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Studies of asymmetric Pictet-Spengler reaction and total synthesis of d-tubocurarine

Research Project

Project/Area Number 18K05104
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 33020:Synthetic organic chemistry-related
Research InstitutionOsaka University

Principal Investigator

Uenishi Jun'ichi  大阪大学, 薬学研究科, 招へい教授 (50167285)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsTetrahydroisoquinoline / Arylation of imine / Pictet-Spengler reaction / Promotor free reaction / Neutral conditions / Aminoarylation / C-N bond formation / Reaction of imine / C-C-bond formation / Three component reaction / Cyclization / Imine / Arylation / Reactivity / NMR study / total synthesis / asymmetric reaction / cyclization / isoquinoline alkaloid / curine
Outline of Final Research Achievements

For the synthesis of natural alkaloid d-tubocurarine, the synthesis of its core 1,2,3,4-tetrahydroisoquinoline ring has been investigated by Pictet-Spengler reaction. During the investigation, it was found that its ring was constructed simply by the reaction of 2-phenethylamine with aldehyde in protic solvent at room temperature. The mechanism of Pictet-Spengler reaction has widely been recognized in the organic reaction textbooks, in which an activation of imine with acid is essentially necessary in the electrophilic aromatic substitution. The current results have revealed that an arylation of neutral imine undergoes on the electrophilic rich phenolic aromatics in quite mild neutral conditions. The core 1,2,3,4-tetrahydroisoquinoline ring of d-tubocurarine is formed quite effectively by this new reaction conditions.

Academic Significance and Societal Importance of the Research Achievements

教科書にも掲載されている1911年に見出され110年が経過したPictet-Spengler反応における条件の常識が、成果の概要で記載した通り芳香環部位に電子豊富なフェノール類を用いることで覆った。実際に、極めて温和な中性条件下にイミンと芳香環が炭素-炭素結合反応を起こしテトラヒドロイソキノリン骨格が形成されることを見出すことができた。この成果におけるPictet-Spengler反応の重要性は、脳内の活性アミンであるドーパミンの生理条件下でのアルデヒドとの反応性に新しく大きな知見をもたらすものと考えられる。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (4 results)

All 2021 2020

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] Stereoselective synthesis of (+)-5-thiosucrose and (+)-5-thioisosucrose2020

    • Author(s)
      Ueda, Atsushi; Pi, Jinhong; Makura, Yui; Tanaka, Masakazu; Uenishi, Jun-ichi
    • Journal Title

      RSC Advances

      Volume: 10 Issue: 9 Pages: 9730-9735

    • DOI

      10.21873/anticanres.14506

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Stereoselective synthesis of (+)-5-thiosucrose and (+)-5-thioisosucrose2020

    • Author(s)
      Ueda Atsushi、Pi Jinhong、Makura Yui、Tanaka Masakazu、Uenishi Jun'ichi
    • Journal Title

      RSC Advances

      Volume: 10 Issue: 16 Pages: 9730-9735

    • DOI

      10.1039/d0ra01033b

    • NAID

      120006988253

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 無触媒中性条件下におけるアルデヒドのアミノアリール化反応2021

    • Author(s)
      上西潤一
    • Organizer
      第 118 回有機合成シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] テトラヒドロイソキノリン環構築反応;Pictet-Spengler 反応か、Phenolic cyclization か?2021

    • Author(s)
      上西潤一
    • Organizer
      第50回複素環化学討論会
    • Related Report
      2021 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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