The first comprehensive analysis of surface waters in the Labrador Sea for 236U was completed via Accelerator Mass Spectrometry. Through the analysis of 236U the method for AMS measurement was fine-tuned to allow for more precise results. Surface samples for the anthropogenic isotopes 137Cs and 129I were also collected along with two depth profiles of 129I. Samples were also collected in the Beaufort Sea and analyzed for the aforementioned isotopes. It was found that anthropogenic 129I from reprocessing plants is easily discernible at different concentrations among water bodies in both the Labrador and Beaufort Sea. 137Cs in surface waters is close to global fallout levels with no discernable influence from reprocessing plant inputs, but follows a similar trend to that of 129I with depth in the Beaufort Sea. 236U among surface waters in the Labrador Sea did not follow the same trends as 129I but had concentrations indicative of a mix of global fallout as well as reprocessing plant influenced waters. 236U samples from the Beaufort Sea were contaminated by an unknown source of 236U and were inconclusive but were reproducible and allowed for continued development of the AMS analysis methodology.

Results of I-Xe analyses have been obtained from meteorite samples that experienced different extents of thermal processing in the early Solar System in order to help characterise the movements of iodine and xenon in the early Solar System and constrain the timing of these movements using the I-Xe chronometer. Samples were irradiated to convert 127I to 128Xe* and allow simultaneous measurements of iodine and xenon isotopes. Xe isotopes were measuring using the RELAX mass spectrometer.I-Xe ages of material of different metamorphic grade from R-chondrites NWA 6492, NWA 830 and NWA 3364 suggest a link between the time of closure to Xe-loss and extent of metamorphism on the R-chondrite parent body. However, further I-Xe analyses of R5 material from NWA 6492 and R4 and R6 material from other R-chondrites are needed to confirm this. The most primitive material analysed give I– Xe ages between 4559 – 4554 Myr, slightly later than reported Mn-Cr ages. This may support the ideal of radial heterogeneity of 53Mn in the early Solar System. However differences could also be due to variations in the samples analysed. Future analyses of I-Xe and Mn-Cr ages in mineral separates from the same R-chondrite are recommended in order to investigate this hypothesis. Closure to Xe-loss in chondrules on the R-chondrite parent body appears to have occurred ~5 – 10 Myr later than on the ordinary and enstatite parent bodies. This implies either later accumulation of material or slower cooling in a larger body.Comparisons of I-Xe systematics in anomalous eucrites Bunburra Rockhole and Ibitira and “nomalous” eucrites Juvinas and Béréba show lower 129I/244Pu ratios in the “nomalous” eucrites. This is not due to formation on a less volatile-rich body but instead reflects extended loss of Xe on 4 Vesta. 129I/244Pu ratios indicate igneous processing continued on 4 Vesta for ~50-100 Myr after geological activity had ceased on the anomalous eucrites parent bodies. The extended processing seen in Juvinas and Béréba is attributed to formation on a larger body that retained heat for longer. If, as the data suggest, the anomalous eucrites formed on a separate parent body it must have been catastrophically disrupted as Vesta is thought to be the only remaining differentiated asteroid. The larger size of Vesta may explain why it has uniquely survived the impacts that destroyed its siblings. Analyses of the unique achondrite GRA 06129 show that the I-Xe system in this meteorite has no chronological significance. The data instead suggest that iodine-bearing plagioclase formed early but thermal metamorphism resulted in loss of 129Xe* from iodine bearing sites. Uranium-bearing apatite appears to be a secondary mineral that incorporated parentless 129Xe* and 129Xe*that had been redistributed during earlier metamorphism. A trapped-Xe component released at high-temperatures may be a primitive component such as Q-Xe, though terrestrial–Xe acquired during weathering cannot be ruled out by this study. If Q-Xe is present, it is most likely hosted in a primary phase other than plagioclase. During its terrestrial residence time GRA 06129 acquired iodine via Antarctic weathering. I-Xe analyses on Antarctic meteorites should therefore be carried out with caution. Further Xe analyses of mineral separates from GRA 06129 would help constrain the host phase of the trapped Xe. That the I-Xe system of the plagioclase has been completely reset make it a good candidate mineral for I-Xe dating of primary processes whereas I-Xe dating of apatite appears more problematic.

