title: Chlorination diversifies Cimicifuga racemosa triterpene glycosides.
abstract: 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.
authors.affiliation: UIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois at Chicago, Chicago, Illinois 60612, USA
authors.forename: Shao-Nong
authors.initials: SN
authors.lastname: Chen
authors.forename: David C
authors.initials: DC
authors.lastname: Lankin
authors.forename: Dejan
authors.initials: D
authors.lastname: Nikolic
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Fabricant
authors.forename: Zhi-Zhen
authors.initials: ZZ
authors.lastname: Lu
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ramirez
authors.forename: Richard B
authors.initials: RB
authors.lastname: van Breemen
authors.forename: Harry H S
authors.initials: HH
authors.lastname: Fong
authors.forename: Norman R
authors.initials: NR
authors.lastname: Farnsworth
authors.forename: Guido F
authors.initials: GF
authors.lastname: Pauli
mesh_terms: 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
chemical_list: D006027:Glycosides; D010936:Plant Extracts; D014315:Triterpenes; D002713:Chlorine