Intermolecular C-H Aminocyanation of Indoles via Copper-iodine Cocatalyzed Tandem C-N/C-C Bond Formation.

An efficient copper-iodine cocatalyzed intermolecular C-H aminocyanation of indoles with a broad substrate scope has been developed for the first time. This method enables highly step-economic access to 2-amino-3-cyanoindoles in moderate to good yields and provides a complementary strategy for the regioselective difunctionalization of carbon═carbon double bonds of interest in organic synthesis and related areas. Mechanistic studies suggest that these transformations are initiated by iodine-mediated C2-H amination with azoles, followed by copper-catalyzed C3-H cyanation with ethyl cyanoformate.

Discovery of Oxime Ethers as Hepatitis B Virus (HBV) Inhibitors by Docking, Screening and In Vitro Investigation.

A series of oxime ethers with C6-C4 fragment was designed and virtually bioactively screened by docking with a target, then provided by a Friedel-Crafts reaction, esterification (or amidation), and oximation from p-substituted phenyl derivatives (Methylbenzene, Methoxybenzene, Chlorobenzene). Anti-hepatitis B virus (HBV) activities of all synthesized compounds were evaluated with HepG2.2.15 cells in vitro. Results showed that most of compounds exhibited low cytotoxicity on HepG2.2.15 cells and significant inhibition on the secretion of HBsAg and HBeAg. Among them, compound 5c-1 showed the most potent activity on inhibiting HBsAg secretion (IC50 = 39.93 µM, SI = 28.51). Results of the bioactive screening showed that stronger the compounds bound to target human leukocyte antigen A protein in docking, the more active they were in anti-HBV activities in vitro.

A new anthraquinone and eight constituents from Hedyotis caudatifolia Merr. et Metcalf: isolation, purification and structural identification.

Hedyotis caudatifolia Merr. et Metcalf. (HC), a folk medicine in Yao nationalities areas in China, was used to investigate the chemical constituents. Through silica gel and Sephadex LH-20 column chromatography, nine compounds were isolated and purified. By physical and chemical properties, IR, MS (EI-MS, high resolution EI-MS), 1D NMR ((1)H NMR, (13)C NMR) and 2D NMR (HSQC, (1)H-(1)H COSY, HMBC), their structures were identified as ß-sitosterol (1), stigmasterol (2), scopolin (3), 2-hydroxy-1,7,8-trimethoxyanthracene-9,10-dione (4), oleanolic acid (5), ursolic acid (6), methyl barbinervate (7), ß-daucosterol (8) and p-Hydroxybenzoic acid (9). These compounds were isolated from HC for the first time, and 4 a new anthraquinone whose biological activities are worth to be investigated in future. These compounds may contribute to the HC's pharmacological effects on treating diseases, and may be used as candidates for control index in establishing the quality control standard of HC.

In vitro and in vivo anti-hepatitis B virus activities of the lignan nirtetralin B isolated from Phyllanthus niruri L.

ETHNOPHARMACOLOGICAL RELEVANCE: Nirtetralin B, a new lignan first reported by our team, is isolated from Phyllanthus niruri L. This plant has long been used in folk medicine for liver protection and antihepatitis B in many Asian countries. This study was designed to evaluate the anti-hepatitis B virus activity of nirtetralin B using HepG2.2.15 cells and duck hepatitis B virus (DHBV) infected ducks as in vitro and in vivo models. MATERIALS AND METHODS: Nirtetralin B was isolated from Phyllanthus niruri L. (Euphorbiaceae) by extraction and chromatographic procedures and the anti-hepatitis B virus activity was evaluated both in vitro and in vivo. The human HBV-transfected liver cell line HepG2.2.15 was used in vitro assay. And the in vivo anti-hepatitis B virus activity was evaluated on the expression of HBV replication, HBsAg, HBeAg, ALT and AST on day 0, 7, 14, 17 after nirtetralin B was dosed intragastricly (i.g.) once a day for 14 days at the dosages of 25, 50 and 100mg/kg/day in the duck hepatitis B virus (DHBV) infected ducks. RESULTS: In the human HBV-transfected liver cell line HepG2.2.15, nirtetralin B effectively suppressed the secretion of the HBV antigens in a dose-dependent manner with IC50 values for HBsAg of 17.4µM, IC50 values for HBeAg of 63.9µM. In DHBV-infected ducklings, nirtetralin B significantly reduced the serum DHBV DNA, HBsAg, HBeAg, ALT and AST. And analysis of the liver pathological changes confirmed the hepatoprotective effect of nirtetralin B. CONCLUSION: The experimental data demonstrated that nirtetralin B exhibits anti-hepatitis B virus activity both in vitro and in vivo.

