(-) -FR18287777の全合成に対するサイクル添加のカスケードアプローチ
David A Evans1, Jeremy T Starr
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. evans@chemistry.harvard.edu
Journal of the American Chemical Society
|October 30, 2003
まとめ
研究者らは,ボロンアルドール反応とトランスアヌルルダイエルス・アルダー反応を使用して,細胞毒性天然産物 (-) -FR182877の非対称合成を達成しました. この方法により,複雑なペンタサイクルの構造と7つの新しいステレオセンターが効率的に構築されました.
科学分野:
- 有機化学 オーガニック・ケミストリー
- 自然製品合成 自然製品合成
- アシンメトリック・シンセシス
背景:
- (-) -FR182877は,複雑な構造を持つ細胞毒性のある天然製品です.
- 複雑な天然製品への効率的な合成経路の開発は,化学生物学と薬剤開発に不可欠です.
研究 の 目的:
- 自然製品の非対称な合成を達成するために (-) -FR182877.
- ステレオ選択反応を用いて構造全体のキラリティを確立する.
- ポリサイクロン系を構成する際の環横ダイエルス・アルダー反応の有用性を探求する.
主な方法:
- チラリティの確立のために, (4R) -4-ベンジル-2-オクサゾリジノン媒介のボロンアルドール反応を使用した.
- マクロサイクル形成のための地域選択的なスズキカップリングを使用した.
- ベータ・ケトエステルの酸化によるステレオセレクティブ・トランスアヌラー・ディエルス・アルダー反応カスケードを開始した.
主要な成果:
- 細胞毒性のある天然産物 (-) -FR182877.7を成功して合成しました.
- ボロンアルドール反応を用いてキラリティを確立し,19基のマクロカルボサイクルを形成した.
- 環横ダイエルス・アルダー反応カスケードは,4つの新しいリングと7つの新しいステレオセンターを形成した.
結論:
- (-) -FR182877の効率的な非対称合成が開発されました.
- この研究は,複合分子合成におけるボロンアルドールと環横ダイエルス・アルダー反応の力を強調している.
- 半経験的計算により,ディエルス-アルダーカスケードの立体化学的結果に関する洞察が得られた.
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