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Laboratory of Bioorganic Chemistry

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Research Synopsis

     Using interesting bioactive natural products discovered by our research group as lead compounds, we have synthesized various analogues by establishing efficient synthetic methods and performing chemical conversions in order to clarify structure-activity relationships and develop new drugs.  Considering the previously unknown actions of macrolides with unique biological activities and structures, we have also synthesized various derivatives to find new drugs.

     Creation of drugs such as anti-infectious agents from natural products by the techniques of organic synthesis.

  1. Determination of the relative and absolute stereochemistries of bioactive natural products
  2. Establishment of an efficient method for the total synthesis of bioactive natural products
  3. Synthetic studies for the development of new drugs using bioactive natural products as leads
  4. Synthesis of macrolides with novel biological functions and the elucidation of their modes of action
  5. Development of non-natural bioactive products used to analyze body and cell functions
  6. Creation of novel molecules with specific functions from bioactive natural materials

Staff

Name position
Sunazuka Toshiaki   Professor (Chief of a laboratory)
Hirose Tomoyasu   Associate Professor
Sugawara Akihiro   Project Assistant Professor
Yamada Takeshi   Project Assistant Professor

Student

Name Student
Ideguchi Tetsuya   Student, Doctoral Program
Nakano Hayato   Student, Doctoral Program
Oshita Jun   Student, Doctoral Program
Kimishima Aoi   Student, Doctoral Program
Toguchi Shohei   Student, Doctoral Program
Sugita Yuki   Student, Master's Program
Sennari Go   Student, Master's Program
Takada Hirokazu   Student, Master's Program
Maruyama Hitomi   Student, Master's Program
Aranai Haruto   Student, Master's Program
Oikawa Daiki   Student, Master's Program
Kubo Masahiko   Student, Master's Program
Satake Yudai   Student, Master's Program
Hosaka Misato   Student, Master's Program
Horimatsu Yuki   Student, Master's Program

Researcher

Name position
Kobayashi Yutaka   Researcher
Uchiyama Yukari   Assistant Researcher
Kurihara Tomoko   Assistant Researcher

Research Results

  1. Akihiro Sugawara, Toshiaki Tanaka, Tomoyasu Hirose, Aki Ishiyama, Masato Iwatsuki, Yoko Takahashi, Kazuhiko Otoguro, Satoshi Omura, and Toshiaki Sunazuka : Borrelidin analogues with antimalarial activity; design, synthesis and biological evaluation against Plasmodium falciparum parasites. Bioorg. Med. Chem. Lett. 2013 accepted
  2. Ying-Ji Li, Takako Shimizu, Yukiyo Hirata, Hirofumi Inagaki, Hajime Takizawa, Arata Azuma, Tomoyuki Kawada, Isamu Sugawara, Shoji Kudoh, Toshiaki Sunazuka, Satoshi Omura : EM, EM703 inhibit NF-kB activation induced by oxidative stress from diesel exhaust particle in human bronchial epithelial cells: Importance in IL-8 transcription. Pulm Pharmacol Ther. 2013 in press
  3. Ayumi Tsutsui, Tomoyasu Hirose, Aki Ishiyama, Masato Iwatsuki, Arisa Yokota, Hitomi Maruyama, Hidehito Matsui, Kazuhiko Otoguro, Hideaki Hanaki, Satoshi Omura and Toshiaki Sunazuka : Antimalarial C-9 oxime derivatives from tylosin, produced by click chemistry” Journal of Antibiotics 2012, 65, Accepted.
  4. Tsuyoshi Yamamoto, Naoyuki Izumi, Hideaki Ui, Akito Sueki, Rokuro Masuma, Kenichi Nonaka, Tomoyasu Hirose, Toshiaki Sunazuka, Takayuki Nagai, Haruki Yamada, Satoshi Omura and Kazuro Shiomi :Wickerols A and B: Novel anti-influenza virus diterpenes produced by Trichoderma atroviride FKI-3849” Tetrahedron 2012, 68, 9267-9271.
  5. Akihiro Sugawara, Akito Sueki, Tomoyasu Hirose, Hideaki Shima, Kiyoko S Akagawa, Satoshi Omura and Toshiaki Sunazuka :Novel 12-membered non-antibiotic macrolides, EM900 series with anti-inflammatory and/or immunomodulatory activity; Synthesis, structure activity-relationships and in vivo study. Journal of Antibiotics 2012, 65, 487-490.
  6. Tomohiro Suzuki, Jae-Hoon Choi, Takumi Kawaguchi, Kimiko Yamashita, Akio Morita, Hirofumi Hirai, Tomoyasu Hirose, Kaoru Nagai, Satoshi Omura, Toshiaki Sunazuka, Hirokazu Kawagishi. : A novel N-glucoside, Makomotindoline, from Makomotake, Zizania latifolia Infected with Ustilago esculenta, Bioorg. Med. Chem. Lett., 2012, 22, 4246-4248.
  7. Aoi Kimishima, Tomoyasu Hirose, Akihiro Sugawara, Takanori Matsumaru, Kaoru Nakamura, Ken Katsuyama, Masaki Toda, Hirokazu Takada, Rokurou Masuma, Satoshi Omura, Toshiaki Sunazuka. : Toward the total synthesis of luminamicin: construction of 14-membered lacton framework possessing versatile enol ether moiety. Tetrahedron Letters 2012, 53, 2813-2816.

