21 細胞毒性ポリケチドcallystatin Aの全合成とleptomycin Bの絶対立体構造(口頭発表の部)

概要

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During the course of our investigation in search for new bioactive substances from marine organisms, we isolated an extremely potent cytotoxic polyketide designated callystatin A (1) from the marine sponge Callyspongia truncata and elucidated the absolute stereostructure of 1 by both physicochemical and synthetic means. The scarcity of natural supply prompted us to engage in total synthesis of 1 for further biological evaluation and confirmation of the absolute stereostructure. Consequently, the first total synthesis of callystatin A (1) was achieved by use of a trans-selective Wittig olefination utilizing allylic tributylphosphorus ylide and asymmetric Evans aldol condensation as the key reactions. On the other hand, an anti-tumor antibiotic, leptomycin B (23), which has a fairly similar chemical structure to callystatin A (1), was shown to induce arrest of cell cycle at G1 and G2 phase. Additionally, it was very recently found to inhibit nuclear export signal (NES)-mediated transport of Rev and U snRNA protein through specific binding chromosome maintenance region 1 (CRM1) protein. In spite of its attractive biological activities, no study on the stereostructure of 23 as well as those of several congeners has been reported. Thus, we have established the absolute stereostructure of leptomycin B as 23 having 4S, 5R, 10R, 16R, 18S, 19R, and 20S configurations by asymmetric total synthesis.
天然有機化合物討論会の論文
1998-08-31