(R)-ethyl hydrogen <3-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4-hydroxybutyl>phosphonate monoammonium salt

• 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: (R)-ethyl hydrogen <3-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4-hydroxybutyl>phosphonate monoammonium salt
• 英文别名: (R)-ethyl hydrogen {3-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]-4-hydroxybutyl}phosphonate monoammonium salt；[(3R)-3-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]-4-hydroxybutyl]-ethoxyphosphinic acid;azane
• 化学式: C₁₂H₂₀N₅O₆P*H₃N
• 分子量: 378.325
• InChiKey: XGAQSLXYMLXUJL-DDWIOCJRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.19
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  162
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (R)-1-((tert-butyldiphenylsilyl)oxy)-4-chloro-2-(methoxymethoxy)butane 在 苯磺酰胺 、 sodium hydroxide 、 phosphodiesterase 、 三氟甲磺酸三甲基硅酯 、 四丁基氟化铵 、 甲胺 作用下， 以 乙腈 为溶剂， 反应 22.25h， 生成 (R)-ethyl hydrogen <3-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4-hydroxybutyl>phosphonate monoammonium salt
  参考文献：
  名称：

  An Enantiospecific Synthesis of the Human Cytomegalovirus Antiviral Agent [(R)-3-((2-Amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4- hydroxybutyl]phosphonic Acid

  摘要：

  The racemic isosteric phosphonate of ganciclovir monophosphate (BW2482U89, SR3745, [3-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4-hydroxybutyl]phosphonic acid, 1) has potent and selective in vitro;activity against human cytomegalovirus. An enantiospecific synthesis of the R-enantiomer of compound 1 starting from L-arabinose was developed. The synthesis involved (1) the preparation of a chiral acyclic moiety, (2) the coupling of the chiral acyclic moiety to diacetylguanine, (3) the introduction; of phosphorus, and (4) the final deprotection. The R-enantiomer, which has stereochemistry analogous to the natural compound GMP, was tested against human cytomegalovirus and had an IC50 Of 1.7 mu M, which was approximately 2-fold more active than the racemic material. Both racemic and chiral compounds were less toxic than ganciclovir to bone marrow progenitor cells in an in vitro assay.

  DOI：

  10.1021/jm00035a018

文献信息

• An Enantiospecific Synthesis of the Human Cytomegalovirus Antiviral Agent [(R)-3-((2-Amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4- hydroxybutyl]phosphonic Acid
  作者：Stanley D. Chamberlain、Karen K. Biron、Ronna E. Dornsife、Devron R. Averett、Lilia Beauchamp、George W. Koszalka

  DOI：10.1021/jm00035a018

  日期：1994.4

  The racemic isosteric phosphonate of ganciclovir monophosphate (BW2482U89, SR3745, [3-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4-hydroxybutyl]phosphonic acid, 1) has potent and selective in vitro;activity against human cytomegalovirus. An enantiospecific synthesis of the R-enantiomer of compound 1 starting from L-arabinose was developed. The synthesis involved (1) the preparation of a chiral acyclic moiety, (2) the coupling of the chiral acyclic moiety to diacetylguanine, (3) the introduction; of phosphorus, and (4) the final deprotection. The R-enantiomer, which has stereochemistry analogous to the natural compound GMP, was tested against human cytomegalovirus and had an IC50 Of 1.7 mu M, which was approximately 2-fold more active than the racemic material. Both racemic and chiral compounds were less toxic than ganciclovir to bone marrow progenitor cells in an in vitro assay.