KINDAI UNIVERSITY


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TANABE Genzoh

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FacultyDepartment of Pharmacy / Graduate School of Medicine / Pharmaceutical Research and Technology Institute
PositionProfessor
Degree
Commentator Guidehttps://www.kindai.ac.jp/meikan/354-tanabe-genzou.html
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Last Updated :2020/09/04

Research Activities

Research Areas

  • Life sciences, Pharmaceuticals - chemistry and drug development

Research Interests

  • α-glucosidase, salacia, kotalanol, salacinol

Published Papers

  • Probing the compatibility of an enzyme-linked immunosorbent assay toward the reprogramming of nonribosomal peptide synthetase adenylation domains, Fumihiro Ishikawa, Maya Nohara, Katsuki Takashima, Genzoh Tanabe, ChemBioChem, DOI: 10.1002/cbic.2000206, ChemBioChem, DOI: 10.1002/cbic.2000206, Jun. 2020 , Refereed
  • Synthesis of thiazinoimidazoles by lewis acid-catalyzed [3+3] cycloaddition reactions of propargyl alcohols with 2-mercaptoimidazoles, N. Mishima, T. Ogawa, G. Tanabe, O. Muraoka, H. Wasada, N. Hatae, M. Yoshimatsu, 3117 - 3121, May 2019 , Refereed
  • An engineered aryl acid adenylation domain with an enlarged substrate binding pocket, TANABE Genzoh, Angew. Chem. Int. Ed., Angew. Chem. Int. Ed., 58, 6906 - 6910, May 2019 , Refereed
  • An engineered aryl acid adenylation domain with a capacious active site microenvironment., Ishikawa F, Miyanaga A, Kitayama H, Nakamura S, Nakanishi I, Kudo F, Eguchi T, Tanabe G, Angewandte Chemie (International ed. in English), Angewandte Chemie (International ed. in English), 58(21), 6906 - 6910, Apr. 2019 , Refereed
  • Facile synthesis of neokotalanol, a potent α-glycosidase inhibitor isolated from the Ayurvedic traditional medicine “Salacia”., G. Tanabe, S. Ueda, K. Kurimoto, N. Sonoda, S. Marumoto, F. Ishikawa, W. Xie, O. Muraoka, ACS Omega, ACS Omega, 4, 7533 - 7533, Apr. 2019 , Refereed
  • Design, synthesis and biological evaluation of nitrate derivatives of sauropunol A and B as potent vasodilatory agents, L. Lu, X. Rao, R. Cong, C. Zhang, Z. Wang, J. Xu, G. Tanabe, O. Muraoka, X. Wu, W. Xie, Molecules, Molecules, 24, 583, Feb. 2019 , Refereed
  • Practical route to neokotalanol and its natural analogues: sulfonium sugars with antidiabetic activities., Y. Huang, Y. Gao, W. He, Z. Wang, W. Li, Z. Wang, W. Li, A. Lin, G. Tanabe, O. Muraoka, X. Wu, W. Xie, Angew. Chem. Int. Ed., Angew. Chem. Int. Ed., 58, 6400 - 6404, Feb. 2019 , Refereed
  • Unprecedented nucleophile-promoted 1,7-S or Se shift reactions under Pummerer reaction conditions of 4-alkenyl-3-sulfinylmethylpyrroles, T. Go, A. Morimatsu, H. Wasada, G. Tanabe, O. Muraoka, Y. Sawada, M. Yoshimatsu, Beilstein J. Org. Chem., Beilstein J. Org. Chem., 14, 2722 - 2729, Oct. 2018 , Refereed
  • Synthesis of salacinol-d4 as an internal standard for mass-spectrometric quantitation of salacinol, a potent a-glucosidase inhibitor found in a traditional Ayurvedic medicine “Salacia”, G. Tanabe, S. Teramae, Y.e Kunikata, S. Marumoto, S. Okugawa, F. Ishikawa, W. Xie, T. Morikawa, O. Muraoka, Heterocycles, Heterocycles, 97, 314 - 332, Sep. 2018 , Refereed
  • Expanding the Scope of Functionalized Small Nonprotein Components for Holoabzyme 27C1, F. Ishikawa, M. Shirahashi, H. Hayakawa, G. Tanabe, T. Tsumuraya, I. Fujii, ChemistrySelect, ChemistrySelect, 3, 9313 - 9317, Aug. 2018 , Refereed
  • Structural Basis of Protein-Protein Interactions between a trans-Acting Acyltransferase and Acyl Carrier Protein in Polyketide Disorazole Biosynthesis, Akimasa Miyanaga, Risako Ouchi, Fumihiro Ishikawa, Ena Goto, Genzoh Tanabe, Fumitaka Kudo, Tadashi Eguchi, Journal of the American Chemical Society, Journal of the American Chemical Society, 140(25), 7970 - 7978, Jun. 27 2018 , Refereed
    Summary:Acyltransferases (ATs) are responsible for the selection and incorporation of acyl building blocks in the biosynthesis of various polyketide natural products. The trans-AT modular polyketide synthases have a discrete trans-acting AT for the loading of an acyl unit onto the acyl carrier protein (ACP) located within each module. Despite the importance of protein-protein interactions between ATs and ACPs in trans-AT assembly lines, the dynamic actions of ACPs and trans-acting ATs remain largely uncharacterized because of the inherently transient nature of ACP-enzyme interactions. Herein, we report the crystal structure of the AT-ACP complex of disorazole trans-AT polyketide synthase. We used a bromoacetamide pantetheine cross-linking probe in combination with a Cys mutation to trap the transient AT-ACP complex, allowing the determination of the crystal structure of the disorazole AT-ACP complex at 2.03 Å resolution. On the basis of the cross-linked AT-ACP complex structure, ACP residues recognized by trans-acting AT were identified and validated by mutational studies, which demonstrated that the disorazole AT recognizes the loop 1 and helix III′ residues of disorazole ACP. The disorazole AT-ACP complex structure presents a foundation for defining the dynamic processes associated with trans-acting ATs and provides detailed mechanistic insights into their ability to recognize ACPs.
  • Diastereoselective Synthesis of Salacinol-Type α-Glucosidase Inhibitors, Ishikawa, F., Jinno, K., Kinouchi, E., Ninomiya, K., Marumoto, S., Xie, W., Muraoka, O., Morikawa, T., Tanabe, G., Journal of Organic Chemistry, Journal of Organic Chemistry, 83(1), 185 - 193, 2018 , Refereed
  • Total Synthesis of γ-Alkylidenebutenolides, Potent Melanogenesis Inhibitors from Thai Medicinal Plant Melodorum fruticosum, Tanabe, G., Manse, Y., Ogawa, T., Sonoda, N., Marumoto, S., Ishikawa, F., Ninomiya, K., Chaipech, S., Pongpiriyadacha, Y., Muraoka, O., Morikawa, T., Journal of Organic Chemistry, Journal of Organic Chemistry, 83(15), 8250 - 8261, 2018 , Refereed
  • First total synthesis of cyclic pentadepsipeptides Hikiamides A–C, Donglin Fu, Xuemin Rao, Jinyi Xu, Genzoh Tanabe, Osamu Muraoka, Xiaoming Wu, Weijia Xie, Tetrahedron Letters, Tetrahedron Letters, 59, 2876 - 2879, 2018 , Refereed
    Summary:The first total syntheses of naturally occurring cyclodepsipeptides Hikiamides A–C are described. The key linear pentapeptide precursors, prepared efficiently via Fmoc-solid-phase synthesis, were cyclized in dilute solution to provide the target Hikiamides A–C. The structures of the synthetic Hikiamides A–C were characterized by NMR and HRMS spectroscopy which were in agreement with those of natural products.
  • Identification of ACA-28, a 1'-acetoxychavicol acetate analogue compound, as a novel modulator of ERK MAPK signaling, which preferentially kills human melanoma cells., Satoh Ryosuke, Hagihara Kanako, Matsuura Kazuki, Manse Yoshiaki, Kita Ayako, Kunoh Tatsuki, Masuko Takashi, Moriyama Mariko, Moriyama Hiroyuki, Tanabe Genzoh, Muraoka Osamu, Sugiura Reiko, Genes to cells : devoted to molecular & cellular mechanisms, Genes to cells : devoted to molecular & cellular mechanisms, 22(7), 608-618, Jul. 2017 , Refereed
    Summary:Here, we carried out a chemical genetic screen using a fission yeast phenotypic assay and showed that ACA-28, a synthetic derivative of 1'-acetoxychavicol acetate (ACA), which is a natural ginger compound, effectively inhibited the growth of melanoma cancer cells wherein ERK MAPK signaling is hyperactivated due to mutations in the upstream activating regulators. ACA-28 more potently inhibited the growth of melanoma cells than did the parental compound ACA. Importantly, the growth of normal human epidermal melanocytes (NHEM) was less affected by ACA-28 at the same 50% inhibitory concentration. In addition, ACA-28 specifically induced apoptosis in NIH/3T3 cells which were oncogenically transformed with human epidermal growth factor receptor-2 (HER2/ErbB2), but not in the parental cells. ACA-28 might serve as a promising seed compound for melanoma treatment.
  • Computational study on the comparative differences in the activity of inhibitors of human versus rat alpha-glucosidase, TANABE Genzoh, Open Journal of Medicinal Chemistry, Open Journal of Medicinal Chemistry, 7(2), 19 - 28, Jun. 2017 , Refereed
  • In Vitro Regio- and Stereoselective Oxidation of beta-Ionone by Human Liver Microsomes, Shinsuke Marumoto, Ryoyu Shimizu, Genzoh Tanabe, Yoshiharu Okuno, Mitsuo Miyazawa, PLANTA MEDICA, PLANTA MEDICA, 83(3-4), 292 - 299, Feb. 2017 , Refereed
    Summary:The metabolism of the norisoprenoid beta-ionone was investigated in vitro using human liver microsomes and 11 different recombinant cytochrome P450 enzymes expressed in Trichoplusia ni cells. beta-Ionone was found to be oxidized via 4S-hydroxylation by CYP2B6 in human liver microsomes. CYP1A2 also regioselectively catalyzed the hydroxylation of beta-ionone to yield 4-hydroxylation; this conversion was not stereoselective. Further kinetic analysis revealed that CYP2B6 exhibited the highest activity for beta-ionone 4-hydroxylation. Kinetic analysis showed that K-m and V-max for oxidation of beta-ionone by CYP1A2 and CYP2B6 was 107.9 +/- 36.0 mu M and 3200.3 +/- 323.0 nmol/min/nmol P450 and 5.6 +/- 1.2 mu M and 572.8 +/- 29.8 nmol/min/nmol P450, respectively. The reaction rates observed using human liver microsomes and recombinant CYP2B6 were very high compared with those of other CYP2B6 substrates reported thus far. These results suggest that beta-ionone, a norisoprenoid present in nature, is one of the effective substrates for CYP2B enzymes in human liver microsomes. To the best of our knowledge, this is the first time that 4-hydroxy beta-ionone has been described as a human metabolite of beta-ionone.
  • Structure-activity relationship studies on acremomannolipin A, the potent calcium signal modulator with a novel glycolipid structure 4: Role of acyl side chains on D-mannose, Nozomi Tsutsui, Genzoh Tanabe, Nami Ikeda, Saika Okamura, Marika Ogawa, Kuniko Miyazaki, Ayako Kita, Reiko Sugiura, Osamu Muraoka, EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 121, 250 - 271, Oct. 2016 , Refereed
    Summary:As part of an ongoing study on the structure-activity relationship of acremomannolipin A (1)-the novel glycolipid isolated from Acremonium strictum possessing potent calcium signal-modulating activity-the role of acyl substituents on the D-mannose moiety was examined. Three partially deacylated homologs (2a-2c) and 20 homologs (2d-2w) bearing different acyloxy side chains were synthesized via the stereoselective beta-mannosylation of appropriately protected mannosyl sulfoxides (3) with D-mannitol derivatives (4), and their calcium signal-modulating activities were examined. The activities of 2a-2c were completely lost. Homologs bearing relatively short acyloxy groups at C-3, C-4, and C-6 positions (2t-2v) exhibited less activity than 1, whereas a heptanoyl homolog (2w: C-7) maintained activity nearly equal to that of 1. When the acyl groups at these three positions were substituted by an octanoyl group (2i: C-8), the activity was completely lost. On the other hand, of the 10 homologs in which the octanoyl at C-2 was substituted by other acyloxy moieties (2j-2s), three (2m: C-7, 2n: C-9, 2o: C-10) maintained potent activity. These results suggested that peracylated mannose structure is critical for calcium signal modulating activity, and this activity is precisely dependent on the length of four acyl side chains on D-mannose. (C) 2016 Published by Elsevier Masson SAS.
  • Hydrophobic substituents increase the potency of salacinol, a potent alpha-glucosidase inhibitor from Ayurvedic traditional medicine 'Salacia', Genzoh Tanabe, Weijia Xie, Gorre Balakishan, Mumen F. A. Amer, Nozomi Tsutsui, Haruka Takemura, Shinya Nakamura, Junji Akaki, Kiyofumi Ninomiya, Toshio Morikawa, Isao Nakanishi, Osamu Muraoka, BIOORGANIC & MEDICINAL CHEMISTRY, BIOORGANIC & MEDICINAL CHEMISTRY, 24(16), 3705 - 3715, Aug. 2016 , Refereed
    Summary:Using an in silico method, seven analogs bearing hydrophobic substituents (8a: Me, 8b: Et, 8c: n-Pent, 8d: n-Hept, 8e: n-Tridec, 8f: isoBu and 8g: neoPent) at the 3'-O-position in salacinol (1), a highly potent natural alpha-glucosidase inhibitor from Ayurvedic traditional medicine 'Salacia', were designed and synthesized. In order to verify the computational SAR assessments, their alpha-glucosidase inhibitory activities were evaluated in vitro. All analogs (8a-8g) exhibited an equal or considerably higher level of inhibitory activity against rat small intestinal alpha-glucosidases compared with the original sulfonate (1), and were as potent as or higher in potency than the clinically used anti-diabetics, voglibose, acarbose or miglitol. Their activities against human maltase exhibited good relationships to the results obtained with enzymes of rat origin. Among the designed compounds, the one with a 3'-O-neopentyl moiety (8g) was most potent, with an approximately ten fold increase in activity against human maltase compared to 1. (C) 2016 Elsevier Ltd. All rights reserved.
  • Mangiferin enhances the sensitivity of human multiple myeloma cells to anticancer drugs through suppression of the nuclear factor κB pathway., Tomoya Takeda, Masanobu Tsubaki, Toshiki Kino, Ayako Kawamura, Shota Isoyama, Tatsuki Itoh, Motohiro Imano, Genzoh Tanabe, Osamu Muraoka, Hideaki Matsuda, Takao Satou, Shozo Nishida, International journal of oncology, International journal of oncology, 48(6), 2704 - 12, Jun. 2016 , Refereed
    Summary:Multiple myeloma (MM) is still an incurable hematological malignancy with a 5-year survival rate of ~35%, despite the use of various treatment options. The nuclear factor κB (NF-κB) pathway plays a crucial role in the pathogenesis of MM. Thus, inhibition of the NF-κB pathway is a potential target for the treatment of MM. In a previous study, we showed that mangiferin suppressed the nuclear translocation of NF-κB. However, the treatment of MM involves a combination of two or three drugs. In this study, we examined the effect of the combination of mangiferin and conventional anticancer drugs in an MM cell line. We showed that the combination of mangiferin and an anticancer drug decreased the viability of MM cell lines in comparison with each drug used separately. The decrease in the combination of mangiferin and an anticancer drug induced cell viability was attributed to increase the expression of p53 and Noxa and decreases the expression of XIAP, survivin, and Bcl-xL proteins via inhibition of NF-κB pathway. In addition, the combination treatment caused the induction of apoptosis, activation of caspase-3 and the accumulation of the cells in the sub-G1 phase of the cell cycle. Our findings suggest that the combination of mangiferin and an anticancer drug could be used as a new regime for the treatment of MM.
  • Highly Diastereoselective Route to alpha-Glucosidase Inhibitors, Neosalacinol and Neoponkoranol, Genzoh Tanabe, Youya Matsuda, Misato Oka, Yousuke Kunikata, Nozomi Tsutsui, Weija Xie, Gorre Balakishan, Mumen F. A. Amer, Shinsuke Marumoto, Osamu Muraoka, JOURNAL OF ORGANIC CHEMISTRY, JOURNAL OF ORGANIC CHEMISTRY, 81(8), 3407 - 3415, Apr. 2016 , Refereed
    Summary:A facile and highly diastereoselective route to potent natural a-glucosidase inhibitors, i.e., neosalacinol (4) and neoponkoranol (6), isolated from the traditional Ayurvedic medicine "Salacia" was developed by intramolecular cyclization of appropriately substituted sulfides (9 and 12).
  • Design, synthesis and biological evaluation of 3 '-benzylated analogs of 3 '-epi-neoponkoranol as potent alpha-glucosidase inhibitors, Dan Liu, Weigang He, Zihao Wang, Long Liu, Chengqian Wang, Chenxi Zhang, Chengcheng Wang, Yuxuan Wang, Genzoh Tanabe, Osamu Muraoka, Xiaoming Wu, Liang Wu, Weijia Xie, EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 110, 224 - 236, Mar. 2016 , Refereed
    Summary:A group of 3'-epi-neoponkoranol analogs with different hydrophobic substituents attached at 3'-position of side chain moiety were designed and synthesized in order to further improve the inhibitory activities against alpha-glucosidases. Biological evaluation of these compounds revealed that sulfonium salts attached with ortho-substituted benzyl groups showed best alpha-glucosidase inhibitory activities. The most potent compound 10i showed greater inhibitory activities than all natural products. Moreover, docking studies on 10i with ntMGAM presented a new binding mode, indicating that amino residue Asp542 should be the key interacting point for strong inhibitory activity of small molecules against alpha-glucosidase enzymes. The strongest alpha-glucosidase inhibitory activity of 10i could be rationalized by van der Waals interactions between the 3'-attached substituent and particularly the ortho-substituted trifluoromethyl on benzyl group with the adjacent hydrophobic amino residues. Cytotoxicity evaluation assay demonstrated a high level of safety profile of the synthesized sulfonium salts against normal cell line. The enzyme kinetic studies showed a fully competitive inhibition of these sulfonium salts on each alpha-glucosidase. (C) 2016 Elsevier Masson SAS. All rights reserved.
  • Synthesis of Azepines via a [6 + 1]Annulation of Ynenitriles with Reformatsky Reagents., Yoshimatsu Mitsuhiro, Tanaka Miki, Fujimura Yu, Ito Yukiteru, Goto Yusuke, Kobayashi Yuka, Wasada Hiroaki, Hatae Noriyuki, Tanabe Genzoh, Muraoka Osamu, The Journal of organic chemistry, The Journal of organic chemistry, 80(19), 9480 - 9494, Oct. 2015 , Refereed
    Summary:A protocol for the direct synthesis of azepines using a hafnium(III)-catalyzed [6 + 1]annulation of N-tethered ynenitriles with Reformatsky reagents is reported. A broad range of3-amino-2,7-dihydro-1H-azepine-4-carboxylates 4aa-4he were obtained in high yields and with excellent functional group tolerance. The copper-mediated reactions of isolable Blaise intermediates (enamino esters 3), uniquely underwent 5-endo cyclization to afford the β-2,5-dihydropyrrolyl α,β-unsaturated esters 5aa-5fc, which exhibit anticancer activity.
  • Mangiferin suppresses CIA by suppressing the expression of TNF-α, IL-6, IL-1β, and RANKL through inhibiting the activation of NF-κB and ERK1/2., Masanobu Tsubaki, Tomoya Takeda, Toshiki Kino, Tatsuki Itoh, Motohiro Imano, Genzo Tanabe, Osamu Muraoka, Takao Satou, Shozo Nishida, American journal of translational research, American journal of translational research, 7(8), 1371 - 81, 2015 , Refereed
    Summary:Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic inflammation of synovial joints, ultimately leading to a progressive and irreversible joint destruction. Activation of nuclear factor-kappa B (NF-κB) promotes production of proinflammatory cytokines in various inflammatory diseases including rheumatoid arthritis. Mangiferin, 1,3,6,7-tetrahydroxyxanthone-C2-β-D-glucoside (C-glucosyl xanthone), is a naturally occurring polyphenol. Our previous results showed that mangiferin suppressed NF-κB activation. However, it is unclear, whether mangiferin can prevent rheumatoid arthritis through suppression of NF-κB activation and expression of various cytokines, such as tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), which play a critical role in the pathogenesis of rheumatoid arthritis. In the present study, we found that mangiferin suppressed the progression and incidence of CIA in DBA1/J mice. In CIA mice, mangiferin inhibited the mRNA expression of cytokine genes in thymus and spleen of CIA mie and led to decreased serum levels of IL-1β, IL-6, TNF-α, and receptor activator NF-κB ligand (RANKL) via inhibition of NF-κB and activation of extracellular signal-regulated kinase 1/2 (ERK1/2). In addition, mangiferin markedly inhibited not only developing but also clinically evident CIA. These findings suggest that mangiferin has potential clinical applications for the treatment of rheumatoid arthritis.
  • Evaluation of Salacia Species as Anti-diabetic Natural Resources Based on Quantitative Analysis of Eight Sulphonium Constituents: A New Class of alpha-Glucosidase Inhibitors, Junji Akaki, Toshio Morikawa, Sohachiro Miyake, Kiyofumi Ninomiya, Mayumi Okada, Genzoh Tanabe, Yutana Pongpiriyadacha, Masayuki Yoshikawa, Osamu Muraoka, PHYTOCHEMICAL ANALYSIS, PHYTOCHEMICAL ANALYSIS, 25(6), 544 - 550, Nov. 2014 , Refereed
    Summary:IntroductionStems and roots of Salacia genus plants have been used in Ayurveda as a specific remedy for early stage diabetes. Previous investigations identified four sulphonium sulphates, that is, salacinol (1), kotalanol (3), ponkoranol (5) and salaprinol (7), as the compounds responsible for the anti-diabetic activity. Their desulphonates (2, 4, 6 and 8) were also isolated as active constituents. Two separate quantitative analytical protocols, that is, for 1 and 3 and for 2 and 4, have been developed recently. ObjectiveTo: validate the two analytical protocols with respect to all eight sulphoniums; evaluate the quality of a variety of Salacia samples collected in different geographical regions, that is, Thailand, Sri Lanka and India; and determine their distribution in each part of the plant, that is, stems/roots, leaves and fruits. MethodsAnalyses of four sulphonium sulphates in 32 Salacia extracts were carried out on an Asahipak NH2P-50 column, and those of the corresponding desulphonates were conducted on an Inertsil ODS-3 column. ResultsNeokotalanol (4) was the major constituent in Salacia samples from Thailand, whereas 1 was the primary constituent in extracts of the stems/roots of plants from Sri Lanka and India. These sulphoniums were only present in trace amounts in leaves and fruits of the plants. ConclusionTwo analytical protocols were successfully applied to analyse 32 Salacia samples, and revealed that sulphoniums (1-8) had characteristic distributions due to the plant part and/or due to geographical region. Copyright (c) 2014 John Wiley & Sons, Ltd. Using the recently developed two analytical protocols, the distributions of eight sulphoniums (1-8) responsible for the anti-diabetic activity of Salacia, a specific remedy for the treatment of early stage diabetes in Ayurveda, were examined in 32 extracts of Salacia samples collected in Thailand, Sri Lanka and India. The distribution of these sulphoniums in the different plant parts was also examined. Each constituent had characteristic distributions in the different plant parts and different geographical regions.
  • Synthetic study on neoponkoranol and its side chain epimer as potent alpha-glucosidase inhibitors, optimization of protecting group, Dan Liu, Weijia Xie, Long Liu, Hequan Yao, Jinyi Xu, Genzoh Tanabe, Osamu Muraoka, Xiaoming Wu, TETRAHEDRON LETTERS, TETRAHEDRON LETTERS, 54(47), 6333 - 6336, Nov. 2013 , Refereed
    Summary:Coupling reaction between thiosugar and triflate as the key protocol to synthesize neoponkoranol, a naturally occurring potent alpha-glucosidase inhibitor, and its related sulfonium salts was optimized by applying different esters as protecting group, with the yields of desired products being greatly improved. Our proposed mechanism of the coupling reaction indicated that the nucleophilicity of C3-hydroxyl moiety on monosaccharide structure is closely related to the reaction mode. (C) 2013 Elsevier Ltd. All rights reserved.
  • Total synthesis of neokotalanol, a potent α-glucosidase inhibitor isolated from Salacia reticulata., Xie WJ, Tanabe G, Tsutsui N, Wu XM, Muraoka O, Chinese journal of natural medicines, Chinese journal of natural medicines, 11(6), 676 - 683, Nov. 2013 , Refereed
  • Chemistry of propargyl compounds activated by sulfur functional groups-development of methodology for the synthesis of heterocyles triggered by functionalizations, Mitsuhiro Yoshimatsu, Genzoh Tanabe, Osamu Muraoka, Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, 71(12), 1282 - 1293, 2013 , Refereed
    Summary:In this paper, molecular activation of sulfur functional groups, including the 7-sulfur-stabilization effect on propargyl cations generated from the corresponding alcohols and sulfur-activated cyclizations of oxygen- and nitrogen-tethered 1,6-diynes triggered by some useful transformations, is described. With respect to propargylation, Lewis acid-catalyzed C-C, C-O and C-N bond formations in nitromethane or nitromethane - H2O have been developed. Moreover, C-N bond formation for the synthesis of pyrazoles via intra- and intermolecular cyclizations is investigated. Thioamides underwent cycloaddition with allenyl cation intermediates, while this reaction did not occur with propargyl cations. In sulfur-activated cyclizations, nucleophile-triggered cyclization provided alkoxymethyl-, aryloxymethylfurans and tanshinon derivatives. Furthermore, the alkynylation- and amination-triggered cyclizations of 1,6-diynes are also described.
  • Research progress of synthesis and structure-activity relationship studies on sulfonium-type α-glucosidase inhibitors isolated from salacia genus plants, Weijia Xie, Genzoh Tanabe, Jinyi Xu, Xiaoming Wu, Toshio Morikawa, Masayuki Yoshikawa, Osamu Muraoka, Mini-Reviews in Organic Chemistry, Mini-Reviews in Organic Chemistry, 10(2), 141 - 159, 2013 , Refereed
    Summary:Salacinol was isolated as the first naturally occurring sulfonium type α-glucosidase inhibitor from Salacia reticulata, a large woody, climbing plant widely distributed in Sri Lanka and South India, in 1997. This compound presents a quite unique zwitterionic sulfonium sulfate structure and its α-glucosidase inhibitory activity (in vitro) was revealed to be as potent as those of anti-diabetics used in clinic. Since then, great efforts have been made to discover other bioactive ingredients as potent α-glucosidase inhibitors from the same genus of plants, which directly led to the identification of several side chain analogs of salacinol such as kotalanol, salaprinol and ponkoranol together with their de-Osulfonated analogs. In the mean time, much attention has been focused on the total syntheses, structure activity relationship (SAR) studies on this group of natural products in order to design molecules with improved activities. Thus, as a possible result of present findings, this class of natural products has the potential to become lead compounds with potent α- glucosidase inhibitory activities, which could be further developed to a new class of hypoglycemic drug candidates. The present review was developed as a summary of the recent researches of total synthesis and SAR of this series of natural products. In addition, several important structural determinants including the most recent discoveries on SAR are summarized, which may provide new insights into the development of novel anti-diabetic agents. © 2013 Bentham Science Publishers.
  • Role of the side chain stereochemistry in the alpha-glucosidase inhibitory activity of kotalanol, a potent natural alpha-glucosidase inhibitor. Part 2, Genzoh Tanabe, Kanjyun Matsuoka, Masahiro Yoshinaga, Weijia Xie, Nozomi Tsutsui, Mumen F. A. Amer, Shinya Nakamura, Isao Nakanishi, Xiaoming Wu, Masayuki Yoshikawa, Osamu Muraoka, BIOORGANIC & MEDICINAL CHEMISTRY, BIOORGANIC & MEDICINAL CHEMISTRY, 20(21), 6321 - 6334, Nov. 2012 , Refereed
