2',3'-O-isopropylidene-5'-O-(p-toluenesulfonyl)-5-methyluridine | 37085-43-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2',3'-O-isopropylidene-5'-O-(p-toluenesulfonyl)-5-methyluridine
• 英文别名: 5'-toluenesulfonyl-2',3'-O-isopropylidenethymidine；2’,3’-O-isopropylidene-5-methyl-5’-O-tosyluridine；2’,3’-O-isopropylidene-5’-O-(p-toluenesulfonyl)-5-methyluridine；((3aR,4R,6R,6aR)-2,2-dimethyl-6-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl 4-methylbenzenesulfonate；[(3aR,4R,6R,6aR)-2,2-dimethyl-4-(5-methyl-2,4-dioxopyrimidin-1-yl)-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methyl 4-methylbenzenesulfonate
• CAS: 37085-43-1
• 化学式: C₂₀H₂₄N₂O₈S
• 分子量: 452.485
• InChiKey: IKBIPJWPUPCPFX-YFHUEUNASA-N

物化性质

• 密度：
  1.347±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2',3'-O-isopropylidene-5'-O-(p-toluenesulfonyl)-5-methyluridine 在 sodium azide 、 水 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 5'-azido-5-methyluridine
  参考文献：
  名称：

  紧密连接的吗啉代核苷嵌合体：新型、紧凑的阳离子寡核苷酸类似物

  摘要：

  核酸的聚阴离子磷酸二酯主链导致高核酸酶敏感性和低细胞摄取，因此是天然寡核苷酸的生物应用的主要障碍。主链修饰，特别是电荷改变是一种经过验证的策略，可以提供具有改进特性的人工寡核苷酸。在这里，我们描述了由吗啉代和核糖或脱氧核糖核苷组成的新型寡核苷酸类似物的合成，其中核苷单元的5'-氨基提供吗啉环的氮。该合成方案与三苯甲基和二甲氧基三苯甲基保护基团和叠氮基官能团兼容，并扩展到高级低聚物的合成。由于吗啉单元的N-烷基化叔胺结构，嵌合体在水介质中带正电荷。

  DOI：

  10.1039/d1ob01174j
• 作为产物：
  描述：

  5-甲基尿甙 在 吡啶 、 硫酸 作用下， 生成 2',3'-O-isopropylidene-5'-O-(p-toluenesulfonyl)-5-methyluridine
  参考文献：
  名称：

  低温光诱导的硫醇-烯点击反应：一种温和而有效的糖修饰核苷合成方法

  摘要：

  糖修饰的核苷是抗癌和抗病毒药物开发中的主要合成靶标。自由基介导的硫醇-烯耦合施加首次上核苷enofuranoside衍生物，以产生宽范围的硫取代d -核糖， -阿糖， -低聚木糖和大号- L-来苏构型的嘧啶核苷。与简单的糖外亚甲基的类似反应相反，令人惊讶的是，在各种引发方法的标准条件下，核苷烯烃的氢硫醇化显示出低至中等的产率和非常低的立体选择性。优化反应条件后，我们发现冷却反应混合物对转化率和立体选择性均具有显着的有益作用，并且紫外光引发的C 2' -，C 3'-和C 2的氢硫醇化反应在-80°C时，核苷的4'-异亚甲基衍生物的产率高至高，并且在大多数情况下，其非对映异构选择性极好。在温度之外，溶剂，核苷上的保护基以及在某些情况下硫醇的构型也影响添加的立体化学结果。异常大号- L-来苏非对映选择性当加入1-硫代β-观察d -gluco-和半乳糖衍生物到Ç 4'，5'-尿苷不饱和归因于之间的空间位失配d

  DOI：

  10.1039/c7ob02184d

文献信息

• Introduction of an alkyl group into the sugar portion of uracilnucleosides by the use of Gilman reagents.
  作者：Hiroyuki HAYAKAWA、Hiroshi ASHIZAWA、Hiromichi TANAKA、Tadashi MIYASAKA

  DOI：10.1248/cpb.38.355

  日期：——

  Substitution of a p-toluenesulfonyloxy group in the sugar portion of uracilnucleosides by an alkyl group was investigated by using Gilman reagents (R2CuLi). In the cases of 5'-O-tosyl derivatives of 2', 3'-O-isopropylideneuridine, moderate vields of 5'-alkylated products were obtained. In contrast to this, the reactions of the corresponding 2'-deoxyuridine derivatives gave higher yields of products. A similar substitution reaction at the 3'-position of 2'-deoxyuridine derivatives was also examined.

