During the last decades, pi-conjugated organic materials have received tremendous attention due to their applications in organic optoelectronics, sensors, and bioimaging. Hereby, the focus has shifted towards the development of electron-deficient building blocks. A powerful tool is the doping of the pi-conjugated framework with trivalent boron, thereby incorporating a vacant p-orbital in the pi-system. In this development, pyrrole derivatives were only sparsely studied, in contrast to their thiophene or furan counterparts. This is due to the high reactivity and electron-rich nature of the pyrrole heterocycle, as well as the third valence of the nitrogen atom. However, these characteristics of pyrrole are frequently used in metal complexes or catalytic active materials. In this work, computational studies and synthetic approaches towards pyrryl-borane materials are described. Overall, an extensive series of boron-doped heterocyclic and macrocyclic systems for optoelectronic applications were investigated using quantum chemical methods. The pyrrole derivatives were thereby compared to their thiophene and furan analogues in regard to their optoelectronic and aromatic properties. In addition, the aromatic and antiaromatic properties of substituted pentalenes and its dianionic species were studied, as well as the charge delocalization properties of flanking alkyl- or aryl groups on the pentalene core unit. Furthermore, fundamental synthetic routes towards p-pi*-conjugated pyrryl-borane materials were developed. Regarding the synthesis of dipyrrolodiborepins, no conversion to the desired compounds could be achieved, but various interesting precursor molecules were synthesized and analyzed. A synthesis of boron-doped macrocycles with pyrrole using a template approach was not successful. It was however possible to synthesize the first di(N-methyl-2-pyrryl)(2,4,6-tri-iso-propylphenyl)borane and its unprotected NH-pyrrole analogue. These compounds showed a strong solvent-dependent fluorescence, which is attributed to a twisted intramolecular charge-transfer (TICT) excited-state structure, according to quantum chemical analysis. These compounds were further derivatized to form a pi-extended borane derivative, and the first NH-pyrrole triarylborane complex as a zirconocene complex, respectively. Additionally, the methyl-protected derivative was used in Stille coupling reactions to form polymers, with different oligo(N-methylpyrrole) linkers between the boron centers. These polymers showed a bathochromic shift with extension of this linker. The di(N-methylpyrryl)borane was further substituted and used as starting material for coupling reactions, e.g., McMurry coupling or Si-B-exchange. The usage of different protecting groups for the formation of pyrryl-based boranes was also studied, leading to a better understanding of the influence of the protective group on the nitrogen atom for the synthesis of such compounds. / In den letzten Jahrzehnten haben pi-konjugierte organische Materialien aufgrund ihrer Anwendungen in der organischen Optoelektronik, Sensorik und Bioimaging viel Aufmerksamkeit erhalten. Der Fokus der Entwicklung hat sich dabei auf die Herstellung elektronenarmer Bausteine verlagert. Ein leistungsstarkes Werkzeug hierfür ist die Dotierung des pi-konjugierten Gerüsts mit dreiwertigem Bor, wodurch ein unbesetztes p-Orbital in das pi-System eingebunden wird. Pyrrol-Derivate wurden in diesen Entwicklungen im Gegensatz zu Thiophen oder Furan bisher nur wenig untersucht. Dies kann auf die hohe Reaktivität und die elektronenreiche Natur des Pyrrol-Heterozyklus sowie die dritte Valenz des Pyrrol-Stickstoffatoms zurückgeführt werden. Allerdings werden diese Eigenschaften von Pyrrol in Metallkomplexen oder katalytisch aktiven Materialien häufig genutzt. Die vorliegende Arbeit befasst sich daher mit quantenchemischen Studien und synthetischen Ansätzen zu Pyrryl-Boran Materialien. Hierfür wurde eine Vielzahl von Bor-dotierter heterocyclischer und makrocyclischer Systeme für optoelektronische Anwendungen mittels quantenchemischer Methoden untersucht. Dabei wurden die Pyrrol-Derivate mit ihren Thiophen- und Furan-Analoga verglichen. Zudem wurden die aromatischen und antiaromatischen Eigenschaften substituierter Pentalene sowie deren dianionischer Spezies untersucht. Es wurden ebenso die Ladungsdelokalisierung durch flankierende Alkyl- oder Arylgruppen an der Pentalen-Kerneinheit untersucht. Darüber hinaus wurden grundlegende Synthesen zu p-pi*‐konjugierten Pyrryl-Boran Materialien entwickelt. Die Synthese von Dipyrrolodiborepinen und von Bor-dotierten Makrozyklen mit Pyrrol war nicht erfolgreich. Es gelang aber, das erste Di(N-methyl-2-pyrryl)(2,4,6-tri-iso-propylphenyl)boran und dessen ungeschütztes NH-Pyrrol-Analogon zu synthetisieren. Diese Verbindungen zeigten eine starke lösungsmittelabhängige Fluoreszenz, die einer „twisted intramolecular charge-transfer“ (TICT) Struktur des angeregten Zustands zugeschrieben wird. Die Verbindungen wurden weiter derivatisiert, um ein pi-erweitertes Boran-Derivat beziehungsweise den ersten NH-Pyrrol-Triarylboran-Komplex in der Form eines Zirconocen-Komplexes zu erhalten. Zusätzlich konnten Polymere des methyl-geschützten Derivats, mit einem in der Länge variierenden N-Methylpyrrol-Linker zwischen den Borzentren, über Stille-Kupplungsreaktionen hergestellt werden. Diese Polymere zeigten eine bathochrome Verschiebung der Emission mit der Verlängerung des Linkers. Das Di(N-methylpyrrol)boran wurde mit verschiedensten funktionellen Gruppen substituiert und als Ausgangsmaterial für Kupplungsreaktionen, wie z. B. die McMurry-Kupplung oder den Si-B-Austausch, verwendet. Der Einsatz verschiedener Schutzgruppen für die Bildung pyrryl-basierter Borane wurde untersucht, was zu einem besseren Verständnis des Einflusses der Schutzgruppe auf das Stickstoffatom bei der Synthese solcher Verbindungen führte.

