O⁶-benzyl-8-bromo-N9-[3',5'-O-(1,1,3,3-tetrakis(isopropyl)-1,3-disiloxanediyl)-β-D-2'-deoxyribofuranosyl]guanine | 328394-26-9

• 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: O⁶-benzyl-8-bromo-N9-[3',5'-O-(1,1,3,3-tetrakis(isopropyl)-1,3-disiloxanediyl)-β-D-2'-deoxyribofuranosyl]guanine
• 英文别名: O6-Benzyl-8-bromo-N9-[3',5'-O-(1,1,3,3-tetrakis(isopropyl)-1,3-disiloxanediyl)-b-D-2'-deoxyribofuranosyl]guanine；9-[(6aR,8R,9aS)-2,2,4,4-tetra(propan-2-yl)-6a,8,9,9a-tetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl]-8-bromo-6-phenylmethoxypurin-2-amine
• CAS: 328394-26-9
• 化学式: C₂₉H₄₄BrN₅O₅Si₂
• 分子量: 678.774
• InChiKey: JDXBCEWMDJONPM-RBZQAINGSA-N

物化性质

• 熔点：
  125-127°C
• 溶解度：
  可溶于丙酮、氯仿、DMF、DMSO、乙酸乙酯、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  6.99
• 重原子数：
  42
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  O⁶-benzyl-8-bromo-N9-[3',5'-O-(1,1,3,3-tetrakis(isopropyl)-1,3-disiloxanediyl)-β-D-2'-deoxyribofuranosyl]guanine 在 palladium on activated charcoal tris(dibenzylideneacetone)dipalladium (0) 、 氢气 、 氟化氢吡啶 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 20.0~100.0 ℃ 、101.33 kPa 条件下， 反应 24.5h， 生成 8-((1,1'-联苯)-4-基氨基)-2'-脱氧鸟苷
  参考文献：
  名称：

  含有膳食诱变剂 IQ​​ 的 C8-脱氧鸟苷加合物的寡核苷酸的定点合成和特性

  摘要：

  已实现含有高致突变杂环胺2-氨基-3-甲基咪唑并[4,5-f]喹啉(IQ)的C8-脱氧鸟苷加合物的寡核苷酸的定点合成，并通过UV熔解温度表征寡核苷酸分析、圆二色性和紫外吸收光谱。对这些数据的检查表明 IQ 加合物适应于截然不同的环境。这种依赖于序列的构象偏好可能在 IQ 修饰的寡核苷酸的致突变性和修复中发挥关键作用。

  DOI：

  10.1021/ja0487022
• 作为产物：
  描述：

  8-溴-2'-脱氧鸟苷 在 吡啶 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 1,4-二氧六环 为溶剂， 生成 O⁶-benzyl-8-bromo-N9-[3',5'-O-(1,1,3,3-tetrakis(isopropyl)-1,3-disiloxanediyl)-β-D-2'-deoxyribofuranosyl]guanine
  参考文献：
  名称：

  含有膳食诱变剂 IQ​​ 的 C8-脱氧鸟苷加合物的寡核苷酸的定点合成和特性

  摘要：

  已实现含有高致突变杂环胺2-氨基-3-甲基咪唑并[4,5-f]喹啉(IQ)的C8-脱氧鸟苷加合物的寡核苷酸的定点合成，并通过UV熔解温度表征寡核苷酸分析、圆二色性和紫外吸收光谱。对这些数据的检查表明 IQ 加合物适应于截然不同的环境。这种依赖于序列的构象偏好可能在 IQ 修饰的寡核苷酸的致突变性和修复中发挥关键作用。

  DOI：

  10.1021/ja0487022

文献信息

• Synthesis of the C8-Deoxyguanosine Adduct of the Food Mutagen IQ
  作者：Zhiwei Wang、Carmelo J. Rizzo

