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Stereochemical Studies of Nucleosides and Nucleotides

Research Project

Project/Area Number 59470117
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Chemical pharmacy
Research InstitutionHokkaido University

Principal Investigator

TOHRU Ueda  Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (00001032)

Co-Investigator(Kenkyū-buntansha) AKIRA Matsuda  Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (90157313)
AKIHIKO Nomura  Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 助教授 (10001041)
KIYOMI Tsuchida  Faculty of Pharmaceutical Sciences, Assistant, 薬学部, 教務職員 (60088862)
HIDEO Inoue  Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (80088856)
KAZUNOBU Miura  Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (70001980)
Project Period (FY) 1984 – 1986
Project Status Completed (Fiscal Year 1986)
Budget Amount *help
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1986: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1985: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1984: ¥5,800,000 (Direct Cost: ¥5,800,000)
KeywordsNucleosides / Nucleotides / Stereochemistry / Cyclonucleosides / Nucleoside conformation / Ribonuclease / アデノシンデアミナーゼ
Research Abstract

It has been generally recognized that the syn-anti conformation around the glycosylic linkages of nucleosides is one of the important determinants in the interaction of nucleosides and nucleotides with various enzymes utilizing them. To elucidate the stereochemistry of such interactions, the cyclonucleosides would be useful. In this respect, cyclonucleosides where the glycosyl torsion angle is fixed in an appropriate degree by the carbon bridge is regarded as useful model. This report summarized the result of synthesis of C-cyclonucleosides of pyrimidines and purines. Synthesis of some their phosphates and certain biological properties are also described.
1. Synthesis of carbon-bridged pyrimidine cyclonucleosides.
The following new compounds have been prepared: 5'-deoxy-6,5'-methanouridine; 2'-deoxy-6,2'-ethanouridine; 2'-deoxy-6,2'-methanouridine; 6,2'-methanouridine; 6,3'-methanouridine; 6,3'-methanocytidine; 6,3'-methanothymidine; 6,5'-cyclo-2',5'-di-deoxyuridine 6,5'-cyclo5'-deoxythymidine; 6,5'-cyclo-5'-deoxy-5'-hydroxyethyluridine, and related intermediates.
2. The 2',3'-cyclic phosphates of 5'-deoxy-6,5'-cyclouridines were the substrates of pancreatic ribonuclease (RNase). The 3'-phosphates were strong inhibitors. This means that the RNase recognizes the anti form of the pyrimidine nucleosides.
3. Synthesis of carbon-bridged purine cyclonucleosides.
The following compounds were newly synthesized: 2'-deoxy-8,2'-ethanoadenosine; 3'-deoxy-8,3'-ethanoadenosine; 8,2'-ethanoadenosine; 2'-deoxy-8,2'-methanoadenosine; 8,2'-methanoadenosine; 8,2'-methanoguanosine and its alpha anomer. The 8,2'-cyclo-adenosines were the substrates of adenosine deaminase whereas the 8,3'-compound was not. The conformation of the 5'-hydroxyl group may also be important for the binding of the substrate to the enzyme.
4. Some of the cyclonucleosides were tested for the antitumor (L1210) and antiviral (HSV-I) properties. None of them showed distinct activities to a level of 100 <micro> g/ml.

