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Medicinal chemistry on marine alkaloid as a seed of the development for a new anticancer drug in Malaya area

Research Project

Project/Area Number 14370725
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical pharmacy
Research InstitutionFaculty of Pharmaceutical Sciences, Meiji Pharmaceutical University

Principal Investigator

KUBO Akinori  Meiji Pharmaceutical University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (60097201)

Co-Investigator(Kenkyū-buntansha) SAITO Naoki  Meiji Pharmaceutical University, Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 助教授 (80142545)
MIKAMI Yuzuru  Chiba University, Research center for Pathbenic Fungi and Microbiol Toxicoses, Professor, 真菌医学研究センター, 教授 (40092100)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥11,900,000 (Direct Cost: ¥11,900,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2002: ¥7,700,000 (Direct Cost: ¥7,700,000)
KeywordsNatural Marine Product / Alkaloid / Isoquinoline / Ecteinascidin / Renieramy / Anticancer Drug / Structure Elucidation / Large amount Supply / イソキノリンアルカロイド / 制癌剤 / 脱N-メチル化 / エステル化 / 炭素繊維 / 養殖 / ジョルマイシン / 酸化的分解反応 / 変換反応 / サフラマイシン / 全合成
Research Abstract

Ecteinascidin 743 is a natural product isolated from the marine tunicate Ecteinascida turbinata, which has been demonstrated to be a highly promising, exceeding potent antitumor agent currently in phase II/III clinical trials in USA and EU. As a part of our search for new anticancer metabolites in the isolation and characterization of biologically active compounds from Thai marine animals, we have succeeded to find a Thai tunicate, Ecteinascida thurstoni Herdman 1891, which is the first example of the Asian tunicate containing this class of molecules, growing around Phuket Island. We report the isolation and structural elucidation of ecietnascidins 770 and 786 from the KCN pretreated Thai tunicate. Isolation of natural marine products using this procedure has the advantage of increasing the yield of labile Ecteinascidin-type compounds. Furthermore, we found a blue sponge, Xestospongia sp., growing around Sichang Island in the Gulf of Thailand, and by the same strategy, we are succeeded the gram-scale isolation of renieramycins M, which has also potent amtitumor activity.
By the way, one of the most intriguing problems, which is how to maintain a consistent supply of ecteinascidins for drug development : by isolation from marine sources or by total synthesis still remains. In connection with the development of a short-step synthesis of this series of natural product, we have previous reported the preparation of the tricyclic lactam intermediate, and the partial synthesis of the ABC ring model compound. Encourage by the results of our studies, we apply these strategies for preparation of the ABCDE ring system of ecteinascidins, having characteristic substituents in both benzene rings.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (22 results)

All 2004 2003 2002 2001 2000 Other

All Journal Article (11 results) Patent(Industrial Property Rights) (1 results) Publications (10 results)

  • [Journal Article] Synthesis of a Simple Natural Marine Product, 6-Hydroxy-7-methoxyisoquino linemethanol2004

    • Author(s)
      Naoki Saito et al.
    • Journal Title

      Chem.Pharm.Bull. 52

      Pages: 282-286

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Synthesis of a Simple Natural Marine Product, 6-Hydroxy-7-methoxyisoquinolinemethanol2004

    • Author(s)
      Naoki Saito et al.
    • Journal Title

      Chem.Pharm.Bull. 52

      Pages: 282-286

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Chemistry of Renieramycins. Part 5. Structure Elucidation of Renieramycin Type Derivatives O, Q, R, and S from Thai Marine Sponge Xestospongia Species Pretreated with potassium cyanide2004

    • Author(s)
      Surattana Amnuoypol et al.
    • Journal Title

      J.Nat.Prod. 67(6)

      Pages: 1023-1028

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Chemistry of Renieramycins. Part 6 : Transformation of Renieramycin M into Jorumycin J including Oxidative Degradation Products, Mimosamycin, Renierone, and Renierol Acetate2004

    • Author(s)
      Naoki Saito et al.
    • Journal Title

      Tetrahedron 60

      Pages: 3873-3881

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Synthetic Approaches toward Ecteinascidins. Part 2. Preparation of the ABCDE Ring System of Ecieinascidins having Characteristic Substituents in Both Benzene Rings2003

    • Author(s)
      Naoki Saito et al.
    • Journal Title

      Chem.Pharm.Bull. 51

      Pages: 821-831

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Chemistry of Renieramycins. Part 3. Isolation and Structure of Stabilized Renieramycin Type Derivatives Possessing Antitumor Activity from Thai Sponge, Xestospongia Species, Pretreated with Potassium Cyanide2003

