Chin. J. Org. Chem. ›› 2014, Vol. 34 ›› Issue (6): 1222-1226.DOI: 10.6023/cjoc201311005 Previous Articles     Next Articles

Notes

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).

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