Report

(1 results)
  • 1986 Final Research Report Summary
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Tohru Ueda: Nucleosides and Nucleotides. 4(1&2). 67-75 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Tomoharu Sano: (Chem.Pharm.Bull.)Chemical and Pharmaceutical Bulletin. 33(5). 1856-1860 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Tohru Ueda: Nucleosides and Nucleotides. 4(3). 401-409 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Tomoharu Sano: Chem.Pharm.Bull.33(9). 3595-3598 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Tomoharu Sano: Chem.Pharm.Bull.33(9). 3617-3622 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Jerzy Boryski: Nucleosides and Nucleotides. 4(4). 477-486 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Akira Matsuda: Chem.Pharm.Bull.34(4). 1573-1578 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Hiroyuki Usui: Chem.Pharm.Bull.34(5). 1961-1967 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yuichi Yoshimura: Nucleic Acids Research Symposium Series. No.17. 53-55 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yukari Suzuki: Chem.Pharm.Bull.in press. 35. (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yukari Suzuki: Chem.Pharm.Bull.in press. 35. (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Akira Matsuda: Tetrahedron. 41(24). 6013-6017 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yuriko Yamagata: Acta Crystallographyca. C41. 1653-1656 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yuriko Yamagata: Acta Crystallographyca. C41. 1656-1658 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Hiroyuki Usui: Chem.Pharm.Bull.34(1). 15-23 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Tomoharu Sano: Chem.Pharm.Bull.34(1). 423-425 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Hiroyuki Usui: Chem.Pharm.Bull.34(4). 1518-1523 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Tohru Ueda: "Synthesis and some biological properties of carbon-bridged cyclonucleosides and their phosphates" Nucleosides and Nucleotides. 4(1&2). 67-75 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Tomoharu Sano: "Nucleosides and nucleotides LIV. Synthesis of 6,6'-cyclo-5',6'-dideoxyhexofuranosyluracils via radical cyclization of a 6-cyano-uridine" Chemical Pharmaceutical Bulletin (Chem. Pharm. Bull.). 33(5). 1856-1860 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Tohru Ueda: "Synthesis of 2'-deoxy-6,2'-ethano-cyclouridine (Nucleosides and nucleotides 57)" Nucleosides and Nucleotides. 4(3). 401-409 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Tomoharu Sano: "Synthesis of 2'-deoxy-6,2'-methano-cyclouridine (Nucleosides and Nucleotides LIX)" Chem. Pharm. Bull.33(9). 3595-3598 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Tomoharu Sano: "Synthesis of 6,2'-methano-cyclouridine, a uridine fixed in high-anti conformation (Nucleosides and Nucleotides LX)" Chem. Pharm. Bull.33(9). 3617-3622 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Akira Matsuda: "Synthesis of 8,6'-cyclo-6'-deoxyhexofuranosyladenine: Adenosine fixed in an anti-conformation (Nucleosides and Nucleotides LXVI)" Chem. Pharm. Bull.34(4). 1573-1578 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Hiroyuki Usui: "Synthesis of 8,2'-methanoguanosine and 9-(a-D-arabinofuranosyl)-8,2'-methanoguanine (Nucleosides and Nucleotides LXVII)" Chem. Pharm. Bull.34 (5). 1961-1967 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yuichi Yoshimura: "Synthesis of 2'-deoxy-6,3'-methano-cyclo-pyrimidine nucleosides" Nucleic Acids Research Symposium Series. No. 17. 53-55 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yukari Suzuki: "Synthesis of 6,5'-cyclo-2',5'-dieoxypyrimidine nucleosides (Nucleosides and Nucleotides LXXII)" Chem. Pharm. Bull.35. in press (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yukari Suzuki: "Synthesis of 6,5'-cyclo-5'-deoxy-5'(R and S)-(2-hydroxyethyl)-uridines (Nucleosides and Nucleotides LXXIII)" Chem. Pharm. Bull.35. in press (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Akira Matsuda: "Synthesis and properties of 2'-deoxy-8,2'-methylene-cycloadenosine" Tetrahedron. 41(24). 6013-6017 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yuriko Yamagata: "Structural studies of pyrimidine cyclonucleoside dericatives X. Structure of 5'-O-acetyl-6,3'-anhydro-2'-deoxy-6-methyl-1-B-D-xylofuranosyluracil" Acta Crystallographyca. C41. 1656-1658 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yuriko Yamagata: "Structural studies of pyrimidine cyclonucleoside derivatives IX. Structure of 6,2'-anhydro-6-ethyl-1-B-D-arabinofuranosyluracil" Acta Crystallographyca. C41. 1653-1656 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Hiroyuki Usui: "Synthesis of 2'-deoxy-8,2'-ethanoadenosine and 3'-deoxy-8,3'-ethanoadenosine (Nucleosides and Nucleotides LXIV)" Chem. Pharm. Bull.34(1). 15-23 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Tomoharu Sano: "A facile synthesis of 6,3'-methano-uridine and -cytidine from a 3-ketosugar (Nucleosides and Nucleotides LXVIII)" Chem. Pharm. Bull.34(1). 423-425 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary

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Published: 1987-03-31   Modified: 2016-04-21  

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