有机化学 ›› 2014, Vol. 34 ›› Issue (6): 1222-1226.DOI: 10.6023/cjoc201311005 上一篇    下一篇

研究简报

一种氟代丁酸腺苷衍生物的合成

姚后宗a, 尹伟a,b, 陈晶磊a, 乔春华a   

  1. a. 苏州大学药学院 苏州 215123;
    b. 中国药科大学新药研究中心 南京 210009
  • 收稿日期:2013-11-05 修回日期:2014-01-20 发布日期:2014-03-03
  • 通讯作者: 陈晶磊, 乔春华 E-mail:jlchen@suda.edu.cn;qiaochunhua@suda.edu.cn
  • 基金资助:

    国家自然科学基金(No. 81072514)和国家自然青年科学基金(No. 21002067)资助项目.

Rational Design and Synthesis of a Fluorinated Butyric Adenosine Derivative

Yao Houzonga, Yin Weia,b, Chen Jingleia, Qiao Chunhuaa   

  1. a. College of Pharmaceutical Science, Soochow University, Suzhou 215123;
    b. Center for Drug Discovery, China Pharmaceutical University, Nanjing 210009
  • Received:2013-11-05 Revised:2014-01-20 Published:2014-03-03
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 81072514) and the National Natural Science Foundation for Young Scientists of China (No. 21002067).

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.

关键词: 腺苷衍生物, 泛酸合成酶, 抗结核

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.

Key words: adenosine derivative, pantothenate synthetase, anti-tuberculosis