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研究概要


      構造決定に必要な核磁気共鳴(NMR)や質量分析(MS)に関する新しい手法と技術開発を行い、ケミカルバイオロジー、メタボロミクス研究、 あるいは様々な有機合成化学の研究などで発見あるいは創製される新規化合物の同定、構造解析へ応用する。有機化合物の構造解析において 重要なNMR、MSおよび円二色性分散(CD)などの分析装置を共同利用機器として維持管理・運営を行い、オープンアクセス装置の利用講習、依頼測定、 依頼解析、技術指導など様々な研究支援を全理研に対して行っている。 さらに機器分析に有機合成化学的手法を交えて、有機化合物の同定、構造決定に必要な方法論を開発しその技術を高め、構造解析に関する 様々な応用研究を所内外の共同研究として遂行している。

    2D long-range H(X)C and H(C)X triple-resonance experiment

    • We have developed novel 2D long-range range H(X)C and H(C)X triple-resonance NMR experiments at natural abundance. Available X is one-half spin nucleus such as 15N, 29Si, 31P, 77Se, 119Sn, 195Pt. In structural elucidation, assignment of hydroxyl group position is an important step. We have developed a new method for determining the position of phenolic hydroxyl groups through silylation and application of 2D long-range H(Si)C triple-resonance NMR experiment. We chose tert-butyldimethylsilyl (TBDMS) group as a silyl group because of high sensitivity in 1H by detection of two singlet methyl signals with six and nine equivalent protons, and easiness of handling as protective group.

      • characterization of isomeric mixtures

      • H(Si)C experiment
        • Malon, M., Takahashi, S., and Koshino, H., A new method for determining positions of phenolic hydroxyl groups through silylation and application of H(Si)C triple-resonance NMR experiments, Tetrahedron Lett., 48, 7586-7590 (2007)
      • H(P)C and H(C)P experiments
        • Malon, M. and Koshino, H., H(C)P and (H(P)C triple-resonance experiments at natural abundance employing long-range couplings, Magn. Reson. Chem., 45, 770-776 (2007)
      • H(Se)C and H(C)Se experiments
        • Malon, M., Imakubo, T., and Koshino, H., 1H, 13C and 77Se NMR study of tetraselenafulvalene derivatives supported by novel H(Se)C and H(C)Se triple-resonance experiments at natural abundance, Magn. Reson. Chem., 46, 150-155 (2008)

    Synthesis of Biologically Active Natural Products

      characterization of isomeric mixtures

    • The aims of our research project are development of new chemical and synthetic methods for molecular characterization. As a main theme, we have continued synthesis of a biologically active natural product whose structure is difficult to determine by spectroscopic methods especially. The structure of natural products such as an antitumor annonaceous acetogenin 1 and a p-terphenyl 2 with an inhibition potential of TNF-α production was clarified by systematic total synthesis. Furthermore, syntheses of an angiogenesis inhibitor 3 and the bioactive principles in Brazilian propolis (e. g. 4) were also performed, and their biological activities were evaluated.
      • acetogenins
        • Takahashi, S., Hongo, Y., Tsukagoshi, Y., and Koshino, H., Structural determination of montanacin D by total synthesis, Org. Lett., 10, 4223-4226 (2008)
        • Takahashi, S., Takahashi, R., Hongo, Y., Koshino, H., Yamaguchi, K., and Miyagi, T., Synthesis of all possible isomers corresponding to the proposed structure of montanacin E, and their antitumor activity, J. Org. Chem., 74, 6382-6385 (2009)
      • p-terphenyls
        • Ye, Y. Q., Koshino, H., Onose, J., Yoshikawa, K., Abe, N., and Takahashi, S., First total synthesis of vialinin A, a novel and extremely potent inhibitor of TNF-α production, Org. Lett., 9, 4131-4134 (2007)
        • Ye, Y. Q., Koshino, H., Onose, J., Negishi, C., Yoshikawa, K., Abe, N., and Takahashi, S., Structural revision of thelephantin G by total synthesis and inhibitory activity against TNF-α production, J. Org. Chem., 74, 4642-4645 (2009)
      • ovalicin
        • Takahashi, S., Hishinuma, N., Koshino, H., and Nakata, T., Synthesis of ovalicin starting from D-mannose, J. Org. Chem., 70, 10162-10165 (2005)
      • propolis
        • Tani, H., Hasumi, K., Tatefujji, T., Hashimoto, K., Koshino, H., and Takahashi, S., Inhibitory activity of Brazilian green propolis components and their derivatives on the release of cys-leukotrienes, Bioorg. Med. Chem., 18, 151-157 (2010)

