O(4)-乙基胸苷 | 59495-22-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 中文名称: O(4)-乙基胸苷
• 英文名称: O⁴-ethyl-2'-deoxythymidine
• 英文别名: O⁴-ethylthymidine；4-ethoxy-2'-deoxythymidine；O⁴-EtdT；O⁴-ethyl-dT；1-(β-D-erythro-2-deoxy-pentofuranosyl)-4-ethoxy-5-methyl-1H-pyrimidin-2-one；4-O-Ethyl-1-(2-desoxy-β-D-ribofuranosyl)-thymin；O⁴-Ethylthymidin；4-O-Ethylthymidine；4-ethoxy-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidin-2-one
• CAS: 59495-22-6
• 化学式: C₁₂H₁₈N₂O₅
• 分子量: 270.285
• InChiKey: QZVVYDMWOGPALV-IVZWLZJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 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：

  O(4)-乙基胸苷 在 N,N-二异丙基乙胺 作用下， 以 吡啶 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 5'-O-(4,4'-dimethoxytrityl)-O⁴-ethylthymidine 3'-[2-(4-nitrophenyl)ethyl diisopropylphosphoramidite]
  参考文献：
  名称：

  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

  摘要：

  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).

  DOI：

  10.1002/(sici)1522-2675(19991215)82:12<2172::aid-hlca2172>3.0.co;2-r
• 作为产物：
  描述：

  3,5-双-O-乙酰胸苷 在 1,8-diaza[5.4.0]undec-7-ene 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 27.0h， 生成 O(4)-乙基胸苷
  参考文献：
  名称：

  固相合成含4-烷氧基胸苷残基的寡脱氧核苷酸

  摘要：

  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。

  DOI：

  10.1002/recl.19921110207

文献信息

• 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。
• Sadana, Krishan L.; Razi, M. Tahir; Lee, Terry, Canadian Journal of Chemistry, 1988, vol. 66, p. 1628 - 1634
  作者：Sadana, Krishan L.、Razi, M. Tahir、Lee, Terry、Sebastian, Rudy、Buchko, Garry W.、Hruska, Frank E.

  DOI：——

  日期：——
• Carcinogenic alkylation of nucleic acid bases. Structure and conformation of O4-ethyl-2'-deoxythymidine in the solid state and in solution
  作者：George I. Birnbaum、Krishan L. Sadana、Wayne J. P. Blonski、Frank E. Hruska

  DOI：10.1021/ja00267a042

  日期：1986.4
• SAFFHILL, ROY, NUCLEOSIDES AND NUCLEOTIDES, 6,(1987) N 4, 679-689
  作者：SAFFHILL, ROY

  DOI：——

  日期：——
• 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。