Novel spirocyclic trichothecanes, spirotenuipesine A and B, isolated from entomopathogenic fungus, Paecilomyces tenuipes

Entomopathogenic fungi forming fruiting bodies have been employed as tonics and antitussives from ancient times. Paecilomyces tenuipes, which is also called Isaria japonica, is a very popular entomopathogenic fungus and is often considered a health food in northeast Asian countries such as China, Korea, and Japan. We cultivated the fruiting bodies of Paecilomyces tenuipes. Among the large-scale cultivations, fruiting body grown in barley grain contained two novel spirocyclic trichothecane derivatives, spirotenuipesine A (1) and B (2), and known trichothecane mycotoxins. Compounds 1 and 2 showed potent activity in neurotrophic factor biosynthesis in glial cells. The isolation of these compounds indicated that P. tenuipes is a promising source for producing various biologically active substances including trichothecanes. It is noteworthy that trichothecane mycotoxins are present in Paecilomyces tenuipes, which is typically used in medicinal health food.     

Enantioselective Addition Reaction of Azlactones with Styrene Derivatives Catalyzed by Strong Chiral Brønsted Acids

An enantioselective intermolecular addition reaction of azlactones, as carbon nucleophiles, with styrene derivatives, as simple olefins, was demonstrated using a newly developed chiral Brønsted acid catalyst, namely, F₁₀BINOL‐derived N‐triflyl phosphoramide. Addition products having vicinal tetrasubstituted carbon centers, one of which is an all‐carbon quaternary stereogenic center, were formed in good yields with moderate to high stereoselectivities. Extremely high acidity of the new chiral Brønsted acid was confirmed by its calculated pK_a value based on DFT studies and is the key to accomplishing not only high catalytic activity but also efficient stereocontrol in the intermolecular addition.     

A screw-shaped alignment of pyrene using m-calix[3]amide

m-Calix[3]amide bearing three pyrenes (1a) was prepared by the condensation reaction of 3-nonylaminobenzoic acid derivative using Ph₃PCl₂. Pyrenyl groups were found to be aligned in the screw-like fashion by m-calix[3]amide as confirmed by the X-ray crystallography. Aromatic proton signals observed at the up-field region in the ¹H NMR spectrum at low temperature indicated that pyrenyl groups in 1a are aligned in close proximity in THF solution. UV–vis absorption and fluorescence emission spectra did not show marked peak shift nor concentration fluorescence quenching compared with reference compounds implying no significant electronic interaction between pyrenyl groups. These results can be explained by the steric effect of the m-calix[3]amide platform. On the other hand, an excimer emission was observed for m-calix[3]amide having a flexible spacer between pyrene and m-calix[3]amide (1b).     

Photocatalytic oxidation of 2-propanol under visible light irradiation on TiO<Subscript>2</Subscript> thin films prepared by an RF magnetron sputtering deposition method

Visible light-responsive TiO₂ (Vis-TiO₂) thin films able to absorb UV and visible light in wavelength regions of 250–600 nm were successfully developed by applying a radio-frequency magnetron sputtering deposition method. These Vis-TiO₂ thin films exhibited high activity for the photocatalytic oxidation of 2-propanol diluted in water even under visible light irradiation (λ ≥ 450 nm). The photocatalytic activity of Vis-TiO₂ thin films was dramatically enhanced by the deposition of Pt particles on the surface. Secondary ion mass spectrometry measurements revealed that Pt particles are distributed from the top surface to the deep bulk of Vis-TiO₂ thin films with a columnar structure. The unique columnar structure of Vis-TiO₂ thin films plays an important role in the high photocatalytic performance.     

Protein-bound uremic toxins in hemodialysis patients measured by liquid chromatography/tandem mass spectrometry and their effects on endothelial ROS production

Cardiovascular disease (CVD) is prevalent in patients with chronic kidney disease (CKD). In hemodialysis (HD) patients, some protein-bound uremic toxins are considered to be associated with CVD. However, it is not yet known which uremic toxins are important in terms of endothelial toxicity. Serum samples were obtained from 45 HD patients before and after HD. Total and free serum concentrations of indoxyl sulfate, indoxyl glucuronide, indoleacetic acid, p-cresyl sulfate, p-cresyl glucuronide, phenyl sulfate, phenyl glucuronide, phenylacetic acid, phenylacetyl glutamine, hippuric acid, 4-ethylphenyl sulfate, and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) were simultaneously measured by liquid chromatography/electrospray ionization-mass spectrometry/mass spectrometry (LC/ESI-MS/MS). The effects of these solutes at their pre-HD mean and maximum serum concentrations on reactive oxygen species (ROS) production in human umbilical vein endothelial cells (HUVEC) were measured with a ROS probe. Serum levels of 11 of the solutes (all except 4-ethylphenyl sulfate) were significantly increased in HD patients compared to healthy subjects. All 12 solutes showed changes in their protein-binding ratios. In particular, indoxyl sulfate, p-cresyl sulfate, CMPF, and 4-ethylphenyl sulfate showed high protein-binding ratios (>95 %) and low reduction rates by HD (<35 %). Indoxyl sulfate at its mean and maximum pre-HD serum concentrations-even with 4 % albumin-stimulated ROS production in HUVEC most intensely, followed by CMPF. In conclusion, the serum levels of 11 protein-bound uremic toxins were increased in HD patients. Indoxyl sulfate, p-cresyl sulfate, and CMPF could not be removed efficiently by HD due to their high protein-binding ratios. Indoxyl sulfate most intensely induced endothelial ROS production, followed by CMPF.     

