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As basic studies to apply an intestinal pressure-controlled colon delivery capsule (PCDC) for glycyrrhizin (GZ), the characteristics of intestinal absorption and disposition of GZ were investigated in mice. In the in vivo study, after intravenous (iv) administration of GZ, 10 mg/kg dose, plasma GZ disappeared from the systemic circulation with t(1/2(alpha)) of 0.0063 h, thereafter, it slowly declined with t(1/2(beta)) of 15.23 h. The area under the plasma drug concentration versus time curve (AUC) values of iv (10 mg/kg), intracolonic (50 mg/kg) and intraduodenum (50 mg/kg) administrations were 115.1, 16.7 and 2.7 microgh/mL, respectively. The AUC values of plasma glycyrrhetic acid (GA), a degradation product after intracolonic and intraduodenum administrations were 2.8 and 8.4 microgh/mL, respectively. In the in situ closed loop study, the concentrations of GZ in plasma and liver after intracolonic administration were significantly increased (p

The reactions of the lithium enolate of 1-tetralone with reactive alkyl halides were examined in the absence and in the presence of 3 eq of various ligands for the lithium. It is shown that the rates of the reactions are enhanced greatly in the presence a tetradentate amine (1,1,4,7,10,10-hexamethyltriethylenetetramine), and the ratio of the monoalkylated product to the dialkylated product is increased under shorter reaction times.

The pendant E-ring moiety of the podophyllotoxin aza-analogue 1 that is a potent inhibitor of microtubule assembly was modified in order to acquire inhibitory activity of DNA topoisomerase II. The monophenolic analogue 2 did not exhibit human topoisomerase II inhibition, while the ortho-quinone 3 that was obtained by oxidation of 2 inhibited its catalytic activity (decatenation) in a dose-dependent manner and stimulated double strand DNA break in supercoiled circular plasmid DNA, resulting in the production of linear DNA. These results showed that the topoisomerase II inhibition of the ortho-quinone 3 is due to stabilization of the topoisomerase II-DNA covalent binary complex. On the other hand, the ortho-quinone 3 did not inhibit the relaxation process of supercoiled DNA by topoisomerase I at concentrations up to 400 μM, nor was intercalation observed in unwinding measurements of 3. Therefore, the ortho-quinone 3 was shown to be a novel nonintercalative topoisomerase II specific inhibitor that stabilizes the cleavable complex. The present results suggest that the 4'-free hydroxyl group on the E-ring and the sugar moiety on the C-ring are not a prerequisite for topoisomerase II inhibition by podophyllotoxin derivatives.

The regional cerebral blood flow (rCBF) response to vibrotactile stimulation was compared in conscious young (5.9+/-1.8 years old) and aged (18.0+/-3.3 years old) monkeys using [15O]H(2)O and high-resolution positron emission tomography (PET). In addition, the effects of docosahexaenoic acid (DAH), an n-3 polyunsaturated fatty acid (PUFA), on the rCBF response to stimulation were evaluated in aged monkeys. Soybean milk (SBM) or DHA-containing SBM (DHA/SBM) was supplied to aged monkeys for 1 and 4 weeks. Under control conditions, vibrotactile stimulation elicited an increase in the rCBF response in the contralateral somatosensory cortices of both young and aged monkeys, but the degree of increase in the rCBF response was significantly lower in aged monkeys (116% of corresponding 'rest' condition) than that in young animals (141%). The regional cerebral metabolic rate of glucose (rCMRglc) response to the stimulation, an index of neuronal activation, was not significantly different between young and aged monkeys as measured by [18F]-2-fluoro-2-deoxy-D-glucose (FDG). Supply of DHA/SBM at a dose of 150 mg/kg/day as DHA for 1 week resulted in a significant increase in rCBF response to stimulation (127%) in aged monkeys, and 4-week supply of DHA induced further facilitation of the rCBF response (133%). In contrast, the reduced rCBF response in the aged monkeys was not affected by SBM alone for either 1 or 4 weeks. The neuronal activation itself elicited by the stimulation, as measured by [18F]FDG, was not affected by SBM or DHA/SBM. These results suggested the involvement of DHA in the coupling mechanism between the neuronal activation and rCBF response, possibly by modulation of cholinergic neuronal transmission.

