Showing papers by "Min Xu published in 2014"

Design, synthesis, and biological evaluation of deuterated C-aryl glycoside as a potent and long-acting renal sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes.

Abstract: SGLT2 inhibitors deuterated at sites susceptible to oxidative metabolism were found to have a slightly longer tmax and half-life (t1/2), dose-dependent increase in urinary glucose excretion (UGE) in rats, and slightly superior effects on UGE in dogs while retaining similar in vitro inhibitory activities against hSGLT2. In particular, deuterated compound 41 has the potential to be a robust long-acting antidiabetic agent.

Anti-hepatitis B virus norbisabolane sesquiterpenoids from Phyllanthus acidus and the establishment of their absolute configurations using theoretical calculations.

Abstract: Nineteen new highly oxygenated norbisabolane sesquiterpenoids, phyllanthacidoid acid methyl ester (1), and C-T (4-21), were isolated from Phyllanthus acidus Skeels, together with two known ones, phyllanthusols A (2) and B (3), whose sugar moiety was revised as glucosamine-N-acetate, rather than the previously assigned mannosamine-N-acetate. Compounds 2 and 3 were renamed respectively as phyllanthacidoids A (2) and B (3) to avoid confusion. All of the isolates except for 1 are glycosides, whose saccharide moieties possess a pentaoxy cyclohexane (scyllo quercitol) connecting with glucosamine-N-acetate or glucosyl moieties, which are first examples in natural products. Phyllanthacidoids N-R (15-19) with 8R configurations and/or 5,8-diketal skeleton, are unprecedented structures among norbisabolane sesquiterpenoids. Phyllanthacidoids S (20) and T (21) have the unusual tricyclo [3.1.1.1] oxygen bridge skeleton formed by a diketal system, of which the relative configurations of the aliphatic chain were assigned on the basis of heteronuclear coupling constants. The absolute configurations of compounds (1-21) were established by means of calculated electronic circular dichroism (ECD) and coupling constants. Compounds 1-5, 7-9, 10, and 14 displayed potential anti-hepatitis B virus (HBV) activities, with IC50 values of 0.8-36 mu M against HBV surface antigen (HBsAg) and HBV excreted antigen (HBeAg), and the results indicated that the S-ketal group and sugar moieties had contributions to the selectivity of HBsAg and HBeAg.

Anti-hepatitis B virus activities and absolute configurations of sesquiterpenoid glycosides from Phyllanthus emblica.

Abstract: During the process exploring anti-viral compounds from Phyllanthus species, eight new highly oxygenated bisabolane sesquiterpenoid glycoside phyllaemblicins G1–G8 (1–8) were isolated from Phyllanthus emblica, along with three known compounds, phyllaemblicin F (9), phyllaemblic acid (10) and glochicoccin D (11). Phyllaemblicin G2 (2), bearing a tricyclo [3.1.1.1] oxygen bridge ring system, is an unusual sesquiterpenoid glycoside, while phyllaemblicins G6–G8 (6–8) are dimeric sesquiterpenoid glycosides with two norbisabolane units connecting through a disaccharide. All the structures were elucidated by the extensive analysis of HRMS and NMR data. The relative configuration of phyllaemblicin G2 was constructed based on heteronuclear coupling constants measurement, and the absolute configurations for all new compounds were established by calculated electronic circular dichroism (ECD) using time dependent density functional theory. The sesquiterpenoid glycoside dimers 6–9 displayed potential anti-hepatitis B virus (HBV) activities, especially for the new compound 6 with IC50 of 8.53 ± 0.97 and 5.68 ± 1.75 μM towards the HBV surface antigen (HBsAg) and HBV excreted antigen (HBeAg) secretion, respectively.

Carboxymethyl- and Carboxyl-Catechins from Ripe Pu-er Tea

Abstract: Ripe Pu-er tea, a special microbial postfermented tea originated from Yunnan Province, China, since ancient times, is made from green Pu-er tea prepared from the leaves of Camellia sinensis var. assamica (Theaceae). Chemical investigation on thearubigin (n-BuOH-soluble) fraction of the commercial ripe Pu-er tea, led to the identification of four new flavan-3-ol derivatives, 8-carboxymethyl-(+)-catechin (1), 8-carboxymethyl-(+)-catechin methyl ester (2), 6-carboxymethyl-(+)-catechin (3), and 6-carboxyl-(-)-gallocatechin (4), together with 18 known compounds, including other three flavan-3-ol derivatives (5-7), 10 flavonoid glycosides (8-17), two hydrolyzable tannins (18 and 19), two quinic acid derivatives (20-21), and a purine alkaloid (22). Flavonoid glycosides 8-11 are reported from tea plants for the first time. The thearubigin fraction of ripe Pu-er tea was qualitatively analyzed by HPLC, and gallic acid was found to be the major component. Compounds 4, 6-17, 21 and 22 were tested for their acute activities on insulin sensitivity in differentiated 3T3-L1 adipocytes, but none of them showed significant bioactivity at a concentration of 10 mu M.

