3a-o e 3-aril-5-tricloro(flúor)metilisoxazóis, 4j, 4p-t, 5j, 5p-t e a posterior avaliação da atividade antimicrobiana dessas séries de compostos. Os testes de avaliação antimicrobiana foram feitos usando a técnica de diluição em caldo, frente a um banco de cepas catalogadas representadas por bactérias Grampositivas (Staphylococcus aureus), Gram-negativas (Escherichia coli e Pseudomonas aeruginosa) e leveduras (Candida spp e Cryptococcus neoformans). Todos os derivados isoxazolínicos testados apresentaram atividade antimicrobiana nas concentrações testadas, sendo que, de modo geral, as espécies de leveduras foram mais sensíveis que as espécies de bactérias e os valores de concentração inibitória mínima variaram de 0,019 a 1,25mg/mL.
18
Rosa, Fernanda Andreia. « Reação de β-dimetilaminovinil cetonas com hidroxilamina : regioquímica de formação de 4,5-diidroisoxazóis e de isoxazóis ». Universidade Federal de Santa Maria, 2005. http://repositorio.ufsm.br/handle/1/10412.
Texte intégralRésumé :
Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorThe regiochemistry study of the formation of a series of aryl-, heteraryl- and haloalkyl-substituted isoxazoles from the reaction of β-dimethylaminovinyl ketones and hydroxylamine is reported. The precursors β-imethylaminovinyl ketones were obtained from the condensation reaction of N,N-dimethylformamide dimethyl acetal and the substituted ketones [R-C(O)-CH3, where R = Ph, MeO-4-C6H4, Me-4-C6H4, F-4-C6H4, Cl- 4-C6H4, Br-4-C6H4, O2N-4-C6H4, Fur-2-yl, Tien-2-yl, Pyrrol-2-yl, Pyrid-2-yl, and CCl3]. The study shown that for R = trichloromethyl substituent was obtained regiospecifically 5-halomethyl-4,5-dihydroisoxazoles. For precursors with R = O2N-4-C6H4, Fur-2-yl were obtained 3-aryl-4,5-dihydroisoxazole, for R = MeO-4-C6H4, F-4-C6H4, Br-4-C6H4, Pyrrol-2-yl were obtained 5-aryl[heteroaryl]isoxazoles, and for remainder substituents (R = Ph, Me-4-C6H4, Cl-4-C6H4, Tien-2-yl, Pyrid-2-yl) were obtained a mixture of the 4,5-dihydroisoxazoles-1,3 and isoxazoles-1,5. The effect of the substituent on the regiochemistry of isoxazoles obtained was discussed with bases on a MO calculations data.
Este trabalho descreve o estudo da regioquímica de formação de uma série de isoxazóis aril-, heteroaril- e haloalquil substituídos, a partir da reação de β- dimetilaminovinil cetonas e hidroxilamina. O precursor β-dimetilaminovinil cetona foi obtido a partir da reação de condensação de N,N-dimetilformamida dimetil acetal e a cetona substituída [R-C(O)-CH3, onde R = Ph, MeO-4-C6H4, Me-4-C6H4, F-4-C6H4, Cl-4-C6H4, Br-4-C6H4, O2N-4-C6H4, Fur-2-il, Tien-2-il, Pirrol-2-il, Pirid-2-il, e CCl3]. O estudo mostrou que para R = triclorometil substituinte foi obtido regioespecificamente 5-halometil-4,5-diidroisoxazóis. Para precursores com R = O2N-4-C6H4, Fur-2-il foram obtidos 3-aril-4,5-diidroisoxazóis, para R = MeO-4-C6H4, F-4-C6H4, Br-4-C6H4, Pirrol-2-il foram obtidos 5-aril[heteroaril]isoxazóis, e para os demais substituintes (R = Ph, MeO-4- C6H4, Cl-4-C6H4, Tien-2-il, Pirid-2-il) foram obtidos uma mistura de 4,5-diidroisoxazóis-1,3 e isoxazóis-1,5. O efeito do substituinte na regioquímica dos isoxazóis obtidos foi discutido com base nos dados de cálculos de orbitais moleculares (AM1).
19
Debleds, Olivier. « Substitutions propargyliques : méthodologie & ; développements synthétiques ». Montpellier 2, 2009. http://www.theses.fr/2009MON20159.
Texte intégralRésumé :
Le travail présenté dans ce manuscrit concerne le développement de nouvelles réactions utilisant la substitution propargylique par des complexes d'or (III) et de fer (III). En premier lieu, une exploration du champ d'application de cette méthodologie a été réalisée, ce qui a conduit par la suite, à la mise au point de nouvelles méthodes d'accès aux 2,3-dihydroisoxazoles, aux isoxazoles et ainsi qu'aux acylaziridines. Enfin, le développement d'une nouvelle méthodologie d'accès aux cycles à quatre chaînons par métathèse a pu être exploréThe work reported in this manuscript concerned the development of new reactions using propargylic substitution reactions with gold (III) and iron (III) complexes. A first part, an exploration of the scope of this methodology was achieved, which led subsequently to the development of new access to 2,3-dihydroisoxazoles, isoxazoles and acylaziridines. Finally, a ring closing metathesis access to four-membered rings has been developed
20
Friedein, Alynne Alegre Souto. « Síntese de novos azóis derivados da 1,1- difenilacetona ». Universidade Federal de Santa Maria, 2014. http://repositorio.ufsm.br/handle/1/10591.
Texte intégralRésumé :
This work describes an efficient method to obtaining new heterocycles from the reaction of acetalization of the ketonic carbonyl, followed by acylation of the enolether, generated in situ from the acetal derivative of 1,1-diphenylacetone, with trifluoroacetic anhydride, tricloroacetila of chloride, clorodiflúoracético anhydride, pentaflúorpropiônico anhydride in the absence of solvents. There were performed reactions of cyclocondensation between 1,1,1-trialo-4-alkoxy-3-alquen-2-ones and hydroxylamine hydrochloride, forming, in general, the 5-trialometil-5-hydroxy-4,5-diidroisoxazóis. To obtaining pyrazoline compounds, was proposed the cyclocondensation between the β-ketones alcoxivinil (ou é β-alcoxivinil ketones?) and four different dinucleophiles: monohydrate hydrazine, phenylhydrazine, thiosemicarbazide and aminoguanidine carbonate. All compounds synthesized on this work, since the acetal to the final heterocycles are inedited and their structures were confirmed by RMN 1H e 13C data. In this work, were also performed antimicrobial activity tests of some compounds against microorganisms, wherein some showed significant result for bacteria of great clinical interest, Staphylococcus aureus.Este trabalho descreve um método eficiente para a obtenção de novos heterociclos a partir da reação de acetalização da carbonila cetônica, seguida pela acilação do enoléter, gerado in situ a partir do acetal derivado da 1,1-difenilacetona, com anidrido trifluoracético, cloreto de tricloroacetila, anidrido clorodiflúoracético e anidrido pentaflúorpropiônico na ausência de solventes. Foram realizadas reações de ciclocondensação entre as 1,1,1-trialo-4-alcoxi-3-alquen-2-onas e cloridrato de hidroxilamina, formando, de maneira geral, os 5-trialometil-5-hidroxi-4,5-diidroisoxazóis. Para obtenção dos compostos pirazolínicos, foi proposta a ciclocondensação entre as β-alcoxivinil cetonas e quatro diferentes dinucleófilos: monohidrato de hidrazina, fenilhidrazina, tiosemicarbazida e carbonato de aminoguanidina. Todos os compostos sintetizados neste trabalho, desde o acetal até os heterociclos finais são inéditos e suas estruturas foram confirmadas por dados de RMN 1H e 13C. Neste trabalho, também foram realizados testes de atividade antimicrobiana de alguns compostos contra microorganismos, sendo que alguns apresentaram significativo resultado para a bactéria de grande interesse clínico, Staphylococcus aureus.
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Roy, Amélie. « Synthetic studies of the formation of oxazoles and isoxazoles from N-acetoacetyl derivatives, scope and limitations ; and Aqueous rhodium-catalyzed Heck-type coupling reactions between boronic acids and olefins ». Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape3/PQDD_0021/MQ53366.pdf.
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Sperança, Adriane. « Síntese de Seleno-Isoxazóis e Seleno-Indóis via Reações de Ciclização Intramolecular mediadas por Cloreto Férrico ». Universidade Federal de Santa Maria, 2013. http://repositorio.ufsm.br/handle/1/4241.
Texte intégralRésumé :
Conselho Nacional de Desenvolvimento Científico e TecnológicoThis work reports the synthesis of a series of 4-organoselenyl-isoxazoles (19 examples), prepared via FeCl3/diorganyl diselenides-promoted intramolecular cyclization of alkynone O-metyloximas. In general, the selenyl-isoxazoles were obtained, in 50 to 70% yield. In addition, an alternative method was developed to promote the intramolecular cyclization reaction of o-alkynyl-N,N-dimethyl-anilines, where FeCl3 and substituted diorganyl diselenides were employed as promoter agents to this process. Through this cyclization protocol a series of N-methyl-3-organoselenyl-indoles could be synthesized (20 examples), in yields varying from 36 to 81%, by using room temperature and ambient atmosphere. In order to evaluate the versatility of the obtained compounds as precursors to the synthesis of functionalized isoxazoles and indoles, the 3,5-diphenyl-4-(phenylselenyl)-isoxazole, N-methyl-2-phenyl-3-(phenylselenyl)-1H-indole and N,5-dimethyl-2-phenyl-3-(phenylselenyl)-1H-indole were submitted to PhSe-Lithium exchange reactions, and the corresponding organolithium intermediates, which were generated by treatment with nBuLi, could be trapped with different electrophiles, affording the functionalized isoxazoles (5 examples) and indoles (4 examples) in good yields (45-80%).
