Oxford University Press (OUP)Acta Medica Okayama0009-26739962026Synthesis of boranils by iodide-mediated demethylative borylation and their propertiesuoag070ENKoichiMitsudoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityRyoMagataGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityEisukeSatoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTomoyaNakamuraInstitute for Chemical Research, Kyoto UniversityAtsushiWakamiyaInstitute for Chemical Research, Kyoto UniversitySeijiSugaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityBoranils, difluoroboron complexes with imine and phenoxy moieties, were synthesized by iodide-promoted demethylative borylation. The use of appropriate amounts of BF3•OEt2, Bu4NI, and Et3N enabled the highly efficient synthesis of boranils. Boranils containing heteroaromatics and highly -extended boranils were also readily obtained by this method. Their physical properties were studied, and the properties were consistent with those calculated by DFT calculations.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2196-02161382026Electrochemical Synthesis of Benzo[b]Phosphole Oxides via Dehydrogenative Annulation Using 1,4-Diazabicyclo [2.2.2]Octane as a Mediatore70175ENKoichiMitsudoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversitySakuraKinjoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYasuyukiOkumuraGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityEisukeSatoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityRikiKatoResearch Institute for Interdisciplinary Science, Okayama UniversityYutaNishinaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversitySeijiSugaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityThe electrochemical intermolecular annulation of diarylphosphine oxides with alkynes for the synthesis of benzo[b]phosphole oxides has been reported. The reaction proceeded under transition-metal- and oxidant-free conditions via indirect electrolysis, using 1,4-diazabicyclo[2.2.2]octane as a mediator. High-surface-area carbon electrodes, such as carbon felt and reticulated vitreous carbon, are essential for this reaction. Several diarylphosphine oxides and alkynes were applied to electrochemical annulation, and the corresponding benzo[b]phosphole oxides were obtained. Mechanistic studies suggested that the reaction proceeds via radical intermediates generated through multiple pathways.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1434-193X2026Informatics]Driven and Automated Optimization in Flow Electrochemical Synthesise202501237ENEisukeSatoDepartment of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityAkineTaniDepartment of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTomohiroNakahamaDepartment of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKoichiMitsudoDepartment of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversitySeijiSugaDepartment of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityElectrochemical synthesis has emerged as a powerful platform for environmentally sustainable chemical transformations. When integrated with flow chemistry, electrosynthetic processes exhibit enhanced scalability, making them suitable for industrial applications. Recently, the integration of electrochemical flow systems with informatics techniques has accelerated the optimization of reaction conditions. Data-driven strategies facilitate rapid exploration of multidimensional parameter spaces, enabling identification of optimal reaction conditions with high efficiency. These advances have enabled the development of automated optimization systems. This review highlights recent progress in combining electrosynthesis, flow chemistry, and computational tools, focusing on representative examples that illustrate efficient optimization protocols and autonomous reaction development. By showcasing these developments, we discuss how the integration of these technologies is driving innovation in electrochemical synthesis.No potential conflict of interest relevant to this article was reported.American Chemical Society (ACS)Acta Medica Okayama2691-37042025Electrochemical Generation of Sulfonamidyl Radicals via Anodic Oxidation of Hydrogen Bonding Complexes: Applications to Electrosynthesis of BenzosultamsENYasuyukiOkumuraDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityEisukeSatoDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKoichiMitsudoDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversitySeijiSugaDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityAmidyl radicals and sulfonamidyl radicals are widely used in the field of organic synthesis. In particular, the electrochemical oxidation of amides in the presence of bases is one of the most practical methods for generating amidyl radicals. However, it is often difficult to observe the gtrueh radical precursor, such as an amide anion and/or a hydrogen bonding complex with an amide and a base. We found that a sulfonamide and Bu4NOAc form a 1:1 hydrogen bonding complex by spectroscopic experiments. Cyclic voltammetry suggested that 1:1 hydrogen bonding complexes should be oxidized predominantly under the optimized conditions to afford a sulfonamidyl radical via the proton-coupled electron transfer (PCET) process by the oxidation of