1-[(2R,4S,5R)-5-[[4-dihydroxyphosphinothioyloxybutoxy-[(2R,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxyphosphinothioyl]oxymethyl]-4-hydroxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione | 867205-16-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 1-[(2R,4S,5R)-5-[[4-dihydroxyphosphinothioyloxybutoxy-[(2R,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxyphosphinothioyl]oxymethyl]-4-hydroxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 867205-16-1
• 化学式: C₂₄H₃₆N₄O₁₄P₂S₂
• 分子量: 730.648
• InChiKey: IZJSKTLLORSRIY-KCASHQHTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  46
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  299
• 氢给体数：
  6
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  1-[(2R,4S,5R)-5-[[4-dihydroxyphosphinothioyloxybutoxy-[(2R,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxyphosphinothioyl]oxymethyl]-4-hydroxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione 在 1X phosphate-buffered saline 作用下， 反应 8.0h， 生成 dithymidylyl-3',5'-phosphorothioate
  参考文献：
  名称：

  Solid-Phase Synthesis of Thermolytic DNA Oligonucleotides Functionalized with a Single 4-Hydroxy-1-butyl or 4-Phosphato-/Thiophosphato-1-butyl Thiophosphate Protecting Group

  摘要：

  Several thermolytic CpG-containing DNA oligonucleotides analogous to 1 have been synthesized to serve as potential immunotherapeutic oligonucleotide prodrug formulations for the treatment of infectious diseases in animal models. Specifically, the CpG motif (GACGTT) of each DNA oligonucleotide has been functionalized with either the thermolabile 4-hydroxy-1-butyl or the 4-phosphato-/thiophosphato-1-butyl thiophosphate protecting group. This functionalization was achieved through incorporation of activated deoxyribonucleoside phosphoramidite 8b into the oligonucleotide chain during solid-phase synthesis and, optionally, through subsequent phosphorylation effected by phosphoramidite 9. Complete conversion of CpG ODNs hbu1555, psb1555, and pob1555 to CpG ODN 1555 (homologous to 2) occurred under elevated temperature conditions, thereby validating the function of these diastereomeric oligonucleotides as prodrugs in vitro. Noteworthy is the significant increase in solubility of CpG ODN psb1555 and CpG pob1555 in water when compared to that of neutral CpG ODN fma1555 (homologous to 1).

  DOI：

  10.1021/jo062087y
• 作为产物：
  描述：

  5‘-O-dimethoxytrityl-2’-deoxyribothymidine 3‘-O-phosphorodiamidite 在 四氮唑 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 1-[(2R,4S,5R)-5-[[4-dihydroxyphosphinothioyloxybutoxy-[(2R,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxyphosphinothioyl]oxymethyl]-4-hydroxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione
  参考文献：
  名称：

  用于脱氧核糖核苷，DNA寡核苷酸及其热解类似物磷酸化的有效试剂。

  摘要：

  [反应：见正文]从2巯基乙酸甲酯分三步制备亚磷酰胺11，并证明了2'-脱氧核糖核苷的常规5'-/ 3'-磷酸酯/硫代磷酸酯单酯衍生物和DNA寡核苷酸的合成效率。而且，使用11使得能够以高收率（＞ 95％）制备二核苷硫代磷酸酯类似物26，而热解硫代磷酸酯保护基团的裂解最小（＜2％）。

  DOI：

  10.1021/ol0516263

文献信息

• Solid-Phase Synthesis of Thermolytic DNA Oligonucleotides Functionalized with a Single 4-Hydroxy-1-butyl or 4-Phosphato-/Thiophosphato-1-butyl Thiophosphate Protecting Group
  作者：Andrzej Grajkowski、Cristina Ausín、Jon S. Kauffman、John Snyder、Sonja Hess、John R. Lloyd、Serge L. Beaucage

  DOI：10.1021/jo062087y

  日期：2007.2.1

  Several thermolytic CpG-containing DNA oligonucleotides analogous to 1 have been synthesized to serve as potential immunotherapeutic oligonucleotide prodrug formulations for the treatment of infectious diseases in animal models. Specifically, the CpG motif (GACGTT) of each DNA oligonucleotide has been functionalized with either the thermolabile 4-hydroxy-1-butyl or the 4-phosphato-/thiophosphato-1-butyl thiophosphate protecting group. This functionalization was achieved through incorporation of activated deoxyribonucleoside phosphoramidite 8b into the oligonucleotide chain during solid-phase synthesis and, optionally, through subsequent phosphorylation effected by phosphoramidite 9. Complete conversion of CpG ODNs hbu1555, psb1555, and pob1555 to CpG ODN 1555 (homologous to 2) occurred under elevated temperature conditions, thereby validating the function of these diastereomeric oligonucleotides as prodrugs in vitro. Noteworthy is the significant increase in solubility of CpG ODN psb1555 and CpG pob1555 in water when compared to that of neutral CpG ODN fma1555 (homologous to 1).
• An Efficient Reagent for the Phosphorylation of Deoxyribonucleosides, DNA Oligonucleotides, and Their Thermolytic Analogues
  作者：Cristina Ausín、Andrzej Grajkowski、Jacek Cieślak、Serge L. Beaucage

  DOI：10.1021/ol0516263

  日期：2005.9.1

  and demonstrated efficiency in the synthesis of conventional 5'-/3'-phosphate/thiophosphate monoester derivatives of 2'-deoxyribonucleosides and DNA oligonucleotides. Moreover, the use of 11 has enabled the preparation of the dinucleoside phosphorothioate analogue 26 in high yields (>95%) with minimal cleavage (<2%) of the thermolytic thiophosphate protecting group.

  [反应：见正文]从2巯基乙酸甲酯分三步制备亚磷酰胺11，并证明了2'-脱氧核糖核苷的常规5'-/ 3'-磷酸酯/硫代磷酸酯单酯衍生物和DNA寡核苷酸的合成效率。而且，使用11使得能够以高收率（＞ 95％）制备二核苷硫代磷酸酯类似物26，而热解硫代磷酸酯保护基团的裂解最小（＜2％）。