Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Featured articles
Displaying 141-140 of 249 articles
  • Volume 67 (2019) Issue 10 Pages 1046-1049
    Lewis Base Assisted Lithium Brønsted Base Catalysis: A New Entry for Catalytic Asymmetric Synthesis of β2,2-Amino Acids Read more
    Editor's pick

    A new catalytic system comprising chiral Ag Lewis acid and lithium Brønsted base is developed for the synthesis of β2,2-amino acids by direct Mannich-type reaction of isoxazolidin-5-ones. Two nitrogen atoms in the product are chemically distinctive and can be easily differentiated. The cover art illuminates these features of this work by a projection onto a mysterious space.

  • Volume 67 (2019) Issue 10 Pages 1131-1138
    Development of a Membrane Curvature-Sensing Peptide Based on a Structure–Activity Correlation Study Read more
    Editor's pick

    Membrane curvature is involved in variety of cellular phenomena. Peptide-based sensors are useful that easily detect or visualize membrane curvatures in cell-related studies. These have advantages over protein-based sensors in terms of the compactness with smaller steric hindrance in their target recognition and the capabilities of chemical modification and easy handling. In this article, a structure–activity correlation study by the authors has led to an amphipathic peptide FAAV that recognizes high-curvature membranes. The FAAV may be a promising prototype of curvature sensors, which enable the capture of the dynamics and roles of membrane curvatures in our life.

  • Volume 67 (2019) Issue 10 Pages 1139-1143
    Non-naturally Occurring Helical Molecules Can Interfere with p53–MDM2 and p53–MDMX Protein–Protein Interactions Read more
    Editor's pick

    a-Helix-a-helix interactions are frequently observed at protein-protein interfaces, and the p53-MDM2/MDMX interaction is considered to involve interactions between a-helix structures of p53 and MDM2/MDMX. This work showed herein even non-naturally occurring artificial helix of bicyclic β-proline oligomer derivatives, bearing pitch and diameter per turn different from the typical a-helix structure of a-amino acid peptides can mimic α-helix structure sufficiently to interfere with the p53-MDM2/MDMX interaction.

  • Volume 67 (2019) Issue 10 Pages 1152-1159
    Controlled-Release Fine Particles Prepared by Melt Adsorption for Orally Disintegrating Tablets Read more
    Editor's pick

    The design of controlled-release particles is required for developing orally disintegrating tablets (ODT). The authors have focused on melt adsorption technique which affords precise control of the size distribution of controlled-release particles and requires neither solvents nor drying processes. In the present study, the authors demonstrated that melt adsorption is a superior manufacturing method for controlled-release particles. Specifically, ODT with adequate strength and disintegration could be prepared by using the particles which have been optimized by Design of Experiment (DoE) and Multiple regression analysis without losing sustained-release. This technique should contribute to the development of ODT to improve medication adherence.

  • Volume 67 (2019) Issue 9 Pages 897-903
    Development of Diagnostic and Therapeutic Probes with Controlled Pharmacokinetics for Use in Radiotheranostics Read more
    Editor's pick

    Radiotheranostics means the integration between diagnosis and therapy using radioisotopes. In the radiotheranostics, the diagnostic probe and corresponding therapeutic probe should show similar biodistribution. Thus, imaging using diagnostic probes before therapy can predict therapeutic and side effects of corresponding therapeutic probes. The author has developed radiolabeled probes with controlled pharmacokinetics for use in radiotheranostics. In this article, bone-seeking probes, sigma-1 targeted probes, and αVβ3 integrin targeted probes containing RGD peptide for cancer diagnosis and therapy are introduced as radiotheranostic probes.

  • Volume 67 (2019) Issue 9 Pages 953-958
    Asymmetric Total Syntheses and Structure Elucidations of (+)-Eurotiumide F and (+)-Eurotiumide G Read more
    Editor's pick

    Determining the stereochemistry of a cyclic acetal moiety is sometimes difficult because it is hard to observe NOESY correlations depending on the substitution pattern and the conformation. While the X-ray crystallographic analysis is a powerful method for structure determination, many natural products are often difficult to form single crystals because of their limited availability. The authors accomplished the first asymmetric total syntheses of (+)-eurotiumide F and (+)-eurotiumide G having such a cyclic acetal moiety, and through their total syntheses, they succeeded to measure the X-ray crystallographic analysis of eurotiumide G and revised the relative configuration between H1 and H4.

  • Volume 67 (2019) Issue 8 Pages 733-771
    Development of Metal Nanoparticle Catalysis toward Drug Discovery Read more
    Editor's pick

    A methodologically and conceptually novel immobilization method to prepare metal nano-particles (NPs) catalyst are currently required for the development of organic, inorganic, green, materials, and medicinal chemistry. Here the authors developed” “in situ metal NP and nanospace simultaneous organization (PSSO) method”, which is different from previously reported metal NPs-immobilizing methods. They also applied the in situ PSSO method to prepare various immobilized transition-metal NPs, including base metals. For example, the in situ PSSO method can be applicable to easily prepare Pd, Ru, Ni, and Fe NPs with good recyclability and low metal leaching for use in organic synthesis.