Este trabalho relata a síntese de uma série de 4-organoseleno-isoxazóis (19 exemplos), preparados a partir da reação de ciclização intramolecular de O-metiloximas alquinílicas promovidas por FeCl3 e diferentes disselenetos de diorganoíla. Em geral, os derivados de seleno-isoxazóis foram obtidos de maneira satisfatória, em rendimentos de 50 a 70%. Desenvolveu-se também, um método alternativo para promover a reação de ciclização intramolecular de o-alquinil-N,N-dimetil-anilinas, empregando-se FeCl3 e disselenetos de diorganoíla diferentemente substituídos, como agentes promotores da ciclização. Através deste protocolo de ciclização pode-se sintetizar uma série de N-metil-3-organosseleno-indóis (20 exemplos), em rendimentos que variaram de 36 a 81%, utilizando condições de reação brandas, uma vez que os experimentos foram realizados a temperatura e atmosfera ambiente. A fim de avaliar a versatilidade dos compostos obtidos, como precursores para a síntese de isoxazóis e indóis com diferentes funcionalizações, o 3,5-difenil-4-(fenilselenil)-isoxazol e o N-metil-2-fenil-3-(fenilselenil)-1H-indol e N,5-dimetil-2-fenil-3-(fenilselenil)-1H-indol, foram submetidos à reações de troca PhSe-lítio, e o intermediário litiado correspondente, formado a partir de uma reação utilizando n-BuLi, pôde ser capturado com diferentes eletrófilos, obtendo-se como produtos uma série de isoxazóis (5 exemplos) e indóis (4 exemplos) diferentemente funcionalizados em bons rendimentos (45-80%).
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Meyer, Alexandre Robison. « Interações intermoleculares e topologia molecular no empacotamento cristalino de 3-amino-4-halo-5-metilisoxazóis ». Universidade Federal de Santa Maria, 2013. http://repositorio.ufsm.br/handle/1/10542.
Texte intégralRésumé :
Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorIn this work is described the intermolecular interactions and the molecular topology present in the crystal packing of 3-amine-4-halo-5-methylisoxazoles. First was described the obtention of the 3-amine-4-halo-5-methylisoxazoles by halogenations of the compound 3-amine-5-methylisoxazol with N-chlorosuccinimide, N-bromosuccinimide and N-iodoosuccinimide. The crystal packing of the 3-amine-4- halo-5-methylisoxazoles show a great variety of intermolecular interactions such as: hydrogen bonding, halogen bonding, π π interactions and C-H π interactions. Further analysis of crystal packing showed that these compounds have a molecular coordination number equal to 14. The correlation between molecule molecule energy contact and the contact area between the molecules showed that, with the exception of dimmers formed by strong hydrogen bonds, all the other interactions have a large dependence of the contact area. The melting enthalpy of the 3-amine-4- halo-5-methylisoxazoles grows with the increases of the total energy of the contacts of the clusters, showing that these physic property depends of the intermolecular interactions present in the crystal. The analysis of theory levels used to determine the molecule molecule energies contact demonstrates that, when is used the method counterpoise for basis set superposition error (BSSE), the level of theory MP2/Augcc- pVDZ show energy values very close to the energy at the MP2/cc-pVTZ level of theory. The functional B97-D and ωB97X-D, based on the DFT theory, also showed satisfactory energy values, very close to those obtained by MP2.
Neste trabalho são descritas as interações intermoleculares e a topologia molecular referente ao empacotamento cristalino de 3-amino-4-halo-5-metilisoxazóis. Primeiramente foi descrita a obtenção dos 3-amino-4-halo-5-metilisoxazóis através da halogenação do composto 3-amino-5-metilizoxazol com N-clorosuccinimida, Nbromosuccinimida e N-iodosuccinimida. O empacotamento cristalino dos 3-amino-4- halo-5-metilisoxazóis apresentou uma grande diversidade de interações intermoleculares incluindo: ligações de hidrogênio, ligações de halogênio, interações π π e C-H π. Uma análise mais detalhada do empacotamento cristalino demonstrou que estes compostos apresentam um número de coordenação molecular igual a 14. A correlação entre a energia de contato molécula molécula e a área de contato entre as moléculas demonstrou que, com exceção dos dímeros formados por ligações de hidrogênio fortes, as demais interações apresentam uma grande dependência da área de contato. A entalpia de fusão dos 3-amino-4-halo-5- metilisoxazol aumenta com o aumento da energia total do cluster demonstrando que esta propriedade física está vinculada as interações intermoleculares presentes no cristal. A análise dos níveis de teoria utilizados para determinar as energias de contato molécula molécula demonstra que ,quando utilizado o método counterpoise para o erro de sobreposição de bases (BSSE), o nível de teoria MP2/Aug-cc-pVDZ apresentou valores de energia muito próximos ao do nível MP2/cc-pVTZ. Os funcionais B97-D E ωB97X-D, baseados na teoria DFT também apresentaram valores de energia satisfatórios, muito próximos aos obtidos pelo MP2.
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Longhi, Kelvis. « Nh-pirazóis e isoxazóis : síntese mecanicamente ativada por grinding ». Universidade Federal de Santa Maria, 2010. http://repositorio.ufsm.br/handle/1/10474.
Texte intégralRésumé :
Conselho Nacional de Desenvolvimento Científico e TecnológicoThe synthesis of twelve NH-pyrazoles from the cyclocondensation reaction of β-dimethylaminovinylketones ([R1C(O)C(R2)=CHN(Me)2], where R1 = Me, C6H5, 3- MeO-C6H4, 4-Me-C6H4, 4-MeO-C6H4, 4-F-C6H4, 4-Cl-C6H4, 4-Br-C6H4, 4-O2N-C6H4, fur-2-il, tien-2-il; R2 = H, 2-MeO-C6H4 and R1, R2 = -(CH2)3C(O)- with hydrazine sulfate is reported. In this work, it was also demonstrated the synthesis of twelve isoxazoles from the cyclocondensation reaction of β-dimethylaminovinylketones where R1 = Me, C6H5, 3-MeO-C6H4, 4-Me-C6H4, 4-MeO-C6H4, 4-F-C6H4, 4-Cl-C6H4, 4-Br-C6H4, 4-biphenyl, naphthalen-2-yl, 4-O2N-C6H4, thien-2-yl and R2 = H, 2-MeOC6H4 with hydroxylamine hydrochloride. The reactions were performed in the presence of p-toluene sulfonic acid as the catalyst through two methodologies: (i) by the solvent-free grinding method, and (ii) using the conventional method, ethanol reflux. In addition, the Grindstone Chemistry methodology demonstrated that largescale synthesis is also possible. Making a comparison with the classical reaction conditions, which employ molecular solvent (ethanol), the grinding method has as main advantages of shorter reaction time (5-15 min), higher product yields (60-92%), mild reaction conditions as well as being environmentally friendly.
Neste trabalho é descrita a síntese de uma série de doze NH-pirazóis a partir da reação de ciclocondensação de β-dimetilaminovinilcetonas ([R1C(O)C(R2)=CHN(Me)2], onde R1 = Me, C6H5, 3-MeO-C6H4, 4-Me-C6H4, 4-MeOC6H4, 4-F-C6H4, 4-Cl-C6H4, 4-Br-C6H4, 4-O2N-C6H4, fur-2-il, tien-2-il; R2 = H, 2-MeOC6H4 e R1, R2 = -(CH2)3C(O)- com sulfato de hidrazina. Também foi realizada a síntese de uma série de doze isoxazóis a partir da reação de ciclocondensação de β-enamino cetonas, onde R1 = Me, C6H5, 3-MeO-C6H4, 4-Me-C6H4, 4-MeO-C6H4, 4- F-C6H4, 4-Cl-C6H4, 4-Br-C6H4, 4-bifenil, naft-2-il, 4-O2N-C6H4, tien-2-il e R2 = H, 2-MeO-C6H4 com cloridrato de hidroxilamina. As reações para obtenção dos compostos heterocíclicos foram realizadas na presença de ácido p-tolueno sulfônico (ác. p-TsOH) como catalisador através de duas metodologias: (i) utilizando o método grinding na ausência de solvente, e (ii) utilizando metodologia convencional, refluxo em etanol. O método Grindstone Chemistry foi testado e demonstrou que a síntese em grande escala também é possível. Os resultados obtidos mostraram que o grinding proporciona uma redução no tempo da reação (5-15 min), altos rendimentos (60-92%), condições de reação brandas, além de ser uma metodologia ambientalmente aceitável.
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Campos, Patrick Teixeira. « β-Enaminonas, 5-hidróxi-4,5-diidropirazóis e 5-Hidróxi-4,5-diidroisoxazóis halometilsubstituídos : estudo molecular por difração de raios-x ». Universidade Federal de Santa Maria, 2008. http://repositorio.ufsm.br/handle/1/10435.
Texte intégralRésumé :
Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorThe molecular study by X-ray diffraction of β-aminovinyl ketones [R3C(O)CH=C(R1)N(R4R5), onde R3 = CF3, CCl3, CHCl2; R1 = H, Me; R4 = H; R5 = benzyl, Ph, 5-methylisoxazol-3-yl; R4, R5 = -(CH2)4-, -(CH2)2O(CH2)2-], methyl 5- hydroxy-5-trihalomethyl-4,5-dihydro-1H-pyrazole-1-carboxylate [3-(R1), 4-(R2), and 5- (R3) substituted, where R1 = H, Me; R2 = H, Me; R3 = CCl3, CF3], 1-cyanoacetyl-5- trifluorometyl-5-hydroxy-4,5-dihydro-1H-pyrazole [3-(R1) and 4-(R2) substituted, where R1 = H, Ph; R1, R2 = -(CH2)4-, R2 = H] and 5-triclorometyl-5-hydroxy-4,5- dihydroisoxazole [3-(R1) substituted, where R1 = Ph, 4Br-Ph, tien-2-yl] were reported. The β-aminovinyl ketones have showed the fragment O=C-C=C-N essentially plane, as well as, the heterocyclic rings 4,5-dihydropyrazole and 4,5-dihydroisoxazole. The shorter bond lengths of b-aminovinyl ketones indicated an eletronic resonance effect in the conjugated system O=C-C=C-N. This effect also was encountered in the double bond N2=C3 of the rings 4,5-dihydropyrazole and 4,5-dihydroisoxazole and the substituent of the 3-position of this rings, when this substituent was an aromatic ring. In general, the molecules studied have its crytalline packing governed by intraand intermolecular hydrogen bond.
