Evaluation of dispersion state of the two racemic compounds of troglitazone in pharmaceutical granules using IR-to-THz imaging

Troglitazone exists as four isomers in equal amount and these isomers compose two racemic compounds, RR/SS and RS/SR. The objective of this study was to discriminate between the racemic compounds and between the crystal and amorphous forms of troglitazone in solid dispersions (SDs) using IR-to-THz imaging. SDs of troglitazone with polyvinylpyrrolidone (PVP, carrier) were prepared by the closed melting method. SDs were heated at various temperatures and water content. The mid-to-far infrared measurements for the powder samples were performed by using the synchrotron radiation source at the BL43IR in SPring-8. Crystalline RR/SS (L) and RS/SR (H) showed different spectra, that is, each form had a specific peak, respectively. However, amorphous forms prepared from each crystalline form exhibited the same spectra. Using the chemo-metric analysis, the existing component was decided in each pixel and the distribution of crystalline L, H and amorphous troglitazone in SDs could be illustrated. For the sample heated at 105 °C, 75%RH, scattered plots of H and amorphous against PVP showed the trend for H was negative; on the other hand, amorphous showed positive correlation. This result suggested that H existed separately, whereas amorphous would be dissolved in PVP. Based on these evaluations, it was clear that the physical state and distribution of troglitazone in SDs, including the discrimination between L, H, and amorphous, reflect the preparation conditions. Chemical imaging can observe a difference in the dispersed state of drug and ingredient in a visible image by performing statistical processing.     

The teacher’s role in guiding children’s mathematical ideas toward meeting lesson objectives

This paper investigates the classroom interactive pattern, in which the teacher aims to introduce new mathematical content to children by focusing on their mathematical thinking. First, by drawing on the results of studies on the features of social interaction patterns in mathematics classrooms, we develop a framework that we call a “guided focusing pattern,” composed of four phases. Next, we use this framework and Sfard’s (J Res Math Educ 31(3):296–327, 2000) theory of focal analysis to examine the social interaction occurring in a series of mathematics lessons conducted by an experienced teacher. In the ten consecutive lessons that we analyzed, the guided focusing pattern was salient; the teacher introduced key mathematical content to children while offering support and guidance in a variety of forms within each phase and when transitioning to the next phase. On the basis of the results, we highlight the teacher’s key instructional actions that facilitate the pattern of progressing through the mathematical content as closely linked to and guided by her lesson objectives.     

A new reagent, 2-[phenyl(methyl)sulfonio]ethyl-4-nitro-phenylcarbonate tetrafluoroborate (Pms-ONp), for preparing water-soluble N-protected amino acids

Peptide syntheses are performed in various organic solvents, the disposal of which is an environmental problem. To avoid this problem, peptide synthesis in water using reagents of low toxicity is desirable. For peptide synthesis in water, we previously reported the design of a water-soluble N-protecting group, 2-[phenyl(methyl)sulfonio]ethoxycarbonyl tetrafluoroborate (Pms) group, but the introduction of this group onto sulfur-containing amino acids was problematic. Here, a new reagent, 2-[phenyl(methyl)sulfonio]ethyl-4-nitrophenylcarbonate tetrafluoroborate (Pms-ONp), has been designed and used to prepare Pms derivatives of sulfur-containing amino acids. Pms-Met was prepared and tested for the solid-phase synthesis of Met-enkephalin amide in water using a crosslinked ethoxylate acrylate resin.     

Efficient synthesis of 3-cyano-6-(2-hydroxyphenyl)pyridines by multi-component condensations on beads

An efficient procedure to perform pyridine ring closure reactions has been developed on beads. A certain number of hydroxyacetophenones were immobilized on Wang resin and condensed with a variety of aldehydes and malononitrile in the presence of ammonium acetate to give 3-cyano-6-(2-hydroxyphenyl)pyridines in a suitable manner for a good example of combinatorial approaches. Chemical yields were better than the corresponding solution-phase chemistry except only a few examples and the best use of inherent advantage of solid-phase chemistry was successfully demonstrated.     

