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Volume 61, Issue 3
Displaying 1-18 of 18 articles from this issue
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Review
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Satoshi YokoshimaArticle type: Review
2013 Volume 61 Issue 3 Pages 251-257
Published: March 01, 2013
Released on J-STAGE: March 01, 2013
JOURNAL FREE ACCESSHerein we present our unique strategies to synthesize natural products. To prepare mersicarpine, an atypical indole alkaloid, our procedure features an Eschenmoser–Tanabe fragmentation to synthesize an alkyne unit, a combination of a Sonogashira coupling and a gold(III) catalyzed cyclization to construct the indole skeleton, and a one-pot process to arrange the cyclic imine and the hemiaminal moieties. Additionally, we synthesized a frog poison, histrionicotoxin, via a chirality transfer from an allenylsilane to prepare a pseudosymmetrical dienyne, dienyne metathesis to produce an optically active bicyclo [5.4.0] system, and an asymmetric propargylation. To synthesize lyconadin A, a Lycopodium alkaloid, a combination of an aza-Prins reaction and electrocyclic ring opening constructed the highly fused tetracyclic compound. The synthesis of isoschizogamine features a facile construction of the carbon framework through a Wagner–Meerwein rearrangement, a tandem metathesis, a stereoselective rhodium-mediated 1,4-addition of an arylboronic acid, and a ring-closing metathesis via a hemiaminal ether.View full abstractDownload PDF (1562K)
Regular Articles
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Kalpana Nagpal, Shailendra Kumar Singh, Dina Nath MishraArticle type: Regular Article
2013 Volume 61 Issue 3 Pages 258-272
Published: March 01, 2013
Released on J-STAGE: March 01, 2013
JOURNAL FREE ACCESSThe minocycline hydrochloride (MH), at higher doses, is useful in the treatment of neurodegenerative disorders and owing to its antioxidant potential, it may have nootropic effects. MH loaded nanoparticles (MHNP) were coated with tween 80 (cMHNP) to improve its brain uptake followed by their optimization employing two factor-three level (32) central composite design (CCD) in order to minimize particle size and maximize drug entrapment efficiency (DEE) and validated. The optimized formulations were further subjected to in vitro drug release study; in vivo biodistribution studies in male wistar rats. The pharmacodynamic study was carried out using elevated plus maze (EPM) and Morris water maze (MWM) behavioral models for nootropic activity in swiss albino mice; and biochemical estimations (acetylcholine esterase, reduced glutathione, malondialdehyde and brain nitrite level). After intravenous (i.v.) administration, the concentration of MH in brain of cMHNP (6.21±0.64 µg/mL) treated rats was significantly higher with MH solution treated (0.70±0.06 µg/mL) as well as MHNP (1.03±0.12 µg/mL) treated animals. Pharmacodynamic studies revealed a significant improvement in memory of MH, MHNP and cMHNP treated swiss albino mice than saline treated control group. However, cMHNP revealed maximum decrease in transfer latency (TL) in EPM and maximum increase in time spent in target quadrant (TSTQ) in MWM. Although cMHNP did not produce significant change in brain acetylcholinesterase, but, significantly increased reduced glutathione, malondialdehyde and reduced brain nitrite level as compared to saline, MH solution and MHNP treated groups. The results suggest that cMHNP is a promising candidate for improved brain uptake of MH with better nootropic effect.View full abstractDownload PDF (6847K) -
Kouichi Yoshizaki, Hari Prasad Devkota, Shoji YaharaArticle type: Regular Article
2013 Volume 61 Issue 3 Pages 273-278
Published: March 01, 2013
Released on J-STAGE: March 01, 2013
Advance online publication: December 14, 2012JOURNAL FREE ACCESSFour new dammarane-type triterpenoid saponins such as chikusetsusaponin LM3 (1), chikusetsusaponin LM4 (2), chikusetsusaponin LM5 (3), chikusetsusaponin LM6 (4), and twenty known triterpenoid saponins such as ginsenoside Rb3 (5), ginsenoside Rc (6), ginsenoside Rd (7), ginsenoside Re (8), ginsenoside Rg1 (9), ginsenoside F3 (10), ginsenoside F5 (11), ginsenoside F6 (12), chikusetsusaponin IVa (13), chikusetsusaponin V (14), chikusetsusaponin L5 (15), chikusetsusaponin L9a (16), chikusetsusaponin L9bc (17), chikusetsusaponin L10 (18), chikusetsusaponin FK2 (19), chikusetsusaponin FK6 (20), chikusetsusaponin FK7 (21), chikusetsusaponin FT1 (22), chikusetsusaponin LM1 (23), and chikusetsusaponin LM2 (24), were isolated from the leaves of Panax japonicus C. A. MEYER collected in Miyazaki prefecture, Japan. The structures of new chikusetsusaponins were elucidated on the basis of spectral and physicochemical evidences.View full abstractDownload PDF (745K) -
