ヘチシン型ディターペノイドアルカロイドに対するベンジン挿入アプローチ:コスソニジン (デイヴィシン) の合成
Kevin G M Kou1, Jason J Pflueger1, Toshihiro Kiho1
1Department of Chemistry , University of California, Berkeley , Berkeley , California 94720 , United States.
Journal of the American Chemical Society
|June 12, 2018
まとめ
研究者は,複雑なヘチシン型ディターペノイドアルカロイドの新合成戦略を開発した. このアプローチにより,A環ヒドロキシル化化合物へのアクセスが可能になり,新しい天然および非天然製品の発見の可能性が広がります.
科学分野:
- 有機化学
- 自然製品合成
- 薬剤化学
背景:
- ヘチシン型の天然製品は,複雑な炭素骨格で知られているディターペノイドアルカロイドのクラスです.
- これらの複雑な分子へのアクセスは 構造の複雑さによって困難です
- 以前の合成方法は,A環水酸化などの特定の構造モチーフへのアクセスに制限があります.
研究 の 目的:
- ヘチシン型ディターペノイドアルカロイドの 新しく効率的な合成戦略を開発する.
- Aリングの水酸化ヘチシン誘導体の合成を可能にします.
- このアルカロイドファミリーの内にある自然と非自然な製品の幅広い範囲にアクセスするための多用途のプラットフォームを提供するためです.
主な方法:
- ネットワーク分析を活用してコンバージェント・シンセシス戦略を設計した.
- ベンジンのアチルアルキル化により,溶融した6−7−6の三環原子核を製造した.
- 化学選択によるニトリル還元と連続的なC-N結合形成が組み込まれている.
- 埋め込まれたアザビサイクルの構築のために,還元サイクルと光化学的水酸化を適用した.
主要な成果:
- ヘチシン型複合性ディターペノイドアルカロイドの合成経路を成功裏に確立した.
- Aリングに水酸化を導入する能力を示した.
- 特徴的な融合型 6-7-6 三輪車と組み込みアザビサイクルのコア構造を設計した.
- ベンジンの化学反応と光化学反応を含む重要な変換を検証した.
結論:
- 開発された合成戦略は,A環水酸化によるヘチシン型アルカロイドへのアクセスに有効である.
- この方法論は,ヘチシンアルカロイドファミリー内の化学空間を探索するための強力なツールを提供します.
- この戦略は,新しい生物活性化合物や同類物の発見に 期待を寄せている.
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