Syntheses of meta-[F]Fluorobenzaldehyde and meta-[F]Fluorobenzylbromide from Phenyl(3-Formylphenyl) Iodonium Salt Precursors.
Syntheses of meta-[F]Fluorobenzaldehyde and meta-[F]Fluorobenzylbromide from Phenyl(3-Formylphenyl) Iodonium Salt Precursors.
复制标题
DOI：
10.1002/jlcr.1853
复制
发表时间：
2011-04
影响因子：
1.8
通讯作者：
Griffiths, Gary L.
中科院分区：
文献类型：
--
作者：
Basuli, Falguni;Wu, Haitao;Griffiths, Gary L.
18F-标记的氟代苯甲醛和氟代苄基溴是用于制备PET放射性药物的有用试剂。尽管邻-和帕拉-[18F]氟苯甲醛可以容易地以高产率制备，但相应的Meta位衍生物更成问题。为了提高Meta-[18F]氟苯甲醛的产率，我们使用相应的二芳基碘鎓盐前体，因为二芳基碘鎓盐已经用作制备18F标记的富电子以及缺电子芳环的前体。合成了具有不同抗衡离子[PhIPhCHO]X（X = Cl，Br，OTs，OTf）的二芳基碘鎓盐。在自由基清除剂2，2，6，6-四甲基哌啶-N-氧基（克里思）的存在下，使用不同的碱在不同的温度下进行18F放射性标记。在110 °C的反应温度下使用CsHCO 3碱获得了向Meta-[18F]氟苯甲醛的最佳转化率（~80%）。为了研究碘鎓盐抗衡离子对放射性活度的影响，在克里思存在下，将每种前体分别用DMF中的CsF[18F]/CsHCO 3在110 ℃下处理5分钟。我们观察到的反应性顺序为OTs<Cl<OTf<Br。在室温下用NaBH 4水溶液将由此获得的Meta-[18 F]氟苯甲醛还原成相应的醇，然后用三苯基膦二溴化物将其转化成间-[18 F]氟苄基溴。通过HPLC确认Meta-[18F]氟苄基溴的形成，并将所需产物在二氧化硅Sep-Pak® plus柱上纯化。
18F-labeled fluorobenzaldehydes and fluorobenzylbromides are useful synthons for the preparation of PET radiopharmaceuticals. Whereas ortho- and para-[18F]fluorobenzaldehydes can easily be prepared with high yields, the corresponding meta- derivatives are more problematic. In order to improve the yield of meta-[18F]fluorobenzaldehyde we used the corresponding diaryliodonium salt precursors, since diaryliodonium salts had already been used as precursors in preparations of 18F-labeled electron rich, as well as electron deficient, aromatic rings. Diaryliodonium salts with different counter ions [PhIPhCHO]X (X = Cl, Br, OTs, OTf) were synthesized. 18F radiolabeling was performed using different bases at different temperatures in the presence of a radical scavenger, 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO). The best conversion (~80%) to meta-[18F] fluorobenzaldehyde was obtained using CsHCO3 base at a reaction temperature of 110 °C. To study iodonium salt counter ion effects on radiofluorination, each precursor was separately treated with CsF[18F]/CsHCO3 in DMF at 110 °C for 5 min in the presence of TEMPO. Our observed reactivity order was OTs<Cl<OTf<Br. Meta-[18F]fluorobenzaldehyde thus obtained was reduced to the corresponding alcohol with aqueous NaBH4 at room temperature and then converted to meta-[18F]fluorobenzylbromide using triphenylphosphine dibromide. Formation of meta-[18F]fluorobenzylbromide was confirmed by HPLC and the desired product was purified on a silica Sep-Pak® plus cartridge.
登录
查看更多内容
影响因子：
1.9
作者：
ARGENTINI, M;WIESE, C;WEINREICH, R
通讯作者：
WEINREICH, R
影响因子：
0.4
作者：
Papash, A. I.;Alenitsky, Yu. G.
通讯作者：
Alenitsky, Yu. G.
影响因子：
1.6
作者：
Guo, Ning;Alagille, David;Baldwin, Ronald M.
通讯作者：
Baldwin, Ronald M.
影响因子：
3.6
作者：
NG, JS;KATZENELLENBOGEN, JA;KILBOURN, MR
通讯作者：
KILBOURN, MR
影响因子：
1.8
作者：
Ermert, J;Hocke, C;Coenen, HH
通讯作者：
Coenen, HH