著者
Kounosuke Oisaki
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.66, no.10, pp.907-919, 2018-10-01 (Released:2018-10-01)
参考文献数
40

To conduct organic synthesis in the field of pharmaceutical science, methodologies that can easily and quickly supply compounds with high drug-likeness are highly desirable. Based on the original catalyst design concept “Radical-Conjugated Redox Catalysis (RCRC)” established during my research, various C(sp3)–H functionalizations and protein modifications have been developed, taking advantage of the high reactivity and chemoselectivity of the single-electron transfer process. This review focuses on the eight-year research efforts by my collaborators and me, from conception to results.
著者
Khem Raj Joshi Hari Prasad Devkota Takashi Watanabe Shoji Yahara
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.62, no.2, pp.191-195, 2014-02-01 (Released:2014-02-01)
参考文献数
24
被引用文献数
3 4

Three new glycosides: thotneoside A (quercetin 3-O-(6″-O-phenylacetyl)-β-D-galactopyranoside) (1), thotneoside B (quercetin 3-O-(6″-O-phenylacetyl)-β-D-glucopyranoside) (2) and thotneoside C (3-methyl-2-butenoic acid 1-O-β-D-glucopyranoside) (3), together with nine known compounds; quercetin (4), quercetin 3-O-β-D-galactopyranoside (5), quercetin 3-O-(6″-O-galloyl)-β-D-galactopyranoside (6), quercetin 3-O-β-D-galacturonopyranoside (7), quercetin 3-O-β-D-glucuronopyranoside (8), quercetin 3-O-α-L-rhamnopyranoside (9), rutin (10), quercetin 3-O-α-L-arabinopyranoside (11) and 2,4,6-trihydroxyacetophenone 2-O-β-D-glucopyranoside (12) have been isolated from the shade dried leaves of Aconogonon molle, commonly known as “Thotne″ in Nepal. The structures were elucidated on the basis of chemical and spectroscopic methods. All of these compounds were isolated for the first time from A. molle and their in vitro antioxidant activity was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay. Quercetin (4) and its glycosides (1–2, 5–11) showed potent free radical scavenging activity.
著者
Kiyosei Takasu
出版者
公益社団法人日本薬学会
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.64, no.7, pp.656-667, 2016-07-01 (Released:2016-07-01)
参考文献数
68
被引用文献数
1 5

The search for new drugs that could treat tropical protozoan diseases, such as malaria or neglected tropical diseases (NTDs), motivates many medicinal chemists. New classes of antiprotozoal drugs that act through a novel mechanism of action must be developed. This review presents our efforts toward finding new candidate treatments for malaria, American trypanosomiasis, human African trypanosomiasis and leishmaniasis based on π-delocalized lipophilic cations (DLCs). DLCs, such as rhodacyanines, azarhodacyanines, β-carbolinium salts, and phenoxazinium salts, displayed strong antiprotozoal activities with highly selective indices. Several DLCs displayed moderate to excellent in vivo efficacies against Plasmodium berghei when administered intraperitoneally or orally. This review also discusses chemical biology approaches to understanding the mechanism of action underlying the antimalarial rhodacyanines.
著者
Hironori Takeuchi Yoshihiro Ueda Takumi Furuta Takeo Kawabata
出版者
公益社団法人日本薬学会
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.65, no.1, pp.25-32, 2017-01-01 (Released:2017-01-01)
参考文献数
27
被引用文献数
5

A short-step total synthesis of the natural glycosides pterocarinin C and tellimagrandin II (eugeniin) has been performed by sequential and site-selective functionalization of free hydroxy groups of unprotected D-glucose. The key reactions are β-selective glycosidation of a gallic acid derivative using unprotected D-glucose as a glycosyl donor and catalyst-controlled site-selective introduction of a galloyl group into the inherently less reactive hydroxy group of the glucoside.
著者
Masao Toyota Takuji Shimamura Hikari Ishii Matt Renner John Braggins Yoshinori Asakawa
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.50, no.10, pp.1390-1392, 2002 (Released:2002-10-01)
参考文献数
5
被引用文献数
26 40

The ether extract of the New Zealand liverwort Radula marginata afforded a new cannabinoid type bibenzyl compound named perrottetinenic acid, and two new bibenzyls, together with a known cannabinoid, perrottetinene. Their structures were established by two dimensional (2D) NMR spectral data. The structure of perrottetinenic acid was a similar to that of Δ1-tetrahydrocannabinol, a known hallucinogen. Cannabinoid type bibenzyls have been isolated from liverwort Radula perrottetii, though have not previously been reported from the liverwort R. marginata.
著者
Arno Hazekamp Young Hae Choi Robert Verpoorte
出版者
公益社団法人日本薬学会
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.52, no.6, pp.718-721, 2004 (Released:2004-06-01)
参考文献数
18
被引用文献数
29 45

