两种放射性同位素碳-14标记毒氟磷的合成与分析

doi:10.6023/cjoc201712001

有机化学 ›› 2018, Vol. 38 ›› Issue (5): 1177-1184.DOI: 10.6023/cjoc201712001 上一篇下一篇

研究论文

两种放射性同位素碳-14标记毒氟磷的合成与分析

杨征敏^a, 见才广^a, 周兵^a, 许亚军^a, 张贵华^a, 徐凌峰^a, 李霄^a, 唐胜华^a, 徐鹏飞^a, 陈沪飞^a, 夏燕婷^a, 李少博^a, 叶庆富^b

a 上海启甄环境科技有限公司同位素标记合成研究中心上海 201403;
b 浙江大学原子核农业科学研究所杭州 310029

收稿日期:2017-12-02 修回日期:2018-01-11 发布日期:2018-01-26
通讯作者: 杨征敏,E-mail:zmyang@qzisotech.com;叶庆富,E-mail:qfye@zju.edu.cn E-mail:zmyang@qzisotech.com;qfye@zju.edu.cn
基金资助:
上海张江国家自主创新示范区专项发展资金重点（No.201609-FX-A2008-002）资助项目.

Synthesis and Analysis of Two Versions of Radioisotope Carbon-14 Labelled Dufulin

Yang Zhengmin^a, Jian Caiguang^a, Zhou Bing^a, Xu Yajun^a, Zhang Guihua^a, Xu Lingfeng^a, Li Xiao^a, Tang Shenghua^a, Xu Pengfei^a, Chen Hufei^a, Xia Yanting^a, Li Shaobo^a, Ye Qingfu^b

a Radiosynthesis Research Center, Shanghai Qizhen Isotech Co. Ltd., Shanghai 201403;
b Institute of Nuclear Agricultural Sciences, Zhejiang University, Hangzhou 310029

Received:2017-12-02 Revised:2018-01-11 Published:2018-01-26
Contact: 10.6023/cjoc201712001 E-mail:zmyang@qzisotech.com;qfye@zju.edu.cn
Supported by:
Project supported by the Key Project of Special Development Foundation of Shanghai Zhangjiang National Innovation Demonstration Zone (No. 201609-FX-A2008-002).

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摘要/Abstract

以[¹⁴C]碳酸钡为放射性同位素原料，通过乙炔环三聚、苯羧基化和甲基化、胺化、环化、亲核取代、格氏、还原、氧化等反应和反相高效液相色谱（HPLC）纯化获得了2种放射性同位素碳-14标记毒氟磷[N-[2-（4-甲基[苯基-U-¹⁴C₆]苯并噻唑基）]-2-氨基-2-氟苯基-O，O-二乙基甲基膦酸酯（2，20.6 mCi）和N-[2-（4-甲基苯并噻唑基）]-2-氨基-2-氟苯基-O，O-二乙基[¹⁴C]甲基膦酸酯（3，32.4 mCi）]，其结构经核磁共振氢谱（¹H NMR）和在线放射性高效液相色谱-二极管阵列检测器/质谱联用（HPLC-FSA/PDA/MS）分析确认，反应总放化收率/化学收率分别为31%和67%.放射性薄层层析-同位素成像分析（TLC-ⅡA）、离线放射性高效液相色谱（HPLC-LSC），HPLC-FSA/PDA/MS和液体闪烁测量（LSC）分析表明，两种标记物的放化纯度和化学纯度均大于98%，比活度分别为25.5，55.5 mCi/mmol.该标记物可作为放射性示踪剂，用于毒氟磷的代谢、残留和环境行为等研究.

关键词: 同位素标记合成, 毒氟磷, 碳-14, 放射性示踪剂, 植物抗病毒剂

Two versions of carbon-14 labelled dufulin, diethyl ((2-fluorophenyl)((4-methyl [phenyl-U-¹⁴C₆]benzo [d]thiazol- 2-yl)amino)methyl)phosphonate (2) and diethyl ((2-fluorophenyl)((4-methylbenzo [d]thiazol-2-yl)amino) [¹⁴C]methyl)phos- phonate (3), were separately synthesized from barium [¹⁴C]carbonate via ethyne cyclotrimerization, carboxylation and methylation of benzene ring, amination, cyclization, nucleophilic substitution, Grignard reaction, oxidation, reduction reaction, etc. The labelled products were obtained independently after reverse phase high-performance liquid chromatography (RP-HPLC) purification in the overall radiochemical/chemical yield of 31% and 67% and identified by using ¹H NMR and flow scintillation analyzer/photo-diode array/mass spectrometry (HPLC-FSA/PDA/MS). Their technical data was determined by using TLC-ⅡA (isotope imaging analysis), HPLC-LSC (liquid scintillation counter), HPLC-FSA/PDA/MS and LSC, respectively. The result demonstrates that radiochemical/chemical purity of 2 and 3 is more than 98% and the specific activities of 2 and 3 are 25.5 and 55.5 mCi/mmol, respectively. The carbon-14 labelled products can be used as radiotracer in the study on its metabolism, residue and environmental behavior by employing radioisotope tracing techniques.

Key words: isotopically labelled synthesis, dufulin, carbon-14, radiotracer, plant antiviral agent

引用此文

杨征敏, 见才广, 周兵, 许亚军, 张贵华, 徐凌峰, 李霄, 唐胜华, 徐鹏飞, 陈沪飞, 夏燕婷, 李少博, 叶庆富. 两种放射性同位素碳-14标记毒氟磷的合成与分析[J]. 有机化学, 2018, 38(5): 1177-1184.

Yang Zhengmin, Jian Caiguang, Zhou Bing, Xu Yajun, Zhang Guihua, Xu Lingfeng, Li Xiao, Tang Shenghua, Xu Pengfei, Chen Hufei, Xia Yanting, Li Shaobo, Ye Qingfu. Synthesis and Analysis of Two Versions of Radioisotope Carbon-14 Labelled Dufulin[J]. Chin. J. Org. Chem., 2018, 38(5): 1177-1184.

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两种放射性同位素碳-14标记毒氟磷的合成与分析

Synthesis and Analysis of Two Versions of Radioisotope Carbon-14 Labelled Dufulin

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