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Divergent Total Syntheses of (−)‐Huperzine Q, (+)‐Lycopladine B, (+)‐Lycopladine C, and (−)‐4‐ epi ‐Lycopladine D
Author(s) -
Hong Benke,
Hu Dachao,
Wu Jinbao,
Zhang Jing,
Li Houhua,
Pan Yingming,
Lei Xiaoguang
Publication year - 2017
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201700364
Subject(s) - chemistry , enamine , stereochemistry , huperzine a , total synthesis , aldol reaction , intramolecular force , epimer , ring (chemistry) , alkylation , metathesis , aldol condensation , claisen rearrangement , olefin metathesis , organic chemistry , catalysis , polymer , acetylcholinesterase , polymerization , enzyme
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 ).
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