2021 Fiscal Year Final Research Report
Studies of asymmetric Pictet-Spengler reaction and total synthesis of d-tubocurarine
| Project/Area Number |
18K05104
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 33020:Synthetic organic chemistry-related
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Keywords | Tetrahydroisoquinoline / Arylation of imine / Pictet-Spengler reaction / Promotor free reaction / Neutral conditions |
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| 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.
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| Free Research Field |
有機合成化学
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| 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。
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