2',5'-di-O-trityluridine | 6554-11-6

• 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: 2',5'-di-O-trityluridine
• 英文别名: 2',5'-Di-O-trityl-uridin；2',5'-bis-O-trityluridine；1-((2R,3R,4R,5R)-4-Hydroxy-3-(trityloxy)-5-((trityloxy)methyl)tetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione；1-[(2R,3R,4R,5R)-4-hydroxy-3-trityloxy-5-(trityloxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 6554-11-6
• 化学式: C₄₇H₄₀N₂O₆
• 分子量: 728.844
• InChiKey: DHKUAWARIDEGPI-QQIQMRLBSA-N

物化性质

• 熔点：
  215-220 °C
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  55
• 可旋转键数：
  12
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  97.3
• 氢给体数：
  2
• 氢受体数：
  6

制备方法与用途

2′,5′-双-O-(三苯基甲基)尿苷是一种尿苷类似物，具有潜在的抗癫痫作用。这类类似物可用于研究抗惊厥和抗焦虑活性，并有望用于开发新的抗高血压药物。

反应信息

• 作为反应物：
  描述：

  2',5'-di-O-trityluridine 在 吡啶 、 sodium hydroxide 、 sodium acetate 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 99.0h， 生成 1-(2',5'-di-O-trityl-β-D-xylofuranosyl)uracil
  参考文献：
  名称：

  Synthesis of 2'-C-Methylcytidine and 2'-C-Methyluridine Derivatives Modified in the 3'-Position as Potential Antiviral Agents

  摘要：

  作为我们的抗丙型肝炎计划的一部分，我们最近发现了2'-C-甲基胞苷（1）和2'-C-甲基尿苷（2），它们在细胞培养中是几种与HCV密切相关的病毒（牛病毒性腹泻病毒（BVDV）、黄热病病毒（YFV））的有效抑制剂。为了表征结构活性关系，我们对2'-C-甲基胞苷和2'-C-甲基尿苷的3'-位置进行了一些结构和功能修饰。这些迄今为止未知的合成化合物被测试其对广泛病毒的活性，结果发现它们均无效。

  DOI：

  10.1135/cccc20060991
• 作为产物：
  描述：

  4-甲氧基三苯基氯甲烷 以 吡啶 为溶剂， 生成 2',5'-di-O-trityluridine
  参考文献：
  名称：

  In search of flavivirus inhibitors: Evaluation of different tritylated nucleoside analogues

  摘要：

  Following up on a hit that was identified in a large scale cell-based antiviral screening effort, a series of triphenylmethyl alkylated nucleoside analogues were synthesized and evaluated for their in vitro antiviral activities against the dengue virus (DENV) and the yellow fever virus (YFV). Hereto, trityl moieties were attached at various positions of the sugar ring combined with subtle variations of the heterocyclic base. Several triphenylmethyl modified nucleosides were uncovered being endowed with submicromolar in vitro antiviral activity against the YFV. The most selective inhibitor in this series was 3',5'-bis-O-tritylated-5-chlorouridine (1b) affording a selectivity index of over 90, whereas the 3',5'-bis-O-tritylated inosine congener (5b) displayed the highest activity, but proved more toxic. The finding of these lipophilic structures being endowed with high antiviral activity for flaviviruses, should stimulate the interest for further structure-activity research. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.034

文献信息

• Studies on the chemistry of pyrimidine derivatives with dimethyldioxirane: synthesis, cytotoxic effect and antiviral activity of new 5,6-oxiranyl-5,6-dihydro and 5-hydroxy-5,6-dihydro-6-substituted uracil derivatives and pyrimidine nucleosides
  作者：Raffaele Saladino、Roberta Bernini、Claudia Crestini、Enrico Mincione、Alberto Bergamini、Stefano Marini、Anna Teresa Palamara

  DOI：10.1016/0040-4020(95)00380-q

  日期：1995.7

  The oxidation of uracil derivatives and pyrimidine nucleosides performed in CH2Cl2 with dimethyldioxirane afforded new 5,6-oxiranyl-5,6-dihydro and cis-/trans-5,6-dihvdroxv-5,6-dihydro-derivatives. When the oxidations were performed in the presence of methanol as nucleophile cis- and trans- 5-hydroxy-6-methoxy-5,6-dihydro derivatives were obtained in acceptable yields. Cis- and trans-1,3- dimethyl

  用二甲基二环氧乙烷在CH 2 Cl 2中进行尿嘧啶衍生物和嘧啶核苷的氧化，得到新的5，6-环氧乙烷基-5，6-二氢和顺式/反式-5，6-二羟基己酮-5，6-二氢衍生物。当在甲醇的存在下以亲核试剂的形式进行氧化时，以可接受的产率获得了顺式和反式5-羟基-6-甲氧基-5,6-二氢衍生物。通过1,3-二甲基-5,6-环氧乙烷基-5,6-二氢的亲核开环获得顺式和反式1,3-二甲基-5-羟基-6-烷基氨基-5,6-二氢尿嘧啶纯化形式的尿嘧啶。有趣的是，一些新的标题产品显示出低的细胞毒性和针对DNA和RNA病毒的选择性抗病毒活性。特别是化合物17b显示出对仙台病毒的强而有选择性的抑制作用，对单纯疱疹1病毒的影响较小。化合物17b在高浓度时也能够轻微抑制HIV-1病毒，但是在这种情况下，观察到了细胞毒性作用。
• Modified nucleosides for the treatment of viral infections and abnormal cellular proliferation
  申请人：——

  公开号：US20030087873A1

  公开（公告）日：2003-05-08

  The disclosed invention is a composition for and a method of treating a Flaviviridae (including BVDV and HCV), Orthomyxoviridae (including Influenza A and B) or Paramyxoviridae (including RSV) infection, or conditions related to abnormal cellular proliferation, in a host, including animals, and especially humans, using a nucleoside of general formula (I)-(XXIII) or its pharmaceutically acceptable salt or prodrug. This invention also provides an effective process to quantify the viral load, and in particular BVDV, HCV or West Nile Virus load, in a host, using real-time polymerase chain reaction (“RT-PCR”). Additionally, the invention discloses probe molecules that can fluoresce proportionally to the amount of virus present in a sample.

  该公开的发明涉及一种用于治疗Flaviviridae（包括BVDV和HCV）、Orthomyxoviridae（包括甲型和乙型流感）或Paramyxoviridae（包括RSV）感染或与异常细胞增殖有关的病况的组合物和方法，适用于宿主，包括动物，尤其是人类，使用通用式（I）-（XXIII）的核苷或其药学上可接受的盐或前药。该发明还提供了一种有效的过程，用于量化病毒载量，特别是BVDV、HCV或西尼罗河病毒载量，使用实时聚合酶链反应（RT-PCR）。此外，该发明揭示了可以与样本中存在的病毒数量成比例发光的探针分子。
• Stereospecific Synthesis and Anti-HIV Activity of (Z)2'- and (E)3'-Deoxy-2'(3')-C-(chloromethylene) Pyrimidine Nucleosides
  作者：Elena Kalinichenko、Elena Rubinova、Evgueny Borisov、Jan Balzarini、Erik De Clercq、Igor Mikhailopulo

  DOI：10.1080/15257779508012420

  日期：1995.5.1

  3,5)-di-O-trityl-β-D-erythro-pentofuran-3 (and 2)-ulosyl]uracil derivatives 5 and 6 with (chloromethyl)triphenylphosphorane resulted in the stereoselective formation of (E)-3′- and (Z)-2′-chloromethylene derivatives 7 (69%) and 8 (53%), respectively, deprotection of which gave 9 and 10. Transformation of the uracil nucleoside 7 into cytosine one followed by deprotection yielded 12. The latter was converted

  摘要1- [2,5（和3,5）-二-O-三苯甲基-β-D-赤型戊呋喃-3（和2）-核糖基]尿嘧啶衍生物5和6与（氯甲基）三苯基膦反应（E）-3'-和（Z）-2'-氯亚甲基衍生物7（69％）和8（53％）的立体选择性形成，其去保护基得到9和10。尿嘧啶核苷7转化为胞嘧啶之一，然后脱保护，得到12。后者被转化为阿拉伯糖苷14。测试了完全脱保护的氯亚甲基核苷对HIV-1和HIV-2的活性。
• Synthesis and anticancer and antiviral activities of various 2'- and 3'-methylidene-substituted nucleoside analogs and crystal structure of 2'-deoxy-2'-methylidenecytidine hydrochloride
  作者：Tai Shun Lin、Mei Zhen Luo、Mao Chin Liu、Regina H. Clarke-Katzenburg、Yung Chi Cheng、William H. Prusoff、William R. Mancini、George I. Birnbaum、Eric J. Gabe、Jerzy Giziewicz

  DOI：10.1021/jm00112a040

  日期：1991.8

  Various 2'- and 3'-methylidene-substituted nucleoside analogues have been synthesized and evaluated as potential anticancer and/or antiviral agents. Among these compounds, 2'-deoxy-2'-methylidene-5-fluorocytidine (22) and 2'-deoxy-2'-methylidenecytidine (23) not only demonstrated potent anticancer activity in culture against murine L1210 and P388 leukemias, Sarcoma 180, and human CCRF-CEM lymphoblastic

  已经合成了各种2'-和3'-亚甲基取代的核苷类似物，并将其评估为潜在的抗癌剂和/或抗病毒剂。在这些化合物中，2'-脱氧-2'-亚甲基-5-氟胞苷（22）和2'-脱氧-2'-亚甲基胞苷（23）不仅在培养中表现出对鼠L1210和P388白血病，肉瘤180的有效抗癌活性。 ，人CCRF-CEM淋巴母细胞性白血病，其ED50值分别为1.2和0.3 microM，0.6和0.4 microM，1.5和1.5 microM，0.05和0.03 microM，但在小鼠L1210白血病中也有活性。在所有测试的药物剂量水平（分别为25、50和75 mg / kg）中，化合物23没有毒性死亡，而化合物22在最高剂量水平下仅产生一个毒性死亡。相反，在同一项研究中，1-β-D-阿拉伯呋喃糖基胞嘧啶（ara-C）分别导致2 / 5、5 / 5和5/5毒性死亡。化合物22和23均显示出比ara-C更好的抗癌活性，产生更高的T
• A new method for introduction of a pyrene group into a terminal position of an oligonucleotide
  作者：Kazushige Yamana、Kenji Nunota、Hidehiko Nakano、Osamu Sangen

  DOI：10.1016/s0040-4039(00)77169-3

  日期：1994.4

  The method for introduction of a pyrenylmethyl group into a 5′- or 3′-terminal hydroxyl function of oligonucleotides has been described. The incorporation of pyrene into the 5′-end was accomplished by preparation of 5′-(1-pyrenylmethyl)thymidine 3′-phosphorobisdiethylamidite which was used for the solid-phase synthesis of 5′-pyrene-modified oligonucleotides. 5′-Dimethoxytrityl 3′-(1-pyrenylmethyl)uridine

  已经描述了将a烯基甲基引入寡核苷酸的5'-或3'-末端羟基官能团的方法。通过制备5'-（1-吡啶基甲基）胸苷3'-磷酸双二乙基酰胺基铝来完成将of掺入5'-末端，该固相用于5'-py修饰的寡核苷酸的固相合成。制备了5'-二甲氧基三苯甲基3'-（1-苯甲基甲基）尿苷负载的二氧化硅，并将其用于3'-修饰的寡核苷酸的固相合成。如此合成的寡核苷酸-re偶联物的纯化通过反相HPLC进行。与互补DNA杂交形成后，这些寡核苷酸的荧光没有被淬灭。