In this work, a method for the synthesis of a series of heterocyclic compounds that preserve the amino group of the starting material, is presented. For this study, a-oxoketene O,N-acetals were obtained from the reaction of b-oxothioxo ester and different primary amines. The reactivity of the elctrophilic centers of O,N-acetals was investigated through cyclization reactions using 1,2-dinucleophiles such as hydrazine and phenylhydrazine with the reaction carried out in solid support. The functionalized heterocycles 5(3)-amino substituted 3(5)-phenyl 1H-pyrazoles and 3-amino substituted 1,5-diphenyl pyrazoles, were obtained selectively. When 1,2-dinucleophiles such as hydrazine and phenylhydrazine hydrochloride were used, ethoxy pyrazoles 5(3)-ethoxy 1H-pyrazole, 3-ethoxy 1,5-diphenyl pyrazole and 5- ethoxy 1,3-diphenyl pyrazole, were obtained, demonstrating the influence of these salts in the formation of different substitution pattern. The investigation of the possible biological activity of the pyrazoles systems obtained was performed in vitro and was accomplished through the analysis of the antimicrobial activity by the Bioautography method and Minimal Inhibitory Concentration (MIC) front to a collection of different indicative microorganisms. The inhibitory activity of the acetylcholinesterase (AChE) enzyme was also investigated. / Neste trabalho, nós estudamos a obtenção de uma série de heterociclos que preservassem o grupo amino dos compostos de partida. Para tanto, obtivemos a-oxocetenos O,N-acetais a partir da reação entre b-oxotioxo éster e diferentes aminas primárias. A reatividade dos centros eletrofílicos dos O,N-acetais foi investigada em reações de ciclização usando 1,2-dinucleófilos como hidrazina e fenil hidrazina em reações com suporte sólido. Obteve-se seletivamente os heterociclos funcionalizados 5(3)-amino substituído 3(5)-fenil 1H-pirazóis e 3-amino substituído 1,5-difenil pirazóis. Quando utilizamos como 1,2-dinucleófilos os cloridratos de hidrazina e fenil hidrazina, obtivemos 5(3)-etóxi 1H-pirazol, 3-etóxi 1,5-difenil pirazol e 5-etóxi 1,3-difenil pirazol demonstrando a influência destes sais na formação de diferentes padrões de substituição. A investigação da possível atividade biológica in vitro dos sistemas pirazólicos obtidos foi realizada por meio da análise da atividade antimicrobiana pelo método de Bioautografia e Concentração Inibitória Mínima (CIM) frente a uma coleção de diferentes microrganismos indicadores; bem como análise da atividade da enzima acetilcolinesterase (AChE).

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Os hidrocarbonetos policíclicos aromáticos (HPA) constituem um grupo de poluentes ambientais persistentes são moléculas com dois ou mais anéis aromáticos condensados, pouco solúveis em água e estão presentes no ambiente como resultante de processos naturais e também de atividades antrópicas; desta forma, os HPA podem ser encontrados em diversas matrizes ambientais. No presente trabalho foram utilizados mexilhões da região de Búzios, no Estado do Rio de Janeiro. Esse organismo foi selecionado devido à facilidade de acumulação de HPA nos tecidos, decorrente das propriedades hidrofóbicas dos HPA. O presente projeto teve como objetivo estudar um novo material de limpeza capaz de minimizar os compostos interferentes da matriz. Os cartuchos de SPE Florisil 5 g, são convencionalmente usados na limpeza de amostras de organismos, porém para diminuir os custos foram testados outros materiais adsorventes que pudessem ser eficientes na remoção dos interferentes presentes nos tecidos de mexilhão. Sendo assim, na etapa de limpeza conhecida como clean-up, foi estudada a recuperação do pireno após a extração por micro-ondas através de duas abordagens diferentes; a) utilização de cartuchos de SPE comerciais de 5 g de Florisil; b) cartuchos preenchidos com argila comercial K-10 bentonite, simulando os cartuchos comerciais. A recuperação e eficiência dos procedimentos de limpeza foram testadas e comparadas. A clean-up com argila K-10 apresentou uma recuperação de até 77% de pireno, sendo eficiente na remoção de compostos de colesteróis; confirmando a eficiência do material escolhido para a limpeza da amostra. A técnica de Cromatografia Gasosa e detecção por Espectrometria de Massas (GC-MS) foi aplicada para identificação e quantificação do contaminante pireno