トレースレススタウディンガー結合の反応機構と運動学
Matthew B Soellner1, Bradley L Nilsson, Ronald T Raines
1Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Journal of the American Chemical Society
|July 6, 2006
まとめ
無痕のスタウディンガー結合は, (ディフェニルフォスフィノ) メタネチオールを使用したペプチドを効率的に結合します. この方法は,残留原子のないアミド結合を形成し,ペプチド合成の高収量と選択性を提供します.
科学分野:
- 有機化学 オーガニック・ケミストリー
- バイオケミストリー バイオケミストリー
- 化学生物学 化学生物学とは
背景:
- スタウディンガー結合は,アミド結合を形成するためのバイオオートホーゴナル反応です.
- 既存の方法は副産物の形成や効率の欠如に苦しむ可能性があります.
- 高効率で追跡不能なペプチド結合方法が必要である.
研究 の 目的:
- ペプチド結合のための無痕スタウディンガー結合のメカニズムと効率を包括的に特徴付ける.
- この結合のための最適な反応剤と条件を特定する.
- 異なるフォスフィンベースの試薬の性能を比較する.
主な方法:
- 同位体として標識された水 ([(18) O]H(2) O) を用いた詳細なメカニズム研究.
- 速度を決定するステップを決定するために,連続 (13) C NMR ベースの運動測定法.
- (ディフェニルフォスフィノ) メタネチオールやフォスフィノアルコールなどの結合剤の評価.
- 様々な反応条件下での副産物形成の分析.
主要な成果:
- 反応は,アザ-ウィッティッグ反応ではなく,イミノフォスフォラン中間物のS->Nアシル移転を経由して進みます.
- (Diphenylphosphino) メタネチオールは,速度を制限するステップとして,フォスファジド中間形成を通じた結合を媒介する.
- この反応剤は,副産物の蓄積なしに,高収量 (95%) と第2次速度常数 7.7 x 10 (((-3) M ((-1) s ((-1) を達成します.
- フォスフィノアルコールは, (ディフェニルフォスフィノ) メタネチオールと比較して,より低い効率と化学選択性を示した.
結論:
- (ディフェニルフォスフィノ) メタネチオールは,ペプチド結合における無痕スタウディンガー結合のために確認された最も効果的な反応剤です.
- 反応メカニズムはS->Nアシル転送を好み,痕跡のないアミド結合形成を保証します.
- この最適化されたスタウディンガー結合は,ペプチド合成と改変のための堅牢で効率的なツールを提供します.
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