[(3aR,4R,6R,6aR)-4-(2,4-dioxopyrimidin-1-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methoxy-methylphosphinic acid | 765243-86-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: [(3aR,4R,6R,6aR)-4-(2,4-dioxopyrimidin-1-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methoxy-methylphosphinic acid
• CAS: 765243-86-5
• 化学式: C₁₃H₁₉N₂O₈P
• 分子量: 362.276
• InChiKey: MCVSRSZFZNCAMZ-QCNRFFRDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  124
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [(3aR,4R,6R,6aR)-4-(2,4-dioxopyrimidin-1-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methoxy-methylphosphinic acid 在 甲酸 作用下， 反应 10.0h， 生成 uridine 5'-methylphosphonate
  参考文献：
  名称：

  5′-Phosphonates of Ribonucleosides and 2′-Deoxyribonucleosides: Synthesis and Antiviral Activity

  摘要：

  5'-Phosphonates of natural 2'-deoxynucleosides and ribonucleosides were synthesized by condensation of 3'-O-acylated 2'-deoxynucleosides or 2',3'-substituted (2',3'-O-isopropylidene, 2',3'-O-methoxymethylene or 2',3'-O-ethoxymethylene) ribonucleosides. As condensing agents, either N,N'-dicyclohexylcarbodiimide or 2,4,6-triisopropylbenzenesulphonyl chloride were used. Nucleoside 5'-ethoxycarbonylphosphonates were converted into corresponding nucleoside 5'-aminocarbonylphosphonates by action of ammonia in methanol or aqueous ammonia. 5'-Hydrogenphosphonothioates of thymidine and 3'-deoxythymidine were obtained by reaction of phosphinic acid in the presence of pivaloyl chloride with 3'-O-acetylthymidine or 3'-deoxythymidine, respectively, followed by addition of powedered sulfur. 5'-O-methylenephosphonates of thymidine and 2'-deoxyadenosine were prepared by intramolecular reaction of corresponding 3'-O-iodomethylphosphonates under basic conditions. All compounds were tested for inhibition of several viruses, including HSV-2 and CMV, but showed no activity. A few compounds insignificantly inhibited HIV-1 reproduction. Thymidine 5'-hydrogenphosphonate neutralized anti-HIV action of 3'-azido-3'-deoxythymidine (AZT) and it indirectly showed that even some nucleoside 5'-phosphonates could be partly hydrolyzed in cell culture to corresponding nucleosides.

  DOI：

  10.1080/07328319308018558
• 作为产物：
  描述：

  甲基膦酸 、 2’,3’邻异亚丙基尿苷 在 吡啶 、 2,4,6-三异丙基苯磺酰氯 、 三正丁胺 作用下， 生成 [(3aR,4R,6R,6aR)-4-(2,4-dioxopyrimidin-1-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methoxy-methylphosphinic acid
  参考文献：
  名称：

  5′-Phosphonates of Ribonucleosides and 2′-Deoxyribonucleosides: Synthesis and Antiviral Activity

  摘要：

  5'-Phosphonates of natural 2'-deoxynucleosides and ribonucleosides were synthesized by condensation of 3'-O-acylated 2'-deoxynucleosides or 2',3'-substituted (2',3'-O-isopropylidene, 2',3'-O-methoxymethylene or 2',3'-O-ethoxymethylene) ribonucleosides. As condensing agents, either N,N'-dicyclohexylcarbodiimide or 2,4,6-triisopropylbenzenesulphonyl chloride were used. Nucleoside 5'-ethoxycarbonylphosphonates were converted into corresponding nucleoside 5'-aminocarbonylphosphonates by action of ammonia in methanol or aqueous ammonia. 5'-Hydrogenphosphonothioates of thymidine and 3'-deoxythymidine were obtained by reaction of phosphinic acid in the presence of pivaloyl chloride with 3'-O-acetylthymidine or 3'-deoxythymidine, respectively, followed by addition of powedered sulfur. 5'-O-methylenephosphonates of thymidine and 2'-deoxyadenosine were prepared by intramolecular reaction of corresponding 3'-O-iodomethylphosphonates under basic conditions. All compounds were tested for inhibition of several viruses, including HSV-2 and CMV, but showed no activity. A few compounds insignificantly inhibited HIV-1 reproduction. Thymidine 5'-hydrogenphosphonate neutralized anti-HIV action of 3'-azido-3'-deoxythymidine (AZT) and it indirectly showed that even some nucleoside 5'-phosphonates could be partly hydrolyzed in cell culture to corresponding nucleosides.

