cytidine 5'-(ethoxycarbonyl)phosphonate | 153527-04-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: cytidine 5'-(ethoxycarbonyl)phosphonate
• 英文别名: [(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-ethoxycarbonylphosphinic acid
• CAS: 153527-04-9
• 化学式: C₁₂H₁₈N₃O₉P
• 分子量: 379.263
• InChiKey: JEBVJUCAKZSSRY-PEBGCTIMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  181
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  cytidine 5'-(ethoxycarbonyl)phosphonate 在 盐酸羟胺 作用下， 以 水 为溶剂， 反应 24.0h， 生成 N⁴-hydroxycytidine 5'-(ethoxycarbonyl)phosphonate
  参考文献：
  名称：

  New N4-Hydroxycytidine Derivatives: Synthesis and Antiviral Activity

  摘要：

  合成了两系列N^4-羟基胞嘧啶衍生物，并作为潜在的抗痘病毒药物进行评价。N^4-羟基胞嘧啶（1）与过量的酰氯或咪唑酰化合物反应，生成相应的N^4-(酰氧基)衍生物。通过胞嘧啶5'-磷酸酯与水合氯化羟胺（pH 6.0）反应制备了1的5'-磷酸酯。核苷1及其N^4-(酰氧基)衍生物抑制了细胞培养中痘病毒的复制，其中N^4-(戊酰氧基)和N^4-(苯甲酰氧基)胞嘧啶具有最强的抑制作用。合成的5'-磷酸酯比母核苷更具细胞毒性。

  DOI：

  10.1135/cccc20061099
• 作为产物：
  描述：

  2',3'-O-Aethoxymethylen-cytidin 在 吡啶 、 甲酸 、 N,N'-二环己基碳二亚胺 作用下， 反应 10.5h， 生成 cytidine 5'-(ethoxycarbonyl)phosphonate
  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

• 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.
• New N4-Hydroxycytidine Derivatives: Synthesis and Antiviral Activity
  作者：Maksim A. Ivanov、Elena V. Antonova、Aleksey V. Maksimov、Lyudmila K. Pigusova、Evgenii F. Belanov、Lyudmila A. Aleksandrova

  DOI：10.1135/cccc20061099

  日期：——

  Two series of N⁴-hydroxycytidine derivatives were synthesized and evaluated as potential antipox virus agents. Acylation of N⁴-hydroxycytidine (1) with an excess of acyl chloride or imidazolide yielded the corresponding N⁴-(acyloxy) derivatives. 5'-Phosphonates of 1 were prepared by the reaction of cytidine 5'-phosphonates with aqueous hydroxylamine hydrochloride (pH 6.0). Nucleoside 1 and its N⁴-(acyloxy) derivatives inhibited replication of pox viruses in cell cultures, N⁴-(pivaloyloxy)- and N⁴-(benzoyloxy)cytidines being the most potent. The synthesized 5'-phosphonates were more cytotoxic than the parent nucleoside.

  合成了两系列N^4-羟基胞嘧啶衍生物，并作为潜在的抗痘病毒药物进行评价。N^4-羟基胞嘧啶（1）与过量的酰氯或咪唑酰化合物反应，生成相应的N^4-(酰氧基)衍生物。通过胞嘧啶5'-磷酸酯与水合氯化羟胺（pH 6.0）反应制备了1的5'-磷酸酯。核苷1及其N^4-(酰氧基)衍生物抑制了细胞培养中痘病毒的复制，其中N^4-(戊酰氧基)和N^4-(苯甲酰氧基)胞嘧啶具有最强的抑制作用。合成的5'-磷酸酯比母核苷更具细胞毒性。