A Scalable Total Synthesis of (-)-Nakadomarin A.

The convergent total synthesis of the manzamine alkaloid (-)-nakadomarin A (1) is described. The retrosynthetic analysis recognized spirocycle 3, assembled via an organocatalyst-promoted Michael addition/cyclization between bicyclic lactam 4 and furan aldehyde 5, both accessible from achiral starting materials and on a multigram scale. Lactam 4 is assembled through an S _N 2'/reduction/Staudinger/retro-aza-Claisen sequence on scale. After spirocyclization, the synthesis of nakadomarin is completed in only six steps.