Scholarlink

<p>Riley oxidation is a powerful method for introducing oxygen functionality but typically relies on toxic reagents and generally lacks enantiocontrol. This limitation has historically restricted the utility of this transformation for the direct asymmetric construction of complex scaffolds. Here, we show that fusion library screening and directed evolution enable the highly enantio- and diastereoselective Riley-type oxidation of a <i>cis</i>-diquinane substrate catalyzed by engineered P450<sub>BM3</sub>. This enzymatic desymmetrization strategy provides streamlined access to key chiral <i>cis</i>-diquinane building block on a gram scale, facilitating rapid downstream diversification. Furthermore, by merging this enzymatic desymmetrization with chemical ring formation and late-stage biosynthetic oxidation, we achieve asymmetric total synthesis of pentalenolactone D and <i>neo</i>-pentalenolactone D. This work highlights the power of integrating protein engineering with synthetic chemistry to synthesis of complex natural products.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Chemoenzymatic synthesis of pentalenolactones via stereoselective Riley oxidation by engineered P450BM3

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月10日

查看全文
  • Yaoyao Xu,
  • Kaifeng Zhang,
  • Quanzhen Lv,
  • Jinxin Wang,
  • Jian Li

摘要

Riley oxidation is a powerful method for introducing oxygen functionality but typically relies on toxic reagents and generally lacks enantiocontrol. This limitation has historically restricted the utility of this transformation for the direct asymmetric construction of complex scaffolds. Here, we show that fusion library screening and directed evolution enable the highly enantio- and diastereoselective Riley-type oxidation of a cis-diquinane substrate catalyzed by engineered P450BM3. This enzymatic desymmetrization strategy provides streamlined access to key chiral cis-diquinane building block on a gram scale, facilitating rapid downstream diversification. Furthermore, by merging this enzymatic desymmetrization with chemical ring formation and late-stage biosynthetic oxidation, we achieve asymmetric total synthesis of pentalenolactone D and neo-pentalenolactone D. This work highlights the power of integrating protein engineering with synthetic chemistry to synthesis of complex natural products.