Complete 1H and 13C NMR assignments of two phytosterols from roots of Piper nigrum

Using modern NMR techniques, including DQF-COSY, NOESY, HETCOR and HMBC, the full assignments of all 1H and 13C chemical shifts were made for stigmastane-3,6-dione and stigmast-4-ene-3,6-dione, isolated from the roots of Piper nigrum (Piperaceae). Their stereochemistry was resolved by a combination of 2D NOESY data and analysis of coupling constants. The two compounds were isolated from the genus Piper for the first time.     

Preparation of prolonged-release spherical micro-matrix of ibuprofen with acrylic polymer by the emulsion-solvent diffusion method for improving bioavailability

Prolonged-release spherical micro-matrices of ibuprofen with acrylic polymer (Eudragit RS) were prepared using a novel emulsion-solvent diffusion method. It was found by examining cross sections of the spherical matrix before and after dissolution tests with a scanning electron microscope and a porosimeter that the resultant micro-matrix had a sponge-like internal structure. The spherical matrices were successfully recovered with a relatively high concentration of the drug in ethanol (0.4-0.6 g/ml) and over a wide range of temperatures (5-35 degrees C). The size of the spherical matrix could be easily controlled by varying the agitation speed of the system and the concentration of emulsifier added to the aqueous medium. The drug release rate from the spherical matrix decreased with increasing concentration of polymer formulated due to the reduced diffusion path and increased tortuosity in the matrix. Spherical matrices with ibuprofen:Eudragit RS = 3:1 improved the bioavailability of the drug and prolonged the drug action in beagle dogs.     

Steady-state and nanosecond spectroscopic studies of triplet sensitized reaction of K-region arene oxides

Photorearrangement reactions of K-region arene oxides, 9,10-epoxy-9,10-dihydrophenanthrene (1a), 3-acetyl-9,10-epoxy-9,10-dihydrophenanthrene (1b), and 3,4-epoxy-3,4-dihydropyrene (1c) in dichloroethane (DCE) solution were investigated by steady irradiation and nanosecond transient spectroscopy. Photorearrangements producing substituted oxepins, 2 occur via the singlet excited state of these compounds, while the phenolic products, 9-hydroxyphenanthrene (3a), 3-acetyl-9-hydroxyphenanthrene (3b), and 4-hydroxypyrene (3c) are formed via the triplet state. Phenol 3 formation from the triplet 1 sensitized by the triplet 3 (i.e. product sensitization) is proposed for the photorearrangement reactions of 1a and 1c, and this process is the only way phenol (3a) is formed because of the negligible intersystem crossing probability of 1a. No product sensitization occurs in the photorearrangement reaction of 1b.     

Studies on antiulcer drugs. III. Synthesis and antiulcer activities of imidazo[1,2-a]pyridinylethylbenzoxazoles and related compounds. A novel class of histamine H2-receptor antagonists.

A series of imidazo[1,2-a]pyridinylalkylbenzoxazole derivatives was synthesized and tested for histamine H2-receptor antagonist, gastric antisecretory and antiulcer activities. Some of 2-amino-6-[2-(imidazo[1,2-a]pyridin-2-yl)ethyl]benzoxazole derivatives were found to have good pharmacological activities. Among them, 2-amino-6-[2-(7-methoxy-3-methylimidazo[1,2-a]pyridin-2-yl)ethyl] benzoxazole (II-11) and 2-acetamido-6-[2-(7-methylimidazo[1,2-a]pyridin-2-yl)ethyl] benzoxazole (II-38) showed potent antisecretory and cytoprotective activity. The structure-activity relationships of these compounds are discussed.     

