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Two pairs of diastereoisomeric isoindoline alkaloids, xylarins A-D (1-4), were isolated from the endolichenic fungus Xylaria sp. Xylarins A and B (1 and 2) possess a previously undescribed 5/6/5-5/6 polycyclic scaffold, featuring a combination of a novel dihydrobenzofurone unit and an isoindoline unit, while xylarins C and D (3 and 4) contain an additional N,N-dimethylaniline at the C-3' position. Their structures were elucidated by comprehensive spectroscopic analyses combined with single-crystal X-ray diffraction and electronic circular dichroism calculations. The plausible biosynthetic pathways and gene clusters for 1-4 were proposed. Compound 1 exhibited significant antithrombotic activity.

Many exceptional labdane-type diterpenoids have been exclusively found in liverworts, which serve as taxonomic molecules or play important ecological roles in interactions among organisms. Three unprecedented labdane-type diterpenoids hapmnioides A (1), B (2), and C (3) formed through cascade rearrangement from the Chinese liverwort Haplomitrium mnioides are reported. Their structures were established by comprehensive spectroscopic analysis coupled with single-crystal X-ray diffraction, and their anti-inflammatory activities were also preliminarily tested.

p21-Activated kinase 4 (PAK4) is a serine/threonine protein kinase that plays important roles in a wide variety of human diseases including cancer. Targeting this kinase with specific inhibitors is of great interest in the treatment of cancer. In this study, PAK4 and its interaction with ATP-competitive inhibitors was investigated by a combined ligand- and structure-based approach. First, a ligand-based pharmacophore model was generated, consisting of five chemical features: a positive ionizable center, two hydrophobic groups, a hydrogen bond donor, and a hydrogen bond acceptor, which is consistent with available SAR information. The characteristics of the active site were then described as a topological region and used in docking of nine selected inhibitors. Combination of the pharmacophore model and results from the docking studies allowed us to weigh the various pharmacophore features and to identify the positive ionizable center as a spacer rather than an essential point. This research led to the proposal of an interaction model inside the PAK4 active site and provided guidance for the design of more potent PAK4 inhibitors.

Sixteen new clerodane diterpenoids, cephaloziellins A-P (1-16), and two known analogues (17 and 18) were isolated from an EtOH extract of the Chinese liverwort Cephaloziella kiaeri. The structures of the new compounds were elucidated from extensive spectroscopic data (IR, UV, HRESIMS, 1D NMR, and 2D NMR), and the structures of 5, 9, and 15 were confirmed by single-crystal X-ray diffraction analyses. The absolute configurations of all new compounds were established by comparing experimental and calculated electronic circular dichroism spectra.

The impact of two types of natural organic matters (NOM), humic acid (HA) and lipid, on char properties and sorption affinities for phenanthrene was studied. Char was coated with HA and lipid at a concentration of 0.060, 0.250 and 0.500 g/g char. HA, lipid, char and coated char were characterized and their sorption behaviors for phenanthrene were compared. Coating with NOM increased the polarity and aliphaticity, and reduced the specific surface area (SSA) of char, depending on the coated amount and the type of NOM. At the lower HA and lipid loading there was a strong attenuation of N(2)-assessible SSA. The SSA attenuation was less pronounced at larger HA and lipid loadings, which was most likely due to the preferential sorption at reactive sites and formation of clusters. The sorption isotherms of phenanthrene on char and coated char fitted Freundlich equation well, suggesting that all sorption isotherms were nonlinear, with N values in the range of 0.495-0.873. Coated char with HA and lipid decreased the organic carbon-normalized sorption coefficients K(Foc) and increased the N values. Lipid was more effective than HA in decreasing SSA. phenanthrene sorption capacity and sorption isotherm nonlinearity. The N values were correlated positively with the aliphaticity and negatively with pore volume of sorbents. The results of this investigation demonstrated that different NOM plays a different role in attenuating the SSA and sorption affinity of char for phenanthrene. (C) 2009 Elsevier B.V. All rights reserved.

Aim To study the chemical constituents of the Chinese liverwort Porella acutifolia subsp. tosana . Methods The compounds were isolated and purified with column chromatography and their structures were determined on the basis of 1D- and 2D-NMR analysis. Results Three compounds were obtained and identified as guaian-3-en-2α, 14-6α, 12-diolide ( 1 ), (20 R )-6β-hydroxystigmasta-4, 22-dien-3-one ( 2 ), and (20 R )-3β-hydroxystigmasta-5, 22-dien-7-one ( 3 ). Conclusion Compound 1 is a new guaiane-type sesquiterpene lactone. Compounds 2 and 3 are known steroids.

