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Study of the Reaction of Unprotected Amino Acids in Aqueous Media and its Application for the Short-Step Synthesis of Ergot Alkaloids

Research Project

Project/Area Number 13672237
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical pharmacy
Research InstitutionToho University

Principal Investigator

YOKOYAMA Yuusaku  Toho University, Department of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (10095325)

Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsBemztrvptophan / Amino acids / Bromination / Racemization / N-Methvlamino acids / Protecting groups / Aqueous media / Tryptophan / ベンズインドール / ビニル化 / リゼルギン酸 / Heck反応 / パラジウム触媒 / アリル化
Research Abstract

1)Several free amino acids, phrnylglycine, phenylalanine, tryptophan were heated at 100-130℃ under alkaline or acidic condition in water or various polar organic solvents.Although serious racemization and decomposition occurred in polar organic solvents such as DMF, DMSO, or ethylene glycol under alkaline condition (K_2CO_3, KOH, Et_3N), those phenomenon did not occur, or were largely decreased in water or water containing organic solvent under the same alkaline condition.
2)Bromination of unprotected phenylalanine with bromoisocyanuric acid sodium salt in strong acidic solution (60% H_2SO_4) gave the mixture of 2-bromo-and 4-bromophenylalanine in 31% and 58% yield, respectively.
3)The reaction of benz[e]-, benz[f]-, benz[g] indoles with dl-serine in the presence of Ac_2O in AcOH at 50-60℃ gave the corresponding dl-N-acetylbenztryptophanes in 42-59% yield accompanied with 2,3-di-subusituted derivatives as by-products. Kinetic resolution of the above dl-N-acetylbenztryptophans by Aspergillus acylase gave corresponding optically pure(S)-benztryptophans.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Yuusaku Yokoyama: "Does Water Suppress the Racemization and Decomposition of Amino Acids?"J.Chem.Soc.,Perkin Trans.1. 1431-1434 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yuusaku Yokoyama: "N-Boc-4-Bromo-N-methyl-1 -tosyl-D-tryptophan Methyl Ester, A Key Intermediate In the Synthesis of Optically Active Ergot Alkaloids"Heterocycles. 55(4). 653-659 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yuusaku Yokoyama: "Synthetic Studies on Indoles and Related Compounds 50.Improved Synthesis of 7,9-Didecarboxymethoxthine"Heterocycles. 56. 515-518 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yuusaku Yokoyama: "A Study for Palladium-Catalyzed Chemoselective Vinylation at C-3 Position of 4-Bromo-1-Tosylindole."Heterocycles. 56. 525-529 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yuusaku Yokoyama: "Total Synthesis without Protection : Three-Step Synthesis of Optically Active Clavicipitic Acids by a Biomimetic Route"Eur.J.Org.Chem.. 1244-1253 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 横山 祐作: "保護基を用いない有機合成"ファルマシア. 39(12). 1163-1167 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Somei M, Yokoyama Y, Murakami Y, Ninomiya I, Kiguchi T: "Recent Synthetic Studies of the Ergot Alkaloids and Related Compounds."The Alkaloids Ed. (Cordell D.A.). 35. 193-253 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hikawa H, Yokoyama Y, Murakami Y: "A Short Synthesis of Optically Active γ,γ-Dimethylallyltryptophan (DMAT)."Synthesis. 214-216 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yokoyama Y, Osanai K, Mitsuhashi M, Kondo K, Murakami Y: "An Efficient Method of Synthesizing Optically Pure N-Boc-4-bromo-N-methyl-1-tosyl-D-tryptophan methyl Ester, A Key Intermediate in the Synthesis of Optically Active Ergot Alkaloids."Heterocycles. 55. 653-659 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yokoyama Y, Hi kawa H, Murakami Y: "Does Water Suppress the racemization and Decomposition of Amino Acids?"J.Chem.Soc., Perkin Trans. 1. 1432-1434 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yokoyama Y, Tsuruta K, Murakami Y: "A Study for Palladium-Catalyzed Chemoselective Vinylation at C-5 Position of 4-Bromo-1-tosylindoles"Heterocycles. 56. 525-529 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yokoyama Y, Hikawa H, Mitsuhashi M, Uyama A, Hiroki H, Murakami Y: "Total Synthesis without Protection: Three-Step Synthesis of Optically Active Clavicipitic Acids via a Biomimetic Route"Eur.J.Org.Chem.. 1244-1253 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yuusaku Yokoyama: "Does Water Suppress the Racemization and Decomposition of Amino Acids?"J.Chem.Soc., Perkin Trans.1. 1431-1434 (2001)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yuusaku Yokoyama: "An Efficient Method of Synthesizing Optically Pure N-Boc-4-bromo-N-methyl-1-tosyl-D-tryptophan Methyl Ester, a Key Intermediate in the Synthesis of Optically Active Ergot Alkaloids"Heterocycles. 55(4). 653-659 (2001)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yuusaku Yokoyama: "Synthetic Studies on Indoles and Related Compounds 50. Improved Synthesis of 7,9-Didecarboxymethoxthine"Heterocycles. 56. 515-518 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yuusaku Yokoyama: "A Study for Palladium-Catalyzed Chemoselective Vinylation at C-3 Position of 4-Bromo-1-Tosylindole"Heterocycles. 56. 525-529 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yuusaku Yokoyama: "Total Synthesis without Protection : Three-Step Synthesis of Optically Active Clavicipitic Acids b a Biomimetic Route"Eur.J.Org.Chem.. 1244-1253 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 横山祐作: "保護基を用いない有機合成"ファルマシア. 39(12). 1163-1167 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yuusaku Yokoyama: "Does Water Suppress the Racemization and Decomposition of Amino Acids?"J. Chem. Soc, Perkin Trans.1. 1431-1434 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yuusaku Yokoyama: "N-Boc-4-bromo-N-methyl-1-tosyl-D-tryptophan Methyl Ester, A Key Intermediate in the Synthesis of Optically Active....."Heterocycles. 55(4). 653-659 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yuusaku Yokoyama: "Synthetic Studies on Indoles and Related Compounds 50. Improved Synthesis of 7,9-Didecarboxymethoxathine"Heterocycles. 56. 515-518 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yuusaku Yokoyama: "A Study for Palladium-Catalyzed Chemoselective Vinylation at C-3 Position of 4-Bromo-1-Tosylindole"Heterocycles. 56. 525-529 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yuusaku Yokoyama: "Does Water Suppress the Racemization and Decomposition of Amino Acids?"J.Chem.Soc.,Perkin Trans.1. 1431-1434 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yuusaku Yokoyama: "N-Boc-4-Bromo-N-methyl-1-tosyl-D-tryptophan Methyl Ester,A Key Intermediate in the Synthesis of Optically Active……"Heterocycles. 55(4). 653-659 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yuusaku Yokoyama: "A Study for Palladium-Catalyzed Chemoselective Vinylation at C-3 Position of 4-Bromo-1-Tosylindole"Heterocycles. 56. 525-529 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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