A 1H-NMR method has been developed for the quantitative analysis of pure cannabinoids and for cannabinoids present in Cannabis sativa plant material without any chromatographic purification. The experiment was performed by the analysis of singlets in the range of δ 4.0—7.0 in the 1H-NMR spectrum, in which distinguishable signals of each cannabinoid are shown. Quantitation was performed by calculating the relative ratio of the peak area of selected proton signals of the target compounds to the known amount of the internal standard, anthracene. For this method no reference compounds are needed. It allows rapid and simple quantitation of cannabinoids with a final analysis time of only 5 min without the need for a pre-purification step.
著者
Hirotomo Moriwaki Yu-Shi Tian Norihito Kawashita Tatsuya Takagi
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.67, no.5, pp.426-432, 2019-05-01 (Released:2019-05-01)
参考文献数
22

Quantitative structure–activity relationship (QSAR) techniques, especially those that possess three-dimensional attributes, such as the comparative molecular field analysis (CoMFA), are frequently used in modern-day drug design and other related research domains. However, the requirement for accurate alignment of compounds in CoMFA increases the difficulties encountered in its use. This has led to the development of several techniques—such as VolSurf, Grid-independent descriptors (GRIND), and Anchor-GRIND—which do not require such an alignment. We propose a technique to construct the prediction model that uses molecular interaction field grid potentials as inputs to convolutional neural network. The proposed model has been found to demonstrate higher accuracy compared to the conventional descriptor-based QSAR models as well as Anchor-GRIND techniques. In addition, the method is target independent, and is capable of providing useful information regarding the importance of individual atoms constituting the compounds contained in the chemical dataset used in the proposed analysis. In view of these advantages, the proposed technique is expected to find wide applications in future drug-design operations.
著者
Jun Shimokawa
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.66, no.2, pp.105-115, 2018-02-01 (Released:2018-02-01)
参考文献数
153
被引用文献数
1

The divergent total syntheses of three types of heteropolycyclic natural products, namely gelsedine-type alkaloids, amathaspiramide alkaloids, and erythrina alkaloids, are outlined. A strategy involving a late-stage pluripotent common synthetic intermediate prepared via original and innovative transformations was employed. A brief description of the philosophy and criteria for choosing the synthetic targets and common synthetic precursors, as well as details regarding the development of the overall synthetic schemes from a common intermediate are discussed.
著者
Yo Muraki Midori Yamasaki Hirohisa Takeuchi Kimio Tohyama Noriyasu Sano Takanori Matsuo
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
pp.c17-00811, (Released:2018-01-06)
参考文献数
36

Pulmonary hypertension (PH) is a life-threatening lung disease. Despite the availability of several approved drugs, the development of a new treatment method is needed because of poor prognosis. Tissue selective drug delivery systems can avoid the adverse effects of current therapy and enhance efficacy. We evaluated the possibility of delivering drugs to the lungs of a PH rat model using fluorescence dye-labeled nanosized liposomes. To evaluate the tissue distribution following systemic exposure, fluorescent dye-labeled, 40-180 nm liposomes with and without polyethylene glycol (PEG) were intravenously administered to a monocrotaline-induced PH (MCT) rat model and tissue fluorescence was measured. Fluorescent dye-containing liposomes were intratracheally administered to the MCT model to evaluate the distribution of the liposome-encapsulated compound following local administration to reduce systemic exposure. The lung vascular permeability, plasma concentration of surfactant protein (SP)-D, lung reactive oxygen species (ROS) production, and macrophage marker gene cluster of differentiation (CD68) expression were measured. PEG and 80-nm liposome accumulation in the lung was elevated in the MCT model compared to that in normal rats. The intratracheally administered liposomes were delivered selectively to the lungs of the MCT model. The lung vascular permeability, plasma SP-D concentration, and CD68 expression were significantly elevated in the lungs of the MCT model, and were all significantly and positively correlated to liposome lung accumulation. Liposomes can accumulate in the lungs of an MCT model by enhancing vascular permeability by the inflammatory response. Therefore, drug encapsulation in liposomes could be an effective method of drug delivery in patients with PH.
著者
兼松 顯 内藤 良 下東 康幸 大野 素徳 小笠原 富夫 黒野 昌庸 八木 國夫
出版者
公益社団法人日本薬学会
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.38, no.5, pp.1438-1440, 1990-05-25 (Released:2008-03-31)
参考文献数
6
被引用文献数
7 13

