2,3'-anhydro-5'-O-(4,4'-dimethoxytrityl)thymidine | 191474-13-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 2,3'-anhydro-5'-O-(4,4'-dimethoxytrityl)thymidine
• 英文别名: 5'-O-(4,4'-dimethoxytrityl)-2,3'-anhydrothymidine；5'-O-(4,4'-dimethoxytrityl)-2,3-anhydrothymidine；2,3'-anhydro-5'-(4,4'-dimethoxytrityl)thymidine；2,5-Methano-5H,9H-pyrimido[2,1-b][1,5,3]dioxazepin-9-one, 3-[[bis(4-methoxyphenyl)phenylmethoxy]methyl]-2,3-dihydro-8-methyl-, (2R,3R,5R)-；(1R,9R,10R)-10-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-methyl-8,11-dioxa-2,6-diazatricyclo[7.2.1.02,7]dodeca-3,6-dien-5-one
• CAS: 191474-13-2
• 化学式: C₃₁H₃₀N₂O₆
• 分子量: 526.589
• InChiKey: SWDIHODJLJEUEJ-JCYYIGJDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  78.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,3'-anhydro-5'-O-(4,4'-dimethoxytrityl)thymidine 在 盐酸 、 potassium fluoride 、 potassium carbonate 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 1.02h， 生成 3’-脱氧-3-氟胸苷
  参考文献：
  名称：

  Synthesis of 3′‐deoxy‐3′‐[ ¹⁸ F]fluoro‐thymidine with 2,3′‐anhydro‐5′‐ O ‐(4,4′‐dimethoxytrityl)‐thymidine

  摘要：

  [C-11]Thymidine has been used as a proliferation marker in positron-emission-tomography (PET) studies of tumors. This compound showed metabolite related problems and the radiosynthesis proved to be difficult. Recently, the more stable 3'-deoxy-3'-[F-18]fluorothymidine ([F-18]FLT) has been suggested as an alternative. One advantage of [F-18]FLT is based on thymidine kinase-1 catalyzed phosphorylation of FLT and the intracellular accumulation of this metabolite without participation in DNA synthesis. The radiosynthesis of [F-18]FLT originally designed by Grierson et al. was found to be demanding especially regarding the workup df the [F-18]fluoride/1-(2-deoxy-3 -O-nosyl-5-O-DMT-beta -D-threo-pento-furanosyl)-3-DMBn-thymine reaction mixture. Instead, we us ed 2,3'-anhydro-5'-0-(4,4'-dimethoxytrityl) thymi dine as a precursor for the synthesis of [F-18]FLT. In DMSO at 175 degreesC and in presence of Kryptofix(R) 2.2.2. we obtained 5.6+/-1,4 % [F-18]FLT (EOS).

  DOI：

  10.1002/1099-1344(20001030)43:12<1211::aid-jlcr408>3.0.co;2-#
• 作为产物：
  描述：

  保护胸苷 在 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 16.0h， 生成 2,3'-anhydro-5'-O-(4,4'-dimethoxytrityl)thymidine
  参考文献：
  名称：

  net 99m标记和胸苷类似物的合成：肿瘤成像的潜在候选者。

  摘要：

  研究了-99m标记和一系列胸苷类似物的合成。通过使用6-肼基吡啶-3-羧酸（HYNIC）作为双功能偶联剂，并使用N-（2-羟基-1,1-双（羟甲基）乙基）甘氨酸（三甲胺）和乙二胺-N，获得目标分子，N'-二乙酸（EDDA）为大肠菌素。还研究了胸苷类似物与HYNIC之间不同间隔区对放射化学收率的影响。

  DOI：

  10.1016/j.bmcl.2007.03.086

文献信息

• Synthesis of C3′ Modified Nucleosides for Selective Generation of the C3′-Deoxy-3′-thymidinyl Radical: A Proposed Intermediate in LEE Induced DNA Damage
  作者：Suaad A. S. Audat、CherylAnn Trzasko Love、Buthina A. S. Al-Oudat、Amanda C. Bryant-Friedrich

  DOI：10.1021/jo300045m

  日期：2012.4.20

  3′-dideoxy-C3′-thymidinyl radical (C3′dephos sugar radical), phenyl selenide and acyl modified sugar and nucleoside derivatives have been synthesized, and their suitability as photochemical precursors of the radical of interest has been evaluated. Upon photochemical activation of C3′-derivatized nucleosides in the presence of the hydrogen atom donor tributyltin hydride, 2′,3′-dideoxythymidine is formed

  据信由低能电子（LEE）诱导的DNA损伤途径涉及2-脱氧核糖自由基的形成。这些自由基形成在核苷酸的C3'和C5'位置，是通过将LEEs从核碱基转移至DNA寡聚体的磷酸基团而裂解C–O磷酸二酯键的结果。已经获得了大量信息，以阐明通过该过程形成的未修饰寡核苷酸产物的身份。然而，关于由这些糖基的降解形成的修饰病变的性质的信息很少。确定通过2'，3'-二脱氧-C3'-胸苷基（C3'dephos糖自由基），苯基硒化物和酰基修饰的糖以及核苷衍生物已经合成，并且已经评估了它们作为目标自由基的光化学前体的适用性。在存在氢原子供体三丁基锡氢化物的情况下，对C3'衍生的核苷进行光化学活化后，形成2'，3'-二脱氧胸苷，表明选择性生成了C3'磷酸基团。这些前体将使鉴定和量化由LEEs产生的自由基引起的DNA损伤的产物成为可能。
• Nucleosidyl‐<i>O</i>‐Methylphosphonates: A Pool of Monomers for Modified Oligonucleotides
  作者：Dominik Rejman、Milena Masojídková、Ivan Rosenberg