The molecular structure of the title compound, [Fe(C 5 H 5 )(C 15 H 12 N)], consists of a ferrocene moiety with an N-phenylpyrrole heterocycle bound to one cyclopentadienyl ring. The 1,3-disubstitution of the pyrrole results in an L- shaped arrangement of the molecule with plane intersections of 2.78 (17)° between the pyrrole and the N-bonded phenyl ring and of 8.17 (18)° between the pyrrole and the cyclopentadienyl ring. In the crystal, no remarkable intermolecular interactions are observed.

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Author: Katharina Zenkerová Supervisors: Assoc. Prof. PharmD. Jan Zitko, Ph.D.; Prof. Romano Silvestri Title of diploma thesis: Design and synthesis of novel 3-aroyl-1-arylpyrrole derivatives as potential tubulin polymerization inhibitors Key word: anticancer agents; pyrrole; tubulin polymerization inhibitors Cancer is a major burden of disease worldwide and it remains one of the most difficult illnesses to treat. Since the percentage of people suffering from cancer is increasing, an enormous effort to design and develop better medicaments is needed. Microtubules are a key component of the cytoskeleton in most eukaryotic cells and they represent an attractive target for antitumor agents, due to the significant mitosis rate of tumor cells. Since cancer cells usually display higher proliferation rates than normal cells, drugs that interfere with microtubules dynamic equilibrium, also known as antimitotic agents, have become a fruitful approach to develop anticancer agents in clinical use. In fact, agents interfering with microtubules may either inhibit the tubulin polymerization or block microtubules to disassembly, both causing the arrest of cell division and the consequent...

