(2S-反式)-1-[2,5-二氢-5-(羟甲基)-2-呋喃基]-5-甲基-2,4(1H,3H)-嘧啶二酮 | 84414-90-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 中文名称: (2S-反式)-1-[2,5-二氢-5-(羟甲基)-2-呋喃基]-5-甲基-2,4(1H,3H)-嘧啶二酮
• 英文名称: 1-(2,3-dideoxy-α-D-glycero-pent-2-enofuranosyl)thymine
• 英文别名: 1-[(2S,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 84414-90-4
• 化学式: C₁₀H₁₂N₂O₄
• mdl: MFCD00132921
• 分子量: 224.216
• InChiKey: XNKLLVCARDGLGL-YUMQZZPRSA-N

物化性质

• 密度：
  1.374±0.06 g/cm3 (20 ºC 760 Torr)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 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：

  (2S-反式)-1-[2,5-二氢-5-(羟甲基)-2-呋喃基]-5-甲基-2,4(1H,3H)-嘧啶二酮 在 水合三氯化钌 、 potassium persulfate 、 potassium hydroxide 作用下， 反应 8.0h， 以50%的产率得到1-(2,3-didehydro-2,3-dideoxy-β-d-pentofuranosyl-4-carboxy)thymine
  参考文献：
  名称：

  A new class of pyrimidine nucleosides: inhibitors of hepatitis B and C viruses

  摘要：

  Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are major health threats worldwide leading to liver cirrhosis, liver cancer and mortality. Herein, we report a new category of dideoxy pyrimidine nucleosides possessing a 4'-carboxyl (or carboxymethyl) function (7-9, 13, 16, 17), which are discovered as potential antiviral agents. For the first time, these nucleosides are recognized to be inhibitors of HBV and/or HCV replication. Among 4'-carboxy compounds, 3',4'-didehydrothymidine (16) was most effective against DHBV, HBV and HCV. Modification of the 4'-position in compound 7 from a carboxyl to carboxymethyl group (17) did not affect the anti-HBV activity but greatly increased the anti-HCV activity. Importantly, 17 yielded synergistic antiviral effect when combined with ribavirin without toxicity. The activity exhibited by a single agent towards both hepatitis viruses and no detectable in vitro cytotoxicity make this new class of compounds of interest. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.042
• 作为产物：
  描述：

  2-deoxy-D-ribose 在 咪唑 、 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 4 A molecular sieve 、 Dowex ^R 50W 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 6-methyl-2,4-bis(trimethylsiloxy)pyrimidine 作用下， 以 吡啶 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2S-反式)-1-[2,5-二氢-5-(羟甲基)-2-呋喃基]-5-甲基-2,4(1H,3H)-嘧啶二酮
  参考文献：
  名称：

  从2-脱氧核糖轻松合成2'，3'-不饱和核苷

  摘要：

  描述了一种从2-脱氧核糖开始合成2'，3'-不饱和核苷的直接方法。这种新颖的途径涉及两种新方法：（1）通过2-脱氧核糖和苯硫酚的直接缩合制备2-脱氧-1-硫代呋喃核糖苷，（2）通过2,3-不饱和的1-硫喷呋喃糖苷与嘧啶碱基的直接偶联形成核苷骨架。

  DOI：

  10.1016/0040-4039(96)01293-2

文献信息

• Synthesis of 2′-Azido, 2,2′-Anhydro and 2′,5′-Anhydro Nucleosides with Potential Anti-HIV Activity
  作者：Ahmed E. -S. Abdel-Megied、Erik B. Pedersen、Carsten M. Nielsen

  DOI：10.1055/s-1991-26454

  日期：——

  Reaction of methyl 2-bromo-2,3-dideoxy-5-O-(4-methylbenzoyl)-D-erythro-pentofuranoside (7) with silylated uracils 9 using trimethylsilyl triflate as catalyst afforded the corresponding 2′-bromonucleosides 10. 2,3-Didehydro sugar 8 was prepared by heating 7 with sodium azide in dimethylformamide. 2,2′-Anhydro nucleosides 1 were prepared by treating the nucleosides 10 with sodium methoxide at room temperature. 1-(2-Azido-2,3-dideoxy-β-D-threo-pentofuranosyl)thymine (15) and its α-anomer (16) were prepared by treating 10c with sodium azide and subsequently methanolic ammonia. Treatment of 1-(2-bromo-2,3-dideoxy-α-D-erythro-pentofuranosyl)thymine (11 c) with excess of sodium methoxide under reflux gave the corresponding 2′,5'′anhydro nucleoside 17.

