An improved synthesis of dopamine D2/D3 receptor radioligands [11C]fallypride and [18F]fallypride
An improved synthesis of dopamine D2/D3 receptor radioligands [11C]fallypride and [18F]fallypride
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DOI：
10.1016/j.apradiso.2009.09.071
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发表时间：
2010-06-01
影响因子：
1.6
通讯作者：
Zheng, Qi-Huang
中科院分区：
文献类型：
--
作者：
Gao, Mingzhang;Wang, Min;Zheng, Qi-Huang
本文报道了多巴胺D-2/D-3受体放射性配体[C-11]Fallypride和[F-18]Fallypride的合成改进。用于C-11标记的酚类前体（9）和Fallypride（10）参比标准品由起始物料2-羟基-3-甲氧基-5-（2-丙烯基）苯甲酸甲酯（1）经7步和8步合成，总化学产率分别为16%和5%。用于F-18标记的甲苯磺酰化前体（15）由化合物1经5步合成，总化学产率为32%。已经开发了Fallypride的替代合成方法，使用相同的起始材料1分5步进行，总化学产率为26%。[C-11]Fallypride（[C-11]10）通过苯酚前体与[C-11]甲基三氟甲磺酸酯的O-[C-11]甲基化制备，并采用半制备型HPLC方法纯化，放射化学产率为50-60%，衰变校正至轰击结束（EOB），基于[C-11]CO2，EOB处的比放射性为370 +/- 185 GBq/μ mol。通过用K[F-18]F/Kryptofix 2.2.2对甲苯磺酰化前体进行亲核取代，并结合HPLC和固相萃取（SPE）纯化，制备[F-18]Fallypride（[F-18]10），K[F-18]F的衰变校正放射化学产率可变（高达50%），EOB时比活度为111- 2.2.2 GBq/μ mol。(C)2010爱思唯尔有限公司版权所有。
Improved syntheses of dopamine D-2/D-3 receptor radioligands [C-11]Fallypride and [F-18]Fallypride are reported. The phenolic precursor (9) for C-11 labeling and the Fallypride (10) reference standard were synthesized from the starting material 2-hydroxy-3-methoxy-5-(2-propenyl)benzoic acid methyl ester (1) in 7 and 8 steps with 16% and 5% overall chemical yields, respectively. The tosylated precursor (15) for F-18 labeling was synthesized from compound 1 in 5 steps with 32% overall chemical yield. An alternate synthetic approach for Fallypride has been developed using the same starting material 1 in 5 steps with 26% overall chemical yield. [C-11]Fallypride ([C-11]10) was prepared by O-[C-11]methylation of the phenolic precursor with [C-11]methyl triflate and purified with a semi-preparative HPLC method in 50-60% radiochemical yield, decay corrected to end of bombardment (EOB), based on [C-11]CO2, and 370 +/- 185 GBq/mu mol specific radioactivity at EOB. [F-18]Fallypride ([F-18]10) was prepared by nucleophilic substitution of the tosylated precursor with K[F-18]F/Kryptofix 2.2.2 and HPLC combined with solid-phase extraction (SPE) purification in variable (up to 50%) decay corrected radiochemical yield from K[F-18]F and 111-222 GBq/mu mol specific activity at EOB. (C) 2010 Elsevier Ltd. All rights reserved.