  DOI：

  10.1080/07328319308018558

文献信息

• 1,8-Diazabicyclo[5.4.0]undecene Mediated Transesterification of<i>p</i>-Nitrophenyl Phosphonates: A Novel Route to Phosphono Esters
  作者：Dan S. Tawfik、Zelig Eshhar、Alfonso Bentolila、Bernard S. Green

  DOI：10.1055/s-1993-25982

  日期：——

  DBU (1,8-diazabicyclo[5.4.0]undecene) was found to efficiently mediate the transesterification of p-nitrophenyl (PNP) phosphonates by various alcohols. The reactions of bis-PNP phosphonates in the presence of DBU, using both primary and secondary alcohols, phenols and amines, proceed rapidly and with high yield to afford the corresponding monoalkyl/aryl mono-PNP phosphonates as sole products (1, Scheme 2). The resulting monoalkyl/aryl mono-PNP phosphonates can be further reacted with a second alcohol to give the corresponding differently disubstituted phosphonates 3, or selectively hydrolysed to yield the monoalkyl/aryl phosphonic acids 2. We have applied this chemistry to the preparation of a series of phosphono ester transition state analogues 11a-e (Scheme 3) that were used as haptens for raising catalytic antibodies.

  研究发现 DBU（1,8-二氮杂双环[5.4.0]十一烯）能有效地介导对硝基苯（PNP）膦酸盐与各种醇的酯交换反应。在 DBU 的存在下，使用伯醇、仲醇、酚和胺对双-PNP 膦酸盐进行反应，反应速度快，产率高，可得到相应的单烷基/芳基单-PNP 膦酸盐作为唯一产物（1，方案 2）。生成的单烷基/芳基单-PNP 膦酸盐可进一步与第二种醇反应，得到相应的不同二取代膦酸盐 3，或选择性水解，得到单烷基/芳基膦酸 2。我们将这种化学方法应用于制备一系列膦酸酯过渡态类似物 11a-e（方案 3），这些类似物可用作催化抗体的触价物。
• 5′-Phosphonates of Ribonucleosides and 2′-Deoxyribonucleosides: Synthesis and Antiviral Activity
  作者：Maxim Jasko、Alexander Shipitsin、Elena Shirokova、Alexander Krayevsky、Bruce Polsky、Penny Baron、Clarinda MacLow、Michael Ostrander、Brian O'Hara

  DOI：10.1080/07328319308018558

  日期：1993.9

  5'-Phosphonates of natural 2'-deoxynucleosides and ribonucleosides were synthesized by condensation of 3'-O-acylated 2'-deoxynucleosides or 2',3'-substituted (2',3'-O-isopropylidene, 2',3'-O-methoxymethylene or 2',3'-O-ethoxymethylene) ribonucleosides. As condensing agents, either N,N'-dicyclohexylcarbodiimide or 2,4,6-triisopropylbenzenesulphonyl chloride were used. Nucleoside 5'-ethoxycarbonylphosphonates were converted into corresponding nucleoside 5'-aminocarbonylphosphonates by action of ammonia in methanol or aqueous ammonia. 5'-Hydrogenphosphonothioates of thymidine and 3'-deoxythymidine were obtained by reaction of phosphinic acid in the presence of pivaloyl chloride with 3'-O-acetylthymidine or 3'-deoxythymidine, respectively, followed by addition of powedered sulfur. 5'-O-methylenephosphonates of thymidine and 2'-deoxyadenosine were prepared by intramolecular reaction of corresponding 3'-O-iodomethylphosphonates under basic conditions. All compounds were tested for inhibition of several viruses, including HSV-2 and CMV, but showed no activity. A few compounds insignificantly inhibited HIV-1 reproduction. Thymidine 5'-hydrogenphosphonate neutralized anti-HIV action of 3'-azido-3'-deoxythymidine (AZT) and it indirectly showed that even some nucleoside 5'-phosphonates could be partly hydrolyzed in cell culture to corresponding nucleosides.