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2013 , Vol. 33 >Issue 07: 1578 - 1582

DOI: https://doi.org/10.6023/cjoc201212001

研究简报

一种氟代腺苷类衍生物的合理设计与合成

  • 许芝祥 ,
  • 尹伟 ,
  • 陈晶磊 ,
  • 乔春华
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  • 苏州大学药学院 苏州 215123

收稿日期: 2012-12-01

  修回日期: 2013-01-26

  网络出版日期: 2013-02-05

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

收起

Rational Design and Synthesis of a Fluorinated Adenosine Derivative

  • Xu Zhixiang ,
  • Yin Wei ,
  • Chen Jinglei ,
  • Qiao Chunhua
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  • College of Pharmacy, Soochow University, Suzhou 215123

Received date: 2012-12-01

  Revised date: 2013-01-26

  Online published: 2013-02-05

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).

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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.

关键词： 氟代腺苷衍生物; 泛酸合成酶; 抗结核; 全合成

本文引用格式

许芝祥 , 尹伟 , 陈晶磊 , 乔春华 . 一种氟代腺苷类衍生物的合理设计与合成[J]. 有机化学, 2013 , 33(07) : 1578 -1582 . DOI: 10.6023/cjoc201212001

Abstract

Pantothenate synthetase (PS), a member of adenosine acylation enzyme family, was the new target of anti-tuberculosis drug development. Employing bioisostere principle, 5'-O-{[(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 vidarabine as the starting materials by 9 steps of reaction, and its structure was fully characterized by 1H NMR, 13C NMR and HR-MS techniques.

Key words： fluorinated adenosine derivative; pantothenate synthetase; anti-tuberculosis; total synthesis

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