    Structural Revision of Natural Products

    • 　We are interested in development of precise structural determination methods and reliable application of them to natural products and related synthetic compounds. It is well known that the NMR chemical shift is useful information and sensitive to the stereochemistry of organic molecules. We developed CAST/CNMR for highly accurate 13C NMR chemical shift prediction with effective consideration of stereochemistry and ring structures in collaboration with NII (National Institute of Informatics). For example, we reported the structural revision of botcinolide 5, eremophilane sesquiterpenoid peribysins C 8 and D 10, and many terpenoids with (3Z)-2-methyl-3-penten-2-ol moiety such as (23Z)-cycloart-23-ene- 3β,25-diol. In case of (23Z)-cycloart-23-ene-3β,25-diol 11 and 23E isomer 12 we synthesized authentic samples and studied NMR chemical shifts in several solvent systems.

      • characterization of isomeric mixtures

      • botcinolides
        • Tani, H., Koshino, H., Sakuno, E., and Nakajima, H., Botcinins A, B, C, and D, metabolites produced by Botrytis cinerea, and their antifungal activity against Magnaporthe grisea, a pathogen of rice blast disease, J. Nat. Prod., 68, 1768-1772 (2005)
        • Tani, H., Koshino, H., Sakuno, E., Cutler, H. G., and Nakajima, H., Botcinins E and F and botcinolide from Botrytis cinerea and structural revision of botcinolides, J. Nat. Prod., 69, 722-725 (2006)
      • CAST/CNMR and application
        • Satoh, H., Koshino, H., Uzawa, J., and Nakata, T., CAST/CNMR: highly accurate 13C NMR chemical shift prediction system considering stereochemistry, Tetrahedron, 59, 4539-4547 (2003)
        • Satoh, H., Koshino, H., Uno, T., Koichi, S., Iwata, S., and Nakata, T., Effective consideration of ring structures in CAST/CNMR for highly accurate 13C NMR chemical shift prediction, Tetrahedron, 61, 7431-7437 (2005)
        • Koshino, H., Satoh, H., Yamada, T., and Esumi, Y., Structural revision of peribysins C and D, Tetrahedron Lett., 47, 4623-4626 (2006)
        • Takahashi, S., Satoh, H., Hongo, Y., and Koshino, H., Structural revision of terpenoids with a (3Z)-2-methyl-3-penten-2-ol moiety by synthesis of (23E)-and (23Z)-cycloart-23-ene-3β, 25-diols, J. Org. Chem., 72, 4578-4581 (2007)

    Organic Mass Spectrometry

    • We provide a wide range of mass spectrometry-related technological and scientific support to the scientists including chemists and biologists work with any kind of organic molecules (small and large, except for proteomic samples). We maintain a choice of instrumentation to meet diverse research needs for characterization of organic molecules. Our supporting activity includes training of open-access facility user, accurate mass analysis of a variety of organic compounds, molecular weight and elemental composition analysis, structural characterization of unknown compounds, characterization of mixtures, support on spectral and data interpretation, consulting and comprehensive support on experimental design and execution for solving any kind of qualitative and quantitative problems that can be solved by mass spectrometry. Taking the advantage of our expertise in mass spectrometry, we also engage in scientific collaboration with scientists (inside/outside RIKEN).
    • Our research activity on mass spectrometry includes exploration of new methods and concepts in mass spectrometry and their applications. The goal of those basic researches is to provide better mass spectrometry tools to the scientific community in future.