  • Volume 67 (2019) Issue 8 Pages 872-876
    Synthesis of Propargylic Ethers by Gold-Mediated Reaction of Terminal Alkynes with Acetals Read more
    Editor's pick

    Gold catalysts have attracted considerable attentions due to their low catalyst loading and the high functional group compatibility. The authors conducted an extensive research on the gold-catalyzed introduction of terminal alkynes to acetals to reveal that thermally stable cationic gold catalysts bearing bulky ligands were particularly suitable for the reaction. Because of its high utility to synthesize a broad range of propargylic ethers, this protocol should find a widespread use for synthesis of various propargylic ethers in the area of chemical biology and medicinal chemistry.

  • Volume 67 (2019) Issue 8 Pages 877-883
    Study of the Inducible Cross-Linking Reaction to mRNA and the Effect on the Translation Read more
    Editor's pick

    The covalent bond formation (crosslinking) of mRNA with the antisense oligonucleotide promotes the translational inhibition. In this study, several derivatives of T-vinyl (4-vinylpyrimidin-2-one) were investigated to obtain the stable derivative so that its reactivity is protected until it access to the target site. Thus, the 2-thiopyrimidinyl T-vinyl derivatives was determined to be a good cross-linking agent with a moderate stability. The investigation using the Luc mRNA, the synthetic mRNA and non-cellular translation system revealed that the translation is terminated at the end of the cross-linked duplex between the mRNA and the oligonucleotide.

  • Volume 67 (2019) Issue 7 Pages 693-698
    Transition in Longgu Surface Associated with Decoction Process of Keishikaryukotsuboreito Read more
    Editor's pick

    Longgu is a fossil crude drug used in Kampo prescriptions, but its role in the decoction is still unclear. The authors hypothesized that it adsorbs foreign organic compounds into its superficial pores, and aimed to reveal it indirectly by 1H magic angle spinning NMR spectroscopic analysis, thermogravimetric analysis and nitrogen adsorption isotherm. These analyses revealed that longgu was macroporous material, and it adsorbed organic compounds during the decoction process. Although further study is required, the authors suggest that the significance of longgu is in adjusting the component profiles in Kampo decoctions as an adsorbent.




  • Volume 67 (2019) Issue 7 Pages 620-631
    Chemical Studies on Bioactive Natural Products Directed toward Development of Novel Antiinfective and Anticancer Medicines Read more
    Editor's pick

    Natural products are potential sources of lead compounds, especially intractable chemotherapeutic targets that require molecules with three-dimensional diversity rather than flatter “drug-like” molecules. This review article highlights the author’s efforts toward establishing synthetic routes to natural anti-tuberculosis and anti-tumor products, including structure−activity relationship studies. The synthetic targets, caprazamycin C, intervenolin, and leucinostatin A, exhibit striking biologic properties, such as antibacterial activity toward highly resistant strains of tuberculosis and interference with growth signals from stromal cells to tumor cells.




  • Volume 67 (2019) Issue 7 Pages 609-619
    Discovery of Nuclear Receptor Ligands and Elucidation of Their Mechanisms of Action Read more
    Editor's pick

    The author developed a series of vitamin D analogues which act as agonist, partial agonist, or antagonist for vitamin D receptor (VDR). The author examined the structures of the ligand-binding domain (LBD) of VDR complexed with the analogues by the X-ray crystal structural analysis, and small-angle X-ray scattering analysis combined with molecular dynamics simulation. All states of the VDR-LBD, which include agonist-, partial agonist- and antagonist-binding structures and apo-state structure, were clarified. Thus the author elucidated the mechanisms of VDR agonism, partial agonism, and antagonism based on structural changes (differences) in VDR-LBD induced by ligand binding.




  • Volume 67 (2019) Issue 6 Pages 566-575
    Design, Synthesis and Biological Evaluation of Novel Nonsteroidal Progesterone Receptor Antagonists Based on Phenylamino-1,3,5-triazine Scaffold Read more
    Editor's pick

    The novel progesterone receptor antagonists based on the multi-template approach were developed. Multi-template strategy enables facile structure-activity relationship (SAR) investigation, and phenylamino-1,3,5-triazine scaffold is a useful core structure for development of transcription modulators targeting nuclear receptors.

