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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Síntese e atividades farmacológicas de derivados da 6-nitro-2H-1,4-benzotiazin-3-ona.

Andrade, Juliana Luisa Teixeira de January 2008 (has links)
Programa de Pós-Graduação em Ciências Farmacêuticas. CIPHARMA, Escola de Farmácia, Universidade Federal de Ouro Preto. / Submitted by Marise Leite (marise_mg@yahoo.com.br) on 2016-03-30T15:06:40Z No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) DISSERTAÇÃO_SínteseAtividadesFarmacológicas.pdf: 1891422 bytes, checksum: cf5d5c669bffa4e653cd7bc06263f0ba (MD5) / Approved for entry into archive by Oliveira Flávia (flavia@sisbin.ufop.br) on 2016-04-13T12:49:09Z (GMT) No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) DISSERTAÇÃO_SínteseAtividadesFarmacológicas.pdf: 1891422 bytes, checksum: cf5d5c669bffa4e653cd7bc06263f0ba (MD5) / Made available in DSpace on 2016-04-15T13:33:06Z (GMT). No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) DISSERTAÇÃO_SínteseAtividadesFarmacológicas.pdf: 1891422 bytes, checksum: cf5d5c669bffa4e653cd7bc06263f0ba (MD5) Previous issue date: 2008 / A necessidade de potencializar determinadas atividades farmacológicas e reduzir efeitos indesejáveis torna necessária a busca por novos fármacos. Utilizando técnicas de modificação molecular, cinco derivados da 2H-1,4-benzotiazin-3-ona foram sintetizados. Suas estruturas foram comprovadas por métodos espectroscópicos de infravermelho, RMN1H, RMN13C e espectrometria de massas. Estes compostos foram submetidos aos testes de toxicidade aguda, analgesia - pelo método da placa quente e das contorções abdominais induzidas pelo ácido acético - e atividade antifúngica. Foram observadas estereotipias e sinais qualitativos indicativos de toxicidade nos animais. Os resultados da Dose Letal Mediana revelaram que as modificações moleculares induziram uma maior toxicidade, principalmente nos compostos que sofreram a redução do grupo nitro a grupo amino. O derivado benzoilado induziu maior redução nas contorções abdominais e aumento no tempo de latência sobre a placa quente. Nos experimentos antifúngicos apenas o composto de partida induziu atividade .___________________________________________________________________________________ / ABSTRACT: The necessity to maximize some pharmacological activities and to reduce unwanted effects makes necessary the search for new therapeutic agents. By means of molecular modifications, five derivatives of 2H-1,4-benzothiazin-3-one had been synthesized. Their structures had been conformed by infrared spectrometry, RMN1H, RMN13C and mass spectrometry. These composites had been submitted to the tests of acute toxicity, analgesy – using the hot plate method and the acetic acid induced abdominal contortions method - and antifungal activity. Stereotypes and qualitative signals that indicate of toxicity in the animals had been observed. Medium Lethal Dose results had disclosed that the molecular modifications had induced to a bigger toxicity, mainly in the composites that had suffered to the reduction from the nitro group to the amino group. The benzoyl derivative induced greater reduction in the abdominal contortions and increase in the time latency on the hot plate. Only the departure composite induced activity in the antifungal experiments.
2

Organocatàlisi d'addicions conjugades mitjançant fosfines. Reciclatge i mecanisme. Síntesi de benzotiazines

