4-O-甲基-胸苷 | 50591-13-4

• 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: 4-O-甲基-胸苷
• 中文别名: 1-硫杂-4,8-二氮杂螺[4.5]癸烷-3-酮,4,8-二甲基-,1-氧化
• 英文名称: O⁴-methyl thymidine
• 英文别名: O⁴-methylthymidine；O⁴-methyl-dT；O⁴-MedT；1-(β-D-erythro-2-deoxy-pentofuranosyl)-4-methoxy-5-methyl-1H-pyrimidin-2-one；O⁴-methyl-thymidine；O4-methylthymidine；O-Methylthymidine；1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-methoxy-5-methylpyrimidin-2-one
• CAS: 50591-13-4
• 化学式: C₁₁H₁₆N₂O₅
• 分子量: 256.258
• InChiKey: SYCUMVXQKYPFDT-DJLDLDEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  91.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-O-甲基-胸苷 在 吡啶 作用下， 生成 Acetic acid (2R,3S,5R)-5-(4-methoxy-5-methyl-2-oxo-2H-pyrimidin-1-yl)-2-(toluene-4-sulfonyloxymethyl)-tetrahydro-furan-3-yl ester
  参考文献：
  名称：

  Rapid synthesis of a 5′-fluorinated oligodeoxy-nucleotide: A model antisense probe for use in imaging with positron emission tomography (PET)

  摘要：

  5'-Deoxy-5'-fluoro-O-4-methylthymidine was synthesized by the reaction of the corresponding 5'-O-tosylate with KF in the presence of Kryptofix [222] and coupled to a 5'-phosphoramidite-activated CPG-bound oligodeoxynucleotide. The sequence of reactions and purifications were accomplished within 4 h, a necessary condition of the development of radiofluorinated antisense oligodeoxynucleotide, probe for use with PET. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00239-x
• 作为产物：
  描述：

  3,5-双-o-(t-丁基二甲基甲硅烷基)胸腺嘧啶脱氧核苷 在 tris(dimethylamino)sulfonium difluorotrimethylsilicate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 18.0h， 生成 4-O-甲基-胸苷
  参考文献：
  名称：

  通过使用 (苯并三唑-1-基氧基)三(二甲氨基)鏻六氟磷酸盐 (BOP) 活化酰胺基团，在嘧啶核苷的 C4 位上轻松官能化，并对产品进行生物学评价†

  摘要：

  Ot-丁基二甲基甲硅烷基保护的胸苷、2'-脱氧尿苷和 3'-叠氮胸苷 (AZT) 与 (苯并三唑-1-基氧基)三(二甲氨基)鏻六氟磷酸盐 (BOP) 的反应导致 C4 酰胺羰基活化，形成推定的O 4 -(苯并三唑-1-基)衍生物。随后用烷基和芳基胺、硫醇和醇取代导致该位置容易官能化。与胺和硫醇的反应可以两步一锅转化或一步转化的方式进行。与醇的反应以两步一锅转化的方式进行。在这些研究过程中，鉴定出从嘧啶核苷形成1-(4-嘧啶基)-1H-苯并三唑-3-氧化物衍生物。然而，这些也经历了转化为所需的产品。通过催化还原将AZT获得的产物转化为3'-氨基衍生物。所有产品均经过检测其抑制癌细胞增殖和抗病毒活性的能力。许多药物被发现对 HIV-1 和 HIV-2 具有活性，其中一种对单纯疱疹病毒 1 (HSV-1) 具有活性。

  DOI：

  10.1039/c6ob02334g

文献信息

• Solid-phase synthesis of oligodeoxynucleotides containing 4-alkoxythymidine residues
  作者：H. C. P. F. Roelen、H. F. Brugghe、H. van den Elst、G. A. van der Marel、J. H. van Boom

  DOI：10.1002/recl.19921110207

  日期：——

  Immobilized and fully protected oligodeoxynucleotides containing a 4-(1,2,4-triazolyl)-thymidine residue at a predetermined position were prepared according to a well-established phosphite triester methodology using 2-cyanoethyl phosphoramidites of a 4-(1,2,4-triazolyl)-substituted thymidine and standard protected nucleosides. Treatment of the immobilized oligomer with methanol, ethanol or n-propanol

