N-{4-[((1R,3S,4R)-3-[(tert-butyldimethylsilyl)oxy]-4-{[(tert-butyldimethylsilyl)oxy]methyl}cyclopentyl)amino]-5-nitro-6-oxo-1,6-dihydro-2-pyrimidinyl}acetamide | 636569-52-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-{4-[((1R,3S,4R)-3-[(tert-butyldimethylsilyl)oxy]-4-{[(tert-butyldimethylsilyl)oxy]methyl}cyclopentyl)amino]-5-nitro-6-oxo-1,6-dihydro-2-pyrimidinyl}acetamide
• 英文别名: N-(4-(((1'R,3'S,4'R)-3-((tert-Butyldimethylsilyl)oxy)-4-(((tert-butyldimethylsilyl)oxy)methyl)cyclopentyl)amino)-5-nitro-6-oxo-1,6-dihydropyrimidin-2-yl)acetamide；N-[4-[[(1R,3S,4R)-3-[tert-butyl(dimethyl)silyl]oxy-4-[[tert-butyl(dimethyl)silyl]oxymethyl]cyclopentyl]amino]-5-nitro-6-oxo-1H-pyrimidin-2-yl]acetamide
• CAS: 636569-52-3
• 化学式: C₂₄H₄₅N₅O₆Si₂
• 分子量: 555.822
• InChiKey: FOWPHWRFMVSMKE-KURKYZTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.24
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  147
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-{4-[((1R,3S,4R)-3-[(tert-butyldimethylsilyl)oxy]-4-{[(tert-butyldimethylsilyl)oxy]methyl}cyclopentyl)amino]-5-nitro-6-oxo-1,6-dihydro-2-pyrimidinyl}acetamide 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 2.5h， 生成 N-[5-amino-6-[[(1R,3S,4R)-3-[tert-butyl(dimethyl)silyl]oxy-4-[[tert-butyl(dimethyl)silyl]oxymethyl]cyclopentyl]amino]-4-oxo-1H-pyrimidin-2-yl]acetamide
  参考文献：
  名称：

  两个主要的DNA损伤物8-Oxo-7,8-dihydroguanine和2,6-diamino-5-formamido-4-hydroxypyrimidine表现出非常不同的配对特性。

  摘要：

  DOI：

  10.1002/anie.200351287
• 作为产物：
  描述：

  (+)-(1S,2R,4R)-4-氨基-2-(羟甲基)-1-环戊醇 在 咪唑 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 N-{4-[((1R,3S,4R)-3-[(tert-butyldimethylsilyl)oxy]-4-{[(tert-butyldimethylsilyl)oxy]methyl}cyclopentyl)amino]-5-nitro-6-oxo-1,6-dihydro-2-pyrimidinyl}acetamide
  参考文献：
  名称：

  两个主要的DNA损伤物8-Oxo-7,8-dihydroguanine和2,6-diamino-5-formamido-4-hydroxypyrimidine表现出非常不同的配对特性。

  摘要：

  DOI：

  10.1002/anie.200351287

文献信息

• A Carbocyclic Analog of the Oxidatively Generated DNA Lesion Spiroiminodihydantoin
  作者：Heiko Müller、Thomas Carell

  DOI：10.1002/ejoc.200600982

  日期：2007.3

  is prone to further oxidation. One-electron oxidants like IrIV oxidize 8-oxo-dG to give secondary lesions such as the spiroiminodihydantoin. This lesion blocks DNA polymerases and induces G T as well as G C transversions. Here, we report the synthesis of a carbocyclic analog of the 8-oxo-dG lesion and the carbocyclic version of the spiroiminodihydantoin lesion. Both lesion analogs were obtained within

  8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) 是一种易于进一步氧化的诱变 DNA 损伤。像 IrIV 这样的单电子氧化剂氧化 8-oxo-dG 以产生继发性病变，如螺亚胺二乙内酰脲。这种损伤会阻断 DNA 聚合酶并诱导 GT 和 GC 颠换。在这里，我们报告了 8-oxo-dG 病变的碳环类似物和螺亚氨基二乙内酰脲病变的碳环版本的合成。两种损伤类似物都是在单链 DNA 中获得的，并作为它们相应的核苷。病变类似物的表征通过 HPLC、ESI-MS 和 ESI-MS/MS 以及寡核苷酸的酶消化来实现。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
• The Two Main DNA Lesions 8-Oxo-7,8-dihydroguanine and 2,6-Diamino-5-formamido-4-hydroxypyrimidine Exhibit Strongly Different Pairing Properties
  作者：Matthias Ober、Uwe Linne、Johannes Gierlich、Thomas Carell

  DOI：10.1002/anie.200351287

  日期：2003.10.20
• Base Pairing and Replicative Processing of the Formamidopyrimidine-dG DNA Lesion
  作者：Matthias Ober、Heiko Müller、Carsten Pieck、Johannes Gierlich、Thomas Carell

  DOI：10.1021/ja0549188

  日期：2005.12.1

  The 2,6-diamino-4-hydroxy-5-formamidopyrimidine of 2'-deoxyguanosine (FaPydG) is one of the major DNA lesions found after oxidative stress in cells. To clarify the base pairing and coding potential of this major DNA lesion with the aim to estimate its mutagenic effect, we prepared oligonucleotides containing a cyclopentane based analogue of the DNA lesion (cFaPydG). In addition, oligonucleoticles containing the cyclopentane analogue of 2'-deoxyguanosine (cdG), and oligonucleotides containing 8-oxo-7,8-dihydro2'-deoxyguanosine (8-oxodG) were synthesized. The thermodynamic stability of duplexes containing these building blocks and all canonical counterbases were determined by concentration dependent melting-point measurements (van't Hoff plots). The data reveal that cFaPydG greatly destabilizes a DNA duplex (Delta Delta G(o)298K approximate to 2-4 kcal mol(-1)). The optimal base pairing partner for the cFaPydG lesion is dC. Investigation of duplexes containing dG and cdG shows that the effect of substituting the deoxyribose by a cyclopentane moiety is marginal. The data also provide strong evidence that the FaPydG lesion is unable to form a base pair with dA. Our computational studies indicate that the syn-conformation required for base pairing with dA is energetically unfavorable. This is in contrast to 8-oxodG for which the syn-conformation represents the energetic minimum. Kinetic primer extension studies using S. cerevisiae Pol eta reveal that cFaPydG is replicated in an error-free fashion. dC is inserted 2-3 orders of magnitude more efficiently than dT or CIA, showing that FaPydG is a lesion which retains the coding potential of dG. This is also in contrast to 8-oxodG, for which base pairing with dC and dA was established.