Combinação de reações organocatalíticas e multicomponentes para a síntese de sistemas heterocíclicos e moleculas híbridas
Autor(a) principal: | |
---|---|
Data de Publicação: | 2019 |
Tipo de documento: | Tese |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFSCAR |
Texto Completo: | https://repositorio.ufscar.br/handle/ufscar/11032 |
Resumo: | Small enantiomerically pure or enriched organic molecules are key starting materials in organic synthesis. Chiral building blocks are in high demand in the overall synthesis of complex natural products and in the discovery and development of drugs as well as in the production of advanced pesticides, fragrances and materials. In this sense, organocatalytic methodologies have emerged as a third pillar of asymmetric catalysis and have a prominent position in the development of more sustainable methods. Similarly, multicomponent reactions (MCRs) present themselves as a powerful tool for the synthesis of bioactive heterocyclic compounds and analogues of natural products. Chiral aldehydes are key components in stereocontrolled MCRs, methods for the asymmetric functionalization of carbonyl compounds are relevant for the development of novel multicomponent stereoselective approaches. In recent years, our group and the Banfi group have been exploring the potential of organocatalysis to generate compounds enantiomerically enriched with the synthetic power of MCRs in the diversification of these chiral compounds. In this work we describe a highly stereoselective methodology for the synthesis of natural product hybrids from an organocatalytic tandem procedure, followed by a multicomponent reaction. Effectively, the procedure comprises an organocatalysed conjugate addition of active methylene compounds (1,3-dicarbonyls and α ester or cyanoketones) to α,β-unsaturated aldehydes to form asymmetric hemiacetals containing orthogonal functional groups. Next, an isocyanate based intramolecular multicomponent reaction is implemented. Through the use of this approach it was possible to synthesize hybrids of natural products, including up to four different molecular fragments, such as hydroquinoline, tetrahydropyridine, peptides, lipid and glycoside units |
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Echemendía Pérez, RadellPaixão, Márcio Weberhttp://lattes.cnpq.br/3773908504964104García Rivera, Danielhttp://lattes.cnpq.br/2938011588420423http://lattes.cnpq.br/7683916091296702a418db2b-556a-4809-9740-ea865e5ddb992019-02-26T18:25:48Z2019-02-26T18:25:48Z2019-02-08ECHEMENDÍA PÉREZ, Radell. Combinação de reações organocatalíticas e multicomponentes para a síntese de sistemas heterocíclicos e moleculas híbridas. 2019. Tese (Doutorado em Química) – Universidade Federal de São Carlos, São Carlos, 2019. Disponível em: https://repositorio.ufscar.br/handle/ufscar/11032.https://repositorio.ufscar.br/handle/ufscar/11032Small enantiomerically pure or enriched organic molecules are key starting materials in organic synthesis. Chiral building blocks are in high demand in the overall synthesis of complex natural products and in the discovery and development of drugs as well as in the production of advanced pesticides, fragrances and materials. In this sense, organocatalytic methodologies have emerged as a third pillar of asymmetric catalysis and have a prominent position in the development of more sustainable methods. Similarly, multicomponent reactions (MCRs) present themselves as a powerful tool for the synthesis of bioactive heterocyclic compounds and analogues of natural products. Chiral aldehydes are key components in stereocontrolled MCRs, methods for the asymmetric functionalization of carbonyl compounds are relevant for the development of novel multicomponent stereoselective approaches. In recent years, our group and the Banfi group have been exploring the potential of organocatalysis to generate compounds enantiomerically enriched with the synthetic power of MCRs in the diversification of these chiral compounds. In this work we describe a highly stereoselective methodology for the synthesis of natural product hybrids from an organocatalytic tandem procedure, followed by a multicomponent reaction. Effectively, the procedure comprises an organocatalysed conjugate addition of active methylene compounds (1,3-dicarbonyls and α ester or cyanoketones) to α,β-unsaturated aldehydes to form asymmetric hemiacetals containing orthogonal functional groups. Next, an isocyanate based intramolecular multicomponent reaction is implemented. Through the use of this approach it was possible to synthesize hybrids of natural products, including up to four different molecular fragments, such as hydroquinoline, tetrahydropyridine, peptides, lipid and glycoside unitsPequenas moléculas orgânicas enantiomericamente puras ou enriquecidas são materiais de partida chave em síntese orgânica. Os