ミニマルテトラジンの設置は,アルリルボロン酸によるシルバーメディエートされたリベスキンド-スログル結合による
William D Lambert1, Yinzhi Fang1, Subham Mahapatra2
1Department of Chemistry and Biochemistry , University of Delaware , Newark , Delaware 19716 , United States.
Journal of the American Chemical Society
|October 12, 2019
まとめ
新しいシルバーメディエートクロスカップリング法により,最小のテトラジン群を複雑な分子に直接結合させ,リンクナーを回避し,安全性を向上させる. このアプローチはバイオオートゴーナル化学の応用と探査機の開発を促進します.
科学分野:
- 有機化学
- バイオオートゴーナル化学
- 薬剤化学
背景:
- 複合分子にバイオオートホーグナルテトラジンを付着させるには,しばしばリンカーが必要で,これは生理化学的性質に悪影響を及ぼします.
- テトラジン装置の従来の方法は,危険な反応剤と副産物を含みます.
研究 の 目的:
- 複雑な分子に最小のテトラジン群を設置するための,新しい,リンカーフリーな方法を開発する.
- テトラジン合成と応用の安全性と効率性を向上させる.
主な方法:
- 銀媒介のリベスキンド-スログルクロスカップリング反応は,新しい反応剤,3- (((p-ビフェニル-4-イルメチル) チオ) -6メチルテトラジン (b-Tz) を使用して採用された.
- 反応は軽度な条件下でPdCl2 ((dppf) によって触媒化された.
- 新しい反応剤 (b-Tz) は,安全でスケーラブルな製剤として設計された.
主要な成果:
- Ag媒介のクロスカップリングは,伝統的な方法と比較してより高い収量を持つ様々なアリルおよびヘテロアリルボロン酸に,リンカーフリーで最小の6-メチルテトラジニル機能を導入することに成功しました.
- フローロゲンテトラジン- BODIPY結合体が合成され,アクセスの改善が示されました.
- MAGL (モノアチルグリセロールリパゼ) の共性プローブが作成され,生細胞における内在的なMAGLを標識するために使用されました.
結論:
- 開発されたAg媒介クロスカップリング方法は,テトラジンサブユニットを複雑な分子に直接インストールするための多用途で安全な経路を提供します.
- このアプローチは,新しい結合体と探査機の作成を可能にすることで,バイオオルトゴン化学,化学生物学,および薬物の発見を前進させると期待されています.
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