Preparation of dry powder inhalation with lactose carrier particles surface-coated using a Wurster fluidized bed

An attempt was made to produce carrier particles for dry powder inhalation with lactose carrier particles surface-coated using a Wurster fluidized bed. The lactose carrier particles were coated with lactose aqueous solution containing hydroxypropyl methyl cellulose (HPMC) as a binder using a Wurster coating apparatus. Drug/carrier powder mixtures were prepared consisting of micronized salbutamol sulfate and lactose carriers under various particle surface conditions. These powder mixtures were aerosolized by a Jethaler((R)), and the in vitro deposition properties of salbutamol sulfate were evaluated by a twin impinger. The in vitro inhalation properties of the powder mixture prepared using the coated lactose carrier differed significantly compared with those of the powder mixture prepared using the uncoated lactose carrier, indicating improvements in in vitro inhalation properties of sulbutamol sulfate. In vitro inhalation properties increased with the surface coating time. This surface coating system would thus be valuable for increasing the in vitro inhalation properties of dry powder inhalation with lactose carrier particles.     

Mechanism of antioxidant action of pueraria glycoside (PG)-1 (an isoflavonoid) and mangiferin (a xanthonoid).

The antioxidant activities of pueraria glycoside (PG)-1 (isoflavonoid) and mangiferin (xanthonoid) were studied and compared with PG-3 and daidzein (isoflavonoids) and with wogonin (flavonoid). PG-1 and mangiferin rapidly scavenged 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, and inhibited lipid peroxidation which was initiated enzymatically by reduced nicotinamide adenine dinucleotide phosphate (NADPH) or non-enzymatically by ascorbic acid or Fenton's reagent (H2O2 + Fe2+) in rat liver microsomes. Wogonin inhibited the enzymatically induced lipid peroxidation but had no scavenging effect on DPPH radical or on the non-enzymatic peroxidation. PG-3 and daidzein did not show any of these effects. Formation of Fe2+ by NADPH-dependent cytochrome P-450 reductase was inhibited by wogonin, but not by PG-1 or mangiferin. PG-1 and mangiferin had no effect on terminating radical chain reaction during the lipid peroxidation in the enzymatic system of microsomes or in the linoleic acid hydroperoxide-induced peroxidation system. These results suggest that PG-1 and mangiferin have an antioxidant activity, probably due to their ability to scavenge free radicals involved in initiation of lipid peroxidation. In contrast, wogonin may affect NADPH-dependent cytochrome P-450 reductase action, since it inhibited only the enzymatically induced lipid peroxidation.     

Efficient synthesis of a 4,5-epoxy-2-cyclohexen-1-one derivative bearing a spirolactone via a Diels-Alder reaction with high pi-facial selectivity: a synthetic study towards scyphostatin

The Diels-Alder reaction of spirolactones with cyclopentadiene afforded the adduct with high pi-facial selectivity; a hydrophilic analogue of scyphostatin was synthesized from the Diels-Alder adduct.     

1,3-Dipolar cycloaddition reaction of phenanthridinium N-imines and N-benzoylimine with acetylenic compounds

N-Aminophenanthridinium salt reacted with dimethyl acetylenedicarboxylate in the presence of potassium carbonate to give a 3,3a-dihydropyrazolo[1,5-f]phenanthridine but with mono-substituted acetylenes (ethyl propiolate and benzoylacetylene) it produced aromatized pyrazolo-[1,5-f]phenanthridines (XII and XIII). The reaction of the N-benzoylimine with di-substituted acetylenes (dimethyl acetylenedicarboxylate and methyl phenylpropiolate) and mono-substituted acetylenes (ethyl propiolate and benzoylacetylene) yielded 1,3a-dihydropyrazolo[1,5-f]phenanthridines and the aromatized products (XII and XIII), respectively.     

Arg-72 of pharaonis phoborhodopsin (sensory rhodopsin II) is important for the maintenance of the protein structure in the solubilized states

In bacteriorhodopsin (bR), Arg-82bR has been proven to be a very important residue for functional role of this light-driven proton pump. The arginine residue at this position is a super-conserved residue among archaeal rhodopsins. pharaonis phoborhodopsin (ppR; or called as "pharaonis sensory rhodopsin II") has its absorption maximum at 498 nm and acts as a sensor in the membrane of Natronobacterium pharaonis, mediating the negative phototaxis from the light of wavelength shorter than 520 nm. To investigate the role of the arginine residue (Arg-72ppR) of ppR corresponding to Arg-82bR, mutants whose Arg-72ppR was replaced by alanine (R72A), lysine (R72K), glutamine (R72Q) and serine (R72S) were prepared. These mutants were unstable in low concentrations of NaCl and lost their color gradually when the proteins were solubilized with 0.1% n-dodecyl-beta-D-maltoside. The order of instability was R72S > R72A > R72K > R72Q > the wild type. The rates of denaturation were reduced in a solution of high concentrations of monovalent anions.     