    Summary:To examine the role of the side chain of kotalanol (2), a potent natural alpha-glucosidase inhibitor isolated from Salacia reticulata, on inhibitory activity, four diastereomers (11a-11d) with reversed configuration (S) at the C-4' position in the side chain were synthesized and evaluated. Two of the four (11b and 11d) significantly lost their inhibitory activity against both maltase and sucrase, while the other two (11a and 11c) sustained the inhibitory activity to a considerable extent, showing distinct activity in response to the change of stereochemistry of the hydroxyls at the 5' and 6' positions. Different activities were rationalized with reference to in silico docking studies on these inhibitors with hNtMGAM. Against isomaltase, all four analogs showed potent inhibitory activity as well as 2, and 11b and 11d exhibited enzyme selectivity. (C) 2012 Elsevier Ltd. All rights reserved.
  • Homology modeling of human alpha-glucosidase catalytic domains and SAR study of salacinol derivatives, S. Nakamura, K. Takahira, G. Tanabe, O. Muraoka, I. Nakanishi, Open J. Med. Chem., Open J. Med. Chem., 2, 50 - 60, Sep. 2012 , Refereed
  • P-7 In Silico Design, Synthesis and Evaluation of Salacinol Analogs, a New Class of α-Glucosidase Inhibitors with Sulfonium Salts Structure(Poster Presentation), Tanabe Genzoh, Yoshikawa Masayuki, Muraoka Osamu, Nakamura Shinya, Yoshinaga Masahiro, Tsutsui Nozomi, Balakishan Gorre, Akaki Junji, Morikawa Toshio, Ninomiya Kiyofumi, Nakanishi Isao, Symposium on the Chemistry of Natural Products, symposium papers, Symposium on the Chemistry of Natural Products, symposium papers, 54(0), 285 - 290, 2012
    Summary:To develop more potent α-glucosidase inhibitors whose seed-compound is salacinol (1), a potent natural α-glucosidase inhibitor isolated from Salacia reticulata of Ayurvedic traditional medicine, a series of 3'-O-benzylated analogs of 1 were designed with the aid of in silico method. Intensive docking studies proposed several promising compounds. To verify the computational SAR assessments, designed derivatives were synthesized and evaluated in vitro. Their α-glucosidase inhibitory activities against rat intestinal α-glucosidases were so potent as were expected by the docking studies, and all the compounds showed superior inhibitory activities to the original sulfonium sulfate (1). Among the sulfonium salts designed, one with 3'-O-(ortho-nitrobenzyl) moiety (8k) was found to be the most potent, and ca. forty times as potent as 1, the compound being the strongest inhibitor among the sulfonium type inhibitors synthesized so far. [chemical formula]
  • In silico design, synthesis and evaluation of 3 '-O-benzylated analogs of salacinol, a potent alpha-glucosidase inhibitor isolated from an Ayurvedic traditional medicine "Salacia", Genzoh Tanabe, Shinya Nakamura, Nozomi Tsutsui, Gorre Balakishan, Weijia Xie, Satoshi Tsuchiya, Junji Akaki, Toshio Morikawa, Kiyofumi Ninomiya, Isao Nakanishi, Masayuki Yoshikawa, Osamu Muraoka, CHEMICAL COMMUNICATIONS, CHEMICAL COMMUNICATIONS, 48(69), 8646 - 8648, 2012 , Refereed
    Summary:With the aid of an in silico method, alpha-glucosidase inhibitors with far more potent activities than salacinol (1), a potent natural alpha-glucosidase inhibitor isolated from an Ayurvedic traditional medicine Salacia reticulata, have been developed.
  • Biological evaluation of 3 '-O-alkylated analogs of salacinol, the role of hydrophobic alkyl group at 3 ' position in the side chain on the alpha-glucosidase inhibitory activity, Genzoh Tanabe, Tetsu Otani, Wenying Cong, Toshie Minematsu, Kiyofumi Ninomiya, Masayuki Yoshikawa, Osamu Muraoka, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 21(10), 3159 - 3162, May 2011 , Refereed
    Summary:Four analogs with 3'-O-alkyl groups (9a: CH(3), 9b: C(2)H(5), 9c: C(13)H(27) or 9d: CH(2)Ph) instead of the 3'-O-sulfate anion in salacinol (1), a naturally occurring potent alpha-glucosidase inhibitor, were synthesized by the coupling reaction of 1,4-dideoxy-1,4-epithio-D-arabinitols (18a and 18b) with appropriate epoxides (10a-10d). These analogs showed equal or considerably higher inhibitory activity against rat small intestinal alpha-glucosidases than the original sulfate (1), and one of them (9d) was found more potent than currently used alpha-glucosidase inhibitors as antidiabetics. Thus, introduction of a hydrophobic moiety at the C3' position of this new class of inhibitor was found beneficial for onset of stronger inhibition against these enzymes. (C) 2011 Elsevier Ltd. All rights reserved.
  • Role of the side chain stereochemistry in the alpha-glucosidase inhibitory activity of kotalanol, a potent natural alpha-glucosidase inhibitor, Weijia Xie, Genzoh Tanabe, Kanjyun Matsuoka, Mumen F. A. Amer, Toshie Minematsu, Xiaoming Wu, Masayuki Yoshikawa, Osamu Muraoka, BIOORGANIC & MEDICINAL CHEMISTRY, BIOORGANIC & MEDICINAL CHEMISTRY, 19(7), 2252 - 2262, Apr. 2011 , Refereed
    Summary:Synthesis and evaluation of four diastereomers (9a, 9b, 9c and 9d) of kotalanol, a potent alpha-glucosidase inhibitor isolated from an Ayurvedic medicinal plant Salacia species, are described. Stereo-inversion at C-3' and C-4' of kotalanol (2) caused significant decrease of the inhibitory activities against maltase and sucrase, whereas inhibitory activity against isomaltase sustained, thus resulted in exerting selectivity against isomaltase. (C) 2011 Elsevier Ltd. All rights reserved.
  • Isolation, structure identification and SAR studies on thiosugar sulfonium salts, neosalaprinol and neoponkoranol, as potent alpha-glucosidase inhibitors, Weijia Xie, Genzoh Tanabe, Junji Akaki, Toshio Morikawa, Kiyofumi Ninomiya, Toshie Minematsu, Masayuki Yoshikawa, Xiaoming Wu, Osamu Muraoka, BIOORGANIC & MEDICINAL CHEMISTRY, BIOORGANIC & MEDICINAL CHEMISTRY, 19(6), 2015 - 2022, Mar. 2011 , Refereed
    Summary:Two hitherto missing members of sulfonium salts family in Salacia genus plants as a new class of a-glucosidase inhibitors, neoponkoranol (7) and neosalaprinol (8), were isolated from the water extracts, and their structures were unambiguously identified. For further SAR studies on this series of sulfonium salts, several epimers of 7 and 8 were synthesized, and their inhibitory activities against rat small intestinal alpha-glucosidases were evaluated. Among them, 3'-epimer of 7 was found most potent in this class of molecules, and revealed as potent as currently used antidiabetics, voglibose and acarbose. (C) 2011 Elsevier Ltd. All rights reserved.
  • Docking and SAR studies of salacinol derivatives as alpha-glucosidase inhibitors, Shinya Nakamura, Kazunori Takahira, Genzoh Tanabe, Toshio Morikawa, Mika Sakano, Kiyofumi Ninomiya, Masayuki Yoshikawa, Osamu Muraoka, Isao Nakanishi, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 20(15), 4420 - 4423, Aug. 2010 , Refereed
    Summary:Salacinol is a potent alpha-glucosidase inhibitor isolated from Salacia reticulata, and a good lead compound for an antidiabetic drug. It is essential to clarify the binding state of salacinol to alpha-glucosidase for efficient optimization study using structure-based drug design. Redocking simulations of two inhibitors, acarbose and casuarine whose complex structures are known, were performed to assure the appropriate docking pose prediction. The simulation reproduced both experimental binding states with accuracy. Then, using the same simulation protocol, the binding mode of salacinol and its derivatives has been predicted. Salacinol bound to the protein with a similar binding mode as casuarine, and the predicted structures could explain most of the structure-activity relationships of salacinol derivatives. (C) 2010 Elsevier Ltd. All rights reserved.
  • alpha-Sulfanyl and alpha-Selanyl Propadienyl Cations: Regioselective Generations and Cycloadditions with Thioamides and Selemides Controlled by MeNO2-H2O System, Mitsuhiro Yoshimatsu, Teruhisa Yamamoto, Arisa Sawa, Tomohiro Kato, Genzoh Tanabe, Osamu Muraoka, ORGANIC LETTERS, ORGANIC LETTERS, 11(13), 2952 - 2955, Jul. 2009 , Refereed
    Summary:alpha-Sultanyl and alpha-selanyl propadienyl cations were easily generated by the catalytic system, scandium triflate-nitromethane-H2O in the presence of Bu4NHSO4, to regioselectively afford the multifunctionalized thiazoles and selenazoles in high yields.
  • Facile synthesis of de-O-sulfated salacinols: Revision of the structure of neosalacinol, a potent alpha-glucosidase inhibitor, Genzoh Tanabe, Weijia Xie, Ai Ogawa, Changnian Cao, Toshie Minematsu, Masayuki Yoshikawa, Osamu Muraoka, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 19(8), 2195 - 2198, Apr. 2009 , Refereed
    Summary:Facile synthesis of de-O-sulfated salacinols (3) was developed by employing the coupling reaction of an epoxide, 1,2-anhydro-3,4-di-O-benzyl-D-erythritol (9) with 2,3,5-tri-O-benzyl-1,4-dideoxy-1,4-epithio-D-arabinitol (10) as the key reaction. The reported structure of a potent alpha-glucosidase inhibitor named neosalacinol (8), isolated recently from Ayurvedic medicine Salacia oblonga, was proved incorrect, and revised to be de-O-sulfated salacinol formate (3c) by comparison of the spectroscopic properties with those of the authentic specimen synthesized. Discrepancies and confusion in the literature concerning the NMR spectroscopic properties of salacinol (1) have also been clarified. (C) 2009 Elsevier Ltd. All rights reserved.
  • SYNTHESES AND EVALUATION AS GLYCOSIDASE INHIBITOR OF 1,5-DIDEOXY-1,5-IMINO-D-GLUCITOL ANALOGS OF SALACINOL, A POTENT alpha-GLUCOSIDASE INHIBITOR ISOLATED FROM AYURVEDIC MEDICINE, SALACIA RETICULATA, Genzoh Tanabe, Takanori Hatanaka, Toshie Minematsu, Hisashi Matsuda, Masayuki Yoshikawa, Osamu Muraoka, HETEROCYCLES, HETEROCYCLES, 79, 1093 - 1100, Apr. 2009 , Refereed
    Summary:N-Alkylated deoxynojirimycin (10) bearing the same alkyl chain as salacinol (1), a potent alpha-glucosidase inhibitor isolated from Ayurvedic traditional medicine, Salacia reticulata, was found to inhibit both rat intestinal maltase and sucrase as strong as 1, while 10 has been reported to be inactive against glucoamylase G2 from Aspergillus niger. Its O-desulfate (12) was also found active against these enzymes, and characteristic sulfate anion moiety of I was found not essential for the alpha-glucosidase inhibitory activity.
  • Salaprinol and ponkoranol with thiosugar sulfonium sulfate structure from Salacia prinoides and α- glucosidase inhibitory activity of ponkoranol and kotalanol desulfate, Masayuki Yoshikawa, Fengming Xu, Seikou Nakamura, Tao Wang, Hisashi Matsuda, Genzoh Tanabe, Osamu Muraoka, Heterocycles, Heterocycles, 75(6), 1397 - 1405, Jun. 01 2008 , Refereed
    Summary:The methanolic extract from the roots and stems of Indian Salacia prinoides and its water-eluted fraction of Diaion HP-20 column were found to exhibit inhibitory activities against α-glucosidase. From the water-eluted fraction, two new unique constituents with thiosugar sulfonium sulfate, salaprinol (1) and ponkoranol (2), were isolated together with 10 known constituents including salacinol and kotalanol. The structures of 1 and 2 were elucidated on the basis of chemical and physicochemical evidence. Furthermore, ponkoranol (2) and kotalanol desulfate (14) were found to show potent inhibitory activities against α- glucosidase. © 2008 The Japan Institute of Heterocyclic Chemistry.
  • Total synthesis of (+/-)-stemonamide and (+/-)-isostemonamide using a radical cascade, Tsuyoshi Taniguchi, Genzo Tanabe, Osamu Muraoka, Hiroyuki Ishibashi, ORGANIC LETTERS, ORGANIC LETTERS, 10(2), 197 - 199, Jan. 2008 , Refereed
    Summary:Total synthesis of stemonamide and isostemonamide is described. The concise construction of the tricyclic core of these alkaloids was achieved by radical cascade involving 7-endo and 5-endo cyclizations.
  • Biological evaluation of de-O-sulfonated analogs of salacinol, the role of sulfate anion in the side chain on the alpha-glucosidase inhibitory activity, Genzoh Tanabe, Kazuya Yoshikai, Takanori Hatanaka, Mizuho Yamamoto, Ying Shao, Toshie Minematsu, Osamu Muraoka, Tao Wang, Hisashi Matsuda, Masayuki Yoshikawa, BIOORGANIC & MEDICINAL CHEMISTRY, BIOORGANIC & MEDICINAL CHEMISTRY, 15(11), 3926 - 3937, Jun. 2007 , Refereed
    Summary:De-O-sulfonated analogs (10a, Y- = CH(3)QSO(3) and 10b, Y- = Cl) of salacinol, a naturally occurring glycosidase inhibitor, and its diastereomer (12a, Y- = CH3OSO3) With L-thiosugar moiety (1,4-dideoxy- 1,4-epithio-L-arabinitol) were prepared. Their inhibitory activities against intestinal maltase and sucrase were examined and compared with those of the parent alpha-glycosidase inhibitor, salacinol (1a). Compounds 10a and 10b showed a potent inhibitory activity equal to that of la against both enzymes, although 12a was a weak inhibitor against sucrase and maltase. These results indicated that the O-sulfonate anion moiety of 1a is not essential for the inhibitory activity. (C) 2007 Published by Elsevier Ltd.
  • Structure-activity relationships of salacinol and kotalanol against alpha-glucosidase inhibitory activity and evaluation of Salacia extracts by LC-MS, Genzoh Tanabe, Kanjyun Matsuoka, Toshie Minematsu, Toshio Morikawa, Kiyofumi Ninomiya, Hisashi Matsuda, Masayuki Yoshikawa, Hideaki Murata, Osamu Muraoka, YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 127, 129 - 130, 2007 , Refereed
    Summary:Kotalanol (1) and salacinol (2) are potent alpha-glucosidase inhibitors isolated from methanol extract of an antidiabetic Ayurvedic traditional medicine, Salacia reticulata. Although 1 is more active against certain glycosidase enzymes than 2, no synthetic trial of 1 has been reported because of the unidentified absolute stereochemistry of the heptitol unit. Herein reported are synthetic study on 1 and evaluation of the inhibitory activities of four synthesized diastereomers 1a-1d, which maintained 2'S and 3'S configuration of 2 in addition to 4'S configuration as common side chain feature. All the analogs showed less inhibitory activity against sucrase and maltase compared to 1, and the results indicated that the 4'S configuration was essential for the inhibitory activity. Newly developed quantitative analytical method of 1 and 2 in the extract of several Salacia species by LC-MS to evaluate the quality of the Salacia extract is also presented.
  • STRUCTURE-ACTIVITY RERATIONSHIPS ON THE .ALPHA.-GLUCOSIDASE INHIBITORY ACTIVITY OF SALACINOL, MURAOKA OSAMU, TANABE GENZO, HATANAKA TAKANORI, MATSUDA HISASHI, YOSHIKAWA MASAYUKI, 薬学雑誌, 薬学雑誌, 126(Suppl.3), 112 - 113, Oct. 01 2006
  • Synthesis of a salacinol analogue and its α-glucosidase inhibitory activity, Ying Shao, Muraoka Osamu, Yoshikai Kazuya, Matsuura Yoshiharu, Yamada Eriko, Minematsu Toshie, Tanabe Genzoh, Matsuda Hisashi, Yoshikawa Masayuki, Qi-Dong You, Yaoxue Xuebao, Yaoxue Xuebao, 41(7), 647 - 653, Jul. 2006 , Refereed
    Summary:Aim: To investigate more efficient synthetic method of the nitrogen analogue 4 of salacinol (1) for searching new antidiabetic agents. Methods: The synthesis of the key intermediate 2,4-O-isopropylidene-L-erythritol 1,3-cyclic sulfate (2a) was accomplished by modification of reports from D-glucose via seven steps in much more less expensive. Using this method, an efficient synthesis of 4 was carried out. The glycosidase inhibitory activity of 4 was tested for the intestinal α-glucosidase in vitro and compared with that of salacinol. Results: A nitrogen analogue 4 of salacinol (1) was synthesized by the coupling reaction between the cyclic sulfate 2a and an azasugar 3b. Conclusion: Substitution of the sulfur atom in 1 with a nitrogen reduced the activity considerably.
  • Synthesis and biological evaluation of deoxy salacinols, the role of polar substituents in the side chain on the alpha-glucosidase inhibitory activity, O Muraoka, K Yoshikai, H Takahashi, T Minematsu, GX Lu, G Tanabe, T Wang, H Matsuda, M Yoshikawa, BIOORGANIC & MEDICINAL CHEMISTRY, BIOORGANIC & MEDICINAL CHEMISTRY, 14(2), 500 - 509, Jan. 2006 , Refereed
    Summary:Three analogs (5, 6, and 7) lacking polar substituents in the side chain of a naturally occurring a-glucosidase inhibitor, salacinol (la), were synthesized by the coupling reaction of a thiosugar, 1,4-dideoxy-1,4-epithio-D-arabinitol (3), with cyclic sulfates (8, 9, and 10), and their a-glucosidase inhibitory activities were examined. All these simpler analogs (5, 6, and 7) showed less inhibitory activity compared to la, and proved the importance of cooperative role of the polar substituents for the a-glucosidase inhibitory activity. A practical synthetic route to 3 starting from D-xylose is also described. (c) 2005 Elsevier Ltd. All rights reserved.
  • Design and synthesis of a simplified analogue of salacinol, Muraoka O, Tanabe G, Shao Y, Daxue Zhongguo Yaoke Daxue Xuebao, Daxue Zhongguo Yaoke Daxue Xuebao, 37, 403 - 406, 2006 , Refereed
  • Z-selective or stereospecific alkenylation reaction: A novel synthetic method for alpha-fluoro-alpha,beta-unsaturated esters, M Yoshimatsu, Y Murase, A Itoh, G Tanabe, O Muraoka, CHEMISTRY LETTERS, CHEMISTRY LETTERS, 34(7), 998 - 999, Jul. 2005 , Refereed
    Summary:The Z-sclective formation of alpha-fluoro-alpha,beta-unsaturated esters was achieved using the deselenenic acid of the synand/or anti-3-aryl-2-fluoro-3-hydroxy-2-organoselanylacetates 3 and 4 with trifluoromethanesuffonic acid. In contrast, the 3-alkyl-substituted propanoates 3f and 4b stereospecifically underwent alkenylation to give the (E)- or (Z)-alpha-fluoro-alpha,beta-unstaurated esters 5f. We were also successful in the one-pot alkenylation reactions.
  • Antidiabetogenic constituents from Salacia species., H. Matsuda, M. Yoshikawa, T. Morikawa, G. Tanabe, O. Muraoka, J. Trad. Med., J. Trad. Med., 22(Suppl. 1), 145 - 153, Jun. 2005 , Refereed
  • サラシノールの側鎖部デオキシ類縁体の合成, MURAOKA OSAMU, YOSHIKAI KAZUYA, TAKAHASHI HIDEO, MINEMATSU TOSHIE, TANABE GENZO, MATSUDA HISASHI, YOSHIKAWA MASAYUKI, 近畿大学薬学総合研究所紀要, 近畿大学薬学総合研究所紀要, (12), 117 - 132, Mar. 05 2004
  • Chalcogeno-Morita-Baylis-Hillman reaction of enones with acetals: Simple alpha-alkoxyalkylation of enones, H Kinoshita, T Osamura, S Kinoshita, T Iwamura, SI Watanabe, T Kataoka, G Tanabe, O Muraoka, JOURNAL OF ORGANIC CHEMISTRY, JOURNAL OF ORGANIC CHEMISTRY, 68(19), 7532 - 7534, Sep. 2003 , Refereed
    Summary:1-[2-(Methylsulfanyl)phenyl]prop-2-en-1-one (1) and the seleno congener (2) reacted with acetals 3 and 21 in the presence of (BF3Et2O)-Et-. to give alpha-alkoxyalkyl enones 4, 5 and 22, 23 in good yields. When the reaction mixtures were worked up with a saturated NaHCO3 solution instead of Et3N, onium salts 6 and 7 were obtained together with 4 and 5. Reactions with cyclic acetal 14 gave alpha-(beta-hydroxy-ethoxy) enones 15 and 16 accompanied by dimeric products 17 and 18.
  • Di-tert-butylsilylene (DTBS) group-directed alpha-selective galactosylation unaffected by C-2 participating functionalities, A Imamura, H Ando, S Korogi, G Tanabe, O Muraoka, H Ishida, M Kiso, TETRAHEDRON LETTERS, TETRAHEDRON LETTERS, 44(35), 6725 - 6728, Aug. 2003 , Refereed
    Summary:We have discovered an unusual alpha-galactosylation using phenylthioglycoside of 4,6-O-di-tert-butylsilylene (DTBS)-protected galactose derivatives as a glycosyl donor, which was not hampered by the neighboring participation of C-2 acyl functionality such as NTroc and OBz. The power of the DTBS effect has been exemplified by the coupling reaction with various glycosyl acceptors. (C) 2003 Elsevier Ltd. All rights reserved.
  • Absolute stereostructure of potent alpha-glucosidase inhibitor, salacinol, with unique thiosugar sulfonium sulfate inner salt structure from Salacia reticulata, M Yoshikawa, T Morikawa, H Matsuda, G Tanabe, O Muraoka, BIOORGANIC & MEDICINAL CHEMISTRY, BIOORGANIC & MEDICINAL CHEMISTRY, 10(5), 1547 - 1554, May 2002 , Refereed
    Summary:A most potent alpha-glucosidase inhibitor named salacinol has been isolated from an antidiabetic Ayurvedic traditional medicine. Salacia reticulata WIGHT, through bioassay-guided separation. The absolute stereostructure of salacinol was determined on the basis of chemical and physicochemical evidence, which included the alkaline degradation of salacinol to 1-deoxy-4-thio-D-arabinofuranose and the X-ray crystallographic analysis, to be the unique spiro-like configuration of the inner salt comprised of 1-deoxy-4-thio-D-arabinofuranosyl sulfonium cation and 1'-deoxy-D-erythrosyl-3'-sulfate anion. Salacinol showed potent inhibitory activities on several alpha-glucosidases, such as maltase, sucrase, and isomaltase, and the inhibitory effects on serum glucose levels in maltose- and sucrose-loaded rats (in vivo) were found to be more potent than that of acarbose, a commercial alpha-glucosidase inhibitor. (C) 2002 Elsevier Science Ltd. All rights reserved.
  • Synthesis of a nitrogen analogue of salacinol and its alpha-glucosidase inhibitory activity, O Muraoka, S Ying, K Yoshikai, Y Matsuura, E Yamada, T Minematsu, G Tanabe, H Matsuda, M Yoshikawa, CHEMICAL & PHARMACEUTICAL BULLETIN, CHEMICAL & PHARMACEUTICAL BULLETIN, 49(11), 1503 - 1505, Nov. 2001 , Refereed
    Summary:A nitrogen analogue 4 of the naturally occurring sulfonium ion salacinol (1), a potent alpha -glucosidase inhibitor isolated from the Ayruvedic medicine Salacia reticulata, was synthesized and its inhibitory activity against alpha -glucosidase tested. Substitution of the sulfur atom in I with a nitrogen reduced the activity considerably. The solid-state stereostructure of the related compound (5) was determined on the basis of single crystal X-ray measurement.
  • A concise construction of an erythrinane skeleton using Mn(III)/Cu(II)-mediated oxidative radical cyclization of alpha-methylthio amides, A Toyao, S Chikaoka, Y Takeda, O Tamura, O Muraoka, G Tanabe, H Ishibashi, TETRAHEDRON LETTERS, TETRAHEDRON LETTERS, 42(9), 1729 - 1732, Feb. 2001 , Refereed
    Summary:Oxidative radical cyclizations of enamide 3 with Mn(OAc)(3) in the presence of Cu(II) were examined. When Cu(OAc)(2) was used as an additive, 4-acetoxyerythrinane derivative 5 was formed, whereas the use of Cu(OTf)(2) afforded simple erythrinane 6. (C) 2001 Elsevier Science Ltd. All rights reserved.
  • Synthesis and reactivity of beta-sulfonylvinylselenonium salts: a simple stereoselective synthesis of beta-functionalized (Z)-vinyl sulfones, S Watanabe, K Yamamoto, Y Itagaki, T Iwamura, T Iwama, T Kataoka, G Tanabe, O Muraoka, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, (3), 239 - 247, 2001 , Refereed
    Summary:The treatment of alkynylselenonium salt with benzenesulfinic acid in (PrOH)-Pr-i gives (Z)-beta -sulfonylvinylselenonium salts in good yields. The alkenylselenonium salts thus prepared react with nucleophiles such as alkoxides, halides, and acetylides to produce beta -functionalized (Z)-vinyl sulfones in high yields. Furthermore, we succeeded in the simple stereoselective one-step synthesis of various chiral (Z)-beta -alkoxyvinyl sulfones by the use of chiral alcohols.
  • Synthesis and structure of 1-methyl-2,6-bis(electron-withdrawing group)-substituted selenabenzenes, E Honda, T Iwamura, S Watanabe, T Kataoka, O Muraoka, G Tanabe, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, (5), 529 - 536, 2001 , Refereed
    Summary:Selenabenzenes 12a-c with two electron-withdrawing groups (EWGs) at the 2- and 6-positions were synthesized from dihalides 1a, 1b and 1c' via seven steps and isolated as stable compounds at room temperature. According to X-ray structural analysis of the dibenzoyl derivative 12c, the six-membered ring containing a selenium atom is almost planar and the structure of the selenium atom is tetrahedral with four sp(3) hybridized orbitals.
  • Synthesis of 2,3-dihydroinosine derivatives by reduction using BH3-THF., K. Hirota, R. Hattori, H. Sajiki, Y. Monguchi, O. Muraoka, G. Tanabe, Nucleic acids symposium series, Nucleic acids symposium series, 113 - 114, Jan. 01 2000
    Summary:A novel reductive method for the chemical modification of nucleosides is described. Reaction of inosine derivatives with boran-THF resulted in the regioselective reduction of purine ring to afford the corresponding 2,3-dihydroinosine derivatives in moderate yields.
  • A new synthesis of alpha-amino acid thioesters by pummerer reaction of 3-substituted-4-sulfinyl-beta-sultams, T Iwama, T Kataoka, O Muraoka, G Tanabe, JOURNAL OF ORGANIC CHEMISTRY, JOURNAL OF ORGANIC CHEMISTRY, 63(23), 8355 - 8360, Nov. 1998 , Refereed
    Summary:alpha-Amino acid thioesters were synthesized by the Pummerer reaction of 3-substituted-4-sulfinyl-beta-sultams with TFAA. The 3-substituted-4-sulfinyl-beta-sultams were prepared from the corresponding beta-sultams by sulfenylation with diphenyl disulfide followed by m-CPBA oxidation. Diastereoselective synthesis of beta-sultams by 1,3-asymmetric induction in [2 + 2] cycloaddition of a sulfene intermediate and chiral imines in solution-phase was studied, and it was found that N-alkylimines gave better diastereoselectivities than N-aralkylimines. The use of imines derived from (R)- and (S)-alpha-methylbenzylamine followed by separation of the major and minor diastereomers gave enantiopure 3-substituted-N-methylbenzyl-beta-sultams. These beta-sultams were then converted to N-methylbenzyl-alpha-amino acid thioesters via sulfenylation and Pummerer rearrangement with high or complete retention of configuration.
  • Reactions of a beta-sultam ring with Lewis acids via the C-S bond cleavage, T Iwama, M Ogawa, T Kataoka, O Muraoka, G Tanabe, TETRAHEDRON, TETRAHEDRON, 54(31), 8941 - 8974, Jul. 1998 , Refereed
    Summary:Selective C-S bond cleavage of a beta-sultam ring was achieved by the reactions with Lewis acids. Aryl ketones or aldehyde were provided from 3-aryl-beta-sultams whereas beta-sultams bearing a poorly migratory substituent at C-3 gave trans-1,2,3-oxathiazolidine 2-oxides and/or cis-aziridines. These reactions were influenced by the cation-stabilizing capability of C-4 substituents and by the configuration of the substituents at C-3 and C-4. Some 4-alkenyl-3-aryl-beta-sultams underwent tandem intramolecular cyclization to give bicyclo[3.2.1]- and [2.2.1]-gamma-sultams via the processes of C-S bond cleavage, 1,2-aryl shift, cation-olefin cyclization and recombination of the sulfonyl anion. (C) 1998 Elsevier Science Ltd. All rights reserved.
  • Reactions of 1,2-thiazetidine 1,1-dioxides with organometallics: beta-elimination and N-S bond cleavage, T Iwama, T Kataoka, O Muraoka, G Tanabe, TETRAHEDRON, TETRAHEDRON, 54(21), 5507 - 5522, May 1998 , Refereed
    Summary:Reactions of 4-nonsubstituted beta-sultams 1 with methyllithium gave only (E)-vinylsulfonamides 2, whereas 2-aminoethyl sulfones 3 were obtained as minor products by use of methylmagnesium bromide. Reactions of 4-monosubstituted beta-sultams 6 with organolithiums gave (E)-vinylsulfonamides 7 stereoselectively regardless of the configuration of 3- and 4-substituents. Treatment of 4,4-dimethyl-beta-sultam 8a with methylmagnesium bromide and methyllithium provided 2-aminoethyl sulfone 9 and bis-sulfone 10, respectively, and isopropyl phenyl sulfone 11 was obtained by use of phenyllithium or phenylmagnesium bromide. (C) 1998 Elsevier Science Ltd. All rights reserved.
