{"title":"Experimental and DFT Studies of Intermolecular Interaction-Assisted Oxindole Cyclization Reaction of Di-t-butyl 2-Aminophenyl-2-methyl Malonate.","authors":"Ryo Kakehi, Yu-Suke Yamai, Akio Tanaka, Kyoji Ishida, Shinichi Uesato, Yasuo Nagaoka, Takaaki Sumiyoshi","doi":"10.1248/cpb.c24-00663","DOIUrl":"10.1248/cpb.c24-00663","url":null,"abstract":"<p><p>Density functional theory calculations on the cyclization of di-t-butyl 2-(2-aminophenyl)-2-methyl malonate (1) to t-butyl 3-methyloxindole-3-carboxylate (2) reveal that acetic acid-assisted protonation of the carbonyl oxygen atom reduces the activation Gibbs free energy significantly lower than methanol-assisted pathways. Experimental data confirm that reaction concentration plays a pivotal role in oxindole formation. Experimental results also indicate distinct reaction mechanisms at low and high concentrations. Achieving high enantioselectivity for chiral compound 2 in high-concentration reactions requires discovering a novel chiral acid.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 1","pages":"63-66"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Brominated 3-Acetyl-11-keto-β-boswellic Acid Derivative from Boswellia serrata Extract Characterized by Single-Crystal X-Ray Structure Analysis and Mass Spectroscopy.","authors":"Masataka Ito, Keisuke Misao, Hironori Suzuki, Shuji Noguchi","doi":"10.1248/cpb.c24-00819","DOIUrl":"10.1248/cpb.c24-00819","url":null,"abstract":"<p><p>3-Acetyl-11-keto-β-boswellic acid is a pentacyclic triterpenoid. It is found in frankincense, which is the resin found in plants from the Boswellia genus. Single crystals of 3-acetyl-11-keto-β-boswellic acid methanol and acetonitrile solvates were obtained from the Boswellia serrata extract. X-Ray crystal structure analysis revealed the coexistence of a brominated derivative, 3-acetyl-11-keto-12-bromo-β-boswellic acid. Mass spectroscopy analysis confirmed the presence of the brominated derivative in the extract. These results provide a structural basis for insights into the chemical reactivity and possibly the biosynthesis of 3-acetyl-11-keto-β-boswellic acid and its related substances in B. serrata.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 4","pages":"314-317"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuta Ito, Kang Juri, Yasufumi Fuchi, Yoshiyuki Hari
{"title":"Concise Synthesis of 4'-Modified Thymidines via 1,5-Hydrogen Atom Transfer/Intermolecular 1,4-Addition Process.","authors":"Yuta Ito, Kang Juri, Yasufumi Fuchi, Yoshiyuki Hari","doi":"10.1248/cpb.c25-00021","DOIUrl":"https://doi.org/10.1248/cpb.c25-00021","url":null,"abstract":"<p><p>A concise approach is presented for preparing 4'-modified thymidines from oxime imidates using readily generated 4'-carbon radicals. This method produces 4'-modified thymidines from natural thymidine using the Mitsunobu reaction, the protection of 3'-hydroxy group (when necessary), and 1,5-hydrogen atom transfer (1,5-HAT)/intermolecular 1,4-addition with electron-deficient olefins. Moreover, using a one-pot synthesis involving 1,5-HAT/intermolecular 1,4-addition, followed by the hydrolysis of the imidate intermediate under basic conditions, 4'-modified thymidine was diastereoselectively isolated. This is because the 4'-isomer transferred to the water layer in the work-up process.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 4","pages":"369-373"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaohan Liu, Xinru Liu, Wenteng Zheng, Jing Xu, Tingting Chen, Tao Peng, Ruixin Liu, Shuchen Liu, Lin Wang, Shouguo Zhang
{"title":"Synthesis and Anti-hypoxic Activity Research of Daidzein Derivatives.","authors":"Xiaohan Liu, Xinru Liu, Wenteng Zheng, Jing Xu, Tingting Chen, Tao Peng, Ruixin Liu, Shuchen Liu, Lin Wang, Shouguo Zhang","doi":"10.1248/cpb.c25-00014","DOIUrl":"https://doi.org/10.1248/cpb.c25-00014","url":null,"abstract":"<p><p>To search for safe and efficient anti-hypoxia active molecules, 27 derivatives were synthesized by introducing aminoalkyl groups at daidzein's position-7 and position-8. The structures of these derivatives were confirmed by <sup>1</sup>H-NMR, <sup>13</sup>C-NMR, and mass spectrometry. The anti-hypoxia activity was evaluated in vitro using a cell hypoxia model established with the AnaeroPack-anaero. The results showed that 9 