2023 Fiscal Year Final Research Report
The Utilization of Highly Active Intermediates in the Low Entropy Reaction Space toward Inovation of Organic Molecular Catalysis
| Project Area | Highly organized catalytic reaction chemistry realized by low entropy reaction space |
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| Project/Area Number |
21H05081
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| Research Category |
Grant-in-Aid for Transformative Research Areas (B)
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| Allocation Type | Single-year Grants |
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| Review Section |
Transformative Research Areas, Section (II)
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Project Period (FY) |
2021-08-23 – 2024-03-31
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| Keywords | 不安定活性種 / ペプチド環化 / 特殊環状ペプチド / アシルアンモニウム |
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| Outline of Final Research Achievements |
The use of short-lived unstable complexes has been avoided in catalytic reaction development. This is because there is a high risk of decomposition of the complex during the progression of the reaction, leading to decreased yields. In this study, we conducted a detailed analysis of reactions using these unstable complexes and advanced the accumulation of knowledge and exploration of reaction design principles. Specifically, we focused on the cyclization reaction of peptides using organic molecule catalysts, revealing the influence of reactants, solvents, and other factors on the reaction. Furthermore, the developed cyclization method proved to be effective for cyclization of linear peptides with high risk of side reactions and difficult-to-cyclize linear peptides.
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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 |
タンパク質を構成するアミノ酸以外のアミノ酸からなり、環状構造をもつ特殊環状ペプチドは医薬品として脚光を浴びている。これは標的生体分子に対する親和性や選択性、代謝安定性の向上が見込まれ、細胞膜透過性や経口投与性さえももつときがあるためである。一方で特殊環状ペプチドの合成には副反応の競合が問題となることが多く、反応性の低さから、長時間、高温条件、過剰量の反応剤の利用を要することが多い。開発した手法では、マイクロフロー合成法を駆使することにより、安価で廃棄物の少ない入手容易な反応剤を用いて、短時間、穏和な条件で特殊環状ペプチドを得ることに成功したため、今後のペプチド創薬加速への貢献が期待される。
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