マノペプチミシンαとβの総合成
Bo Wang1, Yunpeng Liu1, Rui Jiao1
1Department of Chemistry, The Pennsylvania State University , University Park, Pennsylvania 16802, United States.
Journal of the American Chemical Society
|February 26, 2016
まとめ
耐性菌に対する強力な抗生物質 マノペプチミシンが初めて合成されました この突破は,これらのグリコペプチドの天然製品に複雑な糖結合を構築するために,新しい金触媒のN-グリコシレーションを伴う.
科学分野:
- 有機化学
- 薬剤化学
- 自然製品合成
背景:
- マノペプチミシンは,多剤耐性グラム陽性細菌に対する有意な抗生物質活性を持つグリコペプチド天然産物です.
- その複雑な構造には,β-ヒドロキシエンデュラシディンなどの異常なアミノ酸と,複雑なO-およびN-結合グリコシレーションパターンが特徴です.
研究 の 目的:
- マノペプチミシンαとβの最初の完全合成を報告し,その完全なNとO結合糖を含みます.
- マノペプチミシン内の難しいグリコシド結合の構築のための効率的な合成戦略を開発する.
主な方法:
- 高効率でステレオ選択性を有するステリカルに阻害されたN-Man-D-βhEnd単体を合成するために,金触媒によるN-グリコシレーションが使用された.
- L-βMePheユニットを製造するために,パラジウム触媒によるC-Hアリレーションを使用した.
- 環状ペプチド基板の収束組成と,その後のグローバル水解解脱.
主要な成果:
- マノペプチミシンαとβの完全なN-およびO-グリコシル化による完全な合成が成功しました.
- L-βhEnd,D-Tyr(di-Man),およびL-βMePheを含む主要な構成要素のグラムの量を準備した.
- 金で触媒化されたN-グリコシライゼーションは,挑戦的なN-Man-D-βEnd分子を効率的に形成するために重要であることが証明された.
結論:
- マノペプチシンαとβの最初の完全な合成は,これらの複雑なグリコペプチドの天然製品を作る可能性を示しています.
- 開発された合成方法,特に金触媒によるN-グリコシレーションは,関連する複雑な分子にアクセスするための貴重なツールを提供します.
- この研究は,マンノペプチミシンの生物学的活動と潜在的な治療用途のさらなる調査の道を開く.
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