N4-acetyl-1-(2-deoxy-2-fluoro-5-O-DMTr-β-D-arabinofuranosyl)-5-methoxycarbonylcytosine-3-O-(2-cyanoethyl)-N,N-diisopropyl phosphoramidite | 1361198-88-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: N4-acetyl-1-(2-deoxy-2-fluoro-5-O-DMTr-β-D-arabinofuranosyl)-5-methoxycarbonylcytosine-3-O-(2-cyanoethyl)-N,N-diisopropyl phosphoramidite
• 英文别名: methyl 4-acetamido-1-[(2R,3S,4R,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-[2-cyanoethoxy-[di(propan-2-yl)amino]phosphanyl]oxy-3-fluorooxolan-2-yl]-2-oxopyrimidine-5-carboxylate
• CAS: 1361198-88-0
• 化学式: C₄₃H₅₁FN₅O₁₀P
• 分子量: 847.878
• InChiKey: DWOFECKRNAAZJG-TYTSYSAWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  60
• 可旋转键数：
  20
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  171
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  4,4'-双甲氧基三苯甲基氯 在 吡啶 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 N4-acetyl-1-(2-deoxy-2-fluoro-5-O-DMTr-β-D-arabinofuranosyl)-5-methoxycarbonylcytosine-3-O-(2-cyanoethyl)-N,N-diisopropyl phosphoramidite
  参考文献：
  名称：

  Synthesis of DNA oligos containing 2′-deoxy-2′-fluoro-d-arabinofuranosyl-5-carboxylcytosine as hTDG inhibitor

  摘要：

  As an important step of the active demethylation of 5-methylcytosine (5mC), human thymine DNA glycosylase (hTDG) efficiently excises 5-carboxylcytosine (5caC) from double-stranded DNA (dsDNA). Here, we present synthesis of DNA oligos containing a 2'-deoxy-2'-fluoro-D- arabinofuranosyl-5-carboxylcytidine (F-5caC) modification that act as hTDG inhibitors. The glycosylase activity assay showed that F-5caC oligos were resistant to excision by the hTDG catalytic domain (hTDG(cat), residues 111-308) and they could inhibit the excision of DNA oligos containing 5caC. The electrophoretic mobility shift assay confirmed that DNA oligos containing F-5caC could bind well with unmodified hTDG(cat) to form a stable complex, which makes it possible to obtain the crystal structure of the complex to reveal details on how hTDG(cat) recognizes the DNA substrate. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2012.04.031