Chemical & pharmaceutical bulletin最新文献_第3页

Isolation of Compounds Including Two New Compounds from Asiasarum Root and Their Anti-glycation Activity. 亚洲细辛根中两种新化合物的分离及其抗糖化活性研究。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00034

Aiko Sano, Ryuichiro Suzuki

引用次数: 0

Tris(2,2,2-trifluoroethoxy)silane-Enabled Peptide Bond Formation between Unprotected Amino Acids and Amino Acid t-Butyl Esters. 三（2,2,2-三氟乙氧基）硅烷使无保护氨基酸和氨基酸t-丁基酯之间的肽键形成。

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00457

Isai Ramakrishna, Alex Boateng, Tomohiro Hattori, Hisashi Yamamoto

{"title":"Tris(2,2,2-trifluoroethoxy)silane-Enabled Peptide Bond Formation between Unprotected Amino Acids and Amino Acid t-Butyl Esters.","authors":"Isai Ramakrishna, Alex Boateng, Tomohiro Hattori, Hisashi Yamamoto","doi":"10.1248/cpb.c25-00457","DOIUrl":"https://doi.org/10.1248/cpb.c25-00457","url":null,"abstract":"Conventional peptide synthesis involves multiple protection and deprotection steps, and typically relies on stoichiometric amounts of coupling reagents and additives. This makes the process cumbersome, and results in poor atom economy and hazardous waste generation. Therefore, direct peptide bond formation using unprotected amino acids is a promising alternative. However, this approach presents some challenges: 1) Solubility of unprotected amino acids in organic solvents; 2) Control of undesired side reactions; 3) Chemo-selective activation of the carboxylic acid group in the presence of an amine functionality; and 4) Epimerization. To address these challenges, we developed tris(2,2,2-trifluoroethoxy)silane [H-Si(OCH2CF3)3], a cost-effective and accessible coupling reagent. This single reagent efficiently synthesizes N-terminal free peptides from unprotected amino acids and amino acid tert-butyl esters, without the need for any additives. H-Si(OCH2CF3)3 enhances amino acid solubility through coordinating with both termini and plays a dual role, serving as a transient amine-protecting group and as a carboxylic acid activating or promoting reagent for peptide bond formation. This method is operationally simple and versatile, enabling the efficient synthesis of N-terminal free peptides from unprotected amino acids and amino acid tert-butyl esters, with good yields, high optical purity, and broad side-chain compatibility.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 9","pages":"787-792"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991599","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}

引用次数: 0

Characteristics of Calcined Sugarcane Bagasse and Its Ability to Adsorb Cadmium from Aqueous Solutions. 煅烧甘蔗渣的特性及其对镉的吸附能力。

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00282

Kaito Yamashiro, Ryo Miyamoto, Fumihiko Ogata, Naohito Kawasaki

引用次数: 0

Aminoalkylation of Alkenes for Modular Pyrrolidine Synthesis via Electron Donor-Acceptor Complexes Generated from Alkenes and Amine-Tethered N-Hydroxyphthalimide Esters. 由烯和胺系n -羟基邻苯二胺酯生成的电子给体-受体配合物合成模块化吡咯烷的氨基烷基化反应。

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00408

Masanori Tayu, Kakeru Matsukuma, Takumi Ogino, Sayaka Ohrui, Nozomi Saito

引用次数: 0

Functional Characterization of Late-Stage Biosynthetic and Transporter Genes within the Biosynthetic Gene Cluster of the Organoarsenic Natural Product Bisenarsan. 有机砷天然产物双砷胂生物合成基因簇中后期生物合成和转运基因的功能表征

