A convergent enantioselective total synthesis of (-)- perhydrohistrionicotoxin with an intramolecular imino ene-type reaction as a key step

Article abstract of DOI:10.1016/S0040-4020(98)00425-6

A convergent enantioselective total synthesis of the neurotoxic spirocyclic 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 enantiomerically 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 Sharpless kinetic resolution, which allowed access to both chiral electrophiles from a common racemic precursor, 8.