1-(2-deoxy-β-D-erythro-pentofuranosyl)-5-(oct-1-ynyl)uracil | 125422-08-4

• 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: 1-(2-deoxy-β-D-erythro-pentofuranosyl)-5-(oct-1-ynyl)uracil
• 英文别名: α-heptylidynethymidine；1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-oct-1-ynylpyrimidine-2,4-dione
• CAS: 125422-08-4
• 化学式: C₁₇H₂₄N₂O₅
• 分子量: 336.388
• InChiKey: VNEIDGLVUYVVJS-RRFJBIMHSA-N

物化性质

• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2-deoxy-β-D-erythro-pentofuranosyl)-5-(oct-1-ynyl)uracil 在 TEA 、 硫代乙酸 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 26.0h， 生成 6-Hexyl-3-((2R,4S,5R)-4-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-3H-thieno[2,3-d]pyrimidin-2-one
  参考文献：
  名称：

  Bicyclic anti-VZV nucleosides: Thieno analogues retain full antiviral activity

  摘要：

  Thieno analogues of the potent and selective furo-pyrimidine anti-VZV nucleoside family are herein reported. The compounds retain full antiviral potency in comparison to the furo parent. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00471-1
• 作为产物：
  描述：

  1-辛炔 、 碘苷 在 copper(l) iodide 、 四(三苯基膦)钯 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以78%的产率得到1-(2-deoxy-β-D-erythro-pentofuranosyl)-5-(oct-1-ynyl)uracil
  参考文献：
  名称：

  具有二炔基侧链的核苷和寡核苷酸：2'-脱氧尿苷衍生物的碱基配对和铜（I）催化的AlkyneAzide'Click'Cycloaddition的功能化

  摘要：

  描述了包含带有5个取代的2'-脱氧尿苷1b或1d的带有侧链CC端的侧链的寡核苷酸，并将其双链体稳定性与包含5个炔基化合物1a或1c的侧链中只有一个非末端CC键的寡核苷酸进行了比较。。为此，在Sonogashira交叉偶联反应（方案1）中，使用5-碘-2'-脱氧尿苷（3）和二炔或炔作为起始原料。制备了亚磷酰胺2b – d（方案3），并将其用作固相合成的基础。Ť米测量表明，含有辛-1,7-二炔基侧链或二丙酸-2-炔基醚残基，DNA双链体即，含有1B或1D，比仅含有一个三键的那些更稳定的，即，图1A或1C（表3）。通过使用Cu I催化的Huisgen–Meldal–Sharpless [2 + 3]环加成（“点击化学”）方案（方案2），将二炔修饰的核苷用于进一步的官能化反应。脂族叠氮化物，即3'-叠氮基3'-脱氧胸苷（AZT; 4）以及芳香族叠氮化合物5与末端炔基相连，分别得到1 H -1,2,

  DOI：

  10.1002/hlca.200790055

文献信息

• Potent and Selective Inhibition of Varicella-Zoster Virus (VZV) by Nucleoside Analogues with an Unusual Bicyclic Base
  作者：Christopher McGuigan、Christopher J. Yarnold、Garry Jones、Sonsoles Velázquez、Hubert Barucki、Andrea Brancale、Graciela Andrei、Robert Snoeck、Erik De Clercq、Jan Balzarini

  DOI：10.1021/jm990346o

  日期：1999.11.1

  We herein report the discovery of an entirely new category of potent antiviral agents based on novel deoxynucleoside analogues with unusual bicyclic base moieties. Target structures, previously known as byproducts in Pd-catalyzed coupling of terminal alkynes with 5-iodo-nucleosides, are recognized herein for the first time to be potent and selective inhibitors of varicella-zoster virus (VZV) in vitro. As an unusual structure-activity relationship we noted the absolute requirement of a long alkyl side chain, with an optimum length of C-8-C-10, for antiviral activity. We thus report the synthesis and characterization of a series of chain-modified analogues and their extensive in vitro evaluation. The lead compounds have a ca. 300-fold enhancement in anti-VZV activity over the reference compound acyclovir, with no detectable in vitro cytotoxicity. The novel structure of these compounds, coupled with their ease of synthesis, excellent antiviral profile, and promising physical properties, makes them of great interest for possible antiviral drug development.
• Nucleosides and Oligonucleotides with Diynyl Side Chains: Base Pairing and Functionalization of 2′-Deoxyuridine Derivatives by the Copper(I)-Catalyzed AlkyneAzide ‘Click’ Cycloaddition
  作者：Frank Seela、Venkata Ramana Sirivolu

  DOI：10.1002/hlca.200790055

  日期：2007.3

  cycloaddition (‘click chemistry’) (Scheme 2). An aliphatic azide, i. e., 3′-azido-3′-deoxythymidine (AZT; 4), as well as the aromatic azido compound 5 were linked to the terminal alkyne group resulting in 1H-1,2,3-triazole-modified derivatives 6 and 7, respectively (Scheme 2), of which 6 forms a stable duplex DNA (Table 3). The Husigen–Meldal–Sharpless cycloaddition was also performed with oligonucleotides (Schemes 4

  描述了包含带有5个取代的2'-脱氧尿苷1b或1d的带有侧链CC端的侧链的寡核苷酸，并将其双链体稳定性与包含5个炔基化合物1a或1c的侧链中只有一个非末端CC键的寡核苷酸进行了比较。。为此，在Sonogashira交叉偶联反应（方案1）中，使用5-碘-2'-脱氧尿苷（3）和二炔或炔作为起始原料。制备了亚磷酰胺2b – d（方案3），并将其用作固相合成的基础。Ť米测量表明，含有辛-1,7-二炔基侧链或二丙酸-2-炔基醚残基，DNA双链体即，含有1B或1D，比仅含有一个三键的那些更稳定的，即，图1A或1C（表3）。通过使用Cu I催化的Huisgen–Meldal–Sharpless [2 + 3]环加成（“点击化学”）方案（方案2），将二炔修饰的核苷用于进一步的官能化反应。脂族叠氮化物，即3'-叠氮基3'-脱氧胸苷（AZT; 4）以及芳香族叠氮化合物5与末端炔基相连，分别得到1 H -1,2,
• Bicyclic anti-VZV nucleosides: Thieno analogues retain full antiviral activity
  作者：Andrea Brancale、Christopher McGuigan、Berthe Algain、Pascal Savy、Rachid Benhida、Jean-Louis Fourrey、Graciela Andrei、Robert Snoeck、Erik De Clercq、Jan Balzarini

  DOI：10.1016/s0960-894x(01)00471-1

  日期：2001.9

  Thieno analogues of the potent and selective furo-pyrimidine anti-VZV nucleoside family are herein reported. The compounds retain full antiviral potency in comparison to the furo parent. (C) 2001 Elsevier Science Ltd. All rights reserved.