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2002 Fiscal Year Final Research Report Summary

Synthetic Study on Ecteinascidin 743, Potent and Scarcity Antitumor Natural Product

Research Project

Project/Area Number 12307052
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical pharmacy
Research InstitutionThe University of Tokyo

Principal Investigator

FUKUYAMA Tohru  The University of Tokyo Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (10272486)

Co-Investigator(Kenkyū-buntansha) KAN Toshiyuki  The University of Tokyo Graduate School of Pharmaceutical Sciences, Research Associate, 大学院・薬学研究科, 助手 (10221904)
Project Period (FY) 2000 – 2002
KeywordsEcteinascidin 743 / antitumor / anticancer drug / total synthesis / natural scarcity / tetrahydroisoquinoline / Ugi's 4CC reaction / Heck reaction
Research Abstract

Ecteinascidin 743 (Et 743) is an extremely potent antitumor agent isolated from a marine tunicate, Ecteinascidia turbinata. Based on promising results in phase II clinical trials, Et 743 is likely to become the first anticancer drug among marine natural products. The novelty of its structure, the remarkable biological activities, and its natural scarcity have made it an attractive target for total synthesis. We accomplished an efficient total synthesis of Et 743 that would potentially lead to the development of a practical synthesis of this important compound. The synthesis was started from a large scale preparation of left and right segment. These two segments were efficiently coupled by the Ugi's 4CC reaction, and transformed into the cyclic enamide via diketopiperazine. Intramolecular Heck reaction of the enamide proceeded smoothly to give the bicyclo[3.3.1] skeleton. Construction of B-ring was performed by the phenol-aldehyde cyclization, giving the desired pentacyclic compound. After conversion to the sulfur-containing ten-membered lactone, construction of tetrahydroisoquinoline moiety was afforded ecteinascidin 743.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] T.Fukuyama: "Facile Construction of N-Hydroxybenzazocine : Enantioselective Total Synthesis of (+)-FR900482"Angew.Chem.Int.Ed.. 41. 4686-4687 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Fukuyama: "Highly Versatile Synthesis of Polyamines by the Ns-strategy on a Novel Trityl Chloride Resin"Synlett. 1338-1340 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Fukuyama: "Synthetic Approach to Tetrodotoxin"Synlett. 1323-1325 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Fukuyama: "Efficient Macrocyclization by Means of 2-Nitrobenzenesulfonamide and Total Synthesis of Lipogrammistin-A"Tetrahedron. 58. 6267-6277 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Fukuyama: "Total Synthesis of Ecteinascidin 743"J.Am.Chem.Soc.. 124. 6552-6555 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Fukuyama: "Stereocontrolled Total Synthesis of (+)-Vinblastine"J.Am.Chem.Soc.. 124. 2137-2139 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masashi Suzuki, Mika Kambe, Hidetoshi Tokuyama, Tohru Fukuyama: "Facile Construction of N-Hydroxybenzazocine ; Enantioselective Total Synthesis of (+)-FR900482"Angew.Chem.Int.Ed.. 41. 4686 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Toshiyuki Kan, Hideki Kobayashi, Tohru Fukuyama: "Highly Versatile Synthesis of Polyamines by the Ns-strategy on a Novel Trity1 Chloride Resin"Synlett. 1338 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tetsuji Itho, Manabu Watanabe, Tohru Fukuyama: "Synthetic Approach to Tetrodotoxin"Synlett. 1323 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Toshiyuki Kan, Akiko Fujiwara, Hideki Kobayashi, Tohru Fukuyama: "Efficient Macrocyclization by Means of 2-Nitrobenzenesulfonamide and Total Synthesis of Lipogrammistin-A"Tetrahedron. 58. 6267 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Atsushi Endo, Arata Yanagisawa, Masanao Abe, Shigemitsu Tohma, Toshiyuki Kan, Tohru Fukuyama: "Total Synthesis of Ecteinascidin 743"J.Am.Chem.Soc.. 124. 6552 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Satoshi Yokoshima, Toshihiro Ueda, Satoshi Kobayashi, Ayato Sato, Takeshi Kuboyama, Hidetoshi Tokuyama, Tohru Fukuyama: "Stereocontrolled Total Synthesis of (+)-Vinblastine"J.Am.Chem.Soc.. 124. 2137 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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