エナチオセレクティブ・トータル・シンセシス (+) -ヘイロニン
Kyle J Cassaidy1, Viresh H Rawal1
1Department of Chemistry, University of Chicago, Chicago, Illinois 60637, United States.
Journal of the American Chemical Society
|September 29, 2021
まとめ
研究者は,ベラトルムアルカロイドにアクセスするために,移行金属触媒 [2+2+2] サイクロイソメリゼーションを使用して新しい合成戦略を開発しました. この効率的な方法により ヘイロニンの合成は たった21段階で行われました
科学分野:
- 有機化学
- 総合成
- 薬剤化学
背景:
- 移行金属触媒 [2+2+2] サイクロアイソメリゼーションは,複雑な分子構造を構築するための強力なツールです.
- ヴェラトルムのアルカロイドは,潜在的な治療用途を持つ重要な自然製品のクラスです.
- これらのアルカロイドへの効率的で収束した合成経路の開発は,さらなる研究のために不可欠です.
研究 の 目的:
- ヴェラトラムアルカロイドの新たな合成戦略を確立する.
- 複雑な六環セバニン骨格の組み立てにおける分子内 [2+2+2] サイクロイソメリゼーションの有用性を実証する.
- ヘイロニンの最初の完全合成を 達成するために
主な方法:
- ステロイドのA/B環を組み込んだダイヌ断片のエナンチオセレクティブ合成.
- プロパルギル置換ピペリドニン (F環) ユニットの非対称合成
- C/D/Eリングを形成するために,高収量断片結合に続いて分子内 [2+2+2] サイクロイソメリゼーションが行われます.
- 最終製品形成のための後期機能化.
主要な成果:
- 重要な分子内 [2+2+2] サイクロイソメリゼーションを活用したコンバージェント合成戦略が成功しました.
- この戦略は,ヘクササイクルのセバニンのコア構造を1つのステップで効率的に構築しました.
- ヘイロニンの最初の完全合成は,エチルビニルケトンから21段階で行われた.
結論:
- 報告された戦略は,Veratrumアルカロイドへの新しい効率的な経路を提供します.
- 分子内 [2+2+2] サイクロイソメリゼーションは,複雑な多循環系を構成する非常に効果的な方法である.
- この研究は,複雑な天然製品の総合合成を大幅に進める.
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