Síntese de 4-aril-3-bromo-5-arilidenofuran-2(5H)-onas análogas aos rubrolídeos
Autor(a) principal: | |
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Data de Publicação: | 2009 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | LOCUS Repositório Institucional da UFV |
Texto Completo: | http://locus.ufv.br/handle/123456789/2144 |
Resumo: | The γ-alkylidenebutenolides comprise a class of natural products presenting a variety of biological activities. Within this class of substances, there are the rubrolides, lactones isolated from marine ascidians, which are recognized as a source of natural bioactive compounds. Rubrolides are known for its antibiotic, cytotoxic and anti-inflammatory activities. In order to contribute for the knowledge concerning the biological activities of this class of compounds, the present investigation was aimed to synthesize novel arylidenefuranones analogues to rubrolides, and evaluate their phytototoxic and cytotoxic activities. The synthetic route for the preparation of these arylidenefuranones had the mucobromic acid as the starting material which was reduced to 3,4- ibromofuran-2(5H)-one in the presence of sodium borohydrate and methanol in acidic medium. After recrystallization, this brominated furanone was obtained as a white crystalline solid with 80% yield. Afterwards, this lactone was submitted to Suzuki coupling reactions with arylboronic acids. The catalytic system was composed by bis(acetonitrile)dichloropalladium(II), triphenylarsine and silver(II) oxide. Subsequent purification of the crude reaction mixture by column chromatography afforded the lactones 3-bromo-4-(4-fluoro-2- metoxyphenyl)furan-2(5H)-one and 3-bromo-4-(2-fluoro-2-metoxyphenyl)furan-(5H)-one in 76% and 77% yield, respectively. Reaction of these furanones with various substituted aromatic aldehydes in the presence of tert- utyldimethylsilyltrifluoromethanesulfonate and diisopropylethylamine gave the corresponding aldolic adducts which were not isolated. The adducts were subsequently treated with DBU under refluxing conditions. Thus, seven novel rubrolides analogues were synthesized namely 5(Z)-3-bromo-4-(4-fluoro-2- etoxyphenyl)-5-(3,4-methylenedioxibenzylidene) furan-2(5H)-one (79%), 5(Z)-bromo-4-(4-fluoro-2-metoxyphenyl)-5-(4-nitrobenzylidene)furan-2(5H)-one(16%), 5(Z)-3-bromo-4-(4-fluoro-2-metoxyphenyl)-5-(4-trifluoromethylbenzylidene)furan-2(5H)-one (30%), 5(Z)-3-bromo-4-(2-metoxyphenyl)-5-(3,4-methylenedioxibenzylidene)furan-2(5H)-one (54%), 5(Z)-3-bromo-4-(2-metoxyphenyl)-5-(4-nitrobenzylidene)furan-2(5H)-one (41%), 5(Z)-3-bromo-4-(2-metoxyphenyl)-5-(4-trifluoromethylbenzylidene)furan-2(5H)-one (42%) and 5(Z)-3-bromo-4-(2-metoxyphenyl)-5-benzylidenefuran-2(5H)-one (32%). The stereochemistry of the exocyclic double bond was confirmed by X-ray crystallography. Computational calculations were carried out and assisted in the rationalization of the stereochemical outcome of the alkylidenation reactions. |
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Barcelos, Rosimeire Courahttp://lattes.cnpq.br/1813653166290254Barbosa, Luiz Claudio de Almeidahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4781106J2Demuner, Antônio Jacintohttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4783217D3Maltha, Célia Regina álvareshttp://lattes.cnpq.br/7346715444030145Teixeira, Róbson Ricardohttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4723796H8Conceição, Gelson José Andrade dahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4723800Z8Fernandes, Sergio Antôniohttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4760152Y52015-03-26T13:00:32Z2013-05-312015-03-26T13:00:32Z2009-02-06BARCELOS, Rosimeire Coura. Synthesis of 4-aryl-3-bromo-5-arylidenefuran-2(5H)-ones rubrolides analogues. 