2-去氧-2,3-去氢-N-乙酰基神经氨酸8-硫酸酯、9-硫酸酯衍生物的合成及其生物活性  

Syntheses of 2-Deoxy-2,3-Dehydro-N-Acetyl-8-O-and 9-O-Sulfoneuraminic Acid Derivatives and Their Sialidase Inhibitory Activities

作　　者：李绍顺[1] 李文姬[2] 吴岳平 刘建飞[2] 万维勤[2] 

机构地区：[1]上海交通大学药学院,上海200030 [2]第二军医大学药学院,上海200433

出　　处：《中国药物化学杂志》2001年第5期249-254,共6页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目 (3 95 70 83 7)

摘　　要：对 2 去氧 2 ,3 去氢 N 乙酰基神经氨酸 (Neu5Ac2en)的 8 羟基和 9 羟基进行选择性硫酸酯化 ,以比较不同取代位置的硫酸酯基对唾液酸酶抑制活性的影响。采用三苯甲基氯保护 9 羟基后 ,对 8 羟基进行选择性硫酸酯化 ;在 4,7,8 三羟基乙酰化后 ,酸性条件下水解 9 三苯甲基醚 ,对9 羟基进行选择性硫酸酯化。得到 7个结构全新的Neu5Ac2en 8 硫酸酯衍生物、9 硫酸酯衍生物。初步生物活性试验表明 ,这些化合物均具有一定的唾液酸酶抑制活性 ,9 硫酸酯衍生物的酶抑制活性高于 8 硫酸酯衍生物。To synthesize derivatives of 2-deoxy-2,3-dehydro-N-acetyl-8-O-sulfoneuraminic acid(Neu5Ac2en8-sulfate) and 2-deoxy-2,3-dehydro-N-acetyl-9-O-sulfoneuraminic acid(Neu5Ac2en9-sulfate),and compare their inhibitory activities towards sialidase,Neu5Ac2en8-sulfates were synthesized by using triphenylmethyl to protect the 9-hydroxy group and sulfurtrioxide trimethylamine complex as a sulfation agent.Neu5Ac2en9-sulfates were synthesized by using the same sulfation method after deprotection of 9-O-triphenylmethyl in an acidic solution.Seven new derivatives of 8-sulfate and 9-sulfate were synthesized,the preliminary test showed that all the seven compounds possessed sialidase inhibitory activities and the activities of the derivatives of Neu5Ac2en9-sulfate were stronger than those of Neu5Ac2en8-sulfate.

关 键 词：唾液酸衍生物 选择性硫酸酯化 唾液酸酶抑制活性 

分 类 号：R914[医药卫生—药物化学]