Reações multicomponentes para a síntese de 4H-piranos furoxânicos com diversidade e complexidade estruturais
Data
2024-06-03
Autores
Borges, Fabiana Simões Felipe 
Orientadores
Longo Junior, Luiz Sidney
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Reações multicomponentes são uma abordagem sintética na qual três ou mais reagentes são combinados em uma única etapa, resultando em um único produto com alta diversidade e complexidade estrutural. Constituem uma ótima estratégia de síntese, possibilitando a construção de estruturas complexas a partir de reagentes relativamente simples. Recentemente esta estratégia de síntese tornou-se bastante popular para a preparação de diversos compostos heterocíclicos com diferentes potencialidades biológicas e como ferramenta em Química Combinatória para Pesquisa e Desenvolvimento de novos fármacos pela Indústria Farmacêutica. 4H-piranos, em especial os 2-amino-3-ciano-4H-piranos, são heterociclos importantes, que receberam muita atenção recente devido às suas atividades biológicas interessantes, tais como antitumoral, anti-inflamatória, etc. A estratégia mais comumente utilizada para obtenção desses compostos é uma reação multicomponente que faz uso de compostos carbonílicos (aldeídos ou cetonas), malononitrila (ou β-cetoésters equivalentes) e compostos CH2-ácidos enolizáveis, tais como a dimedona ou β-cetoésters. Neste contexto o presente trabalho de conclusão de curso apresenta o estudo da reação multicomponente para obtenção de 4H-piranos funcionalizados com o núcleo furoxano (1,2,5-oxadiazol-2-óxido), um doador de óxido nítrico com potencial atividade antitumoral. Para o desenvolvimento do método foi estudada a reação modelo entre dimedona, malononitrila e 3-metil-4-furoxanocarbaldeído em diversas condições reacionais, sendo que a melhor condição foi aquela em que utilizamos o catalisador DABCO em etanol, a temperatura ambiente. Estas condições foram aplicadas variando os materiais de partida, obtendo uma pequena série de compostos com diferentes funcionalizações, os quais foram obtidos em ótimos rendimentos, (85 a 95%). A partir das mesmas condições, a substituição do furoxanoaldeído pelo benzaldeído possibilitou a síntese de outros três 4H-piranos, os quais foram obtidos na faixa de 45-92% de rendimento. Todos os produtos obtidos foram devidamente caracterizados pelas técnicas espectroscópicas usuais. Na quantificação da liberação de NO, os 4H-piranos furoxânicos foram capazes de liberar NO em baixas quantidades (0,1 – 1,1 μM), mas ainda há espaço para a exploração da síntese de 4H-piranos furoxânicos com maior capacidade de doação de óxido nítrico.
Multicomponent reactions are a synthetic approach in which three or more reagents are combined in a single step, resulting in a single product with high structural diversity and complexity. They are an excellent synthesis strategy, making it possible to build complex structures from relatively simple reagents. This synthetic strategy has recently become very popular for the preparation of various heterocyclic compounds with different biological potentials and as a tool in Combinatorial Chemistry for Research and Development of new drugs by the Pharmaceutical Industry. 4H-pyrans, especially 2-amino-3-cyano-4H-pyrans, are important heterocycles that have received a lot of recent attention due to their interesting biological activities, such as anti-tumor, anti-inflammatory, etc. The most commonly used strategy for obtaining these compounds is a multicomponent reaction using carbonyl compounds (aldehydes or ketones), malononitrile (or equivalent β-ketoesters) and enolizable CH2-acid compounds such as dimedone or β-ketoesters. In this context, this final project presents the study of the multicomponent reaction to obtain 4H-pyrans functionalized with the furoxan scaffold (1,2,5-oxadiazole-2-oxide), a nitric oxide donor with potential antitumor activity. To develop the method, we studied the model reaction between dimedone, malononitrile and 3-methyl-4-furoxanecarbaldehyde under various reaction conditions, the best condition being that in which we used the DABCO catalyst in ethanol at room temperature. These conditions were applied by varying the starting materials, obtaining a small series of compounds with different functionalization, which were obtained in excellent yields (85 to 95%). Under the same conditions, the substitution of furoxanaldehyde by benzaldehyde enabled the synthesis of three other 4H-pyrans, which were obtained in the 45-92% yield range. All the products obtained were duly characterized using the usual spectroscopic techniques. In the quantification of NO release, the furoxan 4H-pyrans were able to release NO in low quantities (0.1 - 1.1 μM), but there is still room to explore the synthesis of furoxan 4H-pyrans with greater nitric oxide donating properties.
Multicomponent reactions are a synthetic approach in which three or more reagents are combined in a single step, resulting in a single product with high structural diversity and complexity. They are an excellent synthesis strategy, making it possible to build complex structures from relatively simple reagents. This synthetic strategy has recently become very popular for the preparation of various heterocyclic compounds with different biological potentials and as a tool in Combinatorial Chemistry for Research and Development of new drugs by the Pharmaceutical Industry. 4H-pyrans, especially 2-amino-3-cyano-4H-pyrans, are important heterocycles that have received a lot of recent attention due to their interesting biological activities, such as anti-tumor, anti-inflammatory, etc. The most commonly used strategy for obtaining these compounds is a multicomponent reaction using carbonyl compounds (aldehydes or ketones), malononitrile (or equivalent β-ketoesters) and enolizable CH2-acid compounds such as dimedone or β-ketoesters. In this context, this final project presents the study of the multicomponent reaction to obtain 4H-pyrans functionalized with the furoxan scaffold (1,2,5-oxadiazole-2-oxide), a nitric oxide donor with potential antitumor activity. To develop the method, we studied the model reaction between dimedone, malononitrile and 3-methyl-4-furoxanecarbaldehyde under various reaction conditions, the best condition being that in which we used the DABCO catalyst in ethanol at room temperature. These conditions were applied by varying the starting materials, obtaining a small series of compounds with different functionalization, which were obtained in excellent yields (85 to 95%). Under the same conditions, the substitution of furoxanaldehyde by benzaldehyde enabled the synthesis of three other 4H-pyrans, which were obtained in the 45-92% yield range. All the products obtained were duly characterized using the usual spectroscopic techniques. In the quantification of NO release, the furoxan 4H-pyrans were able to release NO in low quantities (0.1 - 1.1 μM), but there is still room to explore the synthesis of furoxan 4H-pyrans with greater nitric oxide donating properties.