Zhi-Gang Yang, Xiu-Feng Wen, Yong-Hai Li, Keiichi Matsuzaki, Susumu Ki ...Article type: Regular Article
2013 Volume 61 Issue 3 Pages 279-285
Published: March 01, 2013
Released on J-STAGE: March 01, 2013
JOURNAL FREE ACCESSThree new flavonol glycosides, hippophaeosides A–C (1–3), together with 27 known constituents, were isolated from Hippophae rhamnoides L. leaves. Their structures were determined by spectroscopic analyses. Their inhibitory activities on 3T3-L1 preadipocyte differentiation and triglyceride accumulation in maturing adipocytes, and nitric oxide production in RAW264.7 cells were examined.View full abstractDownload PDF (689K) -
Hideaki Amada, Hajime Asanuma, Takeshi Koami, Atsushi Okada, Mayumi En ...Article type: Regular Article
2013 Volume 61 Issue 3 Pages 286-291
Published: March 01, 2013
Released on J-STAGE: March 01, 2013
JOURNAL FREE ACCESS7-Methoxy-6-[4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-5-yl]-1,3-benzothiazole 11 (TASP0382088) was synthesized and evaluated as transforming growth factor-β (TGF-β) type I receptor (also known as activin receptor-like kinase 5 or ALK5) inhibitor. Compound 11, a potent and selective ALK5 inhibitor, exhibited good enzyme inhibitory activity (IC50=4.8 nM) as well as inhibitory activity against TGF-β-induced Smad2/3 phosphorylation at a cellular level (IC50=17 nM). The introduction of a methoxy group to the benzothiazole ring in 1 and the break up of the planarity between the imidazole ring and the thiazole ring improved the solubility in the lotion base of 11. Furthermore, the topical application of 3% 11 lotion significantly inhibited Smad2 phosphorylation in mouse skin at 8 h after application (71% inhibition, compared with vehicle-treated animals).View full abstractDownload PDF (2297K) -
Toshihiko Hamashima, Yoshiaki Mori, Kazunori Sawada, Yuko Kasahara, Da ...Article type: Regular Article
2013 Volume 61 Issue 3 Pages 292-303
Published: March 01, 2013
Released on J-STAGE: March 01, 2013
Advance online publication: December 06, 2012JOURNAL FREE ACCESS
Supplementary materialA convenient method for the synthesis of 3-methylthioindoles has been established which does not use smelly compounds such as thiol derivatives. The method, which introduces an alkyl- or arylthio-group into the C3-position of the indole skeleton, was extended to the direct introduction of a methylthio or bromo group at the C2-position using 3-methylthioindoles. No dimerization occurred, and the reaction mechanism was confirmed. The products have the partial structure of potent anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) bromomethylthioindoles (MC 5–8) isolated from marine algae. Furthermore, this reaction could be applied to the synthesis of 3,3-diindolyl thioether which is a core structure of Echinosulfone A.View full abstractDownload PDF (1166K) -
Akihito Yasuda, Yoshinori Onuki, Yasuko Obata, Rie Yamamoto, Kozo Taka ...Article type: Regular Article
2013 Volume 61 Issue 3 Pages 304-309
Published: March 01, 2013
Released on J-STAGE: March 01, 2013
JOURNAL FREE ACCESSThe “quality by design” concept in pharmaceutical formulation development requires the establishment of a science-based rationale and a design space. We integrated thin-plate spline (TPS) interpolation and Kohonen’s self-organizing map (SOM) to visualize the latent structure underlying causal factors and pharmaceutical responses. As a model pharmaceutical product, theophylline tablets were prepared based on a standard formulation. The tensile strength, disintegration time, and stability of these variables were measured as response variables. These responses were predicted quantitatively based on nonlinear TPS. A large amount of data on these tablets was generated and classified into several clusters using an SOM. The experimental values of the responses were predicted with high accuracy, and the data generated for the tablets were classified into several distinct clusters. The SOM feature map allowed us to analyze the global and local correlations between causal factors and tablet characteristics. The results of this study suggest that increasing the proportion of microcrystalline cellulose (MCC) improved the tensile strength and the stability of tensile strength of these theophylline tablets. In addition, the proportion of MCC has an optimum value for disintegration time and stability of disintegration. Increasing the proportion of magnesium stearate extended disintegration time. Increasing the compression force improved tensile strength, but degraded the stability of disintegration. This technique provides a better understanding of the relationships between causal factors and pharmaceutical responses in theophylline tablet formulations.View full abstractDownload PDF (3905K) -