  根据公认的亚磷酸酯三酯方法，使用4-（1,2,4-，1,2,3-三氟乙烷基）的2-氰基乙基亚磷酰胺，制备在预定位置上含有4-（1,2,4-三唑基）-胸苷残基的固定化和完全保护的寡脱氧核苷酸。 4-三唑基）-取代的胸苷和标准保护的核苷。在DBU存在下于50℃用甲醇，乙醇或正丙醇处理固定的低聚物，得到相应的含有4-甲氧基，4-乙氧基-或4-正丙氧基胸苷残基的寡核苷酸。
• In search of Flavivirus inhibitors part 2: Tritylated, diphenylmethylated and other alkylated nucleoside analogues
  作者：Milind Saudi、Joanna Zmurko、Suzanne Kaptein、Jef Rozenski、Johan Neyts、Arthur Van Aerschot

  DOI：10.1016/j.ejmech.2014.02.011

  日期：2014.4

  hit 3′,5′-bistritylated uridine 1, a series of alkylated nucleoside analogues were synthesized and evaluated for their in vitro antiviral activities against dengue fever virus and yellow fever virus. Hereto, alkyl and aryl groups were attached at various positions of the sugar ring combined with subtle variation of the heterocyclic base. Among the new series of derivatives, 3′,5′-di-O-trityl-5-fluoro-2′-deoxyuridine

  几种黄病毒，例如黄热病病毒和登革热病毒，会在人体内引起严重的致命感染。继我们最初的命中3'，5'-双歧化尿苷1之后，合成了一系列烷基化核苷类似物，并评估了它们对登革热病毒和黄热病病毒的体外抗病毒活性。迄今为止，烷基和芳基连接在糖环的各个位置，并带有杂环碱基的细微变化。在新的衍生物系列中，3'，5'- di- O-三苯甲基-5-氟-2'-脱氧尿苷（39）是该系列中最有效的衍生物，可抑制黄热病病毒和登革热病毒的复制，其50有效浓度百分比（EC 50）〜1μg/ mL，无明显细胞毒性。其他氟化衍生物被证明更具毒性。几乎所有具有3'，5'-二-O-苯甲酰基-2'-脱氧尿苷（50）的二苯基甲基化嘧啶核苷都具有很强的低至1μg/ mL的细胞毒性作用。
• Cytotoxic and mutagenic properties of<i>O</i>⁴-alkylthymidine lesions in<i>Escherichia coli</i>cells
  作者：Pengcheng Wang、Nicholas J. Amato、Qianqian Zhai、Yinsheng Wang

  DOI：10.1093/nar/gkv941

  日期：2015.12.15

  Due to the abundant presence of alkylating agents in living cells and the environment, DNA alkylation is generally unavoidable. Among the alkylated DNA lesions, O4-alkylthymidine (O4-alkyldT) are known to be highly mutagenic and persistent in mammalian tissues. Not much is known about how the structures of the alkyl group affect the repair and replicative bypass of the O4-alkyldT lesions, or how the latter process is modulated by translesion synthesis polymerases. Herein, we synthesized oligodeoxyribonucleotides harboring eight site-specifically inserted O4-alkyldT lesions and examined their impact on DNA replication in Escherichia coli cells. We showed that the replication past all the O4-alkyldT lesions except (S)- and (R)-sBudT was highly efficient, and these lesions directed very high frequencies of dGMP misincorporation in E. coli cells. While SOS-induced DNA polymerases play redundant roles in bypassing most of the O4-alkyldT lesions, the bypass of (S)- and (R)-sBudT necessitated Pol V. Moreover, Ada was not involved in the repair of any O4-alkyldT lesions, Ogt was able to repair O4-MedT and, to a lesser extent, O4-EtdT and O4-nPrdT, but not other O4-alkyldT lesions. Together, our study provided important new knowledge about the repair of the O4-alkyldT lesions and their recognition by the E. coli replication machinery.

  由于活细胞和环境中大量存在烷基化剂，DNA烷基化通常是不可避免的。在烷基化 DNA 损伤中，已知 O4-烷基胸苷 (O4-烷基dT) 在哺乳动物组织中具有高度诱变性和持久性。关于烷基的结构如何影响 O4-烷基dT 损伤的修复和复制旁路，或者后一个过程如何由跨损伤合成聚合酶调节，人们知之甚少。在此，我们合成了含有八个位点特异性插入的 O4-烷基dT 损伤的寡脱氧核糖核苷酸，并检查了它们对大肠杆菌细胞中 DNA 复制的影响。我们表明，除了 (S)-和 (R)-sBudT 之外，经过所有 O4-烷基dT 损伤的复制都是高效的，并且这些损伤导致大肠杆菌细胞中非常高频率的 dGMP 错误掺入。虽然 SOS 诱导的 DNA 聚合酶在绕过大多数 O4-烷基dT 损伤方面发挥着多余的作用，但 (S)-和 (R)-sBudT 的绕过需要 Pol V。此外，Ada 不参与任何 O4-烷基dT 的修复Ogt 能够修复 O4-MedT，并在较小程度上修复 O4-EtdT 和 O4-nPrdT，但不能修复其他 O4-烷基dT 损伤。总之，我们的研究提供了有关 O4-烷基dT 损伤修复及其被大肠杆菌复制机制识别的重要新知识。
• Amplification, Enrichment, and Sequencing of Mutagenic Methylated DNA Adduct through Specifically Pairing with Unnatural Nucleobases
  作者：Wuyuan Zhu、Honglei Wang、Xiaohuan Li、Wenchao Tie、Bianbian Huo、Anlian Zhu、Lingjun Li

