アルデヒドへの分子間基質添加によって可能になったヒキジミシンの収束総合成
Haruka Fujino1, Takumi Fukuda1, Masanori Nagatomo1
1Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Journal of the American Chemical Society
|July 7, 2020
まとめ
研究者らは新しい激素結合反応を用いて 複雑な核酸抗生物質ヒキジミシンを合成した. この効率的な17段階の合成は 価値ある生物活性天然製品を作るための新しい戦略を提供します
科学分野:
- 有機化学
- 薬剤化学
- 合成化学
背景:
- ヒキジミシン (1) は強力な甲虫駆除性核酸抗生物質である.
- それは10のステレオセンターを持つ高度に機能した4-アミノ-4-デオキシンドコースのコアを特徴としています.
- その複雑な構造は,総合成に重大な課題を提示します.
研究 の 目的:
- ヒキジミシンを完全に合成する (1).
- 核アンデコス鎖の構築のための新しい根性結合反応を開発し,適用する.
- 効率的な合成経路を確立し 機能的グループ操作を最小限に抑える
主な方法:
- グルコース派生体 (4),サイトシン (5),d-マノース (9),d-ガラクトース派生体 (10) の4つの既知の成分を用いた収束合成.
- 水酸化アルデヒドとα-アルコキシアシルテロリドの間の新しい根 coupling 反応の開発.
- アルデヒドにラジカル生成と分子間添加を用い,選択的グリコシル化とデプロテクションを繰り返す.
主要な成果:
- ハキジミシン (1) をd-ガラクトーゼ派生物 (10) から17段階で成功して合成した.
- 新しく開発されたラジカルカップリング戦略により,C5とC6のステレオセンターが効率的に設置されました.
- 複合分子合成におけるアルデヒドへの分子間激素添加の汎用性を示した.
結論:
- 開発された合成戦略は,ヒキジミシンへの効率的な経路を提供します.
- この研究は,複雑な核酸抗生物質の全合成のための新しいアプローチを示しています.
- この方法は他の生物活性天然製品を合成する可能性を秘めている.
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