An S-activated sulfhydrylmorphine derivative was synthesized, and its linking to the μ-opioid receptor through a disulfide bond was demonstrated.
著者
Shinji Katsura Nobuo Yamada Atsushi Nakashima Sumihiro Shiraishi Mihoko Gunji Takayuki Furuishi Tomohiro Endo Haruhisa Ueda Etsuo Yonemochi
出版者
公益社団法人日本薬学会
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.65, no.4, pp.373-380, 2017-04-01 (Released:2017-04-01)
参考文献数
14

We observed that uncoated furosemide tablets turned yellow in a light-shielded automatic packaging machine and discoloration of the furosemide tablets was heterogeneity and occurred on the surface of the tablets only. The machine was equipped with an internal blower to maintain a constant temperature. Therefore, we investigated the effect of air flow on the discoloration of the furosemide tablets using a blower in a dark environment. The color difference (ΔE) of the furosemide tablets increased linearly as the blowing time increased. We performed structural analysis of the yellow compound in the furosemide tablets by LC-MS and identified the compound as a hydrolysate of furosemide. This suggested that furosemide hydrolysis was accelerated by the air flow. The furosemide tablets were prepared with the most stable furosemide polymorph, form I. X-Ray powder diffractometry and IR spectroscopy showed that during tablet preparation, no crystal transition occurred to an unstable furosemide polymorph. Furthermore, IR spectroscopy showed that the crystal form of furosemide in the yellow portion of the tablets was form I. To elucidate the factors producing the discoloration, we investigated the effect of humidity and atmosphere (air, oxygen, and nitrogen) on the discoloration of the furosemide tablets. The results suggested that the discoloration of the furosemide tablets was accelerated by oxidation, although humidity did not affect the hydrolysis. Therefore, we concluded that the discoloration of the furosemide tablets in the automatic packing machine was caused by acceleration of oxidative degradation by air flow.
著者
大野 雅二 藤田 かがり 中井 久雄 小林 進 井上 圭三 野島 庄七
出版者
公益社団法人日本薬学会
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.33, no.2, pp.572-582, 1985-02-25 (Released:2008-03-31)
参考文献数
21
被引用文献数
41 43

Acetyl glyceryl ether phosphorylcholines (platelet-activating factors ; PAFs), their enantiomers, and their analogues were efficiently synthesized in a stereochemically unambiguous manner starting from D-and L-tartaric acids as chiral synthons. The enantiomer of C16-PAF (S-comfiguration) showed far less activity than the natural PAF (R-configuration), and the N-methylpiperidine and N-methylpyrrolidine analogues were found to possess much higher activity than natural C16-PAF.
著者
Takuya Izawa Koji Nakayama Noritaka Uchida Kazuhiro Nojima
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
pp.c17-00938, (Released:2018-02-22)
参考文献数
30
被引用文献数
1

Dehydroacetic acid (1) was found to induce photoisomerization, converting aldrin (3) and dieldrin (4) into photoaldrin (5) and photodieldrin (6), respectively, not only when irradiated with artificial light at wavelengths longer than 290 nm in air but also when exposed to sunlight in air. By contrast, sodium dehydroacetate (2) induced both photoisomerization, primarily converting 3 to 5 and photoepoxidation, partially forming 6. Thus, because 2 is usually used as a water-soluble antiseptic, photo-erethism might occur due to the isomerization and epoxidation properties of this compound. The difference between the photoreactivity of 1 and that of 2 might be attributed to the spin density of the odd electron on the carbon atom in the respective radicals that were formed after photo-excited 1 and 2 caused H-abstraction.
著者
Hideyuki Konishi
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.66, no.1, pp.1-19, 2018-01-01 (Released:2018-01-01)
参考文献数
110
被引用文献数
1

The use of toxic gas surrogates in organic reactions instead of the gas itself contributes to enhancing the safety, practicality, and efficiency of the reactions involved. Our efforts toward the creation of toxic gas surrogates and the development of a series of catalytic reactions using these surrogates are described. Improvements in substrate scope during the hydroesterification of alkenes using formates facilitated by the Ru–imidazole catalyst system provided the opportunity to discover that phenyl formate is a useful carbon monoxide (CO) surrogate for the generation of CO and phenol under weakly basic conditions. This discovery triggered the development of highly reactive but stable CO surrogates and a variety of Pd-catalyzed carbonylative transformations. N-Formylsaccharin facilitated the use of additional nucleophiles in carbonylation reactions that provided access to a variety of carbonyl compounds. Detailed experimental and theoretical mechanistic studies into the generation of CO from phenyl formate suggest that CO generation proceeds via a concerted E2 α-elimination. Furthermore, a known surrogate of sulfur dioxide was applied for the first time to the selective syntheses of cyclic sulfonamides and sulfinamides, confirming that the surrogate operates as an “S=O” source. Notably, the reactions described herein are scalable and can be performed without the use of external toxic gases and specialized reaction vessels; they are easy and simple to perform and demonstrate enormous potential for industrial application.
著者
Chihiro Tsukano Satoshi Suetsugu Nobusuke Muto Yoshiji Takemoto
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.65, no.12, pp.1167-1174, 2017-12-01 (Released:2017-12-01)
参考文献数
43

