Cimipronidine, a cyclic guanidine alkaloid from Cimicifuga racemosa

A new cyclic guanidine alkaloid, cimipronidine (1), together with the known compound fukinolic acid (2), was isolated from the n-BuOH-soluble fraction of Cimicifuga racemosa roots that showed 5-HT7 receptor binding activity. Structure elucidation of 1, a minor constituent, presented unique challenges based on its polarity, but was accomplished with the use of a combination of one- and two-dimensional NMR as well as MS analyses. The relative configuration was established by analyzing the H,H-coupling constants and the results of the 2-D gradient NOESY spectrum. The previously reported serotonergic (5-HT7), highly polar, n-BuOH-soluble fraction was characterized by HPLC-ELSD and was shown to be a mixture containing the following compounds: cimicifugic acids A, B, and F, fukinolic acid, ferulic acid, isoferulic acid, and compound 1, potentially significant as a marker compound of C. racemosa.