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Synthesis of pure stereoisomers of benzo[b]thienyl dehydrophenylalanines by Suzuki cross-coupling. Preliminary studies of antimicrobial activity
| Resumo: | Several benzo[b]thienyldehydrophenylalanines were synthesized from pure stereoisomers of the methyl ester of N-(tertbutoxycarbonyl)- b-bromodehydrophenylalanine as an extension of our previously reported method for the synthesis of dehydrotryptophan analogues to dehydrophenylalanine derivatives. The latter were obtained in high yields by N-deprotection and bromination of N,N-bis-(tertbutoxycarbonyl)-( Z)-dehydrophenylalanine using TFA and NBS. This was carried out in two steps or in a one pot procedure resulting in different E/Z ratios. These compounds were coupled under Suzuki cross-coupling conditions [Pd(PPh3)4, Na2CO3, DME/H2O] with several boronic benzo[b]thienyl acids in good to high yields maintaining the stereochemistry of the starting materials. The best yields were obtained when the boronic acid was in position 7 of the benzo[b]thiophene and with the E isomer of the brominated dehydrophenylalanine. In some cases it was possible to increase the lower yields by changing the Pd source to PdCl2(PPh3)2. A model dipeptide was prepared coupling a benzo[b]thienyldehydrophenylalanine with the methyl ester of alanine. Preliminary antimicrobial studies were performed with both isomers of one of the b, b-diaryldehydroalanines obtained. The results show that the compounds are selective and very active (very low MICs) against Gram positive bacteria (B. cereus and B. subtilis) the Z-isomer being more active. The compounds are also active against Candida albicans presenting similar MICs. |
|---|---|
| Autores principais: | Abreu, Ana S. |
| Outros Autores: | Ferreira, Paula M.T.; Monteiro, Luís S.; Ferreira, Isabel C.F.R.; Calhelha, Ricardo C.; Estevinho, Leticia M. |
| Assunto: | Amino acids Dehydrophenylalanines Benzo[b]thiophenes Suzuki coupling Palladium Antimicrobial |
| Ano: | 2004 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Instituto Politécnico de Bragança |
| Idioma: | inglês |
| Origem: | Biblioteca Digital do IPB |
| _version_ | 1867173368991580160 |
|---|---|
| author | Abreu, Ana S. |
| author2 | Ferreira, Paula M.T. Monteiro, Luís S. Ferreira, Isabel C.F.R. Calhelha, Ricardo C. Estevinho, Leticia M. |
| author2_role | author author author author author |
| author_facet | Abreu, Ana S. Ferreira, Paula M.T. Monteiro, Luís S. Ferreira, Isabel C.F.R. Calhelha, Ricardo C. Estevinho, Leticia M. |
| author_role | author |
| contributor_name_str_mv | Biblioteca Digital do IPB |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Abreu, Ana S.\"},{\"Person.name\":\"Ferreira, Paula M.T.\"},{\"Person.name\":\"Monteiro, Luís S.\"},{\"Person.name\":\"Ferreira, Isabel C.F.R.\",\"Person.identifier.orcid\":\"0000-0003-4910-4882\"},{\"Person.name\":\"Calhelha, Ricardo C.\",\"Person.identifier.orcid\":\"0000-0002-6801-4578\"},{\"Person.name\":\"Estevinho, Leticia M.\",\"Person.identifier.orcid\":\"0000-0002-9249-1948\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Biblioteca Digital do IPB |
| datacite.creators.creator.creatorName.fl_str_mv | Abreu, Ana S. Ferreira, Paula M.T. Monteiro, Luís S. Ferreira, Isabel C.F.R. Calhelha, Ricardo C. Estevinho, Leticia M. |
| datacite.date.Accepted.fl_str_mv | 2004-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2008-09-12T14:19:39Z |
| datacite.date.embargoed.fl_str_mv | 2008-09-12T14:19:39Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Amino acids Dehydrophenylalanines Benzo[b]thiophenes Suzuki coupling Palladium Antimicrobial |
| datacite.titles.title.fl_str_mv | Synthesis of pure stereoisomers of benzo[b]thienyl dehydrophenylalanines by Suzuki cross-coupling. Preliminary studies of antimicrobial activity |
| dc.contributor.none.fl_str_mv | Biblioteca Digital do IPB |
| dc.creator.none.fl_str_mv | Abreu, Ana S. Ferreira, Paula M.T. Monteiro, Luís S. Ferreira, Isabel C.F.R. Calhelha, Ricardo C. Estevinho, Leticia M. |
| dc.date.Accepted.fl_str_mv | 2004-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2008-09-12T14:19:39Z |
| dc.date.embargoed.fl_str_mv | 2008-09-12T14:19:39Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10198/822 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Elsevier |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Amino acids Dehydrophenylalanines Benzo[b]thiophenes Suzuki coupling Palladium Antimicrobial |