Neste trabalho foi descrito o estudo molecular por difração de raios-X de β- aminovinil cetonas [R3C(O)CH=C(R1)N(R4R5), onde R3 = CF3, CCl3, CHCl2; R1 = H, Me; R4 = H; R5 = benzila, Ph, 5-metilisoxazol-3-ila; R4, R5 = -(CH2)4-, -(CH2)2O(CH2)2- ], 1-metilcarboxilato-5-trialometil-5-hidróxi-4,5-diidropirazóis [3-(R1), 4-(R2) e 5-(R3) substituídos, onde R1 = H, Me; R2 = H, Me; R3 = CCl3, CF3], 1-cianoacetil-5- trifluormetil-5-hidróxi-4,5-diidropirazóis [3-(R1) e 4-(R2) substituídos, onde R1 = H, Ph; R1, R2 = -(CH2)4-, R2 = H] e 5-triclorometil-5-hidróxi-4,5-diidroisoxazóis [3-(R1) substituído, onde R1 = Ph, 4-BrPh, tien-2-ila]. As b-aminovinil cetonas apresentaram o fragmento O=C-C=C-N e os anéis heterocíclicos, 4,5-diidropirazol e 4,5- diidroisoxazol, essencialmente planos. Os dados relacionados aos comprimentos de ligações do sistema conjugado O=C-C=C-N indicaram um efeito de ressonância eletrônica nas β-aminovinil cetonas. Esse efeito foi encontrado também na ligação dupla N2=C3 dos anéis 4,5-diidropirazóis e 4,5-diidroisoxazóis e o substituinte da posição-3 dos mesmos, quando este fosse um anel aromático. De maneira geral, as moléculas estudadas têm seu empacotamento cristalino governado por ligações de hidrogênio intra- e intermoleculares.
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Meunier, Andreas. « Cyclooxygenase-2 inhibitors and knee prosthesis surgery ». Doctoral thesis, Linköping : Department of Clinical and Experimental Medicine, Linköping University, 2008. http://www.bibl.liu.se/liupubl/disp/disp2008/med1077s.pdf.
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Garcia, Fábio Dutra. « Novos Espirocromenil-Trifluoretanonas a partir de Reações de Trifluoracetilação de Adutos de Kabbe e seus Espiro[diidrocromeno-cicloalcan]pirazóis e Isoxazóis Derivados ». Universidade Federal de Santa Maria, 2013. http://repositorio.ufsm.br/handle/1/10564.
Texte intégralRésumé :
Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorThis work describes firstly an efficient and regioselective method for the synthesis of a new series of 2,2,2-trifluoro-1-[4-methoxy-spiro(2H-chromen-2,1 -cycloalkan)-3-yl]ethanones from the Kabbe adducts (spiro[chroman-2,1 -cycloalkan]-4-ones). Yields of 38 % to 61 % were obtained when trifluoroacetylation reactions of mixtures of enolethers and/or acetals derived from four spiro ketones (Kabbe adducts) were performed at a temperature of 45 oC and employing anhydrous chloroform as the solvent. Subsequently, when the respective trifluoroacetylated Kabbe adducts reacted with phenylhydrazine and methylhydrazine at a 1:1 molar ratio in refluxing ethanol for 24 hours, a new series of seven examples of a novel spiro-condensed heterocyclic system, namely 1(2)-methyl(phenyl)-3-(trifluoromethyl)-1,4(2,4)-dihydro-spiro(chromen[4,3-c]pyrazole-4,n -cycloalkanes) where cycloalkanes are cyclopentane, cyclohexane and cycloheptane (n = 1) and tetrahydro-2H-pyran (n = 2) were isolated at yields of between 35 % and 51 %. NMR and X-ray diffraction techniques demonstrated clearly that reactions from methylhydrazine and phenylhydrazine were regioselective and allowed to isolate separately the 1,3- and 2,3-trifluoromethylated isomers, respectively. Subsequently, two examples of new 3-hydroxy-3-(trifluoromethyl)-3,3a-dihydro-4H-spiro(chromen[4,3-c]isoxazole-4,1 -cycloalkanes), derivated from cyclopentanone and cyclopentanone, were obtained from the reaction of 2,2,2-trifluoro-1-[4-methoxy-spiro(2H-chromen-2,1 -cycloalkan)-3-yl]ethanones with hydroxylamine hydrochloride in yields of 42% and 58%, respectively. Finally, the structures of new spiro heterocycles were determined with the aid and simultaneous application of 1H-, 13C{1H}- and 19F-NMR, X-ray monocrystal diffraction, Mass Spectrometry and DFT calculation techniques and their purity were proved by elemental analysis or High Resolution Mass Spectrometry (HRMS).
O presente trabalho descreve inicialmente um método eficiente e regiosseletivo para a síntese de uma nova série de 2,2,2-triflúor-1-[4-metóxi-espiro(2H-cromen-2,1 -cicloalcan)-3-il]etanonas a partir de adutos de Kabbe (espiro[croman-2,1 -cicloalcan]-4-onas). Rendimentos de 38% a 61% foram obtidos quando reações de trifluoracetilação de misturas de enoléteres e/ou acetais derivados de quatro espiro cetonas (adutos de Kabbe) foram realizadas a 45 ºC usando clorofórmio anidro como solvente. Subsequentemente, quando os respectivos adutos de Kabbe trifluoracetilados foram reagidos com fenilhidrazina ou metilhidrazina, em relação molar de 1:1, sob refluxo de etanol por 24 horas, uma série de sete exemplares de um novo sistema heterocíclico espiro-condensado, denominado 1(2)-metil(fenil)-3-(trifluormetil)-1,4(2,4)-diidro-espiro(chromen[4,3-c]pirazol-4,n -cicloalcanos) onde os cicloalcanos são ciclopentano, ciclohexano e cicloheptano (n = 1) e tetraidro-2H-pirano (n = 2), foi isolada em rendimentos entre 35 % e 51 %. Técnicas de RMN e de difração de raios-X demonstraram claramente que as reações a partir da metilhidrazina e da fenilhidrazina foram regiosseletivas e permitiram isolar separadamente os isômeros trifluormetilados 1,3 e 2,3, respectivamente. Em sequência, dois exemplares de novas 3-hidróxi-3-(trifluormetil)-3,3a-diidro-4H-espiro(cromen[4,3-c]isoxazol-4,1 -cicloalcanos), derivados da ciclopentanona e ciclohexanona, foram obtidos a partir da reação de 2,2,2-triflúor-1-[4-metóxi-espiro(2H-cromen-2,1 -cicloalcan)-3-il]etanonas com cloridrato de hidroxilamina em rendimentos de 42% e 58%, respectivamente. Finalmente, as estruturas dos novos espiro heterociclos foram determinadas com o auxílio e aplicação simultânea de experimentos de RMN de 1H, 13C{1H}, 19F, difração de raios-X em monocristais, Espectrometria de Massas e cálculos DFT e, a sua pureza comprovada por Análise Elementar ou por Espectrometria de Massas de Alta Resolução (HRMS).
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Yuen, Wing Hoi. « An isoxazole approach to the coleophomones ». Thesis, Loughborough University, 2007. https://dspace.lboro.ac.uk/2134/11718.
Texte intégralRésumé :
Coleophomones, metabolites reported first in a Japanese patent in 1998 and then by Merck in 2000 from a Coleophoma fungus, have antifungal and antibacterial properties and inhibit bacterial cell-wall transglycosylase and human heart chymase. Their unique molecular architecture contains a cyclic tricarbonyl moiety embedded in an ll-membered macrocycle. In our synthetic strategy the reactive ~,~-tricarbonyl structure is masked as an isoxazole to allow elaboration elsewhere in the molecule. We have investigated two isoxazole based approaches to these targets: 1) via an isoxazole ring with ketone or ester substituents; and 2) via a reduced benzisoxazole. The formation of isoxazole building blocks for the two approaches was by nitrile oxide l,3-dipolar cycloaddition. Several substituted phenylisoxazole diesters were made from approach 1 successfully, however, the attempt for 6-membered ring closure failed. For approach 2, a number of benzisoxazoles with different substituted phenyl groups were made in moderate to good yield. The side chain additions towards these building blocks have also been elaborated, and the formation of II-membered macrocycles have been attempted by ring closing metathesis (RCM) with Grubbs II catalyst. Precursors for total synthesis of coleophomone A, B, C and D have been made. Irradiation reactions have been used to prepare oxime precursors for coleophomone D and use of co-solvent (HMAP and DMPU) was applied in the synthesis to alkylate the benzisoxazole ring.
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Silva, Givanildo Santos da. « Estudos estruturais e em química medicinal visando a identificação de novos inibidores da acetilcolinesterase Ipisox, Prisox, Ocisox, 4d, b07, 13b e c90 ». Universidade Federal de Alagoas, 2016. http://www.repositorio.ufal.br/handle/riufal/1865.
Texte intégralRésumé :
This work presents a crystal chemistry study of seven compounds grouped into three classes: isoxazoles, pyrazoles and pyrazolines here called IPISOX, PRISOX, 4D, OCISOX, C90, B07 e 13B, in order to identify novel acetylcholinesterase inhibitors. The structures of the listed compounds were determined by X-ray diffraction method using monocrystalline samples of the aforementioned substances. The disagreement rates seen between the model and the model defined by the diffraction pattern were: 0.0708; 0.0399; 0.0513; 0.0562; 0.0726; 0.0519; 0.0457 to IPISOX, PRISOX, OCISOX, 4D, B07, 13B e C90, respectively. A appendix refers to several methods involved in the process of recrystallization was attached to work, since it received 13 of the 16 substances to study were improperly to be subjected to the technique of Xray diffraction. To obtain factors responsible for the stability of the lens system were carried Closed Layer Interactions Analysis (ICF). The average values of delocalized electron energies determined in kcal.mol-1 were: 19.00 (IPISOX) ; 23.00 (PRISOX) ;
12.00 (OCISOX and B07) ; 9.00 (4D) ; 6,00 (13B) and 5.00 (C90) . Such relocations are from electronic transitions of the type n * (donor receiver). Other electronic relocation of C-N *O-H and C-H *O-H were also observed for some compounds. However, the first mentioned are relevant to the stability of the electron lens packaging.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Este trabalho apresenta um estudo cristaloquímico de sete compostos agrupados em três classes: isoxazóis, pirazóis e pirazolinas aqui denominados de IPISOX, PRISOX, 4D, OCISOX, C90, B07 e 13B, no intuito de identificar novos inibidores da Acetilcolinesterase. As estruturas dos compostos mencionados foram determinadas por método de difração de Raios X usando amostras monocristalinas das substâncias mencionadas anteriormente. Os índices de discordância verificado entre o modelo proposto e o modelo definido pelo padrão de difração foram: 0,0708; 0,0399; 0,0513; 0,0562; 0,0726; 0,0519; 0,0457 para IPISOX, PRISOX, OCISOX, 4D, B07, 13B e C90, respectivamente. Um apêndice referente aos diversos métodos envolvidos no processo de recristalização foi anexado ao trabalho, uma vez que 13 das 16 substâncias recebidas para estudo estavam em forma inadequada para serem submetidas à técnica de difração de raios X. Visando obter fatores responsáveis pela estabilidade do sistema cristalino foram realizadas Análises de Interações de Camada Fechada (ICF). Os valores médios das energias de deslocalização eletrônica determinados, em kcal.mol-1, foram: 19,00 kcal.mol-1 (IPISOX); 23,00 (PRISOX); 12,00 (OCISOX E B07); 9,00 (4D); 6,00 (13B) E 5,00 (C90). Tais deslocalizações são oriundas de transições eletrônicas do tipo n * (doador receptor). Outras deslocalizações eletrônicas do tipo C-N *O-H e C-H *O-H também foram observadas para alguns compostos. No entanto, as primeiras mencionadas são relevantes para a estabilidade eletrônica do empacotamento cristalino.
