化学ネットワーク分析にインスパイアされた戦略を用いたディテルペノイドアルカロイドアルクチニジンの総合成
Kyle R Owens1, Shelby V McCowen1, Katherine A Blackford1
1Department of Chemistry , University of California , Berkeley , California 94720 , United States.
Journal of the American Chemical Society
|July 6, 2019
まとめ
この研究は,複雑なディターペノイドアルカロイドであるアルクチニジンの最初の完全な合成を報告しています. この新しい合成戦略は,アーキュティニジンの複雑な橋渡し構造を構築するために,ユニークなサイクル添加と結合反応を使用しています.
科学分野:
- 有機化学
- 自然製品合成
- 薬剤化学
背景:
- アルクチニジンおよび関連するアルクチニジン型ディターペノイドは,ユニークな接続性を持つ複合的,多循環的,ブリッジ構造を有する.
- これらの天然製品の合成を理解することは,それらの潜在的な生物学的活動と生物合成経路の探索に不可欠です.
研究 の 目的:
- アルクチニジンの最初の完全合成を 達成するために
- 複合的なブリッジアルカロイドフレームワークの構築のための新しい合成方法論を開発する.
- 関連するディターペノイドアルカロイドの生合成関係を調査するための基礎を提供すること.
主な方法:
- 化学的なネットワーク分析により,単純化されたレトロ合成の断絶を特定する.
- 前例のないオキシピロリウム・ディエルス・アルダー・サイクロアディションが 主要な四輪 intermediate を形成した.
- ダイアステレオ選択的酸化脱オロマ化/サイクロアディション配列
- サマリウム (II) ヨーデット (SmI2) 介在の炭素-炭素結合で,橋渡されたフレームを組み立てます.
主要な成果:
- アルクチニジンの完全合成が成功しました
- 複雑なポリサイクルシステムを構築するための新しいオキシピロリウムダイエルス-アルダー反応の実証.
- 橋渡しされたディターペノイドアルカロイド骨格の形成のための主要なC-C結合の形成.
結論:
- 開発された合成経路は,アルクチニジンおよびそのアナログへの効率的なアクセスを提供します.
- 合成戦略は,自然製品の合成におけるレトロ合成分析と新しいサイクル添加反応の力を強調しています.
- この研究は,アルクタンおよび関連するディターペノイドアルカロイドの生物合成に関する将来の研究のための基礎を築く.
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