| 吉西他滨-~(13)C,~(15)N_2及其代谢产物的合成 |
| |
| 引用本文： | 朱称古,杨绍祖,颜盛旺,方宁静,蔡定龙,李刚.吉西他滨-~(13)C,~(15)N_2及其代谢产物的合成[J].同位素,2014,27(2):82-86. |
| |
| 作者姓名： | 朱称古 杨绍祖 颜盛旺 方宁静 蔡定龙 李刚 |
| |
| 作者单位： | 无锡贝塔医药科技有限公司，江阴 江苏214437 |
| |
| 摘 要： | 以自制的尿素-~(13)C,~(15)N_2为前体,与3-乙氧基丙烯腈反应制备胞嘧啶-~(13)C,~(15)N_2,用BSA保护后,经与2-脱氧-2,2-二氟-D-赤式-五呋喃糖-3,5-二苯甲酯-1-甲磺酸酯反应生成2′,2′-二氟-2′-脱氧胞嘧啶核苷-3′,5′-二苯甲酸酯-~(13)C,~(15)N_2,分离纯化后经NaOH水解生成吉西他滨-~(13)C,~(15)N_2,再进一步降解脱氨得到吉西他滨-~(13)C,~(15)N_2代谢产物。产品经HPLC,LC-MS和~1H NMR表征确定,化学纯度高于98%,~(13)C同位素丰度为99%,~(15)N同位素丰度为98%。结果表明,合成的吉西他滨-~(13)C,~(15)N可用于药物代谢研究。
|
| 关 键 词： | 同位素标记 合成 吉西他滨-13C 15N2 吉西他滨代谢物-13C 15N2 |
Synthesis of Gemcitabine-13C, 15N2 and Gemcitabine-13C, 15N2 Metabolites |
| |
| ZHU Cheng-gu,YANG Shao-zu,YAN Sheng-wang FANG Ning-jing,CAI Ding-long,LI Gang.Synthesis of Gemcitabine-13C, 15N2 and Gemcitabine-13C, 15N2 Metabolites[J].Isotopes,2014,27(2):82-86. |
| |
| Authors: | ZHU Cheng-gu YANG Shao-zu YAN Sheng-wang FANG Ning-jing CAI Ding-long LI Gang |
| |
| Affiliation: | Wuxi Beita Pharmatech CO. LTD., Jiangyin 214437, China |
| |
| Abstract: | Homemade urea-13C, 15N2 was used to react with 3-methyl acrylonitrile closure to form cytosine-13C, 15N2 （2）,which was protected by trimethylsilylation with BSA and condensed with 2-deoxy-2,2-difluoro-D-erythro-pentofuranose-3,5-dibenzoate-1-methanesulfonate at 120 ℃ to afford blocked gemcitabine-13C, 15N2. Hydrolytic removal of the blocking groups of gemcitabine-13C, 15N2 with NaOH gave gemcitabine-13C, 15N2, and its metabolite was obtained by further hydrolytic deamination of gemcitabine-13 C, 15N2. The final products were characterized and detected by HPLC, LC-MS and NMR, and confirmed that the chemical purities were higher than 98%, isotopic abundances were 99% 13C, 98% 15N, and they were suitable for drug metabolism studies. |
| |
| Keywords: | isotope labeling synthesis gemcitabine-13C 15N2 gemcitabine-13C 15N2 metab-olites |
| 本文献已被 CNKI 维普 等数据库收录！ |
| 点击此处可从《同位素》浏览原始摘要信息 |
|
点击此处可从《同位素》下载全文 |
|
