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Enantioselective Synthesis of Unsymmetrically-Substituted Organophosphorus Compounds with Stereogenic Phosphorus Atoms

Research Project

Project/Area Number 08454200
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Organic chemistry
Research InstitutionNagoya University

Principal Investigator

HAYAKAWA Yoshihiro  Graduate School of Human Informatics, Professor, 大学院・人間情報学研究科, 教授 (50022702)

Co-Investigator(Kenkyū-buntansha) MURATA Sizuaki  Graduate School of Human Informatics, Associate Professor, 大学院・人間情報学研究科, 助教授 (50157781)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1996: ¥2,700,000 (Direct Cost: ¥2,700,000)
Keywordsasymmetric synthesis / optically active imidazole / optically active tetrazoles / dynamic kinetic resolution / phosphoramidite method / DNA synthesis / acid / base complex-type promoter / antisense nucleic acid / DNA合成 / 光学活性リン酸エステル / 光学活性アゾール / ヌクレオチドホスホロチオエ-ト / 酸 / 塩基複合活性化剤 / ホスホロアミダイト / アミダイト法
Research Abstract

Asymmetric synthesis of optically active organophosphorus compounds via the phosphoramidite method using an optically active promoter, where the enantioselection is caused by kinetic resolution of the intermediates, was investigated. A number of enantioselective syntheses of an unsymmetrically substituted trialkyl phosphite were attempted using an optically pure tetrazole compound such as (R) - (-) -2-methoxy-2'- (1H-tetrazol-5-yl) -l, l'-binaphthyl or (lR, 2R) - (+) - 1-trimethylsilyl-2- (1H-tetrazol-5-yl) ferrocene, or an optically pure imidazole derivative such as (S)- 1 - [2- (6-methoxynaphthyl) ] -1- (2-benzimidazolyl) ethane or (S) -l- (2- imidazolyl) -l- (tert-butyldimethylsiloxy) ethane as the promoter. However, little selectivity was observed in all attempts.
Although the intended objective has not been achieved, this research disclosed that imidazole triflate and benzimidazolium triflate serve as highly reactive promoters in the synthesis of oligonucleotides via the phosphoramidite approach. Particularly, imidazole triflate is a useful reagent which allows 0-selective phosphitylation, i.e, intemucleotide-linkage formation of N-unprotected nucleosides and has opened an ideal synthesis of oligodeoxyribonucleotides without nucleoside-base protection. This novel method allows low-cost supply of the products and accordingly will be useful for large-scale synthesis of DNA-related compounds including DNA phosphorothioates important as antisense molecules.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (39 results)

All Other

All Publications (39 results)

