Total Syntheses of Naucleamides A–C and E, Geissoschizine, Geissoschizol, (<i>E</i>)-Isositsirikine, and 16-<i>epi</i>-(<i>E</i>)-Isositsirikine

Abstract

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.