Epiquinamide: A Poison That Wasn't From a Frog That Was1

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2009-02, Vol.72 (2), p.243-247
• Main Authors: Fitch, Richard W., Sturgeon, Gordon D., Patel, Shaun R., Spande, Thomas F., Garraffo, H. Martin, Daly, John W., Blaauw, Richard H.
• Format: Article
• Language: English
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np8005452

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, β2-selective nicotinic acetylcholine receptor agonist. Based on chiral GC analysis of synthetic and natural samples, the absolute structure of this alkaloid is established as (1 S , 9a S )-1-acetamidoquinolizidine. The synthetic epiquinamide is inactive at nicotinic receptors, in accord with recently published reports. However, the natural material retains activity that is not easily traced to known active components of the original extract. We report herein our results and possible reasons for this discrepancy.