Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Featured articles
Displaying 41-40 of 249 articles
  • Volume 69 (2021) Issue 9 Pages 877-885
    Monitoring of Cocrystal Dissociation during the Wet Granulation Process in the Presence of Disintegrants by Using Low-Frequency Raman Spectroscopy Read more
    Editor's pick

    Understanding the dissociation behavior of cocrystals is an essential task in particular during manufacturing process of the solid dosage forms containing cocrystals as active pharmaceutical ingredients (APIs). The authors have established the promising technique with low-frequency Raman spectroscopy as a monitoring tool for molecular state of APIs during wet granulation, which can detect the dissociation of cocrystals successively and the rate calculated from the spectra enabled to evaluate the stable cocrystal and the formulation with various disintegrants. These findings would help researchers to consider developable pharmaceuticals containing cocrystals.

  • Volume 69 (2021) Issue 9 Pages 926-930
    Construction of Acyclic All-Carbon Quaternary Stereocenter Based on Asymmetric Michael Addition of Chiral Amine Read more
    Editor's pick

    An all-carbon quaternary stereocenter is found in many biologically and pharmaceutically active compounds, in spite of being one of the most difficult structures to construct in the field of synthetic organic chemistry. In the present study, we were able to construct all-carbon quaternary stereocenters in an acyclic system by utilizing a face-selective alkylation of enolate intermediates derived from an asymmetric Michael addition reaction of a chiral lithium amide with trisubstituted α,β-unsaturated esters. Moreover, the obtained Michael adduct was able to be converted to the β-amino ester having the all-carbon quaternary stereocenter by an oxidative deprotection.

  • Volume 69 (2021) Issue 8 Pages 707-716
    Construction of N-Heterocycles Fused with a Highly Substituted Benzene Ring by a Benzyne-Mediated Cyclization/Functionalization Cascade Reaction and Its Application to the Total Synthesis of Marine Natural Products Read more
    Editor's pick

    The cover figure schematically illustrates the divergent synthesis of various nitrogen-containing heteroaromatic marine natural products by benzyne-mediated cyclization / functionalization cascade reactions. The figure in the center is a slot machine, which represents the flask used in the Cascade reaction, showing that several coins with the structure of nitrogen-containing heteroaromatic complex marine natural products are popping out when three numbers 7 hit at the same time.

  • Volume 69 (2021) Issue 8 Pages 721-726
    Application of Quantitative NMR Spectroscopy to the Quality Evaluation of Diclofenac Gargles as Hospital Preparations Read more
    Editor's pick

    Hospital preparations are frequently prepared in Japanese hospitals, but quality evaluation is not necessarily sufficient. In this article, quantitative 1H NMR spectroscopy (qNMR) was applied to the quality evaluation of diclofenac gargles as an example of a hospital preparation. Aliquots of the gargles were analyzed by qNMR using an internal standard method, where the medicinal ingredients in the preparations were accurately and precisely determined, with the water signal being effectively suppressed by water suppression enhanced through T1 effects (WET). The quality and stability of the gargles were elucidated based on the results. As such, qNMR with WET is potentially useful for the quality control of various aqueous preparations because of its simplicity and convenience.

  • Volume 69 (2021) Issue 8 Pages 747-759
    Preparation of Fine-Drugs Layered Spherical Particles with Good Micromeritic and Dissolution Properties through Ultra Cryo-Milling and Mechanical Powder Processing Read more
    Editor's pick

    The authors have developed the novel composite ordered-mixed (OM) particles containing fine drug-particles. The composite OM particles were found to be double-structured spherical particles consisting of finely-milled particles layered around the core particles. It was also found that they have excellent characteristics from both pharmaceutical and micromeritic perspectives and could overcome manufacturing problems of solid dosage forms. Such unique OM particles could be precisely designed by ultra cryo-milling in liquid nitrogen and subsequent mechanical powder processing which would be a potential platform approach to develop the oral dosages (tablet, capsule, granule) with improved dissolution property of poorly water-soluble drugs.

  • Volume 69 (2021) Issue 8 Pages 796-801
    Photoinduced Atom Transfer Radical Addition Reaction of Olefins with α-Bromo Carbonyls Read more
    Editor's pick

    The authors developed ATRA reactions of olefins with bromomalonate ester catalyzed by an in situ-formed halogen-bonding complex. The use of 4-phenylpyridine as the halogen-bonding acceptor, the desired reaction proceeded well under external irradiation of 380 nm LED light to furnish the corresponding ATRA reaction product. The substrate activation through the halogen bonding from the CT complex is a novel activation method that can be used for challenging synthetic routes since halogen bond acceptors such as pyridine are relatively inexpensive and readily available. This approach offers a new strategy for other classes of compounds for photocatalysis, including alkyl halides with amines or phosphine.

  • Volume 69 (2021) Issue 7 Pages 601-607
    Functional Peptides That Target Biomembranes: Design and Modes of Action Read more
    Editor's pick

    Biological membranes are an important target for molecular design. Properly designed membrane-interacting peptides can induce physicochemical and physiological responses in cell membrane and modulate cell structure and function.