the complex. Thus-generated sulfonamidyl radicals could be used in the electrochemical synthesis of a variety of benzosultams.No potential conflict of interest relevant to this article was reported.American Chemical Society (ACS)Acta Medica Okayama1523-706027262025Transformation of ,-Unsaturated Aldehydes with a Small Amount of Electricity: Cyanosilylation, Isomerization, and Nucleophilic Addition69536958ENMayuFujiiDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNanahoUenoDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKoichiMitsudoDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityEisukeSatoDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversitySeijiSugaDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityAn electrochemical method was developed to convert ,-unsaturated aldehydes into carboxylic acid derivatives via cyanosilylation, isomerization, and nucleophilic addition. This reaction is more sustainable than the usual electrochemical organic reaction because this reaction proceeds catalytically with active species generated by a very small amount of electricity. Furthermore, scale-up synthesis with a flow reactor has been achieved.No potential conflict of interest relevant to this article was reported.American Chemical Society (ACS)Acta Medica Okayama1523-706027182025Electrochemical Oxidation of Benzyl Alcohols via Hydrogen Atom Transfer Mediated by 2,2,2-Trifluoroethanol47374741ENTakahiroKawajiriAPI R&D Laboratory, Research Division, Shionogi & Co., Ltd.MasahiroHosoyaAPI R&D Laboratory, Research Division, Shionogi & Co., Ltd.SatoshiGodaAPI R&D Laboratory, Research Division, Shionogi & Co., Ltd.EisukeSatoDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversitySeijiSugaDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityWe report a novel electrochemical oxidation of benzyl alcohols. We found that trifluoroethanol plays a role as a hydrogen atom transfer (HAT) mediator, enabling the oxidation of electron-deficient substrates that are difficult to directly oxidize on electrode surfaces. Density functional theory calculations, cyclic voltammetry measurements, and constant potential electrolysis studies supported the proposed HAT mechanism. Moreover, the obtained carbonyl compounds could be functionalized in an electrochemical one-pot manner, further highlighting their synthetic utility.No potential conflict of interest relevant to this article was reported.American Chemical Society (ACS)Acta Medica Okayama1523-706026512024Electrogenerated Lewis Acid-Catalyzed Claisen Rearrangement of Allyl Aryl Ethers1111111116ENYutaNikiDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKoichiMitsudoDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityEisukeSatoDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversitySeijiSugaDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityCatalysts for Claisen rearrangement have been intensively studied to overcome the need for high temperature. However, previous studies have encountered challenges, such as the need for heating, a long reaction time, and/or the need for equivalent amounts of catalyst. In this study, we introduce an effective electrogenerated boron-based Lewis acid catalyst for the aromatic Claisen rearrangement, which proceeds in a few minutes at ambient temperature. Generation of the electrogenerated Lewis acid catalyst is discussed based on NMR analysis and DFT calculations.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama0366-702253112024SNAr hexafluoroisopropoxylation of electron-rich aryl fluoride with a catalytic electrical inputupae196ENEisukeSatoDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTomohiroNakahamaDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKoichiMitsudoDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversitySeijiSugaDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityAnodic oxidation–promoted SNAr reactions of electron-rich aryl fluoride were developed. The anodic oxidation of 4-fluoroanisole in hexafluoroisopropyl alcohol (HFIP) with K2CO3 led to SNAr-type hexafluoroisopropoxylation, and the reaction was completed with a catalytic electrical input. The results of cyclic voltammetry suggest that the radical cation of 4-fluoroanisole, which would react with the alkoxide of HFIP, is generated. Electron transfer between the intermediate and the starting material constructs the catalytic cycle, and the elimination of fluoride from the Meisenheimer complex produces the desired compound.No potential conflict of interest relevant to this article was reported.Anticancer Research USA Inc.Acta Medica Okayama1109-65352152024Terrein Exhibits Anti-tumor Activity by Suppressing Angiogenin Expression in Malignant Melanoma Cells464473ENTAIRAHIROSEDepartment of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYUKIKUNISADADepartment of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKOICHIKADOYADepartment of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHIROKIMANDAIDepartment of Pharmacy, Faculty of Pharmacy, Gifu University of Medical ScienceYUMISAKAMOTODepartment of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKYOICHIOBATADepartment of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKISHOONODepartment of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHIROAKITAKAKURADepartment