A cascade strategy enables a total synthesis of (-)-gephyrotoxin.
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-d...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Wiley
2014
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| Summary: | 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. |
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