3-N-benzoyl-3',5'-di-O-benzoyl-5-(3-tert-butyldimethylsilyloxypropyl)-2'-deoxyuridine | 1037176-25-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 3-N-benzoyl-3',5'-di-O-benzoyl-5-(3-tert-butyldimethylsilyloxypropyl)-2'-deoxyuridine
• 英文别名: [(2R,3S,5R)-5-[3-benzoyl-5-[3-[tert-butyl(dimethyl)silyl]oxypropyl]-2,4-dioxopyrimidin-1-yl]-3-benzoyloxyoxolan-2-yl]methyl benzoate
• CAS: 1037176-25-2
• 化学式: C₃₉H₄₄N₂O₉Si
• 分子量: 712.872
• InChiKey: JKBDMPALJOZBQQ-WIHCDAFUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.02
• 重原子数：
  51
• 可旋转键数：
  15
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  129
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  3-N-benzoyl-3',5'-di-O-benzoyl-5-(3-tert-butyldimethylsilyloxypropyl)-2'-deoxyuridine 在 盐酸 作用下， 以 乙醇 为溶剂， 生成 3-N-benzoyl-3',5'-di-O-benzoyl-5-(3-hydroxypropyl)-2'-deoxyuridine
  参考文献：
  名称：

  Synthesis of 5-Fluoroalkylated Pyrimidine Nucleosides via Negishi Cross-Coupling

  摘要：

  5-Fluoroalkylated pyrimidine nucleosides (1) have potential as therapeutic agents and molecular imaging agents targeting HSV1-tk suicide gene therapy. Thus, straightforward preparation of 5-fluoroalkylated nucleoside derivatives has been developed. Reported herein are the first examples of Pd-catalyzed Negishi cross-coupling of 3-N-benzoyl-3',5'-di-O-benzoyl-5-iodo-2'-deoxyuridine (2a) and 3-N-benzoyl-3',5'-di-O-benzoyl-5-iodo-2'-deoxy-2'-fluoroarabinouridine (2b) with unactivated CSp(3) fluoroalkylzinc bromides. This paper demonstrates the first synthesis of six 5-fluoroalkyl-2'-deoxypyrimidine nucleoside derivatives with three to five methylene chain lengths (5). Furthermore, this methodology has been extended to create a series of 13 5-alkyl-substituted nucleosides, including the target nucleosides 5 and 5-silyloxypropyl and 5-cyanobutyl derivatives.

  DOI：

  10.1021/jo800444y
• 作为产物：
  描述：

  (3-溴丙氧基)叔丁基二甲基硅烷 、 3-N-benzoyl-3',5'-di-O-benzoyl-5-iodo-2'-deoxyuridine 在 Pd(P(t-Bu)3) 碘 、 锌 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 0.5h， 以30%的产率得到3-N-benzoyl-3',5'-di-O-benzoyl-5-(3-tert-butyldimethylsilyloxypropyl)-2'-deoxyuridine
  参考文献：
  名称：

  Synthesis of 5-Fluoroalkylated Pyrimidine Nucleosides via Negishi Cross-Coupling

  摘要：

  5-Fluoroalkylated pyrimidine nucleosides (1) have potential as therapeutic agents and molecular imaging agents targeting HSV1-tk suicide gene therapy. Thus, straightforward preparation of 5-fluoroalkylated nucleoside derivatives has been developed. Reported herein are the first examples of Pd-catalyzed Negishi cross-coupling of 3-N-benzoyl-3',5'-di-O-benzoyl-5-iodo-2'-deoxyuridine (2a) and 3-N-benzoyl-3',5'-di-O-benzoyl-5-iodo-2'-deoxy-2'-fluoroarabinouridine (2b) with unactivated CSp(3) fluoroalkylzinc bromides. This paper demonstrates the first synthesis of six 5-fluoroalkyl-2'-deoxypyrimidine nucleoside derivatives with three to five methylene chain lengths (5). Furthermore, this methodology has been extended to create a series of 13 5-alkyl-substituted nucleosides, including the target nucleosides 5 and 5-silyloxypropyl and 5-cyanobutyl derivatives.

  DOI：

  10.1021/jo800444y

文献信息

• Synthesis of 5-Fluoroalkylated Pyrimidine Nucleosides via Negishi Cross-Coupling
  作者：Ann-Marie Chacko、Wenchao Qu、Hank F. Kung

  DOI：10.1021/jo800444y

  日期：2008.7.1

  5-Fluoroalkylated pyrimidine nucleosides (1) have potential as therapeutic agents and molecular imaging agents targeting HSV1-tk suicide gene therapy. Thus, straightforward preparation of 5-fluoroalkylated nucleoside derivatives has been developed. Reported herein are the first examples of Pd-catalyzed Negishi cross-coupling of 3-N-benzoyl-3',5'-di-O-benzoyl-5-iodo-2'-deoxyuridine (2a) and 3-N-benzoyl-3',5'-di-O-benzoyl-5-iodo-2'-deoxy-2'-fluoroarabinouridine (2b) with unactivated CSp(3) fluoroalkylzinc bromides. This paper demonstrates the first synthesis of six 5-fluoroalkyl-2'-deoxypyrimidine nucleoside derivatives with three to five methylene chain lengths (5). Furthermore, this methodology has been extended to create a series of 13 5-alkyl-substituted nucleosides, including the target nucleosides 5 and 5-silyloxypropyl and 5-cyanobutyl derivatives.
• Synthesis and in Vitro Evaluation of 5-[¹⁸F]Fluoroalkyl Pyrimidine Nucleosides for Molecular Imaging of Herpes Simplex Virus Type 1 Thymidine Kinase Reporter Gene Expression
  作者：Ann-Marie Chacko、Wenchao Qu、Hank F. Kung

  DOI：10.1021/jm800501d

  日期：2008.9.25

  Two novel series of 5-fluoroalkyl-2'-deoxyuridines (FPrDU, FBuDU, FPeDU) and 2'-fluoro-2'-deoxy-5-fluoroalkylarabinouridines (FFPrAU, FFBuAU, FFPeAU) that have three, four, or five methylene units (propyl, butyl, or pentyl) at C-5 were prepared and tested as reporter probes for imaging herpes simplex virus type I thymidine kinase (HSV1-tk) gene expression. The Negishi coupling methodology was employed in efficiently synthesizing the radiolabeling precursors. All six 5-[F-18]fluoroalkyl pyrimidines were readily prepared from 3-N-benzoyl-3',5'-di-O-benzoyl-protected 5-O-mesylate Precursors in 17-35% radiochemical yield (decay-corrected). In vitro studies highlighted that all six [F-18]-labeled nucleosides selectively accumulated in cells expressing the HSV1-TK protein and there was negligible uptake in control cells. [F-18]FPrDU, [F-18]FBuDU, [F-18]FPeDU, and [F-18]FFBuAU had the best uptake profiles. Despite their selective accumulation in HSV1-tk-expressing cells, all 5-fluoroalkyl pyrimidine nucleosides had low-to-negligible cytotoxic activity (CC50 > 1000-1209 mu M). Ultimately, the results demonstrated that 5-[F-18]fluoropropyl, [F-18]fluorobutyl, and [F-18]fluoropentyl pyrimidine nucleosides have the potential to be in vivo HSV1-TK PET reporter probes over a dynamic range of reporter gene expression levels.