Im Rahmen dieser Arbeit wurden Siliciumkomplexe mit dianionischen Pyrrol-2-carbaldimin-funktionalisierten N,N,O- und N,N,N,N-Chelatliganden synthetisiert und kristallografisch, NMR- und UV/Vis-spektroskopisch und mittels quantenchemischer Berechnungen charakterisiert. Die pentakoordinierten Si-Komplexe mit N,N,O-Ligandrückgraten wiesen in Abhängigkeit von den weiteren Si-gebundenen Substituenten unterschiedlich konfigurierte verzerrt trigonal-bipyramidale Si-Koordinationssphären auf. Die Ursache der Farbigkeit dieser Verbindungen konnte mittels quantenchemischer Berechnungen detailliert erklärt werden. – Die Si-Komplexe mit N,N,N,N-Ligandrückgraten liegen in Abhängigkeit von den weiteren Si-gebundenen Substituenten als 5-fach koordinierte kationische oder neutrale 6-fach koordinierte Si-Komplexe vor. Deren Farbigkeit wurde mittels UV/VIS-Spektroskopie untersucht. Von ausgewählten Komplexen wurden die Tensoren der 29Si-NMR-Verschiebung rechnerisch und CP/MAS-NMR-spektroskopisch bestimmt.

Im Rahmen dieser Arbeit wurden Siliciumkomplexe mit dianionischen Pyrrol-2-carbaldimin-funktionalisierten N,N,O- und N,N,N,N-Chelatliganden synthetisiert und kristallografisch, NMR- und UV/Vis-spektroskopisch und mittels quantenchemischer Berechnungen charakterisiert. Die pentakoordinierten Si-Komplexe mit N,N,O-Ligandrückgraten wiesen in Abhängigkeit von den weiteren Si-gebundenen Substituenten unterschiedlich konfigurierte verzerrt trigonal-bipyramidale Si-Koordinationssphären auf. Die Ursache der Farbigkeit dieser Verbindungen konnte mittels quantenchemischer Berechnungen detailliert erklärt werden. – Die Si-Komplexe mit N,N,N,N-Ligandrückgraten liegen in Abhängigkeit von den weiteren Si-gebundenen Substituenten als 5-fach koordinierte kationische oder neutrale 6-fach koordinierte Si-Komplexe vor. Deren Farbigkeit wurde mittels UV/VIS-Spektroskopie untersucht. Von ausgewählten Komplexen wurden die Tensoren der 29Si-NMR-Verschiebung rechnerisch und CP/MAS-NMR-spektroskopisch bestimmt.

No description available.

No description available.

The molecular structure of the title compound, [Fe(C 5 H 5 )(C 15 H 12 N)], consists of a ferrocene moiety with an N-phenylpyrrole heterocycle bound to one cyclopentadienyl ring. The 1,3-disubstitution of the pyrrole results in an L- shaped arrangement of the molecule with plane intersections of 2.78 (17)° between the pyrrole and the N-bonded phenyl ring and of 8.17 (18)° between the pyrrole and the cyclopentadienyl ring. In the crystal, no remarkable intermolecular interactions are observed.

