Total Synthesis of the Originally Assigned Structure of Vannusal B
Total Synthesis of the Originally Assigned Structure of Vannusal B
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DOI：
10.1002/anie.200804228
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Dagneau, Philippe
中科院分区：
文献类型：
--
作者：
Nicolaou, K. C.;Zhang, Hongjun;Dagneau, Philippe
Vannusals A（1a，图 1）和 B（1b）是两种海洋天然产品，以其独特的分子结构而闻名。这些有趣的分子从热带间质纤毛虫 Euplotes vannus 菌株 Si121 和 BUN3 中分离出来，其 C30 分子框架中包含七个环和十三个立体中心，其中三个是四级中心。它们的结构是根据质谱、核磁共振波谱数据和化学转化确定的。[1, 2] 在此，我们报告了结构 1b 的全合成，证明它并不代表 vannusal B 的真实结构。我们对 vannusal 分子的逆合成分析对其进行了剖析，如图 2 所示，揭示了碘乙烯 2 和醛 3 是预计全合成所需的关键构建单元。设计的策略预期它们通过两个碳-碳键形成反应进行融合，即2的锂化，然后添加3加入它们，以及钐诱导后续中间体的闭环，以形成目标分子的最终环。
Vannusals A (1a, Figure 1) and B (1b) are two marine natural products notable for their unusual molecular architectures. Isolated from the tropical interstitial ciliate Euplotes vannus strains Si121 and BUN3, these intriguing molecules include in their C30 molecular framework seven rings and thirteen stereogenic centers, three of which are quaternary. Their structures have been assigned on the basis of mass spectrometric and NMR spectroscopic data and chemical transformations.[1, 2] Herein we report the total synthesis of structure 1b that proved that it does not represent the true structure of vannusal B.Our retrosynthetic analysis of the vannusal molecule dissected it as shown in Figure 2, revealing vinyl iodide 2 and aldehyde 3 as the key building blocks required for the projected total synthesis. The devised strategy anticipated their fusion through two carbon–carbon bond forming reactions, namely lithiation of 2 followed by addition of 3 to join them, and a samarium-induced ring closure of a subsequent intermediate to forge the final ring of the target molecule.