(+) -インゲノールの簡潔な合成の開発

Steven J McKerrall¹, Lars Jørgensen, Christian A Kuttruff

¹Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.

Journal of the American Chemical Society

|April 10, 2014

まとめ

研究者らは,抗癌薬の重要な成分である複合体ディテルペノイド (+) -インゲノールの新合成を開発しました. この2段階のアプローチは,天然のテルペン生物合成を模倣し,重要な化学的課題を克服します.

科学分野:

有機化学オーガニック・ケミストリー
自然製品合成自然製品合成
薬用化学薬用化学について

背景:

複合型ディテルペノイド (+) -インゲノールは,最近承認された抗癌薬の核構造である.
その独特で挑戦的な脚立は,重要な合成障害を提示します.
そのバイオシンセシスを理解することで,薬の開発と合成戦略に情報を与えることができます.

研究の目的:

(+) -インゲノールの短時間かつ効率的な合成を開発する.
天然のテルペン生物合成経路に従って合成をモデル化する.
ピナコール再配列を含む重要な化学的変換を調査する.

主な方法:

2段階の合成アプローチ: 7段階のサイクラス相と7段階の酸化相.
初期炭素フレームワークの構築にパウソン・カンド反応を用いた.
密度関数理論 (DFT) の計算を用いて,ピボタルピナコール再配置を分析した.

主要な成果:

チグリアン型コアを (+) - 3 - カレンからサイクラース相で成功して合成した.
競合するピナコール再配列とサイクル反応からの課題を克服しました.
7段階の酸化酵素相を開発し, (+) -インゲノール. を生成した.

結論:

(+) -インゲノルの簡潔で二相合成が達成され,自然生物合成にインスパイアされました.
この研究は,複雑なディターペノイド合成における合成的な課題を克服するための洞察を提供します.
ピナコール再配列のDFT分析は,反応機構と生物合成の影響をより深く理解することができます.

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