Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Featured articles
Showing 21-20 articles out of 199 articles
  • Volume 69 (2021) Issue 2 Pages 222-225
    Activity, Binding, and Modeling Studies of a Reprogrammed Aryl Acid Adenylation Domain with an Enlarged Substrate Binding Pocket Read more
    Editor’s picks

    Adenylation (A) domain functions as a gatekeeper, by selecting building blocks from a pool of 20 proteinogenic amino acids, non-proteinogenic amino acids, and aryl acids. Therefore, the A-domain is an attractive target for the reprogramming of non-ribosomal peptide synthetase machinery for the production of non-native peptides. Author determined the substrate profiles of a reprogrammed A-domain toward naturally occurring aminobenzoic acid substrates, synthesized sulfamoyloxy-linked acyl-AMP analogues, and conducted binding and modeling studies of them toward the reprogrammed A-domain. The study outcomes would help a better understanding of the unique substrate binding site of the reprogrammed A-domain, facilitating reprogramming of the A-domain.

  • Volume 69 (2021) Issue 2 Pages 226-231
    Tetracyclic Triterpenoids, Steroids and Lignanes from the Aerial Parts of Oxypetalum caeruleum Read more
    Editor’s picks

    The genus Oxypetalum was classified to the Asclepiadaceaus family, and this family was recently included in Apocynaceae. Oxypetalum caeruleum is a plant indigenous to South America and distributed as a garden plant in Japan. In the course of studying phytochemicals in Asclepiadaceaus plants, authors investigated the constituents in O. caeruleum. In this investigation, triterpenoids, pregnanes, one pregnane glycoside, lignanes and lignane glycosides were afforded. Many kinds of pregnanes and their glycosides are detected in the Apocynaceaus (including Asclepiadaceaus) plants. The fact that O. caeruleum only yielded pregnanes and their glycosides still indicates that these compounds are characteristic of this family.

  • Volume 69 (2021) Issue 2 Pages 232-235
    Concise Syntheses of Violaceoids A and C Read more
    Editor’s picks

    Boronic acids are well-known as coupling partners of Suzuki-Miyaura cross-coupling reaction, and also known as protecting reagents of diols. In this note, two alkylated hydroquinone natural products, violaceoids A and C, were synthesized by the protecting-group-free method employing commercially available 2,5-dihydroxybenzaldehyde as the starting material. The key step of the synthesis was the one-pot protection/Suzuki–Miyaura cross-coupling of hydroquinone utilizing alkenylboronic acid. This reaction enabled the protecting-group-free and concise synthesis of violaceoid A. Furthermore, the conversion of violaceoid A into violaceoid C was also described.

  • Volume 69 (2021) Issue 1 Pages 48-51
    Four New Pregnane-10,2-carbolactones from an Epipolasis sp. Marine Sponge Read more
    Editor’s picks

    The extract of an Epipolasis sp. marine sponge collected in the Republic of Palau provided four new pregnane 10,2 carbolactone derivatives. The structures of these rare pregnane analogues were fully elucidated through HRMS measurements and detailed analysis of their one- and two-dimensional NMR spectroscopic data. Pregnane steroids possessing a 10,2-carbolactone ring have only been reported previously from Hawaiian collections of Myrmekioderma and Petrosia (Stongylophora) sponges, so the current results suggest this class of steroid is more widely distributed in the marine environment than previously recognized.

  • Volume 69 (2021) Issue 1 Pages 72-80
    Phase Separation in Lipid Lamellae Result from Ceramide Conformations and Lateral Packing Structure Read more
    Editor’s picks

    The packing structure of intercellular lipids in the stratum corneum plays a critical role in the skin’s barrier function. The mechanism of packing structure disruption is not fully understood. The authors constructed models for collapsed skin intercellular lipids composed of short-chain free fatty acids and α-hydroxy ceramide. To investigate the packing structure’s characteristics, they changed the lipid composition and used temperature-scanning, simultaneous small-angle and wide-angle X-ray diffraction to determine resulting structural changes. The results suggest a change in ceramide conformation into a V-shape structure. The authors discussed the relationship between the V-shape structure formation and a reduction in the skin’s barrier function.

