Network-analysis-guided synthesis of weisaconitine D and liljestrandinine.
Network-analysis-guided synthesis of weisaconitine D and liljestrandinine.
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DOI：
10.1038/nature16440
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发表时间：
2015-12-24
期刊：
影响因子：
64.8
通讯作者：
Sarpong R
中科院分区：
文献类型：
--
作者：
Marth CJ;Gallego GM;Lee JC;Lebold TP;Kulyk S;Kou KG;Qin J;Lilien R;Sarpong R
有机化合物的化学合成的一般策略，特别是结构复杂的天然产物，不容易确定。在这里，我们提出了一种方法来建立这样的合成，这开始于一个过程称为“网络分析”的战略。这项工作，沿着与其他考虑，已被用来确定一个多功能的合成中间体，促进合成的二萜生物碱魏乌头碱D和liljestandinine，以及核心的gomandestine。二萜类生物碱包括一些结构上最复杂和功能团密集的次生代谢产物。由于这些原因，它们对化学合成提出了重大挑战。本文所述的合成方法与用于合成相关结构的其他策略显著不同，并且不仅提供了目标天然产物，而且还提供了二萜生物碱的三个亚家族（即，C-18，C-19和C-20），为这些天然产物提供了第一个统一的合成策略。这项工作验证了效用的网络分析作为一个起点，确定策略的合成结构复杂的次级代谢产物。一个易于访问的基于网络的绘图程序已经开发了这一目的。
General strategies for the chemical synthesis of organic compounds, especially of architecturally complex natural products, are not easily identified. Here, we present a method to establish a strategy for such syntheses, which begins with a process termed ‘network analysis’. This exercise, along with other considerations, has been used to identify a versatile synthetic intermediate that facilitated syntheses of the diterpenoid alkaloids weisaconitine D and liljestrandinine, as well as the core of gomandonine. The diterpenoid alkaloids comprise some of the most architecturally complex and functional group dense secondary metabolites ever isolated. For these reasons, they present a significant challenge for chemical synthesis. The synthesis approach described herein is a notable departure from other strategies adopted for the syntheses of related structures and affords not only the targeted natural products, but also intermediates and derivatives in the three subfamilies of diterpenoid alkaloids (i.e., C-18, C-19, and C-20), providing the first unified synthetic strategy to these natural products. This work validates the utility of network analysis as a starting point for identifying strategies for the syntheses of architecturally complex secondary metabolites. An easily accessible web-based graphing program has been developed for this purpose.