Chlorination diversifies Cimicifuga racemosa triterpene glycosides.
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-beta-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 (DeltatR[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.
Chen
Shao-Nong
SN
UIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois at Chicago, Chicago, Illinois 60612, USA
Lankin
David C
DC
Nikolic
Dejan
D
Fabricant
Daniel S
DS
Lu
Zhi-Zhen
ZZ
Ramirez
Benjamin
B
van Breemen
Richard B
RB
Fong
Harry H S
HH
Farnsworth
Norman R
NR
Pauli
Guido F
GF
D002713:Chlorine / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D031885:Cimicifuga / Q000737:chemistry* / Q000187:drug effects; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D027343:Rhizome / Q000737:chemistry; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014768:Virginia
D006027:Glycosides; D010936:Plant Extracts; D014315:Triterpenes; D002713:Chlorine