  DOI：10.1081/ncn-200033912

  日期：2004.1.1

  2′‐deoxyribonucleosides, 1‐(2‐deoxy‐β‐D‐threo‐pentofuranosyl)thymine, 5′‐O‐ and 2′‐O‐phosphonomethyl derivatives of 1‐(3‐deoxy‐β‐D‐erythro‐pentofuranosyl)thymine, and 1‐(3‐deoxy‐β‐D‐threo‐pentofuranosyl)thymine has been synthesized as a pool of monomers for the synthesis of modified oligonucleotides. The phosphonate moiety was protected with 4‐methoxy‐1‐oxido‐2‐pyridylmethyl ester group, serving also as an intramolecular

  四种天然 2'-脱氧核糖核苷、1-（2-脱氧-β-D-苏式-戊呋喃糖基）胸腺嘧啶、5'-O- 和 2' 的一组独特的 5'-O- 和 3'-O-膦酰基甲基衍生物1-(3-脱氧-β-D-赤型-戊呋喃糖基)胸腺嘧啶和1-(3-脱氧-β-D-苏式-戊呋喃糖基)胸腺嘧啶的-O-膦酰基甲基衍生物已被合成为单体库修饰寡核苷酸的合成。膦酸酯部分用 4-甲氧基-1-氧化-2-吡啶基甲酯基团保护，在偶联步骤中也作为分子内催化剂。
• A novel and practical synthesis of S-(1- and 2-halogenoalkyl)sugars by reaction of carbohydrate S-(O,O-dialkyl)phosphorodithioates and monothioates with fluoride anion
  作者：Halszka Bielawska、Maria Michalska

  DOI：10.1016/j.tetlet.2003.12.155

  日期：2004.3

  A useful synthesis has been developed of S-(1- and 2-halogenoalkyl)sugars in high yield and purity. Readily available sugar S-(O,O-dialkyl)phosphorodithioates undergo S–P bond rupture on reaction with fluoride ions to yield the corresponding sugar thiolates, which further react in situ with dichloromethane or 1,2-dihalogenoalkanes in the reaction medium. In this reaction, the halogenoalkanes play the

  已经开发了高产率和高纯度的S-（1-和2-卤代烷基）糖的有用的合成方法。易得的糖S-（O，O-二烷基）硫代二硫代磷酸酯在与氟离子反应后发生S-P键断裂，生成相应的糖硫醇酸酯，然后与二氯甲烷或1,2-二卤代烷烃在反应介质中进一步原位反应。在该反应中，卤代烷烃起反应物和溶剂的作用。
• Reverse-direction (5′→3′) synthesis of oligonucleotides containing a 3′-S-phosphorothiolate linkage and 3′-terminal 3′-thionucleosides
  作者：James W. Gaynor、Michael M. Piperakis、Julie Fisher、Richard Cosstick

  DOI：10.1039/b923545k

  日期：——

  5′-oxygen to the 3′-thiol function. 5′→3′ Synthesis of oligonucleotides gave relatively poor yields for the internal incorporation of 3′-thionucleosides [to give a 3′-S-phosphorothiolate (3′-SP) linkage] and multiple 3′-SP modifications could not be introduced by this method. However, the reverse direction approach provided an efficient route to oligonucleotides terminating with a 3′-thionucleoside

  含3'- thionucleosides寡脱氧核苷酸的合成已使用反向方向（5'→3'）的方法探讨的基础上，其含有一个或三苯甲基二甲氧基三苯甲基保护的核苷单体3'-硫醇和一个5'- ø -亚磷酰胺。这些单体相对容易制备，因为基于三苯甲基的保护基优先于5'-羟基以3'-硫醇选择性引入。作为替代方法，可以诱导三苯甲基从5'-氧迁移至3'-硫醇功能。5'→3'的合成寡核苷酸的合成相对内部3'-thionucleosides [产生3'- S]的收率相对较低-硫代磷酸酯（3'-SP）键]和多个3'-SP修饰不能通过该方法引入。然而，反向方法提供了以3'-硫代核苷终止的寡核苷酸的有效途径。这些硫封端的低聚物的直接合成以前没有报道，并且所描述的方法适用于衍生自胸腺嘧啶，胞嘧啶和腺嘌呤的2'-脱氧-3'-硫核苷。
• Investigations into the regioselective deuteriation of enolates derived from silyl enol ethers and enolacetates
  作者：Gregory S. Coumbarides、Jason Eames、Neluka Weerasooriya

  DOI：10.1002/jlcr.519

  日期：2001.10.30

  Results are reported on the regioselective C-deuteriation of a series of enolates derived from the addition of MeLi to the related enolacetate and silyl enol ether and discussed in terms of the similarity between these methods; comments are made on the possible role of the additive, lithium tert-butoxide. Copyright © 2001 John Wiley & Sons, Ltd.

  结果报告了一系列烯醇的区域选择性 C-氘化，这些烯醇是将 MeLi 添加到相关的烯醇乙酸酯和甲硅烷基烯醇醚中而衍生的，并讨论了这些方法之间的相似性；评论了添加剂叔丁醇锂的可能作用。版权所有 © 2001 John Wiley & Sons, Ltd.