  • [Publications] Y.Hayakawa: "Benzimidazolium Triflate as an Efficient Promoter for the Nucleotide Synthesis via the Phosphoramidite Method." J.Org.Chem.61. 7996-7997 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Kataoka: "Nucleotide Synthesis via the Phosphoramidite Method Using Benzimidazolium Triflate as a Promoter." Nucleic Acids Symp.Ser.35. 69-70 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Hirose: "Preparation of (R)-(-)-2-Methoxy-2'-(1H-tetrazol-5-y1)-1,1'-binaphthy1 and (1R,2R)-(+)-1-Trimethylsilyl-2-(1H-tetrazol-5-Y1)ferrocene: Optically Active Tetrazoles with Axial or Planar Chira" Synlett. 495-497 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Kataoka: "Imidazolium Triflate as an Efficient Promoter for O-Selective Phosphitylation of N-Unprotected Nucleosides via the Phosphoramidite Approach." Nucleic Acids Symp.Ser.37. 21-22 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Hayakawa: "Preparation of Short Oligonucleotides via the Phosphoramidite Method Using a Tetrazole Promoter in a Catalytic Manner." J.Am.Chem.Soc.119. 11758-11762 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Hayakawa: "Electrochemical Removal of Allylic Protecting Group in Nucleotide Synthesis." Nucleosides Nucleotides. 17. 441-449 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] R.Kawai: "Synthesis and Stability of 2'-C-Cyano-2'-deoxy-1-β-D-arabino-pentafuranosylcytosylyl-(3'-5')thymidine." Nucleic Acids Symp.Ser.39. 5-6 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] A.Sakakura: "Preparation of Phosphate-Linked Nucleotide-Amino Acid and -Peptide Conjugates via the Phosphoramidite Approach with Allyl/Allyloxycarbonyl Protection." Nucleic Acids Symp.Ser.39. 25-26 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.B.Heidenhain: "A Convenient Way to N-Allyloxycarbonyl Protected Adenosine and Cytidine Derivatives." Synlett. 853-854 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Hayakawa: "Evidence Supporting the Activity of 2'-C-Cyano-2'-deoxy-1-β-D-arabino-pentafuranosylcytosine as a Terminator in Enzymatic DNA-Chain Elongation." Bioorg.Med.Chem.Lett.8. 2559-2562 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Hayakawa: "A Facile Synthesis of Oligodeoxyribo-nucleotides via the Phosphoramidite without Nucleoside-Base Protection." J.Am.Chem.Soc.120. 12395-12401 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.B.Heidenhain: "Improved Methods for the Preparation of 2'-Deoxyribonucleoside and Ribonucleoside 3'-Phosphoramidites with Allylic Protectors." Nucleosides Nucleotides. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.B.Heidenhain and Y.Hayakawa: "An Improved Method for the Preparation of 2'-Deoxyguanosine and Guanosine 3'-Phosphoramidites with Allylic Protecting Groups." Nucleosides Nucleotides. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Hayakawa and M.Kataoka: "A Facile Synthesis of Oligodeoxyribonucleotides via the Phosphoramidite without Nucleoside-Base Protection." J.Am.Chem.Soc.120. 12395-12401 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Hayakawa, R.Kawai, K.Otsuki, M.Kataoka, and A.Matsuda: "Evidence Supporting the Activity of 2'-C-Cyano-2'-deoxy-1-beta-D-arabino-pentafuranosyl-cytosine as a Terminator in Enzymatic DNA-Chain Elongation." Bioorg.Med.Chem.Lett.8. 2559-2562 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.B.Heidenhain and Y.Hayakawa: "A Convenient Way to N-Allyloxycarbonyl Protected Adenosine and Cytidine Derivatives." Synlett. 853-854 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] A.Sakakura and Y.Hayakawa: "Preparation of Phosphate-Linked Nucleotide-Amino Acid and-Peptide Conjugates via the Phosphoramidite Approach with Allyl/Allyloxycarbonyl Protection." Nucleic Acids Symp.Ser.39. 25-26 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] R.Kawai, K.Otsuki, M.Kataoka, Y.Hayakawa, and A.Matsuda: "Synthesis and Stability of 2'-C-Cyano-2'-deoxy-1-beta-D-arabino-pentafuranosylcytosylyl-(3'-5')thymidine." Nucleic Acids Symp.Ser.39. 5-6 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Hayakawa, R.Kawai, S.Wakabayashi, M.Uchiyama, and R.Noyori: "Electrochemical Removal of Allylic Protecting Group in Nucleotide Synthesis." Nucleosides Nucleotides. 17. 441-449 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Hayakawa and M.Kataoka: "Preparation of Short Oligonucleotides via the Phosphoramidite Method Using a Tetrazole Promoter in a Catalytic Manner." J.Am.Chem.Soc.119. 11758-11762 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Kataoka, S.Heidenhain, and Y.Hayakawa: "Imidazolium Triflate as an Efficient Promoter for O-Selective Phosphitylation of N-Unprotected Nucleosides via the Phosphoramidite Approach." Nucleic Acids Symp.Ser.37. 21-22 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Hirose, R.Kawai, and Y.Hayakawa: "Preparation of (R)-(-)-2-Methoxy-2'-(1H-tetrazol-5-yl)-1,1'-binaphthyl and (1R,2R)-(+)-1-Trimethylsilyl-2-(1H-tetrazol-5-yl)ferrocene. Optically Active Tetrazoles with Axial or Planar Chirality." Synlett. 495-497 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Hayakawa, M.Kataoka, and R.Noyori: "Benzimidazolium Triflate as an Efficient Promoter for the Nucleotide Synthesis via the Phosphoramidite Method." J.Org.Chem.61. 7996-7997 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Kataoka and Y.Hayakawa: "Nucleotide Synthesis via the Phosphoramidite Method Using Benzimidazolium Triflate as a Promoter." Nucleic Acids Symp.Ser.35. 69-70 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Hayakawa, et al.: "Electrochemical Removal of Allylic Protecting Group in Nucleotide Synthesis" Nucleosides Nucleotides. 17(1-3). 441-449 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] A.Sakakura and Y.Hayakawa: "Preparation of Phosphate-Linked Nucleotide-Amino Acid and -Peptide Conjugates via the Phosphoramidite Approach with Allyl/Allyloxycarbonyl Protection" Nucleic Acids Symp.Ser.39. 5-6 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.B.Heidenhain and Y.Hayakawa: "A Convenient Way to N-Allyloxycarbonyl Protected Adenosine and Cytidine Derivatives" Synlett. 5. 853-854 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Hayakawa, et al.: "Evidence Supporting the Activity of 2'-C-Cyano-2'-deoxy-1-β-D-arabino-pentafuranosyl-cytosine as a Terminator in Enzymatic DNA-Chain Elongation" Bioorg.Med.Chem.Lett.8. 2559-2562 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Hayakawa and M.Kataoka: "A Facile Synthesis of Oligodeoxyribonucleotides via the Phoramidite without Nucleoside-Base Protection" J.Am.Chem.Soc.120(48). 12395-12401 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.B.Heidenhain and Y.Hayakawa: "Improved Methods for the Preparation of 2'-Deoxyribonucleoside and Ribonucleoside 3'-Phosphoramidites with Allylic Protectors" Nucleosides Nucleotides. (印刷中).

