Multi-synthesis of deuterium-labelled biological compounds and the evaluation

2022 Fiscal Year Final Research Report

• Project Area: Deuterium Science
• Project/Area Number: 20H05738
• Research Category: Grant-in-Aid for Transformative Research Areas (B)
• Allocation Type: Single-year Grants
• Review Section: Transformative Research Areas, Section (II)
• Research Institution: Osaka University (2021-2022); Gifu Pharmaceutical University (2020)
• Principal Investigator: Sawama Yoshinari 大阪大学, 大学院薬学研究科, 准教授 (80552413)
• Co-Investigator(Kenkyū-buntansha): 江坂 幸宏 岐阜薬科大学, 薬学部, 教授 (70244530)
• Project Period (FY): 2020-10-02 – 2023-03-31
• Keywords: 重水素 / 重医薬品 / 重水素化反応 / 生細胞イメージング

Outline of Final Research Achievements

Carbon-deuterium bonds are more stable than carbon-hydrogen bonds. Therefore, the introduction of deuterium into the reaction (metabolic) site is important for the improvement of the functionalities of drugs and so on. In this project, the direct deuteration methods for organic molecules, which was previously considered difficult to achieve, were developed using platinum group catalysts, base catalysts and photocatalyst. The evaluation of physical properties of deuterated drugs have revealed that water solubility and metabolic stability are improved by deuteration. The deuterated drug was also successfully used for live cell Raman imaging. Additionally, the efficient deuterations of quaternary ammonium salts, sulphur-containing compounds (such as methionine and biotin) and PEG were also developed.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

近年、多様な分野で重水素化体の利用性が注目されている。例えば、医薬品の代謝部位C-H結合を安定なC-D結合に置換することで、代謝遅延による生物活性の向上や副反応の抑制へと繋がる。また、C-Dの特徴的な物性を利用することで、蛍光や放射性タグを用いる事なく、生細胞イメージングが可能となる。しかし、これら対象となる重水素化体を合成する手法は限定的である。今回、我々は重水素化の今後の発展に寄与できる多様な分子の重水素化法を達成した。これら手法は、今後望まれる重水素化分子の提供を可能とし、多様な科学分野の発展に貢献できる。