First total synthesis of ampullosine, a unique isoquinoline alkaloid isolated from Sepedonium ampullosporum, and of the related permethylampullosine
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2019-10-16
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Royal Society of Chemistry
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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 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).
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
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
Palabras clave
Ampullosine, 3-Methyl-isoquinoline-6-carboxylic Acid, Isoquinoline Alkaloid, Sepedonium ampullosporum, Permethylampullosine, Biopharmaceutics