A new hydrogen-bonding motif for chiral recognition in the diastereomeric salts of racemic 1-phenylethylamine derivatives with enantiopure O-ethyl phenylphosphonothioic acid

An enantiopure phosphonothioic acid showed a unique and superior chiral recognition ability, arising from its P-stereogenicity, for racemic 1-phenylethylamine derivatives through diastereomeric crystallization. Spherical molecular clusters, associated by hydrogen bonds and CH/pi interactions, aggregated with high symmetry in the less-soluble diastereomeric salts.     

Enantioselective total synthesis of eurylene, 14-deacetyl eurylene, and their 11-epimers: the relation between ionophoric nature and cytotoxicity

[structure: see text] Enantioselective synthesis of eurylene, 14-deacetyl eurylene, and their 11-epimers was achieved. The characteristic structural feature of these compounds is two tetrahydrofuran (THF) rings substituted in different stereochemistry. The synthetic approach involves nonstereoselective THF ring formation to afford both segments from a common precursor. We also investigated their ionophoric nature and cytotoxicity. The complexation of these compounds with K(+) might be related to their cytotoxic activity.     

Chemical modification of butyl rubber. III. Butyl rubber with D-maltose derivative as pendant groups

A new type of amphiphilic elastomer was synthesized, which consisted of butyl rubber and a D-maltose derivative as a backbone and side groups, respectively. The synthesis was accomplished by the sequence of the three following reactions: (1) Hydroxyl groups of D-maltonolactone were protected by a trimethylsilyl group. (2) The resulting maltonolactone derivative was subjected to a reaction with chemically modified butyl rubber having pendant amino groups. (3) The protecting trimethylsilyl groups on the maltose residues were removed by treating with tetra-n-butylammonium fluoride. This new amphiphilic elastomer behaved as a thermoplastic elastomer and showed good mechanical properties. The saccharide seg-ments aggregated in the hydrophobic butyl rubber matrix to form a microphase-separated structure, as confirmed by differential scanning calorimetry, transmission electron mi-croscopy, small-angle x-ray scattering, and dynamic mechanical measurements. The ag-gregated saccharide domains are estimated to function both as crosslinking sites and rein-forcing fillers in the rubber matrix. © 1995 John Wiley & Sons, Inc.     

Dietary,but not topical,alpha-linolenic acid suppresses UVB-induced skin injury in hairless mice when compared with linoleic acids

Peroxidizability of fatty acids in the air is roughly proportional to the number of double bonds, but in vivo peroxidation proceeds in a more complex manner. Here, we compared the effects of dietary and topically applied oils enriched with linoleic acid (LA, 18:2n-6) or alpha-linolenic acid (ALA, 18:3n-3) on UV-induced skin injury in a strain of hairless mice. The UVB-induced erythema score was significantly lower in mice with topically applied creams containing LA and ALA than in mice with the basal cream; no significant increase in the score was detected in the ALA group compared with the LA group. However, dietary ALA inhibited the increase in erythema score after UVB irradiation compared with LA. The peroxidizability index of the skin total lipids was significantly higher, but UVB-induced prostaglandin E2 (PGE2) production was significantly lower in the group fed an ALA-rich diet compared with the group fed an LA-rich diet. The levels of thiobarbituric acid-reactive substances, estimated in the presence of butylated hydroxytoluene in the assay mixture, were not affected by UVB treatment or by the dietary fatty acids, but the severity of the skin lesion was associated with PGE2 levels. These results indicate that the type of fatty acids, n-6 or n-3, is critical for the suppression of UVB-induced skin lesion when the skin fatty acids are modified by dietary manipulation. Anti-inflammatory activity of dietary flaxseed oil with relatively high ALA and low LA contents was demonstrated in UVB-irradiated hairless mice.     

Synthesis of styrenes using ruthenium-catalyzed ring-closing enyne metathesis

The synthesis of substituted styrenes was achieved by ring-closing enyne metathesis (RCEM)/elimination of enyne substrates 12. The synthetic approach was also effective for a different type of enyne substrate 14, yielding corresponding styrene 15.