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: | , , |
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| Formato: | article artículo publishedVersion |
| Lenguaje: | Inglés |
| Publicado: |
Royal Society of Chemistry
2020
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| Materias: | |
| Acceso en línea: | http://hdl.handle.net/2133/19543 http://hdl.handle.net/2133/19543 |
| Aporte de: |
| Sumario: | 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). |
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