天然有機化合物討論会講演要旨集
Online ISSN : 2433-1856
第59回天然有機化合物討論会実行委員会
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38 天然物のハイブリッド化によるアプリロニン A の構造活性相関研究 (口頭発表)
*高野 敦弘並木 真悠宮崎 悠斗小倉 寛敬大好 孝幸早川 一郎木越 英夫
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会議録・要旨集 オープンアクセス

p. 225-230

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Aplyronine A (1) is a 24-membered macrolide isolated from sea hare by our group. Aplyronine A (1) shows cell growth inhibition, anticancer, and actin depolymerizing activities. Our previous works disclosed the novel action mechanism that the side chain part of aplyronine A binds actin, and then, the trimethylserine group interacts with tubulin α,β-heterodimer to form a ternary complex. Now, we investigate structure-activity relationship of aplyronine A for development of new anticancer drugs. We have already succeeded in total synthesis of aplyronine A, however, it required 86 steps. Thus, we designed a simpler analog, aplyronine A - swinholide A hybrid compound 3, which consists of the macrolactone part of aplyronine A and the side chain part of swinholide A (2), an actin depolymerizing dimeric macrolide with a structurally simpler side chain. Our synthetic strategy contains esterification between C1-C19 segment 5 and C20-C34 segment 6, followed by intramolecular NHK coupling for construction of macrocycle. Finally, we synthesized hybrid compound 3 in 70 steps (vs 86 steps for aplyronine A). Hybrid compound 3 was found to show a potent cell growth inhibitory activity, revealing the importance of combination of macrocycle and side chain parts for potent bioactivity.

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