Synthesis of 6-benzyl-1-[ (benzyloxy) methyl ]-3-hydroxy-5-(hydroxymethyl) pyrimi-dine-2,4(1H,3H)-dione
10.3969/j.issn.1671-167X.2015.05.021
- VernacularTitle:1-苄氧甲基-3-羟基-5-羟甲基-6-苄基尿嘧啶的合成
- Author:
Xiaowan TANG
;
Liang ZHANG
;
Jianxiong ZHAO
;
Yu ZHANG
;
Ying GUO
;
Zhili ZHANG
;
Chao TIAN
;
Xiaowei WANG
;
Junyi LIU
- Publication Type:Journal Article
- Keywords:
Hydroxylation;
HIV reverse transcriptase;
HIV integrase;
Pyrimidinones;
Enzyme inhibitors
- From:
Journal of Peking University(Health Sciences)
2015;(5):838-841
- CountryChina
- Language:Chinese
-
Abstract:
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 .