A DFT and direct MO dynamics study on the structures and electronic states of phenyl-capped terthiophene

The structures and electronic states of phenyl-capped terthiophene (denoted by P3T) and the ionic species of P3T have been investigated by means of density functional theory (DFT) and direct MO dynamics calculations. P3T is one of the high-performance molecular devices, which has been utilized as a semi-conductor. The calculations indicated that the neutral P3T has a non-planar structure whose the phenyl rings in both ends of thiophene chain are largely deviated from the molecular plane. The cation and anion radicals, dication and dianion were considered as its ionic states. The structure for cation radical of P3T is close to more planar than that of neutral P3T. The structures for anion radical, dication and dianion take a pure planar structure. The first excitation energy of neutral P3T is calculated to be 2.90 eV at the TD-B3LYP/6-31G(d)//B3LYP/6-311+G(d) level, while the P3T cation and anion radicals have lower excitation energies (1.22 and 1.10 eV, respectively). The direct MO dynamics calculation showed that neutral, cation and anion hold near planar structure at 300 K. On the other hand, oligothiophene (n = 5) and its ionic species are strongly deformed from the planar structure, and thiophene rings in both ends of chain rotate rapidly by thermal activation. The mechanism of the electron conductivity in P3T was discussed on the basis of theoretical results.     

Plaunol A and B,new anti-ulcer diterpenelactones from Crotonsublyratus

Two new diterpenelactones named plaunol A ($\text{2}$) and B ($\text{3}$) exhibiting anti-Shay ulcer activity were isolated from Thai medicinal plant, $\text{Croton}$$\text{sublyratus}$. Structure of $\text{2}$ was determined by X-ray analysis of its $\text{p}$-bromobenzoate and structure of $\text{3}$ was deduced from the results of chemical correlation and the spectral data.     

Novel synthesis of 1,3-dienes from 1-alkenes via /ldene/rd reaction with pummerer rearrangement product: a short synthesis of the sex pheromone of the red bollworm moth

A Pummerer rearrangement product, 4-chlorophenylthiomethyl trifluoroacetate (6), obtained from 4-chlorophenyl methyl sulfoxide (5) and trifluoroacetic anhydride, reacted with 1-alkenes in trifluoroacetic acid to give the ene products 8, which were readily converted into the terminal 1,3-dienes 10 by oxidation and subsequent pyrolysis. Using this method, 9,11-dodecadien-1-yl acetate (12), a sex pheromone of the red bollworm moth, was synthesized.     

SbF5/PAF—a novel fluorinating reagent in preparing fluorine compounds

A novel fluorination reagent and catalyst, SbF₅/PAF (porous aluminum fluoride), was prepared by impregnating SbCl₅ into PAF and then treating with anhydrous hydrogen fluoride. The prepared reagent had an excellent catalytic activity in halogen-exchange, and also improved the properties of SbF₅, such as hydroscopicity, corrosion, and toxicity. SbF₅/PAF was successfully used in organic synthesis as a fluorinating reagent, and a fixed bed catalyst for F/Cl exchange.     

Condensed pyridazines. Part IV. Reductive cyclization of (Z)-methyl 3-(6-azido-3-chloro-1-methyl-4-oxo-1,4-dihydropyridazin-5-yl)-2-rnethylacrylatc (I) to pyrido[2,3-c] pyridazines and the acid-catalysed cyclization of I to a pyrano[2,3-d] pyridazine

Reduction followed by cyclization of (Z)-methyl 3-(6-azido-3-chloro-1-methyl-4-oxo-1,4-dihydropyridazin-5-yl)-2-methylacrylate (I) to pyrido[2,3-c]pyridazines by treatment with triethyl phosphite or hydrazine hydrate as the reducing agents is described. Compound I was also reductively cyclized with sodium borohydride. Treatment of I with concentrated sulfuric acid gave 8-chloro-3,6-dimethyl-2,5-dioxo-5,6-dihydro-2H-pyrano[2,3-d] pyridazine (VII) which also could be synthesized by another independent route. A mechanism for the cyclization is proposed.