Ryoichi Komaki, Takashi Ikawa, Kozumo Saito, Kazuyo Hattori, Natsuyo I ...Article type: Regular Article
2013 Volume 61 Issue 3 Pages 310-314
Published: March 01, 2013
Released on J-STAGE: March 01, 2013
JOURNAL FREE ACCESSBoth enantiomers of dihydro-β-ionol and β-ionol, contained in the aromatic components of Osmanthus flower and of Hakuto peach, were obtained with high optical purity by lipase-catalyzed kinetic resolution of the racemates. It was found that all these enantiomers had different characteristic favorable scents and high antimelanogenetic effects. The absolute configuration and the enantiomer ratios of dihydro-β-ionol in the aromatic components of Osmanthus flower and of Hakuto peach were determined. The asymmetric synthesis of (R)-dihydro-β-ionol, one of the most valuable raw materials for fragrance and flavor, was performed from inexpensive β-ionone via lipase-catalyzed dynamic kinetic resolution followed by reduction.View full abstractDownload PDF (562K) -
Takuji Harada, Kohsaku Kawakami, Yasuo Yoshihashi, Etsuo Yonemochi, Ka ...Article type: Regular Article
2013 Volume 61 Issue 3 Pages 315-319
Published: March 01, 2013
Released on J-STAGE: March 01, 2013
JOURNAL FREE ACCESSA practical protocol to obtain accurate heat capacity values of pharmaceutical compounds using modulated-temperature differential scanning calorimetry was established. Three pharmaceutical compounds, acetaminophen, indomethacin, and tri-O-methyl-β-cyclodextrin were used as model compounds. Powder samples did not produce reproducible results, presumably due to inclusion of gas in gap of powders that influenced the measured heat capacity and thermal homogeneity in the sample. Thus, the amorphous characteristics were evaluated using quench-cooled samples. Crystalline samples were obtained by partially melting the sample to allow recrystallization using the residual crystal as a template. Optimum sample mass was about 10 mg. Use of too small sample size resulted in poor reproducibility due to localization of the sample in the pan, while too large size resulted in low heat capacity values probably because of heterogeneity of the sample temperature. The optimum modulation period was in the range of 60 s and 90 s, to which the ramp rates of 2°C/min and 1°C/min, respectively, were applied. The ramp amplitude was less significant in the evaluation. This information should help in comprehending basic characteristics of pharmaceutical compounds.View full abstractDownload PDF (722K) -
Maya Fujiwara, Masafumi Dohi, Tomoko Otsuka, Kazunari Yamashita, Kazuh ...Article type: Regular Article
2013 Volume 61 Issue 3 Pages 320-325
Published: March 01, 2013
Released on J-STAGE: March 01, 2013
JOURNAL FREE ACCESSHere, we statistically identified the critical factor of the granulation rate during the fluidized bed granulation process. Lactose was selected as the excipient and was granulated with several binders, including hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and polyvinylpyrrolidone. The viscosity, density, and surface tension of the binder solution, contact angle, and the work done during adhesion and cohesion between the binder and lactose, mist diameter, Stokes number, and the dimension of the droplet were considered. The Stokes number was defined as the ratio of the inertial force to the viscous-damping force of a particle. We confirmed that droplet diameter after adhesion had the highest correlation coefficient with the granulation rate constant in our investigated parameters. Partial least squares regression revealed two critical principal components of the granulation rate: one relating to the droplet dimension, which is composed of mist diameter and diameter and thickness of the droplet after adhesion of the binder to the lactose surface; and the other relating to wettability, which involves the work done during adhesion and cohesion, surface tension, and the thickness of the droplet after adhesion of the binder to the lactose surface.View full abstractDownload PDF (781K) -