  用Gilman试剂（R2CuLi）研究了尿嘧啶核苷糖部分的p-甲苯磺酰氧基被烷基取代的反应。对于2',3'-O-异亚丙基尿苷的5'-O-甲苯磺酸衍生物，得到了中等收率的5'-烷基化产物。与此相反，相应的2'-脱氧尿苷衍生物的反应则得到了更高收率的产物。还考察了在2'-脱氧尿苷衍生物的3'位进行类似取代反应的情况。
• Synthesis of 1-Aryl-1<i>H</i> -indazoles via a Ligand-Free Copper- Catalyzed Intramolecular Amination Reaction
  作者：Fengjuan Shen、Xiaoliu Li、Xiaojuan Zhang、Zhanbin Qin、Qingmei Yin、Hua Chen、Jinchao Zhang

  DOI：10.1002/cjoc.201190224

  日期：2011.6

  A general synthesis of 1‐aryl‐1‐H‐indazoles from o‐halogenated aryl aldehydes or ketones and aryl hydrazines was described. This protocol included an intermolecular condensation and a ligand‐free copper‐catalyzed intramolecular Ullmann‐type coupling reaction. This method was applied to a wide range of substrates to produce the indazole products in good yields.

  描述了由邻卤代的芳基醛或酮和芳基肼合成1-芳基-1- H-吲唑的一般方法。该方案包括分子间缩合和无配体的铜催化的分子内Ullmann型偶联反应。该方法适用于多种底物，以高收率生产吲唑产品。
• Deploying solid-phase synthesis to access thymine-containing nucleoside analogs that inhibit DNA repair nuclease SNM1A
  作者：Christine A. Arbour、Ellen M. Fay、Joanna F. McGouran、Barbara Imperiali

  DOI：10.1039/d3ob00836c

  日期：——

  Nucleoside analogs show useful bioactive properties. A versatile solid-phase synthesis that readily enables the diversification of thymine-containing nucleoside analogs is presented. The utility of the approach is demonstrated with the preparation of a library of compounds for analysis with SNM1A, a DNA damage repair enzyme that contributes to cytotoxicity. This exploration provided the most promising

  核苷类似物显示出有用的生物活性特性。提出了一种通用的固相合成方法，可以轻松实现含胸腺嘧啶核苷类似物的多样化。该方法的实用性通过制备用于 SNM1A 分析的化合物库来证明，SNM1A 是一种有助于细胞毒性的 DNA 损伤修复酶。这项探索提供了迄今为止最有前途的 SNM1A 核苷衍生抑制剂，IC 50为 12.3 μM。
• Synthesis and structure–activity relationship of uracil nucleotide derivatives towards the identification of human P2Y 6 receptor antagonists
  作者：Diana Meltzer、Ophir Ethan、Guillaume Arguin、Yael Nadel、Ortal Danino、Joanna Lecka、Jean Sévigny、Fernand-Pierre Gendron、Bilha Fischer

  DOI：10.1016/j.bmc.2015.07.004

  日期：2015.9

  P2Y(6) receptor (P2Y(6)-R) is involved in various physiological and pathophysiological events. With a view to set rules for the design of UDP-based reversible P2Y(6)-R antagonists as potential drugs, we established structure-activity relationship of UDP analogues, bearing modifications at the uracil ring, ribose moiety, and the phosphate chain. For instance, C5-phenyl- or 3-NMe-uridine-5'-alpha,beta-methylene-diphosphonate, 16 and 23, or lack of 2'-OH, in 12-15, resulted in loss of both agonist and antagonist activity toward hP2Y(6)-R. However, uridylyl phosphosulfate, 19, selectively inhibited hP2Y(6)-R (IC50 112 mu M) versus P2Y(2)/(4)-Rs. In summary, we have established a comprehensive SAR for hP2Y(6)-R ligands towards the development of hP2Y(6)-R antagonists. (C) 2015 Elsevier Ltd. All rights reserved.
• Insight into the Chemical Mechanism of Thymidylate Synthase-Catalyzed Reaction Through the Evaluation of Chemical Models: The Role of C6 Sulfhydryl Addition During the Reductive Elimination Step of the Reaction1
  作者：B.H. Wang、J.R. Kagel、M.P. Mertes、K. Bowmanjames

  DOI：10.1006/bioo.1994.1034

  日期：1994.12

  Thymidylate synthase catalyzes the last step of the de novo synthesis of thymidine-5'-monophosphate (TMP), which has long been a target for the development of effective anticancer agents. Model compounds (15, 16, 17) were used to study the effect of C6 nucleophilic addition on the reductive elimination step of the TS-catalyzed reaction. Results suggest that C6 addition facilitates the reductive elimination of the H(2)folate moiety of the ternary intermediate (3). Therefore, the reaction pathway (pathway (b)) with the participation of C6 sulfhydryl addition during the reductive elimination process is the energetically favored process. Consequently, the elimination of the cysteine sulfhydryl group from the C6 position is the last step of the reaction before the dissociation of the products from the enzyme. (C) 1994 Academic Press, Inc.