Síntese e avaliação biológica de derivados de carboidratos e nucleosídeos
Autor(a) principal: | |
---|---|
Data de Publicação: | 2005 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFSCAR |
Texto Completo: | https://repositorio.ufscar.br/handle/ufscar/6123 |
Resumo: | In the last few years, the carbohydrate chemistry has been growing surprisingly, especially because of the diversity of biological applications of this class of compounds. This present work aimed to synthesize and evaluate a series of carbohydrates and nucleosides, in order to contribute for the study of their structure-activity relationship. A series of sugar esters from glucose, mannose, galactose and fructose with stearic and palmitic acids was synthesized with the respective acid chlorides in aqueous basic medium in the presence of DMAP with 30 - 40% yield. Mannofuranose, galactofuranose and fructose derivatives were prepared for the synthesis of β-L-mannofuranosyl(6→2)-fructosyl(2→6)-β-L-galactofuranose, however the coupling reactions were not successful and the synthesis was interrupted. Purinic nucleosides and analogs were synthesized under Mitsunobu conditions, using the appropriated purine and the respective alcohols, as for example, menthol, dodecanol, benzyl alcohol, oleic alcohol and glucose and mannose derivatives, with 37 - 86% yield. Synthesis of the carbocyclic nucleoside, 4-(6-amino-9H-purin-9-yl)-2-[(trityloxy)methyl] cyclopentanol, was carried out until intermediate 6-chloro-9-(6-oxabicyclo[3.1.0]hex-3-yl)-9H-purine. After several attempts in order to open the epoxide with cyanides, the synthesis was discontinued. All synthetic compounds and a series of 22 commercial carbohydrates were biologically evaluated against T. cruzi gGAPDH and L. tarentolae APRT enzymes, several microorganisms and the leaf-cutting ant Atta sexdens. The evaluated carbohydrates were inactive or showed moderate inhibition against gGAPDH enzyme at 200 μM. D-isoascorbic acid showed an inhibition of 67% (100 μM) against the APRT enzyme. The evaluated nucleosides and analogs were inactive or showed low inhibition against the gGAPDH enzyme at 200 μM. 6-Chloro-9-dodecyl-9H-purine showed an inhibition of 63% (100 μM) against the APRT enzyme. The sugar esters of fatty acids presented no toxic effect to the ants. In the case of 6-O-estearoyl-D-glucopiranose, 6-O-palmitoyl-D-mannopiranose e 6-O-palmitoyl-D-galactopiranose, it was observed a small growth of the survival of the worker ants. They showed no inhibition or low inhibition (20%) of the symbiotic fungus Leucoagaricus gongylophorus. 6-Chloro-9-dodecyl-9H-purine showed a moderate inhibition against Escherichia coli. The compounds analyzed will be employed as models for the design and synthesis of more active compounds. |
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Nogueira, Christiane MapheuCorrêa, Arlene Gonçalveshttp://genos.cnpq.br:12010/dwlattes/owa/prc_imp_cv_int?f_cod=K4781708P5http://lattes.cnpq.br/2522406207908377fdc38246-f146-41cf-90b7-b81d199fde632016-06-02T20:34:12Z2009-10-012016-06-02T20:34:12Z2005-02-25NOGUEIRA, Christiane Mapheu. SYNTHESIS AND BIOLOGICAL EVALUATION OF CARBOHYDRATE AND NUCLEOSIDE DERIVATIVES. 2005. 280 f. Tese (Doutorado em Ciências Exatas e da Terra) - Universidade Federal de São Carlos, São Carlos, 2005.https://repositorio.ufscar.br/handle/ufscar/6123In the last few years, the carbohydrate chemistry has been growing surprisingly, especially because of the diversity of biological applications of this class of compounds. This present work aimed to synthesize and evaluate a series of carbohydrates and nucleosides, in order to contribute for the study of their structure-activity relationship. A series of sugar esters from glucose, mannose, galactose and fructose with stearic and