of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKAZUHIROOMORIDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySHOGOTAKASHIBADepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySEIJISUGADivision of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama UniversitySOICHIROIBARAGIDepartment of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground/Aim: Malignant melanoma is a tumor with a poor prognosis that can metastasize distally at an early stage. Terrein, a metabolite produced by Aspergillus terreus, suppresses the expression of angiogenin, an angiogenic factor. However, the pharmacological effects of natural terrein have not been elucidated, because only a small amount of terrein can be extracted from large fungal cultures. In this study, we investigated the antineoplastic effects of terrein on human malignant melanoma cells and its underlying mechanisms. Materials and methods: Human malignant melanoma cell lines were cultured in the presence of terrein and analyzed. Angiogenin production was evaluated using ELISA. Ribosome biosynthesis was evaluated using silver staining of the nucleolar organizer region. Intracellular signaling pathways were analyzed using western blotting. Malignant melanoma cells were transplanted subcutaneously into the backs of nude mice. The tumors were removed at 5 weeks and analyzed histopathologically. Results: Terrein inhibited angiogenin expression, proliferation, migration, invasion, and ribosome biosynthesis in malignant melanoma cells. Terrein was shown to inhibit tumor growth and angiogenesis in animal models. Conclusion: This study demonstrated that terrein has anti-tumor effects against malignant melanoma. Furthermore, chemically synthesized non-natural terrein can be mass-produced and serve as a novel potential anti-tumor drug candidate.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama0366-70225382024Electrochemical synthesis of heterocyclic compounds via carbon–heteroatom bond formation: direct and indirect electrolysisupae146ENYasuyukiOkumuraDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityEisukeSatoDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKoichiMitsudoDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversitySeijiSugaDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityElectrochemical organic synthesis has attracted attention as an environmentally friendly method for constructing heterocyclic compounds via carbon–heteroatom bond formation. Herein, we describe the representative examples of electrochemical reactions to produce heterocycles and discuss them according to whether they involve direct or indirect electrolysis.No potential conflict of interest relevant to this article was reported.Georg Thieme Verlag KGActa Medica Okayama0039-788156162024Sequential Paired Electrochemical Transformation of Styrene Oxide via Anodic Meinwald Rearrangement and Cathodic Nitromethylation in an Electrochemical Flow Reactor with Catalytic Electrical Input25072512ENEisukeSatoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversitySeijiSugaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKanonNagamineGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityChikaSasakiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityShumpeiKunimotoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKoichiMitsudoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityPaired electrosynthesis, which utilize both anodic and cathodic events in electrolysis, enables attractive transformations with higher current efficiency than conventional electrosynthesis. The electrochemical flow technique has been widely employed to ensure stable reaction conditions and mitigate issues stemming from mass transfer. In this study, the electrochemical Meinwald rearrangement of styrene oxides was investigated, yielding aldehydes as intermediates, followed by the nitromethylation of aldehydes to produce -nitro alcohols. These reactions were achieved with catalytic electrical input, enabling the conversion of various styrene oxides into the corresponding -nitro alcohols.No potential conflict of interest relevant to this article was reported.Electrochemical Society of JapanActa Medica Okayama1344-354291112023Cathodic N-O Bond Cleavage of N-Alkoxy Amide112005ENEisukeSatoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversitySayakaOgitaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKoichiMitsudoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversitySeijiSugaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityCathodic reduction efficiently cleaved N-O bonds. The simple cathodic reduction of Weinreb amides in a divided cell afforded the corresponding amide in good yields. Cyclic voltammetry experiments and density functional theory calculations suggested that the direct reduction of the N-methoxy amide generates the methoxy radical and amide anion. The release of methanol derived from methoxy radical would be the driving force of the N-O bond cleavage.No potential conflict of interest relevant to this article was reported.Electrochemical Society of JapanActa Medica Okayama1344-354291112023Electrochemical Synthesis of Dibenzothiophene S,S-Dioxides from Biaryl Sulfonyl Hydrazides112007ENYasuyukiOkumuraDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityEisukeSatoDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKoichiMitsudoDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversitySeijiSugaDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityThe electrochemical synthesis of dibenzothiophene S,S-dioxides was achieved by the anodic oxidation of biaryl sulfonyl hydrazides. The use of Bu4NOTf as the electrolyte in HFIP/CH3NO2 (15 : 1) is essential. Several biaryl sulfonyl hydrazides followed by dibenzothiophene S,S-dioxides under mild electrochemical conditions. Control experiments and density functional theory calculations suggested that the electrooxidation of biaryl sulfonyl hydrazides would generate sulfonyl radicals or sulfonyl cations which were converted to dibenzothiophene S,S-dioxides.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1434-193X26472023Electrochemical Coupling Reactions Using Non]Transition Metal Mediators: Recent Advancese202300835ENKoichiMitsudoDivision of Applied Chemistry Graduate School of Environmental Life, Natural Science and Technology, Okayama UniversityYasuyukiOkumuraDivision of Applied Chemistry Graduate School of Environmental Life, Natural Science and Technology, Okayama UniversityEisukeSatoDivision of Applied Chemistry Graduate School of Environmental Life, Natural Science and Technology, Okayama UniversitySeijiSugaDivision of Applied Chemistry Graduate School of Environmental Life, Natural Science and Technology, Okayama UniversityIndirect electrolysis method using appropriate mediators enables numerous chemical reactions. The general principles of mediators were described herein with a particular focus on non-transition metal mediators. Recent representative examples of bond formation reactions by indirect electrolysis are summarized and discussed here.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2309-608X932023The Fungal Metabolite (+)-Terrein Abrogates Inflammatory Bone Resorption via the Suppression of TNF- Production in a Ligature-Induced Periodontitis Mouse Model314ENHidefumiSakoDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalKazuhiroOmoriDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasaakiNakayamaDepartment of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirokiMandaiDepartment of Pharmacy, Faculty of Pharmacy, Gifu University of Medical ScienceHidetakaIdeguchiDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySakiYoshimura-NakagawaDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalKyosukeSakaidaDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalChiakiNagata-KameiDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroyaKobayashiDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySatokiIshiiDivision of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama UniversityMitsuakiOnoDepartment of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySoichiroIbaragiDepartment of Oral and Maxillofacial Surgery and Biopathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTadashiYamamotoDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySeijiSugaDivision of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama UniversityShogoTakashibaDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityCurrent periodontal treatment focuses on the mechanical removal of the source of infection, such as bacteria and their products, and there is no approach to control the host inflammatory response that leads to tissue destruction. In order to control periodontal inflammation, we have previously reported the optimization of (+)-terrein synthesis methods and the inhibitory effect of (+)-terrein on osteoclast differentiation in vitro. However, the pharmacological effect of (+)-terrein in vivo in the periodontitis model is still unknown. In this study, we investigated the effect of synthetic (+)-terrein on inflammatory bone resorption using a ligature-induced periodontitis mouse model. Synthetic (+)-terrein (30 mg/kg) was administered intraperitoneally twice a week to the mouse periodontitis model. The control group was treated with phosphate buffer. One to two weeks after the induction of periodontitis, the periodontal tissues were harvested for radiological evaluation (micro-CT), histological evaluation (HE staining and TRAP staining), and the evaluation of inflammatory cytokine production in the periodontal tissues and serum (quantitative reverse-transcription PCR, ELISA). The synthetic (+)-terrein-treated group suppressed alveolar bone resorption and the number of osteoclasts in the periodontal tissues compared to the control group (p < 0.05). In addition, synthetic (+)-terrein significantly suppressed both mRNA expression of TNF- in the periodontal tissues and the serum concentration of TNF- (both p < 0.05). In conclusion, we have demonstrated that synthetic (+)-terrein abrogates alveolar bone resorption via the suppression of TNF- production and osteoclast differentiation in vivo. Therefore, we could expect potential clinical effects when using (+)-terrein on inflammatory bone resorption, including periodontitis.No potential conflict of interest relevant to this article was reported.Beilstein-InstitutActa Medica Okayama1860-5397182022Electrochemical hydrogenation of enones using a