论文部分内容阅读
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a N-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1H NMR、13C 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 study the best synthetic method of 1-benzyloxymethyl-3-hydroxy-5-hydroxymethyl-6-benzyluracil e - Benzyluracil a N-3 position after the introduction of hydroxyl changes in its biological activity. Methods: A variety of nitrogen atom hydroxylation methods were attempted. Finally, 1-benzyloxymethyl-3-hydroxy-5 -hydroxymethyl-6-benzyluracil e. The target compounds were detected by enzyme-linked immunesorbent assay (ELISA) and phosphorylated DNA coating method, respectively. Human immunodeficiency virus HIV) reverse transcriptase (RT) and integrase (IN) inhibitory activity. Results: The m-CPBA oxidation was only one-step in the N-3 hydroxylation at a yield of 60% -70%. The target compounds were identified by 1H NMR, 13C NMR and MS. The results of the activity determination showed that 1- Benzyloxymethyl-5-hydroxymethyl-6-benzyl uracil a N-3 position into the hydroxyl group retains HIV reverse transcriptase inhibitory activity, but also produced HIV integrase inhibitory activity. CONCLUSION: 1-BENZYLOXYMETHYL-3-HYDROXY-5-HYDROXYMETHYL-6-BENZYL UUQUIN e can be synthesized easily and efficiently by the improved m-CPBA oxidation method and the activity of this compound against HIV reverse transcriptase And integrase all have inhibitory activity.