Synthesis and anti-HIV-1 activity of novel 10-thiaisoalloxazines,a structural analog of C-5 and/or C-6 substituted pyrimidine acyclonucleoside

A series of novel 10-thiaisoalloxazine derivatives bearing an alkoxymethyl or benzyloxymethyl moiety at the N-1 position has been synthesized through the bromination of 1-substituted-5-hydroxyuracils and subsequent condensation with aminobenzenethiol in a one-pot reaction. Contrary to the previous report, the formation of intermediary 5,6-diethoxy-5-hydroxy-5,6-dihydrouracil seems to be not the necessary factor for the formation of the thiaisoalloxazines, since the reaction proceeds in tetrahydrofuran (THF) or acetonitrile far more smoothly than in ethanol. The anti-human immunodeficiency virus (HIV)-1 activity of the resulted thiaisoalloxazine derivatives was evaluated in lymphocyte cells based on the inhibitory activity against the viral-induced cytopathic activity. Among the derivatives, compounds 6, 7, and 8 bearing an alkoxymethyl moiety at the N-1 position exhibited modest inhibitory activity towards the cytotopathic effect of HIV-1.     

Sulfonylamidation of alkylbenzenes at benzylic position with p-toluenesulfonamide and 1,3-diiodo-5,5-dimethylhydantoin

Treatment of alkylbenzenes with p-toluenesulfonamide and 1,3-diiodo-5,5-dimethylhydantoin (DIH) in a small amount of carbon tetrachloride at 60 °C gave the corresponding α-p-toluenesulfonylamido)alkylbenzenes in good to moderate yields. The present reaction is a simple method for the α-sulfonylamidation of the benzylic position in alkylbenzenes.     

Hierarchical structure in polymer‐based drug delivery systems as probed by calorimetric measurements

Thermoporosimetry (TPM), a differential scanning calorimetry technique that relies on the shift of transition temperatures caused by the confinement of liquids, was applied to elucidate the complex morphology of drug‐loaded polymeric microcapsules prepared by the emulsion solvent evaporation method. For the very first time, TPM has been applied simultaneously with two liquids as structural probes. It was found that Miglyol, which dissolves the selected drug (Ibuprofen), is confined inside vesicles having a mean radius of 26.3 nm, whereas water, which is the continuous phase, is trapped inside a swollen polymeric network of Eudragit with an average mesh radius of 1.7 nm. A proposed hierarchical structure is given, which predicts that Eudragit microcapsules are formed from a collection of inert oil vesicles partitioned by polymeric Eudragit membranes swollen by water. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 1939–1945, 2010     

Long-term observation of fluorescence of free single molecules to explore protein-folding energy landscapes

A method was developed to detect fluorescence intensity signals from single molecules diffusing freely in a capillary cell. A unique optical system based on a spherical mirror was designed to enable quantitative detection of the fluorescence intensity. Furthermore, "flow-and-stop" control of the sample can extend the observation time of single molecules to several seconds, which is more than 1000 times longer than the observation time available using a typical confocal method. We used this method to scrutinize the fluorescence time series of the labeled cytochrome c in the unfolded state. Time series analyses of the trajectories based on local equilibrium state analysis revealed dynamically differing substates on a millisecond time scale. This system presents a new avenue for experimental characterization of the protein-folding energy landscape.     

Fast separation of oligonucleotide and triplet repeat DNA on a microfabricated capillary electrophoresis device and capillary electrophoresis

A laser-induced fluorescence detection system coupled with a highly sensitive silicon-intensified target (SIT) camera is successfully applied to the imaging of a band for DNA fragment labeling by fluorescence dye in a microchannel, and to the visualizing of the separation process on a microfabricated chip. We demonstrated that an only 6 mm separation channel is sufficient for the separation of triplet repeat DNA fragment and DNA molecular marker within only 12 s. The separation using the microfabricated capillary electrophoresis device is confirmed to be at least 18 times faster than the same separation carried out by conventional capillary electrophoresis with 24.5 cm effective length. The use of a short capillary with 8.5 cm effective length is also efficient for fast separation of DNA; however, the microchip technology is even faster than capillary electrophoresis using a short capillary.     

A novel injection method for high-speed proteome analysis by capillary electrophoresis

We have developed a new sample injection method for capillary electrophoresis (CE) that reduces the required migration time. We demonstrated a pressurization technique that was performed with buffer in the outlet after the electrokinetic sample injection with no buffer in the outlet. To reduce the migration time, the sample injection had to be performed with no buffer in the outlet; water should be pressurized while the buffer is in the outlet. Though the resolution was slightly decreased using this method, the addition of a separation carrier (curdlan) to the run buffer restored the resolution without delaying the migration time. The use of our new sample injection method combined with our high-quality separation carrier will enable us to improve the efficiency of the high-throughput screening (HTS) system for proteome analysis.     

Synthesis and simple separation of β-pyrrole sulfonated porphycenes

New water-soluble porphycenes having sulfonic acid groups at the β-pyrrolic positions were synthesized and characterized by UV-vis, NMR, IR, and mass spectroscopy as well as elemental analyses. The series of mono- to tri-sulfonato derivatives were simply separated by the extraction method.     

Four guaianolides from Sinodielsia yunnanensis

Four new guaianolides, sinodielides A-D (1-4), were isolated from Sinodielsia yunnanensis WOLFF together with a known polyacetylene, falcarindiol, and two known coumarins, bergapten and scopoletin. Their structures were established by spectral and X-ray analyses.     

Methyl 3‐para‐anisyl‐4‐(2‐hydroxy­benzoyl)­isoxazole‐5‐carboxyl­ate

The title compound, C₁₉H₁₅NO₆, contains a planar isoxazole ring. An intramolecular hydrogen bond is formed between the OH group attached to a phenyl ring and a carbonyl O atom.