(5'R)-N6-benzoyl-3'-O-(tert-butyldimethylsilyl)-5',8-cyclo-2'-deoxyadenosine | 222736-08-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (5'R)-N6-benzoyl-3'-O-(tert-butyldimethylsilyl)-5',8-cyclo-2'-deoxyadenosine
• 英文别名: (5'R)-N⁶-benzoyl-3'-O-(tert-butyldimethylsilyl)-5',8-cyclo-2'-deoxyadenosine；(5'R)cdA(NBz)TBDMSi；N-[(1R,11R,12R,13S)-13-[tert-butyl(dimethyl)silyl]oxy-11-hydroxy-15-oxa-2,4,6,9-tetrazatetracyclo[10.2.1.02,10.03,8]pentadeca-3,5,7,9-tetraen-7-yl]benzamide
• CAS: 222736-08-5
• 化学式: C₂₃H₂₉N₅O₄Si
• 分子量: 467.6
• InChiKey: DFDGDTYAHOKPQZ-MVJTYMMSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (5'R)-N6-benzoyl-3'-O-(tert-butyldimethylsilyl)-5',8-cyclo-2'-deoxyadenosine 在 吡啶 、 2-氯-1,3,2-苯并二氧磷杂环己烷-4-酮 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 25.0h， 生成
  参考文献：
  名称：

  Effects of 5′,8-Cyclodeoxyadenosine Triphosphates on DNA Synthesis

  摘要：

  Hydroxyl radicals generate a broad range of DNA lesions in living cells. Cyclopurine deoxynucleosides (CPUs) are a biologically significant class of oxidative DNA lesions due to their helical distortion and chemically stability. The CPUs on DNA are substrates for the nucleotide excision repair (NER) but not for base excision repair or direct damage reversal. Moreover, these lesions block DNA and RNA polymerases, resulting in cell death. Here, we describe the chemical synthesis of 5'S and 5'R isomers of 5',8-cyclodeoxyadenosine triphosphate (cdATP) and demonstrate their ability to be incorporated into DNA by replicative DNA polymerases. DNA synthesis assays revealed that the incorporation of the stereoisomeric cdATPs strongly inhibits DNA polymerase reactions. Surprisingly, the two stereoisomers had different mutagenic profiles, since the S isomer of cdATP could be inserted opposite to the dTMP, but the R isomer of cdATP could be inserted opposite to the dCMP. Kinetic analysis revealed that the S isomer of cdATP could be incorporated more efficiently (25.6 mu M-1 min(-1)) than the R isomer (1.13 mu M-1 min(-1)) during DNA synthesis. Previous data showed that the S isomer in DNA blocked DNA synthesis and the exonuclease activity of DNA polymerase and is less efficiently repaired by NER This indicates that the S isomer has a tendency to accumulate on the genome DNA, and as such, the S isomer of cdATP may be a candidate cytotoxic drug.

  DOI：

  10.1021/tx300351p
• 作为产物：
  描述：

  [(1R,11S,12S,13S)-7-benzamido-13-[tert-butyl(dimethyl)silyl]oxy-15-oxa-2,4,6,9-tetrazatetracyclo[10.2.1.02,10.03,8]pentadeca-3,5,7,9-tetraen-11-yl] methanesulfonate 在 18-冠醚-6 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 以58%的产率得到(5'R)-N6-benzoyl-3'-O-(tert-butyldimethylsilyl)-5',8-cyclo-2'-deoxyadenosine
  参考文献：
  名称：

  Synthesis and Characterization of Oligodeoxynucleotides Containing 5′,8-Cyclopurine-2′-Deoxyribonucleosides

  摘要：

  DOI：

  10.1080/07328319908044708

文献信息

• Synthesis and Characterization of Oligonucleotides Containing 5‘,8-Cyclopurine 2‘-Deoxyribonucleosides: (5‘<i>R</i>)-5‘,8-Cyclo-2‘-deoxyadenosine, (5‘<i>S</i>)-5‘,8-Cyclo-2‘-deoxyguanosine, and (5‘<i>R</i>)-5‘,8-Cyclo-2‘-deoxyguanosine
  作者：Anthony Romieu、Didier Gasparutto、Jean Cadet

  DOI：10.1021/tx9802668

  日期：1999.5.1

  Radiation-induced degradation of purine and pyrimidine nucleosides gave rise to carbon-bridged cyclocompounds. Such cyclonucleosides represent a class of tandem lesions in which modification of both the base and 2-deoxyribose has occurred. A solid-phase synthetic method was designed for the incorporation of both 5'R and 5'S diastereoisomers of 5',8-cyclopurine 2'-deoxyribonucleosides into oligodeoxynucleotides

  辐射诱导的嘌呤和嘧啶核苷的降解产生碳桥联的环化合物。这样的环核苷代表了一类串联损伤，其中碱基和2-脱氧核糖都发生了修饰。设计了一种固相合成方法，将5'，8-环嘌呤2'-脱氧核糖核苷的5'R和5'S非对映异构体掺入寡聚脱氧核苷酸中，以利于评估此类病变的生化和生物物理特征。我们报告的（5'R）-5'，8-cyclo-2'-deoxyadenosine（2），（5'S）-5'，8-cyclo-2'-deoxyguanosine（3）的亚磷酰胺合成子的制备（5′R）-5′，8-环-2′-脱氧鸟苷（4）。然后通过自动程序将完全保护的化合物10、18和25插入几个寡核苷酸中。
• (5′R)-5′,8-Cyclo-2′-deoxyadenosine: NMR and DFT study of its influence on TPOcdA structure
  作者：Bolesław T. Karwowski

  DOI：10.1016/j.tetasy.2008.10.025

  日期：2008.10

  Oxidatively generated damage to DNA frequently appears in the human genome as an effect of aerobic metabolism or as the result of exposure to exogenous oxidizing agents, Such as ionizing radiation and solar light, a product of radiation. 5',8-Purine cyclonucleosides constitute an important class of oxidatively generated tandem lesions. The present Study deals with the synthesis of the (5'R)-diastereomer of 5',8-cyclo-2'-deoxyadenosine (cdA) containing T(PO)cdA, in an attempt to delineate the conformational changes induced in the DNA fragments by the presence of this lesion. For this purpose, extensive I D and 2D NMR measurements were performed and completed by theoretical calculations. It was found that the covalent bond between C(5') and C(8) in the (5'R)-5',8-cyclo-2'-deoxyadenosine induces an unusual West (T-0(1)) conformation of the furanose ring. It is similar to the opposite (5'S)-diastereoisomer: however, the three-dimensional Structure of the dinucleoside investigated has shown art analogy to natural d(T(PO)A). Thus, it can be postulated that the rigid structure of (5'R)-5',8-cyclo-2'-deoxyadenosine would perturb the global geometry of oligonucleotides at the site of the modification less strongly than (5'S) and therefore be less toxic for cells. In this article, the influence of the (5'R)-diastereomer of 5',8-cyclo-2'-deoxyadenosine oil the dinucleotide Structure will be presented for the first time. (C) 2008 Elsevier Ltd. All rights reserved.