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Completion of the total synthesis of several bioactive sarpagine/macroline alkaloids including the important NF-κB inhibitor N4-methyltalpinine
Rahman, M. T., Tiruveedhula, V. V. N. P. B., Stephen, M. R., Rallipalli, S. K., Pandey, K. P., & Cook, J. M. (2022). Completion of the total synthesis of several bioactive sarpagine/macroline alkaloids including the important NF-κB inhibitor N4-methyltalpinine. Molecules, 27(5), Article 1738. https://doi.org/10.3390/molecules27051738
The unification of the general synthetic strategy regarding the important and emerging group of C-19 methyl-substituted sarpagine/macroline alkaloids has culminated in the completion of the total synthesis of several bioactive alkaloids. Key transformations include an ACE-Cl mediated late-stage N(4)-demethylation and an anhydrous acid-mediated intramolecular quaternary hemiaminal formation between a tertiary amine and an aldehyde function to allow efficient access to several biologically important alkaloids from this group. Herein, the enantiospecific total synthesis of the first known sarpagine/macroline alkaloid with NF-κB inhibitory activity, N(4)-methyltalpinine (as a chloride salt), as well as the anticancer alkaloids talpinine, O-acetyltalpinine, and macrocarpines F–G, are described.