Synthetic Studies Towards Caulophyllumine and its Derivatives

Caulophyllum thalictroides (L.) Michx. (Blue Cohosh) is a popular herb, roots and rhizomes of which have been extensively used for women's health [1] and it is also considered a poisonous plant. A detailed phytochemical analysis revealed that alkaloids and saponins are the major components responsible for its pharmacological effects. In addition to their biological activity, recently we have demonstrated that the piperidine alkaloid isolated from Blue Cohosh, Caulophyllumine B inhibits the major drug metabolizing P450 (Cyp450) enzymes [2]. In continuation of our efforts in safety and efficacy of dietary supplements, we need Caulophyllumine B and its analogs. To achieve these piperidine based alkaloids here we propose and demonstrate a four step synthesis starting from commercially available 2-piperidinone. Furthermore, the flexibility of the current strategy to introduce any substituted aromatic ring attached to piperidine scaffold allows construction of various structurally similar natural products and its analogs. Our synthetic strategy and the full chemical details will be presented.

Caulophyllumine A

Caulophyllumine B

Acknowledgements: This research is supported in part by Science Based Authentication of Dietary Supplements funded by the Food and Drug Administration grant No. 1U01FD004246–01; and the United States Department of Agriculture, Agricultural Research Service, Specific Cooperative Agreement No. 58–6408–2-0009. References: [1] Jhoo J, Sang S, et al. (2001)J Agric Food Chem 49: 5969–5974. [2] Vamsi L, Ali Z, et al, (2009) Pharmacology letter, Planta Med 75(4): 329–332.