  • Stereoselective reduction of (+/-)-bicyclo[3.3.1]nonane-2,6-dione by microorganisms, M Miyazawa, M Nobata, S Okamura, O Muraoka, G Tanabe, H Kameoka, JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, 71(4), 281 - 284, Apr. 1998 , Refereed
    Summary:The biotransformation of (+/-)-bicyclo[3.3.1]nonane-2,6-dione by Aspergillus niger and Glomerella cingulara was investigated. The diketone was reduced to the ketoalcohol 2-endo-hydroxy-bicyclo[3.3.1]nonane-6-one and the diol endo,endo-bicyclo[3.3.1]nonane-2,6-diol respectively. Endo,endo-bicyclo[3.3.1]nonane-2,6-diol and ketoalcohols produced by G. cingulata had high optical purity, on the other hand, reduction by A. niger yielded optically active (-)-(1R, 2S, 5R, 6S)-bicyclo[3.3.1]nonane-2,6-diol(99.9% e.e.). (C) 1998 SCI.
  • Furan-2(3H)- and -2(5H)-ones .8. Conformation and di-pi-methane reactivity of the 4,7-disubstituted tetrahydroisobenzofuran-1-one system: a mechanistic and exploratory study, O Muraoka, G Tanabe, E Yamamoto, M Ono, T Minematsu, T Kimura, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, (19), 2879 - 2890, Oct. 1997 , Refereed
    Summary:Photoirradiation of cis-and trans-4,7-diphenyl-1,3,4,7-tetrahydroisobenzofuran-1-one cis-and trans-14 and its 4-methyl analogues cis-and trans-15 afford the corresponding di-pi-methane rearrangement products 27, 28 and 24 in moderate yields. MM2 calculations for the cis-and trans-4,7-diphenyl substrates cis-and trans-14 showed that the planar structure is most stable for both compounds and that the molecular energy difference between the planar structure and the boat conformation is small enough for a boat-planar-boat conversion. On the basis of the calculations, the di-pi-methane rearrangement of the compounds 14 and 15 is supposed to proceed via the boat conformation with a pseudoaxial phenyl substituent. An X-ray structure determination of the two diphenyl substrates cis-and trans-14 provides strong support for the validity of the calculations in predicting optimum structures for cis-and trans-disubstituted tetrahydroisobenzofuranone.
  • Convenient synthesis of 2-alkynyl-cyclopropanes and -oxiranes, M Yoshimatsu, S Gotoh, E Gotoh, G Tanabe, O Muraoka, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, (20), 3035 - 3041, Oct. 1997 , Refereed
    Summary:Addition of nucleophiles such as dimethylsulfoxonium methylide and (BuOOLi)-O-t to the conjugate enyne sulfones 4-7, 11-14, 27-28 and 31 occurs at the beta-position to the phenylsulfonyl group to give the corresponding cyclopropanes 15-17 and 19-22 and the oxiranes 33-38 in high yields. The thermal reactions of vinyloxirane 36 show an oxy-Cope rearrangement to give 2-phenylsulfonylphenol 39.
  • Tandem Beckmann and Huisgen-White rearrangement of the 9-azabicyclo[3.3.1]nonan-3-one system .2. The second mode of the rearrangement leading to 6-(prop-l-enyl)piperidin-2-ylacetic acid, a versatile intermediate for the syntheses of piperidine alkaloids (+)-pinidine and (+)-monomorine I, O Muraoka, BZ Zheng, K Okumura, E Tabata, G Tanabe, M Kubo, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, (2), 113 - 119, Jan. 1997 , Refereed
    Summary:The second mode of the Huisgen-White rearrangement of the bicyclic lactam, (-)-2-ethyl-4-oxo-3,10-diazabicyclo[4.3.1]decane (-)-13, leading to cis-[6-(prop-1-enyl)piperidin-2-yl]acetic acid (-)-9a under alkaline conditions is described. A reasonable reaction mechanism accounting for the preferable formation of the (E)-propenyl isomer (E)-9a is presented. Conversions of the olefinic acid 9a into two piperidine alkaloids (+)-pinidine (+)-10 and (-)-dihydropinidine (-)-21, and (-)-cis-2-formyl-6-methylpiperidine (-)-22, a key synthetic intermediate for an ants' trail pheromone (+)-monomorine I (+)-11, are also described.
  • Photochemical behavior of ω-thiabicyclo[3.n.1]alkan-3-one: a mechanistic and exploratory study, O. Muraoka, B.-Z. Zheng, M. Nishimura, G. Tanabe, J. Chem. Soc. , Perkin Trans. 1, J. Chem. Soc. , Perkin Trans. 1, 1996, 2265 - 2270, Aug. 1996 , Refereed
  • Tandem Beckmann and Huisgen-White rearrangement as an alternative to the Baeyer-Villiger oxidation of the bicyclo[3.3.1]nonane system: First asymmetric synthesis of (-)-dihydropalustramic acid. X-ray molecular structure of 2 beta-ethyl-9-phenylsulfonyl-9-azabicyclo[3.3.1]nonan-3-one, O Muraoka, BZ Zheng, K Okumura, G Tanabe, T Momose, CH Eugster, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, (13), 1567 - 1575, Jul. 1996 , Refereed
    Summary:The transformation of the 'fork head ketone' 3b into the corresponding bicyclic lactone 13 via the Beckmann followed by the Huisgen-White rearrangement is described. Application of the method to a homochiral 2-ethyl-substituted bicyclic ketone(+)-3da gave efficiently(-)-dihydropalustramic acid (-)-2a, a degradation product from the alkaloid palustrine 1, in good optical yield.
  • Enantioselective total synthesis of the di-O-methyl ethers of (-)-agatharesinol, (+)-hinokiresinol and (-)-sugiresinol, characteristic norlignans of Coniferae, O Muraoka, BZ Zheng, N Fujiwara, G Tanabe, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1996(5), 405 - 411, Mar. 1996 , Refereed
    Summary:Facile enantioselective syntheses of the di-O-methyl ethers of the norlignans, (-)-agatharesinol (-)-1a, (+)-hinokiresinol (+)-2a and (-)-sugiresinol (-)-3a are described. Grignard addition of vinylmagnesium bromide to an aldimine (-)-13, prepared from the tert-butyl ester 11 and 4-methoxycinnamaldehyde 12, afforded a homochiral vinyl aldehyde, (-)-3-(4-methoxyphenyl)pent-4-enal (-)-14 in >95% ee, which was converted into a diastereoisomeric mixture of 1,3-bis(4-methoxyphenyl)pent-4-enal-ols (3R)-6 by a second Grignard reaction with 4-methoxyphenylmagnesium bromide. Sharpless' asymmetric dihydroxylation of the vinyl alcohols (3R)-6 proceeded diastereoselectively to give the triol of desired relative stereochemistry (2S,3S)-7. This, upon dehydration, afforded (-)-di-O-methylsugiresinol (-)-3b, the subsequent acid-catalysed cyclization of which gave (-)-di-O-methyl agatharesinol (-)-1b, (+)-Di-O-methylhinokiresinol (+)-2b was readily obtained by the dehydration of the vinyl alcohols (3R)-6.
  • FURAN-2(3H)-ONES AND FURAN-2(5H)-ONES .6. DI-PI-METHANE REARRANGEMENT OF THE ALPHA-SUBSTITUTED 4-BENZYLFURAN-2(5H)-ONE SYSTEM, G TANABE, M HIGASHIURA, T MINEMATSU, O MURAOKA, T MOMOSE, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, (11), 1437 - 1443, Jun. 1995 , Refereed
    Summary:The effect of the 'central methane' substitution on the di-pi-methane rearrangement in 4-benzyl-2,5-dihydrofuran-2-ones 8a-d was investigated. Significant enhancement of efficiency in the rearrangement leading in high combined yields to two isomeric products, endo-12, is discussed in terms of both the substituent effects at the benzylic carbon and the restrained features of the ring-enrolled pi-system. The origin of the difference in chemoselectivity compared with that of the 3-benzyl counterpart 5 where a photoarylated product 6 resulted upon photoirradiation was also investigated, and was rationalized by postulating a higher reactivity at the beta-position of the enone system.
  • NORRISH TYPE-I CLEAVAGE OF 9-OXABICYCLO[3.3.1]NONAN-3-ONE - A STRAIGHTFORWARD SYNTHESIS OF (+/-)-(CIS-6-METHYLTETRAHYDROPYRAN-2-YL)ACETIC ACID, A CONSTITUENT OF CIVET, O MURAOKA, M OKUMURA, T MAEDA, LC WANG, G TANABE, CHEMICAL & PHARMACEUTICAL BULLETIN, CHEMICAL & PHARMACEUTICAL BULLETIN, 43(3), 517 - 519, Mar. 1995 , Refereed
    Summary:The photo-reaction of 9-oxabicyclo[3.3.1]nonan-3-one (2) was investigated. Upon irradiation in methanol, the ketone (2) predominantly gave the methanol adduct, 3-hydroxymethyl-9-oxabicyclo[3.3.1]nonan-3-ol (3), accompanied with photo-reduced products, exo- and endo-9-oxabicyclo[3.3.1]nonan-3-ol (4 and 5). Irradiation in water resulted in Norrish type I cleavage to give directly (cis-6-methyltetrahydropyran-2-yl)acetic acid (1), a constituent of civet, in moderate yield.
  • THE NORRISH TYPE-I PHOTO-CLEAVAGE OF (+)-2-BETA-ETHYL-9-AZABICYCLO[3.3.1]NONAN-3-ONE - A SHORT, ENANTIOSELECTIVE FORMAL SYNTHESIS OF (-)-INDOLIZIDINE-223AB, O MURAOKA, K OKUMURA, T MAEDA, G TANABE, T MOMOSE, TETRAHEDRON-ASYMMETRY, TETRAHEDRON-ASYMMETRY, 5(3), 317 - 320, Mar. 1994 , Refereed
    Summary:The enantioselective alkylation of the ''fork head ketone'' (1) followed by the Norrish Type I photo-cleavage provided the short enantioselective synthesis of (-)-indolizidine 223AB (4).
  • THE TANDEM BECKMANN AND HUISGEN-WHITE REARRANGEMENT AS AN ALTERNATIVE TO THE BAEYER-VILLIGER OXIDATION OF THE 9-AZABICYCLO[3.3.1]NONAN-3-ONE SYSTEM - A FACILE ROUTE TO (+/-)-DIHYDROPALUSTRAMIC ACID, T MOMOSE, K OKUMURA, H TSUJIMORI, K INOKAWA, G TANABE, O MURAOKA, Y SASAKI, CH EUGSTER, HETEROCYCLES, HETEROCYCLES, 36(1), 7 - 11, Jan. 1993 , Refereed
    Summary:The transformation of the ''fork head ketone'' (1) into the corresponding bicyclic lactone (4) via the Beckmann followed by the Huisgen-White Rearrangement is described. An alpha-ethyl-substituted bicyclic ketone (5) was converted efficiently to dihydropalustramic acid (6), a degradation product from the alkaloid palustrine.
  • Chalcones as Synthetic Intermediates. A Facile Route to (±)-Magnosalicin, an Antiallergy Neolignan, Osamu Muraoka, Tomoaki Sawada, Eiichiro Morimoto, Genzoh Tanabe, Chemical and Pharmaceutical Bulletin, Chemical and Pharmaceutical Bulletin, 41(4), 772 - 774, 1993 , Refereed
    Summary:A facile synthetic route was developed to (+)-magnosalicin (1), a new type of neolignan with antiallergy activity isolated from Magnolia salicifolia, starting from a chalcone, (3). © 1993, The Pharmaceutical Society of Japan. All rights reserved.
  • A breakthrough for the photochemical arylation in the 3-(phenylmethyl)-2(5H)-furanone system leading to the tetrahydroindenofuranone system, O. Muraoka, G. Tanabe, K. Sano, T. Momose, Heterocycles, Heterocycles, 34, 1093 - 1096, May 1992 , Refereed
  • 1ST ASYMMETRIC-SYNTHESIS OF (-)-SUGIRESINOL DIMETHYL ETHER, O MURAOKA, N FUJIWARA, G TANABE, T MOMOSE, TETRAHEDRON-ASYMMETRY, TETRAHEDRON-ASYMMETRY, 2(5), 357 - 358, 1991 , Refereed
    Summary:Efficient enantioselective synthesis of (-)-sugiresinol dimethyl ether was accomplished based upon two asymmetric induction processes: asymmetric beta-alkylation of alpha,beta-unsaturated aldimines and enantioselective dihydroxylation of olefins.
  • ACCENTUATION OF THE DI-PI-METHANE REACTIVITY BY CENTRAL CARBON SUBSTITUTION IN THE 4-(PHENYLMETHYL)-2(5H)-FURANONE SYSTEM, O MURAOKA, G TANABE, T MOMOSE, HETEROCYCLES, HETEROCYCLES, 31(9), 1589 - 1592, Sep. 1990 , Refereed
  • THE DI-PI-METHANE REARRANGEMENT IN 3,4-DIBENZYL-2(5H)-FURANONE, T MOMOSE, G TANABE, H TSUJIMORI, M HIGASHIURA, IMANISHI, I, K KANAI, HETEROCYCLES, HETEROCYCLES, 29(2), 257 - 262, Feb. 1989 , Refereed
  • Discovery of new benzhydrol biscarbonate esters as potent and selective apoptosis inducers of human melanomas bearing the activated ERK pathway: SAR studies on an ERK MAPK signaling modulator, ACA-28., Ryosuke Satoh, Naoya Hamada, Ami Yamada, Yuki Kanda, Fumihiro Ishikawa, Teruaki Takasaki, Genzoh Tanabe, Reiko Sugiura, Bioorganic chemistry, Bioorganic chemistry, 103, 104137 - 104137, Jul. 25 2020 , Refereed
    Summary:The recent discovery that an ERK signaling modulator [ACA-28 (2a)] preferentially kills human melanoma cell lines by inducing ERK-dependent apoptosis has generated significant interest in the field of anti-cancer therapy. In the first SAR study on 2a, here, we successfully developed candidates (2b, 2c) both of which induce more potent and selective apoptosis towards ERK-active melanoma cells than 2a, thus revealing the structural basis for inducing the ERK-dependent apoptosis and proposing the therapeutic prospect of these candidates against ERK-dependent cancers represented by melanoma.
  • First Total Syntheses of Amorfrutin C and pseudo-Amorfrutin A, Qi Miao, Yunzhi Li, Jinyi Xu, Aijun Lin, Genzoh Tanabe, Osamu Muraoka, Xiaoming Wu, Weijia Xie, European Journal of Organic Chemistry, European Journal of Organic Chemistry, 2018(12), 1443 - 1448, Mar. 29 2018 , Refereed
    Summary:Syntheses of amorfrutin C, a natural product with potent antitumor activity, as well as pseudo-amorfrutin A were accomplished. Protected 2,4-dihydroxybenzoic acid derivative 5 was used as a common synthetic intermediate. The introduction of a prenyl moiety to 5 was achieved through bromination followed by a CuCN-meditated alkylation reaction. Interestingly, N-bromosuccinimide promoted monobromination at the 6-position, leading to pseudo-amorfrutin A 1,3-dibromo-5,5-dimethylhydantoin triggered bromination at both the 6- and 8-positions, leading to naturally occurring amorfrutin C.
  • An efficient gram-scale total synthesis of neoponkoranol as potent α-glucosidase inhibitor, Wang Zihao, Huang Yuhao, Liu Dan, Xu Jinyi, Tanabe Genzoh, Muraoka Osamu, Wu Xiaoming, Xie Weijia, Current Organic Chemistry, Current Organic Chemistry, 22(9), 930 - 935, 2018 , Refereed
    Summary:Background: Neoponkoranol is one of de-O-sulfonated sulfonium salts isolated from Genus Salacia showing potent inhibitory activities against α-glucosidases. In previously reported synthetic strategies, the two key coupling partners should be firstly constructed from different starting materials and the following coupling reaction is usually time-consuming. Thus, a more efficient and scalable synthetic protocol would be necessary for further SAR studies of this bioactive natural product. Objective: Based on our previous synthetic studies on this series of natural products, the aim of the present study is to develop a novel total synthesis of neoponkoranol in a divergent and efficient way starting from inexpensive commercially available D-glucose. This is the first report of gram-scale synthesis of neoponkoranol. Method and Results: Unlike all other reported strategies, the two coupling partners epoxide (14) and thiosugar (19) were firstly synthesized from an identical intermediate diol (12) which could be easily obtained in 3 steps from D-glucose. Notably, the construction of 14 and 19 could be achieved without any purification process. The subsequent acid mediated coupling reaction between resulted coupling partners was accomplished in only 4 hours while previous strategies usually took several days to complete the process. A gram-scale quantity of coupling reaction was then conducted under the same reacting condition and the desired sulfonium salt was isolated without any loss of the yield. Conclusion: The newly developed scalable synthesis of neoponkoranol provided a good opportunity for further pharmaceutical studies on this bioactive natural product.
  • Visualizing the Adenylation Activities and Protein-Protein Interactions of Aryl Acid Adenylating Enzymes, Fumihiro Ishikawa, Shota Kasai, Hideaki Kakeya, Genzoh Tanabe, CHEMBIOCHEM, CHEMBIOCHEM, 18(22), 2199 - 2204, Nov. 2017 , Refereed
    Summary:Structural and activity studies have revealed the dynamic and transient actions of carrier protein (CP) activity in primary and secondary metabolic pathways. CP-mediated interactions play a central role in nonribosomal peptide biosynthesis, as they serve as covalent tethers for amino acid and aryl acid substrates and enable the growth of peptide intermediates. Strategies are therefore required to study protein-protein interactions efficiently. Herein, we describe activity-based probes used to demonstrate the protein-protein interactions between aryl CP (ArCP) and aryl acid adenylation (A) domains as well as the substrate specificities of the aryl acid Adomains. If coupled with in-gel fluorescence imaging, this strategy allows visualization of the protein-protein interactions required to recognize and transfer the substrate to the partner ArCP. This technique has potential for the analysis of protein-protein interactions within these biosynthetic enzymes at the molecular level and for use in the combinatorial biosynthesis of new nonribosomal peptides.
  • A Chemoproteomics Approach to Investigate Phosphopantetheine Transferase Activity at the Cellular Level, Sho Konno, Fumihiro Ishikawa, Takehiro Suzuki, Naoshi Dohmae, Hideaki Kakeya, Genzoh Tanabe, CHEMBIOCHEM, CHEMBIOCHEM, 18(18), 1855 - 1862, Sep. 2017 , Refereed
    Summary:Phosphopantetheinylation is an essential post-translational protein modification to primary and secondary metabolic pathways that ensures bacterial cell viability and virulence, and it is used in the production of many pharmaceuticals. Traditional methods have not provided a comprehensive understanding of these modifications. By using chemical proteomic probes for adenylation and thiolation domains in nonribosomal peptide synthetases (NRPSs), chemoproteomics has been applied to survey and validate the cellular activity of 4-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-N-(4-methoxypyridin-2-yl)piperazine-1-carbothioamide (ML267), which is a potent and selective small-molecule 4-phosphopantetheinyl transferase (PPTase) inhibitor that attenuates secondary metabolism and viability of bacterial cells. ML267 inhibited Sfp-type PPTase and antagonized phosphopantetheinylation in cells, which resulted in a decrease in phosphopantetheinylated NRPSs and the attenuation of Sfp-PPTase-dependent metabolite production. These results indicate that this chemoproteomics platform should enable a precise interpretation of the cellular activities of Sfp-type PPTase inhibitors.
  • Total syntheses of the aromatase inhibitors, mammeasins C and D, from Thai medicinal plant Mammea siamensis, Genzoh Tanabe, Nozomi Tsutsui, Kanae Shibatani, Shinsuke Marumoto, Fumihiro Ishikawa, Kiyofumi Ninomiya, Osamu Muraoka, Toshio Morikawa, TETRAHEDRON, TETRAHEDRON, 73(30), 4481 - 4486, Jul. 2017 , Refereed
    Summary:The first total syntheses of the geranylated pyranocoumarins, mameasins C (1) and D (2), aromatase inhibitors isolated from the flowers of Mammea siamensis, were accomplished in five steps, starting from phloroglucinol 3. In this strategy, the characteristic pyran ring-fused coumarin core of 1 and 2 was effectively constructed by Friedel-Crafts acylation of 3, followed by Reformatsky reaction of the resultant ketone to give a key coumarin intermediate 9. Compound 9 was converted to targets 1 and 2 in a stepwise manner by successive C-acylation and O-geranylation, followed by a [1,3]-sigmatropic geranyl shift. Furthermore, screening of intermediates obtained in the synthetic pathway to 1 and 2 revealed that de-geranylated pyranocoumarins (10 and 11) show superior aromatase inhibitory activity as compared to the natural products 1 and 2. (C) 2017 Elsevier Ltd. All rights reserved.
  • Identification of ACA-28, a 1 '-acetoxychavicol acetate analogue compound, as a novel modulator of ERK MAPK signaling, which preferentially kills human melanoma cells, Ryosuke Satoh, Kanako Hagihara, Kazuki Matsuura, Yoshiaki Manse, Ayako Kita, Tatsuki Kunoh, Takashi Masuko, Mariko Moriyama, Hiroyuki Moriyama, Genzoh Tanabe, Osamu Muraoka, Reiko Sugiura, GENES TO CELLS, GENES TO CELLS, 22(7), 608 - 618, Jul. 2017 , Refereed
    Summary:The extracellular signal-regulated kinase (ERK) signaling pathway is essential for cell proliferation and is frequently deregulated in human tumors such as melanoma. Melanoma remains incurable despite the use of conventional chemotherapy; consequently, development of new therapeutic agents for melanoma is highly desirable. Here, we carried out a chemical genetic screen using a fission yeast phenotypic assay and showed that ACA-28, a synthetic derivative of 10-acetoxychavicol acetate (ACA), which is a natural ginger compound, effectively inhibited the growth of melanoma cancer cells wherein ERK MAPK signaling is hyperactivated due to mutations in the upstream activating regulators. ACA-28 more potently inhibited the growth of melanoma cells than did the parental compound ACA. Importantly, the growth of normal human epidermal melanocytes (NHEM) was less affected by ACA-28 at the same 50% inhibitory concentration. In addition, ACA-28 specifically induced apoptosis in NIH/3T3 cells which were oncogenically transformed with human epidermal growth factor receptor-2 (HER2/ErbB2), but not in the parental cells. Notably, the ACA-28-induced apoptosis in melanoma and HER2-transformed cells was abrogated when ERK activation was blocked with a specific MEK inhibitor U0126. Consistently, ACA-28 more strongly stimulated ERK phosphorylation in melanoma cells, as compared in NHEM. ACA-28 might serve as a promising seed compound for melanoma treatment.
  • Mangiferin, a novel nuclear factor kappa B-inducing kinase inhibitor, suppresses metastasis and tumor growth in a mouse metastatic melanoma model., Tomoya Takeda, Masanobu Tsubaki, Kotaro Sakamoto, Eri Ichimura, Aya Enomoto, Yuri Suzuki, Tatsuki Itoh, Motohiro Imano, Genzoh Tanabe, Osamu Muraoka, Hideaki Matsuda, Takao Satou, Shozo Nishida, Toxicology and applied pharmacology, Toxicology and applied pharmacology, 306, 105 - 12, Sep. 01 2016 , Refereed
    Summary:Advanced metastatic melanoma, one of the most aggressive malignancies, is currently without reliable therapy. Therefore, new therapies are urgently needed. Mangiferin is a naturally occurring glucosylxanthone and exerts many beneficial biological activities. However, the effect of mangiferin on metastasis and tumor growth of metastatic melanoma remains unclear. In this study, we evaluated the effect of mangiferin on metastasis and tumor growth in a mouse metastatic melanoma model. We found that mangiferin inhibited spontaneous metastasis and tumor growth. Furthermore, mangiferin suppressed the nuclear translocation of nuclear factor kappa B (NF-κB) and expression of phosphorylated NF-κB-inducing kinase (NIK), inhibitor of kappa B kinase (IKK), and inhibitor of kappa B (IκB) and increases the expression of IκB protein in vivo. In addition, we found that mangiferin inhibited the expression of matrix metalloproteinases (MMPs) and very late antigens (VLAs) in vivo. Mangiferin treatment also increased the expression of cleaved caspase-3, cleaved Poly ADP ribose polymerase-1 (PARP-1), p53 upregulated modulator of apoptosis (PUMA), p53, and phosphorylated p53 proteins, and decreased the expression of Survivin and Bcl-associated X (Bcl-xL) proteins in vivo. These results indicate that mangiferin selectivity suppresses the NF-κB pathway via inhibition of NIK activation, thereby inhibiting metastasis and tumor growth. Importantly, the number of reported NIK selective inhibitors is limited. Taken together, our data suggest that mangiferin may be a potential therapeutic agent with a new mechanism of targeting NIK for the treatment of metastatic melanoma.
  • Quantitative Determination of Alkaloids in Lotus Flower (Flower Buds of Nelumbo nucifera) and Their Melanogenesis Inhibitory Activity, Toshio Morikawa, Niichiro Kitagawa, Genzoh Tanabe, Kiyofumi Ninomiya, Shuhei Okugawa, Chiaki Motai, Iyori Kamei, Masayuki Yoshikawa, I-Jung Lee, Osamu Muraoka, MOLECULES, MOLECULES, 21(7), 931, Jul. 2016 , Refereed
    Summary:A quantitative analytical method for five aporphine alkaloids, nuciferine (1), nornuciferine (2), N-methylasimilobine (3), asimilobine (4), and pronuciferine (5), and five benzylisoquinoline alkaloids, armepavine (6), norarmepavine (7), N-methylcoclaurine (8), coclaurine (9), and norjuziphine (10), identified as the constituents responsible for the melanogenesis inhibitory activity of the extracts of lotus flowers (the flower buds of Nelumbo nucifera), has been developed using liquid chromatography-mass spectrometry. The optimum conditions for separation and detection of these 10 alkaloids were achieved on a NAP column, a reversed-phase column with naphthylethyl group-bonded silica packing material, with CH3CN-0.2% aqueous acetic acid as the mobile phase and using mass spectrometry equipped with a positive-mode electrospray ionization source. According to the protocol established, distributions of these 10 alkaloids in the petal, receptacle, and stamen parts, which were separated from the whole flower, were examined. As expected, excellent correlations were observed between the total alkaloid content and melanogenesis inhibitory activity. Among the active alkaloids, nornuciferine (2) was found to give a carbamate salt (2) via formation of an unstable carbamic acid (2) by absorption of carbon dioxide from the air.
  • Mangiferin induces apoptosis in multiple myeloma cell lines by suppressing the activation of nuclear factor kappa B-inducing kinase., Tomoya Takeda, Masanobu Tsubaki, Toshiki Kino, Misa Yamagishi, Megumi Iida, Tatsuki Itoh, Motohiro Imano, Genzoh Tanabe, Osamu Muraoka, Takao Satou, Shozo Nishida, Chemico-biological interactions, Chemico-biological interactions, 251, 26 - 33, May 05 2016 , Refereed
    Summary:Mangiferin is a naturally occurring glucosyl xanthone, which induces apoptosis in various cancer cells. However, the molecular mechanism underlying mangiferin-induced apoptosis has not been clarified thus far. Therefore, we examined the molecular mechanism underlying mangiferin-induced apoptosis in multiple myeloma (MM) cell lines. We found that mangiferin decreased the viability of MM cell lines in a concentration-dependent manner. We also observed an increased number of apoptotic cells, caspase-3 activation, and a decrease in the mitochondrial membrane potential. In addition, mangiferin inhibited the nuclear translocation of nuclear factor kappa B (NF-κB) and expression of phosphorylated inhibitor kappa B (IκB) and increased the expression of IκB protein, whereas no changes were observed in the phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase 1/2 (JNK1/2), and mammalian target of rapamycin (mTOR). The molecular mechanism responsible for mangiferin-induced inhibition of nuclear translocation of NF-κB was a decrease in the expression of phosphorylated NF-κB-inducing kinase (NIK). Moreover, mangiferin decreased the expression of X-linked inhibitor of apoptosis protein (XIAP), survivin, and Bcl-xL proteins. Knockdown of NIK expression showed results similar to those observed with mangiferin treatment. Our results suggest that mangiferin induces apoptosis through the inhibition of nuclear translocation of NF-κB by suppressing NIK activation in MM cell lines. Our results provide a new insight into the molecular mechanism of mangiferin-induced apoptosis. Importantly, since the number of reported NIK inhibitors is limited, mangiferin, which targets NIK, may be a potential anticancer agent for the treatment of MM.
  • Synthesis of Azepines via a [6+1] Annulation of Ynenitriles with Refornnatsky Reagents, Mitsuhiro Yoshimatsu, Miki Tanaka, Yu Fujimura, Yukiteru Ito, Yusuke Goto, Yuka Kobayashi, Hiroaki Wasada, Noriyuki Hatae, Genzoh Tanabe, Osamu Muraoka, JOURNAL OF ORGANIC CHEMISTRY, JOURNAL OF ORGANIC CHEMISTRY, 80(19), 9480 - 9494, Oct. 2015 , Refereed
    Summary:A protocol for the direct synthesis of azepines using a hafnium(III)-catalyzed [6 + 1] annulation of N-tethered ynenitriles with Reformatsky reagents is reported. A broad range of 3-amino-2,7-dihydro-1H-azepine-4-carboxylates 4aa-4he were obtained in high yields and with excellent functional group tolerance. The copper-mediated reactions of isolable Blaise intermediates (enamino esters 3), uniquely underwent beta-endo cydization to afford the beta-2,5-dihydropyrrolyl alpha,beta-unsaturated esters 5aa-5fc, which exhibit anticancer activity.