Tetrahydrobiphenylene consists of cyclobutene fused with benzene and cyclohexene rings. In this paper, a direct method for synthesizing tetrahydrobiphenylenes based on a palladium (Pd)(0)-catalyzed C(sp2)–H functionalization was investigated. The developed method was applied to the synthesis of several tetrahydrobiphenylenes having an oxygen functionality at the ring juncture. The derivatization of a tetrahydrobiphenylene is also reported.
著者
Kazuhiro Morisaki Yuta Kondo Masanao Sawa Hiroyuki Morimoto Takashi Ohshima
出版者
公益社団法人日本薬学会
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.65, no.11, pp.1089-1092, 2017-11-01 (Released:2017-11-01)
参考文献数
20

This note describes the construction of tetrasubstituted carbon stereocenters via palladium-catalyzed allylation of sp3 C–H bonds of 2,2,2-trifluoroethylamine derivatives. The presence of 2-pyridyl group of the imines derived from 1-substituted-2,2,2-trifluoroethylamine was key to promoting the reaction efficiently, allowing an access to a variety of 1-allylated 2,2,2-trifluoroethylamine derivatives with tetrasubstituted carbon stereocenters.
著者
Yusai Ito Naoki Harikai Kyoko Ishizuki Kazufusa Shinomiya Naoki Sugimoto Hiroshi Akiyama
出版者
公益社団法人日本薬学会
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
pp.c17-00404, (Released:2017-07-01)
参考文献数
18
被引用文献数
1

Cochineal extract prepared from the scale insect Dactylopus coccus (American cochineal) has been used as a natural red dye for food, cosmetics, and pharmaceuticals. The major pigment in cochineal extract is carminic acid (CA), an anthraquinone glucoside, and several minor pigments have been previously reported. Our investigation aimed at establishing the safety of cochineal dye products using UPLC-PDA-ESI-TOF/MS found an unknown minor pigment, spiroketalcarminic acid (1), in three commercial cochineal extract samples; cochineal extract used in food additives, carmine that is an aluminum salt of cochineal extract used as natural dye, and a research reagent of CA. The purification of 1 from cochineal extract involved sequential chromatographic techniques, including preparative reversed-phase HPLC. 2D NMR and mass analyses established the structure of 1 to be a novel anthraquinone with an unusual 6,5-spiroketal system instead of the C-glucosyl moiety of CA. The absolute stereochemistry of the spiroketal moiety in 1 was determined by NOESY correlations and optical rotation. No data corresponding to 1 had previously been reported for extracts of dried cochineal insects and traditional art products dyed with cochineal extract, indicating that 1 is likely produced during the preparation of commercial cochineal extract.
著者
野中 源一郎 松本 陽子 西岡 五夫
出版者
公益社団法人日本薬学会
雑誌
Chemical & pharmaceutical bulletin (ISSN:00092363)
巻号頁・発行日
vol.29, no.4, pp.1184-1187, 1981-04-25

A novel hydrolyzable tannin named trapain has been isolated from Trapa japonica FLEROV. (Oenotheraceae), and the structure has been established as II on the basis of the spectroscopic and chemical evidences.
著者
三橋 博 金子 光 佐々木 希吉
出版者
公益社団法人 日本薬学会
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.10, no.11, pp.1119-1122, 1962
被引用文献数
1

It was shown that DL-phenylalanine [2-<SUP>14</SUP>C] was incorporated into C-3 of two kinds of isoflavone, formononetin and genistein, by <I>Trifolium pratense</I> sp., <I>in vivo</I>.<BR>These results indicate that the aryl group undergoes a migration within the C<SUB>6</SUB>-C-C-C fragment, and this observation agrees with Grisebach's experimental data.
著者
梅澤 勲 野澤 雅子 南雲 紳史 秋田 弘幸
出版者
公益社団法人日本薬学会
雑誌
Chemical & pharmaceutical bulletin (ISSN:00092363)
巻号頁・発行日
vol.43, no.7, pp.1111-1118, 1995-07-15
被引用文献数
1

Three kinds of oudemansin X, (-)-1,(+)-1 and (±)-1,were totally synthesized. The key point in the present chiral synthesis was the enantioselective acetylation of the racemic alcohols, (±)-5 and (±)-8,using lipase in an organic solvent. The synthetic (-)-1 was found to exhibit strong antifungal activity against several molds and yeasts.