高等学校化学学报

高等学校化学学报

• 研究论文 • 上一篇    下一篇

2-氨基-二氢丁苯那嗪非对映异构体分离及其氟[18F]标记研究

刘春仪1, 方 毅1, 李靓雯1,2, 李 倩1, 陈正平1   

  1. 1. 国家卫生健康委员会核医学重点实验室, 江苏省分子核医学重点实验室, 江苏省原子医学研究所 2. 南京医科大学药学院核药学系
  • 收稿日期:2025-06-20 修回日期:2025-08-13 网络首发:2025-08-18 发布日期:2025-08-18
  • 通讯作者: 陈正平 E-mail:chenzhengping@jsinm.org
  • 基金资助:
    江苏省卫生健康委医学科研项目(批准号: M2022047)、国家自然科学基金项目(批准号: 82172054, 82402427)和江苏省医学重点学科(实验室)基金项目(批准号: ZDXYS202211)资助

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 First: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)

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摘要： 基于新型VMAT2显像探针开发需求, 本研究聚焦于2-氨基-二氢丁苯那嗪(2-NH2-DTBZ)非对映异构体的分离技术及其氟[18F]标记标记方法开发. 以丁苯那嗪为起始原料, 通过Borch还原氨化反应合成2-NH2-DTBZ粗品, 继而采用柱层析分离技术实现α型和β型非对映异构体的有效分离, 并通过质谱(ESI-MS)及核磁共振波谱(1H/13C NMR)完成结构确证. 鉴于α型异构体潜在的生物活性优势, 本文建立两步一锅法策略实现氟[18F]标记α型2-NH2-DTBZ. 经高效液相色谱分析证实, 所得放射性标记产物的放射化学纯度>99%. 进一步的体内实验表明, 该标记化合物具有穿透血脑屏障的能力, 为其在中枢神经系统显像应用提供了重要基础. 本研究构建的2-NH2-DTBZ非对映异构体有效分离体系及同位素标记方法, 为基于α型2-NH2-DTBZ分子骨架的新型脑内PET探针研发提供了关键技术支撑.

关键词: 二氢丁苯那嗪, 非对映异构体, 囊泡单胺转运体, 18F标记

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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