一种氟代腺苷类衍生物的合理设计与合成  

Rational Design and Synthesis of a Fluorinated Adenosine Derivative

作　　者：许芝祥[1] 尹伟[1] 陈晶磊[1] 乔春华[1] 

机构地区：[1]苏州大学药学院,苏州215123

出　　处：《有机化学》2013年第7期1578-1582,共5页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.81072514);国家自然青年科学基金(No.21002067)资助项目~~

摘　　要：针对抗结核药物新靶酶——腺苷酰化酶家族的泛酸合成酶,以生物电子等排原理,模拟泛酸合成酶催化的中间体,用氟取代中间体糖环上2'位羟基,合理设计了目标化合物5'-O-{[(R)-2-羟基-3,3-二甲基丁酰基]磺酰胺基}-2'-去氧-2'-氟腺苷(1).以D-叔亮氨酸和阿糖腺苷为原料,通过9步反应合成得到目标产物.其结构经1H NMR,13C NMR和HRMS表征确认.Pantothenate synthetase （PS）, a member of adenosine acylation enzyme family, was the new target of anti-tuberculosis drug development. Employing bioisostere principle, 5＇-0-{[（R）-2-hydroxy-3,3-dimethylbutanoyl]sulfamoyl}- 2＇-deoxy-2＇-fluoroadenosine （1）, a mimic of the PS catalyzed reaction intermediate, was rational designed by substituting the 2＇-hydroxyl group of intermediate sugar ring with fluorine. This compound was synthesized using D-tertiary leucine and vida- rabine as the starting materials by 9 steps of reaction, and its structure was fully characterized by 1H NMR, 13C NMR and HR-MS techniques.

关 键 词：氟代腺苷衍生物 泛酸合成酶 抗结核 全合成 

分 类 号：TQ463[化学工程—制药化工]