2'-脱氧-6-O-[2-(4-硝基苯基)乙基]鸟苷 | 86137-72-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 中文名称: 2'-脱氧-6-O-[2-(4-硝基苯基)乙基]鸟苷
• 英文名称: 2'-deoxy-O⁶-<2-(4-nitrophenyl)ethyl>guanosine
• 英文别名: 2'-deoxy-O⁶-[2-(4-nitrophenyl)ethyl]guanosine；2'-deoxy-O6-[2-(4-nitrophenyl)ethyl]guanosine；6-O-(4-nitrophenylethyl)-2'-deoxyguanosine；O-6-(p-nitrophenylethyl)-2'-deoxyguanosine；(2R,3S,5R)-5-[2-amino-6-[2-(4-nitrophenyl)ethoxy]purin-9-yl]-2-(hydroxymethyl)oxolan-3-ol
• CAS: 86137-72-6
• 化学式: C₁₈H₂₀N₆O₆
• 分子量: 416.393
• InChiKey: BJWXZOBLBMGQCJ-BFHYXJOUSA-N

物化性质

• 密度：
  1.71

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 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：
  174
• 氢给体数：
  3
• 氢受体数：
  10

制备方法与用途

2'-脱氧-O6-[2-(4-硝基苯乙基)]鸟苷是一种嘌呤核苷类似物，具有广泛的抗肿瘤活性，尤其针对惰性淋巴系统恶性肿瘤。其抗癌机制主要依赖于抑制DNA合成和诱导细胞凋亡等过程。

反应信息

• 作为反应物：
  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 、 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 56.0h， 生成 9-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxyoxolan-2-yl]-2-(2-phenylethylamino)-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 、 ammonium hydroxide 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 147.5h， 生成 2'-脱氧-6-O-[2-(4-硝基苯基)乙基]鸟苷
  参考文献：
  名称：

  Synthesis of Oligonucleotide Adducts of the Bay Region Diol Epoxide Metabolites of Carcinogenic Polycyclic Aromatic Hydrocarbons

  摘要：

  An efficient method for the site-specific synthesis of adducts between the biologically active diol epoxide metabolites of carcinogenic polycyclic aromatic hydrocarbons (PAHs) and oligonucleotides in which a PAH component of predetermined stereochemistry is linked covalently to the exocyclic amino groups of deoxyadenosine (dA) and deoxyguanosine (dG) is described. The synthetic strategy involves in the key step coupling a protected halopurine derivative with an amino derivative (or an aminotriol derivative) of the PAH. This method was initially employed to prepare the dA and dG adducts of the model PAH 1-methylpyrene. The appropriately protected dA adduct was then incorporated into the oligonucleotide sequence d(GCAGGTCA(*)AGAG) where A(*) represents N6-pyrenylmethyl-dA. This methodology was extended to the synthesis of trans adducts of anti-diol epoxide metabolites of benzo[a]pyrene and 5-methylchrysene linked to the 6-amino function of dA. The parent hydrocarbons are widespread environmental carcinogens. This synthetic approach, dubbed the total synthesis method, complements the direct synthesis method which involves the direct reaction of PAH diol epoxides with oligonucleotides. The total synthesis method is broader in scope than the latter, and it is readily adaptable to the large scale preparation of PAH-oligonucleotide adducts required for structure determination by high resolution NMR and X-ray crystallographic techniques.

  DOI：

  10.1021/jo00122a048

文献信息

• Nucleotides, Part LXVII, The 2-Cyanoethyl and (2-Cyanoethoxy)carbonyl Group for Base Protection in Nucleoside and Nucleotide Chemistry
  作者：Claudia Merk、Tilman Reiner、Evgeny Kvasyuk、Wolfgang Pfleiderer

  DOI：10.1002/1522-2675(20001220)83:12<3198::aid-hlca3198>3.0.co;2-q

  日期：2000.12.20

  The amino functions of the common 2′-deoxyribo- and ribonucleosides were blocked by the (2-cyanoethoxy)carbonyl group on treatment with 2-cyanoethyl carbonochloridate (5) or 1-[(2-cyanoethoxy)carbonyl]-3-methyl-1H-imidazolium chloride (6) leading to 7, 18, 8, 19, 9, and 20. In 2′-deoxyguanosine, the amide group was additionally blocked at the O6 position by the 2-cyanoethyl (27) and 2-(4-nitrophenyl)ethyl

  在用 2-氰基乙基碳氯酸酯 (5) 或 1-[(2-氰基乙氧基)羰基]-3-甲基-处理时，常见的 2'-脱氧核糖和核糖核苷的氨基官能团被 (2-氰基乙氧基)羰基封闭。 1H-咪唑氯化物 (6) 产生 7, 18, 8, 19, 9 和 20。在 2'-脱氧鸟苷中，酰胺基团在 O6 位被 2-氰乙基 (27) 和 2-( 4-硝基苯基)乙基(31, 32)。关于通过 β-消除裂解 ce/ceoc 和 npe/npeoc 基团的比较动力学研究揭示了有关核碱基不同位点的各种封闭基团的容易性和顺序脱保护的有价值的信息。
• The p-nitrophenylethyl (NPE) group
  作者：Frank Himmelsbach、Bernd S. Schulz、Thomas Trichtinger、Ramamurthy Charubala、Wolfgang Pfleiderer

  DOI：10.1016/0040-4020(84)85103-0

  日期：1984.1

  aprotic solvents. 5'-O-Monomethoxytritylation (12,29,43) as well as phosphorylations at the 3'-OH group can be effected to give the corresponding 3'-(2,5-dichlorophenyl,/-nitrophenylethyl)-phosphotriesters (13,22,30,44) also in high yields. Oximate cleavage of the latter compounds to the phosphodiesters (14,24,32,46) and detritylation to the 5'-unblocked phosphotriesters (15,23,31,45) do not affect the

  描述了用于合成寡核苷酸的新的单体结构单元的合成，该新的单体结构单元通过磷酸三酯方法进行合成，该方法包含对-硝基苯基乙基用于磷酸盐和糖苷配基的保护。在澳在鸟苷的酰胺官能团的阻断6可以通过Mitsunobu反应形成对应的O来实现6 - p -nitrophenylethyl衍生物（4，5，10）。糖保护胸苷（16）和尿苷（17）已经被在澳烷基化4以S Ñ 1型反应通过p在苯，以形成将O碳酸盐-nitrophenylethyl碘化银4 - p -nitrophenylethyl衍生物（18，19）。在-2'-脱氧胞苷（氨基的保护25）和胞苷（26）可以通过1-（直接进行p -nitrophenylethoxycarbonyl） -苯并三唑的DMF，得到相应的氨基甲酸酯（27，28）作为一种新的类型为N 4-酰化胞苷衍生物。p 2'-脱氧腺苷（33）和腺苷（34）中氨基的硝基苯基乙氧基羰基化作用需
• Nucleotides. Part L. Aglycone protection by the (2-dansylethoxy)carbonyl (= {2-{[5-(dimethylamino)naphthalen-l-yl]sulfonyl}ethoxy}carbonyl; dnseoc) group a new variation in oligodeoxyribonucleotide synthesis
  作者：Thomas Wagner、Wolfgang Pfleiderer

  DOI：10.1002/hlca.19970800118

  日期：1997.2.10

  (2-dansylethoxy)carbonyl (= 2-[5-(dimethylamino)naphthalen-l-yl]sulfonyl}ethoxy}carbonyl; dnseoc) group was employed for protection of the amino functions of the aglycone residues. The lactam function of 2′-deoxyguanosine was on the one hand unprotected and on the other hand alkylated at O6 of the aglycone with the 2-(4-nitrophenyl)ethyl (npe) and 2-(phenylsulfonyl)ethyl (pse) group, respectively. The syntheses

  （2-丹酰基乙氧基）羰基（＝ 2-[5-（二甲基氨基）萘-1-基]磺酰基}乙氧基}羰基； dnseoc）基团用于保护糖苷配基残基的氨基官能团。2'-脱氧鸟苷的内酰胺功能一方面未受保护，另一方面在O 6处烷基化糖苷配基分别具有2-（4-硝基苯基）乙基（npe）和2-（苯基磺酰基）乙基（pse）的基团。描述了三种常见的2'-脱氧核苷（2'-脱氧胞苷，2'-脱氧腺苷，2'-脱氧鸟苷）的单体结构单元（亚磷酰胺和核苷官能化载体）的合成。正如对三苯甲基化核苷的动力学研究表明，与相应的2-（4-硝基苯基）乙基-（npe）和[2-（4-硝基苯基）乙氧基]羰基（npeoc）-保护的dnseoc基团相比，Dse裂解更不稳定。类似物（参见表2）。这些结果被dnseoc基团在某些寡核苷酸上的快速去保护率所证实。
• 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。
• Festphasensynthese von Oligonucleotiden
  申请人：HOECHST AKTIENGESELLSCHAFT

  公开号：EP0818460A2

  公开（公告）日：1998-01-14

  Gegenstand der Erfindung ist daher ein Verfahren zur Herstellung von Oligonukleotiden mittels Festphasensynthese durch a) sequentiellen Aufbau der Nucleotide an einem festen Träger nach bekannten Methoden, wobei vorhandene exocyclische Aminogruppen an den Nucleobasen durch eine cyclische Diacylgruppe geschützt sind und gegebenenfalls vorhandene Phosphatschutzgruppen durch starke, nicht nukleophile Basen abspaltbar sind, b) Entschützung der am festen Träger gebundenen Oligonukleotide, und c) Abspaltung der entschützten Oligonukleotide vom festen Träger nach bekannten Methoden, dadurch gekennzeichnet, daß die am festen Träger gebundenen Oligonukleotide in Gegenwart einer starken, nicht nukleophilen Base in einem geeigneten organischen Lösungsmittel entschützt werden.

  因此，本发明的主题是一种通过固相合成制备寡核苷酸的工艺，其方法是 a) 根据已知方法将核苷酸依次组装在固体支持物上，其中核碱基上存在的任何外环氨基均由环二酰基保护，存在的任何磷酸保护基均可由强的、非亲核碱基裂解掉、 b) 对与固体支持物结合的寡核苷酸进行脱保护，以及 c) 用已知方法将脱保护的寡核苷酸从固体支持物上裂解、 其特征在于，与固体支持物结合的寡核苷酸是在强的、非亲核碱存在下，在合适的有机溶剂中进行脱保护的。