All issues
Volume 61, Issue 12
Displaying 1-16 of 16 articles from this issue
- |<
- <
- 1
- >
- >|
Review
-
Yoshiharu Iwabuchi2013 Volume 61 Issue 12 Pages 1197-1213
Published: December 01, 2013
Released on J-STAGE: December 01, 2013
JOURNAL FREE ACCESS FULL-TEXT HTMLThe oxidation of primary and secondary alcohols to the corresponding aldehydes (or carboxylic acids) or ketones is a fundamental transformation in organic synthesis. Stable organic nitroxyl radicals as represented by 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) (1) have been used extensively to catalyze the oxidation of a number of alcohol substrates employing environmentally benign co-oxidants such as bleach (NaOCl) or PhI(OAc)2. Although TEMPO oxidation is better known as a method for selective oxidation of primary alcohols to the corresponding aldehydes, the TEMPO-based method is not very efficient for the oxidation of structurally hindered secondary alcohols. We designed and synthesized 2-azaadamantane N-oxyl [AZADO (11)] and 1-Me-AZADO (20), a structurally less hindered class of nitroxyl radical. AZADOs were found to exhibit excellent catalytic activity enabling oxidation of a variety of alcohols with which TEMPO exhibits poor reactivity. Based on structure–activity relationships (SAR) employing AZADO (11), 1-Me-AZADO (20), 1,3-dimethyl-AZADO (33), 9-azabicyclo[3.3.1]nonane-N-oxyl [ABNO (34)] and 9-azanoradamantane N-oxyl [Nor-AZADO (37)], we concluded that the α-methyl group flanked nearby the nitroxyl group affects the reactivity for the oxidation of sterically hindered alcohols and the azaadamantane skeleton contributes to the high turnover of the catalyst. The highly active nature of AZADOs spurred us to exploit their further use in alcohol oxidations. A facile, green, one-pot oxidation of primary alcohols to carboxylic acids with broad substrate applicability has been developed by employing an expedient catalytic system consisting of the oxoammonium salt [1-Me-AZADO+X− (X=Cl, BF4)]/NaClO2. The synthetic use of AZADOs and the related nitroxyl radicals/oxoammonium salts-based methods for alcohol oxidation have been demonstrated in several total syntheses of natural products. We also describe the development of a Nor-AZADO (37)/DIAD/AcOH method that offers exceptionally mild and highly chemoselective oxidation of alcohols.View full abstractDownload PDF (3552K) Full view HTML
Communication to the Editor
-
Tokihiro Niiya, Masahiko Kimura, Hiroyuki Tsutsumi, Takashi Ishizu, No ...2013 Volume 61 Issue 12 Pages 1214-1219
Published: December 01, 2013
Released on J-STAGE: December 01, 2013
JOURNAL FREE ACCESS FULL-TEXT HTMLDifferences in molecular interaction between bases (adenine (A), guanine (G), and cytosine (C)) and the methyl (Me)-radical were investigated by perturbation analysis using the quantum chemical method. Part of the source of damage to the DNA was elucidated at the molecular level. In the reaction of each of the saccharide derivatives (dA, dG, and dC) with Me-radical, the reactivity of dG (≈dA) is more than about 10 times larger than that of dC. Therefore, it is expected that the base G (and A) was more than about 10 times than the base C in radical-reactivity of the base. For the reaction of dA and dG with the radical, the C8 site of the partial purine ring of dA and dG, and the C5 site of the pyrimidine ring of dC were the main reaction sites for methylation. In the reaction of DNA composed of hydrogen-bonded base pairs G-C and A-T with the radical, the purine ring in the constituent base G reacted preferentially with the radical to yield 8-methyl-guanines.View full abstractDownload PDF (7529K) Full view HTML
Regular Articles
-
Erdal Dinç, Nurten Özdemir, Özgür Üstündağ, Müşerref Günseli Tilkan2013 Volume 61 Issue 12 Pages 1220-1227
Published: December 01, 2013
Released on J-STAGE: December 01, 2013
