Innovation of Multimetal-Mediated Rapid Carbon-11 Labeling Chemistry and its Versatile Application

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06987
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: ZHANG ZHOUEN 国立研究開発法人理化学研究所, 生命機能科学研究センター, 研究員 (00416207)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 11C-シアノ化標識法 / マルチメタル協同型反応 / 芳香族塩化物 / 芳香族フッ化物 / 芳香族スズ化合物 / 11C-カルボニル化標識法 / Ni錯体 / Pd錯体

Outline of Final Research Achievements

Based on the strategy of multimetallic cooperativity, we developed a series of novel rapid carbon-11 labeling reactions, in which C-Sn, C-F or C-Cl bonds could be directly transformed into C-11CN bond. Thus, novel C-11C-cyanation methods were established by using readily available (hetero)aromatic stannanes (Ar-Sn), aromatic fluorides (Ar-F), and aromatic chlorides (Ar-Cl) as precursors. Furthermore, we also developed the nickel-mediated 11C-carbonylation of aromatic chlorides with [11C]CO, by which various [11C]aromatic carboxylic acids, esters, and amides could be synthesized. All these C-11 labeling methods show excellent functional group tolerance.

Free Research Field

創薬化学

Academic Significance and Societal Importance of the Research Achievements

マルチメタル協同型高速11C-シアン標識法を初めて開発できた。安定性高い、種類豊富な（ヘテロ）芳香族スズ化合物（Ar-Sn)、芳香族フッ化物（Ar-F)、芳香族塩化物（Ar-Cl）を前駆体として利用でき、標識可能の[cyano-11C]芳香族ニトリル類トレーサー範囲は大幅に上げました。また本研究で、高い汎用性な芳香族塩化物の11C-カルボニル化反応も初めて確立できた。これらの標識法と誘導体化戦略を活用し、多彩な機能性PETトレーサーの効率創出、PET化学の発展とPETイメージング研究応用の促進に幅広く貢献に期待できます。