Structural confirmation of oligosaccharides newly isolated from sugar beet molasses

ABSTRACT: BACKGROUND: Sugar beet molasses is a viscous by-product of the processing of sugar beets into sugar. The molasses is known to contain sucrose and raffinose, a typical trisaccharide, with a well-established structure. Although sugar beet molasses contains various other oligosaccharides as well, the structures of those oligosaccharides have not been examined in detail. The purpose of this study was isolation and structural confirmation of these other oligosaccharides found in sugar beet molasses. RESULTS: Four oligosaccharides were newly isolated from sugar beet molasses using high-performance liquid chromatography (HPLC) and carbon-Celite column chromatography. Structural confirmation of the saccharides was provided by methylation analysis, matrix-assisted laser desorption/ionaization time of flight mass spectrometry (MALDI-TOF-MS), and nuclear magnetic resonance (NMR) measurements. CONCLUSION: The following oligosaccharides were identified in sugar beet molasses: beta-D-galactopyranosyl-(1- > 6)-beta-D-fructofuranosyl-(2 <-> 1)-alpha-D-glucopyranoside (named beta-planteose), alpha-D-galactopyranosyl-(1- > 1)-beta-D-fructofuranosyl-(2 <-> 1)-alpha-D-glucopyranoside (named1-planteose), alpha-D-glucopyranosyl-(1- > 6)-alpha-D-glucopyranosyl-(1 <-> 2)-beta-D-fructofuranoside (theanderose), and beta-D-glucopyranosyl-(1- > 3)-alpha-D-glucopyranosyl-(1 <-> 2)-beta-D-fructofuranoside (laminaribiofructose). 1-planteose and laminaribiofructose were isolated from natural sources for the first time.     

A new geranylated aromatic compound from the mushroom Hericium erinaceum

A new geranylated aromatic compound, 5-[(2'E)-3',7'-dimethyl-2',6'-octadienyl]-4-hydroxy-6-methoxy-1-isoindolinone (1), was isolated from the fruiting bodies of the mushroom Hericium erinaceum (Bull.: Fr.) Pers. (Hericiaceae) together with three known sterols, 5alpha,6alpha-epoxy-(22E)-ergosta-8(14),22-diene-3beta,7alpha-diol (2), (22E)-ergosta-7,9(11),22-triene-3beta,5alpha,6beta-triol (3) and (22E)-ergosta-7,22-diene-3beta,5alpha,6alpha,9alpha-tetrol (4). The structure of the new compound was elucidated on the basis of spectral data.     

No-wash protein labeling with designed fluorogenic probes and application to real-time pulse-chase analysis

Small molecule labeling techniques for cellular proteins under physiological conditions are very promising for revealing new biological functions. We developed a no-wash fluorogenic labeling system by exploiting fluorescence resonance energy transfer (FRET)-based fluorescein-cephalosporin-azopyridinium probes and a mutant β-lactamase tag. Fast quencher elimination, hydrophilicity, and high resistance against autodegradation were achieved by rational refinement of the structure. By applying the probe to real-time pulse-chase analysis, the trafficking of epidermal growth factor receptors between cell surface and intracellular region was imaged. In addition, membrane-permeable derivatization of the probe enabled no-wash fluorogenic labeling of intracellular proteins.     

Relationship between diffusivity of water molecules inside hydrating tablets and their drug release behavior elucidated by magnetic resonance imaging

We reported previously that sustained release matrix tablets showed zero-order drug release without being affected by pH change. To understand drug release mechanisms more fully, we monitored the swelling and erosion of hydrating tablets using magnetic resonance imaging (MRI). Three different types of tablets comprised of polyion complex-forming materials and a hydroxypropyl methylcellulose (HPMC) were used. Proton density- and diffusion-weighted images of the hydrating tablets were acquired at intervals. Furthermore, apparent self-diffusion coefficient maps were generated from diffusion-weighted imaging to evaluate the state of hydrating tablets. Our findings indicated that water penetration into polyion complex tablets was faster than that into HPMC matrix tablets. In polyion complex tablets, water molecules were dispersed homogeneously and their diffusivity was relatively high, whereas in HPMC matrix tablets, water molecule movement was tightly restricted within the gel. An optimal tablet formulation determined in a previous study had water molecule penetration and diffusivity properties that appeared intermediate to those of polyion complex and HPMC matrix tablets; water molecules were capable of penetrating throughout the tablets and relatively high diffusivity was similar to that in the polyion complex tablet, whereas like the HPMC matrix tablet, it was well swollen. This study succeeded in characterizing the tablet hydration process. MRI provides profound insight into the state of water molecules in hydrating tablets; thus, it is a useful tool for understanding drug release mechanisms at a molecular level.     

Phenolic compounds from the aerial parts of Diplomorpha canescens

One new C-methyl flavanone glucoside, farrerol 4'-O-β-D-glucopyranoside (1) was isolated from the aerial parts of Diplomorpha canescens (MEISN.) C. A. MEYER. Fourteen known phenolic compounds such as farrerol (2), luteolin 7-methyl ether 5-O-β-D-glucopyranoside (3), (-)-pinoresinol (4), (-)-lariciresinol (5), (-)-dihydrosesamin (6), (±)-dehydrodiconiferyl alcohol (7), rutarensin (8), umbelliferone (9), coniferyl aldehyde (10), sinapyl aldehyde (11), p-coumaric acid methyl ester (12), p-hydroxybenzaldehyde (13), p-hydroxyacetophenone (14) and syringaldehyde (15) were also isolated for the first time from this plant. Structure of 1 was determined on the basis of spectroscopic data including two dimensional (2D)-NMR, circular dichroism (CD) and by the application of Klyne's rule.