5'-O-(tert-butyldimethylsilyl)-2'-deoxyuridine | 76223-04-6

• 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: 5'-O-(tert-butyldimethylsilyl)-2'-deoxyuridine
• 英文别名: 5'-O-TBDMS-dU；1-[(2R,4S,5R)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-4-hydroxyoxolan-2-yl]pyrimidine-2,4-dione
• CAS: 76223-04-6
• 化学式: C₁₅H₂₆N₂O₅Si
• 分子量: 342.467
• InChiKey: HCSHWGNMXQKRCF-DMDPSCGWSA-N

物化性质

• 溶解度：
  DMSO：100 mg/mL（292.00 mM；超声加热并加热至 80°C）

计算性质

• 辛醇/水分配系数(LogP)：
  1.21
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  88.1
• 氢给体数：
  2
• 氢受体数：
  5

制备方法与用途

5'-O-TBDMS-dU可以用于寡核苷酸的合成。

反应信息

• 作为反应物：
  描述：

  5'-O-(tert-butyldimethylsilyl)-2'-deoxyuridine 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以68%的产率得到2,3'-anhydro-5'-O-(tert-butyldimethylsilyl)-2'-deoxy-1-(β-D-threo-pentofuranosyl)uracil
  参考文献：
  名称：

  一锅法合成含有 α-氨基膦酸酯部分的新型 2'-脱氧尿苷衍生物

  摘要：

  已经从 5'-O-叔丁基二甲基甲硅烷基-3'-氨基-2', 3'-双脱氧尿苷以良好的收率制备了一系列 2'-脱氧尿苷 (8a-k) 的 α-氨基膦酸酯衍生物。所有产物的结构均经1H NMR、31P NMR、31C NMR、IR光谱、质谱和元素分析确证。© 2007 Wiley Periodicals, Inc. 杂原子化学 18:230–235, 2007; 在线发表于 Wiley InterScience (www.interscience.wiley.com)。DOI 10.1002/hc.20288

  DOI：

  10.1002/hc.20288
• 作为产物：
  描述：

  叔丁基二甲基氯硅烷 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 6.0h， 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

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。
• N3‘→P5‘ Oligodeoxyribonucleotide Phosphoramidates:  A New Method of Synthesis Based on a Phosphoramidite Amine-Exchange Reaction
  作者：Jeffrey S. Nelson、Karen L. Fearon、Mark Q. Nguyen、Sarah N. McCurdy、Jeff E. Frediani、Michael F. Foy、Bernard L. Hirschbein

  DOI：10.1021/jo970801t

  日期：1997.10.1

  for the synthesis of N3'-->P5' phosphoramidate oligodeoxynucleotides is demonstrated. Described herein is the synthesis of the monomers utilized in the phosphoramidite amine-exchange process and the experimental details pertaining to this new mode of chain assembly. The phosphoramidite amine-exchange method generates coupling yields in the 92-95% range per cycle and further enables the synthesis of chimeric

  展示了一种合成N3'-> P5'氨基磷酸亚氨基寡脱氧核苷酸的新方法。本文描述了亚磷酰胺交换反应中所用单体的合成以及与这种新的链组装方式有关的实验细节。亚磷酰胺交换法在每个循环中产生的偶联收率在92-95％的范围内，并且无需进行仪器修饰即可合成嵌合的氨基磷酸酯/磷酸二酯或氨基磷酸酯/硫代磷酸酯寡核苷酸。
• Synthesis and biological assay of new 2’-deoxyuridine dimers containing a 1,2,3-triazole linker. Part I
  作者：Lucyna Michalska、Dariusz Wawrzyniak、Agnieszka Szymańska-Michalak、Jan Barciszewski、Jerzy Boryski、Dagmara Baraniak

  DOI：10.1080/15257770.2018.1514122

  日期：2019.3.4

  Abstract We describe a simple method for the synthesis of modified dinucleosides containing pyrimidine nucleoside analogues (2’-deoxyuridine, thymidine and 5-fluoro-2’-deoxyuridine). Six different dimers with a 1,2,3-triazole linkage were obtained by azide–alkyne 1,3-dipolar cycloaddition (click reaction), starting from propargylated 2’-deoxyuridine and 5’-azido-nucleoside derivatives. Their cytotoxic