no extrato finaa / Polycyclic aromatic hydrocarbons (PAH) are a group of persistent environmental pollutants are molecules containing two or more condensed aromatic rings, little soluble in water and are present in the environment as a result of natural processes and human activities; in this way, the HPA can be found in various environmental matrices. In this work we used mussels in Búzios, Rio de Janeiro State. That body was selected due to the ease of accumulation of HPA in the tissues, due to the hydrophobic properties of HPA. This project aimed to study a new cleaning material able to minimize interfering compounds of the array. The 5 g Florisil SPE cartridges, are conventionally used in the cleaning of samples of organisms, however for lower costs have been tested other adsorbent materials which could be effective in the removal of the present in the tissues of mussels interfering. Therefore, in step of cleaning known as clean-up, recovery of pyrene was studied after extraction by microwave through two different approaches; a) use of commercial SPE cartridges 5 g of Florisil; b) cartridges filled with K-10 clay bentonite commercial, simulating the commercial cartridges. Recovery and efficiency of cleaning procedures were tested and compared. The clean-up with K-10 clay presented a recovery of up to 77% of pyrene, being effective in removing compounds of cholesterols; confirming the efficiency of the chosen material for cleaning of the sample. The technique of gas chromatography and detection by mass spectrometry (GC-MS) was applied for identification and quantification of contaminant pyrene in the final extract

Smoking related conditions kill approximately 5,000,000 people every year. There is evidence that smoking behaviour varies for men and women. Yet, determinants of smoking remain poorly understood, especially by gender. This Ph.D. thesis remediates this important gap in the literature, adopting a novel, transdisciplinary approach. The thesis was an epidemiological investigation of the joint and separate utility of sociodemographic factors, mental health and Social Cognitive Theory constructs as predictors of smoking for men and women. Participants were 3,502 residents of Queensland, Australia, taking part in a larger statewide population-based study investigating cancer risk knowledge and behaviours. The study consisted of a CATI telephone interview and a subsequent battery of self-report questionnaires. The thesis entailed four empirical studies. Study 1 (Chapter Two) investigated the utility of sociodemographic factors as predictors of smoking status by gender and by area by gender. Results revealed that sociodemographic variables were poor predictors of smoking status and that predictors of smoking differed by gender when analyses were conducted separately. Younger men and men involved in a relationship were more likely to be smokers, while younger women and women who were well educated were more likely to be smokers. Gender differences were also present when analyses were conducted by area by gender. In addition, smoking status for urban women was not significantly predicted by any of the employed sociodemographic variables. These results indicated that additional determinants of smoking, such as mental health, should be investigated. Study 2 (Chapter Three) was a psychometric evaluation of a tool utilized in the thesis to measure symptoms of anxiety and depression, the Kessler Scale of Non-Specific Psychological Distress, also known as the K-10. Results revealed that the K-10 is a psychometrically sound scale, ideal for measuring symptoms of anxiety and depression in the general population. It was also concluded that the K-10 is multidimensional, and that the best model for its factor structure is a first-order model composed by four first-order factors: nervousness, restlessness, negative affect and fatigue. Study 3 (Chapter Four) evaluated the discriminant utility of mental health variables measured with the K-10, separately and jointly with sociodemographic variables, in predicting group membership. The study investigated whether these variables could discriminate between ever-smokers and neversmokers, and among ever-smokers, between current smokers and former smokers by gender. This was intended to provide a glimpse into smoking initiation and smoking persistence. Analyses