compounds significantly enhanced cell viability under hypoxic conditions, with compounds 2a, 2b, 4d, 5a, and 5d exhibiting in vitro anti-hypoxia activity significantly superior to daidzein. And the drug-like properties prediction results of the target compounds indicated that compounds 2a, 2b, 4d, 5a, and 5d may also demonstrate favorable pharmacokinetic properties. Further, the anti-hypoxia activity in vivo of these 5 derivatives were evaluated via normobaric hypoxia and hypobaric hypoxia models. The results indicated that all of the 5 compounds extended the survival time of mice under normobaric hypoxia to varying degrees, and they also alleviated oxidative stress damage to the brain and heart of mice under hypobaric hypoxia. Among these, compound 2a demonstrated superior anti-hypoxia activity both in vitro and in vivo compared to daidzein, making it worthy of further study as a potential candidate for an anti-hypoxia drug.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 5","pages":"434-444"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparative Analysis of Needleless and Needle-Based Electrospinning Methods for Polyamide 6: A Technical Note.","authors":"Arash Yavari, Takaaki Ito, Kouji Hara, Kohei Tahara","doi":"10.1248/cpb.c24-00611","DOIUrl":"10.1248/cpb.c24-00611","url":null,"abstract":"<p><p>This study investigates the influence of needleless versus needle-based electrospinning methods on the fiber diameter of polyamide 6 (PA6) nanofibers under comparable conditions, with an emphasis on potential pharmaceutical applications. Additionally, it examines how varying solvent systems impact fiber diameter specifically in needleless electrospinning. In this study, it was found that fibers produced by the needleless method were thicker compared to those produced by the needle-based method, a trend attributable to the specific solution characteristics and parameter settings unique to this study. Notably, a 2 : 1 acetic acid : formic acid solvent mixture yielded the largest fiber diameters among the solvent systems assessed for needleless electrospinning. These results underscore the potential of PA6 nanofibers in pharmaceutical applications, suggesting that further optimization of electrospinning conditions could enhance their suitability. The study also discusses the implications of scale-up production using needleless technology, highlighting its viability for industrial applications over single-needle electrospinning.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 1","pages":"18-24"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Permeation of Model Chemicals through Medical Gowns Used in Anticancer Drug Preparation.","authors":"Takuya Sotome, Takeshi Oshizaka, Tomoaki Toyama, Keiko Shinozaki, Satoru Usui, Kenji Mori, Kenji Sugibayashi","doi":"10.1248/cpb.c24-00838","DOIUrl":"https://doi.org/10.1248/cpb.c24-00838","url":null,"abstract":"<p><p>The wearing of medical gowns during anticancer drug preparation is recommended for the prevention of drug exposure. Non-breathable and breathable gowns (gown- and gown+, respectively) are both available. However, anticancer drugs may permeate \"gown+.\" In the present study, water, hydrophilic and lipophilic dyes, and aqueous solutions of several model chemicals with different physical properties (pyridoxine, antipyrine, ethyl p-hydroxybenzoate, and butyl p-hydroxybenzoate) were applied to four types of gowns and their chemical permeabilities were measured. The permeability of gowns to vaporized ethanol was also investigated because several volatile anticancer drugs are currently used in the treatment of cancer. The results obtained showed that the hydrophilic chemical, pyridoxine, did not permeate any of the gowns tested. Furthermore, gowns became more permeable as the lipophilicity of chemicals increased. No significant changes were observed in the chemical permeability between \"gown-\" and \"gown+,\" suggesting that the protective efficacy of the gowns against permeation by anticancer drugs was similar regardless of breathability. On the contrary, \"gown + \" was permeable to vaporized ethanol, whereas \"gown-\" was not. The present study demonstrates the need for safety measures in lipophilic or volatile anticancer drug handling and the importance of developing medical gowns that are highly resistant to chemical permeation.