  DOI：10.1021/ol006968h

  日期：2001.2.1

  [GRAPHICS]The C8-2'-deoxyguanosine adduct of the food mutagen 2-amino-3-methylimadazo[4,5-f]-quinoline (IQ) has been synthesized, The key step is a palladium catalyzed N-arylation of a suitably protected 8-bromo-2'-deoxygunaosine derivative.
• The C8-2′-Deoxyguanosine Adduct of 2-Amino-3-methylimidazo[1,2-<i>d</i>]naphthalene, a Carbocyclic Analogue of the Potent Mutagen 2-Amino-3-methylimidazo[4,5-<i>f</i>]quinoline, Is a Block to Replication in Vitro
  作者：Plamen P. Christov、Goutam Chowdhury、Craig A. Garmendia、Feng Wang、James S. Stover、C. Eric Elmquist、Albena Kozekova、Karen C. Angel、Robert J. Turesky、Michael P. Stone、F. Peter Guengerich、Carmelo J. Rizzo

  DOI：10.1021/tx100053n

  日期：2010.6.21

  2-Amino-3-methylimidazo[1,2-d]naphthalene (cIQ) is a carbocyclic analogue of the dietary carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in which a naphthalene ring system replaces the quinoline unit of IQ. The activity of cIQ in Ames Salmonella typhimurium tester strain TA98 is known to be 4-5 orders of magnitude lower than IQ. cIQ undergoes efficient bioactivation with rat liver microsomes. The C8-dGuo adduct was formed when calf thymus DNA was treated with the N-hydroxy-cIQ metabolite and either acetic anhydride or extracts from cells that overexpress N-acetyl transferase (NAT). These studies indicate that bioactivation, the stability of the N-hydroxylamine ester, and the reactivity of the nitrenium ion with DNA of cIQ are similar to IQ and that none of these factors account for the differences in mutagenic potency of these analogues in Ames assays. Oligonucleotides were synthesized that contain the C8-dGuo adduct of cIQ in the frameshift-prone CG-dinucleotide repeat unit of the Narl recognition sequence. We have examined the in vitro translesion synthesis of this adduct and have found it to be a strong replication block to Escherichia coli DNA polymerase I, Klenow fragment exo(-) (Kf(-)), E. coli DNA polymerase II exo(-) (pol II-), and Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4). Previous studies by Fuchs and co-workers identified E. coli pol II as the polymerase responsible for two-base deletions of the C8-dGuo adduct of N-acetyl-2-aminofluorene in the Narl sequence. Our observation that pol II is strongly inhibited by the C8-dGuo adduct of cIQ suggests that one of the other SOS inducible polymerases (E. coli pol IV or pol V) is required for its bypass, and this accounts for the greatly attenuated mutagenicity in the Ames assays as compared with IQ.
• Site-Specific Synthesis and Properties of Oligonucleotides Containing C8-Deoxyguanosine Adducts of the Dietary Mutagen IQ
  作者：C. Eric Elmquist、James S. Stover、Zhiwei Wang、Carmelo J. Rizzo

  DOI：10.1021/ja0487022

  日期：2004.9.1

  The site-specific synthesis of oligonucleotides containing the C8-deoxyguanosine adduct of the highly mutagenic heterocyclic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) has been achieved, and the oligonucleotides were characterized by UV melting temperature analysis, circular dichroism, and UV absorption spectroscopy. Examination of these data indicated that the IQ-adduct is accommodated in

  已实现含有高致突变杂环胺2-氨基-3-甲基咪唑并[4,5-f]喹啉(IQ)的C8-脱氧鸟苷加合物的寡核苷酸的定点合成，并通过UV熔解温度表征寡核苷酸分析、圆二色性和紫外吸收光谱。对这些数据的检查表明 IQ 加合物适应于截然不同的环境。这种依赖于序列的构象偏好可能在 IQ 修饰的寡核苷酸的致突变性和修复中发挥关键作用。