触媒的非対称性およびステレオダイバーゲントオリゴヌクレオチド合成
Aaron L Featherston1, Yongseok Kwon1, Matthew M Pompeo1
1Department of Chemistry, Yale University, New Haven, CT 06520, USA.
Science (New York, N.Y.)
|February 12, 2021
まとめ
チラルのリン酸触媒は,ダイヌクレオチドのステレオ制御合成を可能にします. この方法は,STING経路を標的とした免疫腫瘍学アプリケーションにとって不可欠な特定のリン酸二酸化物へのアクセスを提供します.
科学分野:
- 有機化学
- カタリシス
- 薬剤化学
背景:
- ディヌクレオチドのステレオ制御合成は難しい
- リン性ステレオセンターはダイヌクレオチドの構造と機能において重要な役割を果たします.
- 既存の方法はしばしばステキオメトリックアクティベーターまたはキラル補助器を必要とします.
研究 の 目的:
- ステレオ制御のダイヌクレオチド合成のための触媒的方法を開発する.
- phosphoramidite 転送反応で高いダイアステロディバージェンスを達成する.
- ディヌクレオチド合成におけるキラルリン酸 (CPA) 触媒の応用について調べる.
主な方法:
- カイラルリン酸 (CPA) の触媒を用いて,フォスフォラミド酸の移転を行いました.
- ペプチド埋め込みのフォスフォトレオニン誘導体とC2対称のBINOL誘導体の2つの異なるCPA基板を使用しています.
- ダイアステロエーマーとサイクリック・ディヌクレオチドを合成するために触媒法を適用した.
主要な成果:
- ステレオジェニック・フォスファース・センター形成に対する触媒制御を証明した.
- 前例のないレベルのダイアステロディバージェンスを達成し,フォスフィートダイアステロエーマーへのアクセスを可能にしました.
- 異なるCPAスキャフォールドが基質のステレオ化学的偏好を強めるか逆転させる能力を示した.
結論:
- 容易に入手可能なフォスフォラミド酸塩を用いたダイヌクレオチドの新種の触媒的非対称合成を開発した.
- この方法はステキオメトリックアクティベーターとキラル補助器を避けます.
- STING経路アゴニストとして免疫腫瘍学における潜在的な応用を持つダイヌクレオチドとサイクルダイヌクレオチドを成功裏に合成した.
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