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 3","pages":"227-233"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Methylene Blue Removal from the Aqueous Phase Using a Magnetic-Calcined Bamboo Composite Adsorbent.","authors":"Fumihiko Ogata, Kazuya Ujita, Yugo Uematsu, Noriaki Nagai, Chalermpong Saenjum, Shigeharu Tanei, Naohito Kawasaki","doi":"10.1248/cpb.c24-00648","DOIUrl":"10.1248/cpb.c24-00648","url":null,"abstract":"<p><p>In the present study, magnetic-calcined bamboo composite adsorbents (MCBC200, MCBC400, MCBC600, MCBC800, and MCBC1000) were prepared, and their physicochemical characteristics (scanning electron microscope images, differential thermogravimetric analysis, Fourier transform-IR, specific surface area, surface functional groups, and point of zero charge [pH<sub>pzc</sub>]) were evaluated. Furthermore, the adsorption capacity of methylene blue (MB, cationic dye) using the prepared adsorbents was assessed. The value of pH<sub>pzc</sub> and the specific surface area of MCBC400 were 7.8 and 50.6 m<sup>2</sup>/g, respectively. The amounts of acidic or basic functional groups of MCBC400 were relatively greater than those of the other adsorbents. The amount of MB adsorbed onto MCBC400 (31.9 mg/g) was higher than that onto other adsorbents. The adsorption of MB using MCBC400 was evaluated in relation to various parameters, including coexistence, solution pH, adsorption temperature, and contact time. The results followed the Langmuir isotherm model and a pseudo-second-order model with correlation coefficients of 0.980-1.000 and 0.996, respectively. MB was selectively adsorbed by MCBC400 in a binary solution system containing anionic dyes. Finally, one of the adsorption mechanisms was determined by analyzing the elemental distribution and the binding energy before and after the adsorption of MB. The current findings provide important information for removing MB with MCBC400 from the aqueous phase.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 3","pages":"205-212"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Physical Properties for Novel Cilostazol Co-amorphous; Effect of Preparation Method and Molar Ratio on the Co-amorphous.","authors":"Tomoki Takayama, Shun Kaneko, Vasanthi Palanisamy, Makoto Ono, Varin Titapiwatanakun, Kenjirou Higashi, Toshiro Fukami","doi":"10.1248/cpb.c24-00732","DOIUrl":"10.1248/cpb.c24-00732","url":null,"abstract":"<p><p>Co-amorphous materials have gained special attention in the pharmaceutical field due to their high potential to enhance the oral bioavailability of poorly aqueous soluble drugs. In co-amorphous studies, few reports have examined the physical properties and molecular states of different active pharmaceutical ingredients (APIs) : co-amorphous former (CF) molar ratios and preparation methods. Therefore, we investigated the effect of molar ratio and preparation method on the physical properties of a novel co-amorphous system consisting of cilostazol and l-tryptophan, which we identified through screening. Co-amorphous consisting of molar ratios of 1 : 1 (co-milling (CM) 1 : 1), 1 : 1.5 (CM 1 : 1.5), and 1 : 2 (CM 1 : 2) were prepared by the CM method, while samples with a molar ratio of 1 : 1 (spray drying (SD) 1 : 1) were prepared by the spray drying method. CM 1 : 1.5 and CM 1 : 2 showed the highest solubility. Storage stability was excellent for CM 1:1.5, CM 1 : 2, and SD 1 : 1, whereas physical properties were improved by co-amorphization. To investigate the factors responsible for the improved physical properties, the molecular state of the co-amorphous system was evaluated, and it was inferred that hydrogen bonds were formed between cilostazol and l-tryptophan. Solid-state <sup>13</sup>C-NMR showed several new peaks specific to the solid state in the co-milled sample compared to SD 1 : 1 and cilostazol amorphous, suggesting that the molecular state may differ depending on the preparation method. As described above, different physical properties and molecular states were observed in the novel co-amorphous system consisting of cilostazol and l-tryptophan when the molar ratio of APIs and CF, and the preparation method differed.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 4","pages":"318-326"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}