JOURNAL FREE ACCESS FULL-TEXT HTMLDissolution testing has a very vital importance for a quality control test and prediction of the in vivo behavior of the oral dosage formulation. This requires the use of a powerful analytical method to get reliable, accurate and precise results for the dissolution experiments. In this context, new signal processing approaches, continuous wavelet transforms (CWTs) were improved for the simultaneous quantitative estimation and dissolution testing of lamivudine (LAM) and zidovudine (ZID) in a tablet dosage form. The CWT approaches are based on the application of the continuous wavelet functions to the absorption spectra-data vectors of LAM and ZID in the wavelet domain. After applying many wavelet functions, the families consisting of Mexican hat wavelet with the scaling factor a=256, Symlets wavelet with the scaling factor a=512 and the order of 5 and Daubechies wavelet at the scale factor a=450 and the order of 10 were found to be suitable for the quantitative determination of the mentioned drugs. These wavelet applications were named as mexh-CWT, sym5-CWT and db10-CWT methods. Calibration graphs for LAM and ZID in the working range of 2.0–50.0 µg/mL and 2.0–60.0 µg/mL were obtained measuring the mexh-CWT, sym5-CWT and db10-CWT amplitudes at the wavelength points corresponding to zero crossing points. The validity and applicability of the improved mexh-CWT, sym5-CWT and db10-CWT approaches was carried out by the analysis of the synthetic mixtures containing the analyzed drugs. Simultaneous determination of LAM and ZID in tablets was accomplished by the proposed CWT methods and their dissolution profiles were graphically explored.View full abstractDownload PDF (749K) Full view HTML -
Shoko Nakashima, Katsuhiko Yamamoto, Yuta Arai, Yukihiro Ikeda2013 Volume 61 Issue 12 Pages 1228-1238
Published: December 01, 2013
Released on J-STAGE: December 01, 2013
JOURNAL FREE ACCESS FULL-TEXT HTMLSolid-state characterization plays a vital role in lead optimization and candidate selection with the appropriate physicochemical properties for proper oral dosage formulation. Aqueous solubility is an important parameter in the successful development of oral dosage formulation since poor aqueous solubility limits absorption. In this study, we summarized an efficient approach using a small amount of sample for solid-state characterization, including thermodynamic solubility, which is defined as physicochemical profiling. By using the physicochemical profiling results of 75 anti-cancer drugs and clinical candidates, we examined the relationship between thermodynamic solubility and molecular structural parameters and assessed the effects of thermodynamic solubility on pharmacokinetic profile for rational soluble drug design. The Log DpH 7.4, aromatic ring count, and hydrogen bond count were good indicators for predicting sparingly soluble compounds that increase the lattice energy because of π–π stacking and hydrogen bonds, resulting in lowered thermodynamic solubility. The level of thermodynamic solubility in simulated intestinal fluid (pH 6.8) in the presence and absence of bile acid, which is required for minimal acceptable bioavailability (>30%), was 1 µg/mL and 10 µg/mL, respectively. Physicochemical profiling, which includes thermodynamic solubility considering its solid-state properties, contributes to rational lead optimization and efficient candidate selection for drug development.View full abstractDownload PDF (1304K) Full view HTML -
Chae Jo Lim, Jun Young Choi, Byung Ho Lee, Kwang-Seok Oh, Kyu Yang Yi2013 Volume 61 Issue 12 Pages 1239-1247
Published: December 01, 2013
Released on J-STAGE: December 01, 2013
JOURNAL FREE ACCESS FULL-TEXT HTMLThe discovery that novel naphtho[1,2-b]furan-2-carboxamides containing linked piperidinylphenylacetamide groups serve as melanin concentrating hormone receptor 1 (MCH-R1) antagonists is described. An extensive structure–activity relationship (SAR) study, probing members of this family that contain a variety of aryl and heteroaryl groups at C-5 of the naphtho[1,2-b]furan-2-carboxamide skeleton and having different chain linker lengths, led to the identification of the 5-(4-pyridinyl) substituted analog 10b as a highly potent MCH-R1 antagonist with an IC50 value of 3 nM. This substance also displays good metabolic stability and it does not significantly inhibit cytochrome P450 (CYP450) enzymes. However, 10b has unacceptable oral bioavailability.View full abstractDownload PDF (770K) Full view HTML -
Yoshihiro Shibata, Katsuji Kagechika, Mitsuhiro Yamaguchi, Kenji Yoshi ...2013 Volume 61 Issue 12 Pages 1248-1263
Published: December 01, 2013
Released on J-STAGE: December 01, 2013
