3',5'-Bis-O-[(1,1-dimethylethyl)dimethylsilyl]-a-[[(1,1-dimethylethyl)dimethylsilyl]oxy]thymidine | 1210427-80-7

• 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'-Bis-O-[(1,1-dimethylethyl)dimethylsilyl]-a-[[(1,1-dimethylethyl)dimethylsilyl]oxy]thymidine
• 英文别名: 1-[(2R,4S,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-5-[[tert-butyl(dimethyl)silyl]oxymethyl]pyrimidine-2,4-dione
• CAS: 1210427-80-7
• 化学式: C₂₈H₅₆N₂O₆Si₃
• 分子量: 601.019
• InChiKey: VWNYSLBEKMNLIZ-YTFSRNRJSA-N

物化性质

• 密度：
  1.03±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于二氯甲烷、乙醇

计算性质

• 辛醇/水分配系数(LogP)：
  6.76
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  86.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3',5'-Bis-O-[(1,1-dimethylethyl)dimethylsilyl]-a-[[(1,1-dimethylethyl)dimethylsilyl]oxy]thymidine 在 4-二甲氨基吡啶 、 2,4,6-三异丙基苯磺酰氯 、 三乙胺 、 氨 作用下， 以 乙腈 、 水 为溶剂， 反应 25.0h， 以51%的产率得到
  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：

  5-羟甲基脱氧尿苷 、 叔丁基二甲基氯硅烷 在 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 60.0h， 以69%的产率得到3',5'-Bis-O-[(1,1-dimethylethyl)dimethylsilyl]-a-[[(1,1-dimethylethyl)dimethylsilyl]oxy]thymidine
  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

• Quantification of the Sixth DNA Base Hydroxymethylcytosine in the Brain
  作者：Martin Münzel、Daniel Globisch、Tobias Brückl、Mirko Wagner、Veronika Welzmiller、Stylianos Michalakis、Markus Müller、Martin Biel、Thomas Carell

  DOI：10.1002/anie.201002033

  日期：——

  allowed the amount of the post‐replicatively formed DNA base 5‐hydroxymethylcytosine (see picture; left) to be quantified in brain tissue. The nucleoside is most abundant in areas that are associated with higher cognitive functions, and its content in mouse hippocampi seems to increase with age. The new method enables hydroxymethylcytosine to be quantified with unprecedented accuracy.

  注意事项：LC-MS允许在脑组织中量化复制后形成的DNA碱基5-羟甲基胞嘧啶的量（参见图片；左图）。核苷在与更高的认知功能相关的区域中含量最高，并且其在小鼠海马中的含量似乎随着年龄的增长而增加。新方法使羟甲基胞嘧啶的定量达到前所未有的准确性。
• 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.