(5'S)-N⁵-benzoyl-3'-O-(tert-butyldimethylsilyl)-5',8-cyclo-2'-deoxyadenosine | 211919-88-9

• 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: (5'S)-N⁵-benzoyl-3'-O-(tert-butyldimethylsilyl)-5',8-cyclo-2'-deoxyadenosine
• 英文别名: (5'S)-N6-benzoyl-3'-O-(tert-butyldimethylsilyl)-5',8-cyclo-2'-deoxyadenosine；(5'S)-N⁶-benzoyl-3'-O-(tert-butyldimethylsilyl)-5',8-cyclo-2'-deoxyadenosine；(5'S)cdA(NBz)TBDMSi；N-[(1R,11S,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: 211919-88-9
• 化学式: C₂₃H₂₉N₅O₄Si
• 分子量: 467.6
• InChiKey: DFDGDTYAHOKPQZ-IDCNUPLLSA-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'S)-N⁵-benzoyl-3'-O-(tert-butyldimethylsilyl)-5',8-cyclo-2'-deoxyadenosine 在 18-冠醚-6 、 三乙胺 作用下， 以 吡啶 、 乙二醇二甲醚 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 14.0h， 生成 (5'R)-N6-benzoyl-3'-O-(tert-butyldimethylsilyl)-5',8-cyclo-2'-deoxyadenosine
  参考文献：
  名称：

  含有5'，8-环嘌呤2'-脱氧核糖核苷：（5'R）-5'，8-cyclo-2'-脱氧腺苷，（5'S）-5'，8-cyclo-2'-脱氧鸟苷的寡核苷酸的合成与表征，和（5'R）-5'，8-环-2'-脱氧鸟苷。

  摘要：

  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。

  DOI：

  10.1021/tx9802668
• 作为产物：
  描述：

  N-benzoyl-O3'-(tert-butyldimethylsilyl)-5'-oxo-2'-deoxyadenosine 以 甲醇 、 氟苯 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 (5'S)-N⁵-benzoyl-3'-O-(tert-butyldimethylsilyl)-5',8-cyclo-2'-deoxyadenosine
  参考文献：
  名称：

  环核苷的自由基环化方法

  摘要：

  报道了基于连续自由基反应制备环核苷 5 和 13 的有效方法。使用 (TMS)3SiH 作为还原剂在修饰的胸苷和 2'-脱氧腺苷底物上进行反应。受保护的 5'-甲醛 3 以 85% 的产率和非对映异构体比率 4a/4b = 3:7 提供环核苷 4。这些环核苷的 5'-O 位的单脱甲硅烷基化已通过紫外线照射成功实现，得到定量的衍生物 5a 和 5b。受保护的 5'-甲醛 10 在脱氧溶液中以 70-75% 的收率提供环核苷 12，作为单一非对映异构体 (5'R)，然后通过氯苯醌原位氧化反应混合物，或在有氧条件下。12 的光化学 5'-O-脱甲硅烷基化以 56% 的收率获得了环嘌呤 13。已经使用自由基时钟方法的变体对反应机理进行了一些详细研究。通过将 (TMS)3Si· 自由基加成到相应的醛上而生成的 C5' 自由基 6 或 15，在终止前在碱基部分发生 6-exo-trig 环化。据估计，6-exo-trig

  DOI：

  10.1002/ejoc.200500398

文献信息

• Effects of 5′,8-Cyclodeoxyadenosine Triphosphates on DNA Synthesis
  作者：Naoto Kamakura、Junpei Yamamoto、Philip J. Brooks、Shigenori Iwai、Isao Kuraoka

  DOI：10.1021/tx300351p

  日期：2012.12.17

  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.
• C5‘-Adenosinyl Radical Cyclization. A Stereochemical Investigation
  作者：Maria Luisa Navacchia、Chryssostomos Chatgilialoglu、Pier Carlo Montevecchi

  DOI：10.1021/jo060197z

  日期：2006.6.1

  A variety of substituted 2'-deoxyadenosin-5'-yl radicals 3 were generated under different reaction conditions. Radicals 3 underwent intramolecular cyclization onto the C8-N7 double bond of the adenine moiety leading to aminyl radicals (5'S,8R)-4 and (5'R,8R)-4 and, eventually, to the corresponding cyclonucleosides 5 and 6. The effect of the solvent, the nature of the substituents, and the generation method of radicals 3 on the stereoselectivity of the C5'-radical cyclization have been considered. The observed increase of the (5'S)/(5'R) ratio by increasing the bulkiness of the R-1 group is explained in terms of steric repulsion between R-1 and the purine moiety which favors the C5'-endo conformation, whereas the effect of the water solvent in promoting the (5'R)-stereoselective cyclization is ascribed to intermolecular hydrogen bonding stabilizing the C5'-exo confomation.
• Site-Specific Introduction of (5‘<i>S</i>)-5‘,8-Cyclo-2‘-deoxyadenosine into Oligodeoxyribonucleotides
  作者：Anthony Romieu、Didier Gasparutto、Didier Molko、Jean Cadet

  DOI：10.1021/jo980083q

  日期：1998.7.1
• Synthesis and Characterization of Oligodeoxynucleotides Containing 5′,8-Cyclopurine-2′-Deoxyribonucleosides
  作者：Anthony Romieu、Didier Gasparutto、Didier Molko、Jean Cadet

  DOI：10.1080/07328319908044708

  日期：1999.6
• (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.