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Syntheses of biological active natural products having highly alkylated piperazine ring

Research Project

Project/Area Number 63571010
Research Category

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

Allocation TypeSingle-year Grants
Research Field Chemical pharmacy
Research InstitutionMeiji College of Pharmacy

Principal Investigator

KUBO Akinori  Meiji College of Pharm. Fac. of Pharm. Sciences Professor, 薬学部, 教授 (60097201)

Co-Investigator(Kenkyū-buntansha) NAKAI Tatuya  Meiji College of Pharm. Fac. of Pharm. Sciences Assistant, 薬学部, 助手 (80217645)
SAITO Naoki  Meiji College of Pharm. Fac. of Pharm. Sciences Assistant, 薬学部, 助手 (80142545)
NAKAHARA Shinsuke  Meiji College of Pharm. Fac. of Pharm. Sciences Lecturer, 薬学部, 講師 (60180337)
KITAHARA Yoshiyasu  Meiji College of Pharm. Fac. of Pharm. Sciences Lecturer, 薬学部, 講師 (70114460)
Project Period (FY) 1988 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1989: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1988: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsAntibiotics / Isoquinoline / Saframycin / Total Synthesis / Partial Synthesis / Piperazine / Piperazine-2,5-dione / Protective Group / イソキノリンキノン / ピペラジン-2、5-ジオン / ピペラジン-2.5ジオン / サフラマイシンA / レニエラマイシンA / 立体選択的合成 / 超電導NMRスペクトル / 立体化学
Research Abstract

Recently several naturally occurring isoquinolinequinone antibiotics have been isolated from Actinomycetes and from marine organisms. The unique structure of this antibiotics, coupled with their great biological activities, offers a formidable challenge to the synthetic chemist. Our basic plan involves the use of the 2,5-piperazinediones to construct the basic skeleton of this target having highly alkylated piperazine ring. The purpose of this paper is outline the general approach and progress that we have made toward this challenging target. The results are summarized as followed:
1) We succeed in a 19-step total synthesis of (<plus-minus>)-saframycin B from (Z)-1-acetyl-3-arylidene-6-(arylmethyl)-2,5-piperazinedione. 2) Three minor components of safiamycin group antibiotics, saframycins F, G, H were isolated and their structure were determined by comparison with the spectral data of natural products and the intermediates of a total synthesis of saframycin B. 3) An efficient synthesis of 1-methyl-3-(2,4,5-trimethoxy-3-methylphenylmethyl)-2,5-piperazinedione, which is shown to be a useful intermediate for preparation of the 1,5-imino-3-benzazocine derivative (right half of safraniycins). 4) A mild and efficient method for the synthesis of 1,2,3,4-tetrahydioisoquinolines by a modified Pictet-Spengler reaction involving Lewis acid-mediated cyclization of the O, N-acetals. This reaction is demonstrated with a preparation of the basic skeleton of the left half of saframycins. 5) A synthetic strategy for the preparation of isoquinoline antibiotic, saframycin A is outlined. 6) 9-Methoxy-3,8,11-trimeth-oxy-4-oxo-1,2,3,4,5,6-hexahydro-1,5-imino-3-benzazocin-7,10-dione is oxidized to the corresponding 6-hydroxy compound with selenium oxide. This is a good way to make saframycins C and D from saframycin B. 7) Synthetic approach of renieramycin A and a revised structure for renieramycins are presente

Report

(3 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Akinori Kubo: "Stereoselective Total Synthesis of(±)-Saframycin B." J.Org.Chem.53. 4295-4310 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yuzuru Mikami: "Structural Studies on Minor Components of Saframycin Group Antibiotics Saframycins F,G,and H." J.Antibiot.41. 734-740 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Akinori Kubo: "Synthesis of Saframycins.II.Preparations and Reactions of N-Methyl-2,5-piperazinediones." Chem.Pharm.Bull.36. 2607-2614 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Naoki Saito: "A Faclle Synthesis of 1,2,3,4-Tetrahydroisoquinolinequinones through Cyclization of O,N-Acetals.II.Syntheses of isoquinolinequinone Antibiotics." Chem.Pharm.Bull.37. 1493-1499 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Naoki Saito: "Synthesis of Saframycins.3.Preparation of a Key Tricyclic Lactam intermediate to Saframycin A." J.Org.Chem.,. 54. 5391-5395 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Naoki Saito: "Synthesis of Saframycins.IV.Selenium Oxide Oxidation of 4-Oxo-Hexahydro-1,5-imino-3-Benzazocin-7,10-Dione;Promising Method to Construct Saframycins C and D from Saframycin B." Chem.Pharm.Bull.38. 821-823 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Naoki Saito: "J.Org.Chem." Synthesis of Saframycins.V.Synthesis of Saframycins C and D.,