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Moschref, Said-Nadjib. « Synthese und Umlagerung von mono-metallierten Bisallylethersystemen und die Synthese von mono-metallierten Isoxazolen ». [S.l. : s.n.], 1999. http://deposit.ddb.de/cgi-bin/dokserv?idn=962341290.
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Rosa, Rafaela Raupp da. « Isoxazolinas e isoxazóis como reais candidatos na preparação de cristais líquidos polares ». reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2018. http://hdl.handle.net/10183/180639.
Texte intégralRésumé :
A presente tese descreve a síntese e caracterização de 10 novas séries de moléculas na forma de banana contendo os anéis isoxazolina e isoxazol como reais candidatos na preparação de cristais líquidos polares. Foram avaliados parâmetros estruturais tais como o tipo de função conectora do centro curvado com os braços mesogênicos, a natureza do heterociclo e a sua posição relativa ao núcleo. A síntese dos compostos contou com a metodologia de preparação do anel isoxazolina, a cicloadição [3+2] 1,3-dipolar entre alcenos e óxidos de nitrila, os quais foram gerados pelas oximas preparadas a partir de aldeídos alifáticos e aromáticos. Todas as isoxazolinas foram oxidadas aos seus respectivos isoxazóis utilizando dióxido de manganês. Foram utilizadas ainda reações de alquilação, redução, desproteção, hidrogenólise, olefinação, adição de aminas à aldeídos e esterificação. Todas as moléculas sintetizadas foram caracterizadas por RMN de 1H e 13C, além de serem observadas por MOLP para determinação dos seus pontos de fusão. As moléculas que apresentaram comportamento mesomórfico foram ainda caracterizadas por DSC, XRD e voltagem triangular. No capítulo 3 é descrita a síntese dos isoftalatos 19a-b, 20a-b, 26a-b e 27a-b. No subgrupo dos Isoftalatos derivados de isoxazóis e isoxazolinas 3,5-diarilsubstituídos foi possível a síntese apenas do composto 11d que não apresentou comportamento líquido cristalino No subgrupo dos isoftalatos derivados de isoxazóis e isoxazolinas 3-alquil-5-arilsubstituídos as isoxazolinas 19a-b não apresentaram comportamento líquido-cristalino. Foram encontradas mesofases para os compostos 20a-b que ainda não foram determinadas com as técnicas disponíveis. Os isoxazóis 20a-b apresentaram uma provável Blue Phase logo após o resfriamento do isotrópico, que rapidamente se converte em uma provável mesofase monotrópica ferroelétrica com texturas e padrão de XRD peculiares até então não observada na literatura. No subgrupo dos isoftalatos derivados de isoxazóis e isoxazolinas 3-aril-5-alquilsubstituídos 26a-b e 27a-b não foi observado comportamento líquido-cristalino. O capítulo 4 descreve a síntese das isoftaliminas 35, 36, 44, 45, 50a-b, 51a-b, 56a-d, 57a-d, 63a-b e 64a-b. No subgrupo dos isoxazóis e isoxazolinas 3,5-diarilsubstituídos 35, 36, 44 e 45 foram observadas as mesofases B7 e B1 apenas com a inversão da orientação do anel isoxazol como braçomesogênicos dos compostos finais, enquanto que as isoxazolinas não apresentaram mesofases. A mesofase B7 do composto 36 apresentou comportamento antiferroelétrico enquanto que a mesofase B1 do composto 45 não mostrou resposta frente ao campo elétrico aplicado, além disso, o XRD mostrou que tal mesofase colunar B1 pode ser uma fase 3D modulada. No subgrupo das isoxazolinas e isoxazóis 3-alquil-5-arilsubstituídos 50a-b e 51a-b foram observadas fases do tipo DC para as isoxazolinas 50a-b, a qual deve ser confirmada por FFTEM. No subgrupo dos materiais 3-aril-5-alquilsubstituídos 56a-d, 57a-d, 63a-b e 64a-b foram observadas mesofases SmXPF para os compostos 56b-d. Os isoxazóis 57a-d apresentaram texturas similares, porém não apresentaram mesofase, mas os mesmos seguem o mesmo padrão de difração das isoxazolinas do capítulo 3. Apenas a isoxazolina 63b dos compostos perfluorados apresentou mesofase No capítulo 5 é descrita a síntese de ésteres não-simétricos contendo os heterociclos isoxazol e isoxazolinas como núcleo central 71a-f, 82, 83, 84 e 85. No primeiro subgrupo todos os ésteres cinâmicos 71a-f apresentaram comportamento mesomórfico com grandes faixas de temperaturas nas mesofases. No segundo subgrupo as isoxazolinas 82 e 83 apresentaram comportamento completamente distinto, onde só foi observada a formação de uma mesofase SmB para o composto que tem a posição éster localizada na direção do nitrogênio do heterociclo. Já os isoxazóis 84 e 85 deste subgrupo apresentaram as mesofases N e SmC em temperaturas bastante similares, porém, a observação desses materiais em uma cela alinhada revelou o crescimento de filamentos na transição N-SmC apenas para o composto 85, o qual também possui a porção éster na direção do nitrogênio do anel isoxazol. O capítulo 6 traz a síntese dos ésteres e iminas simétricos 88, 89, 94 e 95 utilizando os heterociclos como núcleo central, os quais apresentaram mesofases SmC e N. Além disso, o diéster 89 derivado de isoxazol apresentou a mesma característica que o composto 85 do capítulo 5, apresentando uma transição N-SmC com crescimento de filamentos perpendiculares à direção de alinhamento da amostra dentro da cela, podendo estar relacionada à uma mesofase NTB.This thesis describe the synthesis and characterization of 10 new series of banana shaped molecules containing the isoxazoline and isoxazole rings as real players for preparation of polar liquid crystals. It was evaluate structural parameters such as the type of connecting function of the bent core with the mesogenic arms, the heterocycle nature and its position relative to the central core. The synthesis of the compounds included the methodology of preparation of the isoxazoline ring, the [3 + 2] 1,3-dipolar cycloaddition between alkenes and nitrile oxides, which were generated by the oximes prepared from aliphatic and aromatic aldehydes. Furthermore, all isoxazolines were oxidized to its respective isoxazoles using manganese dioxide. Besides the described methodologies, alkylation, reduction, deprotection, hydrogenolysis, olefination, addition of amines to the aldehydes and esterification reactions were used. All the synthesized molecules were characterized by 1H NMR and 13C NMR, and also observed by POM for determination of its melting points. The molecules previously analyzed by POM that showed mesomorphic behavior were characterized by DSC, XRD and triangular voltage still. Chapter 3 describes the synthesis of isophthalates 19a-b, 20a-b, 26a-b e 27a-b. In the subgroup of isophthalates derived from isoxazoles and isoxazolines 3,5-diarylsubstituted it was possible to synthesize only compound 11d which did not show liquid crystalline behavior In the subgroup of the isophthalates derived from isoxazoles and isoxazolines 3-alkyl-5-arylsubstituted the isoxazolines 19a-b did not show liquid crystalline behavior. It was found mesophases for compounds 20a-b that still could not be determined with the available techniques. The isoxazoles 20a-b presented a probable Blue Phase soon after cooling from the isotropic which quickly converts into a probable ferroelectric monotropic mesophase with peculiar textures and pattern of XRD until then not observed in the literature. In the subgroup of the isophthalates of isoxazoles and isoxazolines 3-aryl-5-alkylsubstituted 26a-b and 27a-b no liquid crystalline behavior was observed. Chapter 4 describes the synthesis of isophthalimines 35, 36, 44, 45, 50a-b, 51a-b, 56a-d, 57a-d, 63a-b and 64a-b. In the subgroup of the isoxazoles 3,5-diarylsubstituted 35, 36, 44 and 45 the B7 and B1 mesophases were observed only with the inversion of the isoxazole ring orientation as mesogenic arm of thefinal compounds whereas the isoxazolines did not present mesophases. The B7 mesophase of the compound 36 showed antiferroelectric switching while the B1 mesophase of the compound 45 showed no response to the applied electric field, in addition, the XRD showed that such B1 columnar mesophase could be a 3D modulated phase one. In the subgroup of 3-alkyl-5-arylsubstituted isoxazolines and isoxazoles 50a-b and 51a-b DC phases were observed for isoxazolines 50a-b which should be confirmed by FFTEM. The SmXPF mesophase were observed for componds 56b-d in the subgroup of 3-aryl-5-alkylsubstituted materials 56a-d, 57a-d, 63a-b e 64a-b. The isoxazoles 57a-d presented similar textures although did not showed mesophase, but they follow the same diffraction pattern of the chapter 3 isoxazolines. Only the isoxazoline 63b of the perfluorinated compounds showed mesophase In chapter 5 is described the synthesis of non-symmetric esters containing isoxazol and isoxazolines heterocycles as central core 71a-f, 82, 83, 84 e 85. In the first subgroup all the cinnamic esters 71a-f showed mesomorphic behavior with large mesophases temperature ranges. In the second subgroup the isoxazolines 82 and 83 showed completely different behavior which only was observed the SmB mesophase formation for compound having the ester position towards the heterocycle nitrogen. Furthermore, the isoxazoles 84 and 85 of this subgroup showed the N and SmC mesophases at very similar temperatures, however, the observation of these materials in an aligned cell revealed the filamentary growth in the N-SmC transition only for compound 85, which also has the ester moiety in the direction of the isoxazole ring nitrogen. Chapter 6 brings forward the synthesis of symmetrical esters and imines 88, 89, 94 and 95 using the heterocycles as the central cores, which showed SmC and N mesophases. Moreover, the isoxazole derived diester 89 showed the same feature as compound 85 of Chapter 5, exhibiting a N-SmC transition with filament growth perpendicular to the rubbing direction of the cell which may be related to a NTB mesophase.
