Journal Article

Network-analysis-guided synthesis of weisaconitine D and liljestrandinine

Sarpong, R., Lebold, T. P., Gallego, G. M., Qin, J., Marth, C. J., Kulyk, S., Lilien, R., Lee, J. C., Kou, K. G. M.

2015

Overview

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 uses network analysis. This approach has led to the identification of a versatile synthetic intermediate that facilitated syntheses of the diterpenoid alkaloids weisaconitine D and liljestrandinine, and the core of gomandonine. We also developed a web-based graphing program that allows network analysis to be easily performed on molecules with complex frameworks. The diterpenoid alkaloids comprise some of the most architecturally complex and functional-group-dense secondary metabolites isolated. Consequently, they present a substantial challenge for chemical synthesis. The synthesis approach described here is a notable departure from other single-target-focused strategies adopted for the syntheses of related structures. Specifically, it affords not only the targeted natural products, but also intermediates and derivatives in the three subfamilies of diterpenoid alkaloids (C-18, C-19 and C-20), and so provides a unified synthetic strategy for 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. WebNetwork analysis to determine the maximally bridged ring (or rings) of molecules is used as part of a strategy for the syntheses of architecturally complex natural chemicals; this strategy is demonstrated via the synthesis of the diterpenoid alkaloids weisaconitine D and liljestrandinine. To complex molecules via network analysis Rich Sarpong and colleagues have developed a unified strategy for the synthesis of multiple members of the diterpenoid alkaloid family using a development of the 'network analysis' approach formalized by E. J. Corey in the 1970s. The authors used this framework to identify a versatile synthetic intermediate that facilitates syntheses of weisaconitine D and liljestrandinine, as well as the core of gomandonine. The web-based deterministic graphing program developed for this work has the potential to be more generally applicable to the analysis and synthesis of other architecturally challenging molecules.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 639/638/403/937 / 639/638/549/977 / Aconitine - analogs & derivatives / Aconitine - chemical synthesis / Aconitine - chemistry / Alkaloids / Binding sites / Biological Products - chemical synthesis / Biological Products - chemistry / Chemical properties / Chemical synthesis / Chemistry Techniques, Synthetic / Humanities and Social Sciences / Internet / Metabolites / Molecular Structure / multidisciplinary / Natural products / Organic chemicals / Organic compounds / Science / Secondary metabolites / Software / Stereoisomerism / Synthesis