Eucalmaidials A and B, phloroglucinol-coupled sesquiterpenoids from the juvenile leaves of Eucalyptus maideni

Abstract: Two new phloroglucinol-coupled sesquiterpenoids, eucalmaidials A and B (1 and 2), were isolated from the juvenile leaves of Eucalyptus maideni, along with eight known macrocarpals (3–10), eucalyptone (11), and three known triterpenoids (12–14). Eucalmaidials A and B represent a new skeleton of phloroglucinol-coupled iphionane. Their structures were elucidated by extensive NMR spectroscopic analysis and theoretical calculation of the 13C NMR chemical shifts. The biosynthetic pathway of 1 and 2 was also postulated. Compounds 1, 3, 5, 7, 8, and 10–14 were evaluated for their antifungal and antibacterial activities. Compound 1 exhibited antifungal activity against Candida glabrata with an IC50 value of 0.75 μg mL−1.

Solving the supply of resveratrol tetramers from Papua New Guinean rainforest anisoptera species that inhibit bacterial type III secretion systems.

Abstract: : The supply of (−)-hopeaphenol (1) was achieved via enzymatic biotransformation in order to provide material for preclinical investigation. High-throughput screen- ing of a prefractionate ...

Comparative study on "long-dan", "qin-jiao" and their adulterants by HPLC analysis.

Abstract: “Long-Dan” and “Qin-Jiao” are two important TCM herbs since ancient times in China. In the Chinese Pharmacopoeia, the dried roots and rhizomes of four species from the genus Gentiana, e.g. Gentiana manshurica, G. scabra, G. triflora and G. rigescens, are recorded under the name of Gentianae Radix et Rhizoma (“Long-Dan” in Chinese), while the other four species from the same genus including G. macrophylla, G. crassicaulis, G. straminea and G. duhurica are recorded and used as the raw materials of Gentianae Macrophyllae Radix (“Qin-Jiao” in Chinese). On the basis of the establishment of a validated HPLC–UV method for quantifying simultaneously, five iridoid glycosides, e.g. loganic acid (1), swertiamarinin (2), gentiopicroside (3), sweroside (4) and 2′-(o,m-dihydroxybenzyl)sweroside (5) have been used successfully as chemical markers for the comparison of the species used as “Long-Dan”, “Qin-Jiao” and their adulterants in the present study. The results suggested that four iridoid glycosides 1–4 commonly existed in both “Long-Dan” and “Qin-Jiao”, while 2′-(o,m-dihydroxybenzyl)sweroside (5) also existed as one of the major components in “Dian-Long-Dan” species. Moreover, the contents of compounds 1–5 were various in different “Long-Dan” and “Qin-Jiao” species. Herein, we profiled and compared three “Long-Dan” species, four “Qin-Jiao” species and five adulterants by applying multivariate statistical techniques to their HPLC data sets to establish the differences and/or similarities. Electronic supplementary material The online version of this article (doi:10.1007/s13659-014-0039-x) contains supplementary material, which is available to authorized users.

New Phenylpropanoid-Substituted Flavan-3-ols from Pu-er Ripe Tea

Abstract: Pu-er ripe tea is a special microbial post-fermented tea made from Pu-er raw tea, a kind of green tea produced from the leaves of Camellia sinensis var. assamica. It is one of the most consumed teas in the past two decades in China, due to its special flavor, taste, and beneficial effects. This work aimed to obtain diverse catechin structures from Pu-er ripe tea, which led to the isolation of four new phenylpropanoid-substituted flavan-3-ols, puerins C-F (1-4), together with four known fiavan-3-ols, (+)-catechin (5), (-)-epicatechin (6), (+/-)-gallocatechin (7), and (-)-epigallocatechin (8). Their structures were elucidated on the basis of detailed spectroscopic analysis, including ID and 2D NMR mass and CD spectra. Compounds 1-4, which could be formed in the post-fermentative process of Pu-er tea, were isolated for the first time from tea and Theaceae plant.

Highly Oxygenated Limonoids and Lignans from Phyllanthus flexuosus.