Novel bicyclic chiral crown ethers having an α,α'-p-xylenedioxy unit were synthesized. Crown dithiol 1 with a p-xylenedioxy bridge-structure performed intra-complex thiolysis with α-amino acid p-nitrophenyl ester HBr salts much faster than the corresponding dithiol 3 without the bridge-structure. A 1 H-NMR study suggested that the increased rate of intra-complex thiolysis is due to increased stability of the intermediary complex during the reaction

Enantioselective dihydroxylation of E-stilbene afforded (1S, 2S)-1, 2-diphenyl-1, 2-ethanediol in 70% ee by employing a stoichiometric amount of osmium tetroxide-chiral amine 5, prepared from N-methylephedrine and 2-bromopyridine.

(S)-5-(Trityloxymethyl)pyrrolidin-2-one (1) is an efficient and recyclable chiral auxiliary in the asymmetric Diels–Alder reaction of the imide (2) with dienes, affording cycloadducts (3) with excellent diastereofacial selectivity.

The electron microscopic studies have been done for Au and Au-25 at.% Cu nanoparticles (1–10 nm) prepared by the inert-gas vapor-aggregation technique, and those annealed on amorphous carbon films at 723 K under vacuum. The Au-Cu particles with complex structures have been restructured into icosahedron (1–6 nm in diameter) and polycrystalline (>6 nm) particles by annealing, despite coalescence taken place between the particles. The Au particles, however, did not show such drastic structural changes by annealing. The results suggest that the Au-Cu binary state produces a global minimum for the icosahedral structure on the configurational free energy surface.

A clinicopathological study of surgically resected thymomas was performed using Masaoka's staging and modified Masaoka's staging systems, and the utility of these two staging systems was compared. The modification enabled adjustment for the disproportion in the number of cases between Stage I and Stage II. Analysis of survival rates, according to the tumor stage, indicated that the old classification should be reappraised, that is, division into non-invasive and invasive thymomas, although staging may contribute to the indication for postoperative radiotherapy, especially for Stage II disease. Analysis of the cases showed a wide spectrum of aggressiveness, varying from cases showing slow progression with a relatively favorable prognosis, such as the spindle cell type, to cases with rapid progression leading to tumor death in a relatively short time, such as the epithelial cell predominant and polygonal cell type. The pathological stage at the time of first surgical resection would reflect the degree of aggressiveness of thymoma in many instances. Therefore, not only staging the tumor extent but also grading of its aggressiveness are needed in order to predict the prognosis of patients with thymoma. For the latter, histology and cytopathology are helpful.

To determine the origin of resistivity plateau at ~200 K in the superoxygenated La2CuO4+δ, we have performed several experiments about ceramic samples. The resistivity result of the superoxygenated sample has shown the plateau around 120–260 K, however, magnetic susceptivi1ity and Hall coefficient exhibit no anomaly over this temperature range. On the other hand, the phase separation was found to have been already present at room temperature in this sample from X-ray results. We conclude that the resistivity plateau arises from neither the magnetic transition nor the development of two-phase separation, but from the growth of microstructures.

Five-fold symmetrical star-shaped (s-) multiply twinned particles (MTPs) of molybdenum (s-Mo-MTPs) were successfully prepared by atmospheric H2/Ar microplasma jet. The formation of MTPs in materials whose stable phase is not an fcc structure has been reported in only a few cases with small quantities, and the MTPs have never been prepared in Mo whose stable phase is a body-centered cubic (bcc) structure. In this study, s-Mo-MTPs were formed as the dominant product and densely grown on the substrate. Each s-Mo-MTP grew along a five-fold axis, and the star-shaped cross-section area became larger toward the top. This top-heavy morphology is unique among the morphologies of MTPs reported up to now. Here, we report on a simple method to prepare s-Mo-MTPs using atmospheric H2/Ar microplasma jet, the details of the morphology and the microstructure, and the growth mechanism discussed based on our observations.

beta-N-Acetylhexosaminidase was produced by Trichoderma harzianum cultivated with chitin as the growth substrate. The enzyme was purified 13.2-fold to homogeneity by ultrafiltration and sequential chromatography on SP-Toyopearl and Sephacryl S-200. The molecular weight of the enzyme was estimated to be about 150,000 by gel filtration. The pH and temperature optima were 4.0-5.5 and 50 degrees C, respectively. The enzyme hydrolyzed N-acetylchitooligosaccharides at the non-reducing ends to release GlcNAc monomer. The enzyme showed a strict substrate specificity to the sugar chains in complex carbohydrates, hydrolyzing only the linkage of GlcNAc beta 1-3Gal, but not hydrolyzing the other linkages such as GalNAc beta 1-3Gal and GlcNAc beta 1-2Man.

An external chiral tridentate amino diether ligand 7 catalyzed the condensation reaction of a lithium ester enolate 2 with an imine 3 to give the enantiomerically enriched β-lactam 4 in high yield.