  以三甲基硅烷基三氟甲烷为催化剂，将 2-溴-2,3-二脱氧-5-O-(4-甲基苯甲酰基)-D-赤式戊呋喃糖苷（7）与硅化尿嘧啶 9 反应，得到相应的 2′-溴核苷 10。将 7 与叠氮化钠在二甲基甲酰胺中加热，制备出 2,3-二脱氢糖 8。室温下用甲醇钠处理核苷 10，制备 2,2′-脱氢核苷 1。1-(2-Azido-2,3-dideoxy-δ²-D-threo-pentofuranosyl)thymine (15) 及其 δ-anomer (16) 是用叠氮化钠和甲醇氨处理 10c 而制备的。在回流条件下，用过量甲醇钠处理 1-(2-溴-2,3-二脱氧-δ-D-赤式-戊呋喃糖基)胸腺嘧啶(11 c)，可得到相应的 2′,5'′脱氢核苷 17。
• Antiviral Activity of Lipophilic Nucleoside Tetraphosphate Compounds
  作者：Xiao Jia、Dominique Schols、Chris Meier

  DOI：10.1021/acs.jmedchem.3c02022

  日期：2024.2.22

  characterization of three types of nucleoside tetraphosphate derivatives 4–9 acting as potential prodrugs of d4T nucleotides: (i) the δ-phosph(on)ate is modified by two hydrolytically stable alkyl residues 4 and 5; (ii) the δ-phosph(on)ate is esterified covalently by one biodegradable acyloxybenzyl moiety and a nonbioreversible moiety 6 and 7; or (iii) the δ-phosphate of nucleoside tetraphosphate is masked by

  我们报道了三种类型的核苷四磷酸衍生物 4-9 的合成和表征，这些衍生物充当 d4T 核苷酸的潜在前药：（i） δ-磷酸盐被两个水解稳定的烷基残基 4 和 5 修饰;（ii） δ-磷酸盐被一个可生物降解的酰氧基苄基部分和一个不可生物可逆的部分 6 和 7 共价酯化;或 （iii） 核苷四磷酸的 δ-磷酸盐被两个可生物降解的前药组 8 和 9 掩盖。我们能够证明 d4T 三磷酸盐 （d4TTP， （i））、δ-单烷基化 d4T 四磷酸盐 （20 和 24， （ii）） 和 d4T 四磷酸盐 （d4T4P， （iii）） 的有效释放，分别通过化学或酶法过程。令人惊讶的是，δ-二烷基化的 d4T 四磷酸盐、δ-单烷基化的 d4T 四磷酸盐和 d4T4P 是 HIV-RT 的底物。值得注意的是，与 CEM/TK– 细胞中的母体 d4T 相比，TetraPPPPro-prodrug 7 的抗病毒活性提高了
• Facile synthesis of 2′,3′-unsaturated nucleosides from 2-deoxyribose
  作者：Keiko Sujino、Tomoyasu Yoshida、Hideyuki Sugimura

  DOI：10.1016/0040-4039(96)01293-2

  日期：1996.8

  A straightforward approach for the synthesis of 2′,3′-unsaturated nucleosides starting from 2-deoxyribose is described. This novel route involves two new methods; (1) preparation of 2-deoxy-1-thioribofuranoside by direct condensation of 2-deoxyribose and thiophenol, (2) formation of the nucleoside skeleton by the direct coupling of 2,3-unsaturated 1-thiopentofuranoside with pyrimidine bases.

  描述了一种从2-脱氧核糖开始合成2'，3'-不饱和核苷的直接方法。这种新颖的途径涉及两种新方法：（1）通过2-脱氧核糖和苯硫酚的直接缩合制备2-脱氧-1-硫代呋喃核糖苷，（2）通过2,3-不饱和的1-硫喷呋喃糖苷与嘧啶碱基的直接偶联形成核苷骨架。
• A new class of pyrimidine nucleosides: inhibitors of hepatitis B and C viruses
  作者：Neeraj Shakya、Satish Vedi、Chao Liang、Babita Agrawal、D. Lorne Tyrrell、Rakesh Kumar

  DOI：10.1016/j.bmcl.2012.08.042

  日期：2012.10

  Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are major health threats worldwide leading to liver cirrhosis, liver cancer and mortality. Herein, we report a new category of dideoxy pyrimidine nucleosides possessing a 4'-carboxyl (or carboxymethyl) function (7-9, 13, 16, 17), which are discovered as potential antiviral agents. For the first time, these nucleosides are recognized to be inhibitors of HBV and/or HCV replication. Among 4'-carboxy compounds, 3',4'-didehydrothymidine (16) was most effective against DHBV, HBV and HCV. Modification of the 4'-position in compound 7 from a carboxyl to carboxymethyl group (17) did not affect the anti-HBV activity but greatly increased the anti-HCV activity. Importantly, 17 yielded synergistic antiviral effect when combined with ribavirin without toxicity. The activity exhibited by a single agent towards both hepatitis viruses and no detectable in vitro cytotoxicity make this new class of compounds of interest. (c) 2012 Elsevier Ltd. All rights reserved.