  • Volume 69 (2021) Issue 1 Pages 92-98
    Characteristics of Raw and Acid-Activated Bentonite and Its Application for Improving Electrical Conductivity of Tap Water Read more
    Editor’s picks

    Authors evaluate the characteristics of acid-activated bentonite by focusing on its capability of improving the quality of tap water used during wire electrical discharge machining. This study shows that the acid activation of bentonite using sulfuric acid, nitric acid, and phosphoric acid solutions increases the specific surface area and pore volume. Additionally, authors revealed that the relationship between the concentrations of the removed ions and electrical conductivity were negatively correlated (correlation coefficient: -0.950). Thus, the acid-activated bentonite is useful in controlling the reduction in the electrical conductivity of tap water.

  • Volume 69 (2021) Issue 1 Pages 118-123
    Absolute Purity Determination of a Hygroscopic Substance, Indocyanine Green, Using Quantitative NMR (qNMR) Read more
    Editor’s picks

    Quantitative NMR (qNMR) has emerged as a new absolute quantitation method for small molecules. Authors examined the absolute purity determination of a hygroscopic substance indocyanine green (ICG) using qNMR. The three different humidity conditions yielded comparable purity means of 86.12 ± 2.70%, 84.19 ± 0.47%, and 82.26 ± 0.19% under non-controlled humidity, controlled humidity using a saturated NaBr solution, and using a constant temperature and humidity box, respectively. As the results using the constant temperature and humidity box showed the lowest variability, it is recommended to use it if the reference standard of ICG with its purity value is needed for Japanese Pharmacopoeia assays.

  • Volume 69 (2021) Issue 1 Pages 124-140
    β-Selective Glycosylation Using Axial-Rich and 2-O-Rhamnosylated Glucosyl Donors Controlled by the Protecting Pattern of the Second Sugar Read more
    Editor’s picks

    Stereoselectivity in chemical glycosylation frequently varies in reaction substrates. This paper describes the influence of the protecting groups on rhamnose connected to the 2-O position of a glucosyl donor with axial-rich conformation on stereoselectivity in its glycosylation with cholestanol. The authors revealed that two bulky silyl groups existing at the 3-O and 4-O positions of rhamnose synergistically enhanced β-selectivity. In contrast, the silyl group introduced to the 2-O position decreased the selectivity. These results suggest that appropriately designing a protecting-group pattern for another sugar far from the reaction center of a glycosyl donor can control the stereoselectivity of glycosylation.

  • Volume 68 (2020) Issue 12 Pages 1184-1192
    Design, Synthesis and Biological Evaluation of Novel 4-(4-Methoxynaphthalen-1-yl)-5-arylpyrimidin-2-amines as Tubulin Polymerization Inhibitors Read more
    Editor’s picks

    Tubulin is an important target for developing anticancer drugs. To discover novel tubulin polymerization inhibitors, the authors designed and synthesized a new series of pyrimidine-based compounds based on the principle of molecular hybrid-based approach. Several compounds exhibited potent anti-tubulin activity and showed antiproliferative activities against MCF-7 and HepG2 cancer cell lines. The results indicated that these compounds may have the potential for further development as anticancer agents.

  • Volume 68 (2020) Issue 12 Pages 1201-1209
    Bridged-Selective Intramolecular Diels–Alder Reactions in the Synthesis of Bicyclo[2.2.2]octanes Read more
    Editor’s picks

    Intramolecular Diels-Alder (IMDA) reactions are powerful synthetic methods for construction of complex carbon skeletons from relatively simple starting materials.  Regioselectivity for producing fused or bridged products by the IMDA reactions is very important for planning a rational synthetic route for target molecules.  It has been well known that the IMDA reactions usually provide fused products, while factors for selective formation of bridged products has not been understood well.  The authors experimentally found some factors for giving bridged products selectively in IMAD reactions, and they explained the reasons for the observed bridged selectivity by DFT calculations.