classified only a small percentage of smokers correctly. Nevertheless, results showed that psychological distress examined alone predicted smoking uptake among women. In contrast, smoking initiation for men was vi predicted by sociodemographic variables. In addition, persistent smoking for men was predicted by psychological distress while that for women it was predicted by sociodemographic factors. Study 4 (Chapter Five) investigated the utility of Social Cognitive Theory (SCT) constructs as determinants of smoking. This last empirical study investigated whether the addition of self-efficacy and outcome expectancies to mental health and sociodemographic variables improved prediction of smoking behaviour. Study 4 examined the utility of three models as determinants of measures of smoking among current smokers (smokers who have never attempted to quit and those who attempted to quit and failed). Nicotine dependence, age of smoking initiation, number of cigarettes smoked per day and past quit attempt, as well as intention to quit were the measures of smoking investigated. Results indicated that the full social cognitive model (containing both self-efficacy and outcome expectancy) was the most robust model, although neither self-efficacy nor outcome expectancies as constructs were particularly strong predictors. Nevertheless, self-efficacy was generally better than outcome expectancies. Both self-efficacy and outcome expectancies predicted measures of smoking for men, while only self-efficacy predicted the same measures of smoking for women. None of the models predicted a quit attempt in the last year among males. For women, only decreased fatigue predicted a quit attempt in the last 12 months: In addition, analyses conducted to classify which smokers intended to quit smoking in the near future correctly classified only a small percentage of those who did intend to quit in the near future, but correctly classified most smokers who did not. Analyses investigating which quitting method was most popular among smokers revealed that “going cold turkey” was still the preferred quitting method of more than half of smokers who had attempted to quit in the past 12 months but failed. Less than 15% of those who “went cold turkey” had also employed a cessation aid. The thesis supports the hypothesis that determinants of smoking differ by gender. The role of psychological distress in smoking uptake among women and in smoking persistence among men warrant further investigation. Future research should also examine the effect of other types of selfefficacy upon smoking behaviour. Smoking prevention and/or cessation programs might be more effective if conducted for men and women separately, addressing the particular determinants of smoking for each gender.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Os hidrocarbonetos policíclicos aromáticos (HPA) constituem um grupo de poluentes ambientais persistentes são moléculas com dois ou mais anéis aromáticos condensados, pouco solúveis em água e estão presentes no ambiente como resultante de processos naturais e também de atividades antrópicas; desta forma, os HPA podem ser encontrados em diversas matrizes ambientais. No presente trabalho foram utilizados mexilhões da região de Búzios, no Estado do Rio de Janeiro. Esse organismo foi selecionado devido à facilidade de acumulação de HPA nos tecidos, decorrente das propriedades hidrofóbicas dos HPA. O presente projeto teve como objetivo estudar um novo material de limpeza capaz de minimizar os compostos interferentes da matriz. Os cartuchos de SPE Florisil 5 g, são convencionalmente usados na limpeza de amostras de organismos, porém para diminuir os custos foram testados outros materiais adsorventes que pudessem ser eficientes na remoção dos interferentes presentes nos tecidos de mexilhão. Sendo assim, na etapa de limpeza conhecida como clean-up, foi estudada a recuperação do pireno após a extração por micro-ondas através de duas abordagens diferentes; a) utilização de cartuchos de SPE comerciais de 5 g de Florisil; b) cartuchos preenchidos com argila comercial K-10 bentonite, simulando os cartuchos comerciais. A recuperação e eficiência dos procedimentos de limpeza foram testadas e comparadas. A clean-up com argila K-10 apresentou uma recuperação de até 77% de pireno, sendo eficiente na remoção de compostos de