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Gsour, Amna. « Differentiation of human cell line towards a pancreatic endocrine lineage ». Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/differentiation-of-human-cell-line-towards-a-pancreatic-endocrine-lineage(0c2c21fe-724d-449f-804c-02741c89828c).html.
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Islet transplantations have been successful in restoring glucose homeostasis in patients with diabetes; however, the limited number of donor organs limits the success of this treatment. The lineage reprograming of different cell sources to beta cells potentially provides an unlimited supply of insulin-producing cells for regenerative therapy for patients with diabetes. The aim of this study was to investigate the ability to transdifferentiate two cell lines into an endocrine lineage. Insulin production in pancreatic beta cells can be increased using a small molecule, 3,5-disubstituted isoxazole, N-cyclopropyl-t-(thiophen-2-yl)isoxazole-3-carboxamide (isoxazole) but its effect on other cell types has not been reported. Here, we investigated the lineage reprogramming of PANC-1 pancreatic ductal cells to insulin producing cells by isoxazole treatment. Gene expression was performed using RT-PCR and qPCR for approximately 30 genes critical to beta cell development and function. In addition, quantitative proteomic profiling was performed using LC-MS by monitoring protein abundance in isoxazole-treated PANC-1 cells compared to time-matched controls. Isoxazole treatment stimulated PANC-1 cells to aggregate into islet-like clusters and gene expression analysis revealed induction of important developmental beta cell markers including NGN3, NEUROD1 and INSULIN. In addition, beta cell surface markers were also upregulated such as CD200, GPR50, TROP-2, GLUT2 and SLC30A8. Using LC-MS a catalogue of approximately 2400 identified proteins was generated; 257 proteins were differentially expressed in isoxazole-treated cells compared to DMSO-vehicle controls at p < 0.05. Amongst the proteins upregulated were molecules that regulate metabolic processes and cytoskeletal reorganisation. The expression of the majority of these proteins has not been previously reported or studied in the context of beta cell differentiation. Functional analysis of the relative protein changes was determined using Ingenuity Pathway Analysis, IPA, and gene ontology, GO, software, which revealed the regulation of several cellular canonical pathways including metabolic pathways, cell adhesion, remodelling of epithelial adherens junctions and actin cytoskeleton signalling. The effects of isoxazole were further studied in the A549 lung cancer cell line. Similar effects were observed, such as the induction of pro-endocrine markers NGN3 and NEUROD1 and endocrine-specific hormones INS and GCG. These results indicate that isoxazole has the capacity to transdifferentiate pancreatic and non-pancreatic cell origins into an endocrine lineage. This study reveals the powerful induction capacity of isoxazole in inducing cellular reprogramming events.
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Hollis, Stephen James. « Heterocycles in peptide chemistry ». Thesis, Open University, 2000. http://oro.open.ac.uk/54180/.
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The synthesis of 5-membered heterocyclic rings that bear both amine and carboxylic acid functional groups has been investigated using a 1,3-dipolar cycloaddition reaction strategy. These molecules, on incorporation into a chain of amino acids, have the potential to restrict the conformational freedom of the peptide. Cycloaddition of a nitrile oxide, derived from a Boc-protected naturally-occurring a-amino acid, with a pyrrolidine en amine led to a Boc-protected 3-aminoalkylisoxazole amino acid ester. The nitrogen and carbon termini of this isoxazole were coupled to other a-amino acids. Analysis of the dipeptide from coupling to (S)-alanine indicated that the integrity of the chiral centre of the isoxazole had been retained during the synthesis. Molecular modelling of a tripeptide unit incorporating the isoxazole showed that the presence of the ring had, as intended, restricted the conformational freedom of the molecule. Analogous cycloadditions using azomethine imines as the dipole yielded the corresponding tetrahydropyrazoles (pyrazolidines). These dipoles were generated by reaction of an aldehyde with a 1,2-disubstituted hydrazine, followed by elimination of the elements of water from the resulting aminol. Reaction with a dipolarophile bearing an electron withdrawing substituent gave predominantly the 4-substituted pyrazolidine. A study of the scope of the reaction found that, although the required carboxylic acid group could easily be incorporated by use of methyl acrylate as the dipolarophile, it proved impossible to attach an amine group to the ring using this methodology. However, by using one of the nitrogen atoms in the ring as the N-terminus, two pyrazolidines with protected amine and carboxylic acid groups were prepared, and these can be thought of as conformationally restricted B-amino acids.
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Stiirmer, Júlio César. « Síntese de bismesógenos derivados do isoxazol ». Florianópolis, SC, 2000. http://repositorio.ufsc.br/xmlui/handle/123456789/79050.
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Dissertação (Mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas. Curso de Pós-Graduação em QuímicaMade available in DSpace on 2012-10-17T22:37:56Z (GMT). No. of bitstreams: 0Bitstream added on 2014-09-25T16:14:53Z : No. of bitstreams: 1 182716.pdf: 3357298 bytes, checksum: 7e79e068bbc9aea9bb290a481be0b28d (MD5)
Síntese de Cristais Liquidos Calamíticos constituídos de sistemas chamados de bismesógenos é apresentada. Estes sistemas possuem dois centros rígidos conectados por uma cadeia flexível. O centro rígido é constituído pelo anel isoxazol 3,5-dissubstituido e um anel aromático. A influência dos espaçadores é observado na formação da mesofase.
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Correia, de Almeida Gleybson. « Síntese e avaliação preliminar da atividade antimicrobiana e antichagásica de novas isoxazolil-aril-semicarbazonas, e tiossemicarbazonas e isoxazolil-nitrofurfuril-hidrazonas ». Universidade Federal de Pernambuco, 2010. https://repositorio.ufpe.br/handle/123456789/2969.
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Previous issue date: 2010Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Na literatura, há um grande número de trabalhos que buscam obter derivados de semicarbazonas e tiossemicarbazonas, contendo heterociclos, com aplicações farmacológicas, como antimicrobiana, antichagásica, antifúngica, antineoplásica e anticonvulsivante. Pesquisas vêm obtendo sucesso na busca de novos compostos bioativos híbridos dos núcleos 2-isoxazolina[5,4-b]piperidina e 2-isoxazolina[5,4-b]pirrolidina, como por exemplo os derivados aril-hidrazonas e amidas deste biciclos que apresentaram ação antinociceptiva e anti-inflamatória, respectivamente. Desta forma, dez novos derivados isoxazolil-aril-semicarbazonas e tiossemicarbazonas foram desenvolvidos através de uma condensação catalítica ácida da 4-fenil-semicarbazida ou 4-fenil-tiossemicarbazida com aldeídos isoxazolínicos. No presente estudo, ésteres, derivados da reação de cicloadição [3+2] do óxido de nitrila (CEFNO) com enecarbamato N-benziloxicarbonil-2-pirrolina ou enamidas piperidínicas benzoíladas, foram reduzidos aos respectivos alcoóis pelo NaBH4, que em seguida, foram submetidos a uma oxidação de Swern, resultando nos aldeídos isoxazolínicos. Uma segunda abordagem deste trabalho foi a síntese de uma série de hidrazonas isoxazolínicas conjugadas ao grupamento farmacofórico nitrofurfuril. A presença do farmacóforo nitrofurano em compostos bioativos vem sendo bastante relatada na literatura, demonstrando uma diversidade de atividades biológicas, como antimicrobiana, antichagásica e antifúngica. Para síntese destes novos híbridos isoxazolínicos, foram postos em reação ésteres pirrolidínicos com hidrazina 80%, produzindo as isoxazolil-hidrazidas que foram condensadas ao 5-nitro-2-furfuraldeído. Todos os compostos supracitados foram conduzidos a testes antimicrobianos pelo método de difusão em disco, numa concentração de 100 μg/μL, contra cepas de Staphylococcus aureus, Pseudomonas aeroginosa, Escherichia coli, Candida albicans e Aspergillus Níger. Os novos derivados isoxazolínicos não apresentaram atividade antifúngica, formando apenas alguns halos parciais sobre a C. albicans. Contudo, as hidrazonas se sobressaíram contra as cepas bacterianas analisadas, formando halos de inibição superiores a 15 mm, sendo considerados bons agentes antibacterianos. Todos os novos híbridos isoxazolínicos também foram conduzidos a testes de citotoxicidade e atividade inibitória frente à forma epimastigota das cepas Y de Tripanosoma cruzi. Todos os compostos testados foram ativos em baixas concentrações, tendo destaque para as tiossemicarbazonas que apresentaram as menores citotoxidades (acima de 100 μg/mL), e a nitrofurfuril-hidrazona isoxazolínica p-F-substituída (citotoxicidade 25 μg/mL e IC50 igual a 1,17 μg/mL) que demonstrou ser mais ativo que o benznidazol (citotoxicidade 25 μg/mL e IC50 igual a 1,73 μg/mL), em testes in vitro, além de possuir um alto potencial bactericida (halo de inibição em média 20 mm)
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Fritz, Martina Désirée. « p38 MAP Kinase Inhibitoren : Synthese, Analytik und biologische Testung substituierter Isoxazole / ». [S.l. : s.n.], 2004. http://www.gbv.de/dms/bs/toc/39191703X.pdf.
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Gamage, Disnani W. « Comparison of Isoxazole and Azirine as precursor to triplet vinyl nitrene ». University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1337351136.
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Wierschem, Frank Georg. « Darstellung und Modifizierung von 2-Oxo-piperazin-basierenden Isoxazolinen und Isoxazolidinen in Lösung und an fester Phase ». [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=971626812.
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Lopes, Luana Dezingrini. « Síntese de moléculas fluoradas contendo o núcleo isoxazol ». reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2010. http://hdl.handle.net/10183/107021.