  • Structure-activity relationship studies on acremomannolipin A, the potent calcium signal modulator with a novel glycolipid structure 3: Role of the length of alditol side chain, Nozomi Tsutsui, Genzoh Tanabe, Nao Morita, Yoshitomo Okayama, Ayako Kita, Reiko Sugiura, Osamu Muraoka, BIOORGANIC & MEDICINAL CHEMISTRY, BIOORGANIC & MEDICINAL CHEMISTRY, 23(13), 3761 - 3773, Jul. 2015 , Refereed
    Summary:Five homologs of a novel glycolipid acremomannolipin A (1a), the potential Ca2+ signal modulator isolated from Acremonium strictum, bearing alditols of different length (1g-1k) were synthesized by a stereoselective beta-mannosylation of appropriately protected mannosyl sulfoxide (2) with five alditols (1g: C2, 1h: C3, 1i: C4, 1j: C5 and 1k: C7 units), and their potential in modulating Ca2+ signaling were evaluated. Homologs with alditols of more than 4 carbons (1i, 1j and 1k) were equally or more potent than the parent compound (1a) regardless of the length of the alditol chain. Whereas activities of two homologs with shorter chains (1g and 1h) decreased to a considerable extent. The results indicated that the length of the alditol side chain was a crucial determinant for the potent calcium signal modulating activity. (C) 2015 Elsevier Ltd. All rights reserved.
  • Total Synthesis of 4,5-Didehydroguadiscine: A Potent Melanogenesis Inhibitor from the Brazilian Medicinal Herb, Hornschuchia obliqua, Genzoh Tanabe, Youta Sugano, Miki Shirato, Naoki Sonoda, Nozomi Tsutsui, Toshio Morikawa, Kiyofumi Ninomiya, Masayuki Yoshikawa, Osamu Muraoka, JOURNAL OF NATURAL PRODUCTS, JOURNAL OF NATURAL PRODUCTS, 78(7), 1536 - 1542, Jul. 2015 , Refereed
    Summary:The first total Synthesis of the 7,7-dimethylaporphinoid, 4,5-didehydroguadiscine (6), originally isolated from the stems and roots of Hornschuchia oblique (Annonaceae), was achieved by the condensation of homopiperonylamine (7) with an alpha,alpha-dimethylphenylacetic acid derivative (8) and subsequent Pschorr reaction of the resulting benzylisoquinoline intermediate (22). The reported C-13 NMR data were partially revised on the basis of the analysis of HMBC spectra measured under different conditions. The melanogenesis inhibitory activity (IC50 = 4.7 mu M) of 6 was 40 times stronger than that of arbutin (174 mu M), which was used as reference standard. Furthermore, 6 was the most potent natural melanogenesis inhibitor Within this class of compounds.
  • Salacinol and Related Analogs: New Leads for Type 2 Diabetes Therapeutic Candidates from the Thai Traditional Natural Medicine Salacia chinensis, Toshio Morikawa, Junji Akaki, Kiyofumi Ninomiya, Eri Kinouchi, Genzoh Tanabe, Yutana Pongpiriyadacha, Masayuki Yoshikawa, Osamu Muraoka, NUTRIENTS, NUTRIENTS, 7(3), 1480 - 1493, Mar. 2015 , Refereed
    Summary:The antidiabetic effect of a hot water extract of stems of Salacia chinensis (SCE) was evaluated in vivo in KK-A(y) mice, a typical type 2 diabetes mellitus mice model. Administration of CE-2 dietary feed containing 0.25 and/or 0.50% of SCE for three weeks to KK-A(y) mice significantly suppressed the elevation of both blood glucose and HbA1c levels without significant changes in body weight or food intake. Glucose tolerance was improved by administration to KK-A(y) mice for 27 days of AIN93M purified dietary feed containing 0.12% of SCE. No suppressive effect with respect to HbA1c level was observed when AIN93M/Glc dietary feed in which all digestible glucides were replaced with glucose was administered with SCE. Thus, alpha-glucosidase inhibitory activity approved as the mechanism of action of the antidiabetic effect of SCE by in vitro investigation was reconfirmed also in in vivo studies. Evaluation of the alpha-glucosidase inhibitory activity of the active constituents, salacinol (1), kotalanol (3), and neokotalanol (4), by employing human alpha-glucosidases revealed that these compounds inhibited them as potently (IC50 = 3.9-4.9 mu M for maltase) as they inhibited rat small intestinal alpha-glucosidase. The principal sulfonium constituents (1-4) were highly stable in an artificial gastric juice. In addition, 1-4 were hardly absorbed from the intestine in an experiment using the in situ rat ligated intestinal loop model. The results indicate that these sulfoniums are promising leads for a new type of anti-diabetic agents.
  • Construction of 3,6-Anhydrohexosides via Intramolecular Cyclization of Triflates and Its Application to the Synthesis of Natural Product Isolated from Leaves of Sauropus rostratus, Long Liu, Cheng-Qian Wang, Dan Liu, Wei-Gang He, Jin-Yi Xu, Ai-Jun Lin, He-Quan Yao, Genzoh Tanabe, Osamu Muraoka, Wei-Jia Xie, Xiao-Ming Wu, ORGANIC LETTERS, ORGANIC LETTERS, 16(19), 5004 - 5007, Oct. 2014 , Refereed
    Summary:A novel synthetic approach to construct various 3,6-anhydrohexosides via an intramolecular cyclization of corresponding triflates is described. The nucleophilic attack from C3 p-methoxybenzylated hydroxyl to C6 trifluoromethanesulfonate on triflate structures triggered the cyclization reaction to provide 3,6-anhydrohexosides in excellent yields, making the strategy more efficient with respect to the reported protocols. By applying this methodology, a concise first total synthesis of natural product isolated from leaves of Sauropus rostratus was accomplished.
  • Structure-activity relationship studies on acremomannolipin A, the potent calcium signal modulator with a novel glycolipid structure 2: Role of the alditol side chain stereochemistry, Nozomi Tsutsui, Genzoh Tanabe, Genki Gotoh, Nao Morita, Naohisa Nomura, Ayako Kita, Reiko Sugiura, Osamu Muraoka, BIOORGANIC & MEDICINAL CHEMISTRY, BIOORGANIC & MEDICINAL CHEMISTRY, 22(3), 945 - 959, Feb. 2014 , Refereed
    Summary:Five alditol analogs 1b-1f of a novel glycolipid acremomannolipin A (1a), the potential Ca2+ signal modulator isolated from Acremonium strictum, were synthesized by employing a stereoselective beta-mannosylation of appropriately protected mannose with five hexitols with different stereochemistry, and their potential on modulating Ca2+ signaling were evaluated. All these analogs were more potent compared to the original compound 1a, and proved that mannitol stereochemistry of 1a was not critical for the potent calcium signal modulating. (C) 2014 Elsevier Ltd. All rights reserved.
  • Practical synthesis of neoponkoranol and its related sulfonium salt, an optimised protocol using isopropylidene as an effective protecting group, Dan Liu, Weijia Xie, Long Liu, Jinyi Xu, Hequan Yao, Genzoh Tanabe, Osamu Muraoka, Xiaoming Wu, JOURNAL OF CHEMICAL RESEARCH, JOURNAL OF CHEMICAL RESEARCH, (12), 715 - 719, Dec. 2013 , Refereed
    Summary:A practical synthesis of neoponkoranol and its related sulfonium salt as potent a-glucosidase inhibitors has been developed in which the key step of coupling reaction was optimised by using isopropylidene as an effective protecting group. The characteristic intramolecular cyclisation of the coupling precursor previously encountered as a side reaction has not been detected and coupling yields were dramatically improved in the present study.
  • Total synthesis of neokotalanol, a potent alpha-glucosidase inhibitor isolated from Salacia reticulata, Xie Wei-Jia, Tanabe Genzoh, Tsutsui Nozomi, Wu Xiao-Ming, Muraoka Osamu, CHINESE JOURNAL OF NATURAL MEDICINES, CHINESE JOURNAL OF NATURAL MEDICINES, 11(6), 676 - 683, Nov. 2013 , Refereed
    Summary:Neokotalanol, a potent alpha-glucosidase inhibitor isolated from Salacia reticulata, was synthesized through a key coupling reaction between a perbenzylated thiosugar and an appropriately protected perseitol triflate derived from D-mannose. This key step was found to be quite temperature dependent, and a simultaneous cyclization of the triflate leading to a characteristic 2,4,7-trioxabicyclo[4.2.1]nonane system was detected.
  • Stereoselective total synthesis of acremomannolipin A and its anomer, the potent calcium signal modulators with a novel glycolipid structure: role of the stereochemistry at the anomeric center on the activity, Nozomi Tsutsui, Genzoh Tanabe, Genki Gotoh, Ayako Kita, Reiko Sugiura, Osamu Muraoka, TETRAHEDRON, TETRAHEDRON, 69(47), 9917 - 9930, Nov. 2013
    Summary:A full account of stereoselective total synthesis of a novel glycolipid, acremomannolipin A (1), the potent calcium signal modulator isolated from Acremonium strictum, by employing the stereoselective beta-mannosylation of 4,6-O-benzylidene-protected mannosyl sulfoxide with D-mannitol as the key reaction is described. The alpha-anomer (epi-1) of 1 was also synthesized selectively. The calcium modulating activity was reduced upon inversion of the configuration at the anomeric center, indicating that the beta-configuration of the mannose moiety is preferable for the activity. (C) 2013 Elsevier Ltd. All rights reserved.
  • Clostridium scindens: a human gut microbe with a high potential to convert glucocorticoids into androgens, Jason M. Ridlon, Shigeo Ikegawa, Joao M. P. Alves, Biao Zhou, Akiko Kobayashi, Takashi Iida, Kuniko Mitamura, Genzoh Tanabe, Myrna Serrano, Ainee De Guzman, Patsy Cooper, Gregory A. Buck, Phillip B. Hylemon, JOURNAL OF LIPID RESEARCH, JOURNAL OF LIPID RESEARCH, 54(9), 2437 - 2449, Sep. 2013 , Refereed
    Summary:Clostridium scindens American Type Culture Collection 35704 is capable of converting primary bile acids to toxic secondary bile acids, as well as converting glucocorticoids to androgens by side-chain cleavage. The molecular structure of the side-chain cleavage product of cortisol produced by C. scindens was determined to be 11 beta-hydroxyandrost-4-ene-3,17-dione (11 beta-OHA) by high-resolution mass spectrometry, H-1 and C-13 NMR spectroscopy, and X-ray crystallography. Using RNA-Seq technology, we identified a cortisol-inducible (similar to 1,000-fold) operon (des ABCD) encoding at least one enzyme involved in anaerobic side-chain cleavage. The des C gene was cloned, overexpressed, purified, and found to encode a 20 alpha-hydroxysteroid dehydrogenase (HSDH). This operon also encodes a putative "transketolase" (des AB) hypothesized to have steroid-17,20-desmolase/oxidase activity, and a possible corticosteroid transporter (des D). RNA-Seq data suggests that the two-carbon side chain of glucocorticords may feed into the pentose-phosphate pathway and are used as a carbon source. The 20 alpha-HSDH is hypothesized to function as a metabolic "rheostat" controlling rates of side-chain cleavage. Phylogenetic analysis suggests this operon is rare in nature and the des C gene evolved from a gene encoding threonine dehydrogenase.jlr The physiological effect of 11 beta-OHAD on the host or other gut microbes is currently unknown.
  • Alkaloid constituents from flower buds and leaves of sacred lotus (Nelumbo nucifera, Nymphaeaceae) with melanogenesis inhibitory activity in B16 melanoma cells, Seikou Nakamura, Souichi Nakashima, Genzo Tanabe, Yoshimi Oda, Nami Yokota, Katsuyoshi Fujimoto, Takahiro Matsumoto, Rika Sakuma, Tomoe Ohta, Keiko Ogawa, Shino Nishida, Hisako Miki, Hisashi Matsuda, Osamu Muraoka, Masayuki Yoshikawa, BIOORGANIC & MEDICINAL CHEMISTRY, BIOORGANIC & MEDICINAL CHEMISTRY, 21(3), 779 - 787, Feb. 2013 , Refereed
    Summary:Methanolic extracts from the flower buds and leaves of sacred lotus (Nelumbo nucifera, Nymphaeaceae) were found to show inhibitory effects on melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. From the methanolic extracts, a new alkaloid, N-methylasimilobine N-oxide, was isolated together with eleven benzylisoquinoline alkaloids. The absolute stereostructure of the new alkaloid was determined from chemical and physicochemical evidence. Among the constituents isolated, nuciferine, N-methylasimilobine, (-)-lirinidine, and 2-hydroxy-1-methoxy-6a, 7-dehydroaporphine showed potent inhibition of melanogenesis. Comparison of the inhibitory activities of synthetic related alkaloids facilitated characterization of the structure-activity relationships of aporphine-and benzylisoquinoline-type alkaloids. In addition, 3-30 mu M nuciferine and N-methylasimilobine inhibited the expression of tyrosinase mRNA, 3-30 mu M N-methylasimilobine inhibited the expression of TRP-1 mRNA, and 10-30 mu M nuciferine inhibited the expression of TRP-2 mRNA. (C) 2012 Elsevier Ltd. All rights reserved.
  • The first total synthesis of acremomannolipin A, the potential Ca2+ signal modulator with a characteristic glycolipid structure, isolated from the filamentous fungus Acremonium strictum, Nozomi Tsutsui, Genzoh Tanabe, Ayako Kita, Reiko Sugiura, Osamu Muraoka, TETRAHEDRON LETTERS, TETRAHEDRON LETTERS, 54(6), 451 - 453, Feb. 2013
    Summary:The first total synthesis of acremomannolipin A, the potential Ca2+ signal modulator isolated from Acremonium strictum, was achieved by employing the characteristic stereoselective beta-mannosylation of 4,6-O-benzylidene-protected mannosyl sulfoxide with a D-mannitol derivative in the presence of trifluoromethanesulfonic anhydride as the key reaction. (C) 2012 Elsevier Ltd. All rights reserved.
  • Total synthesis of neokotalanol, a potent α-glucosidase inhibitor isolated from Salacia reticulata, Wei-Jia Xie, Genzoh Tanabe, Nozomi Tsutsui, Xiao-Ming Wu, Osamu Muraoka, Chinese Journal of Natural Medicines, Chinese Journal of Natural Medicines, 11(6), 676 - 683, 2013 , Refereed
    Summary:Neokotalanol, a potent α-glucosidase inhibitor isolated from Salacia reticulata, was synthesized through a key coupling reaction between a perbenzylated thiosugar and an appropriately protected perseitol triflate derived from D-mannose. This key step was found to be quite temperature dependent, and a simultaneous cyclization of the triflate leading to a characteristic 2,4,7-trioxabicyclo[4.2.1]nonane system was detected. © 2013 China Pharmaceutical University.
  • Copper-Catalyzed Complete Regio- and Stereoselective Cyclization of 1-Aryl-3-sulfanyl-4-oxahepta-1,6-diynes Triggered by Alkynylation, Mitsuhiro Yoshimatsu, Hitomi Sasaki, Yuko Sugimoto, Yuya Nagase, Genzoh Tanabe, Osamu Muraoka, ORGANIC LETTERS, ORGANIC LETTERS, 14(12), 3190 - 3193, Jun. 2012 , Refereed
    Summary:Copper(I)-catalyzed alkynylation-cyclization of 4-oxahepta-1,6-diynes 1 with a wide variety of terminal alkynes proceeded to give (3E,4Z)-3-(phenylsulfanylmethylene)-4-(2-propynylidene)tetrahydrofuran-2-yl]benzenes 2aa-he in high yields with complete regio- and stereoselectivity.
  • Synthesis of 3-methyl- and 3,4-dimethylfurans using alkoxide, thiolate, and phenoxide-mediated cyclization of 4-oxahepta-1,6-diynes bearing sulfur and selenium functional groups, Nami Takahashi, Yuya Nagase, Genzoh Tanabe, Osamu Muraoka, Mitsuhiro Yoshimatsu, TETRAHEDRON, TETRAHEDRON, 68(5), 1566 - 1580, Feb. 2012 , Refereed
    Summary:We have reported sodium alkoxide- or aryloxide-mediated cyclization of 4-oxahepta-1,6-diynes bearing the phenylsulfanyl group 1a-d. The reactions with diverse sodium alkoxides and aryloxide produced 4-alkoxymethyl- and 4-aryloxymethylfurans 2aa-2db in good to high yields. Although reactions with sodium benzenethiolate yielded 3,4-bis(phenylsulfanylmethyl)furans 5a-g, they readily desulfanylated in the presence of tributyltin hydride/AIBN to give the 3-methyl- and 3,4-dimethylfuran derivatives 6a-g. This method's utility was demonstrated by the synthesis of tetrahydronaphthalenyl furan derivatives bearing alkoxy- and aryloxymethyl substituents. (C) 2011 Elsevier Ltd. All rights reserved.
  • Another mode of heterocyclization of an enantiopure C-2-symmetric bis-epoxide leading to the symmetric dialkyl sulfide, Weijia Xie, Genzoh Tanabe, Hiroyuki Morimoto, Takanori Hatanaka, Toshie Minematsu, Xiaoming Wu, Osamu Muraoka, TETRAHEDRON, TETRAHEDRON, 66(38), 7487 - 7491, Sep. 2010 , Refereed
    Summary:Reexamination of heterocyclization of an enantiopure C-2-symmetric bis-epoxide (7) with sodium sulfide is described. In addition to the reported processes leading to thiane (4a) and thiepane (6), another mode of cyclization was found to occur to a considerable extent, affording a symmetric dialkyl sulfide (5), and the structure of the main product reported (4a) has been revised. Conditions for the chemoselective formation of 6 were established, and effective transformation of 6 into 4 was accomplished by the modification of the processes. (C) 2010 Elsevier Ltd. All rights reserved.
  • Scandium-Catalyzed Propargylation of 1,3-Diketones with Propargyl Alcohols Bearing Sulfur or Selenium Functional Groups: Useful Transformation to Furans and Pyrans, Katsuki Ohta, Taira Kobayashi, Genzoh Tanabe, Osamu Muraoka, Mitsuhiro Yoshimatsu, CHEMICAL & PHARMACEUTICAL BULLETIN, CHEMICAL & PHARMACEUTICAL BULLETIN, 58(9), 1180 - 1186, Sep. 2010 , Refereed
    Summary:Propargylations of 1,3-diketones using 3-sulfanyl and 3-selanylpropargyl alcohols 1 in MeNO2-H2O gave alkynyl ketones 2a-m, 2o-v and 6,7-dihydro-5H-cyclohexa[b]pyran-5-ones 3k-n. With some bases, the useful propargylated 1,3-diketones underwent intramolecular cyclization to give 6,7-dihydro-5H-benzofuran-4-ones 4a-i or 4,5,6,7-tetrahydrobenzofurans 5p, 6p-v.
  • Characteristic alkaline catalyzed degradation of kotalanol, a potent alpha-glucosidase inhibitor isolated from Ayurvedic traditional medicine Salacia reticulata, leading to anhydroheptitols: another structural proof, Osamu Muraoka, Weijia Xie, Satomi Osaki, Ayumi Kagawa, Genzoh Tanabe, Mumen F. A. Amer, Toshie Minematsu, Toshio Morikawa, Masayuki Yoshikawa, TETRAHEDRON, TETRAHEDRON, 66(21), 3717 - 3722, May 2010 , Refereed
    Summary:Stereochemical structure of kotalanol (2), a highly potent a-glucosidase inhibitor isolated from an Ayurvedic traditional medicine Salacia reticulata, was proved by alkaline catalyzed degradation of natural kotalanol (2), in which characteristic stereospecific cyclization of the degradative side chain leading to anhydroheptitols (10 and 11) was involved. (C) 2010 Elsevier Ltd. All rights reserved.
  • On the structure of the bioactive constituent from ayurvedic medicine Salacia reticulata: revision of the literature, Osamu Muraoka, Weijia Xie, Genzoh Tanabe, Mumen F. A. Amer, Toshie Minematsu, Masayuki Yoshikawa, TETRAHEDRON LETTERS, TETRAHEDRON LETTERS, 49(51), 7315 - 7317, Dec. 2008 , Refereed
    Summary:The reported structure of a potent a-glucosidase inhibitor 7 isolated recently from ayurvedic medicine Salacia reticulata was found incorrect, and the compound was proved to be de-O-sulfated kotalanol 4. Discussion and detailed analysis of the spectral data leading to the revised structure are presented. (C) 2008 Elsevier Ltd. All rights reserved.
  • Synthesis and elucidation of absolute stereochemistry of salaprinol, another thiosugar sulfonium sulfate from the ayurvedic traditional medicine Salacia prinoides, Genzoh Tanabe, Mika Sakano, Toshie Minematsu, Hisashi Matusda, Masayuki Yoshikawa, Osamu Muraoka, TETRAHEDRON, TETRAHEDRON, 64(43), 10080 - 10086, Oct. 2008 , Refereed
    Summary:Synthesis and elucidation of absolute stereochemistry of salaprinol (3) isolated from the root and sterns of Salacia prinoides, which has been used for the treatment of diabetes in India, Sri Lanka, and Southeast Asia countries, is described. Compound 3 and its 2'-epimer, epi-salaprinol (epi-3) were synthesized via the coupling reaction of a cyclic sulfate, 2-O-benzylglycerol 1,3-cyclic sulfate (S), with a thiosugar, 1,4-dideoxy-1,4-epithio-D-arabinitol (6), as the key reaction, and S configuration of the asymmetric center in the side chain of 3 was elucidated by the X-ray crystallographic analysis. (C) 2008 Published by Elsevier Ltd.
  • A new method of constructing dearomatized compounds using triazene, Keiji Nishiwaki, Takashi Ogawa, Ken-ichi Tagami, Genzoh Tanabe, Osamu Muraoka, Keizo Matsuo, TETRAHEDRON, TETRAHEDRON, 62(47), 10854 - 10858, Nov. 2006 , Refereed
    Summary:We are reporting on a new method of constructing dearomatized compounds from alpha-substituted aryltriazenes. Deprotonation occurs at C atom alpha to N3. Nucleophilic attack of generated anion at the ortho-position of aryl group forms a new carbon-carbon bond. A stereoselective reaction was observed when the substituents on the C alpha to N3 are tied together in either a pyrrolidine or a piperidine. The product of this reaction possessed an interesting dearomatized tetrahydrobenzotriazine framework. (c) 2006 Elsevier Ltd. All rights reserved.
  • Asymmetric tandem Michael-aldol reactions between 3-cinnamoyloxazolidine-2-thiones and aldehydes, Hironori Kinoshita, Takashi Osamura, Kazumi Mizuno, Sayaka Kinoshita, Tatsunori Iwamura, Shin-ichi Watanabe, Tadashi Kataoka, Osamu Muraoka, Genzoh Tanabe, CHEMISTRY-A EUROPEAN JOURNAL, CHEMISTRY-A EUROPEAN JOURNAL, 12(14), 3896 - 3904, May 2006
    Summary:Reactions between chiral 3-cinnamoyl-4-methyl-5-phenyl-1,3-oxazolidine-2-thiones and aromatic aldehydes in the presence of BF3 center dot Et2O diastereoselectively produced tricyclic compounds incorporating a bridgehead carbon bound to four heteroatoms in high yields. Four stereocenters were induced during the reaction. The tricyclic products were transformed into propane-1,3-diols bearing three consecutive stereocenters by acid hydrolysis, S-methylation, and reductive removal of the chiral auxiliary.
  • Synthesis of 3-sulfanylpropanols containing three consecutive stereocenters via tandem Michael-aldol reaction of enoylthioamides with acetals as key reaction, H Kinoshita, N Takahashi, T Iwamura, S Watanabe, T Kataoka, O Muraoka, G Tanabe, TETRAHEDRON LETTERS, TETRAHEDRON LETTERS, 46(42), 7155 - 7158, Oct. 2005 , Refereed
    Summary:(2S,3S,1'R)-2-(alpha-Methoxybenzyl)-3-phenyl-3-sulfanylpropionamides were diastereoselectively prepared by the reactions of N-cinnamoyl-4S-isopropyl-5,5-dimethyloxazolidinethione with acetals in the presence of SnCl4. The absolute configuration of the three newly created contiguous stereocenters was determined by the X-ray analysis of the disulfide. The amides were transformed into propanols by the reductive removal of the oxazolidinone moiety. (c) 2005 Elsevier Ltd. All rights reserved.
  • Concise synthesis of the tricyclic skeleton of cylindricines using a radical cascade involving 6-Endo selective cyclization, T Taniguchi, O Tamura, M Uchiyama, O Muraoka, G Tanabe, H Ishibashi, SYNLETT, SYNLETT, 70(5)(7), 1179 - 1181, May 2005 , Refereed
    Summary:On treatment with Bu3SnH and azobis(cyclohexanecarbonitrile) (ACN), enamide 19 underwent a 6-endo-trig/5-endo-trig radical cascade to afford perhydropyrrolo[2.1-j]quinoline derivative 21, a cylindricine skeleton.
  • 7-endo selective aryl radical cyclization onto enamides leading to 3-benzazepines: Concise construction of a cephalotaxine skeleton, T Taniguchi, A Ishita, M Uchiyama, O Tamura, O Muraoka, G Tanabe, H Ishibashi, JOURNAL OF ORGANIC CHEMISTRY, JOURNAL OF ORGANIC CHEMISTRY, 70(5), 1922 - 1925, Mar. 2005 , Refereed
    Summary:Bu3SnH-mediated radical cyclizations of 2-(2-bromophenyl)N-ethenylacetamide gave 6-exo cyclization product 15 as the major product, whereas N-[2-(2-bromophenyl)ethyl]-N-ethenylamides gave almost exclusively 7-endo cyclization products. These results indicated that the position of the carbonyl group on enamide played an important role in deciding the course of the cyclization. The 7-endo selective cyclization was applied to concise construction of a cephalotaxine skeleton.
  • Development of novel diastereoselective alkenylation of enolates using alkenylselenonium salts, S Watanabe, T Ikeda, T Kataoka, G Tanabe, O Muraoka, ORGANIC LETTERS, ORGANIC LETTERS, 5(4), 565 - 567, Feb. 2003 , Refereed
    Summary:[GRAPHICS] A novel alkenylation of enolates using alkenylselenonium salts is described. A reaction of lithium enolates, which were prepared in situ by the reaction of LiHMDS and carbonyl compounds, with alkenylselenonium salts gave the ethenylation products of carbonyl compounds in high yield. Diastereoselective alkenylation was also accomplished by the reaction of the enolates derived from N-acyl-1,3-oxazolidin-2-ones with the alkenylselenonium salt to afford good results (up to 92% yield and up to 95% de).
  • Asymmetric induction of three consecutive chiral centers by reactions of N-enoylthioamides with aldehydes, T Kataoka, H Kinoshita, S Kinoshita, T Osamura, S Watanabe, T Iwamura, O Muraoka, G Tanabe, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 42(25), 2889 - 2891, 2003 , Refereed
  • Potential antitumor-promoting diterpenes from the cones of Pinus luchuensis, T Minami, S Wada, H Tokuda, G Tanabe, O Muraoka, R Tanaka, JOURNAL OF NATURAL PRODUCTS, JOURNAL OF NATURAL PRODUCTS, 65(12), 1921 - 1923, Dec. 2002 , Refereed
    Summary:A new nor-labdane-type diterpene, 15-nor-labda-8(17),12E-dien-13,19-dienoic acid (1), along with five known diterpenes, 15-nor-14-oxolabda-8(17),12E-dien-19-oic acid (2), trans-communic acid (3), sandaracopimaric acid (4), dehydroabietic acid (5), and abieta-8,11,13-triene-15,18-diol (6), was isolated from the cones of Pinus luchuensis. The structure of 1 was established by chemical and spectroscopic methods. Among these isolates, compounds 2, 4, and 6 showed potent inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate.
  • A novel push-pull Diels-Alder diene: Reactions of 4-alkoxy- or 4-phenylsulfenyl-5-chalcogene-substituted 1-phenylpenta-2,4-dien-1-one with electron-deficient dienophiles, M Yoshimatsu, M Hibino, M Ishida, G Tanabe, O Muraoka, CHEMICAL & PHARMACEUTICAL BULLETIN, CHEMICAL & PHARMACEUTICAL BULLETIN, 50(11), 1520 - 1524, Nov. 2002 , Refereed
    Summary:5-(Phenylselenenyl)- and 5-(phenylsulfenyl)-4-ethoxy-1-phenyl-2,4-pentadien-1-ones (2) and (3) underwent [4+2] cycloaddition with N-methyl and N-phenylmaleimides and successive isomerization to give the 7-benzoyl-3a,4,5,7a-tetrahydro-1H-isoindole-1,3(2H)-diones 5, 8 and 9 in good yields. The 4-ethoxy group on the 2,4-pentadien-1-one was found to be effective to facilitate the cycloaddition with dienophiles. We also performed other [4+2] cycloadditions of 2,4-pentadien-1-ones with DMAD or naphthoquinone.
  • The first isolation and characterization of sulfonylbuta-1,3-diynes, M Yoshimatsu, K Oh-Ishi, G Tanabe, O Muraoka, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1413-1416(12), 1413 - 1416, 2002 , Refereed
    Summary:We have isolated the sulfonylbuta-1,3-diynes 3 and 5 as colorless prisms, which demonstrate unprecedented dimerization. Furthermore, the reactions of 3 and 5 with alkoxides or buta-1,3-dienes were examined and the products obtained were either sulfonyl-beta-alkoxybut-1-en-3-ynes 16a-e, beta-alkoxybut-3-en-1-ynes 17a-d or the cycloadducts 23 and 24a, b.
  • Absolute stereostructures of novel norcadinane- and trinoreudesmane-type sesquiterpenes with nitric oxide production inhibitory activity from Alpinia oxyphylla, O Muraoka, M Fujimoto, G Tanabe, M Kubo, T Minematsu, H Matsuda, T Morikawa, Toguchida, I, M Yoshikawa, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 11(16), 2217 - 2220, Aug. 2001 , Refereed