A new and efficient total synthesis has been developed to obtain plagiochin G (22), a macrocyclic bisbibenzyl, and four derivatives. The key 16-membered ring containing biphenyl ether and biaryl units was closed via an intramolecular SNAr reaction. All synthesized macrocyclic bisbibenzyls inhibited Epstein–Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells and, thus, are potential cancer chemopreventive agents.

Six new cembrane-type diterpenoids (1–6) were isolated from two species of Chandonanthus: Chandonanones A, B, and D–F (1, 2, and 4–6) were isolated from C. hirtellus, and chandonanones B, C, E, and F (2, 3, 5, and 6) from C. birmensis. Five known diterpenoids, (8E)-4α-acetoxy-12α,13α-epoxycembra-1(15),8-diene (7), isochandonanthone (8), chandonanthone (9), anadensin (10), and 2,10,14-triacetoxy-7,8,18,19-diepoxydolabell-3(E)-ene (11), were also obtained. The structures of the new metabolites were established by analyses of their spectroscopic data (1D NMR, 2D NMR, HRESIMS, and IR). The absolute configurations of compounds 1 and 2 were unequivocally confirmed using single-crystal X-ray diffraction analysis with Cu Kα radiation. Cytotoxicity tests of the isolated diterpenoids against seven cancer cell lines (DU145, PC3, A549, PC12, NCI-H292, NCI-H1299, and A172) revealed that some of the diterpenoids had weak activity.

Ten new dolabrane-type diterpenoids, notolutesins A-J (1-10), were isolated from the Chinese liverwort Notoscyphus lutescens, along with four known compounds. The structures of the new compounds were established on the basis of extensive spectroscopic data, and that of 1 was confirmed by single-crystal X-ray crystallography. The absolute configuration of 1 was determined by comparing its experimental and calculated electronic circular dichroism spectra. All of the isolates were evaluated for their cytotoxicity against a small panel of human cancer cell lines, and compound 1 exhibited an IC50 value of 6.2 μM against the PC3 human prostate cancer cell line.

Two new cadinane-type sesquiterpenes, frullanic acid (1) and frullanic acid methyl ester (2), together with four known bibenzyls, brittonin B (3), 3,3′-dimethoxy-4,5-methylenedioxybibenzyl (4), 3,4,5,3′,4′-penlamethoxybibenzyl (5) and ( ± )-3-(4′-methoxybenzyl)-5,6-dimethoxyphtbalide (6), were isolated from the Chinese liverwort Frullania serrata. The structures of the new metabolites were elucidated by analysing the spectroscopic data (1D NMR, 2D NMR, HR-ESI-MS and IR). The absolute configurations of compounds 1 and 2 were determined by comparing the experimental and calculated electronic circular dichroism spectra predicted by using time-dependent density functional theory as well as the CD exciton chirality method.

Three new pimarane-type diterpenoids, 7β,11α-dihydroxypimara-8(14),15-diene (1), 1β,11α-dihydroxypimara-8(14),15-diene (2), and 11α-hydroxypimara-8(14),15-diene (3), five 2,3-secoaromadendrane-type sesquiterpenoids, including a new one, ethyoxyplagiochiline A2 (4), and three known fusicoccane-type diterpenoids were isolated from the Chinese liverwort Plagiochila pulcherrima. Their structures were established on the basis of extensive spectroscopic analysis. Compounds 6 and 7 exhibited moderate inhibitory activity on the proliferation of human cancer cell lines Hela, A172, and H460. Moreover, the cytotoxicity of compound 6 to Hela cells was related to apoptotis as confirmed by DAPI nuclear staining and flow cytometry.

Mycobacterium tuberculosis FabH, an essential enzyme in the mycolic acid biosynthetic pathway, is an attractive target for novel anti-tubercolosis agents. Structure-based design and synthesis of 1-(4-carboxybutyl)-4-(4-(substituted benzyloxy)phenyl)-1H-pyrrole-2-carboxylic acid derivatives 7a–h, a subset of eight potential FabH inhibitors, is described in this paper. The Vilsmeier-Haack reaction was employed as a key step. The structures of all the newly synthesized compounds were identified by IR, 1H-NMR, 13C-NMR, ESI-MS and HRMS. The alamarBlue™ microassay was employed to evaluate the compounds 7a–h against Mycobacterium tuberculosis H37Rv. The results demonstrate that the compound 7d possesses good in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (Minimum Inhibitory Concentration value [MIC], 12.5 µg/mL).These compounds may prove useful in the discovery and development of new anti-tuberculosis drugs.