proton- exchange membrane reactor: selectivity and utility10551061ENKoichiMitsudoDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityHarukaInoueDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityYutaNikiDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityEisukeSatoDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversitySeijiSugaDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityElectrochemical hydrogenation of enones using a proton-exchange membrane reactor is described. The reduction of enones proceeded smoothly under mild conditions to afford ketones or alcohols. The reaction occurred chemoselectively with the use of different cathode catalysts (Pd/C or Ir/C).No potential conflict of interest relevant to this article was reported.Frontiers Media SAActa Medica Okayama1663-9812122021The Fungal Metabolite (+)-Terrein Abrogates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor-kappa B Ligand-Induced Osteoclastogenesis by Suppressing Protein Kinase-C alpha/beta II Phosphorylation674366ENKyosukeSakaidaDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhiroOmoriDepartment of Periodontics and Endodontics, Okayama University HospitalMasaakiNakayamaDepartment of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirokiMandaiDepartment of Pharmacy, Faculty of Pharmacy, Gifu University of Medical ScienceSakiNakagawaDepartment of Periodontics and Endodontics, Okayama University HospitalHidefumiSakoDepartment of Periodontics and Endodontics, Okayama University HospitalChiakiKameiDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySatoshiYamamotoDepartment of Periodontics and Endodontics, Okayama University HospitalHiroyaKobayashiDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySatokiIshiiDivision of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama UniversityMitsuakiOnoDepartment of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySoichiroIbaragiDepartment of Oral Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeisukeYamashiroDepartment of Periodontics and Endodontics, Okayama University Hospital, Okayama, Japan, 3Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTadashiYamamotoDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySeijiSugaDivision of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama UniversityShogoTakashibaDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityOsteoporosis is a common disease characterized by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. Severe bone loss due to osteoporosis triggers pathological fractures and consequently decreases the daily life activity and quality of life. Therefore, prevention of osteoporosis has become an important issue to be addressed. We have reported that the fungal secondary metabolite (+)-terrein (TER), a natural compound derived from Aspergillus terreus, has shown receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast differentiation by suppressing nuclear factor of activated T-cell 1 (NFATc1) expression, a master regulator of osteoclastogenesis. TER has been shown to possess extensive biological and pharmacological benefits; however, its effects on bone metabolism remain unclear. In this study, we investigated the effects of TER on the femoral bone metabolism using a mouse-ovariectomized osteoporosis model (OVX mice) and then on RANKL signal transduction using mouse bone marrow macrophages (mBMMs). In vivo administration of TER significantly improved bone density, bone mass, and trabecular number in OVX mice (p < 0.01). In addition, TER suppressed TRAP and cathepsin-K expression in the tissue sections of OVX mice (p < 0.01). In an in vitro study, TER suppressed RANKL-induced phosphorylation of PKC alpha/beta II, which is involved in the expression of NFATc1 (p < 0.05). The PKC inhibitor, GF109203X, also inhibited RANKL-induced osteoclastogenesis in mBMMs as well as TER. In addition, TER suppressed the expression of osteoclastogenesis-related genes, such as Ocstamp, Dcstamp, Calcr, Atp6v0d2, Oscar, and Itgb3 (p < 0.01). These results provide promising evidence for the potential therapeutic application of TER as a novel treatment compound against osteoporosis.No potential conflict of interest relevant to this article was reported.American Chemical Society (ACS)Acta Medica Okayama1523-70602382021Electrosynthesis of Phosphacycles via Dehydrogenative C–P Bond Formation Using DABCO as a Mediator31203124ENYujiKurimotoDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityJunYamashitaDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityKoichiMitsudoDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityEisukeSatoDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversitySeijiSugaDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityThe first electrochemical synthesis of diarylphosphole oxides (DPOs) was achieved under mild conditions. The practical protocol employs commercially available and inexpensive DABCO as a hydrogen atom transfer (HAT) mediator, leading to various DPOs in moderate to good yields. This procedure can also be applied to the synthesis of six-membered phosphacycles, such as phenophosphazine derivatives. Mechanistic studies suggested that the reaction proceeds via an electro-generated phosphinyl radical.