利巴韦林衍生物的合成研究

以2’,3’-异丙叉利巴韦林(Ⅰ)为原料,通过碱催化与3个不同的酰氯缩合酯化和酸催化水解脱除异丙叉保护基两步反应合成了3个化合物,即1-(5-对硝基苯甲酰基-β-D-呋喃核糖基)-1,2,4-三氮唑-3-甲酰胺(Ⅲa),1-5-(3,4,5-三苄氧基苯甲酰基)-β-D-呋喃核糖基]-1,2,4-三氮唑-3-甲酰胺(Ⅲb)和1-(5-苯甲酰基-β-D-呋喃核糖基)-1,2,4-三氮唑-3-甲酰胺(Ⅲc),Ⅲa和Ⅲb通过催化氢化得到1-(5-对氨基苯甲酰基-β-D-呋喃核糖基)-1,2,4-三氮唑-3-甲酰胺(Ⅳa)和1-5-(3,4,5-三羟基苯甲酰基)-β-D-呋喃核糖基]-1,2,4-三氮唑-3-甲酰胺(Ⅳb),考察了不同碱和不同溶剂对酯化反应的影响,不同酸对脱除异丙叉保护基的影响以及催化剂Pd/C的用量对催化氢化的影响.中间体及目标产物均通过IR,1HNMR进行了结构表征.

Synthesis of Ribavirin Derivatives

1-5-(4-nitrobenzoy)-β-D-ribofuranosyl]-1,2,4-triazole-3-carboxamide(Ⅲa),1-5-3,4,5-tribenzyl- oxybenzoyl]-β-D-ribofuranosyl]-1,2,4-triazole-3-carboxamide(Ⅲb) and 1-(5-benzoyl-β-D- ribofuranosyl）-1,2,4-triazole-3-carboxamide(Ⅲc) were synthesized from 1-2,3-O-(1-methylethylidene)-D-ribofuranosyl] -1,2,4-triazole-3-carboxamide(Ⅰ) through esterificated with three different acyl chloride catalyzed by base and hydrolysis reaction catalyzed by TsOH. 1-5-(4-aminobenzoyl)-β-D- ribofuranosyl]-1,2,4-triazole-3-carboxamide(Ⅳa) and 1-5-(3,4,5-trihydroxybenzoyl)-β-D-ribofuranosyl] -1,2,4-triazole-3-carboxamide(Ⅳb) were obtained by hydrogenation catalyzed by Pd/C with MeOH as solvent.Effect of different kinds of bases and solvents on the reaction of condensation,different kinds of acids on the reaction of deprotection,the amount of Pd/C on the reaction of catalytic hydrogenation were investigated.The intermediates and title compounds were confirmed by IR、1HNMR、MS