Tatsuya Higashi, Katsumi Kawasaki, Nagisa Matsumoto, Shoujiro Ogawa, K ...Article type: Regular Article
2013 Volume 61 Issue 3 Pages 326-332
Published: March 01, 2013
Released on J-STAGE: March 01, 2013
JOURNAL FREE ACCESSA derivatization procedure with (3-dimethylaminophenyl)dihydroxyborane (DAPB) was introduced to enhance the detectability of steroids having a vicinal diol in LC/electrospray ionization (ESI)-MS/MS. DAPB reacted with the vicinal diol on the steroids [4β-hydroxycholesterol (4-HCh), pregnanetriol (PT) and 20R,22R-dihydroxycholesterol] in pyridine at 50°C within 1 h. The resulting DAPB-derivatives were highly responsive in ESI-MS operating in the positive-ion mode and gave characteristic product ions during MS/MS, which enabled sensitive detection using a selected reaction monitoring mode; the detection responses of the DAPB-derivatives were increased by 20–160-fold over those of the intact steroids and the limits of detection were in the low femtomole or attomole range. The derivatization procedure was successfully applied to biological sample analysis; the derivatization followed by LC/ESI-MS/MS enabled the specific detection of trace amounts of 4-HCh in human plasma and PT in human urine with a small sample volume, simple pretreatment and short chromatographic run time.View full abstractDownload PDF (733K) -
Tomoyo Ohkawa, Tomonobu Uchino, Daisuke Sasakura, Yasunori Miyazaki, Y ...Article type: Regular Article
2013 Volume 61 Issue 3 Pages 333-339
Published: March 01, 2013
Released on J-STAGE: March 01, 2013
JOURNAL FREE ACCESSWe evaluated the particle state change in emulsion admixtures using in situ flow particle imaging analysis (FPIA). Ropion® intravenous (flurbiprofen axetil: Ropion®) served as the model emulsion formulation. A binary mixture of Ropion® and normal saline (NS), and a ternary admixture of Ropion®, NS, and Gaster® injection (famotidine: Gaster®) or Primperan® injection (metoclopramide hydrochloride: Primperan®) were prepared and the change in emulsion particle state was analyzed using FPIA under in situ condition. The effect of storage on pH change and the chemical stability of flurbiprofen axetil were also investigated. In Ropion®, various particle images (mean diameter: 2.4 µm) were obtained. From our analysis of changes in scattergrams and particle images, changing behaviors of emulsion particles as a function of storage time depended on the systems of admixture samples. In Ropion®/NS and Ropion®/Gaster®/NS systems, mean particle size and particle number increased with lengthening storage time; however, these values were dramatically increased beyond 6 h in the Ropion®/Primperan®/NS system, corresponding to a decrease in measured pH. The decomposition of flurbiprofen axetil due to incompatibility was not observed in all systems. Detailed information on the change in emulsion particle state was obtained using FPIA, indicating that this method is useful to evaluate state changes in emulsion admixtures under in situ condition.View full abstractDownload PDF (3880K)
Notes
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Myeong Hwan Oh, Kwan Hee Park, Manh Heun Kim, Han Hyuk Kim, So Ra Kim, ...Article type: Note
2013 Volume 61 Issue 3 Pages 340-343
Published: March 01, 2013
Released on J-STAGE: March 01, 2013
JOURNAL FREE ACCESSThree new orcinol (3-hydroxy-5-methylphenol)-conjugated hydrolysable tannins, together with two known compounds were isolated from the leaves of Cleyera japonica (CJ), and have been tentatively named cleyeratannin A (1), cleyeratannin B (2) and cleyeratannin C (3). The chemical structures of these compounds were elucidated using 1 dimensional (1D)/2D NMR and high resolution FAB-MS, and the absolute configuration was confirmed by circular dichroism (CD). To evaluate their anti-oxidative activities, 1,1-diphenyl-2-picrylhydrazyl (DPPH)/free radical scavenging activity and nitroblue tetrazolium (NBT)/superoxide anion scavenging activity were determined.View full abstractDownload PDF (381K) -
Kouichi Yoshizaki, Hari Prasad Devkota, Hiroharu Fujino, Shoji YaharaArticle type: Note
2013 Volume 61 Issue 3 Pages 344-350
Published: March 01, 2013
Released on J-STAGE: March 01, 2013
