envelopment of Enantiodivergent reaction and application to the biological active molecules
Project/Area Number |
17H03052
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Synthetic chemistry
|
Research Institution | Tokyo University of Agriculture and Technology |
Principal Investigator |
NAGASAWA KAZUO 東京農工大学, 工学(系)研究科(研究院), 教授 (10247223)
|
Co-Investigator(Kenkyū-buntansha) |
山中 正浩 立教大学, 理学部, 教授 (60343167)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
|
Keywords | 有機触媒 / 不斉多様化反応 / エントロピー / 理論計算 / グアニジン / チオウレア / アルカロイド / 全合成 / 熱力学的パラメータ / 熱力学的パラメーター / 触媒的不斉多様化 / Friedel-Crafts反応 / グラシラミン |
Outline of Final Research Achievements |
An entropy-driven reaction is one of the significant factors to develop a catalytic enantio-divergent reaction, which selectively synthesizes both enantiomers from one chiral source of the catalyst. In the Friedel-Crafts (FC) reaction between phenols and imines in the presence of structurally flexible guanidine-thiourea bifunctional organocatalyst developed by our group, we found that the reaction proceeded under the entropy-driven mode. Then, the thermodynamic parameters of the catalytic FC reaction were investigated by theoretical calculation. As a result, it was found that the entropy factor was significantly affected by the S-shaped catalyst with interacting substrates through a weak interaction such as hydrogen bonding. This catalytic reaction was successfully applied to the total synthesis of (+)-gracilamine.
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Academic Significance and Societal Importance of the Research Achievements |
生理活性物質合成や医薬品開発において、両鏡像異性体の合成が多々求められる。この時、これらを一つのキラル源から触媒的に合成する手法(触媒的不斉多様化反応)は、必要な試薬・時間・エネルギーを大きく削減し、環境負荷を大きく低減することから、次世代のモノ作りに必須である。触媒的不斉多様化反応において、触媒によるエントロピーの駆動力に基づく反応活性が重要であるが、これまで報告されたエントロピー駆動型触媒反応は数例である。本研究で理論計算をもとに見出した、グアニジン-チオウレア型有機触媒によるエントロピー駆動が生ずる触媒構造因子は、今後の新たな不斉多様化反応触媒を開発するための指針となる。
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Report
(4 results)
Research Products
(60 results)
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[Journal Article] Synthesis of C12-keto saxitoxin derivatives with unusual inhibitory activity against voltage‐gated sodium channels.2020
Author(s)
Adachi, K., Yamada, T., Ishizuka, H., Oki, M., Tsunogae, S., Shimada, N., Chiba, O., Orihara, T., Hidaka, M., Hirokawa, T., Odagi, M., Konoki, K., Yotsu-Yamashita, M., Nagasawa, K.
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Journal Title
Chem. Eur. J.
Volume: 26
Issue: 9
Pages: 2025-2033
DOI
Related Report
Peer Reviewed
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