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00356

Shotaro Hoshino, Shinta Ijichi, Hiroyasu Onaka

{"title":"Functional Characterization of Late-Stage Biosynthetic and Transporter Genes within the Biosynthetic Gene Cluster of the Organoarsenic Natural Product Bisenarsan.","authors":"Shotaro Hoshino, Shinta Ijichi, Hiroyasu Onaka","doi":"10.1248/cpb.c25-00356","DOIUrl":"10.1248/cpb.c25-00356","url":null,"abstract":"Bisenarsan is an organoarsenic natural product identified from actinomycetes and a derivative of (2-hydroxyethyl)arsonic acid (2-HEA) esterified with 2,4,6-trimethyl-2-nonenoic acid (2,4,6-TMNA). Our previous study suggested that bisenarsan is biosynthesized from arsenate [As(V)] via arsonoacetaldehyde (AnAA). In contrast, the late-stage biosynthetic steps from AnAA to bisenarsan and the roles of transporter genes within the biosynthetic gene clusters (BGCs) of bisenarsan remain unclear. In this study, through in-frame deletions and heterologous expression targeting the bisenarsan BGC in Streptomyces lividans 1326 (bsn cluster), we identified bsnF (nicotinamide adenine dinucleotide phosphate-dependent oxidoreductase), bsnPKS (iterative type I polyketide synthase), and bsnFB (3-ketoacyl-acyl carrier protein synthase III family protein) as genes encoding enzymes likely responsible for the late-stage biosynthesis of bisenarsan. BsnF, BsnPKS, and BsnFB are presumed to catalyze the reduction of AnAA to 2-HEA, the formation of the 2,4,6-TMNA moiety, and the ester bond formation, respectively. Furthermore, based on the functional analysis of the transporter genes in the bsn cluster, BsnT2 (major facilitator superfamily transporter) appears to be involved in the efflux of bisenarsan. Although the roles of other transporters in bisenarsan biosynthesis remain unclear, they may contribute to the uptake and efflux of inorganic arsenic, presumably to ensure a consistent substrate supply and mitigate toxicity caused by its overaccumulation. Our study provides valuable insights into the biosynthesis of a rare class of organoarsenic natural products, with arsonopyruvate as an intermediate.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 8","pages":"698-706"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871690","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}

引用次数: 0

Concise Total Synthesis of (±)-Makaluvamine F and Its Derivatives. （±）-马芦胺F及其衍生物的简明全合成。

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00458

Masashi Shimomura, Yusuke Kanno, Shunta Kitao, Manaka Horie, Kohta Ide, Juri Sakata, Hidetoshi Tokuyama

引用次数: 0

e3MPH16: A D-Glutamic Acid-Substituted Peptide for Efficient and Low-Cytotoxicity Cytosolic Delivery of Macromolecules. e3MPH16：一种高效、低细胞毒性的大分子胞质递送的d-谷氨酸取代肽。

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00478

Yoshimasa Kawaguchi, Megumi Kiyokawa, Yusei Furuyama, Shiroh Futaki

{"title":"e3MPH16: A D-Glutamic Acid-Substituted Peptide for Efficient and Low-Cytotoxicity Cytosolic Delivery of Macromolecules.","authors":"Yoshimasa Kawaguchi, Megumi Kiyokawa, Yusei Furuyama, Shiroh Futaki","doi":"10.1248/cpb.c25-00478","DOIUrl":"https://doi.org/10.1248/cpb.c25-00478","url":null,"abstract":"Antibody-based therapeutics have shown remarkable success in targeting extracellular molecules, yet their application to intracellular targets remains largely unexplored due to the absence of efficient delivery systems. The large molecular weight and hydrophilicity of immunoglobulin G (IgG) make cytosolic delivery particularly challenging. Previously, we developed a cytosolic delivery peptide, E3MPH16, based on a modified Mastoparan X sequence, which enabled efficient delivery of macromolecules such as dextran with minimal cytotoxicity. However, effective intracellular delivery of antibodies required high concentrations, limiting its practical utility. In this study, we aimed to enhance delivery efficiency while preserving low toxicity by introducing d-amino acid substitutions into E3MPH16. The resulting peptide, e3MPH16, incorporates d-glutamic acid residues at the N-terminus to improve serum stability and protease resistance. Functional analyses demonstrated that e3MPH16 significantly improves cytosolic delivery of Cre recombinase and antibodies compared with the original E3MPH16, without increasing membrane-lytic activity or cytotoxicity. These results underscore the potential of d-amino acid-substituted peptides such as e3MPH16 as a promising platform for the intracellular delivery of unmodified functional antibodies.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 9","pages":"907-913"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136849","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}

引用次数: 0

Design, Synthesis, and Characterization of 1-(Anthracen-9-ylmethyl)-1,5,9-triazacyclododecane (Ant-[12]aneN3) and Its DNA Photocleavage Activity. 1-（蒽-9-甲基）-1,5,9-三氮杂环十二烷（Ant-[12]aneN3）的设计、合成、表征及其DNA光裂解活性

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00705

Yoshimi Ichimaru, Koichi Kato, Yoshihiro Yamaguchi, Takayuki Sakamoto, Wanchun Jin, Masaaki Kurihara, Mikako Fujita, Masami Otsuka, Hiromasa Kurosaki

