総合合成とNMR化学シフト分析による (+) -アンフィディノリドaの構造解明
Barry M Trost1, Paul E Harrington
1Department of Chemistry, Stanford University, California 93405-5080, USA. bmtrost@stanford.edu
Journal of the American Chemical Society
|April 22, 2004
まとめ
研究者らは,NMR分析と全合成を用いて,細胞毒性マクロリドである (+) -アンフィディノリドAの構造を明らかにした. これにより,正しいステレオ化学が確認され,その準備のための信頼できる方法が提供されました.
科学分野:
- 有機化学 オーガニック・ケミストリー
- 自然製品 化学 化学
- 薬用化学 薬用化学について
背景:
- (+) -アンフィディノリドAは,治療用途の可能性のある細胞毒性マクロリドです.
- 以前の構造的割り当ては,相対的立体化学のエラーを含んでいる可能性があります.
- 正確な構造的決定は,生物学的活動を理解し,さらなる研究を可能にするために不可欠です.
研究 の 目的:
- (+) -アンフィディノリドAの構造を明確にするために.
- 以前に報告された相対的立体化学のエラーを修正するために.
- (+) -アンフィディノリドAおよびそのアナログを製造するための信頼性の高い全合成を開発する.
主な方法:
- 合成されたダイアステロエーマーと分離された天然製品を比較するために,核磁気共鳴 (NMR) 化学シフト分析を使用しました.
- さまざまなダイアステロエーマー製剤を含む (+) -アンフィディノリドAの全合成を行った.
- 主要なマクロサイクリングステップのために,ルテニウム触媒によるアルケン-アルキン結合反応を使用した.
主要な成果:
- (+) -アンフィディノリドAの合成に成功し,その提案された構造が確認されました.
- 詳細なNMR分析により,以前に報告された同位体における相対的立体化学の誤差を特定し,修正しました.
- 合成された化合物のスペクトル測定データは,分離された天然製品との優れた一致を示した.
- 合成は,PF6で触媒化された[Cp*Ru(MeCN) 3アルケン-アルキン結合で20個の環を形成した.
結論:
- (+) -アンフィディノリドAの構造は明確に決定されています.
- 開発された全合成は,この細胞毒性マクロリドにアクセスするための実行可能な経路を提供します.
- この研究は,以前の立体化学的割り当てを修正し,将来のアナログ開発のための合成戦略を検証します.
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