Synthesis Of Key Intermediates Of Clitocine Analogues

Clitocine,6-amino-5-nitro-4-(β-D-ribofuranosylamino)-pyrimidine, is used toprepare multidrug resistance anticancer drugs. The researchs of Clitocine importantlyfocuse on the modifications of basic and sugar groups to obtain Clitocine analogues,which have higher biological activity than Clitocine. The paper studied the syntheticroute of1-azido-3,5-di(4-chlorbenzoyl)-2-deoxy-D-ribose and derivatives of4,6-dichloro-5-nitropyrimidine, which are the important intermediates of Clitocinederivatives. The studies laid the foundation for new drug synthesis.Firstly, two successful synthetic routes have been studied:1.2-deoxidation-D-ribose is the starting material, after1-the methylation reacation,3,5-bit groupprotected by parachlorobenzoyl chloride,1-chlorination and1-azidation, the finalproduct1-azido-3,5-di(4-chlorbenzoyl)-2-deoxy-D-ribose is obtained. The yield is51.2%. At the same time, the relationships of yields, different mole ratios of rawmaterials and reaction time have been studied.2.1-methoxy-3,5-di(4-chlorbenzoyl)-2-deoxy-D-ribose is used as the starting material, its reactions include1-acetylationand then1-azidation, finally get the target product of1-azido-3,5-di(4-chlorbenzoyl)-2-deoxy-D-ribose. The yield of the synthic route is34.33%. The experiments explorethe influences of different mole ratios of1-methoxy-3,5-di(4-chlorbenzoyl)-2-deoxy-D-ribose and acetic anhydride, reaction times, reaction temperatures and themounts of concentrated sulphuric acid to the yields.Secondly, the paper is studying the synthetic route of4,6-pyrimidinediamine, the4,6-pyrimidinediamine can be used as the nucleoside bases. The reaction processesinclude5-nitration, chlorination and ammoniation reacations of4and6groups. Theyields of4,6-pyrimidinediamine is42.6%.Finally,4,6-dichloro-5-nitropyrimidine serves as starting material, respectivelyreacted with seven nucleophilic reagents, which are Aniline, P-methoxyaniline,Methylamine, Cyclopentylamine, Cyclohexylamine, Isopropylamine, Pyrrolidine toobtain pyrimidine derivatives of6groups replaced. And then the rest of chloridegroup is ammoniation by saturated ammonia methanol solution. The final products areseven kinds of4,6-dichloro-5-nitropyrimidine derivatives which two chlorine groupsare replaced by amino groups and different nucleophilic reagents. Yields respectively are46.4%、39.7%、51.7%、35.7%、44.8%、33.5%、43.1%. The experiments studiedthe influences of the different mole ratios of raw materials, reaction times and reactiontemperatures to the yield, which the methylamine is the nucleophile.