A Cascade Strategy Enables a Total Synthesis of (−)‐Gephyrotoxin |
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| Authors: | Shuyu Chu Dr Stephen Wallace Prof?Dr Martin D Smith |
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| Affiliation: | Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA (UK) http://msmith.chem.ox.ac.uk |
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| Abstract: | 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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| Keywords: | alkaloids asymmetric synthesis cascade reactions gephyrotoxin total synthesis |
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