Synthesis and SAR study of novel tetrodotoxin analogs.

2009 Fiscal Year Final Research Report

• 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
• 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
  • 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
  • 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
  • Peer Reviewed
• [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)
  • Year and Date: 20091200
• [Book] Stereoselective synthesis of tetrodotoxin from carbohydtates.(Fukugo Toshistsu no Kagaku to Saishin Oyo Gijutsu) (2009)
  • Author(s): Ken-ichi Sato; Shoji Akai
  • Total Pages: 113-128