N-[1-[(2R,4S,5R)-5-[[(2R,3S,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxymethoxymethyl]-4-[tert-butyl(dimethyl)silyl]oxyoxolan-2-yl]-5-methyl-2-oxopyrimidin-4-yl]benzamide | 1054664-26-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: N-[1-[(2R,4S,5R)-5-[[(2R,3S,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxymethoxymethyl]-4-[tert-butyl(dimethyl)silyl]oxyoxolan-2-yl]-5-methyl-2-oxopyrimidin-4-yl]benzamide
• CAS: 1054664-26-4
• 化学式: C₅₅H₆₅N₅O₁₂Si
• 分子量: 1016.23
• InChiKey: BINPLTJZYGEYHT-XZDVQWHVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.01
• 重原子数：
  73
• 可旋转键数：
  20
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  185
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  N-[1-[(2R,4S,5R)-5-[[(2R,3S,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxymethoxymethyl]-4-[tert-butyl(dimethyl)silyl]oxyoxolan-2-yl]-5-methyl-2-oxopyrimidin-4-yl]benzamide 在 吡啶 、 2-氯-1,3,2-苯并二氧磷杂环己烷-4-酮 、 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 生成
  参考文献：
  名称：

  Synthesis and binding properties of pyrimidine oligodeoxynucleoside analogs containing neutral phosphodiester replacements: the formacetal and 3'-thioformacetal internucleoside linkages

  摘要：

  The replacement of the phosphodiester linkage with neutral, achiral, nuclease resistant entities is desirable for the development of oligodeoxynucleotide (ODN) analogs as therapeutic agents in either the antisense or antigene modes. Described herein is the use of the formacetal and 3'-thioformacetal connections as phosphodiester backbone analogs. Pyrimidine dimer blocks containing these moieties were synthesized and incorporated into ODNs in an alternating array with phosphodiester bonds, such that the ODNs had seven acetal and seven phosphodiester linkages. The binding properties of the resulting chimeric ODNs to single-stranded (ss) RNA and double-stranded (ds) DNA were then determined. ssRNA binding properties were determined by thermal denaturation (Tm) analysis, and the 3'-thioformacetal ODN/ssRNA duplex showed a 5.5-degrees-C enhancement in Tm relative to the control phosphodiester ODN. The triple helix formation properties of the 3'-thioformacetal and formacetal ODNs were determined by footprint and restriction enzyme inhibition assays. The 3'-thioformacetal ODN binds to dsDNA with an affinity slightly less than the control ODN. The high affinity and specificity of an ODN containing the 3'-thioformacetal for the ssRNA target and dsDNA target suggest that this linkage is a promising analog for both antisense and triple helix therapeutic applications.

  DOI：

  10.1021/jo00063a014
• 作为产物：
  描述：

  5'-O-(4,4'-dimethoxytrityl)-3'-O-(methylthiomethyl)thymidine 、 N⁴-benzoyl-5-methyl-2'-deoxy-3'-O-(tert-butyldimethylsilyl)cytidine 在 2,6-二乙基吡啶 、 4 A molecular sieve 、 溴 作用下， 生成 N-[1-[(2R,4S,5R)-5-[[(2R,3S,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxymethoxymethyl]-4-[tert-butyl(dimethyl)silyl]oxyoxolan-2-yl]-5-methyl-2-oxopyrimidin-4-yl]benzamide
  参考文献：
  名称：

  Synthesis and binding properties of pyrimidine oligodeoxynucleoside analogs containing neutral phosphodiester replacements: the formacetal and 3'-thioformacetal internucleoside linkages

  摘要：

  The replacement of the phosphodiester linkage with neutral, achiral, nuclease resistant entities is desirable for the development of oligodeoxynucleotide (ODN) analogs as therapeutic agents in either the antisense or antigene modes. Described herein is the use of the formacetal and 3'-thioformacetal connections as phosphodiester backbone analogs. Pyrimidine dimer blocks containing these moieties were synthesized and incorporated into ODNs in an alternating array with phosphodiester bonds, such that the ODNs had seven acetal and seven phosphodiester linkages. The binding properties of the resulting chimeric ODNs to single-stranded (ss) RNA and double-stranded (ds) DNA were then determined. ssRNA binding properties were determined by thermal denaturation (Tm) analysis, and the 3'-thioformacetal ODN/ssRNA duplex showed a 5.5-degrees-C enhancement in Tm relative to the control phosphodiester ODN. The triple helix formation properties of the 3'-thioformacetal and formacetal ODNs were determined by footprint and restriction enzyme inhibition assays. The 3'-thioformacetal ODN binds to dsDNA with an affinity slightly less than the control ODN. The high affinity and specificity of an ODN containing the 3'-thioformacetal for the ssRNA target and dsDNA target suggest that this linkage is a promising analog for both antisense and triple helix therapeutic applications.

  DOI：

  10.1021/jo00063a014