Department of Chemistry, Indiana State University, 600 Chestnut Street, Science S35E, Terre Haute, Indiana 47809, USA.
J Nat Prod. 2009 Feb 27;72(2):243-7. doi: 10.1021/np8005452.
In 2003, we reported the isolation, structure elucidation, and pharmacology of epiquinamide (1), 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, beta2-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.
2003 年，我们报道了 epiquinamide（1）的分离、结构阐明和药理学，这是一种从厄瓜多尔毒蛙 Epipedobates tricolor 中分离出来的新型生物碱。此后，包括我们在内的几个研究小组都进行了合成工作，以生产这种化合物，它最初似乎是一种新型的β2-选择性烟碱型乙酰胆碱受体激动剂。基于先前对合成和天然样品的手性 GC 分析，该生物碱的绝对结构被确定为（1S，9aS）-1-乙酰氨基喹啉啶。我们使用亚胺离子硝酮醇反应作为关键步骤合成了（1R*，9aS*）-异构体（epi-epiquinamide）。我们还通过（-）-lupinine 半合成了 ent-1。合成的 epiquinamide 在烟碱受体上没有活性，这与最近发表的报告一致。我们已经确定，最初报道的活性是由于分离材料中同时存在的 epibatidine 的交叉污染所致。
