1-(2′-deoxy-α-L-threofuranosyl)thymine | 1333503-71-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-(2′-deoxy-α-L-threofuranosyl)thymine
• 英文别名: 1-((2R,4R)-tetrahydro-4-hydroxyfuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione；1-[(2R,4R)-4-hydroxytetrahydrofuran-2-yl]-5-methyl-pyrimidine-2,4-dione；1-[(2R,4R)-4-hydroxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 1333503-71-1
• 化学式: C₉H₁₂N₂O₄
• 分子量: 212.205
• InChiKey: IVRVAANQRDJDJX-RNFRBKRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2′-deoxy-α-L-threofuranosyl)thymine 在 carboxypeptidase Y 、 叔丁基氯化镁 、 水 作用下， 以 四氢呋喃 、 氘代丙酮 为溶剂， 反应 32.5h， 生成
  参考文献：
  名称：

  Synthesis and antiviral evaluation of α-l-2′-deoxythreofuranosyl nucleosides

  摘要：

  The synthesis of a series of alpha-L-2'-deoxythreofuranosyl nucleosides featuring the nucleobases A, T, C and U is described in seven steps from 1,2-O-isopropyledene-alpha-L-threose, involving a Vorbruggen coupling and a Barton-McCombie deoxygenation protocol as the key steps. All analogues, including a phosphoramidate nucleoside phosphate prodrug of the T analogue, were evaluated against a broad panel of different viruses but found inactive, while also lacking notable cellular toxicity. The thymidine analogue showed inhibition to mitochondrial thymidine kinase-2 (TK-2), herpes simplex virus type 1 (HSV-1) TK, varicella-zoster virus (VZV) TK and Mycobacterium tuberculosis thymidylate kinase. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.036
• 作为产物：
  描述：

  O,O-二(三甲基甲硅烷基)胸苷 在 甲醇 、 4-二甲氨基吡啶 、 对甲苯基氯化亚硫代甲酸 、 三氟甲磺酸三甲基硅酯 、 palladium 10% on activated carbon 、 氨 、 氢气 作用下， 以 甲醇 、 1,2-二氯乙烷 、 乙腈 为溶剂， 100.0 ℃ 、101.33 kPa 条件下， 反应 4.0h， 生成 1-(2′-deoxy-α-L-threofuranosyl)thymine
  参考文献：
  名称：

  Synthesis and antiviral evaluation of α-l-2′-deoxythreofuranosyl nucleosides

  摘要：

  The synthesis of a series of alpha-L-2'-deoxythreofuranosyl nucleosides featuring the nucleobases A, T, C and U is described in seven steps from 1,2-O-isopropyledene-alpha-L-threose, involving a Vorbruggen coupling and a Barton-McCombie deoxygenation protocol as the key steps. All analogues, including a phosphoramidate nucleoside phosphate prodrug of the T analogue, were evaluated against a broad panel of different viruses but found inactive, while also lacking notable cellular toxicity. The thymidine analogue showed inhibition to mitochondrial thymidine kinase-2 (TK-2), herpes simplex virus type 1 (HSV-1) TK, varicella-zoster virus (VZV) TK and Mycobacterium tuberculosis thymidylate kinase. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.036

文献信息

• Synthesis of 2′-Deoxy-α-<scp>l</scp>-threofuranosyl Nucleoside Triphosphates
  作者：Saikat Bala、Jen-Yu Liao、Li Zhang、Chantel N. Tran、Nicholas Chim、John C. Chaput

  DOI：10.1021/acs.joc.8b00875

  日期：2018.8.17

  describe the chemical synthesis and polymerase recognition of 2′-deoxy-α-l-threofuranosyl nucleoside 3′-triphosphates (dtNTPs) as chain-terminating reagents in a polymerase-mediated TNA synthesis reaction. The synthesis of dtNTPs should make it possible to investigate the mechanism of TNA synthesis by X-ray crystallography by trapping the polymerase in the catalytically active conformation.

  α-升-苏呋喃糖基核酸（TNA）是一种人工遗传聚合物，其中RNA中发现的天然五碳核糖已被非天然四碳苏糖替代。尽管糖-磷酸骨架不同，TNA仍能与自身以及互补的DNA和RNA链形成稳定的，反平行的Watson-Crick双链体结构。系统间碱基配对的这种特性，加上苏糖相对于核糖的化学简单性，为TNA作为生命进化中的候选RNA祖细胞提供了支持。为了通过体外进化评估TNA的功能特性，已开发出能够在DNA和TNA之间来回复制信息的工程聚合酶。然而，相对于其天然对应物，当前一代的TNA聚合酶的活性降低，这限制了TNA作为原始遗传物质的评估。在这里，我们描述2'-deoxy-α-的化学合成和聚合酶识别在聚合酶介导的TNA合成反应中，1-链呋喃呋喃糖基核苷3'-三磷酸酯（dtNTPs）作为链终止剂。dtNTPs的合成应有可能通过将聚合酶捕获在催化活性构象中，从而通过X射线晶体学研究TNA合成的机理。
• Synthesis and antiviral evaluation of α-l-2′-deoxythreofuranosyl nucleosides
  作者：Kiran S. Toti、Marco Derudas、Christopher McGuigan、Jan Balzarini、Serge Van Calenbergh

  DOI：10.1016/j.ejmech.2011.05.036

  日期：2011.9

  The synthesis of a series of alpha-L-2'-deoxythreofuranosyl nucleosides featuring the nucleobases A, T, C and U is described in seven steps from 1,2-O-isopropyledene-alpha-L-threose, involving a Vorbruggen coupling and a Barton-McCombie deoxygenation protocol as the key steps. All analogues, including a phosphoramidate nucleoside phosphate prodrug of the T analogue, were evaluated against a broad panel of different viruses but found inactive, while also lacking notable cellular toxicity. The thymidine analogue showed inhibition to mitochondrial thymidine kinase-2 (TK-2), herpes simplex virus type 1 (HSV-1) TK, varicella-zoster virus (VZV) TK and Mycobacterium tuberculosis thymidylate kinase. (C) 2011 Elsevier Masson SAS. All rights reserved.