  摘要我们描述了一种简单的合成修饰的二核苷的方法，该修饰的二核苷含有嘧啶核苷类似物（2'-脱氧尿苷，胸苷和5-氟-2'-脱氧尿苷）。通过叠氮化物-炔烃1,3-偶极环加成反应（点击反应），从炔丙基化2'-脱氧尿苷和5'-叠氮基-核苷衍生物开始，获得了具有1,2,3-三唑键的六种不同的二聚体。在五种人类癌细胞系中测试了它们的细胞毒性活性：宫颈癌（HeLa），高级神经胶质瘤（U-118 MG，U-87 MG，T98G），肝脏（HepG2）和正常人类成纤维细胞系（MRC-5）使用磺基罗丹明B（SRB）分析。实验表明，所获得的具有1,2,3-三唑部分的二聚体是非常稳定的化合物，在生理样介质中也没有抗癌活性。
• [EN] CLEAVABLE NUCLEOTIDE ANALOGS AND USES THEREOF<br/>[FR] ANALOGUES NUCLÉOTIDIQUES CLIVABLES ET LEURS UTILISATIONS
  申请人：HARVARD COLLEGE

  公开号：WO2018102554A1

  公开（公告）日：2018-06-07

  Cleavable nucleotide analogs are provided. The nucleotide analog includes a nucleotide molecule attached to a cleavable moiety wherein the cleavable moiety comprises a protective group and/or a linker attached to a fluorophore. The cleavable moiety is linked to the oxygen atom of the 3'-OH of the pentose of the nucleotide molecule. The nucleotide analogs can be used in making polynucleotide molecules using template independent polymerases. The nucleotide analogs can act as reversible terminators during DNA sequencing by synthesis. The cleavage of the cleavable moiety restores a free 3'-OH functional group allowing growth of the polynucleotide molecule. The general structures as well as proposed synthetic schemes for the nucleotide analogs are also provided.

  可切割的核苷酸类似物已提供。该核苷酸类似物包括连接到可切割基团的核苷酸分子，其中可切割基团包括保护基团和/或连接到荧光团的连接物。可切割基团连接到核苷酸分子的五碳糖的3'-OH的氧原子。这些核苷酸类似物可用于使用模板无关聚合酶制备多核苷酸分子。这些核苷酸类似物在DNA合成测序过程中可作为可逆终止子。切割可切割基团恢复自由的3'-OH官能团，从而促进多核苷酸分子的生长。还提供了核苷酸类似物的一般结构以及拟议的合成方案。
• Solid phase synthesis of oligonucleotide N3'-P5' phosphoramidates
  申请人：Lynx Therapeutics, Inc.

  公开号：US05824793A1

  公开（公告）日：1998-10-20

  The invention provides a method of synthesizing oligonucleotide N3'.fwdarw.P5' phosphoramidates using an amine-exchange reaction of phosphoramidites in which a deprotected 3'-amino group of a solid phase supported oligonucleotide chain is exhanged for the amino portion of a 5'-phosphoramidite of an incoming monomer which has a protected 3'-amino group. The resulting internucleotide phosphoramidite linkage is then oxidized to form a stable protected phosphoramidate linkage. The method of the invention greatly improves product yields and reduces reagent usage over currently available methods for synthesizing the above class of compound.

  该发明提供了一种合成寡核苷酸N3'.fwdarw.P5'磷酰胺酯的方法，利用磷酰胺酯的胺交换反应，在这个反应中，固相支持的寡核苷酸链的去保护的3'-氨基团被交换成一个具有保护的3'-氨基团的入射单体的5'-磷酰胺酯的氨基部分。然后，形成的核苷间磷酰胺酯键被氧化以形成一个稳定的保护磷酰胺酯键。该发明的方法大大提高了产物收率，并减少了合成上述类化合物的当前可用方法中的试剂使用量。