(E)-N′-(9-((2R,4S,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)-methyl)-4-hydroxytetrahydrofuran-2-yl)-6-oxo-6,9-dihydro-1H-purin-2-yl)-N,N-dimethylformimidamide

• 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: (E)-N′-(9-((2R,4S,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)-methyl)-4-hydroxytetrahydrofuran-2-yl)-6-oxo-6,9-dihydro-1H-purin-2-yl)-N,N-dimethylformimidamide
• 英文别名: 3'-Deoxy-N2-DMF-5'-O-DMT-guanosine；N'-[9-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxyoxolan-2-yl]-6-oxo-1H-purin-2-yl]-N,N-dimethylmethanimidamide
• 化学式: C₃₄H₃₆N₆O₆
• 分子量: 624.696
• InChiKey: YTRIMRXIMVGPAL-FTBOMTEUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  46
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  132
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (E)-N′-(9-((2R,4S,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)-methyl)-4-hydroxytetrahydrofuran-2-yl)-6-oxo-6,9-dihydro-1H-purin-2-yl)-N,N-dimethylformimidamide 在 ammonium hydroxide 、 溶剂黄146 作用下， 生成 2'-脱氧鸟苷
  参考文献：
  名称：

  Preparation of 2'-O-(.beta.-Cyanoethyl phosphoramidites) of 3'-Deoxycytidine and 3'-Deoxyguanosine and Their Use for Solid-Phase Synthesis of Oligodeoxynucleotides Containing 2',5'-Phosphodiester Linkages

  摘要：

  Convenient, preparative scale synthetic routes to 2'-O-(beta-cyanoethyl N,N-diisopropylphosphoramidites) of 3'-deoxycytidine (1) and 3'-deoxyguanosine (2) are described. The 3'-deoxycytidine nucleoside 5 was constructed by a modified Hilbert-Johnson reaction in which N-(4-isobutyryl)-cytosine (4) was ribosylated with anomeric acetate 3. Nucleoside 5 was converted to 5'-O(dimethoxytrityl)-4-N-isobutyryl-3'-deoxycytidine (7) and phosphitylated to provide phosphoramidite 1. Access to derivatives of 3'-deoxyguanosine was provided by selective removal of the 3'-hydroxyl of guanosine (10). Thus, the 3'-O-thiocarbamate of 5'-O-(dimethoxytrityl)-2-N-(dimethylformamidyl)- 2'-O-(triisopropylsilyl)guanosine (12) was reduced with tributyltin hydride and converted to phosphoramidite 2. In results to be reported elsewhere, phosphoramidites 1 and 2 were used to prepare oligodeoxynucleotides containing novel 2',5'-phosphodiester linkages using automated solid-phase DNA synthesis methods with average stepwise coupling yields of >97%.

  DOI：

  10.1021/jo00103a014
• 作为产物：
  描述：

  鸟苷 在 吡啶 、 咪唑 、 偶氮二异丁腈 、 四丁基氟化铵 、 三正丁基氢锡 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 149.0h， 生成 (E)-N′-(9-((2R,4S,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)-methyl)-4-hydroxytetrahydrofuran-2-yl)-6-oxo-6,9-dihydro-1H-purin-2-yl)-N,N-dimethylformimidamide
  参考文献：
  名称：

  Preparation of 2'-O-(.beta.-Cyanoethyl phosphoramidites) of 3'-Deoxycytidine and 3'-Deoxyguanosine and Their Use for Solid-Phase Synthesis of Oligodeoxynucleotides Containing 2',5'-Phosphodiester Linkages

  摘要：

  Convenient, preparative scale synthetic routes to 2'-O-(beta-cyanoethyl N,N-diisopropylphosphoramidites) of 3'-deoxycytidine (1) and 3'-deoxyguanosine (2) are described. The 3'-deoxycytidine nucleoside 5 was constructed by a modified Hilbert-Johnson reaction in which N-(4-isobutyryl)-cytosine (4) was ribosylated with anomeric acetate 3. Nucleoside 5 was converted to 5'-O(dimethoxytrityl)-4-N-isobutyryl-3'-deoxycytidine (7) and phosphitylated to provide phosphoramidite 1. Access to derivatives of 3'-deoxyguanosine was provided by selective removal of the 3'-hydroxyl of guanosine (10). Thus, the 3'-O-thiocarbamate of 5'-O-(dimethoxytrityl)-2-N-(dimethylformamidyl)- 2'-O-(triisopropylsilyl)guanosine (12) was reduced with tributyltin hydride and converted to phosphoramidite 2. In results to be reported elsewhere, phosphoramidites 1 and 2 were used to prepare oligodeoxynucleotides containing novel 2',5'-phosphodiester linkages using automated solid-phase DNA synthesis methods with average stepwise coupling yields of >97%.

