(2R,3S,5R)-5-{2-Benzylamino-6-[2-(4-nitro-phenyl)-ethoxy]-purin-9-yl}-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-tetrahydro-furan-3-ol | 209785-65-9

• 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: (2R,3S,5R)-5-{2-Benzylamino-6-[2-(4-nitro-phenyl)-ethoxy]-purin-9-yl}-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-tetrahydro-furan-3-ol
• 英文别名: N²-benzyl-O⁶-(2-(4-nitrophenyl)ethyl)-5′-(4,4′-dimethoxytrityl)-2′-deoxyguanosine
• CAS: 209785-65-9
• 化学式: C₄₆H₄₄N₆O₈
• 分子量: 808.891
• InChiKey: BVMKTKMVVIKXJG-NJZAESGASA-N

物化性质

• 沸点：
  993.0±75.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.64
• 重原子数：
  60.0
• 可旋转键数：
  17.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  165.15
• 氢给体数：
  2.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  (2R,3S,5R)-5-{2-Benzylamino-6-[2-(4-nitro-phenyl)-ethoxy]-purin-9-yl}-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-tetrahydro-furan-3-ol 在 吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 反应 15.0h， 以73%的产率得到2-(Benzylamino)-9-((2R,4S,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-4-hydroxytetrahydrofuran-2-yl)-1H-purin-6(9H)-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-6-O-[2-(4-硝基苯基)乙基]鸟苷 在 吡啶 、 亚硝酸特丁酯 、 氢氟酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 41.0h， 生成 (2R,3S,5R)-5-{2-Benzylamino-6-[2-(4-nitro-phenyl)-ethoxy]-purin-9-yl}-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-tetrahydro-furan-3-ol
  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

文献信息

• Synthesis of <i>N</i>²-Deoxyguanosine Modified DNAs and the Studies on Their Translesion Synthesis by the <i>E. coli</i> DNA Polymerase IV
  作者：Pratibha P. Ghodke、Praneeth Bommisetti、Deepak T. Nair、P. I. Pradeepkumar

  DOI：10.1021/acs.joc.8b02082

  日期：2019.2.15

  We report the synthesis of N2-aryl (benzyl, naphthyl, anthracenyl, and pyrenyl)-deoxyguanosine (dG) modified phosphoramidite building blocks and the corresponding damaged DNAs. Primer extension studies using E. coli Pol IV, a translesion polymerase, demonstrate that translesion synthesis (TLS) across these N2-dG adducts is error free. However, the efficiency of TLS activity decreases with increase

  我们报告了N2-芳基（苄基，萘基，蒽基和pyr基）-脱氧鸟苷（dG）修饰的亚磷酰胺结构单元和相应的受损DNA的合成。使用大肠埃希氏大肠杆菌Pol IV（一种跨病变聚合酶）进行引物延伸研究表明，跨这些N2-dG加合物的跨病变合成（TLS）是没有错误的。然而，TLS活性的效率随着加合物的空间体积的增加而降低。受损的DNA-Pol IV复合物的分子动力学模拟揭示了酶和加合物的关键氨基酸残基（Phe13，Ile31，Gly32，Gly33，Ser42，Pro73，Gly74，Phe76和Tyr79）之间的范德华相互作用疏水性口袋中的大块损坏，有利于TLS。总体而言，此处给出的结果为Pol IV对N2-芳基-dG受损DNA上的TLS提供了见解。