Synthetic and structure-activity relationship study on a new anticancer agent, yaku'amide A

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790005
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Chemical pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: KURANAGA Takefumi 東京大学, 薬学研究科(研究院), 助教 (70625201)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: ケミカルバイオロジー / ペプチド / 全合成 / ヤクアミド

Research Abstract

A cytotoxic peptide yaku'amide A was isolated from a marine sponge as an extremely potent cytotoxin. The growth-inhibitory activity of yaku'amide A against a panel of 39 human cancer cell lines is quite unique among known anticancer drugs. Therefore, it is suggested that yaku'amide A possesses new mode of action to exert its bioactivity. In order to evaluate its detailed biological activity, chemical synthesis for supplying material was required.
In this project, the development of a new assembly method of the dehydroamino acid residue utilizing Cu-mediated cross coupling reaction and the first total synthesis of yaku'amide A were achieved. In addition to this, another approach for the synthesis of Z-dehydroamino acid using Staudinger ligation was also established.

Research Products

• [Journal Article] Inoue Control of the cytotoxicity of dansylated polytheonamide mimic, an artificial peptide ion channel, by modification of the N-terminal structure (2014)
  • Author(s): H. Itoh, S. Matsutaka, T. Kuranaga, M.
  • Journal Title: Tetrahedron Lett. Volume: 55 Pages: 728-731
  • Peer Reviewed
• [Journal Article] Cu-mediated enamide formation in the total synthesis of complex peptide natural products (2014)
  • Author(s): T. Kuranaga, Y. Sesoko, M. Inoue
  • Journal Title: Nat. Prod. Rep. Volume: 31 Pages: 514-532
  • Peer Reviewed
• [Journal Article] Total Synthesis and Complete Structural Assignment of Yaku'amide A (2013)
  • Author(s): T. Kuranaga, Y. Sesoko, K. Sakata, N. Maeda, A. Hayata, M. Inoue
  • Journal Title: J . Am. Chem. Soc. Volume: 135 Pages: 5467-5474
  • Peer Reviewed
• [Journal Article] Total syntheses of nobilamides B and D : application of traceless Staudinger ligation
  • Author(s): T. Yamashita, H. Matoba, T. Kuranaga, M. Inoue
  • Journal Title: Tetrahedron Volume: (掲載決定済み)
  • Peer Reviewed
• [Presentation] Staudinger反応を用いたα,β-不飽和アミノ酸の合成 (2014)
  • Author(s): 山下智也、的場博亮、倉永健史、井上将行
  • Organizer: 第67回有機合成化学協会関東支部シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 20140500
• [Presentation] ヤクアミドAの全合成および完全構造決定 (2013)
  • Author(s): 倉永健史、瀬底祐介、坂田光命、前田直也、早田敦、井上将行
  • Organizer: 第103回有機合成シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 20130600
• [Presentation] Total Synthesis and Complete Structural Assignment of Yaku'amide A (2013)
  • Author(s): Takefumi Kuranaga, Yusuke Sesoko, Komei Sakata, Naoya Maeda, Atsushi Hayata, Masayuki Inoue
  • Organizer: 第23回日仏医薬精密化学会議[23rd French-Japanese Symposium on Medicinal and Fine Chemistry (FJS 2013)]
  • Place of Presentation: 長崎
  • Year and Date: 20130500
• [Presentation] ヤクアミドAの全合成 (2013)
  • Author(s): 瀬底祐介、坂田光命、前田直也、早田敦、倉永健史、井上将行
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Year and Date: 20130300
• [Presentation] ポリセオナミドミミックのN末端構造改変による機能制御 (2013)
  • Author(s): 松高祥子、伊藤寛晃、倉永健史、井上将行
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Year and Date: 20130300
• [Presentation] Synthetic Studies on Yaku'amides (2012)
  • Author(s): Takefumi Kuranaga, Yusuke Sesoko, Komei Sakata, Naoya Maeda, Atsushi Hayata, Masayuki Inoue
  • Organizer: The 7th International Conference on Cutting-Edge Organic Chemistry in Asia (ICCEOCA-7)
  • Place of Presentation: シンガポール
  • Year and Date: 20121200
• [Remarks]
  • URL: http://www.f.u-tokyo.ac.jp/~inoue/