A Concise Total Synthesis of Echinacea Diynyl N-Alkylamides

Preparations from plants belonging to the Echinacea genus have been utilized for centuries as popular „cure-alls“ capable of stimulating and strengthening the immune response against a variety of ailments, including symptoms of the common cold and certain respiratory infections. Today, the allure of natural herbal remedies remains strong, with sales for Echinacea supplements topping $132 million in 2009 [1]. However, laboratory and clinical research efforts have yet to offer concrete conclusions regarding the efficacy and mode of action of Echinacea therapy. An analysis of plant extracts revealed several classes of biologically active chemical compounds that may be responsible for the observed health effects. The structurally unique N-alkylamides, consisting of dienyl and diynyl analogues, represent a small fraction of the Echinacea plant matter and are found in only two other plant genera, Xanthoxylum and Spilanthes [2]. Isolation of N-alkylamides from the biomass is tedious and low yielding, and current synthetic methods are quite lengthy and expensive. As such, an efficient synthetic process was designed to provide multi-gram quantities of diynyl N-alkylamide derivatives in good overall yield and high purity. This method allows for the construction of a reference standard library and increases access to challenging N-alkylamides for laboratory and clinical studies.

References: [1] May (2010) Nutr Bus J, [2] Boonen J, Baert B, et al. (2010)J Ethnopharmacol, 127: 77–84.