2009. 102 f. Dissertação (Mestrado em Agroquímica analítica; Agroquímica inorgânica e Físico-química; Agroquímica orgânica) - Universidade Federal de Viçosa, Viçosa, 2009.http://locus.ufv.br/handle/123456789/2144The γ-alkylidenebutenolides comprise a class of natural products presenting a variety of biological activities. Within this class of substances, there are the rubrolides, lactones isolated from marine ascidians, which are recognized as a source of natural bioactive compounds. Rubrolides are known for its antibiotic, cytotoxic and anti-inflammatory activities. In order to contribute for the knowledge concerning the biological activities of this class of compounds, the present investigation was aimed to synthesize novel arylidenefuranones analogues to rubrolides, and evaluate their phytototoxic and cytotoxic activities. The synthetic route for the preparation of these arylidenefuranones had the mucobromic acid as the starting material which was reduced to 3,4- ibromofuran-2(5H)-one in the presence of sodium borohydrate and methanol in acidic medium. After recrystallization, this brominated furanone was obtained as a white crystalline solid with 80% yield. Afterwards, this lactone was submitted to Suzuki coupling reactions with arylboronic acids. The catalytic system was composed by bis(acetonitrile)dichloropalladium(II), triphenylarsine and silver(II) oxide. Subsequent purification of the crude reaction mixture by column chromatography afforded the lactones 3-bromo-4-(4-fluoro-2- metoxyphenyl)furan-2(5H)-one and 3-bromo-4-(2-fluoro-2-metoxyphenyl)furan-(5H)-one in 76% and 77% yield, respectively. Reaction of these furanones with various substituted aromatic aldehydes in the presence of tert- utyldimethylsilyltrifluoromethanesulfonate and diisopropylethylamine gave the corresponding aldolic adducts which were not isolated. The adducts were subsequently treated with DBU under refluxing conditions. Thus, seven novel rubrolides analogues were synthesized namely 5(Z)-3-bromo-4-(4-fluoro-2- etoxyphenyl)-5-(3,4-methylenedioxibenzylidene) furan-2(5H)-one (79%), 5(Z)-bromo-4-(4-fluoro-2-metoxyphenyl)-5-(4-nitrobenzylidene)furan-2(5H)-one(16%), 5(Z)-3-bromo-4-(4-fluoro-2-metoxyphenyl)-5-(4-trifluoromethylbenzylidene)furan-2(5H)-one (30%), 5(Z)-3-bromo-4-(2-metoxyphenyl)-5-(3,4-methylenedioxibenzylidene)furan-2(5H)-one (54%), 5(Z)-3-bromo-4-(2-metoxyphenyl)-5-(4-nitrobenzylidene)furan-2(5H)-one (41%), 5(Z)-3-bromo-4-(2-metoxyphenyl)-5-(4-trifluoromethylbenzylidene)furan-2(5H)-one (42%) and 5(Z)-3-bromo-4-(2-metoxyphenyl)-5-benzylidenefuran-2(5H)-one (32%). The stereochemistry of the exocyclic double bond was confirmed by X-ray crystallography. Computational calculations were carried out and assisted in the rationalization of the stereochemical outcome of the alkylidenation reactions.Os γ-alquilidenobutenolídeos correspondem a uma família de produtos naturais que possui um grande número de representantes com diversas atividades biológicas. Dentre eles, encontram-se os rubrolídeos, lactonas isoladas a partir de algumas ascídias marinhas, que por sua vez também são reconhecidas como uma fonte de compostos naturais bioativos. Os rubrolídeos apresentam atividades antibiótica, citotóxica e antiinflamatória. Visando contribuir