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Synthetic studies on macrolide antibiotics through the cyclic polyketides.

Research Project

Project/Area Number 61470090
Research Category

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

Allocation TypeSingle-year Grants
Research Field 有機工業化学
Research InstitutionFaculty of Science and Technology, Keio University

Principal Investigator

TATSUTA KUNIAKI  Faculty of Science and Technology, Kieo University, 理工学部, 教授 (40051627)

Project Period (FY) 1986 – 1987
Project Status Completed (Fiscal Year 1987)
Budget Amount *help
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1987: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1986: ¥6,400,000 (Direct Cost: ¥6,400,000)
KeywordsBiosynthesis / Macrolide / Antibiotics / Stereospecific Synthesis / Stereoselctive Reduction / Ruthenium Oxidation / 大環状化合物 / 主体配座規制 / ポリケチド / 立体選択的合成 / 立体選択的還元
Research Abstract

The problem of when and how the secondary hydroxy group stereochemistry is controlled remains one of the most challenging aspects of the macrolide biosynthesis.
Here will be described the synthetic studies on macrolide antibiotics, especially, oleandolides, from the cyclic polyketide (polyketide lactone) as a chemical simulation.
An aglycone of oleandomycin, (8R,9S)-9-dihydro-8-methyloleandolide (1) was obtained in a good yield from oleandomycin in 6 steps through removal of the amino sugar moiety by treatment of the N-oxide with trimethylsilyl iodide. Exhaustive oxidation of the four hydroxy groups in 1 was realized by exposure to RuO_4 in CCl_4 to give the polyketide lactone (M^+ 366). The reduction of th epolyketide was achieved by Zn (BH_4)_2 in the presence of MgBr_2 to provide stereoselectively the tetraol as cubes in 80% yeild. The absolute structure was defined by the X-ray analysis to be (5R,8R,9R)-9-dihydro- 8-methyl-epi-oleandolide (2), the stereochemistry of which was incompatible with that of the natural macrolide only at the C-5. The reduction, however, withour MgBr2 gave a 1:1 mixture of the natural 1 and 5-epi-oleandolide 2.
On the other hand, the C-9 ketone, which was obtained from 1 by selective benzylidenation and oxidation, was led to the biosynthetic precursor, 8-methyl- oleandolide, by catalytic hydrogenation.

Report

(2 results)
  • 1987 Final Research Report Summary
  • 1986 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Kazunobuu Toshima;Kuniaku Tatsuta;Mitsuhiro Kinoshita: Tetrahedron Letters. 27. 4741-4744 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Kuniaki Tatsuta;Yoshiyuki Kobayashi;Kohji Akimoto;Mitsuhiro Kinoshita: Chemistry Letters. 1987. 187-190 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Kuniaki Tatsuta;Yoshiyuki Kobayashi;Mitsuhiro Kinoshita: Journal of Antibiotics. 40. 910-912 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Kazunobu Toshima, Kuniaki Tatsuta and Mitsuhiro Kinoshita: "Total synthesis of elaiophylin (azalomycin B)" Tetarahedron Letters. 27. 4741-4744 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Kuniaki Tatsuta, Yoshiyuki Kobayashi, Kohji Akimoto and Mitsuhiro Kinoshita: "An enantioselective synthesis of a macrolide from the polydetide lactone derived from oleandomycin." Chemistry Letters. 1987. 187-190 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Kuniaki Tatsuta, Yoshiyuki Kobayashi and Mitsuhiro Kinoshita: "Synthesis of a biosynthetic precursor of oleandomycin, 8,8a-deoxy- oleandolide (8-methyloleandolide), from oleandomycin." J. Antibiotics. 40. 910-912 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 戸嶋一敦: Tetrahedron Letters. 27. 4741-4744 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 竜田邦明: Chemistry Letters. 1987. 187-190 (1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] 竜田邦明: Journal of Antibiotics.

    • Related Report
      1986 Annual Research Report

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

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