| dc.title.fl_str_mv | Synthesis of pure stereoisomers of benzo[b]thienyl dehydrophenylalanines by Suzuki cross-coupling. Preliminary studies of antimicrobial activity |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Several benzo[b]thienyldehydrophenylalanines were synthesized from pure stereoisomers of the methyl ester of N-(tertbutoxycarbonyl)- b-bromodehydrophenylalanine as an extension of our previously reported method for the synthesis of dehydrotryptophan analogues to dehydrophenylalanine derivatives. The latter were obtained in high yields by N-deprotection and bromination of N,N-bis-(tertbutoxycarbonyl)-( Z)-dehydrophenylalanine using TFA and NBS. This was carried out in two steps or in a one pot procedure resulting in different E/Z ratios. These compounds were coupled under Suzuki cross-coupling conditions [Pd(PPh3)4, Na2CO3, DME/H2O] with several boronic benzo[b]thienyl acids in good to high yields maintaining the stereochemistry of the starting materials. The best yields were obtained when the boronic acid was in position 7 of the benzo[b]thiophene and with the E isomer of the brominated dehydrophenylalanine. In some cases it was possible to increase the lower yields by changing the Pd source to PdCl2(PPh3)2. A model dipeptide was prepared coupling a benzo[b]thienyldehydrophenylalanine with the methyl ester of alanine. Preliminary antimicrobial studies were performed with both isomers of one of the b, b-diaryldehydroalanines obtained. The results show that the compounds are selective and very active (very low MICs) against Gram positive bacteria (B. cereus and B. subtilis) the Z-isomer being more active. The compounds are also active against Candida albicans presenting similar MICs. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://bibliotecadigital.ipb.pt/bitstreams/b2903013-7d89-4596-9611-b03f64476244/download |
| funding.funder.alternateName_str_mv | FCT FCT |
| funding.funder.identifier_str_mv | http://doi.org/10.13039/501100001871 http://doi.org/10.13039/501100001871 |
| funding.funder.name_str_mv | Fundação para a Ciência e a Tecnologia Fundação para a Ciência e a Tecnologia |
| funding.name_str_mv | POCI |
| id | ipb_f8b512ac4e09f1bec7ce649e66a6ef8c |
| identifier.url.fl_str_mv | http://hdl.handle.net/10198/822 |
| instacron_str | ipb |
| institution | Instituto Politécnico de Bragança |
| instname_str | Instituto Politécnico de Bragança |
| language | eng |
| network_acronym_str | ipb |
| network_name_str | Biblioteca Digital do IPB |
| oai_identifier_str | oai:bibliotecadigital.ipb.pt:10198/822 |
| organization_str_mv | urn:organizationAcronym:ipb |
| person_str_mv | Abreu, Ana S. Ferreira, Paula M.T. Monteiro, Luís S. Ferreira, Isabel C.F.R. Ferreira, Isabel C.F.R. https://www.ciencia-id.pt/9418-CF95-9919 9418-CF95-9919 http://orcid.org/0000-0003-4910-4882 0000-0003-4910-4882 Calhelha, Ricardo C. Calhelha, Ricardo C. https://www.ciencia-id.pt/F313-E3CE-554E F313-E3CE-554E http://orcid.org/0000-0002-6801-4578 0000-0002-6801-4578 Estevinho, Leticia M. Estevinho, Leticia M. https://www.ciencia-id.pt/BA14-09D6-A406 BA14-09D6-A406 http://orcid.org/0000-0002-9249-1948 0000-0002-9249-1948 |
| publishDate | 2004 |
| publisher.none.fl_str_mv | Elsevier |
| reponame_str | Biblioteca Digital do IPB |
| repository_id_str | urn:repositoryAcronym:ipb |
| service_str_mv | urn:repositoryAcronym:ipb |
| spelling | engElsevierenSeveral benzo[b]thienyldehydrophenylalanines were synthesized from pure stereoisomers of the methyl ester of N-(tertbutoxycarbonyl)- b-bromodehydrophenylalanine as an extension of our previously reported method for the synthesis of dehydrotryptophan analogues to dehydrophenylalanine derivatives. The latter were obtained in high yields by N-deprotection and bromination of N,N-bis-(tertbutoxycarbonyl)-( Z)-dehydrophenylalanine using TFA and NBS. This was carried out in two steps or in a one pot procedure resulting in different E/Z ratios. These compounds were coupled under Suzuki cross-coupling conditions [Pd(PPh3)4, Na2CO3, DME/H2O] with several boronic benzo[b]thienyl acids in good to high yields maintaining the stereochemistry of the starting materials. The best yields were obtained when the boronic acid was in position 7 of the benzo[b]thiophene and with the E isomer of the brominated dehydrophenylalanine. In some cases it