  • Volume 68 (2020) Issue 12 Pages 1210-1219
    Synthesis of Nucleoside Derivatives of N-Acetyl-7-nitroindoline, Their Incorporation into the DNA Oligomer, and Evaluation of Their Photoreactivity in the DNA/RNA Duplex Read more
    Editor’s picks

    Stimulus-responsive molecules that modify nucleic acids in a site- and base-selective manner play an important role for genomic research. N-Acetyl-7-nitroindoline is a characteristic in that its acetyl group is photo-activated to acetylate amines to form amides. In this study, the N-acetyl-7-nitroindoline part was connected to the 2´-deoxyribose part, which was incorporated into the oligodeoxynucleotide probes, and their photo-reactivities toward the complementary RNA were investigated. One probe was photo-activated to deacetylate to the nitroso derivative. Photo-activation of another probe induced acetylation of the RNA. An interesting finding was the cross-link formation of another probe with the RNA strand.

  • Volume 68 (2020) Issue 12 Pages 1220-1225
    Development of Nitrolactonization Mediated by Iron(III) Nitrate Nonahydrate Read more
    Editor’s picks

    Nitrogen dioxide has been used as an oxidant and nitrating reagent in organic synthesis. However, its use is limited because it is harmful and hard to handle. Iron(III) nitrate nonahydrate has attracted attention as a source of nitrogen dioxide because it is a readily available reagent of low toxicity and cost. This paper describes development of nitrolactonization mediated by iron nitrate as a source of nitrogen dioxide. Nitrolactones obtained by this reaction could lead to useful compounds, such as 1,2-aminoalcohol and amino acid derivatives bearing a tetrasubstituted carbon center.

  • Volume 68 (2020) Issue 12 Pages 1226-1232
    Sequence-Independent Traceless Method for Preparation of Peptide/Protein Thioesters Using CPaseY-Mediated Hydrazinolysis Read more
    Editor’s picks

    Peptide/protein thioesters function as an indispensable synthetic intermediate in Native Chemical Ligation (NCL) that has enjoyed great success in the chemical synthesis of proteins. Facile conversion of recombinant proteins to thioesters allows for the straightforward access to semi-synthetic proteins with chemically synthesized peptides used as an NCL partner. In this paper, the authors developed an efficient thioester-producing protocol. The protocol features the traceless conversion of the CysPro triple repeat–Leu-OH-tagged sequence to the corresponding thioesters by treatment with carboxypeptidase Y in the presence of hydrazine followed by an auto-processing of the CysPro units.

  • Volume 68 (2020) Issue 11 Pages 1013-1024
    Effect of the Molecularly Imprinted Polymer Component Ratio on Analytical Performance Read more
    Editor’s picks

    Molecular imprinting has been broadly perceived as the most advanced technology for preparing various materials that have a specific recognition site with selective adsorption. MIPs (Molecular Imprinted Polymer) are three-dimensional polymers with specific recognition sites for a certain molecule. A MIP is formed by crosslinking template with monomers to create copolymers. For every MIP, each template:monomer:crosslinker ratio shows a distinct performance for a specific analyte. Ratio effect on analytical performances are briefly outlined in this review. From all reports in this review, the synthesis of MIP using a template:monomer:crosslinker ratio of 1:4:20 is more likely to provide optimal imprinting efficiency.

  • Volume 68 (2020) Issue 11 Pages 1034-1048
    Development of a Logic Model for Promoting Incorporation of the Concepts of Impurity-Related ICH Guidelines into Pharmacopoeias Based on Cause and Effect Analysis Read more
    Editor’s picks

    With the globalization of the drug supply chain, the quality assurance of drugs is required worldwide. Pharmacopoeias provide public standards for the drug quality assurance, and smooth incorporation of the concepts of the international guidelines into pharmacopoeias is desired. In particular, impurities in drugs are to be controlled to ensure patient safety. The authors focused on the harmonized guidelines for residual solvents, elemental impurities, and mutagenic impurities, and proposed an approach for promoting incorporation of the concepts of the guidelines into pharmacopoeias by combining the cause and effect analysis and the logic model.

