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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
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ラジカルメディエートされた三要素結合と7エンドサイクリングによって可能になった樹脂フェラトキシンの総合成
Satoshi Hashimoto1, Shun-Ichiro Katoh1, Takehiro Kato1
1Graduate School of Pharmaceutical Sciences, The University of Tokyo , Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Journal of the American Chemical Society
|October 19, 2017
まとめ
この研究は,強力なTRPV1アゴニストであるレシニフェラトキシンを合成するための新しい根基ベースの戦略を提示しています. この新しい方法は複雑なトリサイクルコアを効率的に構築し,複雑な分子の合成に多用途なアプローチを提供します.
科学分野:
- 有機化学
- 合成化学
- 薬剤化学
背景:
- レシニフェラトキシン (1) は,疼痛と熱の重要なトランスデューサーであるTRPV1に強力なアゴニスティック効果を持つダフナンのディターペノイドです.
- 濃度の高い酸素を吸収したトランス融合5/7/6トリカルボサイクルの核は,重要な合成課題を提示する.
- 現在の合成戦略は このような複雑な分子構造を 効率的に組み立てる能力に 限界があります
研究 の 目的:
- 樹脂フェラトキシン (1) の全合成のための新しい根基ベースの戦略を開発する.
- 複雑なカーボサイクルのシステム内で阻害された結合を構築する際の急性反応の有用性を実証する.
- 複雑な天然製品の多段階の標的型合成のための新しい戦略的設計を提供すること.
主な方法:
- Aリング,アリルスタナン,Cリングの断片を含む3つの構成要素の戦略が採用されました.
- 最初の基質反応は,AとCのリングの連続結合のためのα-アルコキシブリッジヘッド基質を生成した.
- 第2の急性反応では7基のB環のサイクル化,ステレオセンターの構築,そしてオレフィンの設置が達成された.
主要な成果:
- レシニフェラトキシンを 密度が高い酸素で融合した 5/7/6トリカルボサイクルを 組み立てました
- 効率的に形成された過激な戦略はC9,10結合を阻害し,C4鎖をステレオ選択的に拡張しました.
- 合成は,高度に最適化された化学選択的変換によって樹脂フェラトキシンを生成した.
結論:
- 開発されたラジカルベースの戦略は,レシニフェラトキシンを合成するための効率的で汎用的なアプローチを提供します.
- この方法論は,機能群の損傷なしに複雑な炭水化物を構築するための根性反応の利点を強調する.
- この戦略は,複雑な分子を標的とした多段階合成の設計のための新しいパラダイムを提供します.
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