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1433-785159202020Electrochemical Synthesis of Thienoacene Derivatives: Transition]Metal]Free Dehydrogenative C|S Coupling Promoted by a Halogen Mediator78037807ENKoichiMitsudoDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityRenMatsuoDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityTokiYonezawaDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityHarukaInoueDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityHirokiMandaiDepartment of Medical Technology, Gifu University of Medical ScienceSeijiSugaDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityThe first electrochemical dehydrogenative C|S bond formation leading to thienoacene derivatives is described. Several thienoacene derivatives were synthesized by dehydrogenative C|H/S|H coupling. The addition of nBu4NBr, which catalytically promoted the reaction as a halogen mediator, was essential.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1567-5769832020The fungal metabolite (+)-terrein abrogates osteoclast differentiation via suppression of the RANKL signaling pathway through NFATc1106429ENSakiNakagawaDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroOmoriDepartment of Periodontics and Endodontics, Okayama University HospitalMasaakiNakayamaDepartment of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirokiMandaiDepartment of Medical Technology, School of Health Science, Gifu University of Medical ScienceSatoshiYamamotoDepartment of Periodontics and Endodontics, Okayama University HospitalHiroyaKobayashiDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitHidefumiSakoDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKyosukeSakaidaDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiYoshimuraivision of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama UniversitySatokiIshiiDivision of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama UniversitySoichiroIbaragiDepartment of Oral Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKimitoHiraiDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeisukeYamashiroDepartment of Periodontics and Endodontics, Okayama University HospitalTadashiYamamotoDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySeijiSugaDivision of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama UniversityShogoTakashibaDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPathophysiological bone resorption is commonly associated with periodontal disease and involves the excessive resorption of bone matrix by activated osteoclasts. Receptor activator of nuclear factor (NF)-B ligand (RANKL) signaling pathways have been proposed as targets for inhibiting osteoclast differentiation and bone resorption. The fungal secondary metabolite (+)-terrein is a natural compound derived from Aspergillus terreus that has previously shown anti-interleukin-6 properties related to inflammatory bone resorption. However, its effects and molecular mechanism of action on osteoclastogenesis and bone resorption remain unclear. In the present study, we showed that 10 µM synthetic (+)-terrein inhibited RANKL-induced osteoclast formation and bone resorption in a dose-dependent manner and without cytotoxicity. RANKL-induced messenger RNA expression of osteoclast-specific markers including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), the master regulator of osteoclastogenesis, cathepsin K, tartrate-resistant acid phosphatase (Trap) was completely inhibited by synthetic (+)-terrein treatment. Furthermore, synthetic (+)-terrein decreased RANKL-induced NFATc1 protein expression. This study revealed that synthetic (+)-terrein attenuated osteoclast formation and bone resorption by mediating RANKL signaling pathways, especially NFATc1, and indicated the potential effect of (+)-terrein on inflammatory bone resorption including periodontal disease.No potential conflict of interest relevant to this article was reported.American Chemical SocietyActa Medica Okayama1523706020222018Synthesis and Properties of Dithieno-Fused 1,4-Azaborine Derivatives.73367340ENKoichiMitsudoDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityKeisukeShigemoriDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityHirokiMandaiDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityAtsushiWakamiyaInstitute for Chemical Research, Kyoto UniversitySeijiSugaDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University The first synthesis of dithieno[3,2- b:2',3'- e][1,4]azaborinine (DTAB) derivatives has been achieved by Buchwald-Hartwig coupling and subsequent Friedel-Crafts-type C-H borylation. A facile method for further -extension of DTAB was also developed via stannylation and subsequent Kosugi-Migita-Stille cross-coupling reaction. The fundamental properties of DTAB derivatives were also investigated.No potential conflict of interest relevant to this article was reported.American Chemical SocietyActa Medica Okayama1523706019112017Synthesis of 3-Benzo[b]thienyl 3-Thienyl Ether via an Addition-Elimination Reaction and Its Transformation to an Oxygen-Fused Dithiophene Skeleton: Synthesis and Properties of Benzodithienofuran and Its -Extended Derivatives28212824ENKoichiMitsudoDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityYujiKurimotoDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityHirokiMandaiDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversitySeijiSugaDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University