ストレプチドの総合成とステレオ化学的配分
Nicholas A Isley1, Yusuke Endo1, Zhi-Chen Wu1
1Department of Chemistry and Skaggs Institute for Chemical Biology , The Scripps Research Institute , 10550 North Torrey Pines Road , La Jolla , California 92037 , United States.
Journal of the American Chemical Society
|October 3, 2019
まとめ
複合的なマクロサイクルの天然産物であるストレプチドの最初の完全な合成は,そのユニークなライシン-トリプトファンクロスリンク構造を確認しました. この合成は,自然製品に存在する正しい3Rライシン二酸化物を特定して,ステレオ化学を明確にします.
科学分野:
- 自然製品合成
- 有機化学
- 薬剤化学
背景:
- ストレプチド (1) は2015年に発見されたマクロサイクル天然製品です.
- リジンとトリプトファンの残留を結びつける異常な翻訳後の改変が特徴です.
- この独特な構造は 20個の周期性ペプチドを形成します
研究 の 目的:
- ストレプチドの最初の完全な合成を 達成するために
- リジン・トリプトファン・クロスリンクの 地域化学を確認する
- リスン2のC3センターのステレオ化学を明確に指定します.
主な方法:
- マクロサイクライゼーションのためにPd(0) 介在のインドル無効化を使用した.
- パラジアム触媒によるC-H活性化/β-アリレーションを用いて,高価ヨウ素 (III) アリル基板を使用した.
- 3Rと3Sライシン二ステロエーマーを合成した.
主要な成果:
- ストレプチドの合成が成功し 交差リンクの 提案されたレジオケミストリーが確認されました
- 自然製品には,前述の3Sではなく,3Rライシンダイアステロエーマーが含まれていることが確認された.
- 生物学的調査のために ストレプチドを手に入れた
結論:
- トータル合成は ストレプチドの独特の構造特性を検証します
- リスン残基の正しいステレオ化学は決定的に割り当てられました.
- この研究は,ストレプチドおよび関連化合物の生物学的役割に関する将来の研究を可能にします.
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