  • Volume 69 (2021) Issue 7 Pages 608-611
    Construction of 7-Diethylaminocoumarins Promoted by an Electron-Withdrawing Group Read more
    Editor's pick

    Previously, the authors developed a cyclization reaction-based turn-on probe (TCC probe) for protein labeling. The TCC probe is characterized by its ability to construct coumarin structures easily by conjugate addition to the ynone moiety, but the reactivity of the probe becomes poor when attempting to improve the fluorescence properties. The authors improved the reactivity by increasing the electron-withdrawing property of the leaving ester group and succeeded in constructing the coumarin skeleton with good yields. These results suggest an easy method to introduce a coumarin skeleton with good fluorescence properties.

  • Volume 69 (2021) Issue 7 Pages 674-680
    Latent Structure Analysis of Wet-Granulation Tableting Process Based on Structural Equation Modeling Read more
    Editor's pick

    Quality by design (QbD) is an essential concept for modern manufacturing processes of pharmaceutical products. Understanding the science behind manufacturing processes is crucial; however, the complexity of the manufacturing processes makes implementing QbD challenging. In this study, structural equation modeling (SEM) was applied to understand the causal relationships between variables such as process parameters, material attributes, and quality attributes. Based on SEM analysis, a model composed of the above-mentioned variables and their latent factors without including observational data was identified. The results indicate that SEM analysis could be useful for implementing QbD for the manufacturing processes of pharmaceutical products.

  • Volume 69 (2021) Issue 7 Pages 681-692
    Elaboration of Non-naturally Occurring Helical Tripeptides as p53–MDM2/MDMX Interaction Inhibitors Read more
    Editor's pick

    Because of the wide range of protein-protein interaction surfaces, it is important to develop molecules that satisfy the intrinsic shape recognition of the partner protein. The authors have previously shown that a stable non-naturally occurring helix trimer of all trans-amide-bonded bicyclic β-amino acid inhibits the p53-MDM2/MDMX-helix-helix interaction that plays a role in regulating p53 function. The authors showed herein that modification of the C-terminal/N-terminal residues improved the inhibitory activity, and confirmed that these peptides are membrane-permeable p53-MDM2/MDMX interaction antagonists and can rescue p53 function in cells.

  • Volume 69 (2021) Issue 6 Pages 503-515
    Target Protein-Oriented Isolations for Bioactive Natural Products Read more
    Editor's pick

    Structure and bioactivities of natural products are often beyond human knowledge and imagination. In this article, the author developed original screening methods based on protein binding activity. Protein beads method and protein plate method were described. Protein beads method led to the discovery of neural stem cell differentiation activators which inhibited Hes1 dimer formation as a new mechanism. The author also developed protein plate method for protein-protein interaction inhibitors to find new cancer drug candidates. Because protein binding ability is tightly related to bioactivity, protein-based natural products isolation is a powerful means to find new candidate medicines.

  • Volume 69 (2021) Issue 6 Pages 516-525
    Development of Catalytic Reactions for Precise Control of Chemoselectivity Read more
    Editor's pick

    A cooperative catalyst comprising a soft Lewis acid/hard Brønsted base enabled chemoselective activation of a hydroxyl group over an amino group. The present chemoselective catalysis could be applicable for a variety of amino alcohols, including pharmaceuticals, without requiring a tedious protection-deprotection process. Chemoselective enolization and subsequent α-functionalization of carboxylic acid derivatives were also achieved by a redox active catalyst through the radical process, providing unnatural α-amino/hydroxy acid derivatives bearing a complex carbon framework and a diverse set of functionalities. The present chemoselective catalysis described herein offers new opportunities to expand the chemical space for innovative drug discovery research.

  • Volume 69 (2021) Issue 6 Pages 526-528
    Fluorescent-Oxaboroles: Synthesis and Optical Property by Sugar Recognition Read more
    Editor's pick

    The optical property of fluorescent unit-conjugated aliphatic oxaboroles has been investigated in this featured article. The authors described the synthesis of fluorescent-oxaboroles by originally developed methods and the optical behavior of the boroles with various sugars. The oxaboroles provide good fluorescence quantum yields and selective recognition toward D-ribose and D-ribose-containing molecules. The molecular recognition induced significant fluorescence quenching. The authors also revealed the positive correlation between the LUMO energy of the oxaborole and the relative fluorescence intensity. The property of the boroles showed the possibility of the boron-based NAD sensor probe.

  • Volume 69 (2021) Issue 6 Pages 537-547
    A New Bitterness Evaluation Index Obtained Using the Taste Sensor for 48 Active Pharmaceutical Ingredients of Pediatric Medicines Read more
    Editor's pick

    Quantitative evaluation for bitterness of pediatric medicine is essential for adherence.  The authors proposed criteria, change in concentration-dependent potential (CCDP), dose-response slope of the sensor outputs of active pharmaceutical ingredients measured by an artificial taste sensor, which is new and useful bitterness evaluation index for 48 pediatric medicines from the recent edition of the WHO model list of essential medicines for children (7th ed., 2019). CCDP by individual basic bitterness sensor well correlated to various physicochemical factors related hydrophilicity and hydrophobicity. Therefore, CCDP proved to be useful as a bitterness evaluation index of APIs in pediatric medicines.

