Hong, B.; Hu, D.; Wu, J.; Zhang, J.; Li, H.; Pan, Y.; Lei, X.
Chem. Asian J. 2017, 12, 1557-1567. (VIP paper)
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).
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).