Completion of the Total Synthesis of Several Bioactive Sarpagine/Macroline Alkaloids including the Important NF-κB Inhibitor <i>N</i><sub>4</sub>-Methyltalpinine
Md Toufiqur Rahman,
Veera Venkata Naga Phani Babu Tiruveedhula,
Michael Rajesh Stephen,
Sundari K. Rallapalli,
Kamal P. Pandey,
James M. Cook
Affiliations
Md Toufiqur Rahman
Department of Chemistry and Biochemistry, University of Wisconsin Milwaukee, Milwaukee, WI 53211, USA
Veera Venkata Naga Phani Babu Tiruveedhula
Department of Chemistry and Biochemistry, University of Wisconsin Milwaukee, Milwaukee, WI 53211, USA
Michael Rajesh Stephen
Department of Chemistry and Biochemistry, University of Wisconsin Milwaukee, Milwaukee, WI 53211, USA
Sundari K. Rallapalli
Department of Chemistry and Biochemistry, University of Wisconsin Milwaukee, Milwaukee, WI 53211, USA
Kamal P. Pandey
Department of Chemistry and Biochemistry, University of Wisconsin Milwaukee, Milwaukee, WI 53211, USA
James M. Cook
Department of Chemistry and Biochemistry, University of Wisconsin Milwaukee, Milwaukee, WI 53211, USA
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.