JOURNAL FREE ACCESS FULL-TEXT HTMLWe describe herein the design, syntheses and structure–activity relationships (SAR) of novel zwitterionic compounds as non-thiazolidinedion (TZD) based peroxisome proliferator activated receptor (PPAR) α/γ dual agonists. In the previous report, we obtained compound 1 showing potent PPARα/γ dual agonistic activities, together with a great glucose lowering effect in the db/db mice. However, this compound possessed fatal issues such as potent cytochrome P450 (CYP)3A4 direct inhibitory activity. Thus, we carried out the medicinal optimization to improve these while maintaining the potent PPAR agonistic activity. As a result, the issues were addressed by changing the furan ring to a low lipophilic 1,3,4-oxadiazole ring. Additionally, these oxadiazole derivatives exhibited a significant decrease in plasma glucose and plasma triglyceride levels without marked weight gain.View full abstractDownload PDF (1348K) Full view HTML -
Takamitsu Yoshida, Kazuyoshi Terasaka, Setsuko Kato, Fan Bai, Naoki Su ...2013 Volume 61 Issue 12 Pages 1264-1268
Published: December 01, 2013
Released on J-STAGE: December 01, 2013
Advance online publication: September 26, 2013JOURNAL FREE ACCESS FULL-TEXT HTMLCarthamus Red is a food colorant prepared from the petals of Carthamus tinctorius (Asteraceae) whose major pigment is carthamin. Since an authentic carthamin standard is difficult to obtain commercially for the preparation of calibration curves in HPLC assays, we applied 1H-NMR spectroscopy to the quantitative determination of carthamin in commercial preparations of Carthamus Red. Carthamus Red was repeatedly extracted in methanol and the extract was dissolved in pyridine-d5 containing hexamethyldisilane (HMD) prior to 1H-NMR spectroscopic analysis. The carthamin contents were calculated from the ratios of singlet signal intensities at approximately σ: 9.3 derived from H-16 of carthamin to those of the HMD signal at σ: 0. The integral ratios exhibited good repeatability among NMR spectroscopic analyses. Both the intra-day and inter-day assay variations had coefficients of variation of <5%. Based on the coefficient of absorption, the carthamin contents of commercial preparations determined by 1H-NMR spectroscopy correlated well with those determined by colorimetry, although the latter were always approximately 1.3-fold higher than the former, irrespective of the Carthamus Red preparations. In conclusion, the quantitative 1H-NMR spectroscopy used in the present study is simple and rapid, requiring no carthamin standard for calibration. After HMD concentration has been corrected using certified reference materials, the carthamin contents determined by 1H-NMR spectroscopy are System of Units (SI)-traceable.View full abstractDownload PDF (438K) Full view HTML -
Yvonne Chondo, Ying Li, Fumiya Makino, Ning Tang, Akira Toriba, Takayu ...2013 Volume 61 Issue 12 Pages 1269-1274
Published: December 01, 2013
Released on J-STAGE: December 01, 2013
JOURNAL FREE ACCESS FULL-TEXT HTMLA new method for the analysis of selected nitropolycyclic aromatic hydrocarbons (NPAHs) at ultra-trace levels in water samples is proposed. Particulate NPAHs were collected on a GC glass fiber filter. Soluble NPAHs were collected on a C18 Empore disk. After simple clean-up and concentration of NPAHs in both phases, the NPAHs were analyzed using HPLC equipped with clean-up, reducer, concentration and chemiluminescence detection units. The proposed method showed good linear calibration curves with correlation coefficients (r2) ranging from 0.9954 to 0.9998. The limits of detection ranged from 0.013 to 0.15 nmol/L (soluble NPAHs) and from 0.01 to 0.13 nmol/L (particulate NPAHs) for 5 NPAHs [(9-nitroanthracene, 1-nitropyrene, 6-nitrochrysene (6-NC), 7-nitrobenz[a]anthracene and 6-nitrobenzo[a]pyrene] having 3 to 5 rings analyzed, when 1.5 L of water sample was used. The repeatability for soluble NPAHs ranged between 4.2 and 6.8% (n=5), while for particulate NPAHs, it varied between 2.2 and 2.8% (n=5). The proposed method successfully determined the above NPAHs expect 6-NC in river water samples, suggesting that this method is suitable for the ultra-trace analysis of NPAHs in water samples.View full abstractDownload PDF (677K) Full view HTML -
Rie Yamamoto, Shinri Takasuga, Katsuya Kominami, Chiyo Sutoh, Mine Kin ...2013 Volume 61 Issue 12 Pages 1275-1281
