Total Syntheses of Naucleamides A–C and E, Geissoschizine, Geissoschizol, (E)‑Isositsirikine, and 16-epi-(E)‑Isositsirikine

A divergent approach for the enantioselective total synthesis of eight monoterpenoid indole alkaloids was developed. The approach allows the first total syntheses of naucleamides A–C and E in only 6–8 steps and also enables the efficient synthesis of geissoschizine, geissoschizol, (E)-isositsirikine, and 16-epi-(E)-isositsirikine in 10–11 steps from commercially available crotonic aldehyde. The synthesis features a one-pot organocatalyzed asymmetric Michael addition/Pictet–Spengler reaction. Notably, biomimetic synthesis of naucleamide E was achieved by oxidative cyclization of naucleamide A.