    • Author(s)
      Khanit Suwanborirux et al.
    • Journal Title

      J.Nat.Prod. 66

      Pages: 1441-1446

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Synthetic Approaches toward Ecteinascidins. Part 2. Preparation of the ABCDE Ring System of Ecteinascidins having Characteristic Substituents in Both Benzene Rings2003

    • Author(s)
      Naoki Saito et al.
    • Journal Title

      Chem.Pharm.Bull. 51

      Pages: 821-831

    • NAID

      110003615402

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Chemistry of Renieramycins. Part 3. Isolation and Structure of Stabilized Renieramycin Type Derivatives Possessing Antitumor Activity from Thai Sponge, Xestospongia Species, Pretreated Pottasium Cyanide2003

    • Author(s)
      Khanit Suwanborirux et al.
    • Journal Title

      J.Nat.Prod. 66

      Pages: 1441-1446

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Ecteinascidins 770 and 786 from Thai Tunicate Ecteinascidia thurstoni2002

    • Author(s)
      Khanit Suwanborirux et al.
    • Journal Title

      J.Nat.Prod. 65

      Pages: 935-937

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A Practical Synthesis of the ABC Ring Model of Ecteinascidins2000

    • Author(s)
      Naoki Saito et al.
    • Journal Title

      Chem.Pharm.Bull. 48

      Pages: 1549-1557

    • NAID

      110003635326

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A Practical Synthesis of the ABC Ring of Ecteinascidins2000

    • Author(s)
      Naoki Saito et al.
    • Journal Title

      Chem.Pharm.Bull. 48

      Pages: 1549-1557

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] エクチナサイジン786、その所得方法およびその用途2001

    • Inventor(s)
      久保陽徳ら
    • Industrial Property Rights Holder
      久保陽徳ら
    • Filing Date
      2001-08-31
    • Acquisition Date
      2002-08-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Naoki Saito et al.: "Synthetic Approached Toward Ecteinascidins. Part 2. Preparation of the ABCDE Ring System of Ecteinascidins Having Characteristic Substituetis in Both Benzene Rings"Chem.Pharm.Bull.. 51(7). 821-831 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Khanit Suwanborirux et al.: "Chemistry of Renieramycins. Part 3. Isolation and Structure of Stabilized Renieramycin Type Derivatives Possessing Antitumor Activity from Thai Sponge, Xestospongia Species Pretreated with Potassium Cyanide"J.Nat.Prod.. 66(11). 1441-1446 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Naoki Saito et al.: "Chemistry of Antitumor Isoquinolinequinone Alkaloids : Unexpected Oxidative Degradation of Saframycin S to Generate Simple Isoquinoline Alkaloids, Mimosamycin and Mimocin"Heterocycles. 61. 79-86 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Naoki Saito, et al.: "Chemistry of Renieramycins. Part 4. Synthesis of a Simple Natural Marine Product, 6-Hydroxy-7-methoxyisoquinolinemethanol"Chem.Pharm.Bull.. 52(2). 282-286 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Surattans Amnuoypol et al.: "Chemistry of Renieramycins. Part 5. Structure Elucidation of Renieramycin Type Derivatives O, Q, R, and S, from Thai Marine Sponge Xestospongia Species Pretreated with Potassium Cyanide"J.Nat.Prod.. (発表予定).

    • Related Report
      2003 Annual Research Report
  • [Publications] Naoki Saito, et al.: "Chemistry of Renieramycins. Part 6. Transformation of Renieramycin M into Jorumycin and Renieramycin J Including Oxidative Degradation Products, Mimosamycin, Renierone, and Renierol Acetate"Tetrahedron. (発表予定).

    • Related Report
      2003 Annual Research Report
  • [Publications] Suwanborirux K. et al.: "Ecteinascidins 770 and 786 from the Thai Tunicate Ecteinascidia thurstoni"J. Nat. Prod.. 65. 935-937 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Koizumi Y et al.: "Chemistry of Renieramycins. Part 2. Partial Reduction and Nucleophilic Substitution of Hexahydro-1,5-imino-4-oxo-3-benzazocine-7,10-dione : Promising Method to Construct Renieramycin J from Renieramycin G via Renieramycin E"Heterocycles. 57(12). 2345-2355 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Suwanborirux K. et al.: "Chemistry of Renieramycins. Part 3. Isolation and Structure of Stabilized Renieramycin Type Derivatives Possessing Antitumor Activity from Thai Sponge, Xestospongia Species, Pretreated with Potassium Cyanide"(発表予定).

    • Related Report
      2002 Annual Research Report
  • [Publications] Saito N. et al.: "Synthetic Approaches toward Ecteinascidins. Part 2. Preparation of the ABCDE Ring System of Ecteinascidins Having Characteristic Substituents in Both Benzene Rings"(発表予定).

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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