diethyl 4-(6-amino-9H-purin-9-yl)butylphosphonate | 121149-96-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: diethyl 4-(6-amino-9H-purin-9-yl)butylphosphonate
• 英文别名: diethyl 4-(adenin-9-yl)butylphosphonate；9-(4-Diethoxyphosphorylbutyl)purin-6-amine
• CAS: 121149-96-0
• 化学式: C₁₃H₂₂N₅O₃P
• 分子量: 327.323
• InChiKey: GYYMVMYORVDNTO-UHFFFAOYSA-N

物化性质

• 沸点：
  531.7±60.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  diethyl 4-(6-amino-9H-purin-9-yl)butylphosphonate 在 三甲基溴硅烷 、 水 作用下， 反应 1.0h， 以63%的产率得到4-(6-amino-9H-purin-9-yl)butylphosphonic acid
  参考文献：
  名称：

  具有三键或双键的无环核苷酸膦酸酯类似物合成的新方法

  摘要：

  摘要 在设计核苷酸的膦酸酯类似物的新方法的基础上，通过将4-氯丁二乙基1,2-二烯基膦酸二乙酯与相应的嘌呤或嘧啶核酸碱基偶联，制备了在碳骨架中具有三键的第一系列无环核苷酸在碱催化的烷基化条件下。 在设计核苷酸的膦酸酯类似物的新方法的基础上，通过将4-氯丁二乙基1,2-二烯基膦酸二乙酯与相应的嘌呤或嘧啶核酸碱基偶联，制备了在碳骨架中具有三键的第一系列无环核苷酸在碱催化的烷基化条件下。

  DOI：

  10.1055/s-0031-1289812
• 作为产物：
  描述：

  溴氟甲基膦酸二乙酯 在 palladium on activated charcoal 四丁基氟化铵 、 氢气 、 溴 、 potassium carbonate 、 copper(I) bromide 、 锌 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 25.0 ℃ 、137.9 kPa 条件下， 反应 85.0h， 生成 diethyl 4-(6-amino-9H-purin-9-yl)butylphosphonate
  参考文献：
  名称：

  Unsaturated fluoro analogues of adenine nucleotides. Unusual eliminations of hydrogen halides in α,α-difluorophosphonates containing a heterocyclic base

  摘要：

  Reaction of bromodifluoromethyl phosphonate 3 with zinc and propynyl chloride led to allenyl phosphonate which was brominated to give dibromophosphonate 6. Alkylation of adenine 7 with 6 afforded Z- and E-difluorophosphonates 8 and 9. Hydrogenation of 8 furnished saturated difluorophosphonate 10a which was dealkylated to the corresponding phosphonic acid 10b. Reaction of 8 with tetrabutylammonium fluoride gave fluoroenyne phosphonate 11 whereas 9 and 1,5-diazabicyclo[4.3.0] non-5-ene furnished bromofluorodiene phosphonate 16. Hydrogenation of 11 afforded phosphonates 13 and 14 in addition to defluorinated product 15. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4020(97)00233-0

文献信息

• Metal ion-binding properties of 9-(4-phosphonobutyl)adenine (dPMEA), a sister compound of the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA), and quantification of the equilibria involving four Cu(PMEA) isomers
  作者：Raquel B. Gómez-Coca、Larisa E. Kapinos、Antonín Holý、Rosario A. Vilaplana、Francisco González-Vílchez、Helmut Sigel

  DOI：10.1039/b001588l

  日期：——

  The acidity constants of the threefold protonated acyclic 9-(4-phosphonobutyl)adenine, H3(dPMEA)+, as well as the stability constants of the M(H;dPMEA)+ and M(dPMEA) complexes with the metal ions M2+ = Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+ or Cd2+, have been determined by potentiometric pH titrations, in aqueous solution at I = 0.1 M (NaNO3) and 25 °C. Application of previously determined straight-line plots of log KMM(R-PO3)versus pKHH(R-PO3) for simple phosph(on)ate ligands, R-PO32−, where R represents a residue without an affinity for metal ions, proves that the primary binding site of dPMEA2− is the phosphonate group with all the metal ions studied; in fact, in most instances the stability is solely determined by the basicity of the phosphonate residue. Only for the Ni(dPMEA), Cu(dPMEA) and Cd(dPMEA) systems a stability increase due to macrochelate formation with the adenine residue occurs; the formation degrees are 21 ± 15%, 31 ± 14% and 29 ± 18%, respectively. In these three instances the additional interaction of the phosphonate-coordinated M2+ occurs most probably with N7; hence, dPMEA2− is more similar in its metal ion-binding properties to the parent nucleotide adenosine 5′-monophosphate (AMP2−) than to the antivirally active and structurally more related dianion of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA2−). This result agrees with the observation that replacement of the ether O atom in PMEA by a CH2 unit leads to a compound, i.e. dPMEA, devoid of any biological activity. In addition, use is made of the stability enhancement obtained for the Cu(dPMEA) system due to macrochelate formation to analyze the equilibria regarding the four isomeric complex species possibly formed in the Cu(PMEA) system. It is shown that a macrochelated isomer involving N7 of the adenine residue occurs with Cu(PMEA) only in trace amounts; the important isomers in this system involve the ether oxygen (formation degree ca. 34%) and also N3 of the adenine moiety (ca. 41%).

