[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl [(2R,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] 4-methylsulfanylbutyl phosphate | 1053248-33-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: [(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl [(2R,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] 4-methylsulfanylbutyl phosphate
• CAS: 1053248-33-1
• 化学式: C₂₅H₃₇N₄O₁₂PS
• 分子量: 648.628
• InChiKey: ZZWNGNJTPOFFSI-OYBIWPCZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  43
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  228
• 氢给体数：
  4
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  [(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl [(2R,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] 4-methylsulfanylbutyl phosphate 在 水 作用下， 生成 thymidilyl(3'-5')thymidine
  参考文献：
  名称：

  Assessment of heat-sensitive thiophosphate protecting groups in the development of thermolytic DNA oligonucleotide prodrugs

  摘要：

  Heat-sensitive thiophosphate protecting groups derived from the alcohol 4 or 10 have provided insights in the design of DNA oligonucleotide prodrugs. Indeed, functional groups stemming from the alcohol 9, 15, 16 or 22 may be applicable to thiophosphate protection of immunostimulatory CpG DNA motifs, whereas those originating from the alcohol 3, 5,12,13,18, 20 or 22 offer adequate protection of terminal phosphodiester functions against ubiquitous exonucleases that may be found in biological environments. Functional groups derived from the alcohol 9, 15, 16, 19 or 23 are suitable for the protection of phosphodiester functions flanking the CpG motifs of immunomodulatory DNA sequences. Published by Elsevier Ltd.

  DOI：

  10.1016/j.tet.2009.10.096
• 作为产物：
  描述：

  4-(甲硫基)丁醇 在 四氮唑 、 二异丙胺 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 4.0h， 生成 [(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl [(2R,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] 4-methylsulfanylbutyl phosphate
  参考文献：
  名称：

  DNA寡核苷酸固相合成中的热解4-甲硫基-1-丁基用于磷酸盐/硫代磷酸盐的保护

  摘要：

  已经研究了用于DNA寡核苷酸的不耐热的4-甲基硫基-1-丁基磷酸酯/硫代磷酸酯保护基团，其在诊断芯片上合成寡核苷酸的“热驱动”过程中具有潜在的应用潜力，或者相反，在大规模制备寡核苷酸时具有潜在的应用价值。治疗性寡核苷酸。亚磷酰胺10a - d的制备这是很简单的，并且通过固相技术将这些亚酰胺掺入寡核苷酸的过程与使用2-氰基乙基脱氧核糖核苷亚磷酰胺所实现的过程一样有效。4-甲基硫基-1-丁基磷酸酯/硫代磷酸酯保护基的多功能性可通过在中性条件下于55°C在中性条件下于55°C的水性缓冲液中加热30分钟或在55°C的浓缩条件下2小时内从寡核苷酸中轻松去除而获得。 NH 4 OH。脱保护反应通过分子内环脱酯化机理发生，导致形成salt盐18。与脱氧核糖核苷和N混合时在近似于大规模（> 50 mmol）寡核苷酸脱保护反应的条件下，在保护的2'-脱氧核糖核苷或模型硫代磷酸酯二酯的作用下，盐18不会显着改

  DOI：

  10.1021/jo035861f

文献信息

• Assessment of heat-sensitive thiophosphate protecting groups in the development of thermolytic DNA oligonucleotide prodrugs
  作者：Cristina Ausín、Jon S. Kauffman、Robert J. Duff、Shankaramma Shivaprasad、Serge L. Beaucage

  DOI：10.1016/j.tet.2009.10.096

  日期：2010.1

  Heat-sensitive thiophosphate protecting groups derived from the alcohol 4 or 10 have provided insights in the design of DNA oligonucleotide prodrugs. Indeed, functional groups stemming from the alcohol 9, 15, 16 or 22 may be applicable to thiophosphate protection of immunostimulatory CpG DNA motifs, whereas those originating from the alcohol 3, 5,12,13,18, 20 or 22 offer adequate protection of terminal phosphodiester functions against ubiquitous exonucleases that may be found in biological environments. Functional groups derived from the alcohol 9, 15, 16, 19 or 23 are suitable for the protection of phosphodiester functions flanking the CpG motifs of immunomodulatory DNA sequences. Published by Elsevier Ltd.
• Thermolytic 4-Methylthio-1-butyl Group for Phosphate/Thiophosphate Protection in Solid-Phase Synthesis of DNA Oligonucleotides
  作者：Jacek Cieślak、Andrzej Grajkowski、Victor Livengood、Serge L. Beaucage

  DOI：10.1021/jo035861f

  日期：2004.4.1

  phosphate/thiophosphate protecting group for DNA oligonucleotides has been investigated for its potential application to a “heat-driven” process for either oligonucleotide synthesis on diagnostic microarrays or, oppositely, to the large-scale preparation of therapeutic oligonucleotides. The preparation of phosphoramidites 10a−d is straightforward, and the incorporation of these amidites into oligonucleotides via solid-phase

  已经研究了用于DNA寡核苷酸的不耐热的4-甲基硫基-1-丁基磷酸酯/硫代磷酸酯保护基团，其在诊断芯片上合成寡核苷酸的“热驱动”过程中具有潜在的应用潜力，或者相反，在大规模制备寡核苷酸时具有潜在的应用价值。治疗性寡核苷酸。亚磷酰胺10a - d的制备这是很简单的，并且通过固相技术将这些亚酰胺掺入寡核苷酸的过程与使用2-氰基乙基脱氧核糖核苷亚磷酰胺所实现的过程一样有效。4-甲基硫基-1-丁基磷酸酯/硫代磷酸酯保护基的多功能性可通过在中性条件下于55°C在中性条件下于55°C的水性缓冲液中加热30分钟或在55°C的浓缩条件下2小时内从寡核苷酸中轻松去除而获得。 NH 4 OH。脱保护反应通过分子内环脱酯化机理发生，导致形成salt盐18。与脱氧核糖核苷和N混合时在近似于大规模（> 50 mmol）寡核苷酸脱保护反应的条件下，在保护的2'-脱氧核糖核苷或模型硫代磷酸酯二酯的作用下，盐18不会显着改