5R-(α-thymidyl)-5,6-dihydrothymidine

• 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: 5R-(α-thymidyl)-5,6-dihydrothymidine
• 英文别名: 1-[(2r,4s,5r)-5-(Hydroxymethyl)-4-Oxidanyl-Oxolan-2-Yl]-5-[[(5r)-1-[(2r,4s,5r)-5-(Hydroxymethyl)-4-Oxidanyl-Oxolan-2-Yl]-5-Methyl-2,4-Bis(Oxidanylidene)-1,3-Diazinan-5-Yl]methyl]pyrimidine-2,4-Dione；1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-[[(5R)-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-2,4-dioxo-1,3-diazinan-5-yl]methyl]pyrimidine-2,4-dione
• 化学式: C₂₀H₂₈N₄O₁₀
• 分子量: 484.463
• InChiKey: WCJUEZCRTGBSQU-BZMYHREGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  198
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  beta-胸苷 在 咪唑 、 N-溴代丁二酰亚胺(NBS) 、 四丁基氟化铵 、 四氯化锡 、 N-乙基异丙基胺 、 lithium diisopropyl amide 、 过氧化苯甲酰 作用下， 以 四氢呋喃 、 四氯化碳 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 104.5h， 生成 5R-(α-thymidyl)-5,6-dihydrothymidine
  参考文献：
  名称：

  DNA孢子光产物类似物的合成和立体化学分配。

  摘要：

  缺乏详细酶学研究所需的确定底物，严重阻碍了由孢子光产物（SP）裂解酶修复酶进行的DNA修复过程的研究。该问题特别严重，因为修复酶属于强氧敏感性自由基（S）-腺苷甲硫氨酸（SAM）酶，众所周知，这种酶很难处理。我们报告了孢子光产物类似物1 a和1 b的合成，它们具有开放的骨架和非对映异构体。为了解决立体化学分配的问题，制备了另外两个具有封闭主链的衍生物2a和2b。合成2 a / b的关键步骤是基于易位的大环化，可大大提高合成孢子光产物衍生物的构象刚度。环状异构体的NOESY实验提供了清晰的峰间模式，可以明确地分配立体化学。将结果转移到异构体1a和1b的数据中，随后将其用于酶修复研究。这些研究是用来自嗜热脂肪地芽孢杆菌的新型孢子光产物裂解酶修复酶进行的。研究表明，根据我们最近对枯草芽孢杆菌的孢子光产物裂解酶进行的研究，发现只有S异构体1a被识别和修复。现在，制备确定的功能性底物的能力为SP裂解

  DOI：

  10.1002/chem.200600169

文献信息

• The spore photoproduct lyase repairs the 5S- and not the 5R-configured spore photoproduct DNA lesion
  作者：Marcus G. Friedel、Olivier Berteau、J. Carsten Pieck、Mohamed Atta、Sandrine Ollagnier-de-Choudens、Marc Fontecave、Thomas Carell

  DOI：10.1039/b514103f

  日期：——

  The spore photoproduct lyase is a Fe-S/AdoMet DNA repair enzyme, which directly repairs spore lesions, induced by UV irradiation of spores, using an unknown radical mechanism. The air sensitive radical SAM enzyme was for the first time challenged with synthetically pure substrates. It was found that the enzyme recognizes a synthetic 5S-configured spore lesion without the central phosphodiester bond

  孢子光产物裂解酶是一种Fe-S / AdoMet DNA修复酶，它利用未知的自由基机理直接修复由孢子的紫外线照射诱导的孢子损伤。空气敏感性自由基SAM酶首次受到合成纯底物的挑战。发现该酶识别没有中央磷酸二酯键的合成的5S-构型的孢子损伤。与5R构型的病变相反，目前的看法不是底物。
• An Efficient Deprotection of <i>N</i>-Trimethylsilylethoxymethyl (SEM) Groups From Dinucleosides and Dinucleotides
  作者：Tilak Chandra、William E. Broderick、Joan B. Broderick

  DOI：10.1080/15257771003612847

  日期：2010.2.26

  A convenient and efficient method for deprotection of N-(trimethyl)silylethoxymethyl (SEM) groups from thymidine dinucleoside and dinucleotide has been achieved. The SEM groups were easily removed in excellent yields from protected nucleosides, dinucleosides, and dinucleotides.
• Unusually Large Deuterium Discrimination during Spore Photoproduct Formation
  作者：David M. Ames、Gengjie Lin、Yajun Jian、Jean Cadet、Lei Li

  DOI：10.1021/jo500775b

  日期：2014.6.6

  The deuterium-labeling strategy has been widely used and proved highly effective in mechanistic investigation of chemical and biochemical reactions. However, it is often hampered by the incomplete label transfer, which subsequently obscures the mechanistic conclusion. During the study of photoinduced generation of 5-thyminyl-5,6-dihydrothymine, which is commonly called the spore photoproduct (SP), the Cadet laboratory found an incomplete (similar to 67%) deuterium transfer in SP formation, which contrasts to the exclusive transfer observed by the Li laboratory. Here, we investigated this discrepancy by re-examining the SP formation using d(3)-thymidine. We spiked the d(3)-thymidine with varying amounts of unlabeled thymidine before the SP photochemistry is performed. Strikingly, our data show that the reaction is highly sensitive to the trace protiated thymidine in the starting material. As many as 17-fold enrichment is detected in the formed SP, which may explain the previously observed one-third protium incorporation. Although commercially available deuterated reagents are generally satisfactory as mechanistic probes, our results argue that attention is still needed to the possible interference from the trace protiated impurity, especially when the reaction yield is low and large isotopic discrimination is involved.
• Synthesis and Stereochemical Assignment of DNA Spore Photoproduct Analogues
  作者：Marcus G. Friedel、J. Carsten Pieck、Jochen Klages、Christina Dauth、Horst Kessler、Thomas Carell

  DOI：10.1002/chem.200600169

  日期：2006.8.7

  (SAM) enzymes, which are notoriously difficult to handle. We report the synthesis of the spore photoproduct analogues 1 a and 1 b, which have open backbones and are diastereoisomers. In order to solve the problem of stereochemical assignment, two further derivatives 2 a and 2 b with closed backbones were prepared. The key step of the synthesis of 2 a/b is a metathesis-based macrocyclization that strongly

  缺乏详细酶学研究所需的确定底物，严重阻碍了由孢子光产物（SP）裂解酶修复酶进行的DNA修复过程的研究。该问题特别严重，因为修复酶属于强氧敏感性自由基（S）-腺苷甲硫氨酸（SAM）酶，众所周知，这种酶很难处理。我们报告了孢子光产物类似物1 a和1 b的合成，它们具有开放的骨架和非对映异构体。为了解决立体化学分配的问题，制备了另外两个具有封闭主链的衍生物2a和2b。合成2 a / b的关键步骤是基于易位的大环化，可大大提高合成孢子光产物衍生物的构象刚度。环状异构体的NOESY实验提供了清晰的峰间模式，可以明确地分配立体化学。将结果转移到异构体1a和1b的数据中，随后将其用于酶修复研究。这些研究是用来自嗜热脂肪地芽孢杆菌的新型孢子光产物裂解酶修复酶进行的。研究表明，根据我们最近对枯草芽孢杆菌的孢子光产物裂解酶进行的研究，发现只有S异构体1a被识别和修复。现在，制备确定的功能性底物的能力为SP裂解