Synthesis and SAR study of novel tetrodotoxin analogs.

• Project/Area Number: 19750147
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Chemistry related to living body
• Research Institution: Kanagawa University
• Principal Investigator: AKAI Shoji Kanagawa University, 工学部, 助教 (00322537)
• Research Collaborator: SATO Kenichi 神奈川大学, 工学部, 教授 (40114871)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥3,680,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥1,600,000 (Direct Cost: ¥1,600,000)
• Keywords: 有機化学 / 生理活性 / 合成化学 / テトロドトキシン

Research Abstract

Tetrodotoxin (TTX), one of the best-known marine toxins, was originally isolated from puffer fish. It is known that TTX selectively combines with elements of the sodium channel, thus inhibiting its function in the cell membrane. Therefore, TTX is utilized as a tool for the analysis of various vital phenomena, which occur via the sodium channel. Therefore, it is considered very important to synthesize larger amounts of TTX and its analogues than those available now. In this work, syntheses of optically active- and partially deoxygenated-TTX from D-glucose and myo-inositol in practical amounts, and its stable isotopic labeling are studied. As a result, a crucial key compound for synthesizing the above target compounds is prepared from D-glucose in 24-28 steps. Total synthesis of 8- and 9-deoxyTTX from the key compounds and its stable isotope labeling are now in progress.

Research Products

• [Journal Article] Total Synthesis of (-)-Tetrodotoxin from D-Glucose: A New Route to Multi-Functionalized Cyclitol Employing the Ferrier(II) Reaction toward (-)-Tetrodotoxin (2010)
  • Author(s): S. Akai, H. Seki, N. Sugita, T. Kogure, N. Nishizawa, K. Suzuki, Y. Nakamura, Y. Kajihara, J. Yoshimura, K. Sato
  • Journal Title: Bull. Chem Soc. Jpn 83(3) Pages: 279-287
  • NAID: 10027172694
  • Peer Reviewed
• [Journal Article] Total Synthesis of (-)-Tetrodotoxin from D-Glucose : A New Route to Multi-Functionalized Cyclitol Employing the Ferrier(II) Reaction toward (-)-Tetrodotoxin. (2010)
  • Author(s): Akai, Shoji ; Sato, Ken-ichi, 他8名
  • Journal Title: Bulletin of the Chemical Society of Japan 83 Pages: 279-287
  • NAID: 10027172694
  • Peer Reviewed
• [Journal Article] Total Syntheses of Bistratamides J, E, and H from Two Types of ΔAla-Containing Oligopeptides (2008)
  • Author(s): H. Suzuki, M. Andoh, Y. Yonezawa, S. Akai, C. Shin, K. Sato
  • Journal Title: Bull. Chem. Soc. Jpn 81(4) Pages: 495-501
  • NAID: 10021074971
  • Peer Reviewed
• [Journal Article] Stereoselective and Efficient Total Synthesis of Optically Active Tetrodotoxin from D-Glucose (2008)
  • Author(s): K. Sato, S. Akai, H. Shoji, N. Sugita, S. Yoshida, Y. Nagai, K. Suzuki, Y. Nakamura, Y. Kajihara, M. Funabashi, J. Yoshimura
  • Journal Title: J. Org. Chem 73(4) Pages: 1234-1242
  • Peer Reviewed
• [Journal Article] Synthesis of (-)-Tetrodotoxin (2008)
  • Author(s): K. Sato, S. Akai, H. Shoji, N. Sugita, S. Yoshida, Y. Nagai, K. Suzuki, Y. Nakamura, Y. Kajihara, M. Funabashi, J. Yoshimura
  • Journal Title: Synfacts 8 Pages: 749-749
  • Peer Reviewed
• [Journal Article] Synthesis of (-)-Tetrodotoxin (2008)
  • Author(s): K. Sato, S. Akai, 他9名
  • Journal Title: Synfacts 8 Pages: 749-749
  • Peer Reviewed
• [Journal Article] Total Syntheses of Bistratamides J, E, and H from Two Types of AAIa -Containing Oligopeptides (2008)
  • Author(s): H. Suzud, S. Akai, 他6名
  • Journal Title: Bull. Chem. Soc. Jpn 4 Pages: 495-501
  • Peer Reviewed
• [Journal Article] Stereoselective and Efficient Total Synthesis of Optically Active Tetrodotoxin from D-Glucose. (2008)
  • Author(s): K. Sato, S. Akai et al.
  • Journal Title: The Journal of Organic Chemistry 73(4) Pages: 1234-1242
  • Peer Reviewed
• [Journal Article] A novel method for regioselective ring-opening reduction of 4,6-O-benzylidene hexopyranoside derivatives using CoCI_2 and BH_3・THF (2007)
  • Author(s): S. Akai, K. Sato et al.
  • Journal Title: Tetrahedron Letters 48(17) Pages: 3103-3104
  • Peer Reviewed
• [Presentation] Bu_4NNO_2-Boc_2O/pyridineを用いるN-Phenylcarbamoyl基の改良脱保護法 (2009)
  • Author(s): 赤井昭二, 他2名
  • Organizer: 第58回有機合成化学協会関東支部シンポジウム
  • Place of Presentation: 長岡技術科学大学(新潟)
  • Year and Date: 2009-11-29
• [Presentation] Bu4NNO2-Boc2O/pyridineを用いるN-Phenylcarbamoyl基の改良脱保護法 (2009)
  • Author(s): 赤井昭二, 田中李佳, 佐藤憲一
  • Organizer: 第58回有機合成化学協会関東支部シンポジウム-新潟(長岡)シンポジウム-
  • Place of Presentation: 新潟(長岡)
• [Book] Stereoselective synthesis of tetrodotoxin from carbohydtates.(Fukugo Toshistsu no Kagaku to Saishin Oyo Gijutsu) (2009)
  • Author(s): Ken-ichi Sato; Shoji Akai
• [Book] 複合糖質の化学と最新応用技術(Glycoconjugate Chemistry and Modern Applied Technology) (2009)
  • Author(s): Sato, Ken-ichi ; Akai, Shoji, 他66名
  • Total Pages: 298
  • Publisher: シーエムシー出版