[(2R,3R,4R,5R)-4-benzoyloxy-5-[6-(dibenzoylamino)purin-9-yl]-2-[[1-[dimethoxy(oxido)phosphaniumyl]-2-methoxy-2-oxoethoxy]methyl]oxolan-3-yl] benzoate | 1259874-82-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: [(2R,3R,4R,5R)-4-benzoyloxy-5-[6-(dibenzoylamino)purin-9-yl]-2-[[1-[dimethoxy(oxido)phosphaniumyl]-2-methoxy-2-oxoethoxy]methyl]oxolan-3-yl] benzoate
• CAS: 1259874-82-2
• 化学式: C₄₃H₃₈N₅O₁₃P
• 分子量: 863.774
• InChiKey: NBYANVIDZPEXTH-ZCQVWSSVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  62
• 可旋转键数：
  18
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  220
• 氢给体数：
  0
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  [(2R,3R,4R,5R)-4-benzoyloxy-5-[6-(dibenzoylamino)purin-9-yl]-2-[[1-[dimethoxy(oxido)phosphaniumyl]-2-methoxy-2-oxoethoxy]methyl]oxolan-3-yl] benzoate 在 三甲基溴硅烷 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 2.17h， 以61%的产率得到2-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-2-phosphonoacetic acid
  参考文献：
  名称：

  Design and Synthesis of α-Carboxy Phosphononucleosides

  摘要：

  Rhodium catalyzed O-H insertion reactions employing alpha-diazophosphonate 20 with appropriately protected thymidine, uridine, cytosine, adenosine and guanosine derivatives leads to novel 5'-phosphononucleoside derivatives. Deprotection led to a novel series of phosphono derivatives bearing a carboxylic acid moiety adjacent to the phosphonate group with potential antiviral and/or anticancer activity. The phosphononucleosides bearing an alpha-carboxylic acid group are envisaged as potential diphosphate mimics. Conversion to mono- and diphosphorylated phosphononucleosides has been effected for evaluation as nucleoside triphosphate mimics. Most of the novel phosphononucleosides proved to be inactive against a variety of DNA and RNA viruses. Only the phosphono AZT derivatives 56-59 showed weak activity against HIV-1 and HIV-2.

  DOI：

  10.1021/jo101738e
• 作为产物：
  描述：

  O^5'-tert-butyldimethylsilyl-N⁶,N⁶,O^2',O^3'-tetrabenzoyladenosine 在 rhodium(II) acetate dimer 、 三氟乙酸 作用下， 以 四氢呋喃 、 水 、 苯 为溶剂， 反应 3.0h， 生成 [(2R,3R,4R,5R)-4-benzoyloxy-5-[6-(dibenzoylamino)purin-9-yl]-2-[[1-[dimethoxy(oxido)phosphaniumyl]-2-methoxy-2-oxoethoxy]methyl]oxolan-3-yl] benzoate
  参考文献：
  名称：

  Design and Synthesis of α-Carboxy Phosphononucleosides

  摘要：

  Rhodium catalyzed O-H insertion reactions employing alpha-diazophosphonate 20 with appropriately protected thymidine, uridine, cytosine, adenosine and guanosine derivatives leads to novel 5'-phosphononucleoside derivatives. Deprotection led to a novel series of phosphono derivatives bearing a carboxylic acid moiety adjacent to the phosphonate group with potential antiviral and/or anticancer activity. The phosphononucleosides bearing an alpha-carboxylic acid group are envisaged as potential diphosphate mimics. Conversion to mono- and diphosphorylated phosphononucleosides has been effected for evaluation as nucleoside triphosphate mimics. Most of the novel phosphononucleosides proved to be inactive against a variety of DNA and RNA viruses. Only the phosphono AZT derivatives 56-59 showed weak activity against HIV-1 and HIV-2.

  DOI：

  10.1021/jo101738e

文献信息

• Development of O–H insertion for the attachment of phosphonates to nucleosides; synthesis of α-carboxy phosphononucleosides
  作者：Isabelle Hladezuk、Veronique Chastagner、Stuart G. Collins、Stephen J. Plunkett、Alan Ford、Sebastien Debarge、Anita R. Maguire

  DOI：10.1016/j.tet.2011.12.077

  日期：2012.2

  Development of rhodium catalysed O-H insertion reactions employing alpha-diazophosphonates with appropriately protected adenosine, uridine and thymidine derivatives is described. This synthetic methodology leads, following deprotection, to novel phosphononucleoside derivatives bearing a carboxylic acid moiety adjacent to the phosphonate. Protection strategies are critical to the success of the key O-H insertion. There are two important aspects: avoiding competing insertion pathways or catalyst poisoning, and being able to achieve deprotection without degradation of the phosphononucleosides. (C) 2012 Elsevier Ltd. All rights reserved.
• Design and Synthesis of α-Carboxy Phosphononucleosides
  作者：Sebastien Debarge、Jan Balzarini、Anita R. Maguire

  DOI：10.1021/jo101738e

  日期：2011.1.7

  Rhodium catalyzed O-H insertion reactions employing alpha-diazophosphonate 20 with appropriately protected thymidine, uridine, cytosine, adenosine and guanosine derivatives leads to novel 5'-phosphononucleoside derivatives. Deprotection led to a novel series of phosphono derivatives bearing a carboxylic acid moiety adjacent to the phosphonate group with potential antiviral and/or anticancer activity. The phosphononucleosides bearing an alpha-carboxylic acid group are envisaged as potential diphosphate mimics. Conversion to mono- and diphosphorylated phosphononucleosides has been effected for evaluation as nucleoside triphosphate mimics. Most of the novel phosphononucleosides proved to be inactive against a variety of DNA and RNA viruses. Only the phosphono AZT derivatives 56-59 showed weak activity against HIV-1 and HIV-2.