1,N⁶-ethano-3',5'-bis-O-(tert-butyldimethylsilyl)-2'-deoxyadenosine | 210689-68-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 1,N⁶-ethano-3',5'-bis-O-(tert-butyldimethylsilyl)-2'-deoxyadenosine
• 英文别名: tert-butyl-[[(2R,3S,5R)-3-[tert-butyl(dimethyl)silyl]oxy-5-(7,8-dihydroimidazo[2,1-f]purin-3-yl)oxolan-2-yl]methoxy]-dimethylsilane
• CAS: 210689-68-2
• 化学式: C₂₄H₄₃N₅O₃Si₂
• 分子量: 505.808
• InChiKey: KJKQBXMBKRERBD-IPMKNSEASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.32
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  73.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,N⁶-ethano-3',5'-bis-O-(tert-butyldimethylsilyl)-2'-deoxyadenosine 在 triethylamine trihydrofluoride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以91%的产率得到(2R,3S,5R)-5-(7,8-dihydroimidazo[2,1-f]purin-3-yl)-2-(hydroxymethyl)oxolan-3-ol
  参考文献：
  名称：

  Synthesis of 1,N⁶-Ethano-2‘-deoxyadenosine, a Metabolic Product of 1,3-Bis(2-chloroethyl)nitrosourea, and Its Incorporation into Oligomeric DNA

  摘要：

  1,N-6-Ethano-2'-deoxyadenosine (1) is one of the adducts formed during DNA reaction with the antitumor agent, 1,3-bis(2-chloroethyl)nitrosourea (BCNU), and was synthesized and incorporated into a site-specific deoxyoligonucleotide for the first time. The product 6-chloropurine-2'-deoxyriboside (11) was prepared in high yield by the reaction of 2'-deoxyinosine (6) with SOCl2, which then was derivatized to give compound 12 using tert-butyldimethylsilyl chloride, which was then reacted with 2-hydroxyethylamine to produce compound 13 in 86% yield. Reaction of 13 with (PhO)(8)P+MeI- in DMF gave the cyclized 1,N-6-ethano derivative 10 in 67% yield. Desilylation of 10 with triethylamine trihydrofluoride in THF gave 1,N-6-ethano-dA (1) in 91% yield. Tritylation of compound 1 with DMT+BF4- gave the 5'-O-DMT product 14 in 62% yield, which then was phosphitylated with 2-cyanoethyl N,N-diisopropylchlorophosphoramidite, which yielded a 1:1 mixture of the diastereoisomers 15 in 71% yield. This fully protected compound 15 was incorporated site-specifically into a 25-mer oligonucleotide. The coupling efficiency of ethano-dA phosphoramidite was 93%. Enzymatic hydrolysis and analysis by HPLC confirmed the incorporation of ethano-dA and base composition of the DNA oligomer. The latter is now under investigation for its biochemical and physical properties.

  DOI：

  10.1021/jo980170i
• 作为产物：
  描述：

  2'-脱氧肌苷 在 咪唑 、 氯化亚砜 、 甲基三苯氧基碘磷 、 碳酸氢钠 、 三乙胺 、 三氟乙酸酐 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.75h， 生成 1,N⁶-ethano-3',5'-bis-O-(tert-butyldimethylsilyl)-2'-deoxyadenosine
  参考文献：
  名称：

  Synthesis of 1,N⁶-Ethano-2‘-deoxyadenosine, a Metabolic Product of 1,3-Bis(2-chloroethyl)nitrosourea, and Its Incorporation into Oligomeric DNA

  摘要：

  1,N-6-Ethano-2'-deoxyadenosine (1) is one of the adducts formed during DNA reaction with the antitumor agent, 1,3-bis(2-chloroethyl)nitrosourea (BCNU), and was synthesized and incorporated into a site-specific deoxyoligonucleotide for the first time. The product 6-chloropurine-2'-deoxyriboside (11) was prepared in high yield by the reaction of 2'-deoxyinosine (6) with SOCl2, which then was derivatized to give compound 12 using tert-butyldimethylsilyl chloride, which was then reacted with 2-hydroxyethylamine to produce compound 13 in 86% yield. Reaction of 13 with (PhO)(8)P+MeI- in DMF gave the cyclized 1,N-6-ethano derivative 10 in 67% yield. Desilylation of 10 with triethylamine trihydrofluoride in THF gave 1,N-6-ethano-dA (1) in 91% yield. Tritylation of compound 1 with DMT+BF4- gave the 5'-O-DMT product 14 in 62% yield, which then was phosphitylated with 2-cyanoethyl N,N-diisopropylchlorophosphoramidite, which yielded a 1:1 mixture of the diastereoisomers 15 in 71% yield. This fully protected compound 15 was incorporated site-specifically into a 25-mer oligonucleotide. The coupling efficiency of ethano-dA phosphoramidite was 93%. Enzymatic hydrolysis and analysis by HPLC confirmed the incorporation of ethano-dA and base composition of the DNA oligomer. The latter is now under investigation for its biochemical and physical properties.