colesteróis; confirmando a eficiência do material escolhido para a limpeza da amostra. A técnica de Cromatografia Gasosa e detecção por Espectrometria de Massas (GC-MS) foi aplicada para identificação e quantificação do contaminante pireno no extrato finaa / Polycyclic aromatic hydrocarbons (PAH) are a group of persistent environmental pollutants are molecules containing two or more condensed aromatic rings, little soluble in water and are present in the environment as a result of natural processes and human activities; in this way, the HPA can be found in various environmental matrices. In this work we used mussels in Búzios, Rio de Janeiro State. That body was selected due to the ease of accumulation of HPA in the tissues, due to the hydrophobic properties of HPA. This project aimed to study a new cleaning material able to minimize interfering compounds of the array. The 5 g Florisil SPE cartridges, are conventionally used in the cleaning of samples of organisms, however for lower costs have been tested other adsorbent materials which could be effective in the removal of the present in the tissues of mussels interfering. Therefore, in step of cleaning known as clean-up, recovery of pyrene was studied after extraction by microwave through two different approaches; a) use of commercial SPE cartridges 5 g of Florisil; b) cartridges filled with K-10 clay bentonite commercial, simulating the commercial cartridges. Recovery and efficiency of cleaning procedures were tested and compared. The clean-up with K-10 clay presented a recovery of up to 77% of pyrene, being effective in removing compounds of cholesterols; confirming the efficiency of the chosen material for cleaning of the sample. The technique of gas chromatography and detection by mass spectrometry (GC-MS) was applied for identification and quantification of contaminant pyrene in the final extract

Submitted by (lucia.rodrigues@ufrpe.br) on 2017-02-15T15:25:59Z No. of bitstreams: 1 Valentina Nascimento e Melo.pdf: 1846879 bytes, checksum: 0f435fbf6eac1935724bc84cb61e7e68 (MD5) / Made available in DSpace on 2017-02-15T15:25:59Z (GMT). No. of bitstreams: 1 Valentina Nascimento e Melo.pdf: 1846879 bytes, checksum: 0f435fbf6eac1935724bc84cb61e7e68 (MD5) Previous issue date: 2015-03-16 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Two strategies were considered for the synthesis of 2,3-unsaturated O-glucosyl-1,2,3-triazoles. The reaction between tri-O-acetyl-D-glucal and triazole alcohols gave no stereoselectivity. In fact, β-isomer formation was increased. A second strategy furnished 2,3-unsaturated O-glucosides from tri-O-acetyl-D-glucal and alkynols via Ferrier rearrangement; this methodology employing montmorillonite K-10 doped with FeCl3∙6H2O affords new glycosides in good to excellent yields, short time and high α-stereoselectivity in dichloromethane. Subsequently, the glucosides were coupled with 2-azido-1,4-naphthoquinone to give a new series of 1,2,3-1H-triazolyl O-glucoside derivatives based on click reaction. / Duas estratégias foram consideradas para a síntese de 1,2,3-triazóis O-glicosídeos2,3-insaturados. A reação entre o tri-O-acetil-D-glucal e os alcoóis triazólicos não mostrou seletividade. De fato, a formação do isômero β foi aumentada. Uma segunda estratégia forneceu O-glicosídeos 2,3-insaturados a partir do tri-O-acetil-D-glucal e alquinóis via rearranjo de Ferrier; esta metodologia formou novos glicosídeos, empregando montmorilonite K-10 dopado com FeCl3∙6H2O em diclorometano, em rendimentos de bons à excelentes, baixo tempo reacional e alta α-estereosseletividade. Subsequentemente, os glicosídeos foram acoplados com 2-azido-1,4-naftoquinona formando uma nova série de derivados 1,2,3-1H-triazolil O-glicosídeos através da reação Click.