Development of Molecular Release Reaction based on Nazarov Reaction

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K15283
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 33020:Synthetic organic chemistry-related
• Research Institution: Kyushu University
• Principal Investigator: Iwata Takayuki 九州大学, 先導物質化学研究所, 助教 (00781973)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ナザロフ反応 / 分子放出反応 / 弱酸

Outline of Final Research Achievements

In this study, development of a "molecular release reaction," that can be used in biological environment, was investigated on the basis of Nazarov reaction. The conventional Nazarov reaction requires strong acids such as hydrochloric acid and this was a difficulty in applying the reaction to molecular release reactions. In order to improve the reactivity in the presence of weak acid, we designed a "highly activated divinyl ketone" based on the key concept of improving the Lewis basicity of divinyl ketone, lowering the activation energy for cyclization, and making the reaction irreversible by release of phenol. As a result, it was found that the Nazarov reaction proceeds not only in the presence of weak acid but also in neutral protic solvents such as methanol and water at room temperature. Thus, we successfully developed an unprecedented neutral Nazarov reaction.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

本研究では開発したナザロフ反応は、従来未解決であった強酸の使用というナザロフ反応の課題を解決しただけでなく、細胞内外の酸性環境で利用可能な「分子放出反応」への利用が期待できる。「分子放出反応」は結合切断に伴って分子が放出される反応であり、その開発は、結合形成反応だけでは達成の難しい新たな分子制御技術、例えば、センシング分子、分子標的薬、ドラッグデリバリーシステムなどの創製へと繋がる。