放射性同位素碳-14标记氯虫苯甲酰胺的合成与分析

杨征敏; 宋明钰; 陈沪飞; 余志扬; 周迪; 夏燕婷; 郑东敏; 薛晓娅

doi:10.16801/j.issn.1008-7303.2020.0003

放射性同位素碳-14标记氯虫苯甲酰胺的合成与分析

doi: 10.16801/j.issn.1008-7303.2020.0003

上海启甄同位素标记合成研究中心，上海 201403

详细信息

通讯作者:
杨征敏，通信作者 (Author for correspondence)，男，博士，技术总监，主要从事功能化学品的放射性同位素标记合成与代谢研究，E-mail：zmyang@qzisotech.com

中图分类号: O628.21；S482.3
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出版历程
- 收稿日期: 2019-05-14
- 录用日期: 2019-07-02
- 刊出日期: 2020-02-01

Synthesis and analysis of radioisotope carbon-14 labelled chlorantraniliprole

Shanghai Qizhen Radiosynthesis Research Center, Shanghai 201403, China

摘要

摘要: 以 [ ¹⁴C ] 碳酸钡为放射性同位素原料，通过格氏反应、亲核取代、胺化和缩合等8步放化反应制备了2种放射性同位素碳-14 标记的氯虫苯甲酰胺粗品，经反相高效液相色谱(RP-HPLC)纯化获得标记物纯品¹⁴C-氯虫苯甲酰胺 [ 3-溴-N- [ 4-氯-2-甲基-6-( 甲氨基 [ 羰基-¹⁴C ] 甲酰基) 苯基 ] -1-(3-氯-2-吡啶基)-1H-吡唑-5-甲酰胺 ( 2 , 55.6 mCi)和3-溴-N- [ 4-氯-2-甲基-6- (甲氨基甲酰基) 苯基 ] -1-(3-氯-2-吡啶基)-1H-吡唑-5- [ 羰基-¹⁴C ] 甲酰胺 ( 3 , 58.6 mCi) ] 。以 [ ¹⁴C ] 碳酸钡计，两种标记物的总放化收率分别为32%和52%。其结构经核磁共振氢谱、质谱和在线放射性高效液相色谱 (HPLC-FSA) 分析确认。放射性薄层成像分析 (TLC-IIA)、离线放射性高效液相色谱分析(HPLC-LSC)、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) 和LSC分析表明，两种¹⁴C-氯虫苯甲酰胺的放化纯度分别为99.8%和99.6%，化学纯度分别为99.1%和98.4%，比活度分别为52.45 mCi/mmol和52.30 mCi/mmol。这2种标记物可作为放射性示踪剂，可满足氯虫苯甲酰胺在中国的登记代谢试验研究的需要。
- 杀虫剂 /
- 同位素标记合成 /
- 碳-14 /
- 氯虫苯甲酰胺 /
- 放射性示踪剂
Abstract: Two versions of radioisotope carbon-14 labelled chlorantraniliprole, 3-bromo-N-(4-chloro-2-methyl-6-(methyl[carbonyl-¹⁴C]carbamoyl)phenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide ( 2 , 55.6 mCi, radiochemical purity 99.8%, chemical purity 99.1%, specific activity 52.45 mCi/mmol) and 3-bromo-N-(4-chloro-2-methyl-6-(methylcarbamoyl)phenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-[carbonyl-¹⁴C]carboxamide ( 3 , 58.6 mCi, radiochemical purity 99.6%, chemical purity 98.4%, specific activity 52.30 mCi/mmol), were synthesized from barium [¹⁴C]carbonate via eight-step radioactive reactions including Grignard reaction, nucleophilic substitution, amination reaction, condensation, and etc. Pure C-14 labelled products were obtained after RP-HPLC purification in the overall radiochemical yield of 32% and 52%, respectively. The products were characterized by ESI-MS, ¹H NMR and HPLC-FSA. Their technical data was determined by TLC-IIA, HPLC-LSC, HPLC-FSA/PDA/MS and LSC, respectively. These products could be used as radiotracers and meet the requirement of the study on the metabolism of chlorantraniliprole for registration in China.
- insecticide /
- isotopically labelled synthesis /
- carbon-14 /
- chlorantraniliprole /
- radiotracer

HTML全文

1 氯虫苯甲酰胺 (1) 及其放射性同位素碳-14标记物 ( *表示碳-14标记位点)

1. Chlorantraniliprole (1) and its radioisotope carbon-14 labelled counterparts(*indicates carbon-14 labelled sites)

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2 [ 苯甲酰胺羰基-¹⁴C] 氯虫苯甲酰胺 (2) 的合成路线 (*表示碳-14标记位点)

2. Synthetic route of [benzamide carbonyl-¹⁴C]chlorantraniliprole 2 (*indicates carbon-14 labelled sites)

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3 [ 吡唑甲酰胺羰基-¹⁴C] 氯虫苯甲酰胺 (3) 的合成路线 (*表示碳-14标记位置)

3. Synthetic route of [pyrazolylamide carbonyl-¹⁴C]chlorantraniliprole 3 (*indicates carbon-14 labelled sites)

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图 1 碳-14标记氯虫苯甲酰胺 (2) 的离线放射性高效液相色谱图 (HPLC-LSC)

Figure 1. Offline radio-chromatogram (HPLC-LSC) of the carbon-14 labelled chlorantraniliprole (2)

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图 2 碳-14标记氯虫苯甲酰胺 (2) 的高效液相色谱图(HPLC-UV)

Figure 2. High performance liquid chromatogram of the carbon-14 labelled chlorantraniliprole (2)

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4 丙酯草醚 (15)、氯虫苯甲酰胺 (16) 和环磺酮 (17) 分子中的标记单元

4. Radiolabelling units of pyribambenz-propyl (15), chlorantraniliprole (16) and tembotrione (17)

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