In vitro and in vivo anti-hepatitis B virus activities of the lignan niranthin isolated from Phyllanthus niruri L.

ETHNOPHARMACOLOGICAL RELEVANCE: Niranthin is a lignan isolated from Phyllanthus niruri L. This plant has long been used in folk medicine for liver protection and antihepatitis B in many Asian countries. This study was designed to evaluate the anti-hepatitis B virus activity of niranthin using HepG2.2.15 cells and duck hepatitis B virus (DHBV) infected ducks as in vitro and in vivo models. MATERIALS AND METHODS: Niranthin was isolated from Phyllanthus niruri L. (Euphorbiaceae) by extraction and chromatographic procedures and the anti-hepatitis B virus activity was evaluated both in vitro and in vivo. The human HBV-transfected liver cell line HepG2.2.15 was used in vitro assay. And the in vivo anti-hepatitis B virus activity was evaluated on the expression of HBV replication, HBsAg, HBeAg, ALT and AST on day 0, 7, 14, 17 after niranthin was dosed intragastricly (i.g.) once a day for 14 days at the dosages of 25, 50 and 100 mg/kg/day in the duck hepatitis B virus (DHBV) infected ducks. RESULTS: In the human HBV-transfected liver cell line HepG2.2.15, the secretion of HBsAg and HBeAg were significantly decreased after treatment with niranthin for 144 h, with IC50 values for HBsAg of 15.6 µM, IC50 values for HBeAg of 25.1 µM. In DHBV-infected ducklings, niranthin significantly reduced the serum DHBV DNA, HBsAg, HBeAg, ALT and AST. Furthermore, analysis of the liver pathological changes confirmed the hepatoprotective effect of niranthin. CONCLUSION: The experimental data demonstrated that niranthin exhibits anti-hepatitis B virus activity both in vitro and in vivo.

Simple and effective large-scale preparation of geniposide from fruit of Gardenia jasminoides Ellis using a liquid-liquid two-phase extraction.

Geniposide was prepared on a large-scale using a selective two-phase liquid-liquid extraction. The aqueous residue from the fruit of Gardenia jasminoides Ellis was treated with sodium carbonate and extracted with n-butanol several times. The n-butanol extracts were treated with activated granular charcoal to remove pigments and were then concentrated to produce a residue with a high solid content. The residue was crystallized to obtain geniposide with 98% purity. For large-scale synthesis, the residue (solid content 45%, geniposide 5.5%) was extracted to generate 70g of geniposide with 98% purity and 84.8% recovery using 1500g residue.

Isolation and X-ray crystal structure of a securinega-type alkaloid from Phyllanthus niruri Linn.

A securinega-type alkaloid epibubbialine was isolated from Phyllanthus niruri Linn. Its structure was established by spectroscopic methods and X-ray single-crystal diffraction analysis. Its crystal structure is reported herein for the first time.

Lignans with anti-hepatitis B virus activities from Phyllanthus niruri L.

One new lignan, nirtetralin B, along with its two known stereoisomers were isolated from Phyllanthus niruri L. The structure of the new compound was determined by spectroscopy experiments and x-ray diffraction analysis. These lignans were assayed for anti-hepatitis B virus activities in vitro. Nirtetralin and nirtetralin A, B effectively suppressed the secretion of the HBV antigens in a dose-dependent manner with IC50 values for HBsAg of 9.5 µM (nirtetralin A), 16.7 µM (nirtetralin B) and 97.2 µM (nirtetralin), IC50 values for HBeAg of 17.4 µM (nirtetralin A), 69.3 µM (nirtetralin B) and 232.0 µM (nirtetralin), respectively.

An alkali-soluble heteroxylan from seeds of Phoenix dactylifera L.

Alkali-soluble polysaccharides, isolated from the seeds of dates, have been investigated using methylation and partial hydrolysis studies. The polysaccharides are shown to contain D-xylose and 4-O-methyl-D-glucuronic acid in a molar ratio of 5:1. An aldobiouronic acid from hemicellulose was characterized, and investigation revealed that the hemicellulose consists of a polymer of (1-->4)-linked D-xylopranosyl residues having branches of D-xylopyranosyl and 4-O-methyl-alpha-D-glucopyranosyluronic acid.