1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]-N⁴-cyclopropylcytosine

• 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: 1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]-N⁴-cyclopropylcytosine
• 英文别名: [(2S)-1-[4-(cyclopropylamino)-2-oxopyrimidin-1-yl]-3-hydroxypropan-2-yl]oxymethylphosphonic acid
• 化学式: C₁₁H₁₈N₃O₆P
• 分子量: 319.254
• InChiKey: DVKIJWMRLYLGJP-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  132
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  西多福韦 在 triethylammonium hydrogensulfite 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 16.0h， 生成 1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]-N⁴-cyclopropylcytosine
  参考文献：
  名称：

  Synthesis of N4-Substituted Derivatives of 1-[2-(Phosphonomethoxy)ethyl]cytosine and Its Diisopropyl Ester as a Model Reaction for the Synthesis of N4-Substituted Derivatives of Cidofovir

  摘要：

  我们研究了1-[2-(磷酸甲氧基)乙基]胞嘧啶（1）及其二异丙酯（2）与三乙胺硫酸氢盐在60%水甲醇中的反应。在一些一级或二级胺盐的存在下，反应在25-70℃下产生了转氨化衍生物4a-4e和5a，5b作为主要产物，伴随尿嘧啶化合物。然而，对于某些胺而言，反应失败了。

  DOI：

  10.1135/cccc20052066

文献信息

• Synthesis of Some N4-Substituted Derivatives of 1-[(S)-3-Hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC, Cidofovir)
  作者：Šárka Chalupová、Antonín Holý、Milena Masojídková

  DOI：10.1135/cccc20052053

  日期：——

  N⁴-Substituted derivatives of HPMPC were synthesized in four-step synthesis which included treatment of 4-methoxypyrimidin-2(1H)-one (1) with (S)-[(trityloxy)methyl]oxirane in DMF. Condensation of intermediary 1-[2-hydroxy-3-(trityloxy)propyl]-4-methoxypyrimidin-2(1H)-one (2) with (diisopropoxyphosphoryl)methyl tosylate in the presence of sodium hydride resulted in fully protected 4-methoxypyrimidin-2(1H)-one derivative 3 which gave on reaction with an appropriate primary amine in dioxane N⁴-substituted products 4a-4i. The reaction with bromotrimethylsilane simultaneously cleaved the trityl group and deprotected the phosphonate residue and gave the title HPMP analogues substituted at the cytosine amino group in position N⁴ 5a-5i. Compound 4j was prepared from 4-methoxypyrimidin-2(1H)-one (1) by reaction with cyclopropylamine in dioxane. The intermediary 4-(cyclopropylamino)pyrimidin-2(1H)-one (6) then reacts with (S)-[(trityloxy)methyl]oxirane in DMF. Fully protected phosphonate 4j and its deprotected counterpart 5j was obtained by the same sequence of reactions as in the case of compounds 5a-5i.

  HPMPC的N^4-取代衍生物通过四步合成制备，包括在DMF中用(S)-[(三苯甲氧基)甲基]环氧乙烷处理4-甲氧基嘧啶-2(1H)-酮(1)。中间体1-[2-羟基-3-(三苯甲氧基)丙基]-4-甲氧基嘧啶-2(1H)-酮(2)与(diisopropoxyphosphoryl)甲基对甲苯磺酸酯在氢化钠存在下缩合，得到全保护的4-甲氧基嘧啶-2(1H)-酮衍生物3，与适当的一级胺在二氧六环中反应得到N^4-取代产物4a-4i。与溴三甲基硅烷反应同时裂解三苯甲基基团和去保护磷酸酯残基，得到在胞嘧啶氨基N^4位置取代的标题HPMP类似物5a-5i。化合物4j由4-甲氧基嘧啶-2(1H)-酮(1)与环丙胺在二氧六环中反应制备。中间体4-(环丙胺基)嘧啶-2(1H)-酮(6)然后与(S)-[(三苯甲氧基)甲基]环氧乙烷在DMF中反应。全保护磷酸酯4j及其去保护对应物5j通过与化合物5a-5i相同的反应序列获得。
• Synthesis of N4-Substituted Derivatives of 1-[2-(Phosphonomethoxy)ethyl]cytosine and Its Diisopropyl Ester as a Model Reaction for the Synthesis of N4-Substituted Derivatives of Cidofovir
  作者：Šárka Chalupová、Antonín Holý、Milena Masojídková

  DOI：10.1135/cccc20052066

  日期：——

  We have studied the reaction of 1-[2-(phosphonomethoxy)ethyl]cytosine (1) and its diisopropyl ester (2) with triethylammonium hydrogensulfite in 60% aqueous methanol. In the presence of some primary or secondary amine salts, at 25-70 °C, this reaction affords transaminated derivatives 4a-4e and 5a, 5b as main products accompanied by uracil compounds. However, with certain amines the reaction failed.

  我们研究了1-[2-(磷酸甲氧基)乙基]胞嘧啶（1）及其二异丙酯（2）与三乙胺硫酸氢盐在60%水甲醇中的反应。在一些一级或二级胺盐的存在下，反应在25-70℃下产生了转氨化衍生物4a-4e和5a，5b作为主要产物，伴随尿嘧啶化合物。然而，对于某些胺而言，反应失败了。