| Halenia elliptica D. Don (Family:Gentianaceae, Genus:Halenia), well known as "Zang-Yin-Chen", is distributed across the Tibetan plateau and throughout western China. It has been used in traditional Tibetan and Mongolian medicine to cure hepatitis for centuries. Previous phytochemical investigation by our group led to the isolation of a series of simple oxygenated xanthones, which are believed to contribute to the hepatoprotective effect. During our ongoing search, both EtOAc and water-soluble portion of the aerial part of H. elliptica were found to have potent anti-HBV activity in vitro. This finding prompted us to characterize the chemical constituents present in these two extracts.38 compounds were isolated in this research, among which the structures of 30 compounds were elucidated by comprehensive spectroscopic analysis including MS, ID and 2D NMR and chemical derivatization. We described herein the isolation and structural elucidation of three xanthone aglycones (Hx-1-Hx-3), six xanthone glycosides (Ha-1-Ha-6), five flavonoids (Ha-7-Ha-11), four secoiridoid glucosides (Ha-12-Ha-15), eleven chromones (Hx-4, Ha-16-Ha-25) and one triterpene (oleanolic acid, Hx-5). Xanthone compound, 1,5-dihydroxy-2,3,4-trimethoxyxanthone (Hx-1), chromone compounds,5-hydroxy-6-methoxy-2-methylchromone (Ha-17),3,5-dihydroxy-6-methoxy-2-methylchromone (Ha-19),8-hydroxy-chromone-2-carboylic acid (Ha-20),8-methoxy-chromone-2-carboylic acid (Ha-21),3-acetyl-8-hydroxy-chromone-2-carboxylic acid (Ha-22), 2-(8-hydroxy-2-methyl-chromone-3-yl)-2-oxoacetic acid (Ha-23),5-hydroxy-6-methoxy-chromone-2-carboxylic acid (Ha-24) and 5-hydroxy-8-methoxy-chromone-2-carboxylic acid (Ha-25) were new compounds. Chromone compounds,8-methoxy-2-methylchromone (Hx-4),8-hydroxy-2-methylchromone (Ha-16) and 5-hydroxy-8-methoxy-2-methylchromone (Ha-18) were new natural products. Luteolin-7-(9-gentiobioside (Ha-8) and apigenin-7-O-gentiobioside (Ha-9) were isolated from Gentianaceae family for the first time. 1,5-dihydroxy-3-methoxyxanthone (Hx-3), 2,3,4,5-tetramethoxyxanthone-1-O-gentiobioside (Ha-1),2,3,5-trimethoxyxanthone-1-O-gentiobioside (Ha-2), apigenin (Ha-11), gentiopicroside (Ha-13), vogeloside (Ha-14) and epi-vogeloside (Ha-15) were isolated from this plant for the first time. We reported the detailed NMR spectroscopic data of Ha-1 for the first time. Xanthones,flavonoids,secoiridoid glucosides and some of the chromones in H. elliptica exhibit strong inhibitory effects towards hepatitis B virus (HBV) in vitro.Polar chromones seem to be the characteristic constituents of water-soluble portion of H. elliptica. To our knowledge, this is the first report describing the presence of chromone derivatives in the Gentianaceae family. Chromone derivatives from H. elliptica can be categorized into chromone-2-carboxylic acids and 2-methylchromones. Two unstable compounds,3-acetyl-8-hydroxy-chromone-2-carboxylic acid (Ha-22) and 2-(8-hydroxy-2-methyl-chromone-3-y1)-2-oxoacetic acid (Ha-23) were isomers and could interconvert in equilibrium. Their stable derivatives were obtained after esterification. The mechanism of their isomerization in hydrous solvent was also described. Based on the study of Ha-22 and Ha-23, we design a new derivatization method which could be adopted to effectively isolate the mixture of chromone-carboxylic acids in H. elliptica. The separation of four major chromone-carboxylic acids were greatly facilitated by this method and also, two minor chromone-carboxylic acids were obtained by using this method.We also perform the chemical modification of natural products from Halenia elliptica. A series of camphanoyl-O-chromone or camphanoyl-O-xanthone derivatives were synthesized, which showed more potent inhibition towards HBsAg than their parent compounds.
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