Gimbert Suriñach, Carolina 20 June 2008 (has links)
Les fosfines són organocatalitzadors eficaços d'una gran varietat de reaccions, que han estat revisades en diverses ocasions. Entre elles es troben l'&#945;-hidroxialquilació de Morita-Baylis-Hillman, la reacció de Rauhut-Currier, diverses cicloaddicions o les &#945; i &#947; addicions a compostos insaturats activats. En la present Tesi Doctoral s'han estudiat les addicions conjugades, reaccions que també es poden catalitzar mitjançant fosfines però que no s'havien estudiat exhaustivament utilitzant aquests catalitzadors. Concretament s'ha treballat amb addicions de Michael i addicions conjugades de compostos N-nucleòfils. S'ha estudiat l'abast i les limitacions del mètode així com el mecanisme de la reacció.Com a substrats nucleòfils en les addicions de Michael s'han mostrat actius compostos &#946;-dicarbonílics de tipus dicetona, diester, cetoester i cetoamida substituïts i no substituïts en posició &#945;, així com compostos cíclics o de cadena oberta. És important destacar també la gran diversitat d'electròfils aptes per aquestes reaccions (esters, nitrils, cetones, fosfonats, piridines, azodicarboxilats). Respecte a les addicions conjugades de compostos N-nucleòfils pobres en electrons, han mostrat activitat amides, tioamides, anilines, sulfonamides, benzamides i fenilamines. S'ha observat que la reactivitat d'aquests compostos depèn del pKa del nucleòfil i s'ha establert un valor límit aproximat de pKa = 25 fins al qual el mètode funciona, tot i que per obtenir bons rendiments, es requereix un pKa < 20. En aquells casos que els substrats de la reacció són menys reactius, la reacció de Rauhut-Currier (dimerització de l'acceptor) competeix amb l'addició conjugada però aquesta reacció secundària es pot evitar emprant electròfils que no dimeritzin com el metacrilat d'etil o el fosfonat de dietil. En alguns casos s'ha observat la reacció de retroaddició, que és a causa de la inestabilitat del producte i de la presència de la fosfina.Una altra part del treball de la present Tesi Doctoral ha consistit en sintetitzar dues fosfines polifluorades que s'han emprat amb èxit com a organocatalitzadors de diverses reaccions d'addició de Michael amb l'objectiu de ser reciclades i reutilitzades mitjançant processos de catàlisi bifàsica orgànica-fluorada. Tot i que la seva activitat com a catalitzadors és excel·lent, la seva reciclabilitat és limitada. Aquest resultat s'ha atribuït al fet que l'estat residual del catalitzador en aquestes reaccions no és la fosfina esperada sinó una sal de fosfoni derivada de l'addició conjugada de la fosfina a l'acceptor de Michael. Aquest treball s'ha realitzat en col·laboració amb el Prof. J. A. Gladysz a la Friedrich-Alexander Universität d'Erlangen-Nürnberg.Dels estudis mecanístics sobre les d'addicions conjugades catalitzades per fosfines han aportat proves per corroborar que la reacció s'inicia per l'atac de la fosfina catalítica a l'electròfil, generant un zwitterió que activa el nucleòfil i acaba donant una sal de fosfoni que serà l'estat residual del catalitzador en el cas de les fosfines més nucleòfiles (tributilfosfina per exemple). En canvi per les fosfines menys nucleòfiles com la trifenilfosfina, l'estat residual seria la pròpia fosfina de partida. Els estudis també indueixen a descartar una possible SN2directa del nucleòfil activat a la sal de fosfoni anterior i recolzen la hipòtesi que la ruta més probable implica l'atac del nucleòfil activat a una nova molècula d'olefina.Finalment, s'ha dissenyat una estratègia per sintetitzar benzo[d][1,3]tiazines. La ruta té 3 passos des de compostos comercialment assequibles i l'etapa clau implica una S-addició conjugada intramolecular. / Nucleophilic Phosphine Catalysis (NPC) has recently attracted the attention of many scientists since it has given very good results in many reactions. Some examples are the &#945; -hydroxialkylation of Morita-Baylis-Hillman, Rauhut-Currier reaction, cycloadditions or &#945; and &#947; additions to activated olefins. Conjugate additions are another kind of reaction that phosphines can catalyze but it had not been studied exhaustively.In the present Doctoral Thesis it has been demonstrated that these compounds can effectively catalyze Michael addition reactions of &#946;-carbonyl compounds to a broad diversity of electron poor olefins. Then the same methodology has been applied to a new family of nucleophilic substrates such as non-nucleophilic N-containing compounds obtaining excellent results.Some trends can be described from the former study. First of all, aliphatic phosphines are better catalysts than aromatic ones because of their greater nucleophilicity. The scope of nucleophiles is broad and also many electrophiles are active as Michael acceptors. The yields are very good in reactions where the nucleophile has a pKa < 20 but the method is applicable to substrates with a pKa up to 25, although in these cases the yields are lower and mixtures of mono and bisadducts are obtained. In some cases, Rauhut-Currier reaction (dimerization of the Michael acceptor) competes with the conjugate addition reaction but these secondary reactions can be avoided using electrophiles that can not dimerize, such as ethyl methacrylate or vinyl phosphonate. Finally, some reactions give retroaddition, which is caused by the instability of the compound and not by the presence of the phosphine.Once the efficiency of the method had been proofed, a method to recover and reuse the catalyst was designed based on organic-fluorous biphasic catalysis. This study was carried out in collaboration with Prof. J. A. Gladysz research group in the Friedrich-Alexander Universität d'Erlangen-Nürnberg. Two different polyfluorinated phosphines were successfully synthesized through known routes and then tested as organocatalysts in several Michael addition reactions. Although the activity of these phosphines is good, the recyclability is limited due to the fact that the rest state of the catalyst is a phosphonium salt derived from the addition of the phosphine to the olefin. Some NMR experiments have been carried out in order to study the mechanism of conjugate additions catalyzed by phosphines. It has been corroborated that the reaction starts with the addition of the phosphine to the electron-poor olefin generating a phosphonium salt, which would be the rest state of the catalyst in reactions involving the most nucleophilic phosphines (tributylphosphine for example). However, when the catalyst is less nucleophilic (triphenylphosphine) the rest state is believed to be the phosphine itself. Also a direct SN2 reaction between the activated nucleophile and the phosphonium salt has been discarded for the step where the new C-C bond is generated.Finally, a new synthetic strategy to synthesize benzo[d][1,3]thiazines has been developed. The route has three steps from commercially available compounds and its key step involves an intramolecular conjugate S-addition.

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