2004 Fiscal Year Final Research Report Summary
Medicinal chemistry on marine alkaloid as a seed of the development for a new anticancer drug in Malaya area
| Project/Area Number |
14370725
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | Faculty of Pharmaceutical Sciences, Meiji Pharmaceutical University |
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Principal Investigator |
KUBO Akinori Meiji Pharmaceutical University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (60097201)
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| 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)
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| Project Period (FY) |
2002 – 2004
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| Keywords | Natural Marine Product / Alkaloid / Isoquinoline / Ecteinascidin / Renieramy / Anticancer Drug / Structure Elucidation / Large amount Supply |
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| 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.
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