title: Network-analysis-guided synthesis of weisaconitine D and liljestrandinine.
abstract: 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 families 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.
authors.affiliation: Department of Chemistry, University of California, Berkeley, California 94720, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Marth
authors.affiliation: Department of Chemistry, University of California, Berkeley, California 94720, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Gallego
authors.affiliation: Department of Chemistry, University of California, Berkeley, California 94720, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Chemistry, University of California, Berkeley, California 94720, USA.
authors.forename: T P
authors.initials: TP
authors.lastname: Lebold
authors.affiliation: Department of Chemistry, University of California, Berkeley, California 94720, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kulyk
authors.affiliation: Department of Chemistry, University of California, Berkeley, California 94720, USA.
authors.forename: K G M
authors.initials: KG
authors.lastname: Kou
authors.affiliation: Cadre Research Labs, Chicago, Illinois 60654, USA.
authors.forename: J
authors.initials: J
authors.lastname: Qin
authors.affiliation: Cadre Research Labs, Chicago, Illinois 60654, USA.
authors.forename: R
authors.initials: R
authors.lastname: Lilien
authors.affiliation: Department of Chemistry, University of California, Berkeley, California 94720, USA.
authors.forename: R
authors.initials: R
authors.lastname: Sarpong
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D020407:Internet; D015394:Molecular Structure; D012984:Software; D013237:Stereoisomerism
chemical_list: C000588655:8-O-ethylaconosine; D001688:Biological Products; D000157:Aconitine