First total synthesis of ampullosine, a unique isoquinoline alkaloid isolated from Sepedonium ampullosporum, and of the related permethylampullosine

Autores
Vargas Vargas, Didier Farley; Larghi, Enrique Leandro; Kaufman, Teodoro Saul
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A straightforward and convenient approach toward the first total synthesis of ampullosine, a structurally unique 3-methylisoquinoline alkaloid isolated from Sepedonium ampullosporum, is reported. Access to the related O-methyl ampullosine methyl ester from a common intermediate is also disclosed. The synthetic sequence toward the natural product comprised a Kolbe-type carboxylation of 3,5-dihydroxybenzoic acid and further esterification of the diacid, followed by masking of one of the phenols through selective ester reduction and subsequent acetonide formation. Installation of the three-carbon atom required for the 3-methylpyridine ring was performed by triflation of the remaining free phenol and a Pd-catalyzed Suzuki-Miyaura reaction with potassium E-propenyltrifluoroborate. Deprotection of the acetonide, followed by partial oxidation of the benzylic alcohol to the salicylaldehyde, O-methylation of the free phenol and hydrazonation of the resulting ortho-anisaldehyde derivative gave a hydrazone-based 1-azatriene. This was further subjected to 6π-azaelectrocyclization to afford permethylampullosine (11 steps, 14% overall yield), whereas exhaustive demethylation with AlI3 generated in situ gave ampullosine (12 steps, 3.2% global yield).
Fil: Vargas Vargas, Didier Farley. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Fil: Larghi, Enrique Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Fil: Kaufman, Teodoro Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Materia
Ampullosina
Natural Products synthesis
Isoquinolines
6Pi-Electrocyclization
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/120879
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/120879
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling First total synthesis of ampullosine, a unique isoquinoline alkaloid isolated from Sepedonium ampullosporum, and of the related permethylampullosineVargas Vargas, Didier FarleyLarghi, Enrique LeandroKaufman, Teodoro SaulAmpullosinaNatural Products synthesisIsoquinolines6Pi-Electrocyclizationhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1A straightforward and convenient approach toward the first total synthesis of ampullosine, a structurally unique 3-methylisoquinoline alkaloid isolated from Sepedonium ampullosporum, is reported. Access to the related O-methyl ampullosine methyl ester from a common intermediate is also disclosed. The synthetic sequence toward the natural product comprised a Kolbe-type carboxylation of 3,5-dihydroxybenzoic acid and further esterification of the diacid, followed by masking of one of the phenols through selective ester reduction and subsequent acetonide formation. Installation of the three-carbon atom required for the 3-methylpyridine ring was performed by triflation of the remaining free phenol and a Pd-catalyzed Suzuki-Miyaura reaction with potassium E-propenyltrifluoroborate. Deprotection of the acetonide, followed by partial oxidation of the benzylic alcohol to the salicylaldehyde, O-methylation of the free phenol and hydrazonation of the resulting ortho-anisaldehyde derivative gave a hydrazone-based 1-azatriene. This was further subjected to 6π-azaelectrocyclization to afford permethylampullosine (11 steps, 14% overall yield), whereas exhaustive demethylation with AlI3 generated in situ gave ampullosine (12 steps, 3.2% global yield).Fil: Vargas Vargas, Didier Farley. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Larghi, Enrique Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Kaufman, Teodoro Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaRoyal Society of Chemistry2019-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/120879Vargas Vargas, Didier Farley; Larghi, Enrique Leandro; Kaufman, Teodoro Saul; First total synthesis of ampullosine, a unique isoquinoline alkaloid isolated from Sepedonium ampullosporum, and of the related permethylampullosine; Royal Society of Chemistry; RSC Advances; 9; 57; 10-2019; 33096-331062046-2069CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://xlink.rsc.org/?DOI=C9RA06839Binfo:eu-repo/semantics/altIdentifier/doi/10.1039/C9RA06839Binfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:33:31Zoai:ri.conicet.gov.ar:11336/120879instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:33:32.266CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv First total synthesis of ampullosine, a unique isoquinoline alkaloid isolated from Sepedonium ampullosporum, and of the related permethylampullosine
title First total synthesis of ampullosine, a unique isoquinoline alkaloid isolated from Sepedonium ampullosporum, and of the related permethylampullosine
spellingShingle First total synthesis of ampullosine, a unique isoquinoline alkaloid isolated from Sepedonium ampullosporum, and of the related permethylampullosine
Vargas Vargas, Didier Farley
Ampullosina
Natural Products synthesis
Isoquinolines
6Pi-Electrocyclization