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Naoki Saito: "Tetrahedron" Total Synthesis of Renieramycin A and its Congners.,

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Akinori Kubo.: "Stereoselective Total Synthesis of (<plus-minus>)-Saframycin " J. Org., Chem., 53, 1988, 4295-4310.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Y. Mikami.: "Structural Studies on Minor Components of Saframycin Group Antibiotics F, G, and H." J. Antibiot., 41, 1988, 734-740.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Akinori Kubo.: "Synthesis of Saframycins II. Preparations and Reactions of N-Methyl-2,5-plperazinediones." Chem. Pharm. Bull., 36, 1988, 2607-2614.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Naoki Saito.: "A Facile Synthesis of 1,2,3,4-Tetrahydro-isoquinolines through Cyclization of O, N-Acetals. II. Syntheses of Isoquinolinequinone Antibiotics." Chem. Pharm. Bull., 37, 1989, 1493-1499.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Naoki Saito.: "Synthesis of Saframycins. 3. Preparation of a Key Tricycllc Lactam Intermediate to Saframycin A." J. Org. Chem., 54, 1989, 5391-5395.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Naoki Saito.: "Synthesis of Saframycins IV. Selenium Oxide Oxidation of 4-Oxo-Hexahydro-1,5-Imino-3-Benzazocin-7,10-Dione; Promising Method to Construct Saframycins C and D from Saframycin B." Chem. Parm. Bull., 38, 1990, 821-823.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Naoki Saito.: "Synthesis of Saframycins. V. Synthesis of Saframycins C and D." J. Org. Chem.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Naoki Saito.: "Total Synthesis of Renleramycin A and Its Congners." Tetrahedron.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] AKINORI KUBO: "SYNTHESIS OF SAFRAMYCINS.II.PREPARATIONS AND REACTIONS OF N METHYL 2,5 PIPERAZINEDIONES." Chem.Pharm.Bull.,. 36. 2607-2614 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] AKINORI KUBO: "STEREOSELECTIVE TOTAL SYNTHESIS OF( )SAFRAMYCIN B" J.Org.Chem.53. 4295-4310 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] YUZURU MIKAMI: "STRACTURAL STUDIES ON MINOR COMPONENTS OF SAFRAMYCIN GROUP ANTIBIOTTCS SAFRAMYCINS F,G,AND H." J.Antibiot.41. 734-740 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] NAOKI SAITO: "A FACILE SYNTHESIS OF 1,2,3.4 TETRAHYDROISOQUINOLINES THROUGH CYLCIZATION OF O,N ACETALS.II.SYNTHESES OF ISOQUINOLINEQUINONE ANTIBROTICS." Chem.Pharm.Bull.,. 37. 1493-1499 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] NAOKI SAITO: "SYNTHESIS OF SAFRAMYCINS.III.PREPARATION OF A KEY TRICYCLIC LACTAMINTERMEDIATE TO SAFRAMYCIN A." J.Org.Chem.54. 5391-5395 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] NAOKI SAITO: "SYNTHESIS OF SAFRAMYCINS.IV.SELENIUM OXIDE OXIDATION OF 4 OXO HEXAHYDRO 1,5 IMINO 3 BENZAZOCIN 7,10 DIONE;PROMISING METHOD TO CONSTRACT SAFRAMYCINS C AND D FROM SAFRAMYCIN B." Chem.Pharm.Bull.38. 821-823 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] NAOKI SAITO: "SYNTHESIS OF SAFRAMYCINS.V.SYNTEESIS OF SAFRAMYCINS C AND D FROM SAFRAMYCIN B." J.Org.Chem.

    • Related Report
      1989 Annual Research Report
  • [Publications] NAOKI SAITO: "TOTAL SYNTEHSIS OF RENIERAMYCIN A AND ITS CONGNERS" Tetrahedron.

    • Related Report
      1989 Annual Research Report
  • [Publications] Akinori Kubo.: Chem.Pharm.Bull.36. 2607-2614 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Akinori Kubo.: J.Org.Chem.53. 4295-4310 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Akinori Kubo.: Chem.Pharm.Bull.36. 4355-4363 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Akinori Kubo.: Heterocycles. 27. 2095-2098 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Yoshiyasu Kitahara.: Chem.Pharm.Bull.36. 3623-3627 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Naoki Sato.: Chem.Pharm.Bull.37. No.6 (1989)

    • Related Report
      1988 Annual Research Report

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Published: 1988-04-01   Modified: 2016-04-21  

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