Flow Chemistry-Enabled Divergent and Enantioselective Total Syntheses of Massarinolin A, Purpurolides B, D, E, 2,3-Deoxypurpurolide C, and Structural Revision of Massarinolin A.
Flow Chemistry-Enabled Divergent and Enantioselective Total Syntheses of Massarinolin A, Purpurolides B, D, E, 2,3-Deoxypurpurolide C, and Structural Revision of Massarinolin A.
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DOI：
10.1002/anie.202109625
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发表时间：
2021-11-15
期刊：
影响因子：
--
通讯作者：
Dai M
中科院分区：
文献类型：
--
作者：
Wang YC;Cui C;Dai M
Massarinolin A和purpurolides是生物活性的香柠檬烷倍半萜与多种合成上具有挑战性的环系统缩合：双环[3.1.1]庚烷，oxasipro[3.4]辛烷和二氧杂螺[4.4]壬烷（oxaspirolactone）。本文首次报道了Massarinolin A、purpurolide B、D、E和2，3-deoxypurpurolide C的对映选择性全合成。我们的合成和计算分析也导致了massarinolin A的结构修正。发散方法的特征在于对映选择性有机催化的Diels-Alder反应以在高ee中安装第一个立体中心，可缩放的流动光化学Wolff重排以构建关键的双环[3.1.1]庚烷，呋喃氧化环化以形成氧杂螺内酯，后期烯丙基C-H氧化，以及Myers'NBSH促进的σ迁移消除以安装Massarinolin A的外亚甲基。首次全合成了佛手柑倍半萜化合物massarinolin A，purpurolide B，D，E和2，3-deoxypurpurolide C，其关键步骤包括有机催化的Diels-Alder反应，可扩展的流动光化学Wolff重排，呋喃氧化环化，后期烯丙基C-H氧化和σ迁移消除。我们的合成也导致了massarinolin A的结构修正。
Massarinolin A and purpurolides are bioactive bergamotane sesquiterpenes condensed with a variety of synthetically challenging ring systems: a bicyclo[3.1.1]heptane, an oxasipro[3.4]octane, and a dioxaspiro[4.4]nonane (oxaspirolactone). Herein, we report the first enantioselective total syntheses of massarinolin A, purpurolides B, D, E, and 2,3-deoxypurpurolide C. Our synthesis and computational analysis also led to a structural revision of massarinolin A. The divergent approach features an enantioselective organocatalyzed Diels-Alder reaction to install the first stereogenic center in high ee, a scalable flow photochemical Wolff rearrangement to build the key bicyclo[3.1.1]heptane, a furan oxidative cyclization to form the oxaspirolactone, a late-stage allylic C-H oxidation, and a Myers’ NBSH-promoted sigmatropic elimination to install the exo methylene group of massarinolin A. The first total syntheses of complex bergamotane sesquiterpenes massarinolin A, purpurolides B, D, E and 2,3-deoxypurpurolide C were achieved with key steps involving an enantioselective organocatalyzed Diels-Alder reaction, a scalable flow photochemical Wolff rearrangement, a furan oxidative cyclization, a late-stage allylic C-H oxidation and sigmatropic elimination. Our synthesis also led to a structural revision of massarinolin A.
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影响因子：
5.2
作者：
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通讯作者：
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影响因子：
15
作者：
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15
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通讯作者：
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通讯作者：
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