Reactivity of the Iboga Skeleton: Oxidation Study of Ibogaine and Voacangine.
Journal of natural products June 23, 2023 Bruno González, Nicolás Veiga, Gonzalo Hernández et al. 7 citations
The iboga alkaloids, such as ibogaine and voacangine, are promising scaffolds for developing drugs to treat neuropsychiatric disorders. This work examines how these molecules react under oxidation with dioxygen, peroxo compounds, and iodine. The C16-carboxymethyl ester group in voacangine makes the molecule more stable toward oxidation than ibogaine, particularly in the indole ring, where 7-hydroxy- or 7-peroxy-indolenines form. However, the ester increases reactivity at the isoquinuclidinic nitrogen, leading to C3-oxidized products via regioselective iminium formation. Density functional theory calculations explain this differential reactivity. Additionally, NMR experiments and theoretical calculations revise the absolute stereochemistry at C7 in voacangine's 7-hydroxyindolenine to S, correcting earlier reports of R configuration.