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

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

dc.citation.title	RSC Advances	es
dc.citation.volume	(57)	es
dc.creator	Vargas, Didier F.
dc.creator	Larghi, Enrique Leandro
dc.creator	Kaufman, Teodoro Saúl
dc.date.accessioned	2020-12-23T15:48:33Z
dc.date.available	2020-12-23T15:48:33Z
dc.date.issued	2019-10-16
dc.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).	es
dc.description	This is a post-peer-review, pre-copyedit version of an article published in RSC Advances. The final authenticated version is available online at: https://doi.org/10.1039/c9ra06839b
dc.description.fil	Fil: Vargas, Didier F. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (IQUIR -CONICET); Argentina.	es
dc.description.fil	Fil: Larghi, Enrique Leandro. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (IQUIR -CONICET); Argentina.	es
dc.description.fil	Fil: Kaufman, Teodoro Saúl. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (IQUIR -CONICET); Argentina.	es
dc.description.sponsorship	Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT): PICT 2017-0149	es
dc.description.sponsorship	Agencia Santafesina de Ciencia, Tecnología e Innovación (ASaCTeI): AC 2015-0005	es
dc.format	application/pdf
dc.format.extent	33096–33106	es
dc.identifier.issn	2046-2069	es
dc.identifier.uri	http://hdl.handle.net/2133/19543
dc.language.iso	eng	es
dc.publisher	Royal Society of Chemistry	es
dc.relation.publisherversion	https://pubs.rsc.org/en/content/articlelanding/2019/RA/C9RA06839B#!divAbstract	es
dc.relation.publisherversion	https://doi.org/10.1039/c9ra06839b	es
dc.rights	openAccess	es
dc.rights.holder	Universidad Nacional de Rosario	es
dc.rights.holder	Royal Society of Chemistry	es
dc.rights.holder	Vargas, Didier F.	es
dc.rights.holder	Larghi, Enrique Leandro	es
dc.rights.holder	Kaufman, Teodoro Saúl	es
dc.rights.text	Attribution 3.0 Unported (CC BY 3.0)	es
dc.rights.uri	https://creativecommons.org/licenses/by/3.0/	*
dc.subject	Ampullosine	es
dc.subject	3-Methyl-isoquinoline-6-carboxylic Acid	es
dc.subject	Isoquinoline Alkaloid	es
dc.subject	Sepedonium ampullosporum	es
dc.subject	Permethylampullosine	es
dc.subject	Biopharmaceutics	es
dc.title	First total synthesis of ampullosine, a unique isoquinoline alkaloid isolated from Sepedonium ampullosporum, and of the related permethylampullosine	es
dc.type	article
dc.type	artículo
dc.type	publishedVersion
dc.type.collection	articulo
dc.type.version	publishedVersion	es