Published: December 01, 2013
Released on J-STAGE: December 01, 2013
JOURNAL FREE ACCESS FULL-TEXT HTMLThe aim of the present study was to evaluate the feasibility of transdermal delivery of glycyrrhizin, an agent used in the treatment of chronic hepatitis C, by cathodal iontophoresis using Ag/AgCl electrodes in vitro. The effects of donor pH (pH 4–7), concentration of drug (0.025–0.2% (w/v)), concentration of external chloride ions (Cl−) (0–133 mM), current strength (0–0.5 mA/cm2), and permeation enhancers (urea and Tween 80) on the skin permeability of glycyrrhizin were examined in in vitro skin permeation studies using porcine ear skin as the membrane. The cumulative amount of permeated glycyrrhizin and the steady-state skin permeation flux of glycyrrhizin across porcine skin increased in a pH-dependent manner. The skin permeability of glycyrrhizin was independent of the concentration of drug and competed only with a high external Cl− concentration. The skin permeation flux of glycyrrhizin increased with the current (R2=0.8955). The combination of iontophoresis and enhancers provided an additive or synergistic effect, and a skin permeation flux of about 60 µg/h/cm2 was achieved. The plasma concentration of glycyrrhizin in humans, extrapolated from the in vitro steady-state permeation flux across porcine skin, was within the therapeutic level. These results suggest that cathodal iontophoresis can be used as a transdermal drug delivery system for glycyrrhizin using reasonable patch sizes and acceptable levels of current intensity.View full abstractDownload PDF (434K) Full view HTML -
Ning Wang, Kathryn Jean Wicht, Li Wang, Wen-Jie Lu, Ryuhei Misumi, Min ...2013 Volume 61 Issue 12 Pages 1282-1290
Published: December 01, 2013
Released on J-STAGE: December 01, 2013
Advance online publication: September 24, 2013JOURNAL FREE ACCESS FULL-TEXT HTMLThis report describes the synthesis and in vitro anti-malarial evaluations of certain C2 or C8 and C11-disubstituted 6-methyl-5H-indolo[2,3-b]quinoline (neocryptolepine congener) derivatives. To attain higher activities, the structure–activity relationship (SAR) studies were conducted by varying the kind of alkylamino or ω-aminoalkylamino stubstituents at C11 and with Cl at the C2 position, or CO2Me at the C9 position. The anti-malarial activities of the tested compounds were significantly increased compared to the 11-non(alkylamino) derivatives. The 3-aminopropylamino group at C11 was further modified to urea and thiourea, which improved the cytotoxicity against normal cells. The best results were achieved with compounds 8 and 9d against the NF54 strain with the IC50/SI values as of 86 nM/20 and 317 nM/370, respectively. Furthermore, the compounds were tested for β-haematin inhibition. Twelve were found to have IC50 values below 100 µM and a linear correlation between the β-haematin inhibition and cell growth inhibition in the NF54 strain was found for those derivatives with basic amino side chains. A second correlation was identified between the NF54 activity and physico-chemical factors related to solvation and polarity.View full abstractDownload PDF (751K) Full view HTML -
Guda Mallikarjuna Reddy, Akkarapalli Muralikrishna, Venkatapuram Padma ...2013 Volume 61 Issue 12 Pages 1291-1297
Published: December 01, 2013
Released on J-STAGE: December 01, 2013
JOURNAL FREE ACCESS FULL-TEXT HTMLA new class of mono and bis heterocycles-styrylsulfonylmethyl 1,3,4-oxadiazoles, pyrazolyl/isoxazolyl-1,3,4-oxadiazoles were prepared and studied their antioxidant activity. The compound methyl substituted 2-(p-methylphenylamino-sulfonylmethyl)-5-[Z-(p-methylstyrylsulfonylmethyl)]-1,3,4-oxadiazole displayed slightly higher antioxidant activity than the standard ascorbic acid.View full abstractDownload PDF (676K) Full view HTML -
Kenzo Yahata, Masaki Minami, Yuki Yoshikawa, Kei Watanabe, Hiromichi F ...2013 Volume 61 Issue 12 Pages 1298-1307
Published: December 01, 2013
Released on J-STAGE: December 01, 2013