  DOI：

  10.1021/jo00103a014

文献信息

• Facile Synthesis of Oligodeoxyribonucleotides via the Phosphoramidite Method without Nucleoside Base Protection
  作者：Yoshihiro Hayakawa、Masanori Kataoka

  DOI：10.1021/ja973731g

  日期：1998.12.1

  N-free nucleoside phosphoramidite and an N-unblocked nucleoside to give, after oxidation with bis(trimethylsilyl)peroxide or with tert-butyl hydroperoxide, a dinucleoside phosphate in >95% yield. In the solid-phase synthesis, which requires an excess amount of the phosphoramidite for the condensation, deoxyadenosine and deoxycytidine undergo N-phosphitylation to some extent. The undesired product, however

  已经开发了一种通过亚磷酰胺方法轻松合成寡脱氧核糖核苷酸的方法，无需对构建块进行碱基保护；它依赖于使用咪唑鎓三氟甲磺酸盐作为核苷亚磷酰胺和核苷缩合的促进剂。在溶液相中，通过使用等摩尔量的无 N 核苷亚磷酰胺和 N-未封闭核苷以高度 O 选择性的方式完成缩合，在用双（三甲基甲硅烷基）过氧化物或叔丁基过氧化氢氧化后得到, 产率 > 95% 的磷酸二核苷。在固相合成中，需要过量的亚磷酰胺进行缩合，脱氧腺苷和脱氧胞苷都进行了一定程度的N-亚磷酸化。然而，不想要的产品，可以通过在甲醇中用苯并咪唑鎓三氟甲磺酸盐短暂处理转化为不含 N 的衍生物。因此，整个过程允许化学选择性地形成核苷酸间连接。低聚物制备...
• <i>N</i>⁶-(2-Deoxy-<scp>d</scp>-<i>erythro</i>-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5-<i>N</i>-(2-hydroxy-3-buten-1-yl)-formamidopyrimidine Adducts of 1,3-Butadiene: Synthesis, Structural Identification, and Detection in Human Cells
  作者：Arnold S. Groehler、Dominic Najjar、Suresh S. Pujari、Dewakar Sangaraju、Natalia Y. Tretyakova

  DOI：10.1021/acs.chemrestox.8b00123

  日期：2018.9.17

  1,3-Butadiene (BD) is an environmental and occupational toxicant classified as a human carcinogen. BD is metabolically activated by cytochrome P450 monooxygenases to 3,4-epoxy-1-butene (EB), which alkylates DNA to form a range of nucleobase adducts. Among these, the most abundant are the hydrolytically labile N7-guanine adducts such as N7-(2-hydroxy-3-buten-1-yl)-guanine (N7-EB-dG). We now report that N7-EB-dG can be converted to the corresponding ring open N6-(2-deoxy-d-erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5-N-(2-hydroxy-3-buten-1-yl)-formamidopyrimidine (EB-Fapy-dG) adducts. EB-Fapy-dG lesions were detected in EB-treated calf thymus DNA and in EB-treated mammalian cells using quantitative isotope dilution nanoLC-ESI+-MS/MS. EB-Fapy-dG adduct formation in EB-treated calf thymus DNA was concentration dependent and was greatly accelerated at an increased pH. EB-FAPy-dG adduct amounts were 2-fold higher in base excision repair-deficient NEIL1–/– mouse embryonic fibroblasts (MEF) as compared to isogenic controls (NEIL1+/+), suggesting that this lesion may be a substrate for NEIL1. Furthermore, NEIL1–/– cells were sensitized to EB treatment as compared to NEIL1+/+ fibroblasts. Overall, our results indicate that ring-opened EB-FAPy-dG adducts form under physiological conditions, prompting future studies to determine their contributions to genotoxicity and mutagenicity of BD.