com o estudo dessa classe de compostos, esse trabalho teve como objetivos sintetizar novas arilidenofuranonas análogas aos rubrolídeos e submetê-las a ensaios de atividade fitotóxica e citotóxica. A rota sintética empregada para o preparo das arilidenofuranonas teve como material de partida o ácido mucobrômico, que foi reduzido à lactona 3,4-dibromofuran-2(5H)-ona utilizando-se boroidreto de sódio e metanol em meio ácido. Após recristalização, a furanona dibromada foi obtida como um sólido branco cristalino, com rendimento de 80%. Posteriormente, essa lactona foi submetida às reações de acoplamento de Suzuki com ácidos arilborônicos. O sistema catalítico foi constituído por bis(acetonitrila)dicloropaládio(II), trifenilarsina e óxido de prata. Subseqüente purificação por cromatografia em coluna resultou na formação das lactonas 3-bromo-4-(4-fluoro-2-metoxifenil)furan-(5H)-ona e 3-bromo-4-(2-metoxifenil)furan-2(5H)-ona em 76% e 77% de rendimento, respectivamente. Essas furanonas foram submetidas às reações de alquilidenação com diferentes aldeídos aromáticos substituídos na presença de tert-butildimetilsililtrifluorometanossulfonato e diisopropiletilamina. Os adutos aldólicos obtidos foram posteriomente tratados com 1,8-diazabiciclo[5.4.0]undec-7-eno. Dessa forma, foram obtidos sete novos análogos aos rubrolídeos, denominados 5(Z)-3-bromo-4-(4-fluoro-2-metoxifenil)-5-(3,4-metilenodioxibenzilideno)furan-2(5H)-ona (79%), 5(Z)-3bromo-4-(4-fluoro-2-metoxifenil)-5-(4-nitrobenzilideno)furan-2(5H)-ona (16%), 5(Z)-3-bromo-4-(4-fluoro-2-metoxifenil)-5-(4-trifluorometilbenzilideno)furan-2(5H)-ona (30%), 5(Z)-3-bromo-4-(2-metoxifenil)-5-(3,4-metilenodioxibenzilideno)furan-2(5H)-ona (54%), 5(Z)-3-bromo-4-(2-metoxifenil)-5-(4-nitrobenzilideno)furan-2(5H)-ona (41%), 5(Z)-3-bromo-4-(2-metoxifenil)-5-(4-trifluorometilbenzilideno)furan-2(5H)-ona (42%) e 5(Z)-3-bromo-4-(2-metoxifenil)-5-benzilidenofuran-2(5H)-ona (32%). A confirmação da estereoquímica da ligação dupla exocíclica foi realizada por meio do estudo de difração de raios X. Cálculos computacionais foram realizados e auxiliaram na racionalização do resultado estereoquímico das reações de alquilidenação.Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade Federal de ViçosaMestrado em AgroquímicaUFVBRAgroquímica analítica; Agroquímica inorgânica e Físico-química; Agroquímica orgânicaγ-alquilidenobutenolídeosRubrolídeosAcoplamento de Suzukiγ-alkylidenebutenolidesRubrolidesSuzuki couplingCNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICASíntese de 4-aril-3-bromo-5-arilidenofuran-2(5H)-onas análogas aos rubrolídeosSynthesis of 4-aryl-3-bromo-5-arylidenefuran-2(5H)-ones rubrolides analoguesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:LOCUS Repositório Institucional da UFVinstname:Universidade Federal de Viçosa (UFV)instacron:UFVORIGINALtexto completo.pdfapplication/pdf1485312https://locus.ufv.br//bitstream/123456789/2144/1/texto%20completo.pdfe18f300e5b2fb15f4ddda7bc082dd5c4MD51TEXTtexto completo.pdf.txttexto completo.pdf.txtExtracted texttext/plain131569https://locus.ufv.br//bitstream/123456789/2144/2/texto%20completo.pdf.txte7148494e8e6cb7942817ed97d487d03MD52THUMBNAILtexto completo.pdf.jpgtexto completo.pdf.jpgIM Thumbnailimage/jpeg3632https://locus.ufv.br//bitstream/123456789/2144/3/texto%20completo.pdf.jpg76787c3e6672f2810baa12a86ccae186MD53123456789/21442017-10-06 15:33:29.542oai:locus.ufv.br:123456789/2144Repositório InstitucionalPUBhttps://www.locus.ufv.br/oai/requestfabiojreis@ufv.bropendoar:21452017-10-06T18:33:29LOCUS Repositório Institucional da UFV - Universidade Federal de Viçosa (UFV)false |
