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Doctoral Thesis
DOI
https://doi.org/10.11606/T.59.2017.tde-19012017-090248
Document
Author
Full name
Simone Cavalcante Silva
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2016
Supervisor
Committee
Clososki, Giuliano Cesar (President)
Lourenço, Ricardo Vessecchi
Moraes, Luiz Alberto Beraldo de
Silva Filho, Luiz Carlos da
Souza, Rodrigo Octavio Mendonça Alves de
Title in Portuguese
Aplicação de reagentes organometálicos na funcionalização de imidazo[1,2-ɑ)piridinas e estudo de ressonância magnética nuclear dinâmica da 4-formil-aminoantipirina
Keywords in Portuguese
1. imidazo[1,2-a]piridinas. 2. Reagentes organometálicos. 3. Metalação. 4. Ressonância Magnética Nuclear
Abstract in Portuguese
Atualmente, o núcleo imidazo[1,2-a]piridina vem atraindo considerável interesse pois está presente em uma série de moléculas que apresentam potencial para aplicações farmacêuticas. Entre suas características importantes, cabe ressaltar o isosterismo com o indol, um sistema heterocíclico encontrado em muitos alcaloides. Assim, o principal objetivo deste trabalho foi investigar o desenvolvimento de metodologias versáteis que permitissem a rápida preparação de imidazo[1,2-a]piridinas funcionalizadas e que possam ser aplicadas na síntese de moléculas bioativas. No Capítulo 1 deste trabalho, são apresentados e discutidos os resultados obtidos nos estudos sobre a reatividade de bases organometálicas, dentre as quais os novos reagentes mistos de magnésio e de lítio, frente às imidazo[1,2-a]pyridinas. De acordo com as condições reacionais estabelecidas, as bases LiHMDS e TMPMgCl.LiCl demonstraram melhores resultados nos estudos de metalação dirigida, proporcionando a preparação regiosseletiva de novos reagentes organometálicos a partir destes substratos. Além disso, após as reações do intermediários organometálicos com eletrófilos, várias imidazo[1,2-a]piridinas substituídas com diferentes grupos funcionais puderam ser isoladas e caracterizadas. Com o objetivo de demonstrar a importância sintética da metodologia de funcionalização de imidazo[1,2-a]piridinas mediada por LiHDMS, investigou-se sua aplicação em uma nova rota de síntese do alpidem, um importante ansiolítico. Finalmente, no Capitulo 2 deste trabalho, são apresentados e discutidos os resultados de um estudo de Ressonância Magnética Nuclear Dinâmica do 4-formil-aminoantipirina (4-FAA), um dos principais metabólitos da dipirona (metamizol).
Title in English
Application of organometallic reagents in the functionalization of imidazo[1,2-a]pyridines and study of the Nuclear Magnetic Resonance Dynamics of 4-formyl-aminoantipyrine
Keywords in English
imidazo[1,2-a]pyridines
Metalation
organometallic reagentes
Ressonance Magnetic Nuclear
Abstract in English
Nowadays, the imidazo[1,2-a]pyridine core has attracted considerable interest considering it is present in a series of molecules which have potential for pharmaceutical applications. Among its important properties, it is worth noting the isosterism with indole, a heterocyclic system found in many alkaloids. Thus, the main goal of this work was to investigate the development of versatile methodologies that allow the quickly preparation of functionalized imidazo[1,2-a]pyridines for further applications in the synthesis of bioactive molecules. In Chapter 1 of this work, the results obtained in the studies about the reactivity of organometallic bases against imidazo[1,2-a] pyridines, including new mixed reagents magnesium and lithium, are presented and discussed. According to the established reaction conditions, LiHMDS and TMPMgCl.LiCl bases showed better results in the studies of directed metalation, providing regioselective preparation of new organometallic reagents from these substrates. Moreover, after the reactions of the organometallic intermediate with electrophiles, many imidazo[1,2-a]pyridines substituted with different functional groups were isolated and characterized. In order to demonstrate the synthetic importance of methodology of functionalization imidazo[1,2-a]pyridines mediated by LiHDMS, it application in a new route of synthesis of anxiolytic alpidem was investigated. Finally, in Chapter 2 of this work the results of a study of Nuclear Magnetic Resonance Dynamics of 4-formyl-aminoantipyrine (4-FAA), one of the main metabolites of dipyrone (metamizol), are presented and discussed.
 
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Release Date
2021-01-19
Publishing Date
2017-02-24
 
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