  • Volume 67 (2019) Issue 6 Pages 576-579
    In Cellullo and ex Vivo Availability of a Yellowish-Green-Light-Controllable NO Releaser Read more
    Editor's pick

    Light controllable compounds are very useful tools to manipulate biological signaling. In this paper, authors showed the biological applicability of a yellowish-green light controllable NO releaser, NO-Rosa5, which is more readily synthesizable and efficient NO releaser than its prototype, NO-Rosa1. NO-Rosa5 showed less toxicity in MTT assay than a blue light controllable NO releaser, NOBL-1, and was applicable to photoinduced NO release control in cellular condition. Furthermore, NO-Rosa5 could control vasodilation of rat aortic strip by light stimulation in Magnus test condition. NO-Rosa5 is expected to be useful chemical tool for NO research and utilized for innovative therapeutic method.

  • Volume 67 (2019) Issue 6 Pages 580-586
    T2 Relaxation Study to Evaluate the Crystalline State of Indomethacin Containing Solid Dispersions Using Time-Domain NMR Read more
    Editor's pick

    The aim of this study was to demonstrate the usefulness of T2 measurements conducted with a time-domain NMR (TD-NMR) for the characterization of active pharmaceutical ingredients (APIs) containing solid dosage forms. In the course of the experiments, the authors found that T2 measurements could detect the difference between the amorphous and crystalline API; furthermore, it was effective in monitoring the transformation from amorphous to crystalline during a thermal stress test. From these findings, the authors concluded that T2 measurement by TD-NMR is a promising analysis for the characterization of APIs in solid dosage forms, including SD-based pharmaceuticals.

  • Volume 67 (2019) Issue 6 Pages 587-593
    Direct Formylation of Fluorine-Containing Aromatics with Dichloromethyl Alkyl Ethers Read more
    Editor's pick

    Although fluorine-containing aryl formates have currently flourished as pharmaceutical and agrochemical intermediates, there is limited number of bearable methods in a large scale synthesis. In this article, the authors developed new operationally secure preparation method for dichloromethyl alkyl ethers having long carbon chains, and direct formylation of fluorine-containing aromatics with those reagents, which are applicable in a large scale synthesis. The authors also showed a number of examples for O-formylation of fluorine-containing and non-fluorine-containing aromatics with those reagents and the mechanistic aspect was discussed. The present method is simple and straightforward for laboratory and industrial use.

  • Volume 67 (2019) Issue 6 Pages 594-598
    Total Synthesis of 3-epi-Juruenolide C Read more
    Editor's pick

    This paper describes that the first total synthesis of 3-epi-Juruenolide C. The γ-lactone natural product, which was isolated from roots of Virola surinamensis, exhibits moderate antifungal activity against Cladosporium cladosporioides. The synthesis features a highly selective cross metathesis and the subsequent one-pot regioselective bromination, an intramolecular carbonylation using bis(triphenylphosphine)dicarbonylnickel, and a face-selective hydrogenation using a homogeneous Wilkinson’s catalyst. The sequential synthetic procedures could be useful to complete the synthetic and biological studies of other related γ-lactone natural products.

  • Volume 67 (2019) Issue 5 Pages 397-403
    Nickel-Catalyzed Hydrocyanation of Allenes and Its Application Read more
    Editor's pick

    Regioselective cyanation of simple and non-activated carbon–carbon bonds catalyzed by nickel complexes is described. This protocol enables to use of the substituted allenes for regio- and stereocontrolled transformations and their applications for cyclization, 3-component coupling reaction, heterocycle formation as well as natural product synthesis are demonstrated. The author reveals the origin of the above selectivity by axial chirality transfer process using optically active allenes as substrates. Steric bulk of substituents is found to be a key factor for discrimination of allenyl carbon–carbon double bonds in hydrometallation step.

  • Volume 67 (2019) Issue 5 Pages 439-444
    Measurement of Linezolid and Its Metabolites PNU-142300 and PNU-142586 in Human Plasma Using Ultra-Performance Liquid Chromatography Method Read more
    Editor's pick

    This paper describes the development and validation of a method for measuring linezolid and its metabolites PNU-142300 and PNU-142586 in human plasma, using ultra-performance liquid chromatography (UPLC) method. This method enables the simultaneous measurement of these three components within 3 min. Further, plasma concentrations of linezolid, PNU-142300 and PNU-142586 in patients treated with linezolid could be measured. The developed method is a useful tool for therapeutic drug monitoring and clinical pharmacokinetic/pharmacodynamic (PK/PD) profiling of linezolid, as well as for dose optimization during treatment.

  • Volume 67 (2019) Issue 5 Pages 461-466
    Study on Control of pH-Modulation Crystallization Utilizing Concept of Dissociation Equilibrium Read more
    Editor's pick

    3-Alkenyl cephem compound is a pharmaceutical intermediate. It is typically crystalized by pH adjustment method. However, since the filtration time in the solid-liquid separator is a bottleneck in the production, there is a need to control crystal morphology while changing the pH. This study could be shorten filtration time by pH-modulation operation that repeating the crystallization operation in the vicinity of solubility. The obtained monodisperse particles were like a pseudo-growth body in which a large number of primary particles were aggregated and increased, rather than being a crystallite growth.

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