2'-碘-2'-脱氧尿苷 | 4753-03-1

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 中文名称: 2'-碘-2'-脱氧尿苷
• 英文名称: 1-((2R,3R,4R,5R)-4-hydroxy-5-(hydroxymethyl)-3-iodotetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione
• 英文别名: 1-(2-deoxy-2-iodo-β-D-ribofuranosyl)uracil；2'α-iodo-2'-deoxyuridine；2'-deoxy-2'-iodouridine；2'-iodo-2'-deoxyuridine；2'-iodo-2'-deoxy-uridine；2'-Deoxy-2'-iodo-uridin；1-[(2R,3R,4R,5R)-4-hydroxy-5-(hydroxymethyl)-3-iodooxolan-2-yl]pyrimidine-2,4-dione
• CAS: 4753-03-1
• 化学式: C₉H₁₁IN₂O₅
• 分子量: 354.101
• InChiKey: KVQOKCWRUQHGQR-XVFCMESISA-N

物化性质

• 密度：
  2.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2'-碘-2'-脱氧尿苷 在 咪唑 、 偶氮二异丁腈 、 三正丁基氢锡 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 2.5h， 生成 5'-O-(tert-butyldimethylsilyl)-2'-deoxyuridine
  参考文献：
  名称：

  Nucleic Acid Related Compounds. 91. Biomimetic Reactions Are in Harmony with Loss of 2‘-Substituents as Free Radicals (Not Anions) during Mechanism-Based Inactivation of Ribonucleotide Reductases. Differential Interactions of Azide, Halogen, and Alkylthio Groups with Tributylstannane and Triphenylsilane¹

  摘要：

  The initial step in the mechanism-based inactivation of ribonucleotide reductases by 2'-chloro-2'-deoxynucleotides is abstraction of H3' by a proximal free radical on the enzyme. The C3' radical is postulated to undergo spontaneous loss of chloride, and the resulting cationic radical loses a proton to give a 3'-keto intermediate. Successive beta-eliminations produce a Michael acceptor which causes inactivation. This hypothesis would predict rapid loss of mesylate or tosylate anions from C2', but sluggish loss of azide or thiomethoxide. in contrast, loss of azido and methylthio radicals from C2' should occur readily whereas homolysis to give (methyl or tolylsulfonyl)oxy and fluoro radicals should be energetically prohibitive. Protected 3'-O-(phenoxythiocarbonyl)-2'-substitute nucleosides were treated with tributylstannane/AIBN or triphenylsilane/dibenzoyl peroxide in refluxing toluene. The 2'-O-(mesyl and tosyl) and 2'-fluoro compounds underwent direct radical-mediated hydrogenolysis of the thionocarbonate group to give 3'-deoxy-2'-substituted products, whereas 2'-(azido, bromo, chloro, iodo, and methylthio)-3'-thionocarbonates gave 2',3'-didehydro-2',3'-dideoxy derivatives via loss of 2'-substituents from an incipient C3' radical. These results are in harmony with loss of radicals, but not anions, from C2'. The well-known radical-mediated hydrogenolytic cleavage of halogen and methylthio (slow) groups from C2' of the S'-hydroxy (unprotected) precursors and reduction of 2'-azides to amines occurred with tributylstannane/AIBN. Triphenylsilane/dibenzoyl peroxide gave parallel (but slower) hydrogenolysis with the 2'-(iodo, bromo, and methylthio) compounds, but cleavage of the 2'-chloro group was very slow and no reduction of 2'-azides to amines was detected. Rather, the latter system effected slow hydrogenolytic removal of the 2'-azido group. Thus, chemoselective differentiation of certain functional groups is possible with triphenylsilane and tributylstannane. Reduction of azides to amines with tributylstannane is known, but hydrogenolytic deazidation (slow) with triphenylsilane in the absence of amine formation appears to be novel.

  DOI：

  10.1021/ja962117m
• 作为产物：
  描述：

  2,2'-脱水尿苷 在 对甲苯磺酸 、 sodium iodide 作用下， 以 丙酮 为溶剂， 反应 5.5h， 以100%的产率得到2'-碘-2'-脱氧尿苷
  参考文献：
  名称：

  2'-炔基核苷酸：DNA 中 EPR 光谱的序列和自旋标记灵活策略

  摘要：

  电子顺磁共振 (EPR) 光谱是一种通过测量构象明确定义的自旋标记之间的距离来阐明分子结构的强大方法。在这里，我们报告了一种序列灵活的方法来合成双自旋标记的 DNA 双链体，其中 2'-炔基核苷结合在互补链的末端和内部位置。DNA 合成后铜催化的叠氮化物-炔环加成 (CuAAC) 反应与各种自旋标记物能够使用双电子-电子共振实验来测量双链体上的多个距离，提供高水平的详细结构信息。

  DOI：

  10.1021/jacs.6b05421

文献信息

• Copper‐Catalyzed Difluoromethylation of Alkyl Iodides Enabled by Aryl Radical Activation of Carbon–Iodine Bonds
  作者：Aijie Cai、Wenhao Yan、Chao Wang、Wei Liu

  DOI：10.1002/anie.202111993

  日期：2021.12.20

  An aryl radical activation strategy has been developed that can engage unactivated alkyl iodides in copper-catalyzed Negishi-type cross-coupling reactions. The strategy is based on the largely overlooked yet highly efficient reactivity of aryl radicals to abstract iodine atoms from alkyl iodides.

