2-fluoro-O⁶-(2-(p-nitrophenyl)ethyl)-2'-deoxyinosine | 132183-39-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2-fluoro-O⁶-(2-(p-nitrophenyl)ethyl)-2'-deoxyinosine
• 英文别名: 2-fluoro-O⁶-(2-p-nitrophenylethyl)deoxyinosine；6-O-[2-(4-Nitrophenyl)ethyl]-2'-deoxy-2-fluoroinosine；2'-deoxy-2-fluoro-O6-[2-(4-nitrophenyl)ethyl]inosine；2-fluoro-6-O-(4-nitrophenylethyl)-2'-deoxyinosine；O-6-p-nitrophenylethyl-2-fluoro-2'-deoxyinosine；2-fluoro-O6-(2-p-nitrophenylethyl)deoxyinosine；(2R,3S,5R)-5-[2-fluoro-6-[2-(4-nitrophenyl)ethoxy]purin-9-yl]-2-(hydroxymethyl)oxolan-3-ol
• CAS: 132183-39-2
• 化学式: C₁₈H₁₈FN₅O₆
• 分子量: 419.369
• InChiKey: CDQYNHZEMPHEMV-BFHYXJOUSA-N

物化性质

• 沸点：
  760.4±70.0 °C(Predicted)
• 密度：
  1.68±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  148
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  2-fluoro-O⁶-(2-(p-nitrophenyl)ethyl)-2'-deoxyinosine 在 吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 54.0h， 生成 9-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxyoxolan-2-yl]-2-[(3-phenylphenyl)methylamino]-1H-purin-6-one
  参考文献：
  名称：

  N²- and C⁸-Substituted Oligodeoxynucleotides with Enhanced Thrombin Inhibitory Activity in Vitro and in Vivo

  摘要：

  2'-Deoxyguanosine (G) analogues carrying various hydrophobic substituents in the N-2 and C-8 positions were synthesized and introduced through solid-phase synthesis into 15-mer oligodeoxynucleotide, GGTTGGTGTGGTTGG, which forms a chairlike structure consisting of two G-tetrads and is a potent thrombin inhibitor. The effects of the substitutions at N-2 and C-8 of the G-tetrad-forming G residues on the thrombin inhibitory activity are relatively small, suggesting that these substitutions cause relatively small, perturbations on the chairlike structure formed by the oligodeoxynucleotide. Introduction of a benzyl group into N-2 of G(6) and G(11) and naphthylmethyl groups into N-2 of G(6) increased the thrombin inhibitory activity, whereas other substituents in these positions had almost no effect or decreased the activity. Particularly, the oligodeoxynucleotide carrying a 1-naphthylmethyl group in the N-2 position of G(6) showed an increase in activity by about 60% both in vitro and in vivo. Substitutions on the N-2 position of other G residues had little effect or decreased the activity. Introduction of a relatively small group, such as methyl and propynyl, into the C-8 positions of G(1), G(5), G(10), and G(14) increased the activity, presumably due to the stabilization of a chairlike structure, whereas introduction of a large substituent group, phenylethynyl, decreased the activity, probably due to the steric hindrance.

  DOI：

  10.1021/jm970434d
• 作为产物：
  描述：

  2'-脱氧鸟苷 在 咪唑 、 亚硝酸特丁酯 、 氢氟酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 吡啶 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.25h， 生成 2-fluoro-O⁶-(2-(p-nitrophenyl)ethyl)-2'-deoxyinosine
  参考文献：
  名称：

  吡咯衍生的双功能亲电试剂的 DNA 链间交联反应：DNA 中共同靶位点的证据

  摘要：

  由吡咯衍生的双功能亲电试剂家族鉴定的 DNA 链间交联位点在合成 DNA 双链体中进行了体外研究。该家族包括还原活化的丝裂霉素 C (1)、氧化活化的吡咯里西啶生物碱（例如 2）、简单的吡咯 2,3- 和 3,4-双-（乙酰氧基甲基）-1-甲基吡咯（3 和 4），以及抗肿瘤剂物质 2,3-二氢-5-(3',4'-二氯苯基)-6,7-双(羟甲基)-1H-吡咯嗪双-(异丙基氨基甲酸酯) (IPP, 5)。本文证明这些试剂优先交联双链 DNA 中的共同靶位点，即序列 5'-d(CG) 处脱氧鸟苷残基的环外氨基

  DOI：

  10.1021/ja00062a002

文献信息

• Synthesis of an Oligodeoxyribonucleotide Adduct of Mitomycin C by the Postoligomerization Method <i>via</i> a Triamino Mitosene
  作者：Elise Champeil、Manuel M. Paz、Sweta Ladwa、Cristina C. Clement、Andrzej Zatorski、Maria Tomasz

  DOI：10.1021/ja802118p

  日期：2008.7.1

  residue of the 12-mer oligonucleotide. The N(2)-phenylacetyl protecting group of 14 after its coupling to the 12-mer oligonucleotide could not be removed by penicillinamidase as expected. Nevertheless, the Teoc protecting group of 24 after coupling to the 12-mer oligonucleotide was removed by treatment with ZnBr2 to give the adducted oligonucleotide 26. However, phenylacetyl group removal was successful

