O^3'-acetyl-5'-oxo-5'-deoxy-thymidine | 5983-15-3

• 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: O^3'-acetyl-5'-oxo-5'-deoxy-thymidine
• 英文别名: [(2S,3S,5R)-2-formyl-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] acetate
• CAS: 5983-15-3
• 化学式: C₁₂H₁₄N₂O₆
• 分子量: 282.253
• InChiKey: ZHWPHNXXVHXCPL-IVZWLZJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  O^3'-acetyl-5'-oxo-5'-deoxy-thymidine 在 palladium on activated charcoal 、 N,N'-羰基二咪唑 sodium pyrophosphate 、 sodium hydroxide 、 三正丁胺 、 Dowex 50W-X₂ pyridinium form 、 snake venom phosphodiesterase I 、 ammonium acetate 、 氢气 、 magnesium chloride 作用下， 以 1,4-二氧六环 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 242.0h， 生成 5'-phosphonomethyl-5'-deoxythymidine diphosphate
  参考文献：
  名称：

  The Analogue of Thymidine Triphosphate Containing a Methylene Group in Place of the 5′ Oxygen Can Serve as a Substrate for Reverse Transcriptase

  摘要：

  The thymidine 5'-triphosphate analogue containing a methylene group in place of the 5' oxygen atom can be prepared using modifications of published procedures and can substitute for the natural thymidine triphosphate in chain extension reactions catalyzed by Moloney-MLV reverse transcriptase. Using rabbit P-globin mRNA as the template together with an appropriate primer, the enzyme readily makes full-length DNA transcripts in which all thymidine 5' oxygen atoms have been replaced with methylene groups. In sequence analyses using the partial depurination procedure, the analogue DNA transcript produces electrophoretic gel patterns identical with those of the corresponding natural DNA transcript. Experiments on second strand synthesis using the four regular triphosphates show that the analogue DNA transcript, like the natural transcript, can serve as a template. The two DNA duplexes (natural/natural and analogue/natural) formed by these reactions produce similar electrophoretic cleavage patterns when treated with either of the endonucleases HaeIII and EcoRI. However, further studies on template properties indicate that, while the enzyme makes a full-length product when using the analogue substrate with a natural DNA strand as template, it appears unable to use the analogue transcript as template with the analogue triphosphate as substrate during second strand synthesis. Preliminary experiments have also been carried out with a DNA polymerase. No products are detected in reactions using Taq polymerase with PCR protocols containing the analogue triphosphate as the only source of thymidine.

  DOI：

  10.1081/ncn-120022031
• 作为产物：
  描述：

  3'-O-acetylthymidine 在 吡啶 、 三氟乙酸吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二甲基亚砜 为溶剂， 生成 O^3'-acetyl-5'-oxo-5'-deoxy-thymidine
  参考文献：
  名称：

  The Analogue of Thymidine Triphosphate Containing a Methylene Group in Place of the 5′ Oxygen Can Serve as a Substrate for Reverse Transcriptase

  摘要：

  The thymidine 5'-triphosphate analogue containing a methylene group in place of the 5' oxygen atom can be prepared using modifications of published procedures and can substitute for the natural thymidine triphosphate in chain extension reactions catalyzed by Moloney-MLV reverse transcriptase. Using rabbit P-globin mRNA as the template together with an appropriate primer, the enzyme readily makes full-length DNA transcripts in which all thymidine 5' oxygen atoms have been replaced with methylene groups. In sequence analyses using the partial depurination procedure, the analogue DNA transcript produces electrophoretic gel patterns identical with those of the corresponding natural DNA transcript. Experiments on second strand synthesis using the four regular triphosphates show that the analogue DNA transcript, like the natural transcript, can serve as a template. The two DNA duplexes (natural/natural and analogue/natural) formed by these reactions produce similar electrophoretic cleavage patterns when treated with either of the endonucleases HaeIII and EcoRI. However, further studies on template properties indicate that, while the enzyme makes a full-length product when using the analogue substrate with a natural DNA strand as template, it appears unable to use the analogue transcript as template with the analogue triphosphate as substrate during second strand synthesis. Preliminary experiments have also been carried out with a DNA polymerase. No products are detected in reactions using Taq polymerase with PCR protocols containing the analogue triphosphate as the only source of thymidine.

  DOI：

  10.1081/ncn-120022031

文献信息

• Potential inhibitors of nucleotide biosynthesis. 2. Halomethyl ketone derivatives of pyrimidine nucleosides
  作者：John A. Montgomery、H. Jeanette Thomas、R. Wallace Brockman、Robert D. Elliott

  DOI：10.1021/jm00371a022

  日期：1984.5

  Several halomethyl ketone derivatives of pyrimidine nucleosides have been prepared for evaluation as cytotoxic agents. The first series are 1-(8-halo-2,5,6,8- tetradeoxy -beta-D-erythro-oct-7 - ulofuranosyl )thymines (7-9), whereas the second type are halo derivatives of acetophenone (12-14 and 16). These compounds are cytotoxic, and one (13) showed activity against the P388 leukemia in vivo.

  已经制备了嘧啶核苷的几种卤代甲基酮衍生物作为细胞毒性剂进行评估。第一个系列是1-（8-卤代2,5,6,8-四脱氧-β-D-赤型-辛-7-呋喃呋喃糖基）胸腺嘧啶（7-9），而第二种是乙酰苯的卤代衍生物（ 12-14和16）。这些化合物具有细胞毒性，其中一种（13）在体内具有抗P388白血病的活性。
• Mellor, Ben J.; Thomas, Eric J., Journal of the Chemical Society. Perkin transactions I, 1998, # 4, p. 747 - 757
  作者：Mellor, Ben J.、Thomas, Eric J.

  DOI：——

  日期：——
• Ligands for the affinity chromatography of mammalian thymidine kinase 1: Strategy, synthesis and evaluation
  作者：Rainer A. Beck、Birgitte Munch-Petersen、Michael Dölker、Lisbet Cloos、Gerda Tyrsted、Kurt Eger

  DOI：10.1016/s0031-6865(96)00029-5

  日期：1996.10

  Selected thymidine derivatives were synthesized with various spacers and fixed as model compounds at position N-3', C-5, C-3' and C-5', respectively, to simulate the preparation of an affinity gel matrix. Compounds 3, 6, 7 and 9 were evaluated for their effect on pure human cytosolic thymidine kinase (TK). All four compounds showed competitive inhibition with respect to thymidine, with Ki-values between 80 and 1000 microM. In the same positions as the model compounds were bound to the spacers thymidine derivatives were coupled with different Sepharose gel matrices. These affinity matrices were tested for isolation of thymidine kinase out of placental enzyme material. Except for one matrix, more than 98% of the applied activity was retained by the affinity matrices tested. The strongest binding to the enzyme resulted from a fixation at C-5' of the thymidine molecule to the gel matrix.
• Diazomethyl ketone derivatives of pyrimidine nucleosides
  作者：John A. Montgomery、H. Jeanette Thomas

  DOI：10.1021/jo00316a021

  日期：1981.1
• Meggers, Eric; Dussy, Adrian; Schaefer, Thomas, Chemistry - A European Journal, 2000, vol. 6, # 3, p. 485 - 492
  作者：Meggers, Eric、Dussy, Adrian、Schaefer, Thomas、Giese, Bernd

  DOI：——

  日期：——