  已经开发出一种芳基自由基活化策略，可以在铜催化的 Negishi 型交叉偶联反应中使用未活化的烷基碘。该策略基于芳基自由基从烷基碘化物中提取碘原子的很大程度上被忽视但高效的反应性。
• Sugar modified oligonucleotides
  申请人：ISIS Pharmaceuticals, Inc.

  公开号：US20030004325A1

  公开（公告）日：2003-01-02

  Compositions and methods are provided for the treatment and diagnosis of diseases amenable to modulation of the production of selected proteins. In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically hybridizable with a selected sequence of RNA or DNA wherein at least one of the 2′-deoxyfuranosyl moieties of the nucleoside unit is modified. Treatment of diseases caused by various viruses and other causative agents is provided.

  提供了用于治疗和诊断可通过调节特定蛋白质产生的疾病的组合物和方法。根据优选实施例，提供了可以与RNA或DNA的选定序列特异性杂交的寡核苷酸和寡核苷酸类似物，其中核苷酸单元的至少一个2'-脱氧呋喃糖苷基被修改。提供了治疗由各种病毒和其他致病因素引起的疾病的方法。
• Synthesis of Pyrimidine 2‘-Deoxy Ribonucleosides Branched at the 2‘-Position via Radical Atom-Transfer Cyclization Reaction with a Vinylsilyl Group as a Radical-Acceptor Tether¹
  作者：Makoto Sukeda、Satoshi Shuto、Isamu Sugimoto、Satoshi Ichikawa、Akira Matsuda

  DOI：10.1021/jo000967l

  日期：2000.12.1

  Recently, we developed a regio- and stereoselective method for introducing a vinyl group at the position beta to a hydroxyl group in halohydrins or alpha-phenylselenoalkanols via a radical atom-transfer cyclization reaction with a vinylsilyl group as a temporary connecting radical-acceptor tether. The synthesis of 2'-deoxy-2'-C-vinyl- and 2'-deoxy-2'-C-hydroxymethyluridines (7 and 8, respectively)

  最近，我们开发了一种区域选择性和立体选择性的方法，可通过自由基原子转移环化反应将卤代醇或α-苯基硒代链烷醇中的羟基引入β位置的乙烯基，该反应以乙烯基甲硅烷基为临时连接的自由基受体链。2'-脱氧-2'-C-乙烯基-和2'-脱氧-2'-C-羟甲基尿苷（分别为7和8）和相应的2'-脱氧胞苷同类物（分别为10和11）的合成，使用这种自由基原子转移环化作为关键步骤，可以实现被设计为潜在抗肿瘤和/或抗病毒药物的药物。将在3'-羟基带有乙烯基甲硅烷基的2'-脱氧-2'-碘-5'-O-单甲氧基三苯甲基（MMTr）尿苷衍生物19a与（Me（3）Sn）（2）一起加热和AIBN在苯中，产生相应的自由基原子转移产物，依次将其依次用氟化四丁基铵和TBCS1 /咪唑处理，得到所需的2'-脱氧-5'-O-MMTr-3'-O-TBS-2'-C -乙烯基尿苷（25）。化合物25成功转化为目标2'-脱氧-2'-支链嘧啶核糖核苷7、8、10和11。
• 2' -modified oligonucleotides
  申请人：ISIS Pharmaceuticals, Inc.

  公开号：US20030187240A1

  公开（公告）日：2003-10-02

  Compositions and methods are provided for the treatment and diagnosis of diseases amenable to modulation of the production of selected proteins. In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically hybridizable with a selected sequence of RNA or DNA wherein at least one of the 2′-deoxyfuranosyl moieties of the nucleoside unit is modified. Treatment of diseases caused by various viruses and other causative agents is provided.

  提供了用于治疗和诊断可调节选择蛋白质生成的疾病的组合物和方法。根据优选实施例，提供了可以与RNA或DNA的选择序列特异性杂交的寡核苷酸和寡核苷酸类似物，其中核苷酸单元的至少一个2'-脱氧呋喃糖基团被修饰。提供了治疗由各种病毒和其他致病因子引起的疾病的方法。
• Compositions and methods for detecting and modulating rna activity and gene expression
  申请人：ISIS PHARMACEUTICALS, INC.

  公开号：EP1418179A2

  公开（公告）日：2004-05-12

  Compositions and methods for modulating the activity of RNA and DNA are disclosed. In accordance with preferred embodiments, antisense compositions are prepared comprising targeting and reactive portions. Reactive portions which act, alternatively, through phosphorodiester bond cleavage, through backbone sugar bond cleavage or through base modification are preferably employed. Groups which improve the pharmacodynamic and pharmacokinetic properties of the oligonucleotides are also useful in accordance with certain embodiments of this invention. Delivery of the reactive or non-reactive functionalities into the minor groove formed by the hybridization of the composition with the target RNA is also preferably accomplished. Therapeutics, diagnostics and research methods are also disclosed. Synthetic nucleosides and nucleoside fragments are also provided useful for elaboration of oligonucleotides and oligonucleotide analogs for such purposes.

  本文公开了调节 RNA 和 DNA 活性的组合物和方法。根据优选的实施方案，反义组合物由靶向部分和反应部分组成。反应部分最好通过磷酸二酯键裂解、骨架糖键裂解或碱基修饰起作用。根据本发明的某些实施方案，改善寡核苷酸药效学和药代动力学特性的基团也是有用的。最好还能将反应性或非反应性官能团输送到组合物与目标 RNA 杂交形成的次凹槽中。本发明还公开了治疗、诊断和研究方法。本发明还提供了合成核苷和核苷片段，可用于制备用于上述目的的寡核苷酸和寡核苷酸类似物。