Abstract: Two new highly oxygenated limonoids, flexuosoids A (1) and B (2), and three new arylnaphthalene lignan glycosides, phyllanthusmins D–F (3–5), were isolated from the roots of Phyllanthus flexuosus, in addition to three known lignans, phyllanthusmin C, arabelline, and (+)-diasyringaresinol. Their structures were elucidated on the basis of detailed spectroscopic analysis and chemical methods. Compounds 1 and 2, two new decaoxygenated limonoids with a C-19/29 lactol bridge and heptaoxygenated substituents at C-1, C-2, C-3, C-7, C-11, C-17, and C-30, represent the second example of limonoids in the Euphorbiaceae family. Most of the isolates were tested for their antifeedant, anti-herpes simplex virus 1, and cytotoxic activities. The new limonoids 1 and 2 showed promising antifeedant activity against the beet army worm (Spodoptera exigua) with EC50 values of 25.1 and 17.3 μg/cm2, respectively. In addition, both of them displayed moderate cytotoxicity against the ECA109 human esophagus cancer cell line, along with the known lignan glycoside, phyllanthusmin C, with the IC50 values of 11.5 (1), 8.5 (2), and 7.8 (phyllanthusmin C) μM, respectively. Two new highly oxygenated limonoids, flexuosoids A (1) and B (2), and three new arylnaphthalene lignan glycosides, phyllanthusmins D–F (3–5), were isolated from the roots of Phyllanthus flexuosus, along with three known lignans. Flexuosoids A (1) and B (2) showed promising antifeedant activity against the beet army worm (Spodoptera exigua) with EC50 values of 25.1 and 17.3 μg/cm2, respectively. In addition, both of them and the known lignan glycoside, phyllanthusmin C, displayed moderate cytotoxicity against the ECA109 human esophagus cancer cell line, with the IC50 values of 11.5, 8.5, and 7.8 μM, respectively.

New phenolic glycosides from Phyllanthus cochinchinensis

Abstract: Chemical investigation of the whole plants of Phyllanthus cochinchinensis (Euphorbiaceae) led to the isolation of three new phenolic glycosides, phyllanthuosides A-C, together with 12 known compounds. Their structures were established on the basis of extensive spectroscopic analysis and chemical methods. Among them, phyllanthuosides A and B are two of the rare phenolic glycosides, featuring with a C6-C3-C6 skeleton. The absolute configurations of phyllanthuosides A and B were established by calculated electric circular dichroism (ECD) using time dependent density functional theory (TDDFT). The isolates were also tested for their cytotoxicity and antimicrobial activity.

A New Phloroglucinol Glucoside from the Whole Plants of Glochidion eriocarpum

Abstract: NSFC [21002105]; 973 Program of Ministry of Science and Technology of P. R. China [2011CB915503]; Fourteenth Candidates of the Young Academic Leaders of Yunnan Province [2011CI044]; West Light Foundation of the Chinese Academy of Sciences; Korean Chemical Society

Solving the supply of Resveratrol Tetramers from Papua New Guinean rainforest Anisoptera species (Dipterocarpaceae) that inhibit bacterial type III secretion systems

Abstract: The supply of (–)-hopeaphenol was achieved via enzymatic biotransformation in order to provide material for pre-clinical investigation. High-throughput screening of a pre-fractionated natural product library aimed to identify compounds that inhibit the bacterial virulence type III secretion system (T3SS) identified several fractions derived from two Papua New Guinean Anisoptera species, showing activity against Yersinia pseudotuberculosis outer proteins E and H (YopE and YopH). Bioassay-directed isolation from the leaves of A. thurifera, and similarly A. polyandra, resulted in three known resveratrol tetramers, (–)-hopeaphenol (1), vatalbinoside A (2) and vaticanol B (3). Compounds 1–3 displayed IC50 values of 8.8, 12.5 and 9.9 M in the reporter-gene assay, and IC50 values of 2.9, 4.5 and 3.3 M in the YopH assay, respectively, which suggested that they could potentially act against the T3SS in Yersinia. The structures of 1-3 were confirmed through a combination of spectrometric, chemical methods and single crystal X-ray structure determinations of the natural product 1 and the permethyl ether analogue of 3. The enzymatic hydrolysis of the β-glycoside 2 to the aglycone 1 was achieved through biotransformation using the endogenous leaf enzymes, this significantly enhanced the yield of the desired bioactive natural product from 0.08% to 1.3% and facilitates ADMET studies of (–)-hopeaphenol (1).

A New Phloroglucinol Glucoside from the Whole Plants of Glochidion eriocarpum.

Abstract: NSFC [21002105]; 973 Program of Ministry of Science and Technology of P. R. China [2011CB915503]; Fourteenth Candidates of the Young Academic Leaders of Yunnan Province [2011CI044]; West Light Foundation of the Chinese Academy of Sciences; Korean Chemical Society