5'-O-(4,4'-Dimethoxytrityl)-6-O-[2-(4-nitrophenyl)ethyl]-2'-deoxy-2-fluoroinosine | 153527-28-7

• 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: 5'-O-(4,4'-Dimethoxytrityl)-6-O-[2-(4-nitrophenyl)ethyl]-2'-deoxy-2-fluoroinosine
• 英文别名: 2'-deoxy-5'-O-(4,4'-dimethoxytrityl)-2-fluoro-O6-[2-(4-nitrophenyl)ethyl]inosine；5'-O-(4,4'-dimethoxytrityl)-2-fluoro-6-O-(4-nitrophenylethyl)-2'-deoxyinosine；5'-O-dimethoxytrityl-O-6-p-nitrophenylethyl-2-fluoro-2'-deoxyinosine；5'-O-DMTr-2-fluoro-6-O-nitrophenylethyldeoxyinosine；(2R,3S,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-5-[2-fluoro-6-[2-(4-nitrophenyl)ethoxy]purin-9-yl]oxolan-3-ol
• CAS: 153527-28-7
• 化学式: C₃₉H₃₆FN₅O₈
• 分子量: 721.742
• InChiKey: SOAOMGOSWCAABI-LBFZIJHGSA-N

物化性质

• 沸点：
  924.8±75.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  53
• 可旋转键数：
  13
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  156
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  5'-O-(4,4'-Dimethoxytrityl)-6-O-[2-(4-nitrophenyl)ethyl]-2'-deoxy-2-fluoroinosine 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 39.0h， 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 吡啶 、 亚硝酸特丁酯 、 氢氟酸 、 氨 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.5h， 生成 5'-O-(4,4'-Dimethoxytrityl)-6-O-[2-(4-nitrophenyl)ethyl]-2'-deoxy-2-fluoroinosine
  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 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。
• Duplex Stabilizing Effect and Nuclease Resistant Property of Novel Oligonucleotides Containing C-2 Branched Polyamine-Bearing Deoxyinosine Derivative
  作者：Kazuo Shinozuka、Masaaki Onodera、Hiroshi Ikeda、Hiroaki Sawai

  DOI：10.1246/cl.2002.200

  日期：2002.2

  Novel oligodeoxyribonucleotides containing a C-2 branched polyamine-bearing deoxyinosine moiety at either inside-region or the 5′-terminus of the sequence exhibited enhanced nuclease resistant property. Among them, only the oligomers having the modified deoxyinosine residue at inside-region brought about duplex stabilizing effect upon mixing with the complements.

  在序列的内侧区域或5’末端含有C-2支链多胺-脱氧肌苷部分的新型寡脱氧核糖核苷酸表现出更强的抗核酸酶特性。其中，只有在内侧区域具有修饰脱氧肌苷残基的寡聚物在与互补物混合后能够产生双链稳定作用。
• Synthesis of Polyaminooligonucleotides and Their Combinatorial Libraries
  作者：Wojciech T. Markiewicz、Przemysław Godzina、Maria Markiewicz

  DOI：10.1080/07328319908044749

  日期：1999.6

  A synthesis of phosphoramidites of 2'-deqxyadenosine and 2'-deoxyguanosine carrying a protected spermine moiety at N-6 and N-2 positions respectively is described. An approach to analyse properties of polyaminooligonucleotides using their synthetic combinatorial libraries is described and discussed. A synthesis of a polyaminooligonucleotide combinatorial library was carried out and the analysis of the library clearly showed that the presence of spermine moieties in oligodeoxyribonucleotides increases stability of their complexes.
• Synthetic Oligonucleotide Combinatorial Libraries. 3. Synthesis of Polyamevonucleosides
  作者：Przemyslaw Godzina、Katarzyna Adrych-Rozek、Wojciech T. Markiewicz

  DOI：10.1080/07328319908044615

  日期：1999.11

  Synthesis of polyamino-2'-deoxynucleosides was studied. A synthesis of 2'-deoxyadenosine and 2'-deoxyguanosine derivatives carrying a protected spermine moiety at N-6 and N-2 positions respectively is described using unprotected polyamines as substrates. The question of reactivity of primary and secondary amino groups present in polyamines was studied. The evidence that only primary amino groups react with the synthesised precursors was accomplished from experiments with a secondary amine (di-n-butylamine). An approach to analyse properties of polyaminooligonucleotides using their synthetic combinatorial libraries is discussed.
• Synthesis and Hybridization Properties of Oligonucleotides Containing Polyamines at the C-2 Position of Purines: A Pre-synthetic Approach for the Incorporation of Spermine into Oligodeoxynucleotides Containing 2-(4,9,13-Triazatridecyl)-2′-deoxyguanosine
  作者：Pierre Potier、Adib Abdennaji、Jean-Paul Behr

  DOI：10.1002/1521-3765(20001117)6:22<4188::aid-chem4188>3.0.co;2-n

  日期：2000.11.17

  We have developed a synthesis of spermine-containing oligonucleotides (ODN-sper) which allows incorporation of multiple polyamine residues. This approach was based on the pertrifluoroacetylated 5'DMT-dGsper phosphoramidite synthon. Its coupling yield with resin-bound ODN decreased dramatically when close to the 3'-end. Optimization of the coupling conditions allowed 22-mer ODNs containing up to six spermine residues to be synthesized. Several ODNs of different sequences with 1-4 pendent spermines could be purified and their hybridization properties were evaluated. Duplex melting temperatures increased linearly with the number of polyamine.residues (DeltaT(m)/sper = 3.0 +/- 0.2 degreesC in 100 mM NaCl). This compares very favorably with values reported for duplexes of similar initial stability containing other cation-substituted bases. Moreover, the stability increase was neither sequence nor position-dependent, and even contiguous spermine residues did not crosstalk. Extrapolation based on these findings leads to the conclusion that a duplex formed with a 22-mer oligonucleotide containing seven spermine residues would be as stable as genomic DNA, which highlights its potential for DNA strand invasion.