Efficient syntheses of [11C]zidovudine and its analogues by convenient one-pot palladium(0)-copper(I)co-mediated rapid C-[11C]methylation.
Efficient syntheses of [11C]zidovudine and its analogues by convenient one-pot palladium(0)-copper(I)co-mediated rapid C-[11C]methylation.
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通过方便的一锅法钯(0)-铜(I)共介导的快速 C-[11C]甲基化有效合成[11C]齐多夫定及其类似物。
DOI：
10.1002/jlcr.3213
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Masaaki Suzuki
中科院分区：
文献类型：
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作者：
Zhouen Zhang;Hisashi Doi;Hiroko Koyama;Yasuyoshi Watanabe;Masaaki Suzuki
核苷齐多夫定(AZT)、司他夫定(D4T)和替比夫定(LdT)被批准用于治疗人类免疫缺陷病毒(HIV)和乙肝病毒(HBV)感染。为了促进正电子发射断层扫描(PET)对其药代动力学、药效学的研究及其在癌症诊断中的应用，成功地建立了一种简便的Pd(0)-Cu(I)共催化[11C]甲基碘与锡基前体快速C-C偶联的方法，并应用于合成了[11C]齐多夫定、[11C]司他夫定和[11C]替比夫定的PET示踪剂。经过高效液相纯化和放射性药物配方，得到了高放射性(6.4~7.0 GBq)和比放射性(74~147 GBq/µm ol)、高化学纯度(~gt；99%)和高放射化学纯度(>；99.5%)的PET示踪剂。这种一锅法Pd(0)-Cu(I)共介导的快速C-[11C]甲基化也能很好地用于合成[甲基-11C]胸腺嘧啶核苷和[甲基-11C]4‘-硫代胸苷，其放射性是以前两锅法的两倍。并对一锅法Pd(0)-Cu(I)共介导的快速C-[11C]甲基化的机理进行了探讨。
The nucleosides zidovudine (AZT), stavudine (d4T), and telbivudine (LdT) are approved for use in the treatment of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections. To promote positron emission tomography (PET) imaging studies on their pharmacokinetics, pharmacodynamics, and applications in cancer diagnosis, a convenient one‐pot method for Pd(0)–Cu(I) co‐mediated rapidC–Ccoupling of [11C]methyl iodide with stannyl precursor was successfully established and applied to synthesize the PET tracers [11C]zidovudine, [11C]stavudine, and [11C]telbivudine. After HPLC purification and radiopharmaceutical formulation, the desired PET tracers were obtained with high radioactivity (6.4–7.0 GBq) and specific radioactivity (74–147 GBq/µmol) and with high chemical (>99%) and radiochemical (>99.5%) purities. This one‐pot Pd(0)–Cu(I) co‐mediated rapidC‐[11C]methylation also worked well for syntheses of [methyl‐11C]thymidine and [methyl‐11C]4′‐thiothymidine, resulting twice the radioactivity of those prepared by a previous two‐pot method. The mechanism of one‐pot Pd(0)–Cu(I) co‐mediated rapidC‐[11C]methylation was also discussed.