  1,3-丁二烯 (BD) 是一种环境和职业毒物，被列为人类致癌物。 BD 被细胞色素 P450 单加氧酶代谢激活为 3,4-环氧-1-丁烯 (EB)，后者烷基化 DNA 形成一系列核碱基加合物。其中，最丰富的是水解不稳定的N7-鸟嘌呤加合物，例如N7-(2-羟基-3-丁烯-1-基)-鸟嘌呤(N7-EB-dG)。我们现在报道N7-EB-dG可以转化为相应的开环N6-(2-脱氧-d-赤式-呋喃戊糖基)-2,6-二氨基-3,4-二氢-4-氧代-5-N -(2-羟基-3-丁烯-1-基)-甲酰胺嘧啶 (EB-Fapy-dG) 加合物。使用定量同位素稀释 nanoLC-ESI+-MS/MS 在 EB 处理的小牛胸腺 DNA 和 EB 处理的哺乳动物细胞中检测到 EB-Fapy-dG 损伤。 EB 处理的小牛胸腺 DNA 中 EB-Fapy-dG 加合物的形成具有浓度依赖性，并且在 pH 值升高时大大加速。与同基因对照 (NEIL1+/+) 相比，碱基切除修复缺陷的 NEIL1–/– 小鼠胚胎成纤维细胞 (MEF) 中 EB-FAPy-dG 加合物的量高出 2 倍，表明该病变可能是 NEIL1 的底物。此外，与 NEIL1+/+ 成纤维细胞相比，NEIL1–/– 细胞对 EB 治疗更敏感。总的来说，我们的结果表明，开环 EB-FAPy-dG 加合物在生理条件下形成，促使未来的研究确定它们对 BD 遗传毒性和致突变性的贡献。
• Reagents for reversibly terminating primer extension
  申请人：Benner Steven A.

  公开号：US20110275124A1

  公开（公告）日：2011-11-10

  This invention relates to the field of nucleic acid chemistry, more specifically to the field of compositions of matter that comprise triphosphates of modified 2′-deoxynucleosides and oligonucleotides that are formed when these are appended to the 3′-end of a primer, wherein said modifications comprise NH 2 moiety attached to their 3′-hydroxyl group and a fluorescent species in a form of a tag affixed to the nucleobase via a linker that can be cleaved. Such compositions and their associated processes enable and improve the sequencing of oligonucleotides using a strategy of cyclic reversible termination, as outlined in U.S. Pat. No. 6,664,079. Most specifically, the invention concerns compositions of matter that are 5′-triphosphates of ribo- and 2′-deoxyribonucleosides carrying detectable tags and oligonucleotides that might be derived from them. The invention also concerns processes wherein a DNA polymerase, RNA polymerase, or reverse transcriptase synthesizes said oligonucleotides via addition of said triphosphates to a primer.

  本发明涉及核酸化学领域，更具体地涉及包含经过修饰的2'-去氧核苷酸三磷酸盐和寡核苷酸的物质组成，当它们附加到引物的3'-端时形成，其中所述修饰包括连接到它们的3'-羟基上的NH2基团和通过可断链的连接器固定在核碱基上的荧光物种。这些组成物及其相关的过程使得并改进了使用循环可逆终止策略对寡核苷酸进行测序，如美国专利号6,664,079所概述的。最具体地，本发明涉及载有可检测标记的核糖核苷酸和2'-去氧核糖核苷酸的5'-三磷酸盐以及可能从它们中派生出的寡核苷酸的物质组成。本发明还涉及DNA聚合酶、RNA聚合酶或反转录酶通过向引物添加所述三磷酸盐来合成所述寡核苷酸的过程。
• ARNOLD, LUBOS;TOCIK, ZDENEK;BRADKOVA, ELISKA;HOSTOMSKY, ZDENEK;PACES, VAC+, COLLECT. CZECHOSL. CHEM. COMMUN., 54,(1989) N, C. 523-532
  作者：ARNOLD, LUBOS、TOCIK, ZDENEK、BRADKOVA, ELISKA、HOSTOMSKY, ZDENEK、PACES, VAC+

  DOI：——

  日期：——
• TOCIK, Z.;ARNOLD, L.;SMRT, J., 7TH SYMP. CHEM. NUCL. ACID COMPON., BECHYNE CASTLE, AUG. 30TH - SEPT. 5TH+
  作者：TOCIK, Z.、ARNOLD, L.、SMRT, J.

  DOI：——

  日期：——