14 海洋産抗腫瘍性物質アプリロニンAおよび関連物質の合成と生物活性(口頭発表の部)

概要

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Aplyronine A (1), a novel macrolide isolated from the sea hare Aplysia kurodai, shows potent antitumor activity and interacts with actin, the protein in cytoskeleton. The enantioselective synthesis of 1 was achieved by a convergent approach. Starting from imides 4 and ent-4, the C5-C20 segment 8 and the C21-C34 segment 9 were synthesized by using the Evans aldol reaction and the Sharpless epoxidation reaction as key steps. Julia olefination between the segments 8 and 9 followed by four-carbon homologation reaction and Yamaguchi lactonization led to the 24-membered lactone 10, which was converted into aplyronine A (1) by construction of the terminal N-formyl enamine structure and subsequent introduction of the two amino acids. The use of the [(3,4-dimethoxybenzyl)oxy]methyl group as a protecting group for the hydroxyl at C29 was crucial for this synthesis. The artificial analogs of aplyronine A (1) were synthesized, and the structure-activity (cytotoxicity and actin depolymerizing activity) relationships were examined. The side chain portion of 1 was found to play an essential role in both biological activities, and the trimethylserine moiety and two hydroxyl groups in 1 turned out to be important in the potent cytotoxicity.
天然有機化合物討論会の論文
1997-07-20