C1-Derivatives of macrocyclic spermine alkaloids. Verbamedines versus incasines

The isolation, structure elucidation, and synthesis of the macrocyclic spermine alkaloids verbamedine (3) and isoverbamedine (4) from Verbascum pseudonobile Stoj. and Stef. are reported. The synthesis of N(13)-formimino-verbacine (7) is described. Spectral and chemical evidence is presented to correct the previously published incorrect structures of the incasines A and A′ isolated from Incarvillea sinensis LAM. The similarities between the natural C1-derivatives of verbacine (1) and the biochemical one-carbon units transferring tetrahydrofolate cofactors have been observed.