The potential use of four radioiodinated fatty acids as myocardial imaging agents were evaluated. Preliminary distribution studies revealed that the terminal labeled fatty acids demonstrated higher myocardial uptake. Thus, 10-Iodocapric acid (10-iododecanoic) and 12-Iodolauric acid were subjected to further investigation. Comprehensive tissue distribution studies involving both radioiodinated fatty acids in mice indicated that the highest accumulation of the total injected activity occurred in the muscle and the blood. Other organs investigated included the heart, liver, lung, kidneys, spleen, stomach, intestines, bone and adrenals. The heart exhibited the highest concentration of the radioiodinated fatty acids for the relative accumulation of activity per unit weight. Erom the tissue distribution studies, the optimum scanning time was found to be immediately following injection of the radiopharmaceutical. Toxicity studies were performed in mice after intravenous administration of 10-Bromocapric acid and 12-Bromolauric acid. The LD₅₀ of Sodium Bromolaurate in 10% Human Serum Albumin was found to be 210 mg/kg (194 mg/kg - 228 mg/kg). The stability problem encountered with 10-Bromocapric acid necessitated the use of a different solvent system. The LD₅₀ obtained after intravenous injection was found to be 86.1 mg/kg (83.0 mg/kg - 89.3 mg/kg). However, this observed toxicity may not necessarily reflect the toxicity of the Bromocapric acid solely. Whole body excretion studies were performed in mice and revealed a triexponential excretion curve. For 10-Iodocapric acid, the effective half-lives were .90 hours (36.7%), 3.91 hours (61.6%) and 74.9 hours (14.5%). For 12-Iodolauric acid, the effective half-lives were 1.67 hours (46.6%), 7.68 hours (38.4%), and 71.6 hours (17.8%). For both 10-Iodocapric acid and 12-Iodolauric acid, the first as well as the second component of the excretion curve presumably represented a decrease in the whole body activity due mainly to urinary excretion. The third component appeared to represent activity which was tightly bound and slowly released. The third component presumably represented elimination by fecal excretion. The excretion of the injected activity was primarily in the urine, although some activity was recovered in the feces. For 10-Iodocapric acid, 82.4% of the injected activity had been recovered in the urine within the first 24 hours and 8.88% had been recovered in the feces. For 12-Iodolauric acid, 78.9% of the injected dose was recovered in the urine at 24 hours and 9.4% in the feces. From the urine results, the effective half-life of the radio-iodinated fatty acids in the kidneys was found to be 4.8 hours. Myocardial scans were done on rabbits using ¹³¹I-capric acid, ¹³¹I-lauric acid, NaI-131 (6% Human Serum Albumin), and Thallium-201 at specified time intervals after injection. Iodine-123, a radionuclide possessing more favorable imaging properties, was not readily available due to production problems at the time of scanning. The mean absorbed dose to the whole body, the liver, the kidneys, the muscle, and the heart were computed based on the results from the distribution and excretion studies. The dosimetry calculations were done using Iodine-123 as the radionuclide. For ¹³¹I-capric acid, the radiation doses were calculated as 34.76 mrads/2 mCi for the whole body, 136.3 mrads/2 mCi for the kidneys, 86.6 mrads/2 mCi for the liver, 38.5 mrads/2 mCi for the muscle, and 25.89 mrads/2 mCi for the heart. For ¹³¹I-lauric acid, the radiation doses were 41.73 mrads/2 mCi for the whole body, 199.8 mrads/2 mCi for the kidneys, 185.9 mrads/2 mCi for the liver, 52.07 mrads/2 mCi for the muscle, and 46.39 mrads/2 mCi for the heart. / Pharmaceutical Sciences, Faculty of / Unknown