  癌症化学治疗剂丝裂霉素 C (MC) 在体内和体外单功能和双功能地烷基化和交联 DNA，形成六种已知结构的主要 MC-脱氧鸟苷加合物。通过后寡聚化方法合成一个单加合物 (8) 在核苷和寡核苷酸水平上完成，后者导致 8 位点特异性放置在 12 聚体寡脱氧核糖核苷酸 26 中。这是该方法的首次应用一种合成复杂天然产物 DNA 加合物的方法。必需的选择性保护的三氨基丝氨酸 14 和 24 的制备开始于从 MC 中去除 10-氨基甲酰基，然后还原转化为 10-decarbamoyl-2,7-diaminomitoseene 10。该物质在几个步骤中转化为 14 或 24。两者都成功地与 12 聚体寡核苷酸的 2-氟-O(6)-(2-三甲基甲硅烷基乙基) 脱氧肌苷残基偶联。与 12 聚体寡核苷酸偶联后的 N(2)-苯乙酰基保护基团 14 不能按预期被青霉素酰胺酶去除。然而，与 12 聚体寡核苷酸偶联后的
• Synthesis of Mitomycin C and Decarbamoylmitomycin C N2 deoxyguanosine-adducts
  作者：Elise Champeil、Shu-Yuan Cheng、Bik Tzu Huang、Marta Conchero-Guisan、Thibaut Martinez、Manuel M. Paz、Anne-Marie Sapse

  DOI：10.1016/j.bioorg.2016.02.003

  日期：2016.4

  Mitomycin C (MC) and Decarbamoylmitomycin C (DMC) – a derivative of MC lacking the carbamate on C10 – are DNA alkylating agents. Their cytotoxicity is attributed to their ability to generate DNA monoadducts as well as intrastrand and interstrand cross-links (ICLs). The major monoadducts generated by MC and DMC in tumor cells have opposite stereochemistry at carbon one of the guanine–mitosene bond:

  丝裂霉素C（MC）和脱氨基甲酰丝裂霉素C（DMC）是MC的衍生物，在C10上缺少氨基甲酸酯，它们是DNA烷基化剂。它们的细胞毒性归因于它们产生DNA单加合物以及链内和链间交联（ICL）的能力。MC和DMC在肿瘤细胞中产生的主要单加合物在鸟嘌呤-次油烯键的碳原子上具有相反的立体化学：MC的反式（或α）和DMC的顺式（或β）。我们假设从反式或顺式加合物的DNA结构的局部破坏是由MC和DMC产生不同的生化反应的原因。获得带有顺式和反式MC / DMC损伤的DNA底物对于验证这一假设至关重要。带有反式损伤的合成寡核苷酸可以通过仿生方法获得。但是，这种方法不会产生顺式加合物。该报告介绍了顺式次生多面体DNA加合物的首次化学合成。我们还通过分析脱氧鸟苷与MC或DMC在多种激活条件下反应中顺式和反式加合物的形成，研究了这两种药物在单核苷酸水平上表现出的立体偏好。此外，我们进行了密度泛函理论计算，以评估这
• Synthesis of oligonucleotides containing N2-[2-(imidazol-4-ylacetamido)ethyll-2′-deoxyguanosine
  作者：Guangyi Wang、Donald E. Bergstrom

  DOI：10.1016/s0040-4039(00)61685-4

  日期：1993.10

  Synthesis of 2′-deoxyguanosine tethered through N-2 to an imidazole is described. The modified 2′-deoxyguanosine was converted to two different phosphoramidites, one with and the other without a 6-O-protecting group. The phosphoramidites were incorporated into oligonucleotide alone or together with a 2′-deoxyuridine tethered to a bipyridine. Protection and deprotection of the imidazole are also briefly

  描述了通过N-2连接到咪唑的2'-脱氧鸟苷的合成。修饰的2'-脱氧鸟苷被转化为两种不同的亚磷酰胺，一种具有6- O-保护基，另一种具有6- O-保护基。将亚磷酰胺单独或与束缚到联吡啶的2'-脱氧尿苷一起掺入寡核苷酸中。还简要描述了咪唑的保护和脱保护。
• Synthesis of a major mitomycin C DNA adduct via a triaminomitosene
  作者：Elise Champeil、Manuel M. Paz、Elaan Lukasiewicz、Wan S. Kong、Stephanie Watson、Anne-Marie Sapse

  DOI：10.1016/j.bmcl.2012.09.052

  日期：2012.12

  We report here the synthesis of two amino precursors for the production of mitomycin C and 10-decarbamoylmitomycin C DNA adducts with opposite stereochemistry at C-1. The triamino mitosene precursors were synthesized in 5 steps from mitomycin C. In addition synthesis of the major mitomycin C-DNA adduct has been accomplished via coupling of a triaminomitosene with 2-fluoro-O6-(2-p-nitrophenylethyl)deoxyinosine

  我们在这里报告了两个氨基前体的合成，用于生产丝裂霉素C和10-去氨甲酰丝裂霉素C DNA加合物，在C-1处具有相反的立体化学。从丝裂霉素C分5步合成了三氨基丝裂胺前体。此外，主要的丝裂霉素C-DNA加合物的合成是通过将三氨基丝裂烯与2-氟-O 6-（2-对-硝基苯基乙基）脱氧肌苷偶联，然后在N 2和O 6位置脱保护。
• Syntheses of polycyclic aromatic hydrocarbon-nucleoslde and oligonucleotide adducts specifically alkylated on the amino functions of deoxyguanosine and deoxyadenosine
  作者：Hongmee Lee、Michael Hinz、John J. Stezowski、Ronald G. Harvey

  DOI：10.1016/s0040-4039(00)97168-5

  日期：1990.1

  Efficient syntheses of 1-pyrenylmethyl-mononucleoside adducts with the hydrocarbon moiety attached to the exocyclic amino functions of deoxyguanosine and deoxyadenosine are described.

  描述了具有连接至脱氧鸟苷和脱氧腺苷的环外氨基官能团的烃部分的1-苯甲基甲基单核苷加合物的有效合成。