末期酸化C ((sp3) -Hメチル化
Kaibo Feng1, Raundi E Quevedo1, Jeffrey T Kohrt2
1Department of Chemistry, Roger Adams Laboratory, University of Illinois, Urbana, IL, USA.
Nature
|March 18, 2020
まとめ
この研究は,メチル基を複合分子に添加し,薬剤の効力を高める新しい方法を紹介しています. この後期段階のC ((sp3) -Hメチル化技術は効率的で,医薬品化学において広く適用できる.
科学分野:
- 有機化学
- 薬剤化学
- カタリシス
背景:
- "マジックメチル効果"は,特にヘテロ原子に隣接するメチル群を加えることで,生物学的に活性な分子の効能を大幅に高めます.
- 既存のメチル化方法は,複雑な分子構造への適用範囲と適用範囲に制限があり,薬の開発を妨げています.
研究 の 目的:
- 薬物の構造と天然製品の後期機能化のための地域選択的および化学選択的酸化C ((sp3) -Hメチル化方法を開発する.
- 複雑な分子の効率的で標的化されたメチル化を可能にし",魔法のメチル効果"の探求を容易にする.
主な方法:
- マンガン触媒 (Mn(CF3PDP) を使用して,サイト選択C-H水酸化と軽度の機能群耐性メチル化を組み合わせた新しいアプローチ.
- オルガノアルミニウム反応剤でメチル化するための反応性中間物質の形成を補助するフッ素またはルイス酸を使用した.
- 医学的に重要なコア,薬物,天然製品を含む41の異なる基板にこの方法を適用しました.
主要な成果:
- テディゾリドや天然製品などの薬剤を含む18の薬理学的に重要な分子に,サイト選択的C ((sp3) -Hメチル化が達成された.
- 後期メチル化による2つの"マジックメチル"薬剤候補の成功合成が実証された.
- アビラテロンアナログのリモートメチル化が示され,その方法の汎用性を強調した.
結論:
- 開発された方法は,複雑な薬物構造と天然製品と互換性のある,後期段階のC ((sp3) -Hメチル化のための強力なツールを提供します.
- この技術は合成の努力を大幅に減らし,新しい治療法や化学探査の発見と開発を加速します.
- 医学化学の研究における"魔法のメチル効果"の適用を拡大する.
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