1-(2-O-methyl-β-D-ribofuranosyl)-2-thio-4-(1H,3H)-pyrimidinone | 113886-72-9

• 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: 1-(2-O-methyl-β-D-ribofuranosyl)-2-thio-4-(1H,3H)-pyrimidinone
• 英文别名: 2’-O-methyl-2-thiouridine；2'-O-methyl-2-thiouridine；s²Um；2-thio-2'-O-methyluridine；1-[(2R,3R,4R,5R)-4-hydroxy-5-(hydroxymethyl)-3-methoxyoxolan-2-yl]-2-sulfanylidenepyrimidin-4-one
• CAS: 113886-72-9
• 化学式: C₁₀H₁₄N₂O₅S
• 分子量: 274.298
• InChiKey: WARUUAMZJXEUEA-ZOQUXTDFSA-N

物化性质

• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  6

制备方法与用途

2'-O-甲基-2-硫尿苷是一种嘌呤核苷类似物，而嘌呤核苷类似物具有广泛的抗肿瘤活性，尤其针对惰性淋巴系统恶性肿瘤。其抗癌机制主要依赖于抑制DNA合成和诱导细胞凋亡等过程。

反应信息

• 作为反应物：
  描述：

  1-(2-O-methyl-β-D-ribofuranosyl)-2-thio-4-(1H,3H)-pyrimidinone 在 吡啶 、 四氮唑 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and properties of 2′-O-Methyl-2-thiouridine and oligoribonucleotides containing 2′-O-Methyl-2-thiouridine

  摘要：

  A new method for the synthesis of 2'-O-methyl-2-thiouridine (s(2)Um) found in thermophilic bacterial tRNA was developed. Structural properties of s(2)Um and s(2)Um(p)U were studied by using H-1 NMR spectroscopy. A modified nonaribonucleotide (RNA*: 5'-CGUUs(2)UmUUGC-3') was synthesized to study the base-recognition ability of s(2)Um in formation of RNA-RNA and RNA-DNA duplexes. The UV melting experiments revealed that RNA*-RNA and RNA*-DNA duplexes having an s(2)U-A base pair are more stable than those having a U-A base pair. On the contrary, the thermal stability of RNA*-RNA and RNA*-DNA duplexes having an s(2)U-G wobble base pair was much lower than that of the unmodified duplexes having a natural U-G base pair. It is concluded that s(2)Um has higher selectivity toward A over G than unmodified U. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00342-5
• 作为产物：
  描述：

  2'-O-Me-2'-O-ethyluridine 在 吡啶 、 硫化氢 作用下， 反应 28.0h， 生成 1-(2-O-methyl-β-D-ribofuranosyl)-2-thio-4-(1H,3H)-pyrimidinone
  参考文献：
  名称：

  [EN] MODIFIED NUCLEIC ACID MOLECULES AND USES THEREOF
  [FR] MOLÉCULES D'ACIDE NUCLÉIQUE MODIFIÉES ET LEURS UTILISATIONS

  摘要：

  本公开提供了经修改的核苷、核苷酸和核酸，以及它们的使用方法。

  公开号：

  WO2014093924A1

文献信息

• Synthesis of novel C-2 substituted pyrimidine nucleoside analogs
  作者：Martin Dunkel、P. Dan Cook、Oscar L. Acevedo

  DOI：10.1002/jhet.5570300540

  日期：1993.10

  A series of 2-(2-oxoalkylidene)-4(1H)-pyrimidinone nucleoside analogs were synthesized by the addition of the lithium enolates of methylketones to 2,5′- and 2,2′-anhydrouridines and to 2,5′-anhydrothymidines. Alternatively, 2-thiouridine was alkylated with bromomethyl ketones to yield 2-(2-oxoalkyl)thio-4(1H)-pyrimidinone ribofuranosides in good yields. These intermediates were subsequently transformed

  通过向2,5'-和2,2'-脱水尿苷中添加甲基酮的烯醇锂，合成了一系列2-（2-氧代亚烷基）-4（1 H）-嘧啶酮核苷类似物。 -脱水胸苷。或者，将2-硫代尿苷与溴甲基酮烷基化，以良好的产率得到2-（2-氧代烷基）硫基-4（1H）-嘧啶酮呋喃糖苷。这些中间体随后通过Eschenmoser硫磺挤出反应转化为标题化合物。2-（2-氧代亚烷基）-4-（1 H）-嘧啶酮核苷类似物在其1中显示烯醇质子信号H nmr光谱表明N-3与酮氧之间存在氢键。这些结构提供了具有沃森-克里克氢键潜力的官能团。
• Sensitive and Simultaneous Determination of Uridine Thiolation and Hydroxylation Modifications in Eukaryotic RNA by Derivatization Coupled with Mass Spectrometry Analysis
  作者：Yi Dai、Chu-Bo Qi、Yang Feng、Qing-Yun Cheng、Fei-Long Liu、Ming-Yu Cheng、Bi-Feng Yuan、Yu-Qi Feng