Diethylhydrogensilyl cyclic diethylsilylene derivatives in gas chromatography/mass spectrometry of hydroxylated steroids. III-Fragmentations of 5β-pregnane-17,20,21-triol derivatives

A reaction of N,O-bis-(diethylhydrogensilyl) trifluoroacetamide with 5β-pregnane-17,20,21-triols afforded diethylhydrogensilyl (DEHS) cyclic diethylsilylene (DES) derivatives. 5β-Pregnane-3α,17α,20β,21-tetraol yielded the 3α,21-bis-DEHS-17α,20β-DES compound, whereas the structure of the major product from its 20α isomer was assigned as the 3α,17α-bis-DEHS-20α,21-DES derivative, which would undergo facile isomerization to the unstable 3α,21-bis-DEHS-17α,20α-DES structure under electron ionization. Fragmentations of these DEHS-DES compounds are discussed on the basis of isotope labelling experiments, linked scanning data, and accurate mass measurements.     

Optically active antifungal azoles. VIII. Synthesis and antifungal activity of 1-[(1R,2R)-2-(2,4-difluoro- and 2-fluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]- 3-(4-substituted phenyl)-2(1H,3H)-imidazolones and 2-imidazolidinones

New optically active antifungal azoles, 1-[(1R,2R)-2-(2,4-difluoro- and 2-fluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl ]-3-(4- substituted phenyl)-2(1H,3H)-imidazolones (1,2) and 2-imidazolidinones (3,4), were prepared in a stereocontrolled manner from (1S)-1-[(2R)-2-(2,4- difluoro- and 2-fluorophenyl)-2-oxiranyl]ethanols (15, 16). Compounds 1-4 showed potent antifungal activity against Candida albicans in vitro and in vivo, as well as a broad antifungal spectrum for various fungi in vitro. Furthermore, the imidazolidinones, 3b--e and 4d, e, were found to exert extremely strong growth-inhibitory activity against Aspergillus fumigatus.     

Analyses of structure of photoreceptor organelle and blepharismin-associated protein in unicellular eukaryote Blepharisma

In the ciliated protozoan Blepharisma, step-up photophobic response is believed to be mediated by a novel type of photosensory pigment known as "blepharismins" (BL) that are contained in the pigment granules located just beneath the plasma membrane. We examined the ultrastructure of the pigment granules by freeze-fracture and thin-section electron microscopy and proposed a schematic diagram showing the granules' three-dimensional inner membranous structure. Some of the BL are suggested to be associated with 200 kDa membrane protein. High-pressure liquid chromatography analysis of pigment species associated with 200 kDa protein obtained from blue forms of Blepharisma (oxyblepharisma) revealed that the 200 kDa protein was associated with five types of oxyblepharismin. The fluorescence intensity was increased when the pigments were dissociated from the 200 kDa protein. The result supports the hypothesis that the pigment-200 kDa complex is able to transduce light energy into signals mediating the photobehavior of Blepharisma.     

Biological activities of chemically synthesized derivatives of lipid A: tetraacetyl-monosaccharides linked to 2,3-acyloxyacylglucosamine-4-phosphate

The mitogenicity and lethal toxicity of chemically synthesized lipid A analogs, in which 2,3-acyloxyacylglucosamine-4-phosphate (acyl-GlcN-4P) is linked to a tetraacetyl (Ac4)-monosaccharide, i.e., Ac4-glucose (A-211), Ac4-mannose (A-212), Ac4-galactose (A-213) or Ac4-glucosamine (A-214), were compared with those of tetraacetyl-3-deoxy-D-manno-2-octulosonic acid (Ac4-KDO) linked to acyl-GlcN-4P (A-203). All the compounds were capable of increasing incorporation of 3H-thymidine into splenocytes of C57BL/6 mice at doses of 50 and 100 micrograms/ml, but the mitogenic activity of A-203 at these doses seems to be stronger than those of the analogs. Intravenous injection of A-203, A-211, and A-213 did not exhibit lethal toxicity even at a high dose (50 micrograms/mouse) in C57BL/6 mice loaded with D-galactosamine hydrochloride. However, A-212 and A-214 showed lethality at the doses of 10 and 50 micrograms/mouse, respectively. The findings indicate that the biological activity of these compounds is affected by the kind of monosaccharide linked to acyl-GlcN-4P.