Orientador: Laura Sterian Ward / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T12:12:10Z (GMT). No. of bitstreams: 1 Morari_ElaineCristina_D.pdf: 1770772 bytes, checksum: f0438710dc4ea98d3ad5dcac857c770e (MD5) Previous issue date: 2006 / Resumo: Como a maior parte dos carcinomas diferenciados tem um excelente prognóstico, alguns autores consideram o tratamento convencional, isto é, a tireoidectomia total seguida de ablação actínica de remanescentes glandulares, excessivo. Combinações de fatores específicos do paciente e do tumor foram propostas para classificação prognóstica, mas na prática são pouco utilizadas. Os resultados de alguns trabalhos sugerem relação entre a expressão dos genes MUC, p53 e NIS e a evolução clínica das neoplasias tireoidianas. Com o objetivo de investigar a utilidade clínica de marcadores imonoistoquímicos de prognóstico, estudamos 67 nódulos tireoidianos, incluindo 57 carcinomas, dos quais incluiu 34 (50,74%) carcinomas papilíferos, sendo 21 (31,3%) casos do tipo histológico clássico, 7 (10,4%) da variante de células altas e 6 (9%) da variante folicular. Avaliamos também 16 (23,9%) carcinomas foliculares, 4 (6%) medulares e 3 carcinomas anaplásicos (4,5%). Dez casos (14,9%) foram obtidos de pacientes submetidos à cirurgia com o diagnóstico de doenças benignas da tiróide (3 casos de bócio nodular, 4 adenomas foliculares e 3 tecidos tireoidianos normais). Todos os pacientes foram submetidos a um mesmo protocolo de tratamento e acompanhados por 66±28 meses (mediana de 63 meses) sendo classificados como apresentando evolução favorável ou desfavorável. Consideramos de evolução desfavorável os 19 pacientes que possuíam evidência de recorrência local ou à distância ou que foram a óbito durante o seguimento pela doença. Realizamos estudos imunoistoquímicos da detecção das proteínas NIS, p53 e MUC1 comparando-os com a evolução dos pacientes. Mostramos que pacientes com carcinomas bem diferenciados, ausência de metástases, estadio II e estadiamento T2 têm uma evolução melhor em relação aos pacientes com carcinomas pouco diferenciados, presença de metástases, estadio IV e estadiamento T4. Não encontramos relação entre a expressão das proteínas NIS, p53 e MUC1 e a evolução dos pacientes estudados / Abstract: Because most differentiated thyroid carcinomas have an excellent prognosis, some authors have been claiming that these patients have been over-treated. Combinations of patient-and tumor-specific factors have been proposed for prognostic stratification, but no clinicpathologic staging was demonstrated to be useful at the present time. In order to investigate the clinical utility of immunohistochemistry markers, we studied 67 thyroid nodules including 50 thyroid carcinomas. There were 34 (50,74%) papillary carcinomas, including 21 (31,3%) cases of the classical histological type, 7 (10,4%) tall cell variants and 6 (9%) of the follicular variant type. Also, there were 16 (23,9%) follicular carcinomas, 4 (6%) medullary and 3 anaplastic carcinomas (4,5%). Ten patients (14,9%) were submitted to surgery because of benign thyroid diseases (3 nodular goiter cases, 4 follicular adenomas and 3 thyroid tissues normal). All patients were submitted to a similar management protocol and followed-up for 66±28 months (median of 63 months) and classified as presenting a good or a bad evolution. We considered as presenting a bad evolution 19 patients that presented evidence of local or distant recurrence and the patients that died during the follow-up. Immunohistochemical expression of NIS, p53 and MUC1 proteins was compared to patient¿s evolution. We showed that patient with well differentiated thyroid carcinomas, absence of distant metastases, stage II and staging T2 have a better evolution in relation to the patients with poorly differentiated thyroid carcinomas, presence of metastases, stage IV and staging T4. We were able to find relation between the expression of proteins NIS, p53 and MUC1 and prognostic of the studied patients / Doutorado / Clinica Medica / Doutor em Clínica Médica