title_short First total synthesis of ampullosine, a unique isoquinoline alkaloid isolated from Sepedonium ampullosporum, and of the related permethylampullosine
title_full First total synthesis of ampullosine, a unique isoquinoline alkaloid isolated from Sepedonium ampullosporum, and of the related permethylampullosine
title_fullStr First total synthesis of ampullosine, a unique isoquinoline alkaloid isolated from Sepedonium ampullosporum, and of the related permethylampullosine
title_full_unstemmed First total synthesis of ampullosine, a unique isoquinoline alkaloid isolated from Sepedonium ampullosporum, and of the related permethylampullosine
title_sort First total synthesis of ampullosine, a unique isoquinoline alkaloid isolated from Sepedonium ampullosporum, and of the related permethylampullosine
dc.creator.none.fl_str_mv Vargas Vargas, Didier Farley
Larghi, Enrique Leandro
Kaufman, Teodoro Saul
author Vargas Vargas, Didier Farley
author_facet Vargas Vargas, Didier Farley
Larghi, Enrique Leandro
Kaufman, Teodoro Saul
author_role author
author2 Larghi, Enrique Leandro
Kaufman, Teodoro Saul
author2_role author
author
dc.subject.none.fl_str_mv Ampullosina
Natural Products synthesis
Isoquinolines
6Pi-Electrocyclization
topic Ampullosina
Natural Products synthesis
Isoquinolines
6Pi-Electrocyclization
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv A straightforward and convenient approach toward the first total synthesis of ampullosine, a structurally unique 3-methylisoquinoline alkaloid isolated from Sepedonium ampullosporum, is reported. Access to the related O-methyl ampullosine methyl ester from a common intermediate is also disclosed. The synthetic sequence toward the natural product comprised a Kolbe-type carboxylation of 3,5-dihydroxybenzoic acid and further esterification of the diacid, followed by masking of one of the phenols through selective ester reduction and subsequent acetonide formation. Installation of the three-carbon atom required for the 3-methylpyridine ring was performed by triflation of the remaining free phenol and a Pd-catalyzed Suzuki-Miyaura reaction with potassium E-propenyltrifluoroborate. Deprotection of the acetonide, followed by partial oxidation of the benzylic alcohol to the salicylaldehyde, O-methylation of the free phenol and hydrazonation of the resulting ortho-anisaldehyde derivative gave a hydrazone-based 1-azatriene. This was further subjected to 6π-azaelectrocyclization to afford permethylampullosine (11 steps, 14% overall yield), whereas exhaustive demethylation with AlI3 generated in situ gave ampullosine (12 steps, 3.2% global yield).
Fil: Vargas Vargas, Didier Farley. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Fil: Larghi, Enrique Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Fil: Kaufman, Teodoro Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
description A straightforward and convenient approach toward the first total synthesis of ampullosine, a structurally unique 3-methylisoquinoline alkaloid isolated from Sepedonium ampullosporum, is reported. Access to the related O-methyl ampullosine methyl ester from a common intermediate is also disclosed. The synthetic sequence toward the natural product comprised a Kolbe-type carboxylation of 3,5-dihydroxybenzoic acid and further esterification of the diacid, followed by masking of one of the phenols through selective ester reduction and subsequent acetonide formation. Installation of the three-carbon atom required for the 3-methylpyridine ring was performed by triflation of the remaining free phenol and a Pd-catalyzed Suzuki-Miyaura reaction with potassium E-propenyltrifluoroborate. Deprotection of the acetonide, followed by partial oxidation of the benzylic alcohol to the salicylaldehyde, O-methylation of the free phenol and hydrazonation of the resulting ortho-anisaldehyde derivative gave a hydrazone-based 1-azatriene. This was further subjected to 6π-azaelectrocyclization to afford permethylampullosine (11 steps, 14% overall yield), whereas exhaustive demethylation with AlI3 generated in situ gave ampullosine (12 steps, 3.2% global yield).
publishDate 2019
dc.date.none.fl_str_mv 2019-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/120879
Vargas Vargas, Didier Farley; Larghi, Enrique Leandro; Kaufman, Teodoro Saul; First total synthesis of ampullosine, a unique isoquinoline alkaloid isolated from Sepedonium ampullosporum, and of the related permethylampullosine; Royal Society of Chemistry; RSC Advances; 9; 57; 10-2019; 33096-33106
2046-2069
CONICET Digital
CONICET
url http://hdl.handle.net/11336/120879
identifier_str_mv Vargas Vargas, Didier Farley; Larghi, Enrique Leandro; Kaufman, Teodoro Saul; First total synthesis of ampullosine, a unique isoquinoline alkaloid isolated from Sepedonium ampullosporum, and of the related permethylampullosine; Royal Society of Chemistry; RSC Advances; 9; 57; 10-2019; 33096-33106
2046-2069
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://xlink.rsc.org/?DOI=C9RA06839B
info:eu-repo/semantics/altIdentifier/doi/10.1039/C9RA06839B
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Royal Society of Chemistry
publisher.none.fl_str_mv Royal Society of Chemistry
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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