4-氨甲酰基-4'-叠氮-1,2,3-三氮唑核苷的合成研究

Synthesis study of 4-carbamoyl-4'-azide-1,2,3-triazole nucleoside derivatives

目的合成4-氨甲酰基-4’-叠氮-1,2,3-三氮唑核苷,以期发现具有高抗病毒活性的核苷类药物。方法以商业易得的1,2:5,6-O-双异丙叉-α-D-呋喃葡萄糖为起始原料,经9步反应得到重要糖基叠氮化合物,再与炔丙酸甲酯进行[3+2]偶极环加成反应以构建三氮唑环以及自由基脱羧叠氮化反应和脱保护得到4-氨甲酰基-4’-叠氮-1,2,3-三氮唑核苷。结果以最长线性步骤5步反应,30%的总收率合成了4-氨甲酰基-4'-叠氮-1,2,3-三氮唑,为后期的抗病毒活性测试奠定了基础。

Objective This paper aimed to synthesize 4-carbamoyl-4'-azido-1,2,3-triazole to discover nucleoside drugs with high antiviral activity.Methods Using commercially available 1,2:5,6-Di-O-isopropylidene-a-D-glucofuranose as the starting material,the important glycosyl azide compound was prepared through 9 steps.This intermediate was then subjected to a[3+2]dipolar cycloaddition reaction with methyl propiolate to construct a triazole ring.Finally,4-carbamoyl-4'-azide-1,2,3-triazole nucleoside was obtained by radical decarboxylative azidation reaction and deprotection.Results 4-Carbamoyl-4'-azide-1,2,3-triazole nucleoside was obtained through 5 steps in an overall yield of 30%,which laid a foundation for the later antiviral activity test.