Chem. J. Chinese Universities

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Diastereomers Separation and Fluorine-18 Labeling of 2-Amino-dihydrotetrabenzine

LIU Chunyi1, FANG Yi1, LI Jingwen1,2, LI Qian1, CHEN Zhengping1   

  1. 1. National Health Commission Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine 2. Department of Radiopharmaceuticals, School of Pharmacy, Nanjing Medical University
  • Received:2025-06-20 Revised:2025-08-13 Online:2025-08-18 Published:2025-08-18
  • Contact: CHEN Zhengping E-mail:chenzhengping@jsinm.org
  • Supported by:
    Supported by the Research Foundation of Jiangsu Provincial Commission of Health (No. M2022047), the National Natural Science Foundation of China (No. 82172054, 82402427) and the Foundation of Jiangsu Provincial Medical Key Discipline (Laboratory) (No. ZDXYS202211)

Abstract: Based on the demand for developing novel VMAT2 imaging probes, this study focuses on the synthesis and separation technology of 2-amino-dihydrotetrabenazine (2-NH2-DTBZ) diastereomers and the development of fluorine-18 labeling methods. Starting from tetrabenazine as the raw material, the 2-NH2-DTBZ crude product was synthesized via Borch reductive amination, followed by the effective separation of α- and β-diastereomers using column chromatography. Structural confirmation was achieved through mass spectrometry (ESI-MS) and nuclear magnetic resonance spectroscopy (1H/13C NMR). Given the potential biological activity advantages of the α-diastereomer, a two-step one-pot strategy was established to achieve the 18F labeling of α-2-NH2-DTBZ. High-performance liquid chromatography analysis confirmed that the radiochemical purity of the labeled product was > 99%. Further in vivo experiments demonstrated that the labeled compound can penetrate the blood-brain barrier, providing a crucial foundation for its application in central nervous system imaging. The effective separation system for 2-NH2-DTBZ diastereomers and the 18F labeling methodology established in this study offered a key technical support for the development of novel brain PET probes based on the α-2-NH2-DTBZ scaffold.

Key words: Dihydrotetrabenzine, Diastereomers, Vesicular monoamine transporter, 18F-labeling

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