palmitic acids was synthesized with the respective acid chlorides in aqueous basic medium in the presence of DMAP with 30 - 40% yield. Mannofuranose, galactofuranose and fructose derivatives were prepared for the synthesis of β-L-mannofuranosyl(6→2)-fructosyl(2→6)-β-L-galactofuranose, however the coupling reactions were not successful and the synthesis was interrupted. Purinic nucleosides and analogs were synthesized under Mitsunobu conditions, using the appropriated purine and the respective alcohols, as for example, menthol, dodecanol, benzyl alcohol, oleic alcohol and glucose and mannose derivatives, with 37 - 86% yield. Synthesis of the carbocyclic nucleoside, 4-(6-amino-9H-purin-9-yl)-2-[(trityloxy)methyl] cyclopentanol, was carried out until intermediate 6-chloro-9-(6-oxabicyclo[3.1.0]hex-3-yl)-9H-purine. After several attempts in order to open the epoxide with cyanides, the synthesis was discontinued. All synthetic compounds and a series of 22 commercial carbohydrates were biologically evaluated against T. cruzi gGAPDH and L. tarentolae APRT enzymes, several microorganisms and the leaf-cutting ant Atta sexdens. The evaluated carbohydrates were inactive or showed moderate inhibition against gGAPDH enzyme at 200 μM. D-isoascorbic acid showed an inhibition of 67% (100 μM) against the APRT enzyme. The evaluated nucleosides and analogs were inactive or showed low inhibition against the gGAPDH enzyme at 200 μM. 6-Chloro-9-dodecyl-9H-purine showed an inhibition of 63% (100 μM) against the APRT enzyme. The sugar esters of fatty acids presented no toxic effect to the ants. In the case of 6-O-estearoyl-D-glucopiranose, 6-O-palmitoyl-D-mannopiranose e 6-O-palmitoyl-D-galactopiranose, it was observed a small growth of the survival of the worker ants. They showed no inhibition or low inhibition (20%) of the symbiotic fungus Leucoagaricus gongylophorus. 6-Chloro-9-dodecyl-9H-purine showed a moderate inhibition against Escherichia coli. The compounds analyzed will be employed as models for the design and synthesis of more active compounds.Nos últimos anos, o estudo da química dos carboidratos tem crescido de forma surpreendente, principalmente com relação à diversidade de aplicações biológicas desses compostos. O presente trabalho teve como objetivo sintetizar e avaliar uma série de carboidratos e nucleosídeos, para contribuir com o estudo da relação estrutura-atividade destas classes de compostos. Uma série de ésteres de açúcares derivados da glicose, manose, galactose e frutose com os ácidos esteárico e palmítico foi sintetizada a partir do respectivo cloreto de ácido em meio básico aquoso na presença de DMAP com rendimentos de 30 - 40%. Foram preparados derivados da manofuranose, galactofuranose e frutose com o objetivo de sintetizar a β-L-manofuranosil(6→2)-frutosil(2→6)-β-Lgalactofuranose, mas as reações de acoplamento desses monossacarídeos não tiveram sucesso e a sua síntese foi interrompida. Nucleosídeos purínicos e análogos foram sintetizados utilizando as condições de Mitsunobu para a purina desejada e os respectivos álcoois, como o mentol, dodecanol, álcool benzílico, álcool oléico e derivados da glicose e manose, com rendimentos de 37 - 86%. A síntese do nucleosídeo carbocíclico alvo, 4-(6-amino-9H-purin-9-il)-2-[(tritiloxi)metil]ciclopentanol, foi realizada até o intermediário avançado 6-cloro-9-(6-oxabiciclo[3.1.0]hex-3-il)-9H-purina. Várias metodologias foram empregadas na tentativa de abertura deste epóxido com cianetos, mas nenhuma foi eficiente. Todos os compostos sintetizados e uma série de 22 carboidratos comercias foram avaliados biologicamente com relação à atividade inibitória das enzimas gGAPDH de T. cruzi e APRT de L. tarentolae, atividade antimicrobiana e avaliação frente à formiga Atta sexdens. Os