| Title | 1-苄氧甲基-3-羟基-5-羟甲基-6-苄基尿嘧啶的合成 |
| Other Titles | Synthesis of 6-benzyl-1-[ (benzyloxy) methyl ]-3-hydroxy-5-(hydroxymethyl) pyrimi-dine-2,4(1H,3H)-dione |
| Authors | 唐筱婉 张亮 赵剑雄 张羽 郭莹 张志丽 田超 王孝伟 刘俊义 |
| Affiliation | 开云app体育 药学院化学生物学系,北京,100191 开云app体育 药学院化学生物学系，北京 100191 开云app体育 天然药物与仿生药物国家重点实验室，北京100191 |
| Keywords | 羟基化 HIV逆转录酶 HIV整合酶 嘧啶酮类 酶抑制剂 Hydroxylation HIV reverse transcriptase HIV integrase Pyrimidinones Enzyme inhibitors |
| Issue Date | 2015 |
| Publisher | 开云app体育 学报 医学版 |
| Citation | 开云app体育 学报（医学版）.2015,(5),838-841. |
| Abstract | 目的：研究1-苄氧甲基-3-羟基-5-羟甲基-6-苄基尿嘧啶e的最佳合成方法，以考察在1-苄氧甲基-5-羟甲基-6-苄基尿嘧啶aN-3位引入羟基后其生物活性的变化。方法：尝试多种氮原子羟基化方法，最终通过改进后的间氯过氧苯甲酸（3-chloroperbenzoic acid ，m-CPBA）氧化法成功地合成了1-苄氧甲基-3-羟基-5-羟甲基-6-苄基尿嘧啶e；通过酶联免疫吸附法（ enzyme-linked immunesorbent assay ，ELISA）和磷酸化DNA包被法分别对目标化合物进行了人类免疫缺陷病毒（human immunodeficiency virus，HIV）逆转录酶（reverse transcriptase，RT）和整合酶（integrase，IN）抑制活性的测定。结果：m-CPBA氧化法在N-3位羟基化只需1步反应，收率达到60％～70％，目标化合物通过1 H NMR、13 C NMR和MS鉴定结构正确；活性测定结果显示：1-苄氧甲基-5-羟甲基-6-苄基尿嘧啶a N-3位引入羟基后保留了HIV逆转录酶抑制活性，同时还产生了HIV整合酶抑制活性。结论：利用改进后的m-CPBA氧化法可以简便、高效地合成1-苄氧甲基-3-羟基-5-羟甲基-6-苄基尿嘧啶e，且该化合物对HIV逆转录酶和整合酶都具有抑制活性。 Objective:To find the best synthesis method of 6-benzyl-1-[ ( benzyloxy ) methyl ]-3-hydro-xy-5-(hydroxymethyl)pyrimidine-2,4(1H,3H)-dione e for observing the change of its biological activity after N-3 hydroxylation .Methods:After trying some N-hydroxylation methods , the target compound was successfully synthesized via one-pot oxidizing process by sodium hydride ( NaH) and 3-chloroperbenzoic acid( m-CPBA);the anti-HIV reverse transcriptase ( RT) activity and integrase ( IN) activity of the tar-get compound was assayed via enzyme-linked immunesorbent assay ( ELISA) and phosphorylation of DNA package method .Results:The target compound could be obtained through the improved m-CPBA oxida-tive method by only one step , and the yield of the reaction could reach 60%-70%.And the structure of this compound was identified by 1 H NMR, 13 C NMR and MS;The activity result showed it added the an-ti-HIV IN activity after N-3 hydroxylation as well as retained the anti-HIV RT activity.Conclusion:The improved m-CPBA oxidative method is a convenient and efficient way to prepare the compound 6-benzyl-1-[(benzyloxy)methyl]-3-hydroxy-5-(hydroxymethyl)pyrimidine-2,4(1H,3H)-dione e which has both anti-HIV RT and IN activity . |
| URI | http://hdl.handle.net/20.500.11897/420473 |
| ISSN | 1671-167X |
| DOI | 10.3969/j.issn.1671-167X.2015.05.021 |
| Indexed | 中文核心期刊要目总览(PKU) 中国科技核心期刊(ISTIC) 中国科学引文数据库(CSCD) |
| Appears in Collections: | 药学院 天然药物与仿生药物国家重点实验室 |
