5'-O-(4,4'-dimethoxytrityl)-O⁴-methylthymidine | 117775-90-3

• 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: 5'-O-(4,4'-dimethoxytrityl)-O⁴-methylthymidine
• 英文别名: 5'-O-(4,4'-Dimethoxytrityl)-4-O-methylthymidine；1-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxyoxolan-2-yl]-4-methoxy-5-methylpyrimidin-2-one
• CAS: 117775-90-3
• 化学式: C₃₂H₃₄N₂O₇
• 分子量: 558.631
• InChiKey: JXJWNOAKHVCNBX-ZGIBFIJWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  41
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  99
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5'-O-(4,4'-dimethoxytrityl)-O⁴-methylthymidine 、 2-(4-nitrophenyl)ethyl diisopropylphosphoramidochloridite 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以73%的产率得到5'-O-(4,4'-dimethoxytrityl)-O⁴-methylthymidine 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：

  5'-O-(4,4'-Dimethoxytrityl)-4-thiothymidine 在 potassium cyanide 、 lithium hydroxide 、 18-冠醚-6 、 碳酸氢钠 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 生成 5'-O-(4,4'-dimethoxytrityl)-O⁴-methylthymidine
  参考文献：
  名称：

  5′-O-(4-4′-dimethylthoxytrityl)-4-thiocyanatothymidine A useful intermediate for the preparation of various 4-substituted thymidine analogues

  摘要：

  The thiocyanato group in 5'-O-(4,4'-dimethoxytrityl)-4-thiocyanatothymidine 2 is easily displaced by a variety of O-, N- and S-nucleophiles, making this compound a useful intermediate for the preparation of 4-substituted thymidine analogues.

  DOI：

  10.1016/s0040-4039(00)74367-x

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。