Orientador: Matthieu Tubino / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-22T05:19:24Z (GMT). No. of bitstreams: 1 Castro_AdrianoGomesde_D.pdf: 1872629 bytes, checksum: a53102e92aa91347cbcb783b0cdec7b5 (MD5) Previous issue date: 2013 / Resumo: Óleos vegetais e biodieseis são facilmente oxidados, sendo necessário a adição de anti-oxidantes. Esse trabalho mostra que a curcumina age como antioxidante nos biodieseis de soja, girassol, milho, canola e coco babaçu. No óleo de coco babaçu ela age como antioxidante e nos demais óleos estudados não apresenta efeito ou age como pró-oxidante, de acordo com a sua concentração e do tipo de óleo. A curcumina apresenta-se termicamente estável até em torno de 175°C, podendo ser usada como aditivo até essa temperatura. Ela é solúvel em até 0,10% em massa, nos óleos e nos biodieseis. A estabilidade oxidativa depende da temperatura, da concentração de antioxidante e da composição química dos biodieseis. A ordem da estabilidade oxidativa para os biodieseis estudados é: girassol < soja < canola < milho < coco babacu; e para os óleos vegetais é: girassol < coco babacu < canola < milho < soja. A cinética de retardamento da oxidação dos biodieseis pode ser considerada como de primeira ordem devido às boas correlações linear apresentadas entre logaritmo natural da concentração de aditivo versus o período de indução. As energias de ativação foram obtidas pela equação de Arrhenius e os parâmetros termodinâmicos, DH* e DS* pela equação de Eyring e o DG* pela equação fundamental da termodinâmica. O período de indução dos biodieseis e dos óleos à 25°C foi obtido pela equação que correlaciona o logaritmo natural do período de indução com a temperatura. Observou-se aumento da estabilidade oxidativa nos biodieseis de girassol e de coco babaçu de 0,98 e 149,82 meses respectivamente, com a adição de 0,05% em massa de curcumina, e para os biodieseis de soja, canola e milho, 2,41, 2,35 e 1,10 meses respectivamente, com a adição de 0,10% em massa de curcumina. Observou-se, também, que o período de indução dos biodieseis e dos óleos correlaciona linearmente com o índice de iodo dos mesmos. / Abstract: Vegetable oils and biodiesel are easily oxidized requiring the addition of antioxidants. This study shows that curcumine acts as antioxidant in biodiesel of soybean, sunflower, corn, canola and babassu coconut. In babassu coconut oil it acts as antioxidant however in the other oils studied it present no effect or act as a pro-oxidant, according to the oil and its concentration. Curcumine is thermally stable up to about 175 °C, therefore it can be used as antioxidant until this temperature. It is soluble up to 0.10% by weight in oils and biodiesel. As expected, the oxidative stability is of biodiesel is dependent of the temperature, of its chemical composition and of the concentration of the antioxidant. The order of oxidative stability for biodiesel is: sunflower<soybean<canola<corn<babassu coconut, and for vegetable oil is: sunflower<babassu coconut<canola<corn<soybeans. The kinetics of the oxidation retarding of biodiesel can be considered as a first order due to the good linear correlations displayed between in additive concentration versus the induction period. The activation energies were obtained using Arrhenius equation and the thermodynamic parameters such as DH* and DS* by Eyring equation and DG* by the equation fundamental of thermodynamic. The induction period of oils and biodiesels at 25 °C was obtained by equation that correlates the natural logarithm of the induction period with the temperature. Increase in the oxidative stability biodiesel of babassu coconut and sunflower is of 149.82 months and 0.98 respectively, with the addition of 0.05 % w/w of curcumine, and for the biodiesel of soybean, canola and corn, 2.41, 2.35 and 1.10 months, respectively, by the addition of 0.10% w/w of curcumine. It was also observed that the induction period of biodiesel and oils has a linear relationship with its respectives iodine values. / Doutorado / Quimica Analitica / Doutor em Ciências

