motivated by curiosity.

Epiquinamide: A poison that wasn’t from a frog that was

02.06.09 Posted in Medicinal Chemistry by

In 2003, we reported the isolation, structure elucidation, and pharmacology of epiquinamide, a novel alkaloid isolated from an Ecuadoran poison frog, Epipedobates tricolor. Since then, several groups, including ours, have undertaken synthetic efforts to produce this compound, which appeared initially to be a novel, beta-2-selective nicotinic acetylcholine receptor agonist. Based on prior chiral GC analysis of synthetic and natural samples, the absolute structure of this alkaloid was established as (1S,9aS)-1-acetamidoquinolizidine. We have synthesized the (1R*,9aS*)-isomer (epi- epiquinamide) using an iminium ion nitroaldol reaction as the key step. We have also synthesized ent-1 semisynthetically from (-)-lupinine. Synthetic epiquinamide is inactive at nicotinic receptors, in accord with recently published reports. We have determined that the activity initially reported is due to cross-contamination from co-occurring epibatidine in the isolated material.

Fitch, R., Sturgeon, G., Patel, S.R., Spande T., Garraffo, H., Daly, J., Blaauw, R. Epiquinamide: A poison that wasn’t from a frog that was. Journal of Natural Products, 2009.