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

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....

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Autores principales: Vargas, Didier F., Larghi, Enrique Leandro, Kaufman, Teodoro Saúl
Formato: article artículo publishedVersion
Lenguaje:Inglés
Publicado: Royal Society of Chemistry 2020
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Acceso en línea:http://hdl.handle.net/2133/19543
http://hdl.handle.net/2133/19543
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id I15-R121-2133-19543
record_format dspace
institution Universidad Nacional de Rosario
institution_str I-15
repository_str R-121
collection Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language Inglés
orig_language_str_mv eng
topic Ampullosine
3-Methyl-isoquinoline-6-carboxylic Acid
Isoquinoline Alkaloid
Sepedonium ampullosporum
Permethylampullosine
Biopharmaceutics
spellingShingle Ampullosine
3-Methyl-isoquinoline-6-carboxylic Acid
Isoquinoline Alkaloid
Sepedonium ampullosporum
Permethylampullosine
Biopharmaceutics
Vargas, Didier F.
Larghi, Enrique Leandro
Kaufman, Teodoro Saúl
First total synthesis of ampullosine, a unique isoquinoline alkaloid isolated from Sepedonium ampullosporum, and of the related permethylampullosine
topic_facet Ampullosine
3-Methyl-isoquinoline-6-carboxylic Acid
Isoquinoline Alkaloid
Sepedonium ampullosporum
Permethylampullosine
Biopharmaceutics
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 hydrazonebased 1-azatriene. This was further subjected to 6p-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).
format article
artículo
publishedVersion
author Vargas, Didier F.
Larghi, Enrique Leandro
Kaufman, Teodoro Saúl
author_facet Vargas, Didier F.
Larghi, Enrique Leandro
Kaufman, Teodoro Saúl
author_sort Vargas, Didier F.
title First total synthesis of ampullosine, a unique isoquinoline alkaloid isolated from Sepedonium ampullosporum, and of the related permethylampullosine
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
publisher Royal Society of Chemistry
publishDate 2020
url http://hdl.handle.net/2133/19543
http://hdl.handle.net/2133/19543
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AT kaufmanteodorosaul firsttotalsynthesisofampullosineauniqueisoquinolinealkaloidisolatedfromsepedoniumampullosporumandoftherelatedpermethylampullosine
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