blocos de construção quirais estão em alta demanda na síntese total de produtos naturais complexos e na descoberta e desenvolvimento de drogas, bem como, na produção de pesticidas, fragrâncias e materiais avançados. Nesse sentido, metodologias organocatalíticas emergiram como um terceiro pilar da catálise assimétrica e, possuem posição de destaque no desenvolvimento de métodos mais sustentáveis. De maneira similar, reações multicomponentes (RMCs) apresentam-se como uma poderosa ferramenta para a síntese de compostos heterocíclicos bioativos e análogos de produtos naturais. Aldeídos quirais são componentes chave em RMCs estereocontroladas, os métodos para a funcionalização assimétrica de compostos carbonílicos são relevantes para o desenvolvimento de novas abordagens multicomponentes estereosseletivas. Nos últimos anos, nosso grupo e o grupo de Banfi vêm explorando o potencial da organocatálise para gerar compostos enantiomericamente enriquecidos com o poder sintético das RMCs na diversificação desses compostos quirais. Neste trabalho descrevemos metodologias altamente estereosseletivas para a síntese de hídridos de produtos naturais a partir de um procedimento organocatalítico - one-pot sequencial - seguido de uma reação multicomponente. Efetivamente, o procedimento compreende uma adição conjugada organocatalisada de compostos metileno ativos (1,3-dicarbonilas e α-cianocetonas) a aldeídos α,β- insaturados para a formação de hemiacetais assimétricos contendo grupos funcionais ortogonais. Após esse primeiro evento, de forma sequencial e one-pot é implementada uma reação multicomponente intramolecular baseada em isocianeto. Através do emprego desta abordagem foi possível sintetizar híbridos de produtos naturais, incluindo até quatro fragmentos moleculares diferentes, tais como, unidades hidroquinolinona, tetrahidropiridina, peptídeos, lipídeo e glicosídeo.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CNPq: 141770/2015-5engUniversidade Federal de São CarlosCâmpus São CarlosPrograma de Pós-Graduação em Química - PPGQUFSCarSintese orgánicaOrganic compounds - SynthesisCIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA::SINTESE ORGANICACombinação de reações organocatalíticas e multicomponentes para a síntese de sistemas heterocíclicos e moleculas híbridasMerging organocatalytic and multicomponent reactions for the synthesis of heterocyclic scaffolds and hybrid moleculesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisOnline600c9d783c2-174c-4a51-9643-0e44f6fc9ac9info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINALRadell Echemendia Perez PhD Thesis.pdfRadell Echemendia Perez PhD Thesis.pdfapplication/pdf10385729https://repositorio.ufscar.br/bitstream/ufscar/11032/1/Radell%20Echemendia%20Perez%20PhD%20Thesis.pdffabd805b95ca23f221c8cd3713aee981MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81957https://repositorio.ufscar.br/bitstream/ufscar/11032/3/license.txtae0398b6f8b235e40ad82cba6c50031dMD53TEXTRadell Echemendia Perez PhD Thesis.pdf.txtRadell Echemendia Perez PhD Thesis.pdf.txtExtracted texttext/plain213502https://repositorio.ufscar.br/bitstream/ufscar/11032/4/Radell%20Echemendia%20Perez%20PhD%20Thesis.pdf.txt57e22041bea4ab789dcc7fad332ac3b2MD54THUMBNAILRadell Echemendia Perez PhD Thesis.pdf.jpgRadell Echemendia Perez PhD Thesis.pdf.jpgIM Thumbnailimage/jpeg10113https://repositorio.ufscar.br/bitstream/ufscar/11032/5/Radell%20Echemendia%20Perez%20PhD%20Thesis.pdf.jpg1247dcfdd683a9bad2befc11008688c1MD55ufscar/110322023-09-18 18:31:20.617oai:repositorio.ufscar.br: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Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222023-09-18T18:31:20Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false |
dc.title.por.fl_str_mv |
Combinação de reações organocatalíticas e multicomponentes para a síntese de sistemas heterocíclicos e moleculas híbridas |
dc.title.alternative.eng.fl_str_mv |
Merging organocatalytic and multicomponent reactions for the synthesis of heterocyclic scaffolds and hybrid molecules |
title |
Combinação de reações organocatalíticas e multicomponentes para a síntese de sistemas heterocíclicos e moleculas híbridas |
spellingShingle |
Combinação de reações organocatalíticas e multicomponentes para a síntese de sistemas heterocíclicos e moleculas híbridas Echemendía Pérez, Radell Sintese orgánica Organic compounds - Synthesis CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA::SINTESE ORGANICA |
title_short |
Combinação de reações organocatalíticas e multicomponentes para a síntese de sistemas heterocíclicos e moleculas híbridas |
title_full |
Combinação de reações organocatalíticas e multicomponentes para a síntese de sistemas heterocíclicos e moleculas híbridas |
title_fullStr |
Combinação de reações organocatalíticas e multicomponentes para a síntese de sistemas heterocíclicos e moleculas híbridas |
