A CONVERGENT ENANTIOSELECTIVE TOTAL SYNTHESIS OF (-)-PERHYDROHISTRIONICOTOXIN WITH AN INTRAMOLECULAR IMINO ENE-TYPE REACTION AS A KEY STEP

A convergent enantioselective total synthesis of the neurotoxic spiroc yclic alkaloid (-)-perhydrohistrionicotoxin (2) is described. A Lewis acid-mediated intramolecular imine ene-type reaction was used for the key spirocyclisation step (14 to 3, with 3 being obtained as a single diastereoisomer). Spirocyclisation precursor 14 was prepared from enan tiomerically pure ketone 13, itself available via an efficient one-pot , three-component, coupling reaction involving chiral electrophiles 9 and 10. The stereogenic centres of 9 and 10 derive in turn from Sharpl ess kinetic resolution, which allowed access to both chiral electrophi les from a common racemic precursor, 8. (C) 1998 Elsevier Science Ltd. All rights reserved.