3',5'-di-O-tert-butyldimethylsilyl-5-ethoxycarbonyl-2'-deoxycytidine | 1210427-53-4

• 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: 3',5'-di-O-tert-butyldimethylsilyl-5-ethoxycarbonyl-2'-deoxycytidine
• 英文别名: ethyl 4-amino-1-[(2R,4S,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-2-oxopyrimidine-5-carboxylate
• CAS: 1210427-53-4
• 化学式: C₂₄H₄₅N₃O₆Si₂
• 分子量: 527.809
• InChiKey: GRVRSEXEUMEHKM-IPMKNSEASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  35
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3',5'-di-O-tert-butyldimethylsilyl-5-ethoxycarbonyl-2'-deoxycytidine 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以67%的产率得到5-ethoxycarbonyl-2'-deoxycytidine
  参考文献：
  名称：

  5-Modified-2′-dU and 2′-dC as Mutagenic Anti HIV-1 Proliferation Agents: Synthesis and Activity

  摘要：

  With the goal of limiting HIV-1 proliferation by increasing the mutation rate of the viral genome, we synthesized a series of pyrimidine nucleoside analogues modified in position 5 of the aglycone moiety but unmodified oil the sugar part. The synthetic strategies allow us to prepare the targeted compounds directly from commercially available nucleosides. All compounds were tested for their ability to reduce HIV-1 Proliferation in cell culture. Two of them (5-hydroxymethyl-2'-dU (1c) and 5-hydroxymethyl-2'-dC (2c)) displayed a moderate antiviral activity in single passage experiments. The same two compounds Plus two additional ones (5-carbamoyl-2'-dU (1a) and 5-carbamoylmethyl-2'-dU(1b)) were potent inhibitors of HIV-1 RT activity in serial passage assays, in which they induced a progressive loss of HIV-1 replication. In addition, viruses collected after seven passages in the presence of 1c and 2c replicated very poorly after withdrawal of these compounds, consistent with the accumulation of deleterious mutations in the HIV-1 genome.

  DOI：

  10.1021/jm901758f
• 作为产物：
  描述：

  3',5'-di-O-tert-butyldimethylsilyl-5-ethoxycarbonyl-2'-deoxyuridine 在 4-二甲氨基吡啶 、 2,4,6-三异丙基苯磺酰氯 、 三乙胺 、 ammonium hydroxide 作用下， 以 乙腈 、 水 为溶剂， 反应 22.5h， 以70%的产率得到3',5'-di-O-tert-butyldimethylsilyl-5-ethoxycarbonyl-2'-deoxycytidine
  参考文献：
  名称：

  5-Modified-2′-dU and 2′-dC as Mutagenic Anti HIV-1 Proliferation Agents: Synthesis and Activity

  摘要：

  With the goal of limiting HIV-1 proliferation by increasing the mutation rate of the viral genome, we synthesized a series of pyrimidine nucleoside analogues modified in position 5 of the aglycone moiety but unmodified oil the sugar part. The synthetic strategies allow us to prepare the targeted compounds directly from commercially available nucleosides. All compounds were tested for their ability to reduce HIV-1 Proliferation in cell culture. Two of them (5-hydroxymethyl-2'-dU (1c) and 5-hydroxymethyl-2'-dC (2c)) displayed a moderate antiviral activity in single passage experiments. The same two compounds Plus two additional ones (5-carbamoyl-2'-dU (1a) and 5-carbamoylmethyl-2'-dU(1b)) were potent inhibitors of HIV-1 RT activity in serial passage assays, in which they induced a progressive loss of HIV-1 replication. In addition, viruses collected after seven passages in the presence of 1c and 2c replicated very poorly after withdrawal of these compounds, consistent with the accumulation of deleterious mutations in the HIV-1 genome.

  DOI：

  10.1021/jm901758f

文献信息

• 5-Modified-2′-dU and 2′-dC as Mutagenic Anti HIV-1 Proliferation Agents: Synthesis and Activity
  作者：Yazan El Safadi、Jean-Christophe Paillart、Géraldine Laumond、Anne-Marie Aubertin、Alain Burger、Roland Marquet、Valérie Vivet-Boudou

  DOI：10.1021/jm901758f

  日期：2010.2.25

  With the goal of limiting HIV-1 proliferation by increasing the mutation rate of the viral genome, we synthesized a series of pyrimidine nucleoside analogues modified in position 5 of the aglycone moiety but unmodified oil the sugar part. The synthetic strategies allow us to prepare the targeted compounds directly from commercially available nucleosides. All compounds were tested for their ability to reduce HIV-1 Proliferation in cell culture. Two of them (5-hydroxymethyl-2'-dU (1c) and 5-hydroxymethyl-2'-dC (2c)) displayed a moderate antiviral activity in single passage experiments. The same two compounds Plus two additional ones (5-carbamoyl-2'-dU (1a) and 5-carbamoylmethyl-2'-dU(1b)) were potent inhibitors of HIV-1 RT activity in serial passage assays, in which they induced a progressive loss of HIV-1 replication. In addition, viruses collected after seven passages in the presence of 1c and 2c replicated very poorly after withdrawal of these compounds, consistent with the accumulation of deleterious mutations in the HIV-1 genome.