 

  1. Gouda H, Kobayashi Y, Yamada T, Ideguchi T, Sugawara A, Hirose T, Omura S, Sunazuka T, Hirono S. Three-dimensional solution structure of bottromycin A2: a potent antibiotic active against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci. Chem Pharm Bull (Tokyo). 2012;60(2):169-71.
  2. Noguchi, Yoshihiko; Hirose, Tomoyasu; Furuya, Yujiro; Ishiyama, Aki, Otoguro, Kazuhiko, Omura, Satoshi; Sunazuka, Toshiaki : The first total synthesis and reassignment of the relative stereochemistry of 16-hydroxy-16,22-dihydroapparicine Tetrahedron Lett. 2012, 53, 1802-1807. DOI:10.1016/j.tetlet.2012.01.110
  3. Otsu, K.; Ishinaga, H.; Suzuki, S.; Sugawara, A.; Sunazuka, T.; Omura, S.; Jono, H.; Takeuchi, K. Effects of a Novel Nonantibiotic Macrolide, EM900, on Cytokine and Mucin Gene Expression in a Human Airway Epithelial Cell Line Pharmacology 2011, 88, 327-332. DOI:10.1159/000334339
  4. Tatsuya Shirahata, Asami Kojima, Satoko Teruya, Jun-ichi Matsuo, Masaki Yokoyama, Shogo Unagiike, Toshiaki Sunazuka, Kazuishi Makino, Eisuke Kaji, Satoshi Omura, Yoshinori Kobayashi Sequential one-pot glycosylation with glycosyl N-trichloroacetylcarbamate and trichloroacetate including dehydrative approach using 1-hydroxy sugars Tetrahedron 2011, 67, 6482-6496. DOI: 10.1016/j.tet.2011.06.006
  5. Tomoyasu Hirose, Takako Kasai, Takafumi Akimoto, Ayako Endo, Akihiro Sugawara, Kazuo Nagasawa, Kazuro Shiomi, Satoshi Omura, and Toshiaki Sunazuka Solution-phase total synthesis of the hydrophilic natural product argifin using 3,4,5-tris(octadecyloxy)benzyl tag. Tetrahedron 2011, 67, 6633-6643. DOI: 10.1016/j.tet.2011.05.073
  6. Tomoyasu Hirose, Masato Iwatsuki, Satoshi, Omura, Toshiaki Sunazuka Isolation, total synthesis and determination of the absolute configuration of Guadinomines; potent inhibitors of a bacterial type III secretion system J. Soc. Org. Chem. Jpn. 2011, 69, 775-788. DOI:10.5059/yukigoseikyokaishi.69.775
  7. Akihiro Sugawara, Akito Sueki, Tomoyasu Hirose, Hideaki Shima, Kiyoko Akagawa, Satoshi Omura, Toshiaki Sunazuka Novel 12-membered non-antibiotic macrolides from erythromycin A; EM900 series as novel leads for anti-inflammatory and/or immunomodulatory agents. Bioorg. & Med. Chem. Lett. 2011. 21, 3373-3376.
  8. Inahashi Y, Iwatsuki M, Ishiyama A, Namatame M, Nishihara-Tsukashima A, Matsumoto A, Hirose T, Sunazuka T, Yamada H, Otoguro K, Takahashi Y, Omura S, Shiomi K. Spoxazomicins A-C, novel antitrypanosomal alkaloids produced by an endophytic actinomycete, Streptosporangium oxazolinicum K07-0460(T).
  9. Ishiyama A, Iwatsuki M, Namatame M, Nishihara-Tsukashima A, Sunazuka T, Takahashi Y, Omura S, Otoguro K. Borrelidin, a potent antimalarial: stage-specific inhibition profile of synchronized cultures of Plasmodium falciparum. J. Antibiot. 2011. in press