  • Volume 69 (2021) Issue 6 Pages 564-572
    Discoveries and Syntheses of Highly Potent Antimalarial Troponoids Read more
    Editor's pick

    Novel 25 derivatives of puberulic acid were synthesized by utilizing the authors’ total synthetic route. According to previous structure-activity relationships information, they focused on the carboxylic acid moiety in puberulic acid and converted it into the corresponding esters, amides and ketones. Antimalarial evaluations in vitro and in vivo of these derivatives were carried out and revealed detailed SAR information. It was clarified that several ester and ketone derivatives conserve strong antimalarial activity similar to that of puberulic acid without any obvious toxicity in oral dose of 15 mg/kg.

  • Volume 69 (2021) Issue 5 Pages 421-431
    A Review on the Phytochemical and Pharmacological Properties of Rosa laevigata: A Medicinal and Edible Plant Read more
    Editor's pick

    This present review aims to achieve a comprehensive and up-to-date investigation in the phytochemistry and pharmacology of Rosa laevigata Michx.. To date, phytochemical investigation has exposed the presence of triterpenoids, flavonoids, tannins, ligands and polysaccharides in this plant. The crude extracts and the purified compounds have demonstrated various pharmacological effects in vitro and in vivo. In conclusion, the chemical profiles together with the modern pharmacological properties have been adequately summarized. These evidences have revealed this plant to be a valuable source for therapeutic foodstuff and more attention should be paid to a better utilization of this plant.

  • Volume 69 (2021) Issue 5 Pages 444-446
    Novel Cyclohexyl Meroterpenes Produced by Combinatorial Biosynthesis Read more
    Editor's pick

    Structurally diverse fungal meroterpenoids are promising drug seed compounds. To obtain unnatural, novel meroterpene scaffolds, the authors tested combinatorial biosynthesis by co-expressing functionally distinct terpene cyclase (TPC) genes, pyr4, ascF, andB, or cdmG, with the biosynthetic genes for the production of a TPC substrate, (10’R)-epoxyfarnesyl-dimethylorsellinic acid-3,5-methyl ester, in Aspergillus oryzae NSAR1 as a heterologous host. As a result, all of the tested TPCs afforded the same two novel mono-cyclization products. This study provides important information on the substrate scope of the TPCs, and will contribute to the production of unnatural, novel molecules for future drug discovery.

  • Volume 69 (2021) Issue 5 Pages 456-463
    Preparation of Solifenacin Succinate Functional Particles Embedded in a Gelling–Swelling Layer (PEGS) and Their Formulation in Orally Disintegrating Tablets Read more
    Editor's pick

    The authors developed solifenacin succinate functional drug particles embedded in a gelling–swelling layer (PEGS) made of a three-layer structure consisting of a core drug layer, a gelling–swelling layer, by which both adequate taste-masking of drug and rapid drug elution were successfully achieved. They also optimized incorporation of above PEGS into orally disintegrating tablets (ODTs), by usage of a fibre-shaped microcrystalline cellulose with poor fluidity, which improved the content uniformity of the ODTs, as the crystal fibres became entangled with the PEGS and other additives. Overall, this taste masking system is so unique and propose new platform for taste masking formulation.

  • Volume 69 (2021) Issue 5 Pages 464-471
    Indole Glycosides from Calanthe discolor with Proliferative Activity on Human Hair Follicle Dermal Papilla Cells Read more
    Editor's pick

    A methanol extract from the underground part of Calanthe discolor Lindl. (Orchidaceae) demonstrated significant proliferative activity against human hair follicle dermal papilla cells (HFDPC). Through bioassay-guided separation of the extract, a new indole glycoside named 6′-O-b-D-apiofuranosylindican was isolated along with six known compounds including three indole glycosides. Among the isolates, three indole glycoside such as 6′-O-b-D-apiofuranosylindican, glucoindican, and calanthoside showed significant proliferative activity. Furthermore, these active indole glycosides upregulated the expression of VEGF and FGF-7 mRNA and protein in HFDPC, which could be the mechanism of their proliferative activity.

  • Volume 69 (2021) Issue 5 Pages 488-497
    Expansion of Substrate Scope for Nitroxyl Radical/Copper-Catalyzed Aerobic Oxidation of Primary Alcohols: A Guideline for Catalyst Selection Read more
    Editor's pick

    This manuscript reports aerobic oxidation of primary alcohols into aldehydes with nitroxyl radical/copper catalysis. The reaction method reported herein features that the optimum nitroxyl radical/copper salt catalyst combinations differ depending on the substrate. To express this feature, the catalytic reaction field is represented as a circus tent with three shapes of windows, namely, circle, triangle, and square. Copper plates with different nitroxyl radicals are placed under each of the windows, which indicates different nitroxyl radical/copper salt catalyst combinations. Different alcohol substrates are represented in different forms, namely, sphere, tetrahedron, cube. The sphere, tetrahedral, and cubic alcohols pass through the circular, triangular, and square windows, respectively, to be oxidized into aldehydes.