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A NEW DEVELOPMENT OF SYNTHETIC ORGANIC CHEMISTRY FOR BIOLOGICALLY ACTIVE NATURAL PRODUCTS OF MARINE ORIGINS

Research Project

Project/Area Number 10308027
Research Category

Grant-in-Aid for Scientific Research (A).

Allocation TypeSingle-year Grants
Section一般
Research Field Bioorganic chemistry
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

MURAI Akio  Hokkaido Univ., Grad.School of Sci., Prof., 大学院・理学研究科, 教授 (20000838)

Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥33,100,000 (Direct Cost: ¥33,100,000)
Fiscal Year 2000: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1998: ¥26,600,000 (Direct Cost: ¥26,600,000)
Keywords(+)-obtusenyne / condensed polycyclic ether / ciguatoxin / total synthesis / polycavernoside A / pinnatoxins / pectenotoxins / epoxy alcohol / ランタントリフレート / 貝毒 / Diels-Alder反応 / 中員環エーテル / 環状ポリエーテル / 生合成 / 超微量海産毒 / ラクトンビニルトリフレート法 / オブツセニン / 含臭素中員環エーテル
Research Abstract

1) The first total synthesis of (+)-obtusenyne isolated from a red alga, Laurencia obtusa, has been achieved. Furthermore, two isomers of obtusenyne, which had been isolated by None and undetermined stereochemically, were totally synthesized. These results led to establishment of the absolute configuration of these compounds.
2) The synthetic route has been established toward realization of the proposed biosynthetic pathway for condensed cyclic polyether compounds of marine sources. Eventually, construction of the condensed bicyclic and tricyclic ether compounds were carried out firstly in endo-fashions starting from the corresponding polyepoxy alcohols as the models.
3) Two new efficient methods have been established in order to construct convergently two-condensed cyclic ethers.
4) The synthetic studies were developed toward the total synthesis of ciguatoxin which is the causative compound for ciguatera intoxication. The synthetic strategy was based on the convergent procedure to synthe … More size the four respective fragments and then to combine them constructing three residual 6-7-membered cyclic ether systems (CD,GH,JK). The synthesis of the CD and JK ring systems has been already achieved.
5) The first total synthesis of polycavernoside A isolated from a red alga, Polycavernosa tsudai, regarding as a causative compound for human intoxication, has been achieved. Furthermore, the structure-biological activity relationship has been clarified.
6) The study toward the total synthesis of pinnatoxins causing shell-fish poisoning originated from Pinna attenuata has been developed. Resultingly, the 1-step construction of the common BCDEF-ring system has been achieved. Furthermore, the strategy for construction of the AG-ring system has been established using an intermolecular Diels-Alder reaction by the model experiments.
7) The study toward the total synthesis of pectenotoxins causing shell-fish poisoning originated from Patinopecten yessoensis has been developed. Resultingly, all the fragments were able to be constructed except the C30 position. Less

