アミノ酸の非対称的なα-アリレーション
Daniel J Leonard1, John W Ward1, Jonathan Clayden2
1School of Chemistry, University of Bristol, Bristol, UK.
Nature
|October 5, 2018
まとめ
四次性α-アリルアミノ酸を合成することは,ステレオ化学的完全性を失うことなく実現可能である. この新しい方法は簡単に手に入るアミノ酸を使用し,高価な移行金属を避け,マルチグラムの生産を可能にします.
科学分野:
- 有機化学
- 薬剤化学
- 合成化学
背景:
- クォーターナーアミノ酸はペプチド構造とバイオアクティビティの修正に不可欠です.
- 合成的に難しいアミノ酸のエナチオセレクティブα-アリレーションは,価値ある生物活性分子を作るための鍵です.
- エナチオセレクティブアルキル化のための既存の方法は利用可能ですが,α-炭素での一般的なエナチオセレクティブアリレーションは困難です.
研究 の 目的:
- 四次性α-アリルアミノ酸を合成するための実用的でスケーラブルな方法を開発する.
- ステレオ化学的整合性を損なうことなく,アミノ酸前駆体のエナチオ選択的α-アリレーションを達成する.
- 簡単に手に入る材料を使って様々なα-アリルアミノ酸の合成を可能にします.
主な方法:
- α-アリレーションに用いるエナンチオプアアミノ酸前駆体.
- イミダゾリジノン誘導体のN'-アリルウレア添加物で第二のステレオゲンなセンターを一時的に形成する戦略を採用した.
- 合成過程で移行金属の使用を避けました.
主要な成果:
- 高いステレオ化学的整合性を有するエナンチオプアの前駆体から四次性α-アリルアミノ酸を成功して合成した.
- 電子が豊富で,電子が乏しく,ヘテロサイクルのグループを含む幅広い置換物とのアリレーションが実証されています.
- 単一の前体から製品のどちらかのエナンチオマーを生産する能力を示し,マルチグラムの量でのスケーラビリティを示した.
結論:
- 四次性α-アリルアミノ酸のエナンチオセレクティブ合成のための新しい,実用的でスケーラブルな方法を開発した.
- この方法は,医薬品化学の重要な前駆体である様々なα-アリレートアミノ酸への貴重な経路を提供します.
- このアプローチは,以前の合成の制限を克服し,移行金属なしで複雑なアミノ酸派生体にアクセスを提供します.
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