  DOI：10.1021/jacs.2c06110

  日期：2022.11.9

  but strongly mutagenic DNA base adduct; however, the sequencing method to determine m3T is lacking so far. Two of the main obstacles include the capacity of m3T to stall DNA elongation and its low abundance. To address the challenges, we report an unnatural base pairing strategy in this paper. A new m3T–TPT3 base pair was developed with a Vmax/Km value 82-fold higher than that of the m3T-A pair. The

  3-甲基胸腺嘧啶 (m3T) 是一种众所周知的化学稳定但具有强致突变性的 DNA 碱基加合物；然而，目前缺乏确定m3T的测序方法。两个主要障碍包括 m3T 阻止 DNA 延伸的能力及其低丰度。为了应对这些挑战，我们在本文中报告了一种不自然的碱基配对策略。开发了一个新的 m3T-TPT3 碱基对，其 Vmax/Km 值比 m3T-A 碱基对高 82 倍。TPT3 核碱基可以特异性地掺入 m3T 碱基的对面，并且可以有效地扩展由此产生的 m3T–TPT3 碱基对，从而在商业 DNA 聚合酶存在的情况下产生全长产物。重要的是，m3T–TPT3 对的特征使替代 PCR 扩增能够将 m3T 损伤的确切位置转移到非自然碱基对中，这允许 Sanger 测序以及基于生物素-链霉亲和素的 m3T 病变富集。综上所述，这项工作首次为 m3T 的扩增、富集和测序提供了一种简单、方便、实用的方法。
• Nucleotides, Part LXIII, New 2-(4-Nitrophenyl)ethyl(Npe)- and 2-(4-Nitrophenyl)ethoxycarbonyl(Npeoc)-Protected 2′-Deoxyribonucleosides and Their 3′-Phosphoramidites - Versatile Building Blocks for Oligonucleotide Synthesis
  作者：Holger Lang、Margarete Gottlieb、Michael Schwarz、Silke Farkas、Bernd S. Schulz、Frank Himmelsbach、Ramamurthy Charubala、Wolfgang Pfleiderer

  DOI：10.1002/(sici)1522-2675(19991215)82:12<2172::aid-hlca2172>3.0.co;2-r

  日期：1999.12.15

  A series of new base-protected and 5'-O-(4-monomethoxytrityl)- or 5'-O-(4,4'-dimethoxytrityl)-substituted 3'-(2-cyanoethyl diisopropylphosphoramidites) and 3'-[2-(4-nitrophenyl)ethyl diisopropylphosphoramidites] 52-66 and 67-82, respectively, are prepared as potential building blocks for oligonucleotide synthesis (see Scheme). Thus, 3',5'-di-O-acyl- and N-2,3'-O,5'-O-triacyl-2'-deoxyguanosines can easily be converted into the corresponding O-6-alkyl derivatives 6, 8, 10, 12, 14, and 16 by a Mitsunobu reaction using the appropriate alcohol. Mild hydrolysis removes the acyl groups from the sugar moiety (--> 9, 11, 13, 15, and 19 (via 18), resp.) which can then be tritylated (--> 38-42) and phosphitylated (--> 57-61) in the usual manner. N-2-[2-(4-nitrophenyl)ethoxycarbonyl]-substituted and N-2-[2-(4-nitrophenyl)ethoxycarbonyl]-O-6-[2-(4-nitrophenyl)ethyl]-substituted 2'-deoxyguanosines 5 and 7, respectively, are synthesized as new starting materials for tritylation (--> 28, 35, and 37) and phosphitylation (--> 54, 56, 70, and 78). Various O-4-alkylthymidines (see 20-24) are also converted to their 5'-O-dimethoxytrityl derivatives (see 43-47) and the corresponding phosphoramidites (see 62-66 and 79-82).