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A Cascade Strategy Enables a Total Synthesis of (−)‐Gephyrotoxin
Author(s) -
Chu Shuyu,
Wallace Stephen,
Smith Martin D.
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201409038
Subject(s) - iminium , total synthesis , stereocenter , intramolecular force , chemistry , enamine , cascade , ring (chemistry) , yield (engineering) , stereochemistry , michael reaction , cascade reaction , crystal structure , combinatorial chemistry , enantioselective synthesis , organic chemistry , catalysis , materials science , chromatography , metallurgy
A concise and efficient synthesis of (−)‐gephyrotoxin from L ‐pyroglutaminol has been realized. The key step in this approach is a diastereoselective intramolecular enamine/Michael cascade reaction that forms two rings and two stereocenters and generates a stable tricyclic iminium cation. A hydroxy‐directed reduction of this intermediate plays a key role in establishing the required cis ‐decahydroquinoline ring system, enabling the total synthesis of (−)‐gephyrotoxin in nine steps and 14 % overall yield. The absolute configuration of the synthetic material was confirmed by single‐crystal X‐ray diffraction and is consistent with the structure originally proposed for material isolated from the natural source.