134(P-84) ChAT活性を増進するイリシノン類の全合成研究(ポスター発表の部)

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Tricycloillicinone (1) and bicycloillicinone asaronacetal (2) were both isolated from extracts of the wood of Illicium tashiroi. These compounds were found to enhance the action of choline acetyltransferase (ChAT), which catalyzes the synthesis of acetylcholine from its precursor. Since one of the characteristic symptoms of Alzheimer's disease involves degeneration of cholinergic neurons, resulting in markedly reduced levels of acetylcholine, compounds with the properties of 1 or 2 could well serve as agents in the treatment of such disorders. In this paper, we report the total synthesis of tricycloillicinone (1) and the construction of the core structure (3) of bicycloillicinone asaronacetal (2). The common precursor 13 for the syntheses of both 1 and 3 were prepared with employing a novel strategy to control the regiochemistry of two ortho Claisen rearrangements. A sulfonyl group introduced at C_2 of an allyl group effectively suppressed its unwanted rearrangement to the para-position (5→6). Subsequently, o-Claisen rearrangement was conducted using a reverse O-prenylated derivative 12 to furnish the desired compound 13, selectively. The application of Corey-Snider oxidative cyclization of 13 cleanly furnished 3-oxytricycloillicinone (16). The total synthesis of tricycloillicinone (1) was achieved through the 4-electron reduction of the ketone in 16 to the corresponding methylene group. For bicycloillicinone aldehyde 3, a new tandem reaction using Et_2AlCN to construct the cage structure (21→23) was employed. Bicycloillicinone Aldehyde 3 was obtained through the reduction of TMS acetal 25, followed by acid hydrolysis. Flexible syntheses of the polycyclic illicinones should provide access to analogous structures for future biological and SAR studies.
天然有機化合物討論会の論文
2000-10-01

134(P-84) ChAT活性を増進するイリシノン類の全合成研究(ポスター発表の部)

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