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Enamino carbonylic compounds are important synthetic intermediates used in the synthesis of heterocycles and natural products. Our group of research has been dedicating much of our efforts to the development and implementation of simple and efficient methodologies to obtain β-enamino carbonylic compounds, mainly due to their functionality and ability to react both as ambident nucleophiles and as ambident electrophiles. In this dissertation, we study the synthesis and reactivity of new α-chloro functionalized N-substituted β-enamino acyclic compounds. In the synthesis of α-chlorinated β-enamino esters (2a-g) was employed the condensation of ethyl 2-chloro-acetoacetate with primary amines. This convenient and safe procedure uses the clean chemistry methodology of microwave-assisted solid support (K-10) synthesis in the absence of solvent. The reactivity and regiochemistry of the α-chlorinated β-enamino compounds was assessed through the study of cyclization reactions involving the coupling of these substrates with dinucleophiles such as hydrazine and semicarbazide derivatives. The obtained heterocycles showed the influence of the chloro substituent at the α position, which led to the inversion of reactivity of this center, allowing the preparation of heterocyclic compounds having four and six members. These functionalized heterocycle derivatives are attractive targets for the discovery of new active molecules as they have high potential to present a broad range of biological properties. Therefore, evaluation of the antimicrobial activity of the newly synthesized compounds was carried out using the in vitro Bioautography assay. / Compostos enamino carbonílicos são importantes intermediários sintéticos usados na síntese de heterociclos e produtos naturais. Nosso grupo de pesquisa tem se dedicado ao desenvolvimento e implementação de metodologias simples e eficientes para obter compostos β-enamino carbonílicos, principalmente devido à sua funcionalidade, atuando como sistema ambidentado, tanto com caráter nucleofílico como eletrofílico. Neste trabalho, nós estudamos a síntese e a reatividade de novos β-enamino compostos acíclicos α-cloro funcionalizados Nsubstituídos. Na síntese de β-enamino ésteres α-clorados (2a-g) foi empregada a condensação do 2-cloro acetoacetato de etila com aminas primárias. Este procedimento simples e seguro, emprega a metodologia de suporte sólido (K-10) associada ao uso de energia de microondas (MO) na ausência de solvente, sendo considerado como um protocolo de Química Limpa. A reatividade dos centros eletrofílicos dos β-enamino compostos α-clorados foi estudada em reações de ciclização, reagindo-se estes compostos frente a dinucleófilos como hidrazinas e semicarbazida, avaliando-se o padrão de reatividade destes compostos e a regioquímica dos sistemas heterocíclicos polifuncionalizados 3 e 4 obtidos. Os heterociclos obtidos mostraram a influência do substituinte cloro na posição α, o qual levou a uma inversão na reatividade deste centro, possibilitando a obtenção de compostos heterocíclicos de quatro e seis membros. Os sistemas heterocíclicos funcionalizados obtidos são alvos atrativos para a descoberta de novas moléculas ativas, devido as suas características estruturais com elevado potencial para apresentar propriedades biológicas. Portanto, estudos foram conduzidos para determinar a atividade antimicrobiana de uma série de compostos sintetizados empregando o ensaio in vitro através do método de Bioautografia.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Due to the high chemical versatility of β-keto esters and the β-enamino carbonylic compounds as synthetic precursors, our research group has investigated and developed methodologies for their synthesis and reactivity. In the present work, we aim to establish a methodology for the transesterification of β-keto esters using montmorillonite (K-10) as a support or catalyst by itself or together with microwave irradiation (MW). We used the methodology to evaluate the synthesis and reactivity of β-enamino esters. The cyclic β-keto ester ethyl-2-oxo-1-cyclopentanecarboxilate was synthesized by ethanol esterification followed by Dieckmann Cyclization of adipic acid. To obtain the series of the cyclic β-keto esters derived from ethyl-2-oxo-1-cyclopentanecarboxilate by transesterification reaction with allylic and benzylic alcohol and (1S, 2R, 5S)-(+)-menthol, montmorillonite (K-10) as catalyst with microwaves was used. To validate the methodology chosen for our work, we compared microwave irradiation to the use of reflux in toluene. The use of K-10/MW in the absence of solvent was shown to be more efficient than refluxing in toluene, giving higher yields with a much reduced reaction time. Cyclic β-enamino esters were obtained by condensation of the previously synthesized β-keto esters with primary amines, using the same K-10/MW methodology adapted to a sealed flask. This