A stereoselective synthesis of (-)-perhydrohistrionicotoxin

The first synthesis of (-)-perhydrohistrionicotoxin, which proceeds without recourse to resolution of synthetic intermediates is reported. The absolute stereochemistry is derived from L-glutamic acid, and the key step, in which the critical relative stereochemical relationships are established, is the intramolecular photocycloaddition of a vinylogous amide with a dioxenone. Histrionicotoxin was originally isolated from the skin extracts of the Neotropical poison froog Dendrobates histrionicus. The attention given to the synthesis of the histrionicotoxin alkaloids stems from their unique properties as neurotoxins in conjunction with their scarity. Both histrionicotoxin and perhydrohistrionicotoxin are potent blockers of acetylcholine-mediated ion conductance.