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-04-19T11:21:33Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇAO-GIULLIANA_NOBREGA.pdf: 1803238 bytes, checksum: 3e84c45ed9de31b5cd10607f9f195dca (MD5) / Made available in DSpace on 2016-04-19T11:21:33Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇAO-GIULLIANA_NOBREGA.pdf: 1803238 bytes, checksum: 3e84c45ed9de31b5cd10607f9f195dca (MD5) Previous issue date: 2015-06-15 / CNPq / INTRODUÇÃO: O carcinoma diferenciado de tireoide (CDT) é avaliado e tratado de acordo com fatores prognósticos. Embora tenha um bom prognóstico, 14% dos pacientes considerados como de baixo risco de recorrência podem apresentar doença persistente mesmo com tratamento adequado. Por isso, estudos têm sido realizados no intuito de encontrar outros possíveis preditores de persistência do CDT. OBJETIVO: Avaliar que fatores clínicos, laboratoriais e anatomopatológicos estão associados à persistência do CDT um ano após radioiodoterapia (RIT). METODOLOGIA: Foi realizada uma revisão de prontuários, na qual foram incluídos 375 pacientes portadores de CDT. Foram coletados dos registros os dados clínicos (gênero e idade), resultados de dosagens de hormônio tireoestimulante (TSH), tireoglobulina (Tg) e anticorpo anti-tireoglobulina (AATg) antes e um ano após RIT, resultados de varredura de corpo inteiro (PCI) após dose ablativa de radioiodo (131I) e um ano após tratamento inicial, além de laudos dos exames histopatológicos. A partir dos dados obtidos, foi realizada análise bivariada e as variáveis que apresentaram significância inferior a 20,0% (p < 0,20) foram submetidas à análise multivariada através do modelo de regressão de Poisson. Para se chegar a um valor de Tg estimulada (TgE) capaz de predizer os pacientes que teriam maior chance de persistência de doença, foi realizada uma curva ROC. RESULTADOS: Observou-se associação significativa entre persistência de doença e idade inferior a 45 anos (p=0,001), multifocalidade (p=0.008) e tamanho tumoral entre 2 a 4 cm (p=0,002). Além disso, verificou-se associação significativa entre da TgE e persistência do CDT (p<0,001). O ponto de corte de TgE pré-dose com maior sensibilidade e especificidade para prever persistência de doença foi de 7,4 ng/mL. Utilizando este valor encontramos um valor preditivo negativo (VPN) de 87,5%. CONCLUSÃO: Neste estudo encontramos uma forte associação entre persistência do CDT e faixa etária, tamanho tumoral, multifocalidade e Tg estimulada pré-ablação. A Tg estimulada pré-ablação mostrou-se um valioso preditor de persistência de CDT um ano após RIT. Valores de 7,4 ng/mL ou mais mostraram maior sensibilidade e especificidade para prever este desfecho. / BACKGROUND: Differentiated thyroid carcinoma (CDT) is evaluated and treated according to prognostic factors. Although it has a good prognosis, 14% of the patients which are considered at low risk of recurrence, might have persistent disease despite suitable treatment. Hence, studies have been realized in order to find other possible prognostic predictors for CDT persistence. OBJECTIVE: Assess which clinical, laboratory and pathological factors are associated with persistence of CDT one year after radioiodine therapy (RIT). METHODS: It was performed a chart review, in which was included 375 patients with CDT. Were collected clinical data (age and sex), results of thyroid-stimulating hormone (TSH), thyroglobulin (Tg) and antithyroglobulin antibody (AATg) before and one year after RIT, whole body scan (PCI) results after ablative dose of 131I and one year later and, also histopathological exam reports. From these data, was performed a bivariate analysis and the variables that were significant lower than 20.0% (p <0.20) were submitted to multivariate analysis using Poisson regression model. To achieve a stimulated Tg (TgE) value able to predict which patients would have a greater chance of persistent disease, a ROC curve was performed. RESULTS: A significant association was found between persistence of disease and age less than 45 years (p = 0.001), multifocality (p = 0.008) and tumor size between 2-4 cm (p = 0.002). In addition, there was a significant association between TgE and persistence of CDT (p <0.001). The pre-ablation TgE cutoff with greater sensitivity and specificity in predicting persistence of disease was 7.4 ng / mL. Using this value, we found a negative predictive value (VPN) of 87.5%. CONCLUSION: We found a significant association between persistent CDT and age, tumor size, multifocality and pre-ablation TgE in this study. TgE pre-ablation was shown to be a valuable predictor of persistence CDT one year after RIT. Values of 7.4 ng / ml or more showed greater sensitivity and specificity to predict this outcome.