dc.title.por.fl_str_mv |
Síntese de 4-aril-3-bromo-5-arilidenofuran-2(5H)-onas análogas aos rubrolídeos |
dc.title.alternative.eng.fl_str_mv |
Synthesis of 4-aryl-3-bromo-5-arylidenefuran-2(5H)-ones rubrolides analogues |
title |
Síntese de 4-aril-3-bromo-5-arilidenofuran-2(5H)-onas análogas aos rubrolídeos |
spellingShingle |
Síntese de 4-aril-3-bromo-5-arilidenofuran-2(5H)-onas análogas aos rubrolídeos Barcelos, Rosimeire Coura γ-alquilidenobutenolídeos Rubrolídeos Acoplamento de Suzuki γ-alkylidenebutenolides Rubrolides Suzuki coupling CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA |
title_short |
Síntese de 4-aril-3-bromo-5-arilidenofuran-2(5H)-onas análogas aos rubrolídeos |
title_full |
Síntese de 4-aril-3-bromo-5-arilidenofuran-2(5H)-onas análogas aos rubrolídeos |
title_fullStr |
Síntese de 4-aril-3-bromo-5-arilidenofuran-2(5H)-onas análogas aos rubrolídeos |
title_full_unstemmed |
Síntese de 4-aril-3-bromo-5-arilidenofuran-2(5H)-onas análogas aos rubrolídeos |
title_sort |
Síntese de 4-aril-3-bromo-5-arilidenofuran-2(5H)-onas análogas aos rubrolídeos |
author |
Barcelos, Rosimeire Coura |
author_facet |
Barcelos, Rosimeire Coura |
author_role |
author |
dc.contributor.authorLattes.por.fl_str_mv |
http://lattes.cnpq.br/1813653166290254 |
dc.contributor.author.fl_str_mv |
Barcelos, Rosimeire Coura |
dc.contributor.advisor-co1.fl_str_mv |
Barbosa, Luiz Claudio de Almeida |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4781106J2 |
dc.contributor.advisor-co2.fl_str_mv |
Demuner, Antônio Jacinto |
dc.contributor.advisor-co2Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4783217D3 |
dc.contributor.advisor1.fl_str_mv |
Maltha, Célia Regina álvares |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/7346715444030145 |
dc.contributor.referee1.fl_str_mv |
Teixeira, Róbson Ricardo |
dc.contributor.referee1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4723796H8 |
dc.contributor.referee2.fl_str_mv |
Conceição, Gelson José Andrade da |
dc.contributor.referee2Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4723800Z8 |
dc.contributor.referee3.fl_str_mv |
Fernandes, Sergio Antônio |
dc.contributor.referee3Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4760152Y5 |
contributor_str_mv |
Barbosa, Luiz Claudio de Almeida Demuner, Antônio Jacinto Maltha, Célia Regina álvares Teixeira, Róbson Ricardo Conceição, Gelson José Andrade da Fernandes, Sergio Antônio |
dc.subject.por.fl_str_mv |
γ-alquilidenobutenolídeos Rubrolídeos Acoplamento de Suzuki |
topic |
γ-alquilidenobutenolídeos Rubrolídeos Acoplamento de Suzuki γ-alkylidenebutenolides Rubrolides Suzuki coupling CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA |
dc.subject.eng.fl_str_mv |
γ-alkylidenebutenolides Rubrolides Suzuki coupling |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA |
description |
The γ-alkylidenebutenolides comprise a class of natural products presenting a variety of biological activities. Within this class of substances, there are the rubrolides, lactones isolated from marine ascidians, which are recognized as a source of natural bioactive compounds. Rubrolides are known for its antibiotic, cytotoxic and anti-inflammatory activities. In order to contribute for the knowledge concerning the biological activities of this class of compounds, the present investigation was aimed to synthesize novel arylidenefuranones analogues to rubrolides, and