Protoverbine, the parent member of a class of macrocyclic spermine alkaloids

The 17-membered macrocyclic spermine alkaloids protoverbine ((8S)-8-phenyl- 1,5,9,13-tetraazacycloheptadecan-6-one, 1) and its N(9),N(13)-methylene-bri dged derivative protomethine ((2S)-2-phenyl-1,5,9,14-tetraazabicyclo[12.3.1 ]octadecan-4-one, 2) were isolated from Verbascum pseudonobile STOJ, et STE F, (Scrophulariaceae) and characterized. The synthesis of their racemates i s described. The possible role of (S)-protoverbine (1) and (S)-protomethine (2) as precursors in the biogenesis of the whole class of N(1),N(9)- and/o r N(13)-substituted alkaloids, the groups of verbamethine ((S)-3a-f), verba cine ((S)-4a-f), incasine B'/ verdoline ((S)-5a-f), verbamedine ((S)-6a-f), and verbascenine ((S)-7a-f), is discussed.