 

  1. Yutaka Kobayashi, Maki Ichioka, Tomoyasu Hirose, Kenichiro Nagai, Atsuko Matsumoto, Hidehiro Matsui, Hideaki Hanaki, Rokuro Masuma, Yoko Takahashi, Satoshi Omura, and Toshiaki Sunazuka Bottromycin derivatives: efficient chemical modifications of the ester moiety and evaluation of anti-MRSA and anti-VRE activities. Bioorg. Med. Chem. Lett. 2010, 20, 6116-6120.
  2. Ayumi Tsutsui, Yujiro Furuya, Tomoyasu Hirose, Riyon Kim, Rokuro Masuma, Atsuko Matsumoto, Yoko Takahashi, Aki Ishiyama, Miyuki Namatame, Kazuhiko Otoguro, Satoshi Omura, and Toshiaki Sunazuka Boromycin derivatives: synthesis and antimalarial activity in vitro and in vivo.Heterocycles 2010, 82, 289-295. special issue dedicated to Professor Albert Eschenmoser
  3. Gouda H, Sunazuka T, Hirose T, Iguchi K, Yamaotsu N, Sugawara A, Noguchi Y, Saito Y, Yamamoto T, Watanabe T, Shiomi K, Omura S, Hirono S. NMR spectroscopy and computational analysis of interaction between Serratia marcescens chitinase B and a dipeptide derived from natural-product cyclopentapeptide chitinase inhibitor argifin. Bioorg Med Chem. 2010, 18, 5835-5844.
  4. Nagai T, Shimizu Y, Shirahata T, Sunazuka T, Kiyohara H, Omura S, Yamada H. Oral adjuvant activity for nasal influenza vaccines caused by combination of two trihydroxy fatty acid stereoisomers from the tuber of Pinellia ternata. Int Immunopharmacol., 2010, 10, 655-661.
  5. Shirahata T, Matsuo J, Teruya S, Hirata N, Kurimoto T, Akimoto N, Sunazuka T, Kaji E, Omura S. : Improved catalytic and stereoselective glycosylation with glycosyl N-trichloroacetylcarbamate: application to various 1-hydroxy sugars. Carbohydr. Res., 2010, 345, 740-749.
  6. Tomoyasu Hirose, Toshiaki Sunazuka, Satoshi Omura. : Recent development of two chitinase inhibitor, Argifin and Argadin, produced by soil microorganisms. Proc. Jpn. Acad., Ser. B, 2010, 86, 85-102.
  7. Namikawa H., Sunazuka T., Kitamura Y., Suzuki T., Hamasaki Y., Yamazaki S., Omura S., Hatamochi A. : Effect of erythromycin A and its new derivative EM201 on type I collagen production by cultured dermal fibroblasts. Arch Dermatol Res. 2010, 302, 341-348.