ラジカルSAMメチルトランスファーゼにインスパイアされたヘテロアレンのC-Hメチル化
Jinghan Gui1, Qianghui Zhou, Chung-Mao Pan
1Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Journal of the American Chemical Society
|March 12, 2014
まとめ
研究者らは,亜鉛二酸化硫化フェニルソルフォニルメタネスルフィネート (PSMS) を使用してヘテロアレンをメチル化するための新しいC-H機能化方法を開発しました. この多用途な方法は,薬剤のような分子の遅段階の機能化を,穏やかな条件下で可能にします.
科学分野:
- 有機化学 オーガニック・ケミストリー
- 合成方法論 合成方法論
- 薬用化学 薬用化学について
背景:
- C-H機能化は,有機分子を変更するための直接的な経路を提供します.
- メチル化は,生物活性化合物の合成における重要な変換である.
- 自然のメチル化剤であるS-アデノシルメチオニン (SAM) は,新しい合成アプローチにインスピレーションを与えました.
研究 の 目的:
- ヘテロアレンメチル化のための実用的で汎用的なC-H機能化の方法を開発する.
- 後期段階の機能化のために,敏感な機能群と互換性のあるプロトコルを作成する.
- 異なる合成経路を通って医学的に重要なモチーフにアクセスするために.
主な方法:
- 新型メチル化反応剤として亜鉛ビス・フェニル・スルフォニルメタン・スルフィネート (PSMS) の開発.
- PSMSとヘテロアレンとの反応により,分離可能な (フェニル硫ニル) メチル化中間物質が形成されます.
- メチル化またはデウテリオメチル化製品を得るための中間物の脱硫化または加工.
主要な成果:
- ヘテロアーレンのための軽い,操作的に単純なC-Hメチル化プロトコルが確立されました.
- この方法は,室温の露天条件下で行われます.
- このプロトコルは,敏感な機能群との互換性を実証し,後期段階の機能化を可能にします.
結論:
- PSMSは,ヘテロアレンメチル化のための効率的かつ実用的なアプローチを提供します.
- 開発された方法は,メチル化およびデュテリオメチル化化合物を合成するための多用途のプラットフォームを提供します.
- この戦略は,薬理学的に重要な基質の後期的な機能化を容易にする.
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