    Summary:Novel 14- norcadinane-type sesquiterpenes. oxyphyllenodiols A and B, and 11,12,13-trinoreudesmane-type sesquiterpenes. oxyphyllenones A and B, were isolated from the methanolic extract of kernels of Alpinia oxiphylla. The absolute stereostructures of these norsesquiterpenes were determined on the basis of physicochemical and chemical evidence. In addition, oxyphyllenodiol A and oxyphyllenone A were found to inhibit the NO production in lipopolysuccharide-activated macrophages. (C) 2001 Elsevier Science Ltd. All rights reserved.
  • Percutaneous penetration of ozagrel and the enhancement produced by saturated fatty acids, T Ogiso, K Koike, M Iwaki, T Tanino, G Tanabe, O Muraoka, BIOLOGICAL & PHARMACEUTICAL BULLETIN, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 23(7), 844 - 849, Jul. 2000 , Refereed
    Summary:The effects of a series of fatty acids on the percutaneous penetration of ozagrel (OZ), a selective thromboxane A(2) synthetase inhibitor, through rat skin and the mechanism by which fatty acids enhance the skin penetration of OZ were examined in vitro. Lauric acid, at the fatty acid:OZ molar ratio of 2:1, was the most potent agent as far as increasing the skin penetration was concerned,,vith a flux 24-fold higher than that without fatty acid. A molar ratio of 3:1 also produced a large enhancing effect, comparable with that of a molar ratio of 2:1, When the gel formulation with lauric acid (molar ratio of 2: 1) was applied to the skin for 6 h, the amount of drug penetrating into the skin was significantly increased compared with that after the formulations without lauric acid and with capric and palmitic acids. However Lauric acid did not change the apparent partition coefficient of OZ between n-heptane and phosphate buffer (pH 7.4), The C-13-NMR spectra of OZ was also unaffected by the addition of lauric acid, indicating that a complex or ion pair with lauric acid was not formed, A possible mechanism for the enhancing effect is the increased incorporation of lauric acid with OZ into the bulk lipid phase of the stratum corneum, where the fatty acid would act as a co-penetrant enhancing passage through the stratum corneum.
  • Reexamination of products and the reaction mechanism of the chalcogeno- Baylis-Hillman reaction: Chalcogenide-TiCl4-mediated reactions of electron- deficient alkenes with aldehydes, Tadashi Kataoka, Hironori Kinoshita, Tetsuo Iwama, Shin-Ichiro Tsujiyama, Tatsunori Iwamura, Shin-Ichi Watanabe, Osamu Muraoka, Genzoh Tanabe, Tetrahedron, Tetrahedron, 56(27), 4725 - 4731, Jun. 30 2000 , Refereed
    Summary:Reactions of p-nitrobenzaldehyde (4) with methyl vinyl ketone (5) were conducted in the presence of TiCl4 and dimethyl sulfide (3) or selenopyranone 6. When the raw product was purified by column chromatography on silica gel, α-chloromethyl aldol 8 was obtained as a mixture of diastereoisomers 8a and 8b. In contrast, purification of the raw product by preparative TLC on silica gel gave α-methylene aldol 7. The mechanism for the formation of α-chloromethyl aldol 8 and diasteroselection for the syn- isomer 8a and anti-isomer 8b are discussed. (C) 2000 Elsevier Science Ltd.
  • [4(+)+2]-type polar cycloadditions of 2-benzothiopyrylium salt with alkenes, H Shimizu, N Araki, O Muraoka, G Tanabe, TETRAHEDRON LETTERS, TETRAHEDRON LETTERS, 41(13), 2161 - 2164, Mar. 2000 , Refereed
    Summary:Treatment of 2-benzothiopyrylium salt with alkenes such as styrene, p-methylstyrene, p-methoxystyrene, alpha-methylstyrene, and trans-anethole afforded the corresponding [4(+)+2]-type polar cycloaddition products, respectively. The structures of the cycloadducts were confirmed by X-ray crystal structure determination of the corresponding sulfone derivative. (C) 2000 Elsevier Science Ltd. All rights reserved.
  • Formation of 2-oxa- or 2-azabicyclo[3.3.0]octa-3,7-diene by a novel tandem intramolecular photo-cyclization of 2,4,6-tris(phenylthio)hepta-2,4,6-trienal derivatives, Mitsuhiro Yoshimatsu, Satoshi Gotoh, Genzoh Tanabe, Osamu Muraoka, Chemical Communications, Chemical Communications, (10), 909 - 910, May 21 1999 , Refereed
    Summary:The photo-reactions of 2,4,6-tris(phenylthio)hepta-2,4,6-trienal 1 and its 2,4-dinitrophenylhydrazone 5 gave the 2-oxa- or 2-azabicyclo[3.3.0]octa-3,7-dienes 2 and 9, respectively, via a photo-induced intramolecular tandem cyclization reaction.
  • Enhancement of the oral bioavailability of phenytoin by N-acetylation and absorptive characteristics, T Ogiso, T Tanino, D Kawaratani, M Iwaki, G Tanabe, O Muraoka, BIOLOGICAL & PHARMACEUTICAL BULLETIN, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 21(10), 1084 - 1089, Oct. 1998 , Refereed
    Summary:To improve the absorbability of phenytoin (DPH), a prodrug, N-acetyl-DPH (EDPH), was synthesized, and the absorptive characteristics and pharmacokinetics of the prodrug were evaluated in rats. EDPH was rapidly hydrolyzed to DPH in the intestinal fluid and the mucosa (rate constant, 0.055 and 0.169 min(-1), respectively). The plasma concentrations of DPH after intravenous dosing of EDPH declined in a biexponential manner, although two different elimination patterns were observed in these rats. When dosed orally (25 mg/kg, DPH equivalent), the plasma levels of DPH converted from the prodrug were significantly higher and more sustained than those after DPH alone, giving bioavailability 11.4 (rapid decay) and 9.1 times (slow decay) as high, respectively, as that after DPH alone. The concentrations of DPH distributed into the mucosa of the duodenum and jejunum 1 and 5 h after oral dosing of EDPH were significantly higher than those after DPH alone. The prodrug and DPH converted from the prodrug dissolved 2-4 fold more than DPH alone in bile salt solution and bile salt-oleic acid mixed micelles, indicating the increased solubility of the prodrug in the intestinal fluid. It is concluded from the data that such high solubility of EDPH enhanced the intestinal absorption of the prodrug, part of which would be absorbed in the amide form, and thus gave the high bioavailability.
  • Reactions of diphenyl(phenylethynyl)selenonium salts with active methylene compounds and amides: First isolation of oxyselenuranes [10-Se-4(C3O)] as a reaction intermediate, T Kataoka, S Watanabe, K Yamamoto, M Yoshimatsu, G Tanabe, O Muraoka, JOURNAL OF ORGANIC CHEMISTRY, JOURNAL OF ORGANIC CHEMISTRY, 63(18), 6382 - 6386, Sep. 1998 , Refereed
    Summary:The reaction of the diphenyl(phenylethynyl)selenonium triflate 1a with active methylene compounds 5 and t-BuOK in THF gave furan derivatives 6. The [10-Se-4(C3O)] selenuranes 8a and 8b could be isolated from the reactions with benzoylacetonitrile 5f and with 1,3-indandione 5g, respectively, as reaction intermediates. The structures of the selenuranes 8 were elucidated by X-ray crystallography and Se-77 high-resolution solid-state NMR spectroscopy. The selenuranes 8 underwent ligand coupling on standing at room temperature or refluxing in chloroform and gave the furan derivatives 6 and the ring-opened product 9. Similarly, the reaction of 1a with benzamide 13a and pivalamide 13d in the presence of NaH in THF afforded oxazole derivatives 14.
  • Pummerer reaction of 2-vinylcyclopropyl sulfoxides: generation and reactions of butadienylthionium ion intermediates, T Iwama, H Matsumoto, H Shimizu, T Kataoka, O Muraoka, G Tanabe, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, (9), 1569 - 1576, May 1998 , Refereed
    Summary:Generation of butadienylthionium ions in the Pummerer reactions of 2-vinylcyclopropyl sulfoxides has been investigated. Although the Pummerer reactions of 2-vinylcyclopropyl sulfoxides 1 are complicated, benzothiazinone derivatives 10 smoothly react with trifluoroacetic anhydride to give 1,3-dienes in good yields, The reactions proceed via butadienylthionium ions by proton abstraction from the 2'-methyl group or the cyclopropane ring, Reactions of disubstituted benzothiazinones 10e-h provided cyclic dienes while treatment of mono-or un-substituted derivatives gave acyclic conjugated dienes 11a-d. 2-Vinylcyclopropyl sulfoxides 1 and 10 were prepared by MCPBA oxidation of the corresponding 2-vinylcyclopropyl sulfides 19 and 23, respectively, which were obtained by cyclopropanation of a-chloro sulfides with 1,3-dienes via the 5,6-dihydro-2H-thiopyranium intermediate 22.
  • Enhancement of oral bioavailability of phenytoin by esterification, and in vitro hydrolytic characteristics of prodrugs, T Tanino, T Ogiso, M Iwaki, G Tanabe, O Muraoka, INTERNATIONAL JOURNAL OF PHARMACEUTICS, INTERNATIONAL JOURNAL OF PHARMACEUTICS, 163(1-2), 91 - 102, Mar. 1998 , Refereed
    Summary:To improve the oral absorbability of phenytoin (DPH), prodrugs of DPH with a small acyl substituent, N-carboethoxy- and N-carboisopropoxy-DPH (PT-1 and PT-2, respectively), were synthesized and bioavailabilities of them were evaluated after oral administration in rats, compared to that of DPH dosed. The prodrugs were rapidly hydrolyzed in the intestinal fluid, intestinal mucosa, liver homogenates and plasma of rats, the plasma giving the highest hydrolytic activity. Two different eliminations of DPH, slow and rapid, were observed after intravenous and oral administrations of prodrugs. The bioavailabilities of DPH after oral administration at a dose of 25 mg/kg of PT-1 and PT-2 (DPH equivalent), increased to approximately 8.5- and 6.0-fold for PT-1 and PT-2 (rapid elimination group) or 3.0- and 3.0-fold (slow elimination group), respectively, compared to those after dosing of DPH. The plasma levels of DPH converted from PT-2 dosed were lower, but more sustained in slow elimination groups than those from PT-1. The normalized AUC values after oral dosing of prodrugs at a dose of 50 mg/kg were increased dramatically, compared to those at a dose of 25 mg/kg, suggesting non-linear clearance at a high dose. In order to clarify the mechanism for preponderance of intestinal absorption of the prodrugs, concentrations of parent drug and prodrug were measured in intestinal mucosa after a single oral dosing of 50 mg/kg (DPH equivalent). Upon the administration of PT-I and PT-2, greater amounts of DPH, in comparison with those after dosing of DPH, and small amounts of intact prodrugs were detected in the duodenal and jejunal mucosa. These data indicated that these prodrugs was subjected to the extensive intestinal absorption compared to DPH, giving comparatively high plasma levels. Therefore, PT-1 and PT-2 will be useful prodrugs as an orally applicable form. In particular, PT-2 seems to serve as a benign prodrug with the intention of improving the absorption of DPH. (C) 1998 Elsevier Science B.V. All rights reserved.
  • A new fluoride-mediated 1,2-sulfonyl shift on cyclopropane, M Yoshimatsu, K Konishi, G Tanabe, O Muraoka, TETRAHEDRON LETTERS, TETRAHEDRON LETTERS, 39(13), 1781 - 1782, Mar. 1998 , Refereed
    Summary:A 1,2-sulfonyl shift reaction on cyclopropane proceeded during the reactions of 2-alkynyl-1a-e, 2-aryl-1,1-bis(sulfonyl)cyclopropanes 1f,1j-k and Bu4NF to give trans-1,2-bis(sulfonyl)cyclopropanes 2a-e, 2f, 2J-k. (C) 1998 Elsevier Science Ltd. All rights reserved.
  • Salacinol, potent antidiabetic principle with unique thiosugar sulfonium sulfate structure from the ayurvedic traditional medicine Salacia reticulata in Sri Lanka and India, M Yoshikawa, T Murakami, H Shimada, H Matsuda, J Yamahara, G Tanabe, O Muraoka, TETRAHEDRON LETTERS, TETRAHEDRON LETTERS, 38(48), 8367 - 8370, Dec. 1997 , Refereed
    Summary:A most potent natural alpha-glucosidase inhibitor named salacinol has been isolated from an antidiabetic Ayurvedic traditional medicine, Salacia reticulata WIGHT, through bioassay-guided separation. The stereostructure of salacinol was determined on the basis of chemical and physicochemical evidence, which included the X-ray crystallographic analysis, and the molecular conformation showed the unique spiro-like configuration of the inner salt comprised of 1-deoxy-4-thioarabinofuranosyl cation and 1'-deoxyerythrosyl-3'-sulfate anion. (C) 1997 Elsevier Science Ltd.
  • Furan-2(3H)- and -2(5H)-ones .7. Photochemical behaviour of tetrahydro- and hexahydro-isobenzofuran-1-one systems: A mechanistic and exploratory study, O Muraoka, G Tanabe, Y Igaki, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, (11), 1669 - 1679, Jun. 1997 , Refereed
    Summary:The photoreactivity of two variations of the di-pi-methane system involving the tetrahydro- and hexahydro-isobenzofuran structures 10 and 11 have been examined and compared with those of beta-apolignans 1. The former, 9-phenyl-1,3,4,5,6,7,8,9-octahydronaphtho[2,3-c]furan-1-one 10a and 7-phenyl-1,3,4,7-tetrahydroisobenzofuran-1-one 10b, gave primarily the di-pi-methane rearrangement products 18a and 18b, respectively, while the hexahydro substrate, 7-phenyl-1, 3,4,5,6,7-hexahydroisobenzofuran-1-one 11, afforded mainly the photoreduced products 21-24. This difference in chemoselectivity is explained in terms of the variant configuration of the phenyl group, an axially orientated one migrating most effectively. A new pathway for the reaction leading to the cyclopropano product 18a or 18b, by way of another cyclopropano derivative 19a or 19b, respectively, is described.
  • Synthesis and reactions of lactam sulfonium salts with a sulfonio bridgehead .1. 4,4a,5,6-tetrahydro-5-oxo-1H-thiopyrano[1,2-a]-1,4-benzothiazinium perchlorates, T Kataoka, Y Nakamura, H Matsumoto, T Iwama, H Kondo, H Shimizu, O Muraoka, G Tanabe, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, (3), 309 - 316, Feb. 1997 , Refereed
    Summary:Tricyclic benzothiazinium salts 3 are prepared by [2(+)+4] polar cycloaddition of thionium intermediates 2A, generated from the corresponding alpha-chloro sulfides 2, and dienes in the presence of silver perchlorate. Ring transformation of benzothiazinium salts 3 with a reducing agent such as Mg, NaBH4 and Zn-AcOH or with a base, furnishes spiro-vinylcyclopropane derivatives 4 in moderate to high yields. Electrolysis of 3a at -1.4 V vs. SCE in acetonitrile also affords vinylcyclopropane 4a (60%). These results indicate that both ionic and radical mechanisms may account for the vinylcyclopropane formation, although it is unclear as to the nature of the radical intermediate. The stereochemistry of 4a was determined by X-ray analysis showing that sulfur and the vinyl group are cis-orientated. Ten-membered lactam sulfides 6 are obtained as the major product of SmI2 reduction of 3.
  • Synthesis and reactions of lactam sulfonium salts with a sulfonio bridgehead .2. 1,1a,4,5,6-pentahydro-6-oxo-2H-thiopyrano[1,6-d]-4,1-benzothiazepinium perchlorates, T Kataoka, Y Nakamura, H Matsumoto, T Iwama, H Shimizu, O Muraoka, G Tanabe, CHEMICAL & PHARMACEUTICAL BULLETIN, CHEMICAL & PHARMACEUTICAL BULLETIN, 45(2), 265 - 271, Feb. 1997 , Refereed
    Summary:Tricyclic benzothiazepinium salts (5) were prepared by [2(+) + 4] polar cycloaddition of thionium intermediates (4A), generated from corresponding alpha-chloro sulfides (4) and dienes in the presence of silver perchlorate, X-Ray analysis of 5a revealed that the configuration of the thiazepinone skeleton and the dihydrothiopyran ring is cis-fused, Reactions of benzothiazepinium salts (5) with NaBH4 or NaH afforded 3,6-epithiobenzazocinone derivatives (9) in high yields by [2,3]-sigmatropic rearrangement of an ylide intermediate (11), The stereochemistry of epithiobenzazocinone (9a) was determined by the nuclear Overhauser enhancement (NOE) technique and finally by X-ray analysis of the sulfoxide (10) derived from epithiobenzazocinone (9a) by m-chloroperbenzoic acid (MCPBA) oxidation, Alkylation of epithiobenzazocinone (9a) afforded 3-alkyl-3,6-epithiobenzazocinones (12) with retention of the configuration at C-3. Dihydrothiopyran derivatives (13) were obtained in good yields by SmI2 reduction of benzothiazepinium salts (5).
  • Stereospecific syntheses of 5-alkyl-3-ethoxy-2-((phenylchalcogeno)methylene)tetrahydrofurans, M Yoshimatsu, M Naito, H Shimizu, O Muraoka, G Tanabe, T Kataoka, JOURNAL OF ORGANIC CHEMISTRY, JOURNAL OF ORGANIC CHEMISTRY, 61(23), 8200 - 8206, Nov. 1996 , Refereed
    Summary:2-Ethoxy-4-(phenylchalcogeno)but-3-ynyl ketones 1-10 were reduced with LiBH4 in Et(2)O diastereoselectively to give 5-(phenylchalcogeno)pent-4-yn-1-ols 11-20. Treatment of the phenylchalcogen-substituted alkynyl alcohols 11-20 with t-BuOK in t-BuOH provided useful (Z)-2-((phenylchalcogeno)methylene)tetrahydrofurans 21-31 stereoselectively.
  • Pharmacokinetics of indomethacin ester prodrugs: Gastrointestinal and hepatic toxicity and the hydrolytic capacity of various tissues in rats, T Ogiso, M Iwaki, T Tanino, T Nagai, Y Ueda, O Muraoka, G Tanabe, BIOLOGICAL & PHARMACEUTICAL BULLETIN, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 19(9), 1178 - 1183, Sep. 1996 , Refereed
    Summary:In order to develop a potential prodrug of indomethacin (IM) which causes less irritation to the gastrointestinal mucosa, the ester prodrugs [butyl ester (IM-BE) and octyl ester (IM-OE)] of IM were synthesized and evaluated for their ulcerogenic activity and hepatic injury after oral administration in rats. Additionally, the kinetics of hydrolysis of the prodrugs,were examined to characterize the tissues or organs capable of hydrolyzing the ester bonds. The plasma levels of IM after the oral administration of IM-OE and IM-BE were comparatively low compared with those after IM, with a small bioavailability (2.1 and 15.0%, respectively). Ulcerogenic activity and hepatic injury, expressed by decreased hepatic microsomal enzyme activities, were hardly seen after repeated oral administration of the prodrugs, in contrast with the severely irritating effects of IM alone. Hydrolysis of the prodrugs was adequately described by first-order kinetics. IM-BE was relatively rapidly hydrolyzed in plasma, skin and whole blood, but the hydrolysis in the intestinal mucosa and liver was very slow. The hydrolytic rates for IM-OE were exceedingly small or negligible. These results indicate that the main part of IM-BE and IM-OE administered orally might not be hydrolyzed to IM in the gastrointestinal tract, and that the ester prodrugs themselves were absorbed through the mucosa; also, that the hydrolysis of ester bonds would be carried out mainly in the circulatory system. Consequently, IM-BE seems to be an ideal prodrug of IM.
  • First successful [4(+)+2]-type polar cycloadditions of 2-benzothiopyrylium salt with dienes, H Shimizu, N Araki, O Muraoka, G Tanabe, CHEMICAL COMMUNICATIONS, CHEMICAL COMMUNICATIONS, (18), 2185 - 2186, Sep. 1996 , Refereed
    Summary:2-Benzothiopyrylium salt 1 reacted via a [4(+) + 2]-type polar cycloaddition with dienes 2 in the presence of methanol to afford benzo-fused bicyclo[2.2.2] compounds 5, while in the absence of methanol cycloaddition of 1 with 2,3-dimethylbuta-1,3-diene 2a afforded a novel benzo-fused tricyclic compound 4a, whose structure has been confirmed by X-ray crystallography.
  • A regioselective addition reaction of a sulfonyl radical to conjugate enynesulfones: A convenient synthesis of 1,4-bis(arylsulfonyl)-1,3-butadiene, M Yoshimatsu, M Hayashi, G Tanabe, O Muraoka, TETRAHEDRON LETTERS, TETRAHEDRON LETTERS, 37(24), 4161 - 4164, Jun. 1996 , Refereed
    Summary:p-Tolyl benzeneselenosulfonate regioselectively added to the conjugate enynesulfones 1-9 gave (1E, 3E)-1,4-bis(arylsulfonyl)-1,3-butadienes 10-17, which were converted to the 4-hetero atom-substituted-1-phenylsulfonyl-1,3-butadienes 18, 21 and 22. (C) 1996 Elsevier Science Ltd
  • A facile synthesis of 7-methylenebicyclo[3.3.1]nonan-3-one and its transformation leading to the novel tricyclic system, protoadamantane, O Muraoka, YL Wang, M Okumura, S Nishiura, G Tanabe, T Momose, SYNTHETIC COMMUNICATIONS, SYNTHETIC COMMUNICATIONS, 26(8), 1555 - 1562, 1996 , Refereed
    Summary:A practical synthesis of 7-methylenebicyclo[3.3.1]nonan-3-one 2 by the fragmentation of 1,3-adamantanediol 8, which was prepared effectively by the ruthenium-catalized oxyfunctionalization of 1-adamantanol 7, is described. Characteristic transannular cyclization of 2 leading to a novel tricyclic system, 1-hydroxy-4-protoadamantanone 9, via the corresponding exo-epoxide 10 is also presented.
  • Furan-2(3H)- and -2(5H)-ones. part 6. Di-π-methane rearrangement of the α-substituted 4-benzylfuran-2(5H)-one system, Osamu Muraoka, Genzoh Tanabe, Mié Higashiura, Toshie Minematsu, Takefumi Momose, Journal of the Chemical Society, Perkin Transactions 1, Journal of the Chemical Society, Perkin Transactions 1, 1437 - 1443, 1995 , Refereed
    Summary:The effect of the ‘central methane’ substitution on the di-π-methane rearrangement in 4-benzyl-2,5-dihydrofuran-2-ones 8a-d was investigated. Significant enhancement of efficiency in the rearrangement leading in high combined yields to two isomeric products, endo-12 and exo-12, is discussed in terms of both the substituent effects at the benzylic carbon and the restrained features of the ring-enrolled π-system. The origin of the difference in chemoselectivity compared with that of the 3-benzyl counterpart 5 where a photoarylated product 6 resulted upon photoirradiation was also investigated, and was rationalized by postulating a higher reactivity at the β-position of the enone system. © 1995 by the Royal Society of Chemistry. All Rights Reserved.
  • PHYSICOCHEMICAL AND HYDROLYTIC CHARACTERISTICS OF PHENYTOIN DERIVATIVES, T OGISO, T TANINO, M IWAKI, O MURAOKA, G TANABE, BIOLOGICAL & PHARMACEUTICAL BULLETIN, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 17(10), 1425 - 1429, Oct. 1994 , Refereed
    Summary:To further clarify the pharmacokinetic characteristics of phenytoin (DPH) and its derivatives, DPH-1-methylnicotininate (MNDPH), valeroyl DPH (VADPH) and valproyl DPH (VPDPH), in plasma and brain, we have investigated their physicochemical properties and protein binding characteristics. Additionally, the hydrolytic conversion of these derivatives to DPH was also studied using small intestine, liver and brain tissues, as well as rat plasma. The log partition coefficient (PC) values of all derivatives were much higher than that of DPH. Judging from their pK(a) values (5.68 and 5.91 for VADPH and VPDPH, respectively) and pH-solubilities, VADPH and VPDPH were acidic compounds, while MNDPH was basic. These data indicated that most fractions of VADPH and VPDPH existed as an ionized form (these fractions existed in an ionized form, 0.98 and 0.97, respectively) at physiological pH, whereas MNDPH existed as a unionized form under the same conditions. Rosenthal or Scatchard plots of the binding data of DPH and its derivatives to both rat plasma protein and bovine serum albumin (BSA) exhibited straight lines over their concentration ranges used, indicating that DPH and its derivatives have a single binding site on the protein. The binding potencies (K or n.P-1 value) of the derivatives to both proteins were much greater than that of DPH. No DPH produced from VADPH and VPDPH was found in the biological fluids over a period of 24h. However, the hydrolysis of MNDPH to DPH was observed in plasma and the tissues used, with the most rapid hydrolysis in the small intestine, and the hydrolysis rate constant in plasma was ca. 20-fold greater than that in the brain. The present results lead us to propose that the low uptake of VADPH and VPDPH into the brain, as well as their rapid elimination from plasma is mainly ascribed to both the high protein binding and the large dissociation of derivatives in the plasma, compared with that of DPH.
  • FURAN-2(3H)-ONE AND 2(5H)-ONE .5. PHOTOREACTIONS OF 3-BENZYLFURAN-2(5H)-ONES - CYCLIZATION TO INDENOFURANONES, O MURAOKA, G TANABE, K SANO, T MINEMATSU, T MOMOSE, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, (13), 1833 - 1845, Jul. 1994 , Refereed
    Summary:The effect of substitution at the 'central methane' on the photoreactivity of 3-benzylfuran-2(5H)ones 5a-g was investigated. Despite its di-pi-methane structure, photochemical arylation was effected to give substituted indenofuranones 6 in good yields. Only the substitution by phenyl caused the di-pi-methane rearrangement to give a cyclopropanofuranone 18g in moderate yield.
  • Furan-2(3H)- and 2(5H)-ones. Part 5. Photoreactions of 3-benzylfuran2(5H)-ones; cyclisation to indenofuranones, Osamu Muraoka, Genzoh Tanabe, Kyohko Sano, Toshie Minematsu, Takefumi Momose, Journal of the Chemical Society, Perkin Transactions 1, Journal of the Chemical Society, Perkin Transactions 1, 1833 - 1845, 1994 , Refereed
    Summary:The effect of substitution at the "central methane" on the photoreactivity of 3-benzylfuran-2(5H)ones 5a-g was investigated. Despite its di-π-methane structure, photochemical arylation was effected to give substituted indenofuranones 6 in good yields. Only the substitution by phenyl caused the di-π-methane rearrangement to give a cyclopropanofuranone 18g in moderate yield. © 1994 by the Royal Society of Chemistry. All Rights Reserved.
  • PHARMACOKINETIC ANALYSIS OF PHENYTOIN AND ITS DERIVATIVES IN PLASMA AND BRAIN IN RATS, T OGISO, M IWAKI, T TANINO, O MURAOKA, G TANABE, BIOLOGICAL & PHARMACEUTICAL BULLETIN, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 16(10), 1025 - 1030, Oct. 1993 , Refereed
    Summary:The derivatives of phenytoin (DPH) were synthesized by the reaction at 3 position of hydantoin ring with valproic acid and valeric acid, producing valproyl DPH (VPDPH) and valeroyl DPH (VADPH), respectively. These derivatives showed much higher lipid solubilities than that of DPH. Their distribution and elimination were compared to those of DPH. Additionally, the concentration profiles of the drugs in brain and plasma were analyzed with a modified 2-compartment model. DPH and its derivatives, without hydrolysis to DPH in blood, were found rapidly distributed into brain, although the distribution of derivatives was much less, probably due to the high protein binding capacities. The distribution of DPH and its derivatives into brain regions was similar to that into the cortex cerebri. VPDPH and VADPH were more rapidly eliminated from plasma and brain than DPH, giving smaller mean residence time (MRT) values (0.92 and 0.85 h) and much smaller cortex/plasma concentration ratio than those of DPH. The VPDPH and VADPH concentrations in the cerebrospinal fluid (CSF) were also much lower than that of DPH. The time course of plasma and brain concentrations of DPH and its derivatives after i.v. administration was successfully described by the modified 2-compartment models presented.
  • 2(3H)-FURANONES AND 2(5H)-FURANONES .4. THE DI-PI-METHANE REARRANGEMENT OF 3,4-BIS(PHENYLMETHYL)-2(5H)-FURANONE, T MOMOSE, G TANABE, H TSUJIMORI, O MURAOKA, CHEMICAL & PHARMACEUTICAL BULLETIN, CHEMICAL & PHARMACEUTICAL BULLETIN, 40(9), 2525 - 2530, Sep. 1992 , Refereed
    Summary:The photo-irradiation of 3,4-bis(phenylmethyl)-2(5H)-furanone (5) in acetone or in methanol resulted in selective rearrangement of the 4-phenylmethyl moiety and gave 5-phenyl-1-(phenylmethyl)-3-oxabicyclo[3.1.0]hexan-2-one (9) along with cis- and trans-3,4-bis(phenylmethyl)dihydro-2(3H)-furanone (10a and 10b). The difference in photochemical behavior from that of beta-apolignan (1) is discussed.

