バイオカタリティック非対称ケトン還元における誘導された軸性キラリティ
Rubén Agudo1, Gheorghe-Doru Roiban, Manfred T Reetz
1Department of Chemistry, Philipps-Universität Marburg, Hans-Meerwein Str., 35032 Marburg, Germany.
Journal of the American Chemical Society
|October 19, 2012
まとめ
アルコール脱水酵素は,キラルアルコールへのケトンの非対称的還元を触媒化し,過渡金属触媒を上回る. 誘導的進化は,価値あるキラル構造ブロックを合成するために,エナチオセレクティビティの逆転を可能にしました.
科学分野:
- 有機化学 オーガニック・ケミストリー
- バイオカタリシス バイオカタリシス
- アシンメトリック・シンセシス
背景:
- キラルアルコールは,医薬品と細かい化学薬品の重要な構成要素です.
- プロキラルケトンの非対称的減少は,キラルアルコール合成における重要な変化である.
- この減少のために効率的で選択的な触媒を開発することは,依然として重要な課題です.
研究 の 目的:
- 4-アルキリデネ・サイクロヘクサノンを,R構成のアルコールに触媒的に非対称的に還元する.
- エナチオセレクティビティを逆転させるための誘導進化の可能性を調査する.
- 合成されたキラルアルコールを,その後の触媒反応で利用する.
主な方法:
- アルコールデヒドロゲネーゼを用いた酵素還元.
- 飽和変異による導かれた進化.
- パラジウムで触媒化されたカスケード反応.
主要な成果:
- アルコール脱水素化剤を使用したRアルコールの高エナンチオ選択性 (最大99% ee)
- 誘導演化によるSアルコール (最大98% ee) へのエナンチオセレクティビティの成功逆転.
- Pd触媒のカスケード反応におけるR-およびS-アルコールの有用性が実証された.
結論:
- アルコール脱水素化酵素は,プロキラルケトンの非対称的減少に非常に有効であり,優れたエナチオセレクティブ性を持つR構成のアルコールを生成します.
- 誘導進化は,酵素活性を微調整し,逆のエナチオセレクティブ性を達成するための強力な戦略を提供します.
- 合成されたキラルアルコールは,カスケード反応による複雑な分子合成のための多用途の中間物質として機能する.
関連する概念動画
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