Chlorination Diversifies Cimicifuga racemosa Triterpene Glycosides

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2007-06, Vol.70 (6), p.1016-1023
• Main Authors: Chen, Shao-Nong, Lankin, David C, Nikolic, Dejan, Fabricant, Daniel S, Lu, Zhi-Zhen, Ramirez, Benjamin, van Breemen, Richard B, Fong, Harry H. S, Farnsworth, Norman R, Pauli, Guido F
• Format: Article
• Language: English
• Subjects: 25-chlorodeoxycimigenol-3-O-beta-D-xyloside; Actaea racemosa; Biological and medical sciences; chemical structure; chlorination; Chlorine - chemistry; Chromatography, High Pressure Liquid; Cimicifuga - chemistry; Cimicifuga - drug effects; Food industries; Fundamental and applied biological sciences. Psychology; General pharmacology; glycosides; Glycosides - chemistry; Glycosides - isolation & purification; Glycosides - pharmacology; human health; Medical sciences; medicinal plants; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; phytochemicals; Plant Extracts - chemistry; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plant Roots - chemistry; Plants, Medicinal - chemistry; Ranunculaceae; Research and development. New food products, dietetic foods and beverages; Rhizome - chemistry; spectral analysis; Triterpenes - chemistry; Triterpenes - isolation & purification; Triterpenes - pharmacology; triterpenoids; Virginia
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np0700319

Extracts from the roots and rhizomes of black cohosh (Cimicifuga racemosa) are widely used as dietary supplements to alleviate menopausal symptoms. State-of-the-art quality control measures involve phytochemical fingerprinting of the triterpene glycosides for species identification and chemical standardization by HPLC. In the course of developing materials and methods for standardization procedures, the major C. racemosa triterpene glycoside (1) was isolated and initially thought to be cimicifugoside (2). Detailed HR-LC-MS and 1D and 2D NMR analysis of 1 and 2 unambiguously revealed that 1 is the chlorine-containing derivative of 2, namely, 25-chlorodeoxycimigenol-3-O-β-d-xyloside. Accordingly, HPLC profiles of black cohosh preparations require revision of the assignments of the chlorinated (1) and nonchlorinated (2) pair. Besides explaining the substantial shift in polarity (Δt R[RP-18] ca. 20 min), 25-deoxychlorination opens a new pathway of structural diversification in triterpene glycoside chemistry. As chemical conversion of 2 into 1 could be demonstrated, deoxychlorination may be interpreted as artifact formation. Simultaneously, however, it is a potentially significant pathway for the gastric in vivo conversion (“nature's prodrug”) of the relatively polar triterpene glycosides into significantly less polar chlorinated derivatives with altered pharmacological properties.