Texte intégralRésumé :
No mundo dos heterociclos de 5 membros, o isoxazol recebe atenção devido à sua ampla empregabilidade em produtos biológicos, farmacêuticos e tecnológicos. Além das suas propriedades medicinais bastante conhecidas, isoxazóis são intermediários interessantes em síntese orgânica, e desempenham um papel importante na síntese de novos materiais líquido-cristalinos. A combinação de diferentes características interessantes estimulou o estudo da influência do flúor nas propriedades dos compostos orgânicos. Os atributos importantes desse substituinte asseguram que modificações significativas são frequentemente encontradas em relação ao ponto de fusão, morfologia da mesofase e temperaturas de transição. O presente trabalho descreve a síntese e caracterização de uma nova coleção de cristais líquidos baseados em isoxazóis fluorados. Metodologias sintéticas clássicas foram empregadas na preparação destes compostos, e a cicloadição [3+2] 1,3-dipolar foi a etapa chave da rota sintética. A estrutura e a pureza dos compostos sintetizados foram confirmadas por RMN de 1H, 13C e 19F. Posteriormente, as propriedades térmicas e líquido-cristalinas foram investigadas por MOLP, DSC e TGA. Em paralelo, as propriedades fotofísicas de alguns compostos foram estudadas, em solução, através de espectroscopia de absorção de UV-vis. Além disso, foi realizado um estudo computacional sobre os perfis de torção angular para a construção de curvas de energia potencial dos compostos finais 17a-d. Apesar da existência dos carbonos sp3 nas isoxazolinas, comportamento mesomórfico foi encontrado em três delas, 16l e 16m apresentaram mesofase SmA e a 16n apresentou mesofase colunar. Os isoxazóis 17k-n revelaram a existência de propriedades líquido-cristalinas, exibindo mesofases enantiotrópicas, SmC (17k), a sequência SmC→SmA (17l e 17m) e Colhex para o isoxazol tipo Janus (17n). As isoxazolinas 16k e 16l e os isoxazóis 17k, 17l e 17n foram submetidos a análises de TGA e apresentaram boa estabilidade térmica. Este trabalho contribui para uma melhor compreensão da relação entre estrutura e propriedades em moléculas como os isoxazóis 3,5-dissubstituídos contendo ou não átomos de flúor e facilita a concepção de compostos novos e mais complexos.In the world of 5-membered heterocycles, the isoxazole gets some attention due to its wide employability in biological, pharmaceutical and technological products. Beyond their well-known medicinal properties, isoxazoles are interesting intermediates in organic synthesis, and play an important role in the synthesis of novel liquid crystalline materials. The combination of different interesting characteristics has stimulated the study of fluorine influence on the organic compounds properties. The important attributes of the fluoro substituent ensures that significant modifications are frequently encountered in respect of melting point, mesophase morphology and transition temperatures. The present work describes the synthesis and characterization of a new collection of liquid crystals based on fluorinated isoxazoles. Classical synthetic methodologies were employed in the preparation of these compounds, and the [3+2] 1,3-dipolar cycloaddition was the key step of the synthetic route. The synthesized compounds had their structure and purity confirmed by 1H, 13C and 19F NMR. Subsequently, the thermal and liquid crystalline properties were investigated by POM, DSC and TGA. In parallel, the photophysical properties of some compounds were studied in solution by UV-vis absorption spectroscopy. Additionally, a computational study on torsional profiles to construct potential energy curves of the final compounds 17a-d has been done. The results obtained evidence that despite the existence of sp3 carbons in isoxazolines, mesomorphic behavior was found in three of them, 16l and 16m showed SmA mesophase and 16n showed columnar mesophase. The 17k-n isoxazoles revealed the existence of liquid crystalline properties, exhibiting enantiotropic mesophases, SmC (17k), the sequence SmC→SmA (17l and 17m) and Colhex for the isoxazole Janus type (17n). The 16k and 16l isoxazolines and the 17k, 17l, and 17n isoxazoles were subjected to TGA analysis and showed good thermal stability. This work contributes to a better understanding of the structure-property relationship in molecules such as 3,5-disubstituted isoxazoles containing or not fluorine atoms and facilitates the design of new and more complex compounds.
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Huppé, Sylvain. « La chimie des 5-isoxazolones : des β-cétoesters aux acétyléniques ». Paris 11, 1996. http://www.theses.fr/1996PA112295.
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Lobo, Marcio Marçal. « Síntese regiosseletiva de Dideoxinucleosídeos e 3(5)-Trifluormetil-1H-pirazóis de interesse farmacológico ». Universidade Federal de Santa Maria, 2015. http://repositorio.ufsm.br/handle/1/4276.
Texte intégralRésumé :
Conselho Nacional de Desenvolvimento Científico e TecnológicoThis work reports the synthesis of a series of 29 new 1-(3-aryl-4,5-dihydroisoxazol-5-yl)methyl-4-trihalomethylpyrimidin-2(1H)-ones which have high pharmacological interest, since they are similar to natural and synthetic nucleosides. These compounds were obtained from 1,3-dippolar cycloaddition reaction between the 1-allyl-(6-aryl)-4-trihalomethylpyrimidin-2(1H)-ones and different benzonitrile oxides, obtained from the selected oximes of general formula ArCH=NOH (where Ar = Ph, 4-FC6H4, 2-MeC6H4, 4-MeC6H4, 2-MeOC6H4, 4-MeOC6H4, styryl, 2-OHC6H4 e 4-OHC6H4). The reaction conditions employed were highly regioselective, because it was observed the formation of only 3,5-substituted isomer by both NMR spectral analysis and X-ray diffractometry. The compounds were obtained in good yields (58 99%) and were purified from recrystallization or by column chromatography on silica gel. Some the obtained compounds showed antineoplastic activity in vitro against different tumor cell lines. Additionally, three new N3-substituted pyrimidinic dideoxynucleoside analogues were prepared, which were obtained in good yields (88 97%) from the reaction of N-allyl-2-methylthiopyrimidin-4(3H)-one and some of the benzonitrile oxides mentioned above. The reactions for the formation of N3-substituted nucleoside still require optimization. This thesis also described the regiochemisty controled synthesis of two series of pyrazoles, named 5(3)-aryl-3(5)-trifluoromethyl-(1H-pyrazol-1-yl)benzenesulfonamides, structural analogues of Celecoxib (14 examples), where aryl = Ph, 4-FC6H4, 4-MeC6H4, 4-MeOC6H4, 4-ClC6H4, 4-BrC6H4, furan-2-yl, from the cyclocondensation reaction between 4-aryl-1,1,1-trifluoromethyl-4-methoxy-3-buten-2-ones and 4-hydrazinobenzenosulfonamide hydrochloride. The isolation of either isomer depended on the initial pH medium, where the alkaline pH favored the isolation of the 1,5-substituted isomer at yields of 73 99% and the reaction conducted in acid pH favored the isolation of the 1,3-substituted isomer, with yields of 77 94%. This study also allowed the isolation and spectroscopic characterization of a novel series of 3-aryl(heteroaryl)-5-hydroxy-5-trifluoromethyl-(1H-pyrazol-1-yl)benzenesulfonamides (7 examples) in yields of 75 97% with interesting anti-inflammatory and antinociceptive activities in vivo.
Esta tese apresenta a síntese de uma série de 29 moléculas inéditas de 1-(3-aril-4,5-diidroisoxazol-5-il)metil-4-trialometilpirimidin-2(1H)-onas que possuem alto interesse farmacológico, visto que são análogos a nucleosídeos naturais e sintéticos. Esses compostos foram obtidos a partir de reação de cicloadição 1,3-dipolar entre as 1-alil-(6-aril)-4-trialometilpirimidin-2(1H)-onas e diferentes óxidos de benzonitrila, obtidos a partir das oximas selecionadas, de fórmula geral ArCH=NOH (onde Ar = Ph, 4-FC6H4, 2-MeC6H4, 4-MeC6H4, 2-MeOC6H4, 4-MeOC6H4, Estiril, 2-OHC6H4 e 4-OHC6H4). As condições reacionais empregadas mostraram-se altamente regiosseletivas, uma vez que, por análise dos espectros de RMN e por difratometria de raios-X, observou-se a formação apenas do isômero 3,5-substituído. Os compostos foram obtidos em bons rendimentos (58 99%) e puderam ser purificados a partir de recristalização ou através de coluna cromatográfica em sílica gel. Alguns dos compostos obtidos apresentaram atividade antineoplásica in vitro frente a diferentes linhagens de células tumorais. Também estão apresentados 3 novos análogos nucleosídeos pirimidínicos N3-substituídos, obtidos em bons rendimentos (88 97%) a partir da reação da N-alil-2-metiltiopirimidin-4(3H)-ona e de alguns óxidos de benzonitrila acima citados. As reações para a formação dos nucleosídeos N3-substituídos ainda necessitam de otimização. Nesta tese também está descrito o controle regioquímico para a síntese de duas séries de pirazóis, nomeados 5(3)-aril-3(5)-trifluormetil-(1H-pirazol-1-il)benzenosulfonamidas, análogos estruturais do Celecoxib (14 exemplos), onde aril = Ph, 4-FC6H4, 4-MeC6H4, 4-MeOC6H4, 4-ClC6H4, 4-BrC6H4, fur-2-il, a partir da reação de ciclocondensação entre 4-aril-1,1,1-trifluormetil-4-metóxi-3-buten-2-onas e o cloridrato de 4-hidrazinilbenzenosulfonamida. O isolamento de um ou outro isômero dependeu do pH inicial do meio, onde o pH básico favoreceu o isolamento do isômero 1,5-substituido com rendimentos de 73 99% e a reação conduzida em pH ácido favoreceu o isolamento do isômero 1,3-substituído, com rendimentos de 77 94%. Este estudo também possibilitou o isolamento e caracterização espectroscópica de uma série inédita de 3-aril(heteroaril)-5-hidróxi-5-trifluormetil-(1H-pirazol-1-il)benzenosulfonamidas (7 exemplos) em rendimentos de 75 97%, com interessante atividade anti-inflamatória e antinociceptiva in vivo.
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Bryk, Fernando Rebouças. « Síntese regiosseletiva de cristais líquidos contendo o heterociclo isoxazol ». Florianópolis, SC, 2008. http://repositorio.ufsc.br/xmlui/handle/123456789/91898.
Texte intégralRésumé :
Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas. Programa de Pós-Graduação em QuímicaMade available in DSpace on 2012-10-24T03:40:18Z (GMT). No. of bitstreams: 1 260043.pdf: 3765314 bytes, checksum: 24336dd964ac4d5fddd8cd096f286373 (MD5)
Moléculas com características líquido-cristalinas têm ultimamente atraído um grande interesse por parte de vários grupos de pesquisa e principalmente por empresas do ramo da tecnologia. Esse interesse reside em grande parte, pelas suas propriedades únicas, as quais se aplicam a muitos aspectos do cotidiano da sociedade moderna, principalmente quando se trata de mostradores de informação. Estes compostos envolvem uma ampla classe de materiais, desde sistemas de baixa massa molecular a estruturas poliméricas. Uma grande quantidade de moléculas diferentes tem sido sintetizada em busca das propriedades liquido-cristalinas. Em sua grande maioria, elas são compostas por anéis aromáticos de cinco e seis membros. Neste contexto, o presente trabalho relata a síntese do anel heterociclo isoxazol 3,5-dissubstituído através da reação de cicloadição 1,3-dipolar catalisada por CuI, levando a obtenção de compostos líquido-cristalinos e o estudo de suas propriedades de cristais-líquidos.
