ベンジル系およびアリル系C3) -H結合の酵素性一次アミネーション
Zhi-Jun Jia1, Shilong Gao1, Frances H Arnold1
1Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC 210-41, Pasadena, California 91125, United States.
Journal of the American Chemical Society
|May 27, 2020
まとめ
研究者は,直接のC ((sp3) -H結合アミネーションのための新しい酵素を開発し,ヒドロキシラミン誘導体からプライマリアミンを生成した. この生物触媒法では,有価なアミン化合物を合成するのに高い選択性と効率性があります.
科学分野:
- 生物触媒と酵素工学
- 有機合成
- 薬剤化学
背景:
- アリファティック・プライマリ・アミンは,医薬品,天然製品,および材料科学における重要な構成要素です.
- 既存の合成経路は,多くの場合,多段階のプロセスを必要とする直接のC ((sp3) -H結合機能化がない.
- 活性化されていないC−H結合にアミン群を直接組み込むことは,依然として重要な合成課題である.
研究 の 目的:
- C ((sp3) -H結合の直接アミネーションのための新しい生物触媒方法を開発する.
- 選択的プライマリアミン合成を可能にする 自然に新しい酵素を作り出すこと
- 簡単に手に入るヒドロキシラミン系を窒素源として利用する.
主な方法:
- 誘導進化は,サイトクロームP411酵素 (Cysリガンドの代わりにSerを持つP450変種) を設計するために使用されました.
- エンジニアリングされた酵素は,ベンジルおよびアリルC-H結合の選択的機能化に最適化されました.
- ハイドロキシラミン誘導体は,生物触媒的変換におけるアミン源として使用された.
主要な成果:
- 新種の酵素が生成され,高化学的,地域的,およびエナチオ選択性を持つC ((sp3) -H結合の直接的初次アミネーションを触媒化する.
- 機能化されたベンジルアミンおよびアリルアミンを含め,幅広いエンアンチオ濃縮原始アミンが合成されました.
- 生物触媒プロセスは,高効率 (最大3930 TTN) とエナチオ選択性 (最大96% ee) を示し,製剤スケールに適した.
結論:
- この研究は,直接のC ((sp3) -H初次アミネーションのための最初の前代未聞の生物触媒方法を示しています.
- エンジニアリングされたサイトクロームP411酵素は,多様なプライマリアミンのエナチオセレクティブ合成のための強力なプラットフォームを提供します.
- 開発された方法論は,価値あるアミン化合物にアクセスするための効率的で持続可能な代替手段を提供します.
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