一种氟代丁酸腺苷衍生物的合成  

Rational Design and Synthesis of a Fluorinated Butyric Adenosine Derivative

作　　者：姚后宗 尹伟[1,2] 陈晶磊[1] 乔春华[1] 

机构地区：[1]苏州大学药学院,苏州215123 [2]中国药科大学新药研究中心,南京210009

出　　处：《有机化学》2014年第6期1222-1226,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：泛酸合成酶(Pantothenate Synthetase,PS)是结核杆菌泛酸合成途径中的一个关键酶,成为抗结核药物合适靶位.根据泛酸合成酶催化的反应中间体和生物电子等排原理,用酰基磺酰胺取代不稳定的酰基磷酸接合子,以泛酸内酯和腺苷为原料,通过9步反应合成了5-O-{[(R)-4-氟-2-羟基-3,3-二甲基丁酰基]磺酰胺基}腺苷(1).所合成化合物的结构都经1H NMR,13C NMR和HRMS表征确认.Pantothenate synthetase（PS）, the key enzyme in the biosynthesis of the pantothenate acid, is considered to be a new target for anti-tuberculosis drug development. Based on the structure of the enzyme catalyzed reaction intermediate and bioisosterism principle, 5＇-O-{[（R）-4-fluoro-2-hydroxy-3,3-dimethylbutanoyl]sulfamoyl}adenosine（1） was designed with the sulfamate isoster to replace the unstable phosphate moiety. The synthesis of this compound was achieved using pantolactone and adenosine as the starting materials through 9 steps of reaction. All the compounds were characterized by 1H NMR, 13C NMR and MS techniques.

关 键 词：腺苷衍生物 泛酸合成酶 抗结核 

分 类 号：O621.3[理学—有机化学] TQ464[理学—化学]