  三重质子化无环 9-(4-膦酰丁基)腺嘌呤 H3(dPMEA)+ 的酸度常数以及 M(H. dPMEA)+ 和 M(dPMEA) 与金属离子 M2+ = Mg2+、Ca2+、Sr2+、Ba2+、Mn2+、Co2+ 和 M(dPMEA) 复合物的稳定常数；dPMEA)+ 和 M(dPMEA)与金属离子 M2+ = Mg2+、Ca2+、Sr2+、Ba2+、Mn2+、Co2+、Ni2+、Cu2+、Zn2+ 或 Cd2+ 的配合物的稳定常数，是通过电位 pH 滴定法测定的。1 M (NaNO3)和 25 °C 的水溶液中通过电位 pH 滴定法测定。对于简单的磷配体 R-PO32-（其中 R 代表对金属离子没有亲和力的残基），应用之前确定的 KMM(R-PO3)log 与 pKHH(R-PO3) 的直线图，证明 dPMEA2- 与所有研究金属离子的主要结合位点是膦酸基；事实上，在大多数情况下，稳定性完全由膦酸基残基的碱性决定。只有 Ni(dPMEA)、Cu(dPMEA) 和 Cd(dPMEA) 系统由于与腺嘌呤残基形成大螯合物而增加了稳定性；形成度分别为 21 ± 15%、31 ± 14% 和 29 ± 18%。在这三种情况下，膦酸盐配位的 M2+ 很可能与 N7 发生额外的相互作用；因此，dPMEA2- 与母体核苷酸腺苷酸 5′-单磷酸（AMP2-）相比，其金属离子结合特性更类似于 9-[2-（膦酰甲氧基）乙基]腺嘌呤（PMEA2-）的抗病毒活性和结构上更相关的二元离子。这一结果与以下观察结果一致，即用 CH2 单元取代 PMEA 中的醚 O 原子会产生一种没有任何生物活性的化合物，即 dPMEA。此外，我们还利用 Cu（dPMEA）体系因形成大螯合物而提高的稳定性，分析了 Cu（PMEA）体系中可能形成的四种异构络合物的平衡关系。研究表明，涉及腺嘌呤残基 N7 的大螯合异构体在 Cu(PMEA) 中仅以微量出现；该体系中的重要异构体涉及醚氧（形成率约为 34%）和腺嘌呤分子的 N3（约为 41%）。
• HOLY, ANTONIN;ROSENBERG, IVAN;DVORAKOVA, HANA;DECLERCQ, ERIK, NUCLEOSIDES AND NUCLEOTIDES, 7,(1988) N-6, C. 667-670
  作者：HOLY, ANTONIN、ROSENBERG, IVAN、DVORAKOVA, HANA、DECLERCQ, ERIK

  DOI：——

  日期：——
• A New Approach to the Synthesis of Acyclic Nucleotide Phosphonate Analogues with Triple or Double Bonds
  作者：Valery Brel

  DOI：10.1055/s-0031-1289812

  日期：2012.8

  basis of new methodology to design the phosphonate analogues of nucleotides, the first series of acyclic nucleotides possessing a triple bond in the carbon skeleton were prepared by coupling diethyl 4-chlorobuta-1,2-dienylphosphonate with the corresponding purine or pyrimidine nucleic bases under base-catalyzed alkylation conditions. On the basis of new methodology to design the phosphonate analogues

  摘要 在设计核苷酸的膦酸酯类似物的新方法的基础上，通过将4-氯丁二乙基1,2-二烯基膦酸二乙酯与相应的嘌呤或嘧啶核酸碱基偶联，制备了在碳骨架中具有三键的第一系列无环核苷酸在碱催化的烷基化条件下。 在设计核苷酸的膦酸酯类似物的新方法的基础上，通过将4-氯丁二乙基1,2-二烯基膦酸二乙酯与相应的嘌呤或嘧啶核酸碱基偶联，制备了在碳骨架中具有三键的第一系列无环核苷酸在碱催化的烷基化条件下。
• Unsaturated fluoro analogues of adenine nucleotides. Unusual eliminations of hydrogen halides in α,α-difluorophosphonates containing a heterocyclic base
  作者：Ze-Qi Xu、Jiri Zemlicka

  DOI：10.1016/s0040-4020(97)00233-0

  日期：1997.4

  Reaction of bromodifluoromethyl phosphonate 3 with zinc and propynyl chloride led to allenyl phosphonate which was brominated to give dibromophosphonate 6. Alkylation of adenine 7 with 6 afforded Z- and E-difluorophosphonates 8 and 9. Hydrogenation of 8 furnished saturated difluorophosphonate 10a which was dealkylated to the corresponding phosphonic acid 10b. Reaction of 8 with tetrabutylammonium fluoride gave fluoroenyne phosphonate 11 whereas 9 and 1,5-diazabicyclo[4.3.0] non-5-ene furnished bromofluorodiene phosphonate 16. Hydrogenation of 11 afforded phosphonates 13 and 14 in addition to defluorinated product 15. (C) 1997 Elsevier Science Ltd.