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Hirose: "Preparation of (R)-(-)-2-Methoxy-2′-(1H-tetrazol-5-yl)-1,1′-binaphthyl and (1R,2R)-(+)-1-Trimethylsilyl-2-(1H-tetrazol-5-yl) ferrocene" Synlett. 1997 (5). 495-497 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Kataoka: "Imidazolium Triflate as an Efficient Promoter for O-Selective Phosphitylation of N-Unprotected Nucleosides via the Phosphoramidite Approach" Nucleic Acids Symp.Ser.37. 21-22 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Hayakawa: "Preparation of Short Oligonucleotides via the Phosphoramidite Method Using a Tetrazole Promoter in a Catalytic Manner" J.Am.Chem.Soc.119 (49). 11758-11762 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Hayakawa: "Electrochemical Removal of Allylic Protecting Group in Nucleotide Synthesis" Nucleosides Nucleotides. (印刷中).

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Hayakawa: "A Facile Solid-Phase Synthesis of Oligodeoxyribonucleotides via the Phosphoramidite without Nucleoside-Base Protection" J.Am.Chem.Soc.(印刷中).

    • Related Report
      1997 Annual Research Report
  • [Publications] 早川芳宏: "Benzimidazolium Triflate as an Efficient Promoter for Nucleotide Synthesis via the Phosphoramidite Method" Journal of Organic Chemistry. 61/23. 7996-7997 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 片岡正典: "Nucleotide Synthesis via the Phosphoramidite Method Using Benzimidazolium Triflate as a Promoter" Nucleic Acids Symposium Series. 35. 69-70 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 広瀬雅朗: "Preparation of (R)-(-)-2-Methoxy-2'-(1H-tetrazol-5-y1)-1,1'-hinaphthyl and (1R,2R)-(+)-1-Trimethylsilyl-2(1H-tetrazol-5-yl)-herrocene" Synlett. (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 早川芳宏(共著): "創薬科学の基礎となる先導物質の合成法I 第4章" 広川書店・有機薬科学実験講座第3巻, 109-142 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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