  DOI：10.1021/acs.analchem.0c04630

  日期：2021.5.11

  The discovery of dynamic and reversible modifications in RNA expands their functional repertoires. Now, RNA modifications have been viewed as new regulators involved in a variety of biological processes. Among these modifications, thiolation is one kind of special modification in RNA. Several thiouridines have been identified to be present in RNA, and they are essential in the natural growth and metabolism of cells. However, detection of these thiouridines generally is challenging, and few studies could offer the quantitative levels of uridine modifications in RNA, which limits the in-depth elucidation of their functions. Herein, we developed a chemical derivatization in combination with mass spectrometry analysis for the sensitive and simultaneous determination of uridine thiolation and hydroxylation modifications in eukaryotic RNA. The chemical derivatization strategy enables the addition of easily ionizable groups to the uridine thiolation and hydroxylation modifications, leading up to a 339-fold increase in detection sensitivities of these modifications by mass spectrometry analysis. The limits of detection of these uridine modifications can be down to 17 amol. With the established method, we discovered and confirmed that a new modification of 5-hydroxyuridine (ho5U) was widely present in small RNAs of mammalian cells, expanding the diversity of RNA modifications. The developed method shows superior capability in determining low-abundance RNA modifications and may promote identifying new modifications in RNA, which should be valuable in uncovering the unknown functions of RNA modifications.

  RNA中动态和可逆修饰的发现扩展了其功能范围。现在，RNA修饰被视为参与多种生物过程的新调节因子。在这些修饰中，硫化是一种特殊的RNA修饰。已经识别出几种硫尿苷存在于RNA中，并且它们在细胞的自然生长和代谢中是必不可少的。然而，检测这些硫尿苷通常具有挑战性，且很少有研究能够提供RNA中尿苷修饰的定量水平，这限制了对其功能的深入阐明。在此，我们开发了一种化学衍生化结合质谱分析的方法，以敏感且同时地确定真核RNA中的尿苷硫化和羟基化修饰。该化学衍生化策略能够为尿苷硫化和羟基化修饰添加易于离子化的基团，从而使这些修饰的质谱分析检测灵敏度提高了339倍。这些尿苷修饰的检测限可低至17 amol。通过建立的方法，我们发现并确认一种新修饰5-羟基尿苷（ho5U）在哺乳动物细胞的小RNA中广泛存在，从而扩展了RNA修饰的多样性。该方法在确定低丰度RNA修饰方面表现出卓越的能力，并可能促进识别RNA中的新修饰，这对于揭示RNA修饰的未知功能将具有重要价值。
• A New Route to 2‘-<i>O</i>-Alkyl-2-thiouridine Derivatives via 4-<i>O</i>-Protection of the Uracil Base and Hybridization Properties of Oligonucleotides Incorporating These Modified Nucleoside Derivatives
  作者：Itaru Okamoto、Koh-ichiroh Shohda、Kohji Seio、Mitsuo Sekine

  DOI：10.1021/jo035246b

  日期：2003.12.1

  Oligonucleotides containing 2-thiouridine (s2U) in place of uridine form stable RNA duplexes with complementary RNAs. Particularly, this modified nucleoside has proved to recognize highly selectively adenosine, the genuine partner, without formation of a mismatched base pair with the guanosine counterpart. In this paper, we describe new methods for the synthesis of 2-thiouridine and various 2'-O-alkyl-2-thiouridine

  含有2-硫尿苷（s2U）代替尿苷的寡核苷酸与互补RNA形成稳定的RNA双链体。特别地，已证明该修饰的核苷可高度选择性地识别真正的腺苷腺苷，而不会与鸟苷对应物形成错配的碱基对。在本文中，我们描述了合成2-硫尿苷和各种2'-O-烷基-2-硫尿苷衍生物的新方法。合成了具有这些修饰的核苷衍生物的寡核糖核苷酸，并通过这些修饰的核苷的1 H NMR分析和带有互补RNA链的RNA双链体的Tm实验，详细研究了它们的杂交和结构特性。
• ALTERNATIVE NUCLEIC ACID MOLECULES AND USES THEREOF
  申请人：Moderna Therapeutics, Inc.

  公开号：US20150167017A1

  公开（公告）日：2015-06-18

  The present disclosure provides alternative nucleosides, nucleotides, and nucleic acids, and methods of using them.

  本公开提供了替代核苷、核苷酸和核酸以及它们的使用方法。
• MODIFIED NUCLEIC ACID MOLECULES AND USES THEREOF
  申请人：MODERNA THERAPEUTICS, INC.

  公开号：US20150307542A1

  公开（公告）日：2015-10-29

  The present disclosure provides modified nucleosides, nucleotides, and nucleic acids, and methods of using them.

  本公开提供了修改的核苷酸，核苷酸和核酸，以及使用它们的方法。