Conference Activities & Talks

  • Facile Synthesis of Neokotalanol, a Potent α-Glycosidase Inhibitor Isolated from the Ayurvedic Traditional Medicine “Salacia”, G. Tanabe, S. Ueda, K. Kurimoto, N. Sonoda, S. Marumoto, F. Ishikawa, O. Muraoka,   2019 09
  • An engineered aryl acid adenylation domain with an enlarged substrate binding pocket,   2019 09
  • A reprogrammed aryl acid adenylation domain with an enlarged substrate binding site,   2019 09
  • Reprogramming aryl acid adenylation domains for non-native building block, F. Ishikawa, A. Miyanaga, H. Kitayama, F. Kudo, T. Eguchi, G. Tanabe,   2019 08
  • An engineered aryl acid adenylating enzyme with a capacious active site microenvironment,   2019 06
  • Reprogramming aryl acid adenylating enzymes for non-native building blocks, Fumihiro Ishikawa, Hinano Kitayama, Genzoh Tanabe, 10th International Peptide Symposium (10th IPS),   2018 12
  • Antidiabetic Effects of Naturally Occurring Thiosugar Sulfoniums, Neokotalanol and Salacinol, from Salacia Genus Plants, T. Morikawa, M. Kobayashi, J. Akaki, K. Ninomiya, O. Muraoka, G. Tanabe, 28th International Symposium on the Organic Chemistry of Sulfur (ISOCS-28),   2018 08
  • Highly Diastereoselective Synthesis of Salacinol-type α-Glucosidase Inhibitors and Evaluation of Their in vivo α-Glucosidase Inhibitory Activity, TANABE Genzoh, 28th International Symposium on the Organic Chemistry of Sulfur (ISOCS-28),   2018 08
  • 7. Kazuki Matsuura, Ryosuke Satoh, Kanako Hagihara, Nozomu Tsuchimoto, Yoshimasa Hyodo, Ayako Kita, Genzoh Tanabe, Osamu Muraoka, Reiko Sugiura, TANABE Genzoh,   2016 10
  • Anticancer-drug screening utilizing fission yeast genetics identified Acremomannolipin A, a Calcium signalling modulator with anti-tumor activity, TANABE Genzoh,   2016 10
  • キラルテルリドの合成とエナンチオ選択的シクロプロパン化反応への応用, YAMAOKA NAKI, YOKOI RINA, WATANABE SHIN'ICHI, TANABE GENZO, MURAOKA OSAMU, 日本薬学会第 135 年会,   2015 03
  • バンレイシ科植物,Hornschuchia obliqua由来4,5‐didehydroguadiscineの合成およびそのメラニン形成抑制活性評価, TANABE GENZO, SHIRATO MIKI, KANNO YUTA, MORIKAWA TOSHIO, NINOMIYA KIYOFUMI, TSUTSUI NOZOMI, MURAOKA OSAMU, 日本薬学会第 135 年会,   2015 03
  • アーユルベーダ天然薬物“サラシア”由来α‐グルコシダーゼ阻害剤,neoponkoranolの新規ジアステレオ選択的合成, TANABE GENZO, SHIDA TOMOYUKI, MATSUMOTO HIROAKI, TSUTSUI NOZOMI, MURAOKA OSAMU, 日本薬学会第 135 年会,   2015 03
  • メース(Myristica fragrans,仮種皮)の機能性成分(5)―新規ジアリルノナノイド‐ネオリグナン付加体成分の化学構造―, MORIKAWA TOSHIO, YAWATA IKUKO, NINOMIYA KIYOFUMI, HAYAKAWA TAKAO, TANABE GENZO, MURAOKA OSAMU, 日本薬学会第 135 年会,   2015 03
  • サラシア属植物のα‐グルコシダーゼ阻害活性成分を指標とした品質評価, MORIKAWA TOSHIO, AKAKI JUNJI, NINOMIYA KIYOFUMI, TANABE GENZO, YOSHIKAWA MASAYUKI, MURAOKA OSAMU, 生薬分析シンポジウム講演要旨,   2014 11 07
  • インニトリル類とReformatsky反応剤の触媒的[6+1]付加環化反応を利用した含窒素ヘテロ環構築法の開発, TANAKA MIKI, TAKAHASHI NAMI, TANABE GENZO, MURAOKA OSAMU, YOSHIMATSU, MITSUHIRO, 有機合成シンポジウム,   2014 11
  • アーユルベーダ天然薬物“サラシア”由来salacinolをシードとするα‐グルコシダーゼ阻害剤のin silico設計,合成及びin vivo評価, TANABE GENZO, MATSUDA YUYA, TSUTSUI NOZOMI, MORIKAWA TOSHIO, AKAKI JUNJI, NINOMIYA KIYOFUMI, NAKANISHI ISAO, NAKAMURA SHIN'YA, YOSHIKAWA MASAYUKI, MURAOKA OSAMU, 天然薬物の開発と応用シンポジウム,   2014 11
  • サラシア属植物含有α‐グルコシダーゼ阻害活性成分salacinolおよびその類縁体の食後過血糖改善作用, MORIKAWA TOSHIO, AKAKI JUNJI, NINOMIYA KIYOFUMI, KINOUCHI ERI, TANABE GENZO, NAKANISHI ISAO, NAKAMURA SHIN'YA, YOSHIKAWA MASAYUKI, MURAOKA OSAMU, 天然薬物の開発と応用シンポジウム,   2014 11
  • 新規calciumシグナル調節物質acremomannolipin Aの構造活性相関:糖アルコール側鎖部の構造が活性に及ぼす効果, TSUTSUI NOZOMI, TANABE GENZO, GOTO GENKI, MORITA NAO, NOMURA NAOHISA, OKAYAMA YOSHITOMO, KITA AYAKO, SUGIURA REIKO, MURAOKA OSAMU, メディシナルケミストリーシンポジウム,   2014 11
  • Developement of a New Facile Route to Sulfonium Salts, a New Class of α-Glucosidase Inhibitors Isolated from Ayurvedic Medicine “Salacia”, TANABE Genzoh, 24th French-Japanese Symposium on Medicinal and Fine Chemistry,   2014 09
  • α‐グルコシダーゼ阻害活性物質salacinolおよびその誘導体の血糖値上昇抑制活性, MORIKAWA TOSHIO, KIUCHI ERI, AKAKI JUNJI, NINOMIYA KIYOFUMI, TANABE GENZO, NAKANISHI ISAO, NAKAMURA SHIN'YA, YOSHIKAWA MASAYUKI, MURAOKA OSAMU, 第61回 日本生薬学会年会,   2014 09
  • Salacinol and related analogs, new leads for type 2 diabetes therapeutic candidates from Thai traditional natural medicine, Salacia chinensis, Toshio Morikawa, Junji Akaki, Kiyofumi Ninomiya, Eri Kinouchi, Genzoh Tanabe, Masayuki Yoshikawa, Osamu Muraoka,   2014 05

