5-O-tert-butyldiphenylsilyl-α-thymidine | 906354-75-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 5-O-tert-butyldiphenylsilyl-α-thymidine
• 英文别名: 5'-O-(tert-butyldiphenylsilyl)thymidine
• CAS: 906354-75-4
• 化学式: C₂₆H₃₂N₂O₅Si
• 分子量: 480.636
• InChiKey: DARXFPLZEZMZTP-ZRBLBEILSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.07
• 重原子数：
  34.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  93.55
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  甲烷磺酸 、 5-O-tert-butyldiphenylsilyl-α-thymidine 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 24.2h， 以56%的产率得到
  参考文献：
  名称：

  Potential application of thymidylate kinase in nucleoside analogue activation in Plasmodium falciparum

  摘要：

  Plasmodium falciparum thymidylate kinase (PfTMPK) shows a broad range of substrate tolerance when compared to the corresponding human enzyme. Besides 2'-deoxythymidine monophosphate (dTMP), PfTMPK can phosphorylate 3'-azido-2',3'-dideoxythymidine monophosphate (AZTMP) very efficiently. In contrast, human thymidylate kinase (hTMPK) is 200 times less active towards AZTMP. We were interested to see if we could use PfTMPK to activate 3'-azido-2',3'-deoxythymidine (AZT) derivatives as a strategy to treat malaria. P. falciparum lacks a pyrimidine nucleoside kinase which usually activates nucleoside and nucleoside analogues to the corresponding monophosphates. Therefore, several prodrug analogues of AZT and related nucleoside monophosphates were prepared and analysed for antiparasitic activity. The prodrugs showed an increase in activity over the parent nucleoside analogues, which showed no inhibition of parasite growth at the concentration tested. The evidence here reported provides a strategy that could be exploited for further anti-malarial design. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.07.006
• 作为产物：
  描述：

  叔丁基二苯基氯硅烷 、 Alpha-胸苷 在 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以83%的产率得到5-O-tert-butyldiphenylsilyl-α-thymidine
  参考文献：
  名称：

  Potential application of thymidylate kinase in nucleoside analogue activation in Plasmodium falciparum

  摘要：

  Plasmodium falciparum thymidylate kinase (PfTMPK) shows a broad range of substrate tolerance when compared to the corresponding human enzyme. Besides 2'-deoxythymidine monophosphate (dTMP), PfTMPK can phosphorylate 3'-azido-2',3'-dideoxythymidine monophosphate (AZTMP) very efficiently. In contrast, human thymidylate kinase (hTMPK) is 200 times less active towards AZTMP. We were interested to see if we could use PfTMPK to activate 3'-azido-2',3'-deoxythymidine (AZT) derivatives as a strategy to treat malaria. P. falciparum lacks a pyrimidine nucleoside kinase which usually activates nucleoside and nucleoside analogues to the corresponding monophosphates. Therefore, several prodrug analogues of AZT and related nucleoside monophosphates were prepared and analysed for antiparasitic activity. The prodrugs showed an increase in activity over the parent nucleoside analogues, which showed no inhibition of parasite growth at the concentration tested. The evidence here reported provides a strategy that could be exploited for further anti-malarial design. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.07.006

文献信息

• Practical and Reliable Synthesis of 1,2-Dideoxy-<scp>d</scp>-ribofuranose and its Application in RNAi Studies
  作者：Yuki Nagaya、Yoshiaki Kitamura、Remi Nakashima、Aya Shibata、Masato Ikeda、Yukio Kitade

  DOI：10.1080/15257770.2015.1114128

  日期：2016.2

  glass resin). Chemically modified small interfering RNAs (siRNAs) possessing dRH at their 3′-overhang regions were synthesized. Introducing dRH to the 3′-end of the antisense strand of siRNA reduced its knockdown effect.

  我们开发了用于合成无碱基脱氧核糖核苷，1,2-二脱氧一个实际和可靠的方法d -ribofuranose（DR ħ通过消除从胸苷碱基的）。为了通过标准亚磷酰胺固相法合成带有dR H的寡核苷酸，将dR H转化为相应的亚磷酰胺衍生物，并连接到固相载体（可控孔玻璃树脂）上。合成了在其3'-突出端区域具有dR H的化学修饰的小干扰RNA（siRNA）。将dR H引入siRNA反义链的3'末端可降低其敲低效应。