evaluate their phytototoxic and cytotoxic activities. The synthetic route for the preparation of these arylidenefuranones had the mucobromic acid as the starting material which was reduced to 3,4- ibromofuran-2(5H)-one in the presence of sodium borohydrate and methanol in acidic medium. After recrystallization, this brominated furanone was obtained as a white crystalline solid with 80% yield. Afterwards, this lactone was submitted to Suzuki coupling reactions with arylboronic acids. The catalytic system was composed by bis(acetonitrile)dichloropalladium(II), triphenylarsine and silver(II) oxide. Subsequent purification of the crude reaction mixture by column chromatography afforded the lactones 3-bromo-4-(4-fluoro-2- metoxyphenyl)furan-2(5H)-one and 3-bromo-4-(2-fluoro-2-metoxyphenyl)furan-(5H)-one in 76% and 77% yield, respectively. Reaction of these furanones with various substituted aromatic aldehydes in the presence of tert- utyldimethylsilyltrifluoromethanesulfonate and diisopropylethylamine gave the corresponding aldolic adducts which were not isolated. The adducts were subsequently treated with DBU under refluxing conditions. Thus, seven novel rubrolides analogues were synthesized namely 5(Z)-3-bromo-4-(4-fluoro-2- etoxyphenyl)-5-(3,4-methylenedioxibenzylidene) furan-2(5H)-one (79%), 5(Z)-bromo-4-(4-fluoro-2-metoxyphenyl)-5-(4-nitrobenzylidene)furan-2(5H)-one(16%), 5(Z)-3-bromo-4-(4-fluoro-2-metoxyphenyl)-5-(4-trifluoromethylbenzylidene)furan-2(5H)-one (30%), 5(Z)-3-bromo-4-(2-metoxyphenyl)-5-(3,4-methylenedioxibenzylidene)furan-2(5H)-one (54%), 5(Z)-3-bromo-4-(2-metoxyphenyl)-5-(4-nitrobenzylidene)furan-2(5H)-one (41%), 5(Z)-3-bromo-4-(2-metoxyphenyl)-5-(4-trifluoromethylbenzylidene)furan-2(5H)-one (42%) and 5(Z)-3-bromo-4-(2-metoxyphenyl)-5-benzylidenefuran-2(5H)-one (32%). The stereochemistry of the exocyclic double bond was confirmed by X-ray crystallography. Computational calculations were carried out and assisted in the rationalization of the stereochemical outcome of the alkylidenation reactions. |
publishDate |
2009 |
dc.date.issued.fl_str_mv |
2009-02-06 |
dc.date.available.fl_str_mv |
2013-05-31 2015-03-26T13:00:32Z |
dc.date.accessioned.fl_str_mv |
2015-03-26T13:00:32Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
BARCELOS, Rosimeire Coura. Synthesis of 4-aryl-3-bromo-5-arylidenefuran-2(5H)-ones rubrolides analogues. 2009. 102 f. Dissertação (Mestrado em Agroquímica analítica; Agroquímica inorgânica e Físico-química; Agroquímica orgânica) - Universidade Federal de Viçosa, Viçosa, 2009. |
dc.identifier.uri.fl_str_mv |
http://locus.ufv.br/handle/123456789/2144 |
identifier_str_mv |
BARCELOS, Rosimeire Coura. Synthesis of 4-aryl-3-bromo-5-arylidenefuran-2(5H)-ones rubrolides analogues. 2009. 102 f. Dissertação (Mestrado em Agroquímica analítica; Agroquímica inorgânica e Físico-química; Agroquímica orgânica) - Universidade Federal de Viçosa, Viçosa, 2009. |
url |
http://locus.ufv.br/handle/123456789/2144 |
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Universidade Federal de Viçosa |
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Mestrado em Agroquímica |
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UFV |
dc.publisher.country.fl_str_mv |
BR |
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Agroquímica analítica; Agroquímica inorgânica e Físico-química; Agroquímica orgânica |
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Universidade Federal de Viçosa |
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