Advance online publication: September 21, 2013JOURNAL FREE ACCESS FULL-TEXT HTMLA methodology for selective transformations of ketones, esters, Weinreb amides, and nitriles in the presence of aldehydes has been developed. The use of a combination of PPh3-trimethylsilyl trifluoromethanesulfonate (TMSOTf) promotes selective transformation of aldehydes to their corresponding, temporarily protected, O,P-acetal type phosphonium salts. Because, hydrolytic work-up following ensuing reactions of other carbonyl moieties in the substrates liberates the aldehyde moiety, a sequence involving aldehyde protection, transformation of other carbonyl groups, and deprotection can be accomplished in a one-pot manner. Furthermore, the use of PEt3 instead of PPh3 enables ketones to be converted in situ to their corresponding O,P-ketal type phosphonium salts and, consequently, selective transformations of esters, Weinreb amides, and nitriles in the presence of ketones can be performed. This methodology is applicable to various dicarbonyl compounds, including substrates that possess heteroaromatic skeletons and hydroxyl protecting groups.View full abstractDownload PDF (1230K) Full view HTML
Notes
-
Kazuma Shioe, Shingo Ishikura, Yoshikazu Horino, Hitoshi Abe2013 Volume 61 Issue 12 Pages 1308-1314
Published: December 01, 2013
Released on J-STAGE: December 01, 2013
JOURNAL FREE ACCESS FULL-TEXT HTMLA facile method for the synthesis of dehydrodigallic acid, which is a fundamental structure of ellagitannins, was developed. A classical Ullmann condition was effective for the formation of the highly hindered biaryl ether structure, and we clarified that the suitable protection of the phenolic hydroxy groups was crucial in this reaction. In this way, the synthesis of dehydrodigallic acid and its derivative was successfully performed. The described method would provide a synthetic utility toward ellagitannins.View full abstractDownload PDF (641K) Full view HTML -
Daigo Wakana, Nobuo Kawahara, Yukihiro Goda2013 Volume 61 Issue 12 Pages 1315-1317
Published: December 01, 2013
Released on J-STAGE: December 01, 2013
Advance online publication: September 27, 2013JOURNAL FREE ACCESS FULL-TEXT HTMLA new pyrrolidine alkaloid codonopsinol C (1), and pyrrolidine alkaloidal glycoside, codonopiloside A (2), were isolated from the roots of Codonopsis pilosula, along with four known pyrrolidine alkaloids, codonopsinol A (3), codonopsinol B (4), codonopyrrolidium B (5), and radicamine A (6). The structures of the new compounds were established by acid hydrolysis and spectroscopic methods. We describe those structures in this paper.View full abstractDownload PDF (426K) Full view HTML -
Feng Li, Ken Tanaka, Shiro Watanabe, Yasuhiro Tezuka, Ikuo Saiki2013 Volume 61 Issue 12 Pages 1318-1322
Published: December 01, 2013
Released on J-STAGE: December 01, 2013
Advance online publication: September 27, 2013JOURNAL FREE ACCESS FULL-TEXT HTML
Supplementary materialA new pyridine alkaloid-coupled iridoid glucoside, dipasperoside A (1), and 20 known compounds (2–21) were isolated from a water extract of Dipsacus asper roots. Compound 1 possessed a unique structural feature with a nicotinic acid nucleus coupled through C-5 with C-7 of a secoiridoid/iridoid glucoside dimer, and esterified with a C-7 hydroxyl group of an iridoid glucoside monomer. All isolates were evaluated for their inhibitory activity against nitric oxide (NO) production in a lipopolysaccharide (LPS)-activated murine macrophage cell line, RAW264.7.View full abstractDownload PDF (591K) Full view HTML -
Min Zhao, Xiubao Li, Feng Zhao, Shimiao Cheng, Zheng Xiang, Jianyong D ...2013 Volume 61 Issue 12 Pages 1323-1328
Published: December 01, 2013
Released on J-STAGE: December 01, 2013
Advance online publication: September 19, 2013JOURNAL FREE ACCESS FULL-TEXT HTMLFour new 7,8-epoxycembranoids, namely (2S*,7S*,8S*,12R*,1Z,3E,10E)-7,8:2,16-diepoxycembra-1(15),3,10-trien-12-ol (1), (2S*,7S*,8S*,11R*,1Z,3E)-7,8:2,16-diepoxycembra-1(15),3,12(20)-trien-11-ol (2), (4S*,7S*,8S*,1Z,2E,11E)-16-acetoxy-7,8-epoxycembra-1(15),2,11-trien-4-ol (3), and (7S*,8S*,15S*,1E,3E,11E)-7,8-epoxycembra-1,3,11-trien-15,16-diol (4) were isolated from a Chinese soft coral Lobophytum sp., together with eleven known analogues 5–15. The structures of the new compounds were determined by extensive spectroscopic data analysis. All compounds were tested for the inhibitory effect on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse peritoneal macrophages (PEMΦ).View full abstractDownload PDF (672K) Full view HTML
- |<
- <
- 1
- >
- >|