{"title":"Design, Synthesis, and Characterization of 1-(Anthracen-9-ylmethyl)-1,5,9-triazacyclododecane (Ant-[12]aneN3) and Its DNA Photocleavage Activity.","authors":"Yoshimi Ichimaru, Koichi Kato, Yoshihiro Yamaguchi, Takayuki Sakamoto, Wanchun Jin, Masaaki Kurihara, Mikako Fujita, Masami Otsuka, Hiromasa Kurosaki","doi":"10.1248/cpb.c24-00705","DOIUrl":"10.1248/cpb.c24-00705","url":null,"abstract":"Here, a DNA cleavage reagent (1-(anthracen-9-ylmethyl)-1,5,9-triazacyclododecane = Ant-[12]aneN3) was designed and synthesized, and its DNA photocleavage activity under UV irradiation at λ = 365 nm was evaluated. Ant-[12]aneN3 is a molecule containing anthracene as the photosensitizer and [12]aneN3 ( = 1,5,9-triazacyclododecane) as the DNA-interacting component. The cyclic polyamine [12]aneN3 could coordinate with zinc ions (ZnII) and affect DNA cleavage activity. Therefore, when Ant-[12]aneN3 reacted with Zn(NO3)‧6H2O, the product was not a ZnII complex but an N-protonated form of Ant-[12]aneN3. In DNA cleavage experiments with the pUC19 plasmid, Ant-[12]aneN3 also showed DNA photocleavage activity in a ZnII-independent manner. That is, [12]aneN3 enhances the DNA photocleavage activity of anthracene in a ZnII-independent manner, unlike bpa (bis(2-picolyl)amine), which was previously reported to enhance DNA cleavage activity by chelating ZnII. Under physiological conditions, the nitrogen atoms of [12]aneN3 appear protonated without the addition of ZnII salts and showed an affinity for the negatively charged DNA. The results of this study may facilitate the design of effective DNA cleavage reagents.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 2","pages":"103-107"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432554","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}

引用次数: 0

Preparation of a Stable Indomethacin Supersaturated Solution Using Hydrophobically Modified Hydroxypropylmethylcellulose and α-Cyclodextrin. 疏水改性羟丙基甲基纤维素和α-环糊精制备稳定的吲哚美辛过饱和溶液。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00748

Hiroki Akahoshi, Fumitoshi Hirayama, Kenjirou Higashi, Daisuke Iohara

{"title":"Preparation of a Stable Indomethacin Supersaturated Solution Using Hydrophobically Modified Hydroxypropylmethylcellulose and α-Cyclodextrin.","authors":"Hiroki Akahoshi, Fumitoshi Hirayama, Kenjirou Higashi, Daisuke Iohara","doi":"10.1248/cpb.c24-00748","DOIUrl":"10.1248/cpb.c24-00748","url":null,"abstract":"In the present study, the stability of a supersaturated solution of indomethacin (IM) was evaluated in hydrophobically modified hydroxypropylmethylcellulose (HM-HPMC) solutions, with and without parent cyclodextrins (CDs). A highly supersaturated state of IM was maintained in the HM-HPMC solution and was further stabilized by the addition of α-CD and β-CD. Notably, the highest level of supersaturation was achieved in HM-HPMC/α-CD solution, which maintained a high concentration of IM for up to 120 h. IM concentrations in these solutions exceeded the amorphous solubility, indicating that phase separation had occurred. To explore this phase separation, Nile Red, a fluorescent probe sensitive to hydrophobic environments, was added to the supersaturated solutions. A higher fluorescence intensity was observed in the HM-HPMC/α-CD solution compared with the HM-HPMC solution, indicating a significant formation of colloidal amorphous aggregates in the supersaturated solution. Cryogenic transmission electron microscopy (Cryo TEM) analysis confirmed the presence of these aggregates, which appeared irregularly shaped. These findings suggest that the combination of HM-HPMC and α-CD effectively stabilized the colloidal amorphous aggregates in the IM supersaturated solution. The addition of α-CD facilitated the dissociation of HM-HPMC into smaller particles, increasing the number of hydrophobic stearyl moieties available for interactions with amorphous IM aggregates, thereby enhancing the stability of the supersaturated state. The combination of HM-HPMC and α-CD offers a promising approach to improving the oral bioavailability of drugs with poor water solubility.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 1","pages":"39-45"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022318","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}

引用次数: 0

Toward the Synthesis of Strychnos Alkaloids: Effective Construction of Fused Cyclohexane and Pyrrolidine Portion of the Strychnos Skeleton via Domino Intermolecular and Intramolecular S_N2 Cyclization. 马钱子生物碱的合成研究：用Domino分子间和分子内SN2环化有效构建马钱子骨架的环己烷和吡咯烷部分。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00783

Tadahiro Hosoda, Tomohiro Tsutsumi, Ichiro Hayakawa

引用次数: 0