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 target 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 oxidative method by only one step, and the yield of the reaction could reach  60%－70%.And the structure of this compound was identified by 1H NMR, 13C NMR and MS; The activity result showed it added  the anti-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.

Key words: Hydroxylation, HIV reverse transcriptase, HIV integrase, Pyrimidinones, Enzyme inhibitors