Os antiinflamatórios não-esteróides (AINEs) estão entre os fármacos mais prescritos e utilizados do mundo. Estes fármacos inibem as ciclooxigenases, enzimas responsáveis pela transformação do ácido araquidônico em prostaglandinas flogísticas, pela ação da fosfolipase A2. A síntese de compostos antiinflamatórios contendo núcleo pirrólico em suas estruturas vem sendo um tópico muito atrativo e bastante estudado, que somado ao conhecimento do sítio de interação do fármaco ao receptor possibilita o planejamento de estruturas de novas substâncias candidatas a protótipos de novos fármacos, por meio da modificação molecular. Nesse contexto, o presente trabalho teve como objetivo o planejamento, síntese e avaliação biológica de derivados pirrólicos com potencial atividade antiinflamatória, com base nas estruturas da indometacina, protótipo da classe dos derivados de ácido arilalcanóico e dos diarilheterociclos (COXIBES). Sendo assim, foram obtidos cinco compostos em rendimentos satisfatórios, a partir de acetoacetato de etila, via metodologia de Hantzsch e ciclofuncionalização, utilizando ultrassom, que resultou na redução do tempo de reação e do consumo de solvente, seguindo os princípios da Química Verde. Os compostos 5a e 5b mostraram-se promissores, a partir de ensaios \"in vitro\". / The nonsteroidal antiinflammatory drugs (NSAIDs) are among the most prescribed and used drugs in the world. These drugs inhibit the cyclooxygenases, enzymes responsible for conversion of arachidonic acid into phlogistic prostaglandins, by the action of phospholipase A2. The synthesis of compounds containing pyrrole nucleus in their structures has been a topic very attractive and well studied, that knowledge added to the site of interaction of the drug to the receptor enables the planning of new structures of substances candidates for prototypes of new drugs through of molecular modification. In this context, this work aimed at the design, synthesis and biological evaluation of pyrrole derivatives with potential antiinflammatory activity, based on the structures of indomethacin, the prototype of arylalkanoic acid class and diarylheterocycles (coxibs). Thus, five compounds were obtained in good yields from ethyl acetoacetate, route of Hantzsch and cyclofunctionalization methods, using ultrasound, which resulted in the reduction of the reaction time and consumption of solvent, following the principles of Green Chemistry. The 5a and 5b compounds were shown to be promising, from tests in vitro.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / This work describes the synthesis of 4,5-dihydropirazoles through a sonochemical methodology, from the reaction of cyclocondensation of 1,3-diaryl-2-propen-1-ones with aminoguanidine hydrochloride and thiosemicarbazide. These reactions were carried out in ethanol in periods of reduced time concerning to the methods described in the literature. Then, it presents the use of methyl 7,7,7-trichloro-4-methoxy-6-oxo-4-heptenoate for the preparation of a series of ten 1-alkyl(aryl)-5-(3,3,3-trichloro-2-oxopropylidene)pyrrolidin-2-ones, like at a Paal-Knorr synthesis. This transformation can occur with or without isolation of intermediates methyl 4-alkyl(aryl)amino-7,7,7-trichloro-6-oxo-4-heptenoates without significant change in the yields. Subsequently, it was studied the synthetic potential of the previously synthesized pyrrolidin-2-ones front to bromination for getting eight new 1-alkyl(aryl)- 4-bromo-5-(3,3,3-trihalo-2-oxopropylidene)pyrrolidin-2-ones. Bromination occurred in a regiospecific way at 4-position with good yields. Finally, 1-alkyl(aryl)-5-(3,3,3- trihalo-2-oxopropylidene)-1H-pyrrol-2(5H)-ones were obtained from the elimination of the HBr, in alkaline medium, of the brominated pyrrolidin-2-ones. / Este trabalho descreve a síntese de 4,5-diidropirazóis via metodologia sonoquímica a partir da reação de ciclocondensação de 1,3-diaril-2-propen-1-onas com cloridrato de aminoguanidina e tiosemicarbazida. Estas reações foram realizadas em etanol em períodos de tempo reduzidos em relação aos métodos descritos na literatura. Em seguida, apresenta a utilização do 7,7,7-tricloro-4-metoxi-6-oxo-4-heptenoato de metila na síntese de uma série de dez 1-alquil(aril)-5-(3,3,3-trialo-2-oxopropilideno)pirrolidin-2-onas, semelhante a síntese de Paal-Knorr. Esta transformação pode ocorrer com ou sem o isolamento dos intermediários 7,7,7- tricloro-4-amino-6-oxo-4-heptenoatos de metila sem mudança significativa nos rendimentos. Posteriormente, foi verificado o potencial sintético das pirrolindin-2-onas triclorometilsubstituídas e trifluormetilsubstituídas previamente sintetizadas frente a reações de bromação, para a obtenção de oito 1-alquil(aril)-4-bromo-5-(3,3,3-trialo-2-oxopropilideno)pirrolidin-2-onas. Esta reação ocorreu de maneira regioespecífica e com bons rendimentos. Finalmente, foram preparadas oito 1-alquil(aril)-5-(3,3,3-trialo-2-oxopropilideno)-1H-pirrol-2(5H)-onas a partir da eliminação de HBr das pirrolidin-2-onas bromadas.