title_full_unstemmed |
Combinação de reações organocatalíticas e multicomponentes para a síntese de sistemas heterocíclicos e moleculas híbridas |
title_sort |
Combinação de reações organocatalíticas e multicomponentes para a síntese de sistemas heterocíclicos e moleculas híbridas |
author |
Echemendía Pérez, Radell |
author_facet |
Echemendía Pérez, Radell |
author_role |
author |
dc.contributor.authorlattes.por.fl_str_mv |
http://lattes.cnpq.br/7683916091296702 |
dc.contributor.author.fl_str_mv |
Echemendía Pérez, Radell |
dc.contributor.advisor1.fl_str_mv |
Paixão, Márcio Weber |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/3773908504964104 |
dc.contributor.advisor-co1.fl_str_mv |
García Rivera, Daniel |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/2938011588420423 |
dc.contributor.authorID.fl_str_mv |
a418db2b-556a-4809-9740-ea865e5ddb99 |
contributor_str_mv |
Paixão, Márcio Weber García Rivera, Daniel |
dc.subject.por.fl_str_mv |
Sintese orgánica |
topic |
Sintese orgánica Organic compounds - Synthesis CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA::SINTESE ORGANICA |
dc.subject.eng.fl_str_mv |
Organic compounds - Synthesis |
dc.subject.cnpq.fl_str_mv |
CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA::SINTESE ORGANICA |
description |
Small enantiomerically pure or enriched organic molecules are key starting materials in organic synthesis. Chiral building blocks are in high demand in the overall synthesis of complex natural products and in the discovery and development of drugs as well as in the production of advanced pesticides, fragrances and materials. In this sense, organocatalytic methodologies have emerged as a third pillar of asymmetric catalysis and have a prominent position in the development of more sustainable methods. Similarly, multicomponent reactions (MCRs) present themselves as a powerful tool for the synthesis of bioactive heterocyclic compounds and analogues of natural products. Chiral aldehydes are key components in stereocontrolled MCRs, methods for the asymmetric functionalization of carbonyl compounds are relevant for the development of novel multicomponent stereoselective approaches. In recent years, our group and the Banfi group have been exploring the potential of organocatalysis to generate compounds enantiomerically enriched with the synthetic power of MCRs in the diversification of these chiral compounds. In this work we describe a highly stereoselective methodology for the synthesis of natural product hybrids from an organocatalytic tandem procedure, followed by a multicomponent reaction. Effectively, the procedure comprises an organocatalysed conjugate addition of active methylene compounds (1,3-dicarbonyls and α ester or cyanoketones) to α,β-unsaturated aldehydes to form asymmetric hemiacetals containing orthogonal functional groups. Next, an isocyanate based intramolecular multicomponent reaction is implemented. Through the use of this approach it was possible to synthesize hybrids of natural products, including up to four different molecular fragments, such as hydroquinoline, tetrahydropyridine, peptides, lipid and glycoside units |
publishDate |
2019 |
dc.date.accessioned.fl_str_mv |
2019-02-26T18:25:48Z |
dc.date.available.fl_str_mv |
2019-02-26T18:25:48Z |
dc.date.issued.fl_str_mv |
2019-02-08 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
ECHEMENDÍA PÉREZ, Radell. Combinação de reações organocatalíticas e multicomponentes para a síntese de sistemas heterocíclicos e moleculas híbridas. 2019. Tese (Doutorado em Química) – Universidade Federal de São Carlos, São Carlos, 2019. Disponível em: https://repositorio.ufscar.br/handle/ufscar/11032. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufscar.br/handle/ufscar/11032 |
identifier_str_mv |
ECHEMENDÍA PÉREZ, Radell. Combinação de reações organocatalíticas e multicomponentes para a síntese de sistemas heterocíclicos e moleculas híbridas. 2019. Tese (Doutorado em Química) – Universidade Federal de São Carlos, São Carlos, 2019. Disponível em: https://repositorio.ufscar.br/handle/ufscar/11032. |
url |
https://repositorio.ufscar.br/handle/ufscar/11032 |
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eng |
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eng |
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600 |
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info:eu-repo/semantics/openAccess |
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openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de São Carlos Câmpus São Carlos |
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Programa de Pós-Graduação em Química - PPGQ |
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UFSCar |
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Universidade Federal de São Carlos Câmpus São Carlos |
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