マンザミンAおよび関連アルカロイドの総合成
Pavol Jakubec1, Alison Hawkins, Wolfgang Felzmann
1Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK.
Journal of the American Chemical Society
|October 9, 2012
まとめ
研究者は,海洋天然産物マンザミンA,イルシノールA,イルシナルAの総合合成を達成しました. この効率的な経路は,これらの複雑な分子への迅速なアクセスを可能にする新しいペンタサイクリックエノールトリフラート中間物質を使用しました.
科学分野:
- オーガニック・シンセシス オーガニック・シンセシス
- 自然製品化学 自然製品化学
- 薬用化学 薬用化学について
背景:
- マンザミンAのような海洋天然製品は,重要な生物学的活性を示しています.
- マンザミンAおよびその類似品への以前の合成経路は,長く複雑である.
- これらの化合物への効率的なアクセスは,さらなる生物学的評価と薬物開発に不可欠です.
研究 の 目的:
- マンザミンA,アーチノールA,アーチナルAの簡潔で効率的な全合成を開発する.
- マンザミンA アナログへのアクセスのための後期的な多様化戦略を確立する.
- 複雑なペンタサイクル構造のための新しい合成方法論を紹介する.
主な方法:
- 保護基のないペンタサイクリックエノールトリフラートを使用したコンバージェント合成.
- 主要な反応には,立体選択的ミカエル加法,ニトロマニッヒ乳化,還元性ニトロマニッヒサイクル化,有機金属加法,Z選択的環閉メタテシスが含まれる.
- 異なる合成のためのパラジウム触媒クロスカップリング反応.
主要な成果:
- マンザミンA,アーチノールA,アーチナルAの完全な合成が成功しました.
- マンザミンA (18ステップ) の最も短い合成経路を達成しました.
- 共通の中間商品から後期的な分散点を示した.
結論:
- 開発された合成戦略は,マンザミンAとその関連天然製品への効率的なアクセスを提供します.
- この方法論は,構造-活性関係研究のために,様々なマンザミンA類の合成に適しています.
- この研究は,複雑な海洋アルカロイドの合成アクセシビリティを向上させる.
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