Short, enantioselective, gram-scale synthesis of (-)-zephyranthine

A reasonable synthesis design by strategically integrating functional group manipulation into the ring system construction resulted in a short, enantioselective, gram-scale total synthesis of (-)-zephyranthine. The concise route includes a catalytic Michael/Michael cascade for the asymmetric synthesis of a penta-substituted cyclohexane with three contiguous stereogenic centers, a remarkable 8-step one-pot operation to easily assemble the zephyranthine tetracyclic skeleton, the regioselective construction of a double bond in the C ring and an asymmetric dihydroxylation. This synthesis is also flexible and paves a potential path to a variety of cyclohexylamine-fused tricyclic or polycyclic alkaloids.

Automated summary

Strategically integrating functional group manipulation into the ring system construction resulted in a short, enantioselective, gram-scale total synthesis of (-)-zephyranthine. The concise route includes a catalytic Michael/Michael cascade, an 8-step one-pot operation, regioselective construction of a double bond, and asymmetric dihydroxylation. This synthesis is flexible and paves a potential path to a variety of cyclohexylamine-fused tricyclic or polycyclic alkaloids.