两种^(18)F标记苯乙烯基吡啶衍生物前体化合物的合成研究

Synthesis of Precursors of Two ^(18)F Labeled Styrylpyridine Derivatives as PET Imaging Agents

18F-AV45是首个FDA批准上市的阿兹海默症(AD)显像用PET药物,其异构体18F-YG也可能具有更好的性能。为促进18F-AV45的国产化及评价其异构体18F-YG在AD显像方面的性能,本工作合成了两者的标记前体化合物。具体方法为:以4-氨基苯乙烯为原料,经过碳酸叔丁基保护和碘甲烷甲基化,得到BOC保护的对甲胺基苯乙烯;该苯乙烯结构双键上的氢原子被TEG链修饰过的碘吡啶取代后,以对甲苯磺酸基保护TEG侧链羟基,得到目标产物AV105和YGQT,总产率分别为57%和66%。ESI-MS、1 H NMR验证结果显示,两种前体化合物结构正确。前体化合物AV105和YGQT的合成为进一步研究18F-AV45及其异构体18F-YG在AD显像方面的性能提供了基础。

18F-AV45 was the first PET imaging agent for Alzheimer's disease approved by FDA.Its isomer 18F-YG may have better performance in the same field.To promote the localization of 18F-AV45 and the evaluation of 18F-YG,the precursors of the two 18 F labeled styrylpyridine derivatives were obtained.AV105 and YGQT were synthesized using 4-aminostyrene as starting materials.First,aromatic amido was protected by carbonic acid tert-butyl and methylated by methyl iodide to obtain tert-butyl 4-vinylphenylcarbamate.Then,the hydrogen atom on the double bond of tert-butyl 4-vinylphenylcarbamate was replaced by iodopyridine which was modified by TEG.And the hydroxyl of TEG chains was protected by P-toluene sulfonic acid group.The total yields of AV105 and YGQT were 57%and 66%respectively.Their structures were confirmed to be cor-rect by ESI-MS and 1 H NMR investigations.This work provides a basis to study the performance of 18F-AV45 and 18F-YG in the further.