A Cascade Strategy Enables a Total Synthesis of (−)‐Gephyrotoxin1. (16th October 2014)

• Record Type: Journal Article
• Authors: Chu, Shuyu; Wallace, Stephen; Smith, Martin D.
• Is Part Of: Angewandte Chemie. Volume 126:Number 50(2014)
• Page Start: 14046
• Page End: 14049
• Publication Date: 2014-10-16
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201409038
• Languages: English
• ISSNs: 0044-8249

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>A concise and efficient synthesis of (−)‐gephyrotoxin from <sc>L</sc>‐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 <italic>cis</italic>‐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.</p> </abstract>