エピメリゼーションなしのアンポルングアミド合成によるN-アリルアミドの製造
Michael S Crocker1, Zihang Deng1, Jeffrey N Johnston1
1Department of Chemistry and Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37235, United States.
Journal of the American Chemical Society
|September 6, 2022
まとめ
N-アリルアミド合成の新しい方法は,α-フッ素ニトロアルカンとN-アリルヒドロキシルアミンを用いて直接エナンチオプア製品を生成します. このUmpolungアミド合成 (UmAS) のアプローチは,薬の開発に不可欠なエピメリゼーションを回避します.
科学分野:
- 有機化学
- 合成化学
- 薬剤化学
背景:
- アミド合成は薬物開発とペプチド合成に不可欠ですが,現在の方法は,特にN-アリルアミドの廃棄物削減とα-エピメリゼーションに苦労しています.
- 既存のアミド形成プロトコルは,主に核愛性アミンと反応する電友性アシルドナーに依存しています.
- ウンポルングアミド合成 (UmAS) は,エナチオプアミド合成を提供しているが,N-アリルアミドを形成できないため制限されている.
研究 の 目的:
- N-アリルアミドの直接合成のための新しい方法を開発し,現在のアミド形成戦略の限界に対処する.
- 薬の発見においてますます重要になってきた α-キラルN-アリルアミドの合成を可能にする.
- 立体化学的整合性を保持する N-アリルアミドの触媒的,エナンチオセレクティブ合成を確立する.
主な方法:
- ブロンステッド塩基プロモーターを用いたα-フッ素ニトロアルカンとN-アリルヒドロキシルアミンの反応
- UmAS パラダイムに基づくメカニズム的仮説による反応機構の探索.
- エナンチオ濃縮を完全に保存したキラルα-アミノ-N-アリルアミドの合成
主要な成果:
- N-アリルアミドの直接合成は,α-フッ素ニトロアルカンとN-アリルヒドロキシルアミンを用いて達成される.
- 反応はUmASパラダイムを経て,N-アリルアミドを直接生成する.
- 選択されたキラルα- アミノ- N- アリルアミドの合成において,エンアンチオ濃縮の完全な保存が観察された.
結論:
- N-アリルアミドを合成するための新しい効率的な方法が確立され,以前の制限を克服しました.
- 開発された方法は,製薬用途に不可欠なエナンチオピュア N-アリルアミドを製造するのに適しています.
- このアプローチは,特に基板に挑戦し,ステレオ化学的忠誠性を維持するために,アミド合成の重要な進歩を提供します.
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