Synthesis of (±)-Epibatidine and Its Analogues

Abstract
A nonopiate analgesic, epibatidine (1), isolated from the skin of the Ecuadoran poison frog was synthesized in racemic form starting from tropinone. Distinctly different from the previously published approaches, this synthesis features the novel synthesis of the 7-azabicyclo[2.2.1]heptane ring system by contraction of the tropinone skeleton via Favorskii rearrangement. Five analogues of 1 were also prepared, and their analgesic activities were evaluated.

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