Misc

  • タイ天然薬物Mammea siamensis花部クマリン成分のCYP19阻害活性, 二宮清文, 二宮清文, LUO Fenglin, 柴谷華苗, CHAIPECH Saowanee, CHAIPECH Saowanee, PONGPIRIYADACHA Yutana, 村岡修, 石川文洋, 田邉元三, 田邉元三, 森川敏生, 森川敏生, 天然薬物の開発と応用シンポジウム講演要旨集, 22nd, 129‐131,   2018 10 01 , http://jglobal.jst.go.jp/public/201802213440413492
  • タイ天然薬物Melodorum fruticosum花部含有butenolideの一酸化窒素産生抑制活性, 二宮清文, 坂本裕介, 田邉元三, 田邉元三, 村岡修, 森川敏生, 日本生薬学会年会講演要旨集, 65th, 244, 244,   2018 08 31 , http://jglobal.jst.go.jp/public/201802214723298072
  • 4,5‐ジデヒドロアポルフィン型アルカロイドの合成およびメラニン形成抑制活性評価, 白戸美希, 萬瀬貴昭, 二宮清文, 丸本真輔, 石川文洋, 村岡修, 森川敏生, 田邉元三, 田邉元三, 日本薬学会年会要旨集(CD-ROM), 138th, 2, ROMBUNNO.27PA‐pm093, 186,   2018 03 , http://jglobal.jst.go.jp/public/201802257656280994
  • チオ糖とエポキシドとのS‐アルキル化を鍵反応に用いる“サラシア”由来,サラシノール型α‐グルコシダーゼ阻害剤の高ジアステレオ選択的合成, 石川文洋, 神農佳澄, 薗田直樹, 村岡修, 田邉元三, 田邉元三, 反応と合成の進歩シンポジウム講演要旨集, 43rd, 74,   2017 10 16 , http://jglobal.jst.go.jp/public/201702213296716806
  • 硫黄置換1,6‐ジインのヒドロアミノ化‐環化反応:縮環化合物合成への応用, 郷隆志, 田邊元三, 村岡修, 和佐田裕昭, 吉松三博, 複素環化学討論会講演要旨集, 47th, 172,   2017 10 10 , http://jglobal.jst.go.jp/public/201702274514872211
  • “キャビコール誘導体ACA‐28”は,がん細胞特異的にERK依存的細胞死を誘導する革新的抗がん剤シーズである, 杉浦麗子, 佐藤亮介, 松浦一貴, 萩原加奈子, 神田勇輝, 石川文洋, 田邉元三, 村岡修, 高崎輝恒, メディシナルケミストリーシンポジウム講演要旨集, 35th, 80,   2017 10 04 , http://jglobal.jst.go.jp/public/201802227707522943
  • 天然薬物”サラシア”由来サラシノール類縁体のジアステレオ選択的合成及びin vivo α‐グルコシダーゼ阻害活性評価, 石川文洋, 神農佳澄, 薗田直樹, 木内恵里, 赤木淳二, 二宮清文, 村岡修, 吉川雅之, 森川敏生, 田邉元三, 田邉元三, メディシナルケミストリーシンポジウム講演要旨集, 35th, 252,   2017 10 04 , http://jglobal.jst.go.jp/public/201802280565741383
  • タイ天然薬物Melodorum fruticosum含有butenolide類のメラニン産生抑制活性, 萬瀬貴昭, 田邉元三, 二宮清文, 二宮清文, 今川貴仁, 安藤恵里, 福田梨沙, 福田友紀, 石川文洋, 村岡修, 村岡修, 森川敏生, 森川敏生, 日本生薬学会年会講演要旨集, 64th, 122, 122,   2017 08 25 , http://jglobal.jst.go.jp/public/201802254505833102
  • 蓮花(Nelumbo nucifera,花部)含有メラニン産生抑制アルカロイド成分を指標とした品質評価, 奥川修平, 奥川修平, 北川仁一朗, 北川仁一朗, 甕千明, 甕千明, 田邉元三, 亀井惟頼, 二宮清文, 吉川雅之, 村岡修, 村岡修, 森川敏生, 日本農芸化学会大会講演要旨集(Web), 2017, ROMBUNNO.2C13p08 (WEB ONLY),   2017 03 05 , http://jglobal.jst.go.jp/public/201702219110612021
  • タイ天然薬物Melodorum fruticosum由来成分のNO産生抑制活性および含有butenolide類の全合成, 安藤恵里, 萬瀬貴昭, 田邉元三, 福田梨沙, 福田友紀, 筒井望, 三宅史織, 中屋友紀子, 山添晶子, 松本朋子, 松田久司, 二宮清文, 村岡修, 村岡修, 森川敏生, 日本農芸化学会大会講演要旨集(Web), 2017, ROMBUNNO.2C13p10 (WEB ONLY),   2017 03 05 , http://jglobal.jst.go.jp/public/201702222962860790
  • タイ天然薬物Mammea siamensis花部のアロマターゼ阻害活性, 柴谷華苗, 二宮清文, 田邉元三, 筒井望, CHAIPECH Saowanee, CHAIPECH Saowanee, PONGPIRIYADACHA Yutana, 村岡修, 村岡修, 森川敏生, 日本農芸化学会大会講演要旨集(Web), 2017, ROMBUNNO.2C13p09 (WEB ONLY),   2017 03 05 , http://jglobal.jst.go.jp/public/201702272648563876
  • タイ天然薬物Melodorum fruticosum由来NO産生抑制活性Butenolide類の合成およびその活性評価, 田邉元三, 森川敏生, 福田梨沙, 福田友紀, 萬瀬貴昭, 二宮清文, 松本朋子, 眞野みのり, 松田久司, 村岡修, 村岡修, 日本薬学会年会要旨集(CD-ROM), 137th, ROMBUNNO.27PA‐am098,   2017 , http://jglobal.jst.go.jp/public/201702245629332270
  • タイ天然薬物Melodorum fruticosum由来butenolide類の全合成およびNO産生抑制活性評価, 萬瀬貴昭, 田邉元三, 福田梨沙, 福田友紀, 筒井望, 三宅史織, 中屋友紀子, 山添晶子, 松本朋子, 松田久司, 二宮清文, 村岡修, 森川敏生, 天然薬物の開発と応用シンポジウム講演要旨集, 21st, 172‐174,   2016 10 01 , http://jglobal.jst.go.jp/public/201602279256442841
  • タイ天然薬物Mammea siamensis花部の機能性成分(7)―含有クマリン成分のアロマターゼ阻害活性―, 二宮清文, 柴谷華苗, 田邉元三, 筒井望, 末吉真弓, 佐伯竣介, 杉田秀美, CHAIPECH Saowanee, CHAIPECH Saowanee, PONGPIRIYADACHA Yutana, 早川堯夫, 村岡修, 村岡修, 森川敏生, 日本生薬学会年会講演要旨集, 63rd, 177,   2016 08 25 , http://jglobal.jst.go.jp/public/201602226072640442
  • サラシア・キネンシスに含有される抗糖尿病作用成分, 赤木淳二, 赤木淳二, 小林正和, 森川敏生, 二宮清文, 木内恵里, 田邉元三, PONGPIRIYADACHA Yutana, 吉川雅之, 村岡修, 村岡修, 日本食品化学学会総会・学術大会講演要旨集, 22nd, 66,   2016 06 02 , http://jglobal.jst.go.jp/public/201602234039701751
  • メラニン産生抑制活性を有する蓮華含有アルカロイド成分の安定性評価, 二宮清文, 奥川修平, 奥川修平, 甕千明, 甕千明, 北川仁一朗, 北川仁一朗, 田邉元三, 吉川雅之, 村岡修, 村岡修, 森川敏生, 日本薬学会年会要旨集(CD-ROM), 136th, 2, ROMBUNNO.28AB‐PM278, 230,   2016 03 , http://jglobal.jst.go.jp/public/201602211607935138
  • タイ天然薬物Melodorum fruticosum由来NO産生抑制活性を有するButenolide類の全合成, 田邉元三, 森川敏生, 小川哲平, 薗田直樹, 至田智行, 萬瀬貴昭, 二宮清文, 筒井望, 村岡修, 日本薬学会年会要旨集(CD-ROM), 136th, 2, ROMBUNNO.28AB‐PM319, 236,   2016 03 , http://jglobal.jst.go.jp/public/201602219432413622
  • 蓮華(Nelumbo nucifera,花部)のメラニン産生抑制活性成分を指標とした品質評価, 森川敏生, 北川仁一朗, 北川仁一朗, 奥川修平, 奥川修平, 甕千明, 甕千明, 田邉元三, 亀井惟頼, 二宮清文, 吉川雅之, 村岡修, 村岡修, 食品薬学シンポジウム講演要旨集, 6th, 48, 50,   2015 10 15 , http://jglobal.jst.go.jp/public/201502201082321573
  • タイ天然薬物Melodorum fruticosum由来NO産生抑制活性を有するButenolide類の全合成, 田邉元三, 森川敏生, 小川哲平, 薗田直樹, 至田智行, 萬瀬貴昭, 二宮清文, 筒井望, 村岡修, 村岡修, 香料・テルペンおよび精油化学に関する討論会講演要旨集, 59th, 291, 293,   2015 09 05 , http://jglobal.jst.go.jp/public/201602205886617354
  • メース(Myristica fragrans,仮種皮)の機能性成分(6)―新規ネオリグナン成分の化学構造―, 二宮清文, 八幡郁子, 田邉元三, 早川堯夫, 村岡修, 村岡修, 森川敏生, 日本生薬学会年会講演要旨集, 62nd, 117,   2015 08 31 , http://jglobal.jst.go.jp/public/201602283609548607
  • バンレイシ科植物,Hornschuchia obliqua由来4,5‐didehydroguadiscineの合成およびそのメラニン形成抑制活性評価, 田邉元三, 白戸美希, 菅野雄太, 森川敏夫, 二宮清文, 筒井望, 村岡修, 日本薬学会年会要旨集(CD-ROM), 135th, 2, ROMBUNNO.27PB-PM230S, 233,   2015 03 , http://jglobal.jst.go.jp/public/201502275179876998
  • メース(Myristica fragrans,仮種皮)の機能性成分(5)―新規ジアリルノナノイド‐ネオリグナン付加体成分の化学構造―, 森川敏生, 八幡郁子, 二宮清文, 早川堯夫, 田邉元三, 村岡修, 日本薬学会年会要旨集(CD-ROM), 135th, ROMBUNNO.27PB-PM176S,   2015 , http://jglobal.jst.go.jp/public/201502232437898178
  • アーユルベーダ天然薬物“サラシア”由来α‐グルコシダーゼ阻害剤,neoponkoranolの新規ジアステレオ選択的合成, 田邉元三, 至田智行, 松本裕朗, 筒井望, 村岡修, 日本薬学会年会要旨集(CD-ROM), 135th, ROMBUNNO.27PB-AM037S,   2015 , http://jglobal.jst.go.jp/public/201502254007294213
  • キラルテルリドの合成とエナンチオ選択的シクロプロパン化反応への応用, 山岡奈樹, 横井里奈, 渡邉真一, 田邉元三, 村岡修, 日本薬学会年会要旨集(CD-ROM), 135th, ROMBUNNO.27PB-PM009,   2015 , http://jglobal.jst.go.jp/public/201502275527093692
  • サラシア属植物のα‐グルコシダーゼ阻害活性成分を指標とした品質評価, 森川敏生, 赤木淳二, 二宮清文, 田邉元三, 吉川雅之, 村岡修, 生薬分析シンポジウム講演要旨, 43rd, 60, 71,   2014 11 07 , http://jglobal.jst.go.jp/public/201402214817843443
  • 新規calciumシグナル調節物質acremomannolipin Aの構造活性相関:糖アルコール側鎖部の構造が活性に及ぼす効果, 筒井望, 田邉元三, 後藤元気, 森田直, 野村尚央, 岡山善知, 喜多綾子, 杉浦麗子, 村岡修, メディシナルケミストリーシンポジウム講演要旨集, 32nd, 178,   2014 11 07 , http://jglobal.jst.go.jp/public/201502208431372885
  • サラシア属植物含有α‐グルコシダーゼ阻害活性成分salacinolおよびその類縁体の食後過血糖改善作用, 森川敏生, 赤木淳二, 二宮清文, 木内恵里, 田邉元三, 仲西功, 中村真也, 吉川雅之, 村岡修, 天然薬物の開発と応用シンポジウム講演要旨集, 20th, 75, 77,   2014 11 01 , http://jglobal.jst.go.jp/public/201402243896519257
  • アーユルベーダ天然薬物“サラシア”由来salacinolをシードとするα‐グルコシダーゼ阻害剤のin silico設計,合成及びin vivo評価, 田邉元三, 松田侑也, 筒井望, 森川敏生, 赤木淳二, 二宮清文, 仲西功, 中村真也, 吉川雅之, 村岡修, 天然薬物の開発と応用シンポジウム講演要旨集, 20th, 72, 74,   2014 11 01 , http://jglobal.jst.go.jp/public/201402296037414156
  • インニトリル類とReformatsky反応剤の触媒的[6+1]付加環化反応を利用した含窒素ヘテロ環構築法の開発, 田中美妃, 高橋奈美, 田邉元三, 村岡修, 吉松三博, 有機合成シンポジウム講演要旨集, 106th, 62, 63,   2014 10 27 , http://jglobal.jst.go.jp/public/201402271196724562
  • α‐グルコシダーゼ阻害活性物質salacinolおよびその誘導体の血糖値上昇抑制活性, 森川敏生, 木内恵里, 赤木淳二, 二宮清文, 田邉元三, 仲西功, 中村真也, 吉川雅之, 村岡修, 日本生薬学会年会講演要旨集, 61st, 235, 235,   2014 08 27 , http://jglobal.jst.go.jp/public/201402298435973745
  • ヒトα‐グルコシダーゼに関するサラシノールおよびその類縁体の阻害活性プロフィール, 木内恵里, 赤木淳二, 森川敏生, 二宮清文, 田邉元三, 吉川雅之, 村岡修, 日本栄養・食糧学会大会講演要旨集, 68th, 230, 230,   2014 04 30 , http://jglobal.jst.go.jp/public/201402289222742805
  • サラシア属植物由来スルホニウム塩型および既存α‐グルコシダーゼ阻害剤の同時分析, 赤木淳二, 森川敏生, 二宮清文, 三宅荘八郎, 田邉元三, 吉川雅之, 村岡修, 日本栄養・食糧学会大会講演要旨集, 68th, 230, 230,   2014 04 30 , http://jglobal.jst.go.jp/public/201402290492553689
  • Reformatsky反応剤を用いたインニトリル類の分子内環化反応, 田中美妃, 高橋奈美, 田邉元三, 村岡修, 吉松三博, 日本化学会講演予稿集, 94th, 4, 1077,   2014 03 12 , http://jglobal.jst.go.jp/public/201402278836413563
  • 異なる生物種由来α‐glucosidaseに対するsalacinol類の阻害活性プロフィール, 村岡修, 赤木淳二, 二宮清文, 木内恵里, 田邉元三, 吉川雅之, 森川敏生, 日本薬学会年会要旨集(CD-ROM), 134th, 2, ROMBUNNO.28O-PM01, 85,   2014 03 , http://jglobal.jst.go.jp/public/201402298900950706
  • アーユルベーダ天然薬物“サラシア”由来α‐グルコシダーゼ阻害剤,Neosalacinolの新規ジアステレオ選択的合成, 田邉元三, 松田侑也, 枡見達陽, 筒井望, 村岡修, 日本薬学会年会要旨集(CD-ROM), 134th, 2, ROMBUNNO.28Y-AM07S, 126,   2014 03 , http://jglobal.jst.go.jp/public/201402264504870307
  • A New Approach to Sulfonium-Type Potent α-Glucosidase Inhibitors, originated from Ayurvedic Traditional Medicine, Salacia, Tanabe Genzoh, Matsuda Yuuya, Matsmoto Hiroaki, Tsutsui Mozomi, Osamu Muraoka, Symposium on the Chemistry of Natural Products, symposium papers, 56, 0,   2014 , http://ci.nii.ac.jp/naid/130007399518
    Summary:<p>Salacinol (1) and related sulfonium salts (2–6), isolated from Salacia genus plants which have traditionally been used for the treatment of diabetes in Ayurvedic system, are considered to be a new class of a-glucosidase inhibitors. Their a-glucosidase inhibitory activities are as potent as those of clinically used anti-diabetes, voglibose and acarbose.<sup>1</sup>Because of their intriguing structure and high a-glucosidase inhibitory activities, intensive structure activity relationship (SAR) studies have been conducted worldwide. With the aid of in silico drug design, a series of compounds (7) 40 times more potent than the original salacinol has been developed by the presenters so far.</p><p>In this presentation a facile and general route to a series of these compounds has newly been developed. The key methodology in this sequence is the intramolecular cyclization of the sulfide (13), in which efficient cyclization proceeded to give a-14 in an excellent dr ratio with good yield. The deprotection of a-14 gave the target neosalacinol (4) in good yield.</p>
  • α‐グルコシダーゼ阻害剤,Salacinolの構造活性相関研究―トルイル酸型置換基による3’位疎水化の効果―, 田邉元三, 中村真也, 筒井望, 赤木淳二, 森川敏生, 二宮清文, 仲西功, 吉川雅之, 村岡修, メディシナルケミストリーシンポジウム講演要旨集, 31st, 112,   2013 11 01 , http://jglobal.jst.go.jp/public/201302293709502559
  • α‐グルコシダーゼ阻害剤の酵素阻害活性におけるヒトとラットの種差の計算化学的解析, 島田和子, 中村真也, 田邉元三, 村岡修, 仲西功, メディシナルケミストリーシンポジウム講演要旨集, 31st, 84,   2013 11 01 , http://jglobal.jst.go.jp/public/201302244030510306
  • サラシノールを基点とする新規α‐グルコシダーゼ阻害剤の構造活性相関および創出研究, 中村真也, 高平和典, 島田和子, 田邉元三, 村岡修, 仲西功, 構造活性相関シンポジウム講演要旨集, 41st, 33, 34,   2013 10 21 , http://jglobal.jst.go.jp/public/201302250312323037
  • α‐Glucosidase阻害剤,Salacinolの構造活性相関研究:3’位脂溶性化が活性に及ぼす効果, 田邉元三, 中村真也, 筒井望, 赤木淳二, 森川敏生, 二宮清文, 仲西功, 吉川雅之, 村岡修, 食品薬学シンポジウム講演要旨集, 5th, 178, 180,   2013 10 01 , http://jglobal.jst.go.jp/public/201302287130931814
  • ヒトとラットにおけるα‐グルコシダーゼ阻害剤アカルボースの酵素阻害活性の種差の検討, 島田和子, 中村真也, 高平和典, 田邉元三, 村岡修, 仲西功, 日本薬学会年会要旨集(CD-ROM), 133rd, 2, ROMBUNNO.29AMB-164S, 310,   2013 03 , http://jglobal.jst.go.jp/public/201302248506698436
  • 新規calciumシグナル調節物質acremomannolipin Aの合成およびその構造活性相関:糖アルコール部立体化学の活性に及ぼす効果, 筒井望, 田邉元三, 後藤元気, 森田直, 野村尚央, 喜多綾子, 杉浦麗子, 村岡修, 日本薬学会年会要旨集(CD-ROM), 133rd, 2, ROMBUNNO.29PMA-123, 202,   2013 03 , http://jglobal.jst.go.jp/public/201302244420261404
  • ヒトα‐グルコシダーゼ触媒ドメイン群と阻害剤の横断的構造活性相関, 中村真也, 高平和典, 田邉元三, 村岡修, 仲西功, 日本薬学会年会要旨集(CD-ROM), 133rd, 2, ROMBUNNO.29AMB-162, 309,   2013 03 , http://jglobal.jst.go.jp/public/201302299297181475
  • Salacinolをシードとするスルホニウム塩型α‐グルコシダーゼ阻害剤のin silico設計,合成及び評価:3’位アルキル化の効果, 田邉元三, 國方雄介, 中村真也, 筒井望, 赤木淳二, 森川敏生, 二宮清文, 仲西功, 吉川雅之, 村岡修, 日本薬学会年会要旨集(CD-ROM), 133rd, ROMBUNNO.29K-AM06S,   2013 , http://jglobal.jst.go.jp/public/201302228922628560
  • Medicinal Flowers: Melanogenesis Inhibitors from the Flower Buds of Camellia japonica and Nelumbo nucifera, Nakamura Seikou, Yoshikawa Masayuki, Matsuda Hisashi, Fujimoto Katsuyoshi, Tanabe Genzoh, Nakashima Souichi, Matsumoto Takahiro, Ohta Tomoe, Ogawa Keiko, Muraoka Osamu, Symposium on the Chemistry of Natural Products, symposium papers, 55, 0, PosterP, 6,   2013 , http://ci.nii.ac.jp/naid/130006470673
    Summary:<p>In the course of our studies on biofunctional constituents from medicinal flowers, the methanolic extracts from the flower buds of Camellia japonica (Theaceae) cultivated in China (Yunnan province) and Korea (Cheju Island) and Nelumbo nucifera (Nymphaeaceae) cultivated in Thailand (Khon Kaen province) were found to show inhibitory effects on melanogenesis in theophylline-stimulated B16 melanoma 4A5 cells. From the flower buds of C. japonica cultivated in China and Korea, we have isolated 10 new oleanane-type triterpene saponins, sanchakasaponins A–H and camelliosides E and F, together with 12 known saponins. On the other hand, from the flower buds and leaves ofN. nucifera, 12 benzylisoquinoline alkaloids including a new alkaloidwere isolated. Among them, several saponin and benzylisoquinoline alkaloids significantly inhibited melanogenesis. The inhibitory effects were stronger than that of a reference compound, arbutin. Furthermore, the inhibitory effects of related commercial and synthesized alkaloids on melanogenesis were examined and their structure-activity relationships were characterized. In addition, camellioside B, a major constituent of C. japonica cultivated in Japan, were found to display an inhibitory effect on melanogenesis, but an enhancing effect on fibroblast proliferation. This biological selectivity could make camellioside B useful for treating skin disorders.</p>
  • Salacinolをシードとする新規α‐グルコシダーゼ阻害剤のin silico設計,合成および評価, 田邉元三, 中村真也, 筒井望, 赤木淳二, 森川敏生, 二宮清文, 仲西功, 吉川雅之, 村岡修, メディシナルケミストリーシンポジウム講演要旨集, 30th, 88,   2012 11 01 , http://jglobal.jst.go.jp/public/201302290760779426
  • ロータス(Nelumbo nucifera)のメラニン生成抑制作用成分, 中村誠宏, 中嶋聡一, 田邉元三, 松田久司, 村岡修, 吉川雅之, メディシナルケミストリーシンポジウム講演要旨集, 30th, 180,   2012 11 01 , http://jglobal.jst.go.jp/public/201302221058078523
  • Salacinolをシードとするスルホニウム塩型α‐グルコシダーゼ阻害剤のin silico設計,合成及び評価, 田邉元三, 中村真也, 國方雄介, 土屋聡史, 吉長正紘, 筒井望, 赤木淳二, 森川敏生, 二宮清文, 吉川雅之, 仲西功, 村岡修, 天然薬物の開発と応用シンポジウム講演要旨集, 19th, 125, 127,   2012 10 01 , http://jglobal.jst.go.jp/public/201302201319088644
  • メディシナルフラワー研究:椿花(Camellia japonica,花部)および蓮花(Nelumbo nucifera,花部)の美白作用成分, 中村誠宏, 藤本勝好, 中嶋聡一, 田邉元三, 松本崇宏, 松田久司, 村岡修, 吉川雅之, 天然薬物の開発と応用シンポジウム講演要旨集, 19th, 63, 65,   2012 10 01 , http://jglobal.jst.go.jp/public/201302233996757160
  • 銅触媒下でのアルキニル化を伴う4‐オキサヘプタ‐1,6‐ジイン類の分子内環化反応, 佐々木瞳, 田邉元三, 村岡修, 吉松三博, 日本化学会講演予稿集, 92nd, 4, 1300,   2012 03 09 , http://jglobal.jst.go.jp/public/201202226674341453
  • α‐Glucosidase阻害剤salacinolの構造活性相関:3’位epi体の活性について, 田邉元三, GORRE Balakishan, MUMEN F. A. Amer, 西村彩香, 早阪茉奈美, 筒井望, 峯松敏江, 吉川雅之, 村岡修, 日本薬学会年会要旨集, 132nd, 2, 269, 269,   2012 03 05 , http://jglobal.jst.go.jp/public/201202287217976434
  • α‐Glucosidase阻害剤salacinolの構造活性相関:3’位ベンジル化の効果, 田邉元三, 土屋聡史, 筒井望, 峯松敏江, 赤木淳二, 中村真也, 仲西功, 吉川雅之, 村岡修, 日本薬学会年会要旨集, 132nd, 2, 164, 164,   2012 03 05 , http://jglobal.jst.go.jp/public/201202292088054219
  • アルコキシド及びフェノキシドを用いた4‐オキソ‐1,6‐ヘプタジイン類の分子内環化反応, 高橋奈美, 長瀬雄哉, 吉松三博, 田邉元三, 村岡修, 反応と合成の進歩シンポジウム講演要旨集, 37th, 102, 103,   2011 10 14 , 10.14895/hannou.37.0.59.0, http://jglobal.jst.go.jp/public/201102245700272039
  • ロータス(Nelumbo mucifera)の美白作用成分, 吉川雅之, 中嶋聡一, 中村誠宏, 田邉元三, 村岡修, 松田久司, 食品薬学シンポジウム講演要旨集, 4th, 196, 198,   2011 10 01 , http://jglobal.jst.go.jp/public/201102262728447006
  • メディシナルフラワー研究:ロータス(Nelumbo nucifera)花部アルカロイド成分の構造とメラニン生成抑制および作用メカニズム, 吉川雅之, 中村誠宏, 横田奈美, 前田小百合, 西田紫乃, 松田久司, 中嶋聡一, 田邉元三, 村岡修, 日本生薬学会年会講演要旨集, 58th, 98,   2011 09 01 , http://jglobal.jst.go.jp/public/201302208429344926
  • α‐Glucosidase阻害剤salacinolの側鎖部3’‐O‐アルキル体の合成およびそれらの阻害活性評価, 田邉元三, 大谷徹, 二宮清文, 峯松敏江, 吉川雅之, 村岡修, 日本薬学会年会要旨集, 131st, 2, 187,   2011 03 05 , http://jglobal.jst.go.jp/public/201102226278195153
  • サラキア属植物由来α‐グルコシダーゼ阻害剤neoponkoranolの構造活性相関研究, 謝唯佳, 田邉元三, 二宮清文, 峯松敏江, 吉川雅之, 村岡修, 日本薬学会年会要旨集, 131st, 2, 187,   2011 03 05 , http://jglobal.jst.go.jp/public/201102213086325679
  • Cyclization Reaction of 4-Oxohepta-1,6-diynes Using Alkoxides and Phenoxides, Takahashi Nami, Nagase Yuya, Tanabe Genzoh, Muraoka Osamu, Yoshimatsu Mitsuhiro, Proceedings of the Symposium on Progress in Organic Reactions and Syntheses, 37, 0, 59, 59,   2011 , http://ci.nii.ac.jp/naid/130006995617
    Summary:Sodium alkoxide- and aryloxide-mediated cyclization reactions of <BR>1-sulfanyl-4-oxohepta-1,6-diynes have been developed. The reactions with diverse sodium <BR>alkoxides produced 4-alkoxymethylfurans in good to high yields. The reactions of <BR>4-oxohepta-1,6-diynes with aryloxides, which have higher nucleophilicities than alkoxides, <BR>and the successive desulfanylation using tributyltin hydride/AIBN, provided 3-methylfurans. <BR>While, the cyclizations of 4-oxohepta-1,6-diynes with sodium thiolate and the following <BR>desulfanylations gave the 3,4-dimethylfurans. We further investigated the tyrosine-mediated <BR>cyclizations of the 4-oxohepta-1,6-diynes and the syntheses of tetrahydronaphthyl derivatives, <BR>which have interesting biological activities.
  • サラキア属植物由来α‐グルコシダーゼ阻害剤salacinolの側鎖部に関する構造活性相関研究, 叢文英, 田邉元三, 二宮清文, 峯松敏江, 吉川雅之, 村岡修, 日本薬学会年会要旨集, 130th, 2, 250,   2010 03 05 , http://jglobal.jst.go.jp/public/201002210263057519
  • salacia属植物有効成分のαグルコシダーゼ結合様式の推定, 高平和典, 中村真也, 田邉元三, 村岡修, 仲西功, 日本薬学会年会要旨集, 130th, 2, 258,   2010 03 05 , http://jglobal.jst.go.jp/public/201002240583254440
  • サラキア属植物由来α‐グルコシダーゼ阻害剤kotalanolの構造活性相関研究, 謝唯佳, 田邉元三, 二宮清文, 峯松敏江, 吉川雅之, 村岡修, 日本薬学会年会要旨集, 130th, 2, 258,   2010 03 05 , http://jglobal.jst.go.jp/public/201002272286334124
  • α‐Glucosidase阻害剤salacinolおよびkotalanolの側鎖部デオキシ体の合成およびそれらの阻害活性評価, 田邉元三, 坂野実加, 峯松敏江, 二宮清文, 森川敏生, 吉川雅之, 村岡修, 日本薬学会年会要旨集, 130th, 2, 258,   2010 03 05 , http://jglobal.jst.go.jp/public/201002285728477030
  • サラキア属植物由来α‐グルコシダーゼ阻害剤kotalanolの構造活性相関研究, XIE Weijia, 田邉元三, 二宮清文, 峯松敏江, 吉川雅之, 村岡修, メディシナルケミストリーシンポジウム講演要旨集, 28th, 128, 129,   2009 11 10 , http://jglobal.jst.go.jp/public/201002228174111891
  • New limonoids from the flower of Carapa guianensis, 田中裕治, 山田剛司, 尹康子, 田辺元三, 村岡修, 田中麗子, 香料・テルペンおよび精油化学に関する討論会講演要旨集, 53rd, 281, 283,   2009 11 07 , http://jglobal.jst.go.jp/public/201002211281181827
  • サラキア属植物由来α‐グルコシダーゼ阻害剤kotalanolの構造活性相関研究, XIE Weijia, 田邉元三, 二宮清文, 峯松敏江, 吉川雅之, 村岡修, 食品薬学シンポジウム講演要旨集, 3rd, 165, 167,   2009 10 21 , http://jglobal.jst.go.jp/public/200902248184219844
  • アンデローバ(Carapa guianensis)花油の新規リモノイド, 田中裕治, 山田剛司, 尹康子, 田辺元三, 村岡修, 田中麗子, 食品薬学シンポジウム講演要旨集, 3rd, 80, 82,   2009 10 21 , http://jglobal.jst.go.jp/public/200902263170554208
  • アーユルベーダ薬用植物,Salaciaの新規抗糖尿病成分の構造とその合成研究, 田邉元三, 坂野実加, 峯松敏江, 森川敏生, 二宮清文, 吉川雅之, 村岡修, 食品薬学シンポジウム講演要旨集, 3rd, 162, 164,   2009 10 21 , http://jglobal.jst.go.jp/public/200902278537800534
  • サラキア属植物由来α‐グルコシダーゼ阻害活性成分の構造について:文献提示構造の改訂, 村岡修, 謝唯佳, 田邉元三, AMER F. A. Mumen, 峯松敏江, 吉川雅之, 日本薬学会年会要旨集, 129th, 2, 231, 231,   2009 03 05 , http://jglobal.jst.go.jp/public/200902241393885717
  • 非環式salacinol類縁体の合成とそのα‐glucosidase阻害活性評価, 田邉元三, 長山麻衣子, 赤木淳二, 峯松敏江, 吉川雅之, 村岡修, 日本薬学会年会要旨集, 129th, 2, 125,   2009 03 05 , http://jglobal.jst.go.jp/public/200902210712507272
  • サラキア属植物由来α‐グルコシダーゼ阻害活性成分,salaprinolの全合成, 田邉元三, 坂野美加, 峰松敏江, 松田久司, 吉川雅之, 村岡修, 日本薬学会年会要旨集, 129th, 2, 127,   2009 03 05 , http://jglobal.jst.go.jp/public/200902249340150830
  • 2’位に水酸基を有するアルキル側鎖をもつチオ糖スルホニウム塩の合成とそのα‐glucosidase阻害活性評価, 田邉元三, 濱田有希, 赤木淳二, 峯松敏江, 吉川雅之, 村岡修, 日本薬学会年会要旨集, 129th, 2, 125,   2009 03 05 , http://jglobal.jst.go.jp/public/200902235696472326
  • Synthesis and Structure Elucidation of α-Glucosidase Inhibitors Originated from Ayruvedic Traditional Medicine, Salacia Species, muraoka Osamu, Tanabe Genzoh, Morikawa Toshio, Ninomiya Kiyofumi, Matsuda Hisashi, Yoshikawa Masayuki, Symposium on the Chemistry of Natural Products, symposium papers, 51, 0, 1, 6,   2009 , http://ci.nii.ac.jp/naid/110009757608