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Mancuso, Vincent. « Nouvelle voie de synthèse de bêta-aminocétones via les Delta4-isoxazolines ». Doctoral thesis, Universite Libre de Bruxelles, 1990. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/213161.
Texte intégral
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Lucas-Andrzejak, Virginie. « Conception, synthèse et évaluation pharmacologique de nouveaux inhibiteurs de la Fatty Acid Amide Hydrolase (FAAH) potentiellement utilisables dans le traitement des Maladies Inflammatoires Chroniques de l'intestin (MICI) ». Phd thesis, Université du Droit et de la Santé - Lille II, 2010. http://tel.archives-ouvertes.fr/tel-00590867.
Texte intégralRésumé :
Les MICI (maladies inflammatoires chroniques de l'intestin) invalident 200 000 personnes en France. La région Nord-Pas-de-Calais est particulièrement touchée par ces affections et les traitements disponibles pour ces pathologies demeurent coûteux et peu nombreux. Des études récentes ont suggéré que le système endocannabinoïde, exprimé au seing du tractus gastro-intestinal, est une cible thérapeutique prometteuse pour le traitement des MICI. Ce système se compose des récepteurs aux cannabinoïdes CB1 et CB2, des ligands endogènes de ces récepteurs, notamment l'anandamide et le 2-arachidonoylglycérol et des protéines impliquées dans l'anabolisme et le catabolisme des ligands. L'anandamide a présenté des capacités à prévenir la colite induite par le TNBS à des rongeurs. Toutefois, in vivo ce composé possède un temps de demi-vie court et est rapidement dégradé par une amidase à sérine, la FAAH (Fatty Acid Amide Hydrolase). Nous avons ainsi envisagé la conception, la synthèse et l'évaluation pharmacologique de nouveau inhibiteurs de la FAAH. L'une de nos molécules, le composé 95, présentant une CI50 sur l'enzyme de 88 nM a ensuite été injectée par voie intrapéritonéale à des souris dont la colite a été induite trois jours plus tard par l'injection intrarectale de TNBS. L'évaluation des scores macroscopiques et microscopiques des dommages causés sur le côlon par l'agent irritant a ensuite été effectuée. L'inflammation du côlon a été significativement réduite chez le groupe de souris ayant été traité par le composé 95, montrant que l'inhibition de la FAAH est une stratégie thérapeutique efficace dans le traitement des MICI.
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MESSAOUDI, ABDELKADER. « Extraction liquide-liquide du strontium par le 3-phenyl-4-benzoyl-5-hydroxy-isoxazole. Synergies ». Université Louis Pasteur (Strasbourg) (1971-2008), 1993. http://www.theses.fr/1993STR13112.
Texte intégralRésumé :
La methode de preparation du 3-phenyl-4-benzoyl-5-hydroxy-isoxazole (hpbi) a ete optimisee. Les mesures de constante d'acidite en systeme liquide-liquide ont montre que hpbi est un acide relativement fort compare au 1-phenyl-3-methyl-4-benzoyl-5-hydroxy-pyrazole (hpmbp) ou aux -dicetones. L'etude de l'extraction synergique de sr#2#+, ba#2#+, mg#2#+ et de cs#+ par des melanges de hpbi et d'ethers-couronnes (e), de sels d'ammonium (b#+, x#), et d'oxyde de tri-n-octylphosphine (topo) dans le chloroforme et le toluene, montrent que l'echange proton-metal est operant des ph 2. Avec les ethers-couronnes (e), le strontium est extrait dans le chloroforme sous les formes esr(pbi)#2 et probablement esrx(pbi) (x#=no#3#, cl#), tandis que le cesium l'est sous les formes ecs(pbi) (e=dc18c6, t-bub21c7) et (db18c6)#2cs(pbi). La presence de sodium ou de lithium fait chuter l'extraction. En presence de sel de tri-n-octylammonium (b#+, x#), hpbi ou hpmbp extraient le strontium dans le toluene sous les formes (b#+, sr(pbi)#3#) et (b#+, sr(pmbp)#3#), et aux bas ph sous la forme (b#+, sr(no#3)(pmbp)#2#). En presence de topo, strontium, baryum et magnesium sont extraits dans le toluene selon l'ordre mg#2#+sr#2#+>ba#2#+. Les especes extraites sont de types m(pbi)#2(topo)#2 (m=mg, sr, ba) et ba(pbi)#2(topo)#3. Pour les concentrations en hpbi0,015 m, une forme dimere de hpbi est mise en cause. Les constantes d'equilibre relatives aux differents systemes d'extraction synergique ont ete evaluees et discutees
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Rosa, Rafaela Raupp da. « Núcleo isoxazol na síntese e caracterização de cristais líquidos curvos ». reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2013. http://hdl.handle.net/10183/88550.
Texte intégralRésumé :
Este trabalho descreve a síntese e caracterização de três novas séries de compostos líquido-cristalinos derivados de isoxazóis com estruturas curvas. Foram empregadas metodologias clássicas de síntese na preparação dos compostos, sendo a reação de ciclo-adição [3+2] 1,3-dipolar a etapa chave da rota sintética. Adicionalmente foi feito o estudo teórico de análise conformacional e estado excitado dos compostos finais. A caracterização foi feita utilizando-se técnicas de ressonância magnética nuclear de hidrogênio (RMN de 1H) e carbono 13 (RMN de 13C), espectrometria de massas, microscopia ótica de luz polarizada (MOLP), calorimetria diferencial de varredura (DSC), difração de raio-X (DRX) e absorção no ultravioleta (UV-vis). O comportamento mesomórfico dos compostos finais da série 19a-j é bastante dependente do tamanho das cadeias alquílicas terminais. As moléculas com cadeias terminais maiores apresentaram um rico polimorfismo, apresentando a sequência de mesofases Cr→CrX→SmX→SmC→SmA→I no aquecimento, enquanto que os compostos com cadeias alquílicas menores não apresentaram a mesofase SmX e SmC. Os dados das análises de raio-X sugerem que as mesofases não identificadas sejam de natureza inclinada. Além disso, os compostos dessa série são fluorescentes na região do azul, apresentando bons rendimentos quânticos (56%-83%). Todos os compostos da série 21a-e apresentaram comportamento mesomórfico exibindo a mesofase SmA, mas apenas os compostos contendo bromo e cloro apresentaram a mesofase CrE, indicando que há maior relação com o tamanho dos átomos substituintes do que com o momento dipolar, uma vez que o composto contendo o átomo de flúor (21c) não exibiu esta mesofase. Os compostos da série 23a-e exibiram a mesofase SmA em faixas relativamente grandes de temperatura, porém, degradaram a temperaturas mais elevadas. Esses compostos são importantes precursores na preparação de cristais líquidos poliméricos de cadeia lateral.This work describes the synthesis and characterization of three new series of bent-shaped liquid crystalline compounds based on isoxazoles. Classical synthetic methodologies were employed in the preparation of this compounds, and the [3+2] 1,3-dipolar cycloaddition was the key step of the synthetic route. Additionally, a theoretical study of conformational analysis and excited state of the final compounds have been made. The characterization was performed using proton and carbon nuclear magnetic resonance (1H and 13C NMR) techniques, mass spectrometry, polarized-light optical microscopy (MOLP), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and the ultraviolet absorption (UV-vis). The mesomorphic behavior of the final compounds 19a-j was strongly dependent on the size of the terminal alkyl chains. The molecules with longer terminal chains posses a rich phase polymorphism, showing the mesophase sequence Cr→CrX→SmX→SmC→SmA→I on heating, while shorter alkyl chain compounds showed no SmX and SmC mesophase. Data from X-ray analysis suggest that the unidentified mesophases are tilted. Furthermore, the compounds are fluorescent in the blue region with good quantum yields (56% -83%). All compounds in the series 21a-e displayed the SmA mesophase, but only compounds containing chlorine and bromine atoms had the CrE mesophase, indicating there is a stronger relation on the mesomorphic behavior concerning steric effects of the substituents, since the compound containing fluorine atom (21c) did not exhibit this mesophase. The compounds 23a-e exhibited SmA mesophase in relatively large ranges of temperature, althoug decomposed at higher temperatures. These compounds are important precursors for preparation of side chain liquid crystal polymers.
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Välimäki, M. (Mika). « Discovery of cardioprotective isoxazole-amide compounds targeting the synergy of transcription factors GATA4 and NKX2-5 ». Doctoral thesis, M. Välimäki, 2018. http://urn.fi/urn:isbn:9789529412525.