  DOI：

  10.1021/jo980170i

文献信息

• Unusual Deoxygenation and Reactivity Studies Related to <i>O</i>⁶-(Benzotriazol-1-yl)inosine Derivatives
  作者：Suyeal Bae、Mahesh K. Lakshman

  DOI：10.1021/jo7021795

  日期：2008.2.1

  leading to the formation of C-6 (benzotriazol-1-yl)purine nucleoside derivatives and pinB-O-Bpin. This reaction has been investigated by 11B1H} NMR and compared to pinB-O-Bpin obtained by oxidation of pinB-Bpin. The structures of the C-6 (benzotriazol-1-yl)purine nucleosides have been unequivocally established via Pd-mediated C−N bond formation between bromo purine nucleosides and 1H-benzotriazole. Finally

  报道了与O 6-（苯并三唑-1-基）肌苷衍生物的化学有关的新的和不寻常的进展。首先，已经开发了一种通过使用PPh 3 / I 2 / HOBt合成其的简单，可扩展的方法，并通过31 P 1 H} NMR对其进行了机理研究。然后对O 6-（苯并三唑-1-基）肌苷核苷与双（频哪醇）二硼（pinB-Bpin）之间独特的氧转移反应进行了研究，导致形成C-6（苯并三唑-1-基）嘌呤核苷衍生物和pinB-O-Bpin。该反应已被11 B 11 H NMR并与通过氧化pinB-Bpin获得的pinB-O-Bpin进行比较。C-6（苯并三唑-1-基）嘌呤核苷的结构已通过溴嘌呤核苷与1 H-苯并三唑之间的Pd介导的C-N键形成而明确建立。的1最后，短和极其简单的合成，Ñ 6 -ethano-和1，Ñ 6 -propano-2'-脱氧腺苷被报告以便证明所述的合成的通用性ø 6 - （苯并三唑-1-基）
• WO2008/45535
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis of 1,<i>N</i>⁶-Ethano-2‘-deoxyadenosine, a Metabolic Product of 1,3-Bis(2-chloroethyl)nitrosourea, and Its Incorporation into Oligomeric DNA
  作者：H. Maruenda、A. Chenna、L.-K. Liem、B. Singer

  DOI：10.1021/jo980170i

  日期：1998.6.1

  1,N-6-Ethano-2'-deoxyadenosine (1) is one of the adducts formed during DNA reaction with the antitumor agent, 1,3-bis(2-chloroethyl)nitrosourea (BCNU), and was synthesized and incorporated into a site-specific deoxyoligonucleotide for the first time. The product 6-chloropurine-2'-deoxyriboside (11) was prepared in high yield by the reaction of 2'-deoxyinosine (6) with SOCl2, which then was derivatized to give compound 12 using tert-butyldimethylsilyl chloride, which was then reacted with 2-hydroxyethylamine to produce compound 13 in 86% yield. Reaction of 13 with (PhO)(8)P+MeI- in DMF gave the cyclized 1,N-6-ethano derivative 10 in 67% yield. Desilylation of 10 with triethylamine trihydrofluoride in THF gave 1,N-6-ethano-dA (1) in 91% yield. Tritylation of compound 1 with DMT+BF4- gave the 5'-O-DMT product 14 in 62% yield, which then was phosphitylated with 2-cyanoethyl N,N-diisopropylchlorophosphoramidite, which yielded a 1:1 mixture of the diastereoisomers 15 in 71% yield. This fully protected compound 15 was incorporated site-specifically into a 25-mer oligonucleotide. The coupling efficiency of ethano-dA phosphoramidite was 93%. Enzymatic hydrolysis and analysis by HPLC confirmed the incorporation of ethano-dA and base composition of the DNA oligomer. The latter is now under investigation for its biochemical and physical properties.