Transparency and conductivity are highly desirable qualities in materials for modern gas sensors. Polymer gas sensors have been developed in which the polymer acts as a solid electrolyte. However, these types of sensors are opaque, which limits their potential for integration with dichromatic materials. The development of a sensor integrating conductive polymer films and dichromatic materials requires the implementation of a transparent conductive polymer film. The potential of iodine-doped bisphenol-a polycarbonate films containing bis(ethylenedioxy)-tetrathiafulvalene (BEDO-TTF) dye for sensor applications will be tested through characterization of the films at various stages of their fabrication using Atomic Force Microscopy (AFM), Transmission Electron Microscopy (TEM), transmission Fourier Transform Infrared Spectroscopy (FTIR), Optical Microscopy (OM), and Four Point Probe conductivity measurements (FPP). FTIR results show that there is an interaction between the polycarbonate matrix and the dye-iodine complex. Measured resistivities of the iodine doped films range from 148 Omega-cm to 2.82 kOmega-cm depending on the concentration of the iodine and exposure time. The imaging techniques used show a significant difference in the structure and the surface of the iodine doped-PC-BEDO-TTF films with respect to the bare polycarbonate films or the films mixed with the organic dye. It is also clear that the surface roughness of the prepared conductive films increases with iodine loading. These films have the potential to be used in sensor or photovoltaic applications.

Lors de ce travail de thèse qui visait à développer une méthode générale d’introduction d’halogénures et de pseudo-halogénures en se basant sur l’utilisation de réactifs d’iode hypervalent en tant que promoteurs d’umpolung, diverses avancées ont pu être accomplies. Tout d’abord, une réaction d'alkoxybromation régiosélective mettant en jeu des sels de bromure et du PIDA a été mise au point. Un des intérêts de cette réaction réside dans l'utilisation de LiBr peu coûteux comme source d'halogène électrophile (par inversion de polarité : umpolung). En outre, l'introduction de deux groupements de manière chimio- et régiosélective est possible sans recourir à l'utilisation d’un catalyseur métallique. Une large gamme d'énamides a été testée et les rendements sont généralement excellents (au dessus de 75 %) et les réactions rapides (moins d’une heure). En outre, la diastéréosélectivité oscille entre modérée et excellente. Ces produits éthoxybromés se sont aussi montrés très polyvalents et permettent l’accès à de nombreux motifs structuraux. Une version asymétrique de cette réaction en faisant intervenir des dérivés d’iode hypervalent chiraux n’a pas été couronnée de succès tout comme l’introduction de copules chirales. Le but initial était de mettre au point une méthode générale de difonctionnalisation d’énamides avec l’insertion d’halogénures. C’est pourquoi, notre stratégie a ensuite été étendue au chlore et une réaction d’éthoxychloration a été développée avec des rendements moyens à très bons (de 36% à 86%) un temps de réaction rapide (généralement autour de 30 minutes) et une diastéréosélectivité moyenne à très bonne (de 55/45 à 92/8). Les deux réactions d’éthoxybromation et d’éthoxychloration ont fait l’objet d’une investigation mécanistique (notamment par spectrométrie de masse) et il semblerait que le mécanisme soit ionique. Nous avons alors voulu appliquer cette méthodologie au fluor, élément dont l’introduction sélective sur un substrat est rarement triviale. En accord avec la littérature, nous avons conclu que le fluor ne pouvait être transféré directement en tant qu’électrophile. Enfin, une version d’éthoxyiodation a été validée et est en cours d’optimisation au laboratoire. Concernant les pseudo-halogénures, nous nous sommes uniquement intéressés aux azotures. Ayant réalisé qu’une réaction d’éthoxyazidation ne serait pas possible, une étude poussée des différents paramètres réactionnels adossée à la compréhension des mécanismes mis en jeu a été entreprise. Deux méthodologies ont alors pu être mises au point : une réaction de diazidation dont les rendements sont modérés ( entre 20% et 