The synthesis of 3-benzo[b]thienyl 3-thienyl ether and its dehydrogenative cyclization leading to benzodithienofuran (BDTF; [1]benzothieno[3,2-b]thieno[2,3-d]furan) are described for the first time. Further transformation of BDTF to more -extended BDTF derivatives and their fundamental physical properties are also studied.No potential conflict of interest relevant to this article was reported.Chemical Society of JapanActa Medica Okayama036670224782018Cu/Fe/O=PPh3-Catalyzed Etherification for the Synthesis of Aryl 3-Benzo[b]thienyl Ethers10441047ENKoichiMitsudoDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityTakuyaAsadaDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityTomohiroInadaDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityYujiKurimotoDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityHirokiMandaiDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversitySeijiSugaDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Cu/Fe-cocatalyzed cross-coupling reactions between 3-bromobenzo[b]thiophene and hydroxyaryls are described herein. The combination of Cu and Fe catalysts is important for the progress of the reactions, and the use of triphenylphosphine oxide as a ligand suppresses the dehalogenation of 3-bromobenzo[b]thiophene, and promptly facilitates the reaction. The obtained aryl benzo[b]thienyl ethers can be converted to pextended thienobenzofuran derivatives via Pd-catalyzed dehydrogenative cyclizations.No potential conflict of interest relevant to this article was reported.GEORG THIEMEActa Medica Okayama09365214301020191,10-Phenanthroline- or Electron-Promoted Cyanation of Aryl Iodides12091214ENKoichiMitsudo Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityKazukiYoshioka Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityTakayukiHirata Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityHirokiMandai Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityKojiMidorikawa Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversitySeijiSuga Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University A 1,10-phenanthroline-promoted cyanation of aryl iodides has been developed. 1,10-Phenanthroline worked as an organocatalyst for the reaction of aryl iodides with tetraalkylammonium cyanide to afford aryl cyanides. A similar reaction occurred through an electroreductive process.No potential conflict of interest relevant to this article was reported.American Chemical SocietyActa Medica Okayama152370602172019Iodide-Mediated or Iodide-Catalyzed Demethylation and Friedel-Crafts C-H Borylative Cyclization Leading to Thiophene-Fused 1,2-Oxaborine Derivatives21712175ENKeisukeShigemoriDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityMomokaWatanabeDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityJulieKongDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityKoichiMitsudoDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityAtsushiWakamiyaInstitute for Chemical Research, Kyoto UniversityHirokiMandaiDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversitySeijiSugaDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University The first synthesis of dithieno-1,2-oxaborine derivatives was achieved via iodide-mediated or iodide-catalyzed demethylation of 3-methoxy-2,2'-bithiophene and subsequent C-H borylation. A wide variety of thiophene-fused oxaborines could be synthesized by the procedure.No potential conflict of interest relevant to this article was reported.Royal Society of ChemistryActa Medica Okayama1359-734546482010Electrochemical generation of silver acetylides from terminal alkynes with a Ag anode and integration into sequential Pd-catalysed coupling with arylboronic acids92569258ENKoichiMitsudoTakuyaShiragaJun-ichiMizukawaSeijiSugaHideoTanakaAn electro-oxidative method for generating silver acetylides from acetylenes with a Ag anode was developed. The reaction could be integrated into a Pd-catalysed electrochemical Sonogashira-type reaction. In the presence of the catalytic amount of Pd(OAc)(2) and 4-BzO-TEMPO, electro-generated silver acetylides reacted immediately with arylboronic acids to afford the corresponding coupling adducts in high yields.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1420-304916102011Studies on the Synthesis of DMAP Derivatives by Diastereoselective Ugi Reactions88158832ENHirokiMandaiShunsukeIrieKoichiMitsudoSeijiSugaDiastereoselective Ugi reactions of DMAP-based aldehydes with -amino acids and tert-butyl isocyanide were examined. The reactions of 4-(dimethylamino)-2-pyridine-carboxaldehyde with various -amino acids afforded 2-substituted DMAP derivatives with low diastereoselectivity. On the contrary, reactions with 4-(dimethylamino)-3-pyridine-carboxaldehyde delivered 3-substituted DMAP derivatives with moderate to high diastereoselectivity. The combination of -amino acid and DMAP-based aldehyde is thus important to achieve high diastereoselectivity. Kinetic resolution of a secondary alcohol using a chiral DMAP derivative obtained through these reactions was also examined.No potential conflict of interest relevant to this article was reported.