step gave excellent results. For the study of the β-enamino esters reactivity evaluation we tried several reduction systems for ethyl 2-allylamino-1-cyclopentene-1-carboxylate, without success. For the evaluation of the β-keto esters reactivity we chose ethyl 2-oxo-1-cyclopentanecarboxylate and allyl 2-oxo-1-cyclopentanecarboxylate. They were used in the condensation reaction with secondary amines and also for cyclization using Mn(OAc)3, to give a cyclic amide and a spiro compound, respectively. / Devido à grande versatilidade química como precursores sintéticos, os β-cetoésteres e os compostos β-enamino carbonílicos, têm sido alvo de estudos em nosso grupo de pesquisa no desenvolvimento de metodologias para a síntese e reatividade desses compostos. Neste trabalho buscamos estabelecer metodologias para transesterificação de β-cetoésteres, utilizando montmorillonita (K-10), como suporte ou catalisador associado ou não ao uso de energia de microondas e avaliar a obtenção e a reatividade de β-enamino ésteres. Visando tais objetivos, sintetizamos o β-cetoéster cíclico, 2-oxo-1-ciclopentanocarboxilato de etila a partir do ácido adípico, através da esterificação em etanol, seguida de uma Ciclização de Dieckmann. Na obtenção de uma série de β-cetoésteres cíclicos derivados do 2-oxo-1-ciclopentanocarboxilato de etila, pela reação de transesterificação deste frente a álcool alílico, benzílico e (1S, 2R, 5S)-(+)-mentol, elegeu-se a metodologia utilizando montmorillonita (K-10) como catalisador associada a energia de microondas. Para validação desta metodologia, comparou-se a utilização de energia de microondas com o emprego de refluxo em tolueno. A metodologia empregando K-10/MO na ausência de solvente mostrou-se, mais eficiente, pois apresentou melhores rendimentos e tempos reacionais bastante reduzidos em relação à outra metodologia avaliada. Foram obtidos β-enamino ésteres cíclicos pela condensação dos β-cetoésteres sintetizados com aminas primárias empregando a metodologia de suporte sólido (K-10), associada à energia de microondas adaptada para vaso vedado obtendo ótimos resultados. Para a avaliação da reatividade dos β-enamino ésteres, vários sistemas redutores foram empregados para o 2-alilamino-1-ciclopenteno-1-carboxilato de etila, sem sucesso. Para o estudo da reatividade de β-cetoésteres, elegemos o 2-oxo-1-ciclopentanocarboxilato de etila e o 2-oxo-1-ciclopentanocarboxilato de alila, que foram submetidos à reação de condensação frente à amina secundária e à reação de ciclização promovida por Mn(OAc)3, obtendo-se, respectivamente, uma amida cíclica e um composto espiro.

Diese Dissertation beschreibt die Synthese der vier Flavanone Lonchocarpol A, 6-Dimethylallylnaringenin, Glabrol und Euchrenon A7. Des weiteren konnten drei dieser Naturstoffe enantiomerenrein mit Hilfe einer kinetischen Racematspaltung hergestellt werden. Dabei wurden die Carboxylkohlenstoffe selektiv mit einer asymmetrischen Transferhydrierung nach Noyori reduziert.

Diese Dissertation beschreibt die Synthese der vier Flavanone Lonchocarpol A, 6-Dimethylallylnaringenin, Glabrol und Euchrenon A7. Des weiteren konnten drei dieser Naturstoffe enantiomerenrein mit Hilfe einer kinetischen Racematspaltung hergestellt werden. Dabei wurden die Carboxylkohlenstoffe selektiv mit einer asymmetrischen Transferhydrierung nach Noyori reduziert.

My lecture serves as a critical examination of the Six Sonatas Op. 3, KV. 10-15 by W.A. Mozart. I will engage the variances between the first edition of Op. 3 and those by Joseph Bopp and Louis Moyse edited specifically for the flute in hopes of providing another perspective for students, performers, and pedagogues alike. This study will (1) provide background information regarding the creation of KV. 10-15, (2) include a brief analysis of each sonata, (3) compare adaptions between the first edition, according to NMA, and two modern flute transcriptions, and (4) produce two new transcriptions. My new transcriptions of Sonatas KV. 10 and 13 represent a closer interpretation to the first edition and alerts students and teachers to the differences between the editions by Joseph Bopp and Louis Moyse to that of the first and NMA editions. The goal is to stimulate performers to reappraise their approach to this particular repertoire and to encourage more authentic performances of these engaging sonatas.