title: A cascade strategy enables a total synthesis of (-)-gephyrotoxin.
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.
authors.affiliation: Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA (UK) http://msmith.chem.ox.ac.uk.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Chu
authors.forename: Stephen
authors.initials: S
authors.lastname: Wallace
authors.forename: Martin D
authors.initials: MD
authors.lastname: Smith
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; C014569:gephyrotoxin
keywords: alkaloids; asymmetric synthesis; cascade reactions; gephyrotoxin; total synthesis