高等学校化学学报2025，Vol.46Issue(11)：21-29,9.DOI:10.7503/cjcu20250172
2-氨基-二氢丁苯那嗪非对映异构体的分离及氟[18F]标记
Diastereomers Separation and Fluorine-18 Labeling of 2-Amino-dihydrotetrabenzine
摘要
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 NMR/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 higher than 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 sepa-ration 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.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Key words
Dihydrotetrabenzine/Diastereomer/Vesicular monoamine transporter/18F-labeling分类
化学化工引用本文复制引用
刘春仪,方毅,李靓雯,李倩,陈正平..2-氨基-二氢丁苯那嗪非对映异构体的分离及氟[18F]标记[J].高等学校化学学报,2025,46(11):21-29,9.基金项目
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(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. Supported by the Research Foundation of Jiangsu Provincial Commission of Health,China(No.M2022047),the National Natural Science Foundation of China(Nos.82172054,82402427)and the Foundation of Jiangsu Provincial Medical Key Discipline(Laboratory),China(No.ZDXYS202211). （批准号:M2022047）