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] K.Fujiwara: "La(OTf)_3-Catalyzed 7-endo and 8-endo Selective Cyclizations of Hydroxy Epoxides"Tetrahedron Lett.. 39・5/6. 393-396 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] J.Ishihara: "Studies on the Stability of 1,7,9-Trioxadispiro [5.1.5.2] pentadecane System : The Common Tricyclic Acetal Moiety of Pinnatoxins"Synlett. No.6. 603-606 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Fujiwara: "Total Synthesis and Absolute Configuration of Polycavernoside A"J.Am.Chem.Soc.. 120・41. 10770-10771 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Fujiwara: "Chemical Realization of the Biogenetic Pathways Proposed for the Fused-Polycyclic Ethers of Marine Origins"Heterocycles. 50・1. 561-593 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Fujiwara: "Total Synthesis of (+)-Obtusenyne"J.Org.Chem.. 64・8. 2616-2617 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Sugimoto: "Synthesis of the B,C,D,E,F-Ring Fragment of Pinnatoxins"Synlett. No.5. 541-544 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] D.Awakura: "Determination of the Absolute Configurations of Norte's Obtusenynes by Total Syntheses of (12R,13R)-(-)- and (12S,13R)-(+)-Obtusenynes"Chemistry Lett.. No.6. 461-462 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Fujiwara: "A Simple Convergent Method for the Construction of Fused Tri-and Tetracyclic Ethers"Synlett. No.7. 1037-1040 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] L.Barriault: "Synthesis and Biological Evaluation of Analogues of the Marine Toxin Polycavernoside A"Bioorg.Med.Chem.Lett.. No.9. 2069-2072 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Fujiwara: "Four-Step Convergent Synthesis of trans-Fused Tetracyclic Oxane"Tetrahedron Lett.. 41・4. 507-508 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Tokiwano: "Biomimetic Construction of Fused Tricyclic Ether by Cascaded endo-Cyclization of the Hydroxy Triepoxide"Synlett. No.3. 329-332 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] D.Awakura: "Synthetic Studies on Pectenotoxins : Synthesis of the Common C8-C18 THF Fragment"Synlett. No.12. 1733-1736 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Fujiwara: "La(OTf)_3-Catalyzed 7-endo and 8-endo Selective Cyclizations of Hydroxy Epoxides"Tetrahedron Lett.. 39 5/6. 393-396 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] J.Ishihara: "Studies on the Stability of 1,7,9-Trioxadispiro[5.1.5.2]pentadecane System : The Common Tricyclic Acetal Moiety of Pinnatoxins"Synlett. No.6. 603-606 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Fujiwara: "Total Synthesis and Absolute Configuration of Polycavernoside A"J.Am.Chem.Soc.. 120 41. 10770-10771 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Fujiwara: "Chemical Realization of the Biogenetic Pathways Proposed for the Fused-Polycyclic Ethers of Marine Origins"Heterocycles. 50 1. 561-593 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Fujiwara: "Total Synthesis of (+)-Obtusenyne"J.Org.Chem.. 64 8. 2616-2617 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Sugimoto: "Synthesis of the B,C,D,E,F-Ring Fragment of Pinnatoxins"Synlett. No.5. 541-544 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] D.Awakura: "Determination of the Absolute Configurations of Norte's Obtusenynes by Total Syntheses of (12R, 13R)-(-)- and (12S, 13R)-(+)-Obtusenynes"Chemistry Lett.. No.6. 461-462 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Fujiwara: "A Simple Convergent Method for the Construction of Fused Tri- and Tetracyclic Ethers"Synlett. No.7. 1037-1040 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] L.Barriault: "Synthesis and Biological Evaluation of Analogues of the Marine Toxin Polycavernoside A"Bioorg.Med.Chem.Lett.. No.9. 2069-2072 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Fujiwara: "Four-Step Convergent Synthesis of trans-Fused Tetracyclic Oxane"Tetrahedron Lett.. 41 4. 507-508 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Tokiwano: "Biomimetic Construction of Fused Tricyclic Ether by Cascaded endo-Cyclization of the Hydroxy Triepoxide"Synlett. No.3. 329-332 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] D.Awakura: "Synthetic Studies on Pectenotoxins : Synthesis of the Common C8-C18 THF Fragment"Synlett. No.12. 1733-1736 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Tokiwano: "Biomimetic Construction of Fused Tricyclic Bther by Cascaded end o-Cyclization of the Hydroxy Triepoxide"Synlett. No.3. 329-332 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Fujiwara: "Novel Oxepane Formation by TiCl_4-Catalyzed Nucleophilic Cleavage of 1-Alkoxymethyl-6,8-dioxabicyclo[3.2.1]octanes"Tetrahedron. 56・8. 1065-1080 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Tokiwano: "Effect of Molecular Sieves and Methanol on the endo-Selectivity in La(OTf)_3-catalyzed Cyclization of 5-Hydroxy-2-methoxymethyl-1,2-epoxide System"Chemistry Lett.. No.3. 272-273 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Fujiwara: "Asymmetric Synthesis of the A-ring Part of Ciguatoxin by the Strategy Based on Diastereoselective Hydroboration and Ring Closing Metathesis"Chemistry Lett.. No.6. 610-611 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Fujiwara: "Stereochemistry in the Bromination of 2,7-Dialkyl-3-hydroxyoxepane System Induced by R_3P-Br_2 Complex"Synlett. No.8. 1187-1189 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] D.Awakura: "Synthetic Studies on Pectenotoxins : Synthesis of the Common C8-C18 THF Fragment"Synlett. No.12. 1733-1736 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K. Fujiwara: "Total Synthesis of (+)-Obtusenyne"J. Org. Chem.. 64・8. 2616-2617 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T. Sugimoto: "Synthesis of the B,C,D,E,F-Ring Fragment of Pinnatoxins"Synlett. No.5. 541-544 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] D. Awakura: "Determination of the Absolute Configurations of Norte's Obtusenynes by Total Syntheses of (12R,13R)-(-)- and (12S,13R)-(+)-Obtusenynes"Chemistry Lett.. No.6. 461-462 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K. Fujiwara: "A Simple Convergent Method for the Construction of Fused Tri- and Tetracyclic Ether"Synlett. No.7. 1037-1040 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] L. Barriault: "Synthesis and Biological Evaluation of Analogs of the Marine Toxin Polycavernoside A"Bioorg. Med. Chem. Lett.. No.9. 2069-2072 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K. Fujiwara: "Four-Step Convergent Synthesis of trans-Fused Tetracyclic Oxane"Tetrahedron Lett.. 41・4. 507-508 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Fujiwara: "La(OTf)_3-Catalyzed7-Endo and 8-Endo Selective Cyclizations of Hydroxy Epoxides" Tetrahedron Letters. 39・5/6号. 393-396 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Amano: "The Substituent Effect on Stereoselective Reductive Lithiation of 4,5-Disubstituted 2-Phenylthiooxolane" Chemistry Letters. 5号. 409-410 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] J.Ishihara: "Studies on the Stability of 1,7,9-Trioxadispiro〔5.1.5.2〕pentadecane System : The Common Tricyclic Acetal Moiety of Pinnatoxins" Synlett. 6号. 603-606 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Fujiwara: "Total Synthesis and Absolute Configuration of Polycavernoside A" JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. 120(41). 10770-10771 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Fujiwara: "Chemical Realization of the Biogenetic Pathways Proposed for the Fused-Polycyclic Ethers of Marine Origins" Heterocycles. 50(1). 561-593 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] J.Ishihara: "Synthetic Studies on Azadirachtin (Part3) : Asymmetric Synthesis of the Tricyclic Dihydrofuran Moiety of Azadirachtin" Tetrahedron Letters. 40(10). 1907-1910 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] F.Fei: "Asymmetric Synthesisi ; Graphical Abstracts and Experimental Methods (Kodansha)" T.Hayashi, K.Tomioka, O.Yonemitsu, (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] A.Murai: "Comprehensive Natural Products Chemistry (Elsevier Science Ltd.England)" D.Barton, K.Nakanishi, O.Meth-Cohn (印刷中), 1(P.114) (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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