Facile synthetic routes to a chiral chloro‐substituted biphenyl‐2,2′‐diyl hydrogen phosphate and a chiral O,O‐biphenyl‐2,2′‐diyl phosphoramidothioate are described. The performance of these compounds as catalysts for the hydrophosphonylation of imines and the Friedel–Crafts alkylation of indole was investigated. In the latter reaction, the chloro‐substituted phosphoric acid derivative was found to rival the best Brønsted acid catalysts reported to date.
The indium(III)-catalyzed enantioselective and regioselective addition of pyrroles to isatins is described. The effects of metal and solvent on the reactivity and selectivity are compared and discussed, demonstrating that the indium(III)-indapybox complex provides the most effective catalyst. A case of divergent reactivity between pyrroles and indoles is presented.
BackgroundThe plant genus Fallopia is well-known in Chinese traditional medicine and includes many species that contain bioactive compounds, namely phytoestrogens. Consumption of phytoestrogens may be linked to decreased incidence of breast and prostate cancers therefore discovery of novel phytoestrogens and novel sources of phytoestrogens is of interest. Although phytoestrogen content has been analyzed in the rhizomes of various Fallopia sp., seeds of a Fallopia sp. have never been examined for phytoestrogen presence.MethodsAnalytical chemistry techniques were used with guidance from an in vitro estrogen receptor bioassay (a stably transfected human ovarian carcinoma cell line) to isolate and identify estrogenic components from seeds of Fallopia convolvulus. A transiently transfected human breast carcinoma cell line was used to characterize the biological activity of the isolated compounds on estrogen receptors (ER) α and β.ResultsTwo compounds, emodin and the novel flavan-3-ol, (−)-epiafzelechin-3-O-p-coumarate (rhodoeosein), were identified to be responsible for estrogenic activity of F. convolvulus seed extract. Absolute stereochemistry of rhodoeosein was determined by 1 and 2D NMR, optical rotation and circular dichroism. Emodin was identified by HPLC/DAD, LC/MS/MS, and FT/ICR-MS. When characterizing the ER specificity in biological activity of rhodoeosein and emodin, rhodoeosein was able to exhibit a four-fold greater relative estrogenic potency (REP) in breast cells transiently-transfected with ERβ as compared to those transfected with ERα, and emodin exhibited a six-fold greater REP in ERβ-transfected breast cells. Cell type-specific differences were observed with rhodoeosein but not emodin; rhodoeosein produced superinduction of reporter gene activity in the human ovarian cell line (> 400% of maximum estradiol [E2] induction) but not in the breast cell line.ConclusionThis study is the first to characterize the novel flavan-3-ol compound, rhodoeosein, and its ability to induce estrogenic activity in human cell lines. Rhodoeosein and emodin may have potential therapeutic applications as natural products activating ERβ, and further characterization of rhodoeosein is necessary to evaluate its selectivity as a cell type-specific ER agonist.
I. Materials. All compounds were purchased from Aldrich, Alfa Aesar, TCI America, Matrix Scientific, Strem, and/or Fisher. NMR solvents were purchased from Cambridge Isotope Laboratories, Inc. Chlorobenzene (Acros) was used as-received. The flash chromatography of all compounds was performed utilizing silica gel 60 (32-63 micron) purchased from Bodman Industries. II. Instrumentation. Nuclear magnetic resonance (NMR) spectra were obtained using either a Bruker AvanceIII-500 or Bruker 300 NMR spectrometer. Chemical shifts for protons are reported in parts per million downfield from tetramethylsilane and are referenced to residual protium in the NMR solvent (CHCl 3 : δ 7.26). Chemical shifts for carbon are reported in parts per million downfield from tetramethylsilane and were referenced to the carbon resonances of the solvent (CDCl 3 : δ 77.2). Data are represented as follows: chemical shift, integration, multiplicity (s = singlet, d = doublet, sep = septet, m = multiplet, br = broad), coupling constants in Hertz (Hz), and assignment. Mass spectrometric data were obtained at the Caltech Mass Spectrometry Facility. A Biotage ® Initiator microwave reactor was used for all microwave experiments.Microwave reactions were conducted in septum-sealed, glass vials equipped with magnetic stirbars; an external surface sensor was used to monitor reaction conditions.
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