52%), les temps de réaction courts (environ 1 h) et des diastéréosélectivités moyennes à bonnes (entre 75/25 et 90/10) ainsi qu’une réaction d’oxyamination qui se montre bien plus efficace avec des rendements moyens à très bons (de 31% à 95%), des temps de réaction assez rapides (autour de 2 h), des diastéréosélectivités souvent excellentes (supérieures à 67/33) et un champ d’application bien plus large (Schéma 245). Ces deux méthodes réunies représentent un outil utile pour l’obtention de composés à la fois azotés et azidés. Dans ce cas, les intermédiaires réactionnels semblent être radicalaires même si des études complémentaires restent à effectuer.L’intérêt synthétique de ces deux types de composés a aussi fait l’objet de diverses études. Si la réduction du groupement azido en amine n’a pas pu être systématiquement accomplie, des réactions de cyclisation d’Huisgen sur les produits diazidés ont cependant fonctionné (les produits oxyaminés semblant trop encombrés stériquement). Quant au groupement TEMPO il a notamment pu être oxydé en cétone. Ainsi, des outils méthodologiques ont été développés lors de cette thèse, pour la difonctionnalisation oxydante d’énamides par des dérivés d’iode (III) hypervalent et en particulier, l’introduction d’halogénures et d’azotures. / Hypervalent iodine compounds such as (diacetoxyiodo)benzene (PIDA) are non-toxic and mild reagents that can behave in similar fashion to transition-metal complexes. Indeed, around the central iodine atom, ligands can be exchanged and then transferred through a formal reductive elimination. Following this strategy, halides can be used as ‘ligands’, in which case an umpolung of the salt can occur to give birth to electrophilic halogen species. Using LiBr, ethanol and PIDA, a variety of enamides underwent a regioselective ethoxybromination with high yields, short reaction time and good to excellent diastereoselectivity. One of the main interests of this reaction lies in the use of a cheap and widely available bromide salt (LiBr) to generate electrophilic halogen species by umpolung. Moreover, despite the oxidative nature of the reaction conditions, a wide scope of functional groups (olefins, esters, alcohols…) is tolerated. This reaction provides α-bromo-hemiaminals which are highly versatile synthons. For instance, various nucleophiles can be incorporated on the hemiaminal moeity and then engaged in further transformations. The development of an asymmetric variant of this transformation using chiral pool or chiral hypervalent iodine was unsucceful. This methodoly has been extended to the umpolung of other salts as chlorine with moderate to good yields (from 36% to 86%) and a moderate to very good diastereoselectivity (from 55/45 to 92/8) with a short reaction time (30 minutes). Mechanistic investigation for both reactions has been performed and an ionic parthway has been priviledge. The introduction of fluorine as an electrophile was not possible according to the litterature.Finally, the last halide, iodine can be tansfered and an ethoxyiodation reaction is under optimisation. Concerning the pseudo-halides, we devot a special attention to azides. Two methodologies has been set up : a diazidation reaction which yields are moderate (betwwen 20% and 52%), short reaction times (around 1 h) and moderate to good diastereoselectivity ratios (between 75/25 and 90/10) and an oxyamination reaction whiwh shows to be much more efficient with moderate to very high yields (from 31% to 95%), short reaction times (around 2 h), excellent diastereoselectivity ratio (superior to67/33). These two gathered reactions represent a useful tool for the introduction of a nitrogen. For the diazidation reaction, the intermediatories seem to be radicals whereas for the oxyamination reaction probably ionic species. . Thus, synthetic tools have been developped during this thesis for the difunctionnalisation of enamides by hypervalent iodine and particulary introduction of halides and azides

No description available.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22337号 / 医博第4578号 / 新制||医||1041(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 佐藤 俊哉, 教授 福原 俊一, 教授 鈴木 実 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM