5-(benzyloxy)methyl-2′-deoxyuridine | 19083-35-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 5-(benzyloxy)methyl-2′-deoxyuridine
• 英文别名: 5-[(benzyloxy)methyl]-2'-deoxyuridine；5-(benzyl)oxymethyl-2'-deoxyuridine；5-benzyloxymethyl-2'-deoxyuridine；α-benzyloxy-thymidine；3-<2-Desoxy-β,D-ribofuranosyl>-5-benzyloxymethyl-uracil；5-Benzyloxymethyl-2'-desoxy-uridin；5-Benzyloxymethyl-1-(4-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-1H-pyrimidine-2,4-dione；1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(phenylmethoxymethyl)pyrimidine-2,4-dione
• CAS: 19083-35-3
• 化学式: C₁₇H₂₀N₂O₆
• 分子量: 348.356
• InChiKey: GQDUJQWJZIRFKA-RRFJBIMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-(benzyloxy)methyl-2′-deoxyuridine 在 钯 氮气 、 氢气 作用下， 以 乙醇 为溶剂， 反应 0.58h， 以to yield thymidine (18 mg, 88%) that的产率得到beta-胸苷
  参考文献：
  名称：

  Nucleotides and nucleosides and methods for their use in DNA sequencing

  摘要：

  本发明涉及标记和未标记的可割断终止基团以及DNA测序和其他类型的DNA分析方法。更具体地，该发明部分涉及具有化学可割断、光解、酶解或非光解基团的核苷酸和核苷以及其在DNA测序中的使用及其在生物医学研究中的应用。

  公开号：

  US09200319B2
• 作为产物：
  描述：

  四乙酰核糖 在 4-二甲氨基吡啶 、 sodium hydroxide 、 N,O-双三甲硅基乙酰胺 、 偶氮二异丁腈 、 三氟甲磺酸三甲基硅酯 、 四丁基氟化铵 、 三正丁基氢锡 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 水 、 甲苯 、 乙腈 为溶剂， 反应 60.58h， 生成 5-(benzyloxy)methyl-2′-deoxyuridine
  参考文献：
  名称：

  Aromaticvs. Carbohydrate Residues in the Major Groove: Synthesis of 5-[(Benzyloxy)methyl]pyrimidine Nucleosides and Their Incorporation into Oligonucleotides

  摘要：

  The synthesis of 5-[(benzyloxy)methyl]-substituted pyrimidine 2'-deoxynucleosides 14 and 15 starting from the uracil derivative 6 and tetra-O-acetyl-D-ribose is described (Schemes 1-3). These nucleosides were converted to the corresponding cyanoethyl phosphoramidites 18 and 19, respectively, and incorporated into oligodeoxynucleotide decamers. The 5-[(benzyloxy)methyl]-nucleoside building blocks T-bo(d) and C-bom(d) (bo = benzyloxy, bom = (benzyloxy)methyl) - shape analogs of the naturally occurring glucosylated nucleosides 1 and 2 (see Fig. 1) - lead to weaker binding affinities of oligodeoxynucleotides pairing to DNA as well as RNA complements. The modification is more destabilizing in the case of T-bo(d) than C-bom(d). Analysis of the thermodynamics of duplex formation shows that T-bo(d) and C-bom(d), incorporation leads to a smaller entropy change in duplex formation that is, however, overcompensated by a less Favorable enthalpy term. Molecular-modeling studies suggest that the benzyl groups reside in the major groove which would explain the improved pairing entropy as a result of the exclusion of ordered H2O.

  DOI：

  10.1002/1522-2675(20000809)83:8<1962::aid-hlca1962>3.0.co;2-8

文献信息

• NUCLEOTIDES AND NUCLEOSIDES AND METHODS FOR THEIR USE IN DNA SEQUENCING
  申请人：LITOSH Vladislav A.

  公开号：US20100041041A1

  公开（公告）日：2010-02-18

  The present invention relates generally to labeled and unlabled cleavable terminating groups and methods for DNA sequencing and other types of DNA analysis. More particularly, the invention relates in part to nucleotides and nucleosides with chemically cleavable, photocleavable, enzymatically cleavable, or non-photocleavable groups and methods for their use in DNA sequencing and its application in biomedical research.

  本发明涉及标记和未标记的可断裂终止基团以及用于DNA测序和其他类型的DNA分析的方法。更具体地，本发明部分涉及具有化学可断裂、光解、酶解或非光解基团的核苷酸和核苷以及它们在DNA测序中的使用及其在生物医学研究中的应用。
• Nucleotides and Nucleosides and Methods for their Use in DNA Sequencing
  申请人：Litosh Vladislav A.

  公开号：US20130035237A1

  公开（公告）日：2013-02-07

  The present invention relates generally to labeled and unlabled cleavable terminating groups and methods for DNA sequencing and other types of DNA analysis. More particularly, the invention relates in part to nucleotides and nucleosides with chemically cleavable, photocleavable, enzymatically cleavable, or non-photocleavable groups and methods for their use in DNA sequencing and its application in biomedical research.

  本发明通常涉及带有标记和未标记的可断裂终止基团及其在DNA测序和其他类型的DNA分析中的方法。更具体地，本发明部分涉及具有化学可断裂、光解、酶解或非光解基团的核苷酸和核苷以及它们在DNA测序中的应用及其在生物医学研究中的应用方法。
• Fast Access to 5-Hydroxymethyl Derivatives of 2′-Deoxyuridine Promoted by Acidic Amberlyst 15 Resin
  作者：D. Guianvarc’h、G. Doisneau、D. Liu、O. Monfret、Y. Bourdreux、D. Urban

  DOI：10.1055/a-1961-7251

  日期：2023.1

  5-hydroxymethylated derivatives of pyrimidine nucleosides are an important class of biologically relevant compounds. In addition, such derivatives and related compounds can be functionalized for various applications. To enable fast, economical and efficient access to 5-hydroxymethylated derivatives of 2’-deoxyuridine, we report a method of O-5 chemoselective transformation of unprotected 5-hydroxy

  嘧啶核苷的 5-羟甲基化衍生物是一类重要的生物学相关化合物。此外，这些衍生物和相关化合物可以被功能化以用于各种应用。为了能够快速、经济和有效地获得 2'-脱氧尿苷的 5-羟甲基化衍生物，我们报告了一种 O-5 化学选择性转化未受保护的 5-羟甲基-2'-脱氧尿苷 (5hmdU) 的方法，该方法依赖于在存在的情况下的选择性醚化酒精在室温下由酸性 Amberlyst 15 树脂促进。与先前描述的严酷条件相比，这些温和条件构成了显着改善。适用于各种伯醇或仲醇，反应底物范围广，合成了5hmdU的24 C-5修饰衍生物，分离收率高。
• Base-modified thymidines capable of terminating DNA synthesis are novel bioactive compounds with activity in cancer cells
  作者：Kayla M. Borland、Safnas F. AbdulSalam、Morwena J. Solivio、Matthew P. Burke、Patrick R. Wolfkiel、Sean M. Lawson、Courtney A. Stockman、Joel M. Andersen、Skyler Smith、Julia N. Tolstolutskaya、Purujit N. Gurjar、Aron P. Bercz、Edward J. Merino、Vladislav A. Litosh

  DOI：10.1016/j.bmc.2015.01.057

  日期：2015.4

  Current FDA-approved chemotherapeutic antimetabolites elicit severe side effects that warrant their improvement; therefore, we designed compounds with mechanisms of action focusing on inhibiting DNA replication rather than targeting multiple pathways. We previously discovered that 5-(alpha-substituted-2-nitrobenzyloxy)methyluridine-5 '-triphosphates were exquisite DNA synthesis terminators; therefore, we synthesized a library of 35 thymidine analogs and evaluated their activity using an MTT cell viability assay of MCF7 breast cancer cells chosen for their vulnerability to these nucleoside derivatives. Compound 3a, having an alpha-tert-butyl-2-nitro-4-(phenyl)alkynylbenzyloxy group, showed an IC50 of 9 +/- 1 mu M. The compound is more selective for cancer cells than for fibroblast cells compared with 5-fluorouracil. Treatment of MCF7 cells with 3a elicits the DNA damage response as indicated by phosphorylation of gamma-H2A. A primer extension assay of the 5 '-triphosphate of 3a revealed that 3aTP is more likely to inhibit DNA polymerase than to lead to termination events upon incorporation into the DNA replication fork. (C) 2015 Elsevier Ltd. All rights reserved.
• Megied, Ahmed E.-S. Abdel; Ali, Omar M.; Kofoed, Thomas, Nucleosides and nucleotides, 2001, vol. 20, # 1-2, p. 1 - 10
  作者：Megied, Ahmed E.-S. Abdel、Ali, Omar M.、Kofoed, Thomas、Pedersen, Erik B.

  DOI：——

  日期：——