Advance online publication: December 28, 2012JOURNAL FREE ACCESSA new dammarane-type triterpenoid saponin, chikusetsusaponin VII (1), and nineteen known triterpenoid saponins, ginsenoside Rb1 (2), ginsenoside Rb3 (3), ginsenoside Rc (4), ginsenoside Rd (5), ginsenoside Re (6), ginsenoside Rg1 (7), ginsenoside Rg2 (8), ginsenoside Rh1 (9), notoginsenoside R1 (10), notoginsenoside R2 (11), notoginsenoside Fe (12), chikusetsusaponin IVa (13), chikusetsusaponin IV (14), chikusetsusaponin V (15), chikusetsusaponin VI (16), chikusetsusaponin FK6 (17), gypenoside XVII (18), 28-desglucosylchikusetsusaponin IV (19), and zingibroside R1 (20), were isolated from rhizomes, taproots, and lateral roots of Panax japonicus C. A. Meyer, so-called “Satsuma-ninjin,” grown in southern Miyazaki Prefecture, Japan. The structure of new chikusetsusaponin VII was elucidated on the basis of spectral and physicochemical evidence. Although the chemical composition of the rhizome was found to be similar to that of the “Chikusetsu-ninjin,” the saponin composition of lateral root of “Satsuma-ninjin” was found to be close to that of lateral root of P. ginseng. The total yield of oleanolic acid saponins of the taproot was less than that of rhizome, but the total yield of dammarane-type saponins of the taproot was found to be similar to that of rhizome.View full abstractDownload PDF (714K) -
Xiangduan Tan, Chungang Li, Zhenpeng Yu, Panfeng Wang, Siyun Nian, Yif ...Article type: Note
2013 Volume 61 Issue 3 Pages 351-357
Published: March 01, 2013
Released on J-STAGE: March 01, 2013
Advance online publication: December 17, 2012JOURNAL FREE ACCESSThe design and synthesis of a series of substituted 6-amino-4-(2,4-dimethoxyphenyl)-[1,2]dithiolo[4,3-b]pyrrol-5-ones are described. All the synthesized compounds were evaluated for raising leukocyte count activities in normal mice. Four compounds (8a, b, d, h) exhibited raising leukocyte count activities close or higher than positive control recombinant human granulocyte colony stimulating factor (rhG-CSF), and some (8e–g, k, p, r) had a moderate effect. Among them, the most potent compound 8a was evaluated for its antileukopenia activity in cyclophosphamide (CTX) treated mice. Interestingly, 8a exhibited significant antileukopenia activity as compared to rhG-CSF. The results suggest that this kind of compounds might be utilized for the development of new candidate for treatment of leukocytopenia.View full abstractDownload PDF (506K) -
Duy Hoang Le, Yukiko Takenaka, Nobuo Hamada, Hiromi Miyawaki, Takao Ta ...Article type: Note
2013 Volume 61 Issue 3 Pages 358-362
Published: March 01, 2013
Released on J-STAGE: March 01, 2013
Advance online publication: December 20, 2012JOURNAL FREE ACCESSSpore-derived mycobionts of the crustose lichen Graphis vestitoides collected in Vietnam were cultivated on a malt-yeast extract medium supplemented with 10% sucrose. The investigation of their metabolites resulted in isolation of a novel 14-membered macrolide and a new isocoumarin, together with five known isocoumarin derivatives. Their structures were determined by spectroscopic and chemical means. This is the first instance of isolation of a 14-membered macrolide from a lichen mycobiont.View full abstractDownload PDF (472K) -
Wei Hua Yuan, Nan Jiang, Cai Hong Dong, Zhi Wen Wei, Han Kui Wu, Cai F ...Article type: Note
2013 Volume 61 Issue 3 Pages 363-365
Published: March 01, 2013
Released on J-STAGE: March 01, 2013
JOURNAL FREE ACCESS
Supplementary materialA new 12-membered ring lactone, (3S),(6R)-6-hydroxylasiodiplodin (1), with two known analogues, (3R)-lasiodiplodin (2), and (3R),(5S)-5-hydroxylasiodiplodin (3) were isolated from the EtOH extracts of normal Apriona germari (Hope)-associated fungus Sarocladium kiliense grown in rice medium. The structures of compounds 1–3 were elucidated by a combination of spectroscopic data interpretation, single-crystal X-ray diffraction analysis, and modified Mosher’s method.View full abstractDownload PDF (431K) -
Miho Asano, Koji Yamada, Takashi Tanaka, Yosuke Matsuo, Isao KounoArticle type: Note
2013 Volume 61 Issue 3 Pages 366-369
Published: March 01, 2013
Released on J-STAGE: March 01, 2013
JOURNAL FREE ACCESSA bisabolane type of sesquiterpene was isolated from the culture medium of Amanita virgineoides BAS, together with two known compounds, including lignoren, and harziandion. The structure of the new compound “virgineol” was established using a combination of different NMR spectroscopy techniques, whereas the chemical structure of the known compound was identified as lignoren, and the structure of harziandion was confirmed by X-ray crystallographic analysis.View full abstractDownload PDF (521K)
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