Oxidative Indole Dearomatization for Asymmetric Furoindoline Synthesis by a Flavin-Dependent Monooxygenase Involved in the Biosynthesis of Bicyclic Thiopeptide Thiostrepton
Oxidative Indole Dearomatization for Asymmetric Furoindoline Synthesis by a Flavin-Dependent Monooxygenase Involved in the Biosynthesis of Bicyclic Thiopeptide Thiostrepton
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DOI：
10.1002/anie.202013174
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发表时间：
2021-03-03
影响因子：
16.6
通讯作者：
Liu, Wen
中科院分区：
文献类型：
--
作者：
Lin, Zhi;Xue, Yufeng;Liu, Wen
吲哚脱芳构化反应是生物碱类天然产物全合成中的一种有效手段，近年来，人们对吲哚脱芳构化反应的研究又有了新的进展，目的是开发出既能有效控制产率又能有效控制立体选择性的新方法。在这里，我们报告了一个酶的方法氧化脱芳构化吲哚的不对称合成的各种furoindolines与邻位的季碳立体中心。这种方法依赖于黄素依赖性单加氧酶TsrE的活性，TsrE参与双环硫肽抗生素硫链丝菌素的生物合成。TsrE在2-甲基-吲哚-3-乙酸或2-甲基-甲醇转化为呋喃并吲哚啉的过程中以高度对映选择性的方式催化2，3-环氧化和随后的环氧化物开环，在温和的反应条件下具有高达> 99%的转化率和> 99%ee。补充目前的化学方法氧化吲哚脱芳构化，TsrE活性为基础的方法丰富了工具箱中的不对称合成的产品具有呋喃并吲哚骨架。
The interest in indole dearomatization, which serves as a useful tool in the total synthesis of related alkaloid natural products, has recently been renewed with the intention of developing new methods efficient in both yield and stereoselective control. Here, we report an enzymatic approach for the oxidative dearomatization of indoles in the asymmetric synthesis of a variety of furoindolines with a vicinal quaternary carbon stereogenic center. This approach depends on the activity of a flavin-dependent monooxygenase, TsrE, which is involved in the biosynthesis of bicyclic thiopeptide antibiotic thiostrepton. TsrE catalyzes 2,3-epoxidation and subsequent epoxide opening in a highly enantioselective manner during the conversion of 2-methyl-indole-3-acetic acid or 2-methyl-tryptophol to furoindoline, with up to >99 % conversion and >99 % ee under mild reaction conditions. Complementing current chemical methods for oxidative indole dearomatization, the TsrE activity-based approach enriches the toolbox in the asymmetric synthesis of products possessing a furoindoline skeleton.