(S)-1-<4-hydroxy-3-(phosphonmethoxy)butyl>cytosine | 127517-90-2

• 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: (S)-1-<4-hydroxy-3-(phosphonmethoxy)butyl>cytosine
• 英文别名: [(1S)-3-(4-amino-2-oxo-pyrimidin-1-yl)-1-(hydroxymethyl)propoxy]methylphosphonic acid；[(2S)-4-(4-amino-2-oxopyrimidin-1-yl)-1-hydroxybutan-2-yl]oxymethylphosphonic acid
• CAS: 127517-90-2
• 化学式: C₉H₁₆N₃O₆P
• 分子量: 293.216
• InChiKey: UZUSWPFGPMFMMQ-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.3
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  146
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (S)-diethyl <<3-<(methylsulfonyl)oxy>-1-<(tetrahydro-2H-pyran-2-yloxy)methyl>propoxy>methyl>phosphonate 在 盐酸 、 三甲基溴硅烷 、 sodium hydride 作用下， 反应 10.75h， 生成 (S)-1-<4-hydroxy-3-(phosphonmethoxy)butyl>cytosine
  参考文献：
  名称：

  Synthesis and antiviral activity of (S)-9-[4-hydroxy-3-(phosphonomethoxy)butyl]guanine

  摘要：

  The synthesis of (S)-9-[4-hydroxy-3-(phosphonomethoxy)butyl]guanine (3), starting from (S)-4-(2-hydroxyethyl)-2,2-dimethyl-1,3-dioxolane (4), is described. Alkylation of trityl derivative 7 with (diethylphosphono)methyl triflate provided phosphonate 8, which was readily converted to mesylate 12 in three steps. Nucleophilic substitution of the mesylate group of 12 by 2-amino-6-chloropurine sodium salt led to (S)-2-amino-6-chloro-9-[3-[(diethyl-phosphono)methoxy]-4-(tetrahydro- 2H-pyran-2-yloxy)butyl]purine (13). Sequential treatment of 13 with trimethylsilyl bromide and then with 2 N HCl furnished 3. Preliminary in vitro screening indicated that 3 exhibited a potent activity against human cytomegalovirus (HCMV) but was not active against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). The adenine and cytosine derivatives (14 and 15) did not exhibit activity against HSV-1 and -2 and HCMV.

  DOI：

  10.1021/jm00168a039

文献信息

• KIM, CHOUNG UN;LUH, BING YU;MARTIN, JOHN C., J. MED. CHEM., 33,(1990) N, C. 1797-1800
  作者：KIM, CHOUNG UN、LUH, BING YU、MARTIN, JOHN C.

  DOI：——

  日期：——
• Synthesis and antiviral activity of (S)-9-[4-hydroxy-3-(phosphonomethoxy)butyl]guanine
  作者：Choung Un Kim、Bing Yu Luh、John C. Martin

  DOI：10.1021/jm00168a039

  日期：1990.6

  The synthesis of (S)-9-[4-hydroxy-3-(phosphonomethoxy)butyl]guanine (3), starting from (S)-4-(2-hydroxyethyl)-2,2-dimethyl-1,3-dioxolane (4), is described. Alkylation of trityl derivative 7 with (diethylphosphono)methyl triflate provided phosphonate 8, which was readily converted to mesylate 12 in three steps. Nucleophilic substitution of the mesylate group of 12 by 2-amino-6-chloropurine sodium salt led to (S)-2-amino-6-chloro-9-[3-[(diethyl-phosphono)methoxy]-4-(tetrahydro- 2H-pyran-2-yloxy)butyl]purine (13). Sequential treatment of 13 with trimethylsilyl bromide and then with 2 N HCl furnished 3. Preliminary in vitro screening indicated that 3 exhibited a potent activity against human cytomegalovirus (HCMV) but was not active against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). The adenine and cytosine derivatives (14 and 15) did not exhibit activity against HSV-1 and -2 and HCMV.