81(P-10) α-マンゴスチンとその関連物質の合成と生物活性(ポスター発表の部)

概要

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α-Mangostin 1a, isolated from Garcinia mangostana L., is known as a specific inhibitor of the acidic sphingomyelinase (ASMase). While confirmed as a competitive antagonist of the histamine H1 receptor and an inhibition of topoisomerases I and II, no synthesis of 1a carrying the intriguing highly-functionalized xanthone structure, has been published. Ceramide, produced by the effect of SMase, is suggested to participate in various cell phenomena such as cell proliferation, cell differentiation and apoptosis. Accordingly, an inhibitor of SMase is considered to be an effective tool for investigation of the mode of action. However, direct usage of 1a in cell might be troublesome, because of its strong cytotoxicity. This background prompted us to synthesize 1a and its derivatives, and to evaluate their activities to develop more effective derivatives. We disclose a successful total synthesis of 1a by coupling between Fragment A1 and B1. The key cyclization reaction to construct the xanthone framework was undertaken by employing the PPh_3-CCl_4 conditions. In the biological assay in the presence of ASMase and NBD-sphingomyelin, the benzophenone A exhibited a comparable inhibitory activity and lower cytotoxicity than that of 1a. To investigate the structure-activity relationship, compounds B-E were synthesized and evaluation of their activities will be presented.
天然有機化合物討論会の論文
2002-09-01