Novel synthesis of [18F] labeling reagent [18F] 標識化合物の新規合成


Tetrahedron Lett., 2022, xx, xxxx-xxxx.
DOI: 10.1016/j.tetlet.2022.154010

“Novel synthesis of an [18F]aryl boronic acid ester as a reagent for 18F-labeling via Suzuki coupling”

Yusuke Yagi a,b,c,d,⇑ , Hiroyuki Kimura b,⇑, Yuto Kondo b, Takahiro Higuchi c,d,e

a Department of Radiological Technology, Faculty of Medicinal Science, Kyoto College of Medical Science, 1-3 Imakita, Oyama-higashi, Sonobe, Nantan, Kyoto 622-0022, Japan
b Department of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Sciences, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan
c Department of Nuclear Medicine, University Hospital Würzburg, OberdìrrbacherStrasse 6, 97080 Würzburg, Germany
d Comprehensive Heart Failure Center, University Hospital of Würzburg, Am Schwarzenberg 15, Haus A15, 97078 Würzburg, Germany
e Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan

  Indirect 18F labeling methods using 18F-containing compounds such as N-succinimidyl-4-[18F]fluorobenzoate and 4-[18F]fluoroiodobenzene as labeling reagents have been reported because direct 18F labeling has difficulty in labeling aromatic compounds. In this study, we synthesized the 18F-labeling reagent 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) [18F]fluorobenzene ([18F]TDBFB) using a resonant-type microwave reactor in the presence of (2,2,6,6-tetramethylpiperidine 1-oxyl and a copper catalyst. Compared with a previous report on [18F]fluorophenylboronic acid, [18F]TDBFB was synthesized simply. Moreover, we applied [18F]TDBFB for the Suzuki coupling with triflate and bromide precursors. The Suzuki coupling of [18F]TDBFB and precursors using resonant-type microwave reactor yielded 4-[18F]fluorobiphenyl and the [18F]pitavastatin derivative as the coupling products. These results show the potential of [18F]TDBFB obtained using rapid synthesis as an indirect 18F-labeling reagent.

Equipment information Reactor size: batch-type microwave reactor, Maximum power: 10 W (SAIDA FDS INC.)


京都医療科学大学 屋木 祐亮先生
京都薬科大学 木村 寛之先生、近藤 悠斗様
ヴェルツブルク大学、岡山大学 樋口 隆弘先生
装置情報:バッチ型マイクロ波装置、10 W