58(P-35) 海洋産抗腫瘍性物質アプリロニンA関連化合物の合成と生物活性(ポスター発表の部)

概要

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Aplyronine A (1) is a potent antitumor macrolide isolated from the sea hare Aplysia kurodai, and mycalolide B (2) is a cytotoxic and antifungal macrolide isolated from a sponge of the genus Mycale. These macrolides interact with actin, one of the major proteins in cytoskeleton. We achieved total synthesis of aplyronine A (1) and its analogs and investigated the structure-activity relationships. We improved the synthesis of the side chain portion of aplyronine A (1) by using the Paterson aldol reaction and subsequent stereoselective reduction with Me_4NBH(OAc)_3 as key steps. The synthetic analogs 3 and 4 that only consists of the side chain part of aplyronine A (1) and mycalolide B (2) turned out to exhibit a strong actin depolymerizing activity, considering the size of the molecule. This result revealed that the side chain portion in aplyronine A (1) and mycalolide B (2) was responsible for the potent activity of 1 and 2. Analysis of the interaction of aplyronine analogs, such as 30 and 31, with actin by a photoaffinity labeling method has been carried out. Crystallization and X-ray structure analysis of actin complex with aplyronine A (1) also are in progress.
天然有機化合物討論会の論文
2004-10-01