Divergent Total Syntheses of (−)-Huperzine Q, (+)-Lycopladine B, (+)-Lycopladine C, and (−)-4-epi-Lycopladine D

Abstract We report herein our synthetic efforts towards the divergent syntheses of (−)‐huperzine Q ( 1 ), (+)‐lycopladine B ( 2 ), (+)‐lycopladine C ( 3 ), and (−)‐lycopladine D ( 4 ). The 10‐step total synthesis of (−)‐huperzine Q ( 1 ) and the first total syntheses of (+)‐lycopladines B ( 2 ) and C ( 3 ) were accomplished through a series of cascade reactions. Our approach involved a Michael addition/aldol/intramolecular C‐alkylation sequence to forge the 6/9 spirocycle ring, and this was followed by an ethylene‐accelerated carbonyl–olefin metathesis to construct the common 6/5/9 ring system. Finally, late‐stage enamine bromofunctionalization enabled us to access (−)‐huperzine Q ( 1 ), (+)‐lycopladine B ( 2 ), and (+)‐lycopladine C ( 3 ), and a tandem C4‐epimerization/retro‐Claisen condensation furnished (−)‐4‐ epi ‐lycopladine D ( 63 ).