  • Volume 68 (2020) Issue 11 Pages 1055-1060
    Effect of Disintegrants on Prolongation of Tablet Disintegration Induced by Immersion in Xanthan Gum-Containing Thickening Solution: Contribution of Disintegrant Interactions with Disintegration Fluids Read more
    Editor’s picks

    In clinical practice, a thickening solution is frequently used to allow easy swallowing of tablets as well as foods by patients suffering from dysphagia. This study investigated the effect of thickening solution on tablet disintegration. Model tablets containing different disintegrants were prepared and their disintegration times were measured. The tablet disintegration times were significantly prolonged by immersion in thickening solution containing xanthan gum and the degree of prolongation differed depending on the type of disintegrant contained in the tablets. These findings provide valuable information for design of tablet formulation and clinical medication management for older patients with dysphagia.

  • Volume 68 (2020) Issue 11 Pages 1074-1081
    Fragment-Based Discovery of Irreversible Covalent Inhibitors of Cysteine Proteases Using Chlorofluoroacetamide Library Read more
    Editor’s picks

    Chlorofluoroacetamide (CFA) shows chemically tuned mild reactivity that is suitable as an electrophilic warhead for highly target selective covalent inhibitors. Assembly of a small set of CFA-appended fragment library and its screening against cysteine protease papain demonstrated the potential utility of CFA in novel covalent drug discovery using a fragment-based approach.

  • Volume 68 (2020) Issue 10 Pages 907-945
    Development of New Innovative Synthetic Organic Chemistry Using Lone Pairs of Oxygen Atoms Read more
    Editor’s picks

    This review describes development of innovative reactions utilizing the characteristic reactivity of oxygen atoms, 1) asymmetric synthesis of chiral quaternary carbon centers, 2) asymmetric synthesis using acetal functions, and 3) organic chemistry using acetal-type reactive salt chemical species, and their application to the asymmetric synthesis of natural products such as Fredericamycin A, anthracycline antibiotics, scyphostatin, Sch 642305, stenin, claboronin, rubrenolide, rubrynolide, centrolobine, and decytospolides A and B, etc. In particular, reactions using acetal-type reactive salt chemical species can alter the retrosynthesis planned based on conventional reactions because they allow the coexistence of functional groups that normally cannot coexist.

  • Volume 68 (2020) Issue 10 Pages 954-961
    Binding Assays Using a Benzofurazan-Labeled Fluorescent Probe for Estrogen Receptor–Ligand Interactions Read more
    Editor’s picks

    Binding assays are widely used to study the estrogenic activity of endocrine-disrupting chemicals targeting the estrogen receptor (ER). In this study, the authors synthesized benzofurazan-labeled estradiol (BD-E2) derivatives as a fluorescent ligand for ER binding assays. BD-E2 compounds exhibit spectroscopic properties with high fluorescence intensities and large Stokes shifts in a hydrophobic environment. Analysis of the fluorescent ligands and human recombinant ER interactions revealed that the fluorescence intensity increased in hydrophobic environments, such as the receptor-binding site. By evaluation of the bound ligands based on changes in the fluorescence intensity, the authors established a simple, rapid, reliable ER binding assay.

  • Volume 68 (2020) Issue 10 Pages 989-995
    Evaluation of Dantrolene Granules Extemporaneously Reformulated from Capsules in a Pharmacy Read more
    Editor’s picks

    An extemporaneous preparation, sodium dantrolene granules, has been manufactured using planetary centrifugal granulation method in the pharmacy. The amount of water was determined based on plastic limit value of the formulation, which is a critical parameter of the granulation method. The granulation process completes within 45 s, followed by coating process (20 s). The resultant granules show sharp particle size distribution and excellent flowability. The bulky powder was reformulated to the granules with non-adhesive and free-flowing properties. Thus, the granulation improves the usability of the medicine in the dispensing and dosing processes.