用于阿尔茨海默病成像的PET tau示踪剂[(11)C]PBB3的合成。
Synthesis of a PET tau tracer [(11)C]PBB3 for imaging of Alzheimer's disease.
作者信息
Wang Min, Gao Mingzhang, Xu Zhidong, Zheng Qi-Huang
机构信息
Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, College of Chemistry and Environmental Science, Hebei University, Baoding, Hebei 071002, China.
出版信息
Bioorg Med Chem Lett. 2015 Oct 15;25(20):4587-92. doi: 10.1016/j.bmcl.2015.08.053. Epub 2015 Aug 20.
The authentic standard PBB3 and its precursor N-desmethyl-PBB3 as well as TBS-protected N-desmethyl-PBB3 precursor for radiolabeling were synthesized from 5-bromo-2-nitropyridine, acrolein diethyl acetal, 6-methoxy-2-methylbenzothiazole, and diethylchlorophosphate with overall chemical yield 1% in six steps, 2% in five steps, and 1% in six steps, respectively. [(11)C]PBB3 was prepared from either desmethyl-PBB3 or TBS-protected desmethyl-PBB3 with [(11)C]CH3OTf through N-[(11)C]methylation and isolated by HPLC combined with SPE in 20-25% and 15-20% radiochemical yield, respectively, based on [(11)C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity at EOB was 370-1110 GBq/μmol with a total synthesis time of ~40-min from EOB.
authentic标准品PBB3及其前体N-去甲基-PBB3以及用于放射性标记的TBS保护的N-去甲基-PBB3前体由5-溴-2-硝基吡啶、丙烯醛二乙缩醛、6-甲氧基-2-甲基苯并噻唑和二氯磷酸二乙酯合成，总化学产率分别为6步反应1%、5步反应2%和6步反应1%。[(11)C]PBB3由去甲基-PBB3或TBS保护的去甲基-PBB3与[(11)C]CH3OTf通过N-[(11)C]甲基化反应制备，并通过HPLC结合SPE分离，基于[(11)C]CO2并校正到轰击结束（EOB）时的放射性化学产率分别为20%-25%和15%-20%。放射性化学纯度>99%，EOB时的比活度为370-1110 GBq/μmol，从EOB开始的总合成时间约为40分钟。
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