2'-氯-2'-脱氧尿苷 | 4753-04-2

• 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'-氯-2'-脱氧尿苷
• 中文别名: 1,4-二氯呔嗪；1,4-二氯酚嗪；1,4-二氯肽嗪；1,4-环己二酮单乙二醇缩酮
• 英文名称: 2'-chloro-2'-deoxyuridine
• 英文别名: 2'-deoxy-2'-chlorouridine；2'-Chlor-2'-desoxyuridin；2'-chloro-2'-deoxy-uridine；2'-Chlor-2'-desoxy-uridin；2'-Chloro-2'-deoxy-uridin；2'-Chlor-2'-deoxy-uridin；1-[(2R,3R,4R,5R)-3-chloro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 4753-04-2
• 化学式: C₉H₁₁ClN₂O₅
• 分子量: 262.65
• InChiKey: XOTUXDQKWDTKSI-XVFCMESISA-N

物化性质

• 熔点：
  207-212 °C (decomp)
• 密度：
  1.67±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 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'-氯-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 三氯化铝 作用下， 以95%的产率得到2'-氯-2'-脱氧尿苷
  参考文献：
  名称：

  在BF 3 ·Et 2 O存在下2,2'-脱水尿苷与氰基乙基三甲基甲硅烷基醚的开环反应，轻松合成2' - O-氰基乙基尿苷

  摘要：

  在这种信，对于2'-合成的简便方法Ô -cyanoethyluridine，这是在充分的合成部分2'-O-氰乙基化寡核糖核苷酸以及未修饰的寡核糖核苷酸的关键中间体，并通过开环开发BF 3 ·Et 2 O存在下，在二甲基乙酰胺中，使2,2'-脱水尿苷与2-氰基乙基三甲基甲硅烷基醚反应。2'- Ô -cyanoethyluridine 3'-亚磷酰胺衍生物转化成2'- ø氰乙基-4- Ñ由一系列涉及4-取代反应（1个-acetylcytidine 3'-亚磷酰胺衍生物ħ-1,2,4-三唑-1-基）尿苷衍生物与氨的反应，然后进行乙酰化。

  DOI：

  10.1016/j.tetlet.2007.09.105

文献信息

• Anti-HCV nucleoside derivatives
  申请人：——

  公开号：US20030008841A1

  公开（公告）日：2003-01-09

  The present invention comprises novel and known purine and pyrimidine nucleoside derivatives which have been discovered to be active against hepatitis C virus (HCV). The use of these derivatives for the treatment of HCV infection is claimed as are the novel nucleoside derivatives disclosed herein.

  本发明涉及新颖和已知的嘌呤和嘧啶核苷衍生物，已发现这些衍生物对丙型肝炎病毒（HCV）具有活性。本发明声明利用这些衍生物治疗HCV感染，以及本文所披露的新颖核苷衍生物。
• Influence of substituent groups in regioselective acylation of nucleosides by Novozym 435 lipase
  作者：Zhao-Yu Wang、Yan-Hong Bi、Xiang-Qian Li、Min-Hua Zong

  DOI：10.1016/j.procbio.2013.06.022

  日期：2013.8

  comparative study on the substrate recognition was conducted successfully in Novozym 435-mediated acylation of various 2′- or 5-substituted nucleosides with acyl donors carrying different aliphatic chain lengths (C6, C10, and C14). The unexpected results revealed that the physicochemical property of the substituents (such as the size, hydrophobicity, and substitutional position) in nucleosides profoundly influenced

  在 Novozym 435 介导的各种 2' 或 5 取代核苷与携带不同脂肪链长度（C6、C10 和 C14）的酰基供体的酰化中，成功地进行了底物识别的比较研究。出乎意料的结果表明，核苷中取代基的物理化学性质（如大小、疏水性和取代位置）对酶的行为产生了深远的影响。源自核苷 2'-或 5-位取代基的不同底物结合模式可以解释这一点。此外，除了脂肪酶活性位点的几何构型之外，控制区域选择性的另一个可能因素可能归因于取代基和酰基供体之间的相互作用。
• [EN] NOVEL ANTIVIRAL AND ANTITUMORAL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS ANTIVIRAUX ET ANTITUMORAUX
  申请人：UNIV LEUVEN KATH

  公开号：WO2015158913A1

  公开（公告）日：2015-10-22

  The present invention relates to novel phosphate-modified nucleosides, such as phosphoramidate nucleosides. The invention also relates to the use of these novel phosphate-modified nucleosides to treat or prevent viral infections and proliferative diseases (such as cancer) and their use to manufacture a medicine to treat or prevent viral infections and proliferative diseases particularly infections with viruses belonging to the HCV family.

  本发明涉及新型磷酸酯修饰核苷，如磷酰胺酸酯核苷。该发明还涉及利用这些新型磷酸酯修饰核苷来治疗或预防病毒感染和增殖性疾病（如癌症），以及它们用于制造用于治疗或预防病毒感染和增殖性疾病，特别是感染HCV家族病毒的药物。
• 制备2’-脱氧尿嘧啶核苷的方法
  申请人：上海艾美晶生物科技有限公司

  公开号：CN106146587A

  公开（公告）日：2016-11-23

  本发明公开了一种制备式(Ⅳ)所示2’‑脱氧尿嘧啶核苷的方法，包括以下步骤：按下述化学方程式将式(Ⅰ)所示的尿嘧啶核苷和脱水剂混合于溶剂中，在无机碱催化下，生成式(Ⅱ)所示的尿嘧啶核苷脱水物；加入卤化氢，经卤代反应，生成式(Ⅲ)所示的尿嘧啶核苷卤代物；通入氢气，经还原反应，生成式(Ⅳ)所示的2’‑脱氧尿嘧啶核苷。本发明的制备式(Ⅳ)所示2’‑脱氧尿嘧啶核苷的方法，对环境和人体危害较小，产生的废物也可回收利用，而且，采用一锅法的制备方法，操作简单，人力成本低，设备投入少，生产周期大幅降低，适合于工业化大量生产。。
• 4-Imino-n-alkoxy or oxy-polyalkyl-piperidine compounds and their use as polymerization regulators
  申请人：——

  公开号：US20040176553A1

  公开（公告）日：2004-09-09

  The present invention relates to selected 4-imino-N-alkoxy-polyalkyl-peperidine compounds preparation, a polymerizable composition comprising a) at least one ethylenically unsaturated monomer and b) a 4-imino-N-alkoxy-polyalkyl-piperidine compound. Further aspects of the present invention are a process for polymerizing ethylenically unsaturated monomers, and the use of 4-imino-N-alkoxy-polyalkyl-piperidine compounds for controlled polymerization. The intermediate N-oxyl derivatives, a composition of the N-oxyl derivatives with ethylenically unsaturated monomers and a free radical initiator, as well as a process for polymerization are also subjects of the present invention. 1

  本发明涉及选择的4-亚氨基-N-烷氧基-聚烷基-哌啶化合物的制备，包括a）至少一种乙烯基不饱和单体和b）4-亚氨基-N-烷氧基-聚烷基-哌啶化合物的可聚合组合物。本发明的其他方面包括聚合乙烯基不饱和单体的过程，以及使用4-亚氨基-N-烷氧基-聚烷基-哌啶化合物进行控制聚合的方法。中间体N-氧代衍生物，N-氧代衍生物与乙烯基不饱和单体和自由基引发剂的组合物，以及聚合的过程也是本发明的主题。