Texte intégralRésumé :
Abstract Acute myocardial infarction is a life-threatening condition that occurs as a result of reduced blood flow in the cardiac muscle, eventually leading to tissue damage. In infarcted areas, cardiomyocytes have insufficient ability to proliferate and replace the injured cells, which is associated with a deficient pumping capacity. A strictly regulated combinatorial interplay of transcription factors, e.g., GATA4, NKX2-5, TBX5, and MEF2C, orchestrates cardiac type gene expression during the cardiomyocyte differentiation and maturation processes. The aim of the present study was to (i) characterize the protein-protein interaction of the cardiac transcription factors GATA4-NKX2-5, (ii) evaluate the chemical agents that modify the synergy of GATA4-NKX2-5 in vitro, (iii) examine the capacity of the lead compound to promote myocardial repair in vivo after myocardial infarction and other cardiac injuries and (iv) study the structural features of the compound important for metabolism and cytotoxicity. Integration of the experimental mutagenic data with computational modeling suggests that the structural architecture of the GATA4-NKX2-5 interaction resembles the protein structure of the conserved DNA binding domain of nuclear receptors. Fragment-based screening, reporter gene-based optimization and pharmacophore searching were utilized to identify the most potent lead compound targeting the GATA4-NKX2-5 interaction: N-[4-(diethylamino)phenyl]-5-methyl-3-phenylisoxazole-4-carboxamide. This compound presented anti-hypertrophic effects in vitro and cardioprotective effects in vivo. In addition, structural analysis of the lead compound revealed the signature molecular features for metabolism and cytotoxicity. Current drug treatments are able to delay, but not prevent the progress of the heart failure; therefore, modulators of protein-protein interactions of key transcription factors may represent a novel class of pharmaceuticals for cardiac remodeling and repairTiivistelmä Sydäninfarkti on henkeä uhkaava verenkierron häiriö, joka syntyy veren virtauksen äkillisen vähentymisen seurauksena sydänlihaksessa aiheuttaen kudosvaurion. Vaurioituneen sydänlihaskudoksen kyky uusiutua tai korvata kuolleet sydänlihassolut uusilla on puutteellinen, ja tämän seurauksena sydämen pumppauskyky heikkenee. Transkriptiotekijöiden GATA4, NKX2-5, TBX5 ja MEF2C muodostamat ja koordinoimat proteiinikompleksit säätelevät sydänsolujen geenien ilmenemistä solujen elinkaaren aikana. Väitöskirjatyön tavoitteena oli (i) karakterisoida geeninsäätelytekijöiden GATA4-NKX2-5 molekyylirakenteet ja niiden keskinäinen vuorovaikutus, (ii) seuloa kemiallisia yhdisteitä, jotka muokkaavat GATA4-NKX2-5 proteiinikompleksin aikaansaamaa geeniaktivaatiota, (iii) tutkia johtoyhdisteen vaikutuksia in vivo sydäninfarktia ja painekuormitusta kuvaavissa eläinmalleissa, ja (iv) tutkia johtoyhdisteen molekyylirakenteen yhteyttä yhdisteen metaboliaan ja sytotoksisuuteen. Väitöskirjatyö osoittaa molekyylimallinuksen ja kokeellisten tulosten perusteella, että geeninsäätelytekijöiden GATA4-NKX2-5 proteiinikompleksin orientaatio matkii tumareseptoriperheen DNA domeenin tertiäärirakennetta. Molekyylifragmenttien, lusiferaasi-reportterikokeen ja farmakoforimallin avulla seulottiin ja optimoitiin sitoutumisvoimakkuudeltaan lupaavin GATA4-NKX2-5 proteiinikompleksin toimintaan vaikuttava johtoyhdiste: N-[4-(dietyyliamino)fenyyli]-5-metyyli-3-fenyyli-isoksatsoli-4-karboksamidi. Johtoyhdisteellä havaittiin solu- ja eläinmalleissa hypertrofiaa estäviä vaikutuksia in vitro ja sydäntä suojaavia vaikutuksia in vivo. Väitöskirjatyö osoitti lisäksi aktiivisten molekyylien rakenneominaisuuksia, jotka keskeisesti vaikuttavat yhdisteiden metaboliaan ja sytotoksisuuteen. Nykyinen lääkehoito hidastaa, mutta ei pysäytä sydänlihasvaurioon liittyvän kroonisen sydämen vajaatoiminnan etenemistä. Lääkevaikutuksen kohdentaminen sydämen keskeisten transkriptiotekijöiden yhteisvaikutukseen avaa uuden mahdollisen tutkimuslinjan sydänlihasvaurion estossa ja korjauksessa
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Chatterley, Alexander. « Benzisoxazoles : new routes to coleophomone analogues ». Thesis, Loughborough University, 2014. https://dspace.lboro.ac.uk/2134/16261.
Texte intégralRésumé :
This project has been part of an ongoing interest in metabolites with a cyclic tricarbonyl motif 1, usually enolised. Coleophomones A C have a unique architecture with the cyclic tricarbonyl motif embedded in an 11-membered ring: A & B exist in aldol equilibrium, B & C are geometric isomers, and D lacks the macrocycle.1,2 Antifungal & antibiotic activity, and inhibition of human heart chymase & bacterial cell-wall transglycosylase, has generated synthetic interest. In an approach distinct from reported studies,3 we propose 4-carbonyl-substituted isoxazoles, from dipolar cycloaddition of nitrile oxides, as building blocks for the tricarbonyl framework. During this investigation precursors to the macrocycles of coleophomones A, B, C and analogues were developed. En route to these precursors we have uncovered and probed a facile and highly unusual benzisoxazole to oxazole rearrangement. *Schemes and figures relating to the abstract can be found within the document proper.
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Fritsch, Luma. « Síntese de novos cristais líquidos derivados de base de schiff com núcleo isoxazolina/isoxazol ». reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/129750.
Texte intégralRésumé :
Esta dissertação apresenta a síntese e caracterização espectroscópica e térmica de duas novas series de bases de Schiff líquido cristalinas contendo o anel isoxazolina e isoxazol. Foram sintetizados 22 bases de Schiff da série (E)-N-[4-(alquiloxi)benzilideno]-4-[5-(X)-4,5-dihidroisoxazol-3-il]anilinas (8c-i) e 22 bases de Schiff da série (E)-N-[4-(alquiloxi)benzilideno]-4-[5-(X)-isoxazol-3-il]anilinas (8c´-i´). Em ambas as séries, o grupo X é CH3 para 8c/8c’; Cl para 8d/8d’; Br para 8e/8e’; H para 8f/8f’; n-Butila; para 8h/8h’ e 2-Etilhexila para 8i/8i’. O substituinte alquiloxila em ambas as series de bases de Schiff foi n-hexila, n-octila, n-decila e n-dodecila, exceto para as bases de Schiff 8h/8i´ e 8h´/8i´ para n-hexila e n-octila, respectivamente. A reação de cicloadição [3+2] 1,3-dipolar do óxido de arilnitrila derivado do 4-nitrobenzaldeído (1a) e os alcenos produziu os heterocíclicos isoxazolínicos. Os isoxazóis foram obtidos pela reação de oxidação das respectivas isoxazolinas via MnO2. Os heterocíclicos preparados foram reduzidos para as respectivas anilinas e condensadas com os p-n-alcoxibenzaldeídos para fornecer as bases de Schiff correspondentes. Todas as bases de Schiff apresentaram comportamento líquido-cristalino. 8c-i apresentaram uma pequena faixa de existência de mesofase, enquanto que 8c´-i´ apresentaram uma enorme faixa de mesofase. Bases de Schiff com grupo Metila apresentaram mesofase nemática enquanto que com grupos polares Cloro e Bromo e Hidrogênio a predominância da mesofase esmética A. A base de Schiff 8h com o grupo n-hexila apresentou uma mesofase não identificada com textura dendritica. Bases de Schiff com dois grupos apolares alquilicos apresentaram também mesofase esmética C. As bases de Schiff 8c´-i´ apresentaram uma temperatura de clareamento superior a 250°C, enquanto que 8c-i foi abaixo de 160 °C. Analise térmica das bases de Schiff revelou que elas são instáveis quando aquecidas acima da temperatura de clareamento para aquelas derivadas do isoxazol (8c´-i´) e, ambas as séries hidrolisaram em solução de CDCl3.In this dissertation, the synthesis and characterization of two series of Schiff base liquid crystals (E)-N-[4-(alkyloxy)benzylidene]-4-[5-(X)-4,5-dihydroisoxazol-3-yl]anilines (8c-i) and (E)-N-[4-(alkyloxy)benzylidene]-4-[5-(X)-isoxazol-3-yl]anilines (8c´-i´) are described. For all Schiff bases, X group is CH3 for 8c/8c´; Cl for 8d/8d´; Br for 8e/8e´; H for 8f/8f´; n-Butyl for 8h/8h´ and 2-Ethylhexyl for 8i/8i´. All Schiff bases contain alkyl group (n-hexyl, n-octyl, n-decyl and n-dodecyl), except for 8h/8h´ and 8i/8i´ where the alkyl group is n-hexyl, n-octyl, respectively. The isoxazolines were synthesized by a [3+2] cycloaddition 1,3-dipolar of arylnitrile oxide from p-nitrobenzaldehyde (1) and alkenes. The isoxazoles were obtained by oxidation of the isoxazolines. The isoxazolines and isoxazoles thus obtained were reduced to aniline derivatives and condensed with appropriated aryl-aldehydes. The final Schiff bases series displayed liquid-crystalline properties. Those derived from isoxazolines 8c-i presented a narrow mesophase range, while those from isoxazoles 8c´-i´ showed a large mesophase range. Mesomorphic behavior was also dependent on the nature and size of the terminal group for both series of Shiff bases. Nematic mesophase was observed for Schiff bases with short and non-polar groups, while smectogenic behavior (SmA and SmC) was observed for long and more polar terminal groups. For Schiff base 8h with n-hexyl group an undefined mesophase was observed with dendritic texture. The thermal stability of the SBs studied here is dependent on the clearing temperature. For 8c´-i´ with high clearing temperature (>250 °C), decomposition induced by heat was observed during the first cycle of heating and in solutions of CDCl3. Series 8c-i with low clearing temperature (< 150 °C) was more resistant to the thermal decomposition during the heating and cooling cycles.
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Baranovic, Jelena. « Structural and functional characterization of reconstituted alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors ». Thesis, University of Oxford, 2011. https://ora.ox.ac.uk/objects/uuid:008f579f-828a-4792-8a2c-d2beffda458d.
Texte intégralRésumé :
This thesis describes a novel reconstitution of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) for the purposes of structural characterization by atomic force microscopy (AFM) and functional characterization by electrical recordings of lipid bilayers. AMPARs are glutamate gated ion channels, ubiquitous in the vertebrate central nervous system where they mediate fast excitatory neurotransmission. In a healthy brain, AMPARs are involved in memory formation and learning and their dysfunction has been related to numerous neurological disorders such as Alzheimer's disease, epilepsy, schizophrenia and many others. AMPARs were reconstituted at high and low densities. Densely reconstituted samples contained >100 receptors per μm2, a value comparable to the AMPAR density at synapses. This allowed, for the first time, the imaging of full length tetrameric AMPARs in native-like conditions and with clearly assigned domains: the extracellular domains extended 14 nm above the membrane in agreement with electron microscopy (EM) and X-ray crystallography data. Lipid-protein interactions were studied in samples with low protein density with the receptors showing preference for lipids in the liquid crystalline phase. The activity of the reconstituted receptors was confirmed through single-channel recordings. This is the first case in which an AMPAR has been reconstituted and given (a) single-channel recordings with (b) physiologically plausible conductance levels and (c) pharmacological and no-protein controls and (d) structure. As a result, previously reported biochemistry and EM are now for the first time available in concert with AFM and single-channel recordings for a purified AMPAR of known composition.