カリスポンジオリドの総合成とステレオ化学的配分
Jingjing Zhou1, Bowen Gao1, Zhengshuang Xu1
1Laboratory of Chemical Genomics, Engineering Laboratory for Chiral Drug Synthesis, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School , Xili, Nanshan District, Shenzhen 518055, China.
Journal of the American Chemical Society
|May 27, 2016
まとめ
カリスポンジオリドのステレオアイソマーの総合成は,その構造を正確に定義した. マクロラクトン・コア
科学分野:
- 有機化学
- 薬剤化学
- 化学合成
背景:
- カリスポンジオライドは抗がん性を持つ天然製品です.
- カリスポンジオリドの精密なステレオ化学は,その生物学的活動に極めて重要です.
- 以前の研究では,カリスポンジオリドの活性に対するステレオ化学的要件が完全に解明されていません.
研究 の 目的:
- カリスポンジオリドの4つのステレオアイソマーの全合成を達成する.
- カリスポンジオライドの相対的および絶対的立体化学を明確に指定する.
- カリスポンジオリドの抗癌作用に対するステレオ化学の影響を評価する.
主な方法:
- コンバージェントでステレオ制御された合成経路が設計された.
- 主要な反応には,クリシェ・アリレーション,キヨカ・アルドル反応,コシエンスキ・ジュリア・オレフィネーション,スティル・ジェナリ・オレフィネーション,ヤマグチ・マクロサイクライゼーション,ソノガシラ・カップリングが含まれていた.
- 合成されたステレオアイソマーは,様々な癌細胞系に対して生物学的に評価された.
主要な成果:
- カリスポンジオライドの4つの異なるステレオアイソマーが成功して合成されました.
- 合成経路は相対的および絶対的立体化学の明確な割り当てを提供した.
- 生物学的評価は,マクロラクトン核のステレオ化学が抗がん活動に有意な影響を及ぼすことを示した.
結論:
- 全合成により,カリスポンジオリドの決定的な立体化学構造が確立された.
- ステレオ化学は,がん細胞に対するカルリスポンジオライドの有効性を決定する重要な要素です.
- この研究は,ステレオ化学的に最適化されたカリスポンジオリド類の開発のための基礎を提供します.
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