A slight structural modification of a chiral diamine 1 caused a dramatic change in a sense of enantioselectivity in dihydroxylation of olefins with chiral amine-osmium tetroxide complex.

Reaction of 2,6-di-tert-butyl-4-methoxyphenyl naphthalenecarboxylates with organolithiums provided the addition products to naphthalene nucleus in quantitative yield.

Deprotonation of optically active 3-keto steroids ( 1, 2, 10, 11 ) by chiral lithium amides ((R)- or (S)- 5 ) in the presence of excess trimethylsilyl chloride gave either regioisomers of their corresponding trimethylsilyl enol ethers in reasonably high selectivities.

Kinetic deprotonation of meso-dimethylcyclohexanones by chiral lithium amides in the presence of excess trimethylsilyl chloride afforded the corresponding silyl enol ethers in good yields and in reasonably high enantiomeric excesses

Simple C2-symmetric chiral crown ether 1 complexed with KOtBu was found to work as an efficient chiral catalyst in Michael additions to cause high asymmetric induction. The results with various chiral crown ethers as catalysts suggest that diaxial-like conformation of the vicinal methyl groups of 1·potassium enolate complex is responsible for the chiral induction.

Incomplete deprotonation of racemic 2-substituted cyclohexanones (d1-4) by chiral lithium amides (2) in the presence of trimethylsilyl chloride was found to give the corresponding trimethylsilyl enol ethers (5) and the unreacted ketones (4) in reasonably high enantiomeric excesses.

Demethyl derivatives of steganes and deoxypodorhizon, 3, 4, 6, 7, 9, 10, 12, 13, 18, 23, were prepared by the selective demethylation of the methoxy group of steganes and deoxypodorhizon, 2, 5, 8, 11, 22. The cytotoxicity of these derivatives was evaluated against KB cell and was found not to exceed that of the parent steganes. 4-Demethyldeoxypodorhizon (18) was found to show more potent cytotoxicity than deoxypodorhizon.

Enantioselective dihydroxylation of (7) with osmium tetroxide with mediation by the chiral diamine (–)-(6) afforded (9) of 82% enantiomeric excess which was then successfully converted to (+)-4-demethoxydaunomycinone (5).

Osmium tetroxide is one of the most reliable oxidants for preparing vicinal cis-diols from olefins. In this article are reviewed some aspects of recent progress in diastereoface-selective and enantioface-selective oxidation of olefins with osmium tetroxide. The oxidation mechanism is also discussed.

Podophyllotoxin aza-analogue 7 ( 3 R 1 =H, R 2 =Me, H) was designed and synthesized by a highly stereoselective condensation reaction of a cyclic urethane 5 with 3,4,5-trimethoxybenzaldehyde 6 and was found to show a promising in vitro and in vivo antitumor activity.

Artificial steganacin aza-analogue 3 was designed and synthesized in a quite efficient way. Aza-analogue 3 was shown to be endowed with promising in vitro and in vivo activity higher than natural steganacin (−)- 1 .

Aerobic oxidative coupling of naphthols catalyzed by a copper-amine complex was found to proceed without solvent in high efficacy. The present reaction was applied to a practical synthesis of 1, 1'-binaphthalene-2, 2'-diol on multi-gram scale.

Oxidation of a cytotoxic podophyllotoxin aza-analogue 2 into the quinone 3 succeeded in acquiring DNA topoisomerase II inhibitory activity at a concentration of 25 μM due to stabilization of the cleavable complex.

An α-phenethylamine-derived chiral lithium amide ( (R) - 5c ) possessing a 2,2,2-trifluoroethyl group on the amide nitrogen was found to induce high enantioselectivity in the kinetic deprotonation of 4- tert -butylcyclohexanone ( 1 ) in the presence of excess trimethylsilyl chloride to give the corresponding silyl enol ether ( (S) - 2 ) in up to 92% ee (86% chemical yield). © 1997 Elsevier Science Ltd.

Aerobic oxidative coupling of 2-naphthol derivatives by the use of 1 mol% of CuCl-amine complex afforded binaphthol derivatives in excellent yields.

Chiral lithium alkoxides were designed and applied to enantioselective Michael reaction of methyl phenylacetate and methyl acrylate to give the corresponding adduct in enantiomeric excess up to 84 %. The catalytic enantioselective Michael reaction is also effected by this type of reagents.

In the Presence of both stoichiometric and catalytic amounts of a chiral dieter 1, aryllithiums reacted with BHA-esters of naphthalenecarboxylic acids 2, 5 to afford the corresponding adducts 4, 6 in high ee.