(E)-N′-(9-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-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 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: (E)-N′-(9-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-6-oxo-6,9-dihydro-1H-purin-2-yl)-N,N-dimethylformimidamide
• 英文别名: 2'-Deoxy-N2-DMF-guanosine；N'-[9-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-oxo-1H-purin-2-yl]-N,N-dimethylmethanimidamide
• 化学式: C₁₃H₁₈N₆O₄
• 分子量: 322.324
• InChiKey: ZXECVVVXPHBGGX-NMSRVTMWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  6

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  N2-[(二甲氨基)亚甲基]鸟苷	N-dimethylaminomethylene guanosine	1055407-32-3	C13H18N6O5	338.323
  ——	(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	——	C34H36N6O6	624.696
  2'-脱氧鸟苷	2'-Deoxyguanosine	961-07-9	C10H13N5O4	267.244
  ——	5'-O-(4,4'-Dimethoxytrityl)-2-N-((dimethylamino)methylene)-3'-O-(triisopropylsilyl)guanosine	——	C43H56N6O7Si	797.039
  鸟苷	GUANOSINE	118-00-3	C10H13N5O5	283.244

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(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	——	C34H36N6O6	624.696
  5-O-(4,4-二甲氧基三苯甲游基)-2-脱氧鸟苷	2'-deoxy-5'-O-(dimethoxytrityl)guanosine	81144-43-6	C31H31N5O6	569.617
  2'-脱氧鸟苷	2'-Deoxyguanosine	961-07-9	C10H13N5O4	267.244
  ——	5'-O-(4,4'-dimethoxytrityl)-2'-deoxyguanosine-3'-O-[(2-cyanoethyl)-N,N-diisopropylphosphoramidite]	140613-56-5	C40H48N7O7P	769.838
  ——	2-cyanoethyl [5'-O-(p,p'-dimethoxytrityl)-2'-deoxyguanylyl]-(3',5')-3'-O-(tert-butyldimethylsilyl)thymidine	——	C50H61N8O13PSi	1041.14

反应信息

• 作为反应物：
  描述：

  (E)-N′-(9-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-6-oxo-6,9-dihydro-1H-purin-2-yl)-N,N-dimethylformimidamide 在 ammonium hydroxide 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 、 溶剂黄146 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)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-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。
• Oxidative conversion of N-dimethylformamidine nucleosides to N-cyano nucleosides
  作者：Bashar Mullah、Alex Andrus、Hong Zhao、Roger A. Jones

  DOI：10.1016/0040-4039(95)00816-u

  日期：1995.6

  Reaction of the N-dimethylformamidine (dmf) derivatives of 2'-deoxyguanosine, guanosine, and T-deoxyadenosine with iodine and aqueous ammonia gives the corresponding N-cyano nucleosides. This reaction occurs in oligonucleotides under conditions where iodine is retained on the solid support, or in the synthesis column, prior to cleavage with aqueous ammonia. This base modification can be eliminated with lower iodine concentration in the oxidation reagent.
• OSEI-TWUM, E. Y.;MAMER, O. A.;QUILLIAM, M. A.;GERGELY, R., NUCLEOSIDES AND NUCLEOTIDES, 9,(1990) N, C. 369-372
  作者：OSEI-TWUM, E. Y.、MAMER, O. A.、QUILLIAM, M. A.、GERGELY, R.

  DOI：——

  日期：——
• 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
  作者：Terry L. Sheppard、Andrew T. Rosenblatt、Ronald Breslow

  DOI：10.1021/jo00103a014

  日期：1994.12

  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%.