Síntese, estrutura e avaliação antimicobacteriana de novos 1- (espiro[croman-2,1’-cicloalcan]-4-il)-1h-1,2,3-triazóis

• Ano de defesa: 2018
• Autor(a) principal: Stefanello, Felipe Salvador
• Orientador(a): Bonacorso, Helio Gauze
• Banca de defesa: Machado, Pablo , Souza, Diego de
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Santa Maria; Centro de Ciências Naturais e Exatas
• Programa de Pós-Graduação: Programa de Pós-Graduação em Química
• Departamento: Química
• País: Brasil
• Palavras-chave em Português: Triazóis; Espiro heterociclos; Cromenonas
• Palavras-chave em Inglês: Triazoles; Spiro heterocycles; Chromenones
• Área do conhecimento CNPq: CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
• Link de acesso: http://repositorio.ufsm.br/handle/1/16078

This thesis describes the synthesis, structural study and antimycobacterial evaluation of a series of novel 4-(alkyl/aryl)-1-(spiro[chroman-2,1'-cycloalkan]-4-yl)-1H-2,3-triazoles having as substituent aryl = phenyl, 4- aminophenyl, 3-methoxyphenyl and alkyl = n-hexyl and hydroxymethyl, for the cycloalkanes corresponding to cyclopentane, cyclohexane and cycloheptane. The regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles was performed from 4-azidospiro [chroman-2,1'-cycloalkanes], which in reactions with different terminal alkynes provided cycloaddition reactions 1,3-dipolar regioselective (Click Chemistry) leading to formation of the above-mentioned 1H-1,2,3-triazoles in yields of 47-97%. The novel series of azido spirocycloalkanes precursors were previously obtained in yields of 60-80%, starting from nucleophilic substitution reaction involving a series of 4-mesyl spirochromanes and sodium azide. It is necessary to optimize the reaction conditions due to the occurrence of competition between nucleophilic substitution reactions, which led to the desired azides and elimination, which led to the respective alkenes. The precursor series of 4-mesyl spirochromanes was obtained in two reaction steps comprising a reduction of the respective spiro-chromanones with NaBH4, followed by a mesylation reaction of the secondary alcohols initially originated with mesyl chloride (67-85%). In order to obtain fluorine-derived compounds, fluorination reactions were performed from examples of 1-(spiro [chroman-2,1'-cycloalkan]-4-yl)-1H-1,2,3-triazol-4-yl)methanol which led to the formation of a new series of 4-(fluoroethyl)-1-(spiro[chroman-2,1'-cycloalkan]-4-yl)-1H-1,2,3-triazoles using DAST as a fluorinating agent in yields of 60-73%. The structural study of the novel molecules isolated during this dissertation was performed using 1H, 13C, 19F NMR, 2D 1H-13C HSQC and 1H-13C HMBC NMR, mass spectrometry and by single crystal X-ray diffraction. The present study evaluate the antimicrobial activity of 4-azido-spiro[chroman-2,1'-cycloalkanes] and 4- (alkyl/aryl)-1-(spiro[chroman-2,1'-cycloalkan]-4-yl)-1H-1,2,3-triazoles, which showed low activity at the highest concentrations evaluated against the strain of Micobacterium tubeculusis [H37Rv (ATCC 27294)], with MICs > 20-80 μg/mL versus Isoniazid (MIC 0.31 μg/mL) for both series.