carboidratos avaliados foram inativos ou apenas inibiram moderadamente a enzima gGAPDH à 200 μM. Com relação à inibição da enzima APRT o ácido D-isoascórbico teve uma inibição de 67% (100 μM). Os nucleosídeos e análogos avaliados com relação à enzima gGAPDH à 200 μM foram inativos ou tiveram uma inibição baixa. Com relação à inibição da enzima APRT, a 6-cloro-9-dodecil-9H-purina apresentou uma inibição de 63% (100 μM). Os ésteres de açúcares derivados de ácidos graxos não apresentaram efeitos tóxicos às formigas. No caso dos ésteres, 6-O-estearoil-D-glicopiranose, 6-O-palmitoil-D-manopiranose e 6-O-palmitoil-D-galactopiranose, ocorreu um pequeno aumento da sobrevivência das operárias em relação aos respectivos controles. Com relação ao crescimento do fungo simbionte Leucoagaricus gongylophorus a maioria dos compostos não apresentou atividade e alguns inibiram no máximo a 20%. Dentre os compostos avaliados com relação ao potencial antimicrobiano a 6-cloro-9-dodecil-9Hpurina, mesmo não sendo tão expressivo como o controle, a Escherichia coli se mostrou sensível ao composto em questão. Os compostos analisados serão utilizados no planejamento e síntese de compostos mais ativos.Universidade Federal de Minas Geraisapplication/pdfporUniversidade Federal de São CarlosPrograma de Pós-Graduação em Química - PPGQUFSCarBRSíntese orgânicaCarboidratosNucleosídeosCIENCIAS EXATAS E DA TERRA::QUIMICASíntese e avaliação biológica de derivados de carboidratos e nucleosídeosSYNTHESIS AND BIOLOGICAL EVALUATION OF CARBOHYDRATE AND NUCLEOSIDE DERIVATIVESinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis-1-1d0f2b9e6-a39b-4adb-8930-18725207ea16info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINAL2099.pdfapplication/pdf2520910https://repositorio.ufscar.br/bitstream/ufscar/6123/1/2099.pdf6a3f1c1c7ca45d7fb8121098569f4c5bMD51THUMBNAIL2099.pdf.jpg2099.pdf.jpgIM Thumbnailimage/jpeg9483https://repositorio.ufscar.br/bitstream/ufscar/6123/2/2099.pdf.jpg1a9c4e63ba54423299b62f2ce4aac3d9MD52ufscar/61232023-09-18 18:31:10.952oai:repositorio.ufscar.br:ufscar/6123Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222023-09-18T18:31:10Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false |
dc.title.por.fl_str_mv |
Síntese e avaliação biológica de derivados de carboidratos e nucleosídeos |
dc.title.alternative.eng.fl_str_mv |
SYNTHESIS AND BIOLOGICAL EVALUATION OF CARBOHYDRATE AND NUCLEOSIDE DERIVATIVES |
title |
Síntese e avaliação biológica de derivados de carboidratos e nucleosídeos |
spellingShingle |
Síntese e avaliação biológica de derivados de carboidratos e nucleosídeos Nogueira, Christiane Mapheu Síntese orgânica Carboidratos Nucleosídeos CIENCIAS EXATAS E DA TERRA::QUIMICA |
title_short |
Síntese e avaliação biológica de derivados de carboidratos e nucleosídeos |
title_full |
Síntese e avaliação biológica de derivados de carboidratos e nucleosídeos |
title_fullStr |
Síntese e avaliação biológica de derivados de carboidratos e nucleosídeos |
title_full_unstemmed |
Síntese e avaliação biológica de derivados de carboidratos e nucleosídeos |
title_sort |
Síntese e avaliação biológica de derivados de carboidratos e nucleosídeos |
author |
Nogueira, Christiane Mapheu |
author_facet |
Nogueira, Christiane Mapheu |
author_role |
author |
dc.contributor.authorlattes.por.fl_str_mv |
http://lattes.cnpq.br/2522406207908377 |
dc.contributor.author.fl_str_mv |
Nogueira, Christiane Mapheu |
dc.contributor.advisor1.fl_str_mv |
Corrêa, Arlene Gonçalves |
dc.contributor.advisor1Lattes.fl_str_mv |
http://genos.cnpq.br:12010/dwlattes/owa/prc_imp_cv_int?f_cod=K4781708P5 |
dc.contributor.authorID.fl_str_mv |
fdc38246-f146-41cf-90b7-b81d199fde63 |
contributor_str_mv |
Corrêa, Arlene Gonçalves |
dc.subject.por.fl_str_mv |
Síntese orgânica Carboidratos Nucleosídeos |