was possible to increase the lower yields by changing the Pd source to PdCl2(PPh3)2. A model dipeptide was prepared coupling a benzo[b]thienyldehydrophenylalanine with the methyl ester of alanine. Preliminary antimicrobial studies were performed with both isomers of one of the b, b-diaryldehydroalanines obtained. The results show that the compounds are selective and very active (very low MICs) against Gram positive bacteria (B. cereus and B. subtilis) the Z-isomer being more active. The compounds are also active against Candida albicans presenting similar MICs.application/pdfenSynthesis of pure stereoisomers of benzo[b]thienyl dehydrophenylalanines by Suzuki cross-coupling. Preliminary studies of antimicrobial activityAbreu, Ana S.Ferreira, Paula M.T.Monteiro, Luís S.PersonalFerreira, Isabel C.F.R.DSpacehttp://dspace.org/items/bd0d1537-2e03-41fb-b27a-140af9c35db8DSpacehttp://dspace.org/items/bd0d1537-2e03-41fb-b27a-140af9c35db8FerreiraIsabel C.F.R.Ciência IDhttps://www.ciencia-id.pt9418-CF95-9919ORCIDhttp://orcid.org0000-0003-4910-4882Researcher IDhttps://www.researcherid.comE-8500-2013Scopus Author IDhttps://www.scopus.com36868826600PersonalCalhelha, Ricardo C.DSpacehttp://dspace.org/items/2d5d1a41-7561-4a01-871c-b4c97da35053DSpacehttp://dspace.org/items/2d5d1a41-7561-4a01-871c-b4c97da35053CalhelhaRicardo C.Ciência IDhttps://www.ciencia-id.ptF313-E3CE-554EORCIDhttp://orcid.org0000-0002-6801-4578Researcher IDhttps://www.researcherid.comJ-2172-2014Scopus Author IDhttps://www.scopus.com6507978333PersonalEstevinho, Leticia M.DSpacehttp://dspace.org/items/4a1d5ba2-1854-4ca5-89a4-73f35e964df9DSpacehttp://dspace.org/items/4a1d5ba2-1854-4ca5-89a4-73f35e964df9EstevinhoLetícia M.Ciência IDhttps://www.ciencia-id.ptBA14-09D6-A406ORCIDhttp://orcid.org0000-0002-9249-1948Scopus Author IDhttps://www.scopus.com6506577664Scopus Author IDhttps://www.scopus.com57211945650HostingInstitutionOrganizationalBiblioteca Digital do IPBe-mailmailto:dspace@ipb.ptdspace@ipb.ptISSNIsPartOf0040-4020DOIIsPartOf10.1016/j.tet.2004.09.1072008-09-12T14:19:39Z20042004-01-01T00:00:00ZHandlehttp://hdl.handle.net/10198/822http://purl.org/coar/access_right/c_abf2open accessAmino acidsDehydrophenylalaninesBenzo[b]thiophenesSuzuki couplingPalladiumAntimicrobial300544 bytesFundação para a Ciência e a TecnologiaSynthesis of non-proteinogenic amino acids with biological and/or photochromic activitiesPOCICrossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a TecnologiaSÍNTESE DE NOVOS FOTOBIOSSENSORES DERIVADOS DE AMINOÁCIDOS BENZO b TIOFÉNICOSCrossref Funder IDhttp://doi.org/10.13039/501100001871literaturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://bibliotecadigital.ipb.pt/bitstreams/b2903013-7d89-4596-9611-b03f64476244/download |
| spellingShingle | Synthesis of pure stereoisomers of benzo[b]thienyl dehydrophenylalanines by Suzuki cross-coupling. Preliminary studies of antimicrobial activity Abreu, Ana S. Amino acids Dehydrophenylalanines Benzo[b]thiophenes Suzuki coupling Palladium Antimicrobial |
| status | SINGLETON |
| subject.fl_str_mv | Amino acids Dehydrophenylalanines Benzo[b]thiophenes Suzuki coupling Palladium Antimicrobial |
| title | Synthesis of pure stereoisomers of benzo[b]thienyl dehydrophenylalanines by Suzuki cross-coupling. Preliminary studies of antimicrobial activity |
| title_full | Synthesis of pure stereoisomers of benzo[b]thienyl dehydrophenylalanines by Suzuki cross-coupling. Preliminary studies of antimicrobial activity |
| title_fullStr | Synthesis of pure stereoisomers of benzo[b]thienyl dehydrophenylalanines by Suzuki cross-coupling. Preliminary studies of antimicrobial activity |
| title_full_unstemmed | Synthesis of pure stereoisomers of benzo[b]thienyl dehydrophenylalanines by Suzuki cross-coupling. Preliminary studies of antimicrobial activity |
| title_short | Synthesis of pure stereoisomers of benzo[b]thienyl dehydrophenylalanines by Suzuki cross-coupling. Preliminary studies of antimicrobial activity |
| title_sort | Synthesis of pure stereoisomers of benzo[b]thienyl dehydrophenylalanines by Suzuki cross-coupling. Preliminary studies of antimicrobial activity |
| topic | Amino acids Dehydrophenylalanines Benzo[b]thiophenes Suzuki coupling Palladium Antimicrobial |
| topic_facet | Amino acids Dehydrophenylalanines Benzo[b]thiophenes Suzuki coupling Palladium Antimicrobial |
| url | http://hdl.handle.net/10198/822 |
| visible | 1 |