    Summary:Salacinol and kotalanol are new class of potent glycosidase inhibitors, isolated by presenters from Ayruvedic traditional medicine Salacia reticulata, having the unique zwitter-ionic structure comprising of 1-deoxy-4-thio-D-arabinofranosyl cation and the sulfate anion in the alditol side chain. Elucidation of the stereostructure of kotalanol, which has long been unknown and very recently approved by Pinto and co-workers by the synthesis, by the independent manner involving the degradation of natural kotalanol is presented. In the detradation of 2, characteristic deprotective cyclization of heptitols to anhydroheptitols was found to occur to a large extent. Structural elucidation of salalprinol, one of the sulfonium analogs recently isolated from the same species, by the synthesis is also presented. Revisions of the structures of new constituents from Salacia species, neosalacinol and 13-membered cyclic sulfoxide, recently reported as constituents responsible for the α-glucosidase inhibitory activity by Minami and Osaki and co-workers, respectively, are presented. In relation to this study, synthetic route of de-O-sufonated salacinol, which was proved as potent as 1, has been developed. Finally, conditions for the quantitative analysis of 1, 2, and their de-O-sulfonates (3 and 4) by LC-MS for the qualitative evaluation of Salacia extracts is discussed.
  • Salacinol関連成分の合成研究とLCMS定量分析による品質評価, 村岡修, 田邉元三, 森川敏生, 三宅荘八郎, 赤木淳二, 二宮清文, 吉川雅之, 天然薬物の開発と応用シンポジウム講演要旨集, 17th, 75, 76,   2008 11 01 , http://jglobal.jst.go.jp/public/200902208176168708
  • インド天然薬物Salacia prinoidesのチオ糖スルホニウム硫酸分子内塩構造を有するα‐グルコシダーゼ阻害成分, 吉川雅之, 許鳳鳴, 中村誠宏, 王涛, 松田久司, 田邉元三, 村岡修, 日本薬学会年会要旨集, 128th, 2, 6, 6,   2008 03 05 , http://jglobal.jst.go.jp/public/200902265555669467
  • α‐グルコシダーゼ阻害剤,kotalanol類縁体の合成およびその活性評価, 松岡桓準, 田邉元三, 能島梢司, 大上直人, 金城江里奈, 峯松敏江, 村岡修, 松田久司, 吉川雅之, 日本薬学会年会要旨集, 128th, 2, 146,   2008 03 05 , http://jglobal.jst.go.jp/public/200902206753309305
  • α‐Glucosidase阻害剤,Salacinol脱硫酸エステル体の合成および阻害活性評価, 田邉元三, 小川藍, 峯松敏江, 村岡修, 松田久司, 吉川雅之, 日本薬学会年会要旨集, 128th, 2, 146,   2008 03 05 , http://jglobal.jst.go.jp/public/200902270271659783
  • 機能性食品素材”サラシア”の機能と生物活性成分およびその品質評価, 村岡修, 森川敏生, 二宮清文, 田邊元三, 松田久司, 吉川雅之, 生薬分析シンポジウム講演要旨, 36th, 13, 23,   2007 11 22 , http://jglobal.jst.go.jp/public/200902257862544750
  • α‐Glucosidase阻害剤Salacinolの1,5‐anhydro‐5‐aza‐D‐glucitol型類縁体の合成および阻害活性評価, 田邉元三, 峯松敏江, 畑中上憲, 村岡修, 吉川雅之, 松田久司, 日本薬学会年会要旨集, 127th, 4, 85,   2007 03 05 , http://jglobal.jst.go.jp/public/200902282529598669
  • 保険薬局および病院実務実習に対する学生の意識調査, 北小路学, 石渡俊二, 大床真美子, 船上仁範, 八軒浩子, 多賀淳, 八木秀樹, 和田哲幸, 田邊元三, 市田成志, 西田升三, 社会薬学, 25, 2, 34,   2007 02 28 , http://jglobal.jst.go.jp/public/200902262219415130
  • P-50 Synthetic Studies on a Potent α-Glucosidase Inhibitor, Kotalanol, Tanabe Genzoh, Yoshikawa Masayuki, Matsuoka Kanjun, Nojima Shoji, Ohgami Naoto, Kinjo Erina, Minematsu Toshie, Cao Chang nian, Muraoka Osamu, Matsuda Hisashi, Symposium on the Chemistry of Natural Products, symposium papers, 49, 0, 625, 630,   2007 , http://ci.nii.ac.jp/naid/110006682836
    Summary:Kotalanol (1) is a new class of potent glycosidase inhibitor, isolated together with salacinol (2) from Ayruvedic medicine Salacia reticulata, having the unique zwitterionic structure comprising of 1-deoxy-4-thio-D-arabinofranosyl cation and the sulfate anion in the heptitol side chain. Although 1 is known to possess even stronger inhibitory activity against certain glucosidase enzymes than 2, no synthetic trial of 1 has been reported because of the unidentified absolute stereochemistry of 5 kinds of carbinol carbons in the heptitol unit. During the course of our synthetic study on 1, four diastereomers 1a, 1b, 1c and 1b, which maintained 2'S and 3'S configuration of salacinol (2) in addition to 4'S configuration as common side chain feature, have been synthesized by the use of the coupling reaction of protected cyclic sulfates (5a, 5b, 5c and 5b) derived from D-ribose derivative (9) with thiosugar (4). The inhibitory activities of the synthesized analogs were also evaluated against rat intestinal glucosidases. All analogs showed less inhibitory activity against sucrase and maltase compared to 1 although they possessed the same stereochemistry at C-2' and C-3' as 2, and the results indicated that the C-4' configuration was critical for the inhibitory activity. Interestingly, potent isomaltase inhibitory activity equal to those of 1 and 2 was found for both C-6 epimers 1a and 1d, indicating that the stereochemistry of the hydroxyl at C-6' was not essential for the isomaltase inhibitory activity.
  • α‐Glucosidase阻害剤,Salacinolの構造活性相関研究:アザ類縁体における脱硫酸エステル体の合成とその活性について, 田辺元三, しょう穎, 松浦義治, 羽生恭子, 吉海和哉, 峯松敏江, 村岡修, 王涛, 森川敏生, 松田久司, 吉川雅之, 日本薬学会年会要旨集, 126th, 4, 138,   2006 03 06 , http://jglobal.jst.go.jp/public/200902213033998940
  • α‐Glucosidase阻害剤,salacinolの構造活性相関研究:側鎖デオキシ体の合成とその活性について, 村岡修, 吉海和哉, 畑中上憲, 峯松敏江, 田邉元三, WANG TAO, 森川敏生, 松田久司, 吉川雅之, メディシナルケミストリーシンポジウム講演要旨集, 24th, 72, 73,   2005 11 10 , http://jglobal.jst.go.jp/public/200902269691236731
  • α‐Glucosidase阻害剤Salacinolのアザ類縁体の合成および阻害活性評価, 村岡修, 吉海和哉, 畑中上憲, 峯松敏江, 田辺元三, 吉川雅之, 松田久司, 森川敏生, 王涛, 日本薬学会年会要旨集, 125th, 4, 65,   2005 03 05 , http://jglobal.jst.go.jp/public/200902208344646777
  • 6員環チオ糖構造を有するSalacinol類縁体の合成, 村岡修, 畑中上憲, 森本陽之, 峯松敏江, 田辺元三, 吉川雅之, 松田久司, 森川敏生, 日本薬学会年会要旨集, 125th, 4, 65,   2005 03 05 , http://jglobal.jst.go.jp/public/200902266938066436
  • P-60 Studies on the Structure-activity Relationship of Salacinol, a Potent Naturally Occurring α-Glucosidase Inhibitor, Muraoka Osamu, Wang Tao, Yoshikai Kazuya, Hatanaka Takanori, Minematsu Toshie, Shao Ying, Tanabe Genzoh, Yoshikawa Masayuki, Matsuda Hisashi, Morikawa Toshio, Symposium on the Chemistry of Natural Products, symposium papers, 47, 0, 619, 624,   2005 , http://ci.nii.ac.jp/naid/110006682616
    Summary:Salacinol (1a) is a new class of potent natural glycosidase inhibitor isolated by presenters from Ayruvedic medicine Salacia reticulata, having the unique spirobicyclic-like configuration comprised of 1-deoxy-4-thio-D-arabinofranosyl cation and 1-deoxy-L-erythrosyl-3-sulfate anion. The characteristic feature of 1a represented as sulfonium cation and the side-chain bearing sulfate anion have been supposed to be the origin of its α-glucosidase inhibitory activity. In this study, aza analogue (1b), its enantiomer (4b) and diastereomer (5b) were synthesized by applying the ring-opening method of cyclic sulfate (2a and 2b) with D- and L-azasugars (D- and L-3b) in order to explore the effect of heteroatom substitution in the 5-membered sugar ring on the α-glucosidase inhibitory activity. Three sulfonium analogs (6, 7, 8) lacking hydroxyl and/or hydroxymethyl groups of the side chain of 1a and two O-desulfonated sulfoniums (9a, 9b) with CH_3OSO_3^- or Cl^- as a counter anion were also synthesized and their inhibitory activities were examined and compared with those of 1a. Upon substitution of sulfur atom with nitrogen, 1b sustained the modest inhibitory activity, however, the inhibitory activities of 4b and 5b were reduced considerably. Three deoxy analogs (6, 7, 8) also showed less inhibitory activity compared to 1a, and proved the importance of cooperative role of the polar substituents to exhibit the α-glucosidase inhibitory activity. Interestingly, O-desulfonated analogs 9a and 9b sustained the potent α-glucosidase inhibitory activity equal to that of 1a irrespective of the counter anions, thus the sulfate anion moiety of 1a was found to be not essential for the inhibitory activity.
  • N‐アダマンチル不飽和脂肪酸アミドの合成, 村岡修, 植木千晶, 峯松敏江, 田辺元三, 近畿大学薬学総合研究所紀要, 11, 143, 150,   2003 03 05 , http://jglobal.jst.go.jp/public/200902261436956096
  • ポリマー担持型次亜リン酸のベンゼンジアゾニウム塩還元能について, 田辺元三, 金沢実希, 峯松敏江, 村岡修, 日本薬学会年会要旨集, 123rd, 2, 100,   2003 03 05 , http://jglobal.jst.go.jp/public/200902287958775929
  • サラシノールの含窒素類縁体合成とそのα‐グルコシダーゼ阻害活性に関する構造活性相関の検討, 村岡修, 吉海和哉, 松浦義治, 山田恵理子, 峯松敏江, 田辺元三, 松田久司, 吉川雅之, YING S, 近畿大学薬学総合研究所紀要, 10, 83, 89,   2002 03 05 , http://jglobal.jst.go.jp/public/200902114061889091
  • ポリマー担持型次亜リン酸のジスルフィド還元能について, 村岡修, 吉海和哉, 滝野真偉美, 峯松敏江, 田辺元三, 日本薬学会年会要旨集, 122nd, 2, 87,   2002 03 05 , http://jglobal.jst.go.jp/public/200902177361042610
  • 薬理活性を有するアダマンタンアミン誘導体の合成研究 (3), 村岡修, 田辺元三, 日本薬学会年会要旨集, 121st, 2, 19,   2001 03 05 , http://jglobal.jst.go.jp/public/200902125695914686
  • Percutaneous Absorption of Ozagrel and the Enhancement Producedby Saturated Fatty Acids, Ogiso Taro, Koike Kazunori, Iwaki Masahiro, Tanino Tadatoshi, Tanabe Genzoh, Muraoka Osamu, Bulletin of Pharmaceutical Research and Technology Institute, 9, 35, 48,   2000 12 14 , http://ci.nii.ac.jp/naid/110000560717
  • A Facile Synthesis of Cationic UV Absorbers, Muraoka Osamu, Hosotani Eiji, Tanabe Genzoh, Bulletin of Pharmaceutical Research and Technology Institute, 9, 137, 144,   2000 12 14 , http://ci.nii.ac.jp/naid/110000560726
  • 2,3‐ジヒドロイノシン誘導体の新規合成法, 服部龍司, 門田泰也, 佐治木弘尚, 広田耕作, 田辺元三, 村岡修, 日本薬学会年会要旨集, 120th, 2, 97,   2000 03 05 , http://jglobal.jst.go.jp/public/200902144439014516
  • ジスルフィドの新規還元剤の開発 (III) 次亜リン酸テトラブチルアンモニウムと次亜リン酸メチルの還元能について, 村岡修, 神田宣彦, 田辺元三, 日本薬学会年会要旨集, 120th, 2, 158,   2000 03 05 , http://jglobal.jst.go.jp/public/200902107705951200
  • Tetra-n-butylammonium Hypophosphite as an Effective Hydrogen Source in the Reduction of Disulfides., 村岡修, 青山寛, 徳永裕子, 田辺元三, 近畿大学薬学総合研究所紀要, 8, 111, 126,   1999 12 14 , http://jglobal.jst.go.jp/public/200902160326497028
  • 益智(Alpinia oxyphylla)の薬理活性セスキテルペノイド, 吉川雅之, 森川敏生, 村上敏之, 松田久司, 村岡修, 藤本学, 田辺元三, 久保道徳, 播磨章一, 日本生薬学会年会講演要旨集, 46th, 183,   1999 08 19 , http://jglobal.jst.go.jp/public/200902158019496648
  • A Photo-cyclization Reaction of A 2,4,6-Tris(phenylthio)hepta-2,4,6-trienal., 後藤悟史, 吉松三博, 田辺元三, 村岡修, 日本化学会講演予稿集, 76th, 2, 1460,   1999 03 15 , http://jglobal.jst.go.jp/public/200902116709276891
  • Study on Pharmacologically Active Sesquiterpenoids from the Fruits of Alpinia oxyphylla (Kainan Island)., 村岡修, 藤本学, ZHENG B‐Z, 田辺元三, 久保道徳, 吉川雅之, 近畿大学薬学総合研究所紀要, 7, 59, 66,   1998 12 , http://jglobal.jst.go.jp/public/200902135552735581
  • Study on Pharmacologycally Active Sesquiterpenenoids from the Fruits of Alpinia oxyphylla (Kainan Island)., 村岡修, 藤本学, ZHENG B‐Z, 田辺元三, 久保道徳, 吉川雅之, 香料・テルペンおよび精油化学に関する討論会講演要旨集, 42nd, 180, 182,   1998 10 , http://jglobal.jst.go.jp/public/200902132157006342
  • Antidiabetic action component of Sri Lanka-produced natural drug "Kotala himbutu" (Salacia reticulata). Absolute structure of .ALPHA.-glucosidase inhibitory component Salacinol having novel thiosugar sulfonium sulfuric acid internal salt struct, 吉川雅之, 村上敏之, 島田ひろみ, 森川敏生, 社謙一, 松田久司, 村岡修, 田辺元三, 山原条二, 日本薬学会年会要旨集, 118th, 2, 108,   1998 03 , http://jglobal.jst.go.jp/public/200902128105841157
  • Reaction peculiarity of bicyclo 3.3.1 nonan-endo-diols in acid catalyst. (II)., 村岡修, 渋田憲一, 後藤康弘, 田辺元三, 日本薬学会年会要旨集, 118th, 2, 96,   1998 03 , http://jglobal.jst.go.jp/public/200902182740313420
  • 1,2-Sulfonyl Sift Reactions on the Cyclopropanes., 吉松三博, 小西圭子, 村岡修, 田辺元三, 日本化学会講演予稿集, 74th, 2, 784,   1998 03 , http://jglobal.jst.go.jp/public/200902196792384424
  • 12 Antidiabetic Constituents of Sri Lankan Natural Medicine "Kotala himbutu" (Salacia reticulata) : Absolute Stereostructures of α-Glucosidase Inhibitors, Salacinol and Kotalanol, with Unique Thiosugar Sulfonium Sulfate Inner Salt Structure, Yoshikawa Masayuki, Murakami Toshiyuki, Morikawa Toshio, Yashiro Kenichi, Matsuda Hisashi, Muraoka Osamu, Tanabe Genzou, Yamahara Johji, Symposium on the Chemistry of Natural Products, symposium papers, 40, 0, 67, 72,   1998 , http://ci.nii.ac.jp/naid/110006679618
    Summary:The roots and stems of Salacia reticulata WIGHT ("Kotala himbutu" in Singhalase, Celastraceae) have been extensively used as a specific remedy for diabetes in Ayurvedic system in Indian traditional medicine. As a continuing part of our screening for antidiabetogenic principles of natural medicine and medicinal foods, we have found that the water-soluble fractions from the roots and stems of S. reticulata strongly inhibited the increase of serum glucose levels after the administration of sucrose or maltose, but not glucose, in rats. Furthermore, the fractions inhibited rat intestinal maltase and sucrase in vitro, although the extract even at high dose did not have any effect on experimental hyperglycemia induced by injection of alloxan in mice. On the other hand, the lipophilic fraction showed inhibitory activity for rat lens aldose reductase and, as the active components, new triterpene kotalagenin 16-acetate (5) was isolated together with several diterpenes and triterpenes. Through bioassay-guided separation, two potent α-glucosidase inhibitors called salacinol (1, 0.0079%) and kotalanol (4, 0.0002%) have been isolated from the water-soluble fraction together with many sugars and glycosides. The absolute stereostructure of salacinol was determined on the basis of chemical and physicochemical evidence, which included the alkaline degradation to 1-deoxy-4-thio-D-arabinofuranose (2) and the X-ray crystallographic analysis. The molecular conformation showed the unique spiro-like configuration of the inner salt comprised of 1-deoxy-4-thio-D-arabinofuranosyl sulfonium cation and 1-deoxy-D-erythrosyl-3-sulfate anion. The structure of kotalanol was also elucidated in a similar manner as that of 1 to be the inner salt comprised of 1-deoxy-4-thio-D-arabinofuranosyl sulfonium cation and 1-deoxyheptosyl-3-sulfate anion. Salacinol (1) and kotalanol (4) were found to exhibit the competitive inhibition for the intestinal α-glucosidase of rat. Their inhibitory activities against sucrase and maltase were nearly equal to those of a commercial α-glucosidase inhibitor acarbose, whereas their activities against isomaltase were much more potent than that of acarbose. 1-Deoxy-4-thio-D-arabinofuranose (2) lacked the activity (IC_<50>>400 μg/ml) and its methyl sulfonium iodide (3) showed weak activity (sucrase: IC_<50> 129 μg/ml; maltase: IC_<50>>400μg/ml). This evidence revealed that the spiro-like inner salt structure of 1 and 4 was essential for the potent α-glucosidase inhibitory activity. Furthermore, 1 more strongly inhibited the increase of serum glucose levels in sucrose-loaded rats than acarbose.
  • Basic research on the digestive absorption improvement of phenytoin. (II). Effect of prodrug formation and in vitro hydrolyzability., 谷野公俊, 小木曽太郎, 岩城正宏, 田辺元三, 村岡修, 日本薬学会年会要旨集, 117th, 4, 16,   1997 03 , http://jglobal.jst.go.jp/public/200902128075511050
  • Study on synthesis of chiral cage compound. (1). Synthesis of (-)-4-proto adamantanone and its 1-hydroxyl compound., 村岡修, 中谷真理, 田辺元三, 日本薬学会年会要旨集, 117th, 2, 12,   1997 03 , http://jglobal.jst.go.jp/public/200902156507960660
  • Stereochemistry of photorearrangement of1,3,4 7-tetrahydroisobenzofuran-1-one., 村岡修, 田辺元三, 日本薬学会年会要旨集, 117th, 2, 67,   1997 03 , http://jglobal.jst.go.jp/public/200902196422396229
  • Development of a new reducing agent for disulfide. (II ) . Reducing agent with phase transfer catalytic capability, Hypophosphorous acid tetrabutylammonium., 村岡修, 青山寛, 徳永裕子, 田辺元三, 日本薬学会年会要旨集, 116th, Pt 2, 107,   1996 03 , http://jglobal.jst.go.jp/public/200902171669415754
  • Photochemical reaction of 9 - oxa -, 9 - thiabicyclo 3. 3. 1 nonane - 3 - ones ., 村岡修, 鄭保忠, 伊野美佳, 田辺元三, 日本薬学会年会要旨集, 116th, Pt 2, 104,   1996 03 , http://jglobal.jst.go.jp/public/200902128262993467
  • Absorption character of sugar-decorated phenytoin in small intestine., 谷野公俊, 小木曽太郎, 岩城正宏, 瓦谷大, 村岡修, 田辺元三, 掛樋一晃, 日本薬学会年会要旨集, 116th, Pt 4, 82,   1996 03 , http://jglobal.jst.go.jp/public/200902114843310971
  • 4,7‐Dihydroisobenzofurna‐1(3H)‐one類の光転位機構について, 村岡修, 田辺元三, 小野勝, 百瀬雄章, 日本薬学会年会要旨集, 115th, Pt 2, 115,   1995 03 , http://jglobal.jst.go.jp/public/200902101208692413
  • 9‐Oxa‐,9‐Thiabicyclo[3.3.1]nonan‐3‐one類の光化学反応, 村岡修, てい保忠, 西村麻衣子, 田辺元三, 日本薬学会年会要旨集, 115th, Pt 2, 124,   1995 03 , http://jglobal.jst.go.jp/public/200902125064591591
  • 糖修飾フェニトインの体内動態とin vitro加水分解性, 谷野公俊, 小木曽太郎, 岩城正宏, 関口美香, 村岡修, 田辺元三, 掛樋一晃, 日本薬学会年会要旨集, 115th, Pt 4, 92,   1995 03 , http://jglobal.jst.go.jp/public/200902144545579980
  • 2位置換‐2‐チアゾリン誘導体の新規簡便合成法, 村岡修, 青山寛, 中嶋啓子, 田辺元三, 吉岡正人, 日本薬学会年会要旨集, 115th, Pt 2, 51,   1995 03 , http://jglobal.jst.go.jp/public/200902172465116150
  • ビシクロ[3.3.1]ノナン‐endo‐ジオール類の酸接触における反応特異性, 村岡修, 奥村正文, 田辺元三, 峯松敏江, 百瀬雄章, 日本薬学会年会要旨集, 114th, Pt 2, 60,   1994 03 , http://jglobal.jst.go.jp/public/200902174417686649
  • フェニトインの脳毛細血管内皮細胞の透過性改善に関する研究 (2) フェニトイン誘導体の物理化学的性質,タンパク結合性及び加水分解性, 小木曽太郎, 岩城正宏, 谷野公俊, 野口裕子, 喜多容子, 村岡修, 田辺元三, 日本薬学会年会要旨集, 114th, Pt 4, 97,   1994 03 , http://jglobal.jst.go.jp/public/200902121764791294
  • Barton反応を利用した9‐azabicyclo[3.3.1]‐nonan‐3α‐olの7位官能基化の試み, 村岡修, 田辺元三, 奥村一仁, 百瀬雄章, 日本薬学会年会要旨集, 114th, Pt 2, 111,   1994 03 , http://jglobal.jst.go.jp/public/200902112599793490
  • Dihydropalustramic Acidの不斉合成, 村岡修, 奥村一仁, 田辺元三, 百瀬雄章, 日本薬学会年会要旨集, 113th, Pt 2, 111,   1993 03 , http://jglobal.jst.go.jp/public/200902186294467236
  • フェニトイン及びその誘導体の血中および脳内のPharmacokinetics, 小木曾太郎, 岩城正宏, 谷野公俊, 野口裕子, 村岡修, 田辺元三, 日本薬学会年会要旨集, 113th, Pt 4, 54,   1993 03 , http://jglobal.jst.go.jp/public/200902189152267522
  • 4,7‐二置換dihydro‐1(3H)‐isobenzofuranone類の光転位反応について, 村岡修, 田辺元三, 山口和彦, 山本江美, 百瀬雄章, 日本薬学会年会要旨集, 113th, Pt 2, 51,   1993 03 , http://jglobal.jst.go.jp/public/200902188577445509
  • 立体拘束を有するα位ベンジル置換2(5H)‐Furanoneの光反応, 村岡修, 田辺元三, 辰巳尚美, 井垣裕子, 上坂友美, 百瀬雄章, 日本薬学会年会要旨集, 112th, Pt 2, 29,   1992 03 , http://jglobal.jst.go.jp/public/200902006720445530
  • 2‐Ethyl‐9‐azabicyclo[3.3.1]nonan‐3‐oneのWhite転位による2,6(cis)位置換ピペリジン誘導体への変換, 村岡修, 奥村一仁, 猪川香織, 田辺元三, 百瀬雄章, 日本薬学会年会要旨集, 112th, Pt 2, 90,   1992 03 , http://jglobal.jst.go.jp/public/200902029778795787
  • On the Structure-Anti-Perkinson Activity Relationships in the Aminotricycles. I. Synthetic Studies on Tricyclic Analogues of Symmetrel, Muraoka Osamu, Tanabe Genzoh, Bulletin of Pharmaceutical Research and Technology Institute, 1, 58, 61,   1992 , http://ci.nii.ac.jp/naid/110000560585
  • 85 SYNTHESES OF α,α'-CIS-SUBSTITUTED PIPERIDINE AND PYRROLIDINE ALKALOIDS BY THE REGIOSELECTIVE α-CLEAVAGE OF 2-ALKYL-ω-AZABICYCLO[3.n.1]ALKAN-3-ONE, Muraoka O, Okumura K, Inokawa K, Maeda T, Tanabe G, Momose T, Symposium on the Chemistry of Natural Products, symposium papers, 34, 0, 657, 662,   1992 , http://ci.nii.ac.jp/naid/110006679146
    Summary:α,α'-cis-Substituted piperidine or pyrrolidine alkaloids, indolizidine 223AB (5), monomorine I (6) and pinidine (19) were synthesized efficiently by the regioselective photo-cleavage of 2-alkyl-ω-azabicyclo[3.n.1]alkan-3-one (1: n=1, 0) as a common synthon. The course is a more efficient alternative to the one via the asymmetric deprotonation previously developed. Dihydropalustaramic acid (10), a versatile intermediate for the synthesis of dihydropalustrine, was also synthesized stereospecifically starting from the same material (1: n=1) via the tandem Beckmann and Huisgen-White rearrangement. Unusual stereospecificity encountered in the alkylation of 1 is also discussed.
  • 含窒素架橋双環系ケトンの光α開裂を利用したピペリジンアルカロイドの合成研究, 村岡修, 前田知美, 田辺元三, 百瀬雄章, 日本薬学会年会要旨集, 111th, Pt 2, 20,   1991 03 , http://jglobal.jst.go.jp/public/200902045526241970
  • THE TANDEM BECKMANN AND HUISGEN-WHITE REARRANGEMENT AS AN ALTERNATIVE TO THE BAEYER-VILLIGER OXIDATION OF THE 9-AZABICYCLO[3.3.1]NONAN-3-ONE SYSTEM - A FACILE ROUTE TO +/--DIHYDROPALUSTRAMIC ACID (VOL 36, PG 7, 1993), T MOMOSE, K OKUMURA, H TSUJIMORI, K INOKAWA, G TANABE, O MURAOKA, Y SASAKI, CH EUGSTER, HETEROCYCLES, 36, 4, 921, 921,   1993 04

Research Grants & Projects

  • Synthetic Studies on Pharmacologically Active Adamantane Derivatives by Use of the Bicyclo[3.3.1]nonane System as a Synthon
  • Studies on the Reactivity Reactivity of Tetra-n-butylammonium Hypophosphite as the New Reductant
  • Studies on Potent Antidiabetic Principle from the Ayurvedic Traditional Medicine Kotala himbutu(Salacia recticulata WIGHT)in Sri Lanka and India