topic |
Síntese orgânica Carboidratos Nucleosídeos CIENCIAS EXATAS E DA TERRA::QUIMICA |
dc.subject.cnpq.fl_str_mv |
CIENCIAS EXATAS E DA TERRA::QUIMICA |
description |
In the last few years, the carbohydrate chemistry has been growing surprisingly, especially because of the diversity of biological applications of this class of compounds. This present work aimed to synthesize and evaluate a series of carbohydrates and nucleosides, in order to contribute for the study of their structure-activity relationship. A series of sugar esters from glucose, mannose, galactose and fructose with stearic and palmitic acids was synthesized with the respective acid chlorides in aqueous basic medium in the presence of DMAP with 30 - 40% yield. Mannofuranose, galactofuranose and fructose derivatives were prepared for the synthesis of β-L-mannofuranosyl(6→2)-fructosyl(2→6)-β-L-galactofuranose, however the coupling reactions were not successful and the synthesis was interrupted. Purinic nucleosides and analogs were synthesized under Mitsunobu conditions, using the appropriated purine and the respective alcohols, as for example, menthol, dodecanol, benzyl alcohol, oleic alcohol and glucose and mannose derivatives, with 37 - 86% yield. Synthesis of the carbocyclic nucleoside, 4-(6-amino-9H-purin-9-yl)-2-[(trityloxy)methyl] cyclopentanol, was carried out until intermediate 6-chloro-9-(6-oxabicyclo[3.1.0]hex-3-yl)-9H-purine. After several attempts in order to open the epoxide with cyanides, the synthesis was discontinued. All synthetic compounds and a series of 22 commercial carbohydrates were biologically evaluated against T. cruzi gGAPDH and L. tarentolae APRT enzymes, several microorganisms and the leaf-cutting ant Atta sexdens. The evaluated carbohydrates were inactive or showed moderate inhibition against gGAPDH enzyme at 200 μM. D-isoascorbic acid showed an inhibition of 67% (100 μM) against the APRT enzyme. The evaluated nucleosides and analogs were inactive or showed low inhibition against the gGAPDH enzyme at 200 μM. 6-Chloro-9-dodecyl-9H-purine showed an inhibition of 63% (100 μM) against the APRT enzyme. The sugar esters of fatty acids presented no toxic effect to the ants. In the case of 6-O-estearoyl-D-glucopiranose, 6-O-palmitoyl-D-mannopiranose e 6-O-palmitoyl-D-galactopiranose, it was observed a small growth of the survival of the worker ants. They showed no inhibition or low inhibition (20%) of the symbiotic fungus Leucoagaricus gongylophorus. 6-Chloro-9-dodecyl-9H-purine showed a moderate inhibition against Escherichia coli. The compounds analyzed will be employed as models for the design and synthesis of more active compounds. |
publishDate |
2005 |
dc.date.issued.fl_str_mv |
2005-02-25 |
dc.date.available.fl_str_mv |
2009-10-01 2016-06-02T20:34:12Z |
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2016-06-02T20:34:12Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
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dc.identifier.citation.fl_str_mv |
NOGUEIRA, Christiane Mapheu. SYNTHESIS AND BIOLOGICAL EVALUATION OF CARBOHYDRATE AND NUCLEOSIDE DERIVATIVES. 2005. 280 f. Tese (Doutorado em Ciências Exatas e da Terra) - Universidade Federal de São Carlos, São Carlos, 2005. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufscar.br/handle/ufscar/6123 |
identifier_str_mv |
NOGUEIRA, Christiane Mapheu. SYNTHESIS AND BIOLOGICAL EVALUATION OF CARBOHYDRATE AND NUCLEOSIDE DERIVATIVES. 2005. 280 f. Tese (Doutorado em Ciências Exatas e da Terra) - Universidade Federal de São Carlos, São Carlos, 2005. |
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https://repositorio.ufscar.br/handle/ufscar/6123 |
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UFSCar |
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