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

以[^(14)C]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-^(14)C_6]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 m Ci)和N-[2-(4-甲基苯并噻唑基)]-2-氨基-2-氟苯基-O,O-二乙基[^(14)C]甲基膦酸酯(3,32.4 m Ci)],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 m Ci/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.

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）[^14 C]methyl）phosphonate（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.