Stereoselective Total Synthesis of Hetisine-type C20 -Diterpenoid Alkaloids: Spirasine IV and XI.

The first total synthesis of the architecturally complex hetisine-type heptacyclic C20 -diterpenoid alkaloids (±)-spirasine IV and XI is reported. The A/F/G/C tetracyclic skeleton with the challenging N-C6 and C14-C20 linkages was efficiently constructed by an intramolecular azomethine-ylide-based 1,3-dipolar cycloaddition with unusual regioselectivity. SmI2 -mediated free-radical addition to the arene moiety without prior dearomatization and a stereoselective intramolecular aldol reaction further enabled rapid access to the hetisine core, providing a bicyclo[2.2.2]octane ring with a new oxygen substitution pattern.