tetra(Boc)-araC | 913959-49-6

• 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: tetra(Boc)-araC
• 英文别名: 1-[4-N,N-2',3'-O-tetra-(tert-butyloxycarbonyl)-β-D-arabinofuranosyl]cytosine
• CAS: 913959-49-6
• 化学式: C₂₉H₄₅N₃O₁₃
• 分子量: 643.689
• InChiKey: RCYFLMAZLGMQIL-RSPOEFSDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.45
• 重原子数：
  45.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  191.25
• 氢给体数：
  1.0
• 氢受体数：
  15.0

反应信息

• 作为反应物：
  描述：

  tetra(Boc)-araC 在 四氮唑 、 盐酸 、 叔丁基过氧化氢 作用下， 以 乙醚 、 癸烷 、 乙腈 为溶剂， 反应 4.0h， 生成 ((2R,3S,4S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl bis(S-pivaloyl-2-mercaptoethan-1-yl)phosphate
  参考文献：
  名称：

  Synthetic Approaches to a Mononucleotide Prodrug of Cytarabine

  摘要：

  Synthetic pathways to a mononucleotide prodrug of cytarabine (Ara-C) bearing S-pivaloyl-2-thioethyl (tBuSATE) groups, as biolabile phosphate protections, are reported. Using a common phosphoramidite approach, two different kinds of nucleoside protecting groups have been investigated. During this study, we observed an intermolecular migration of the Boc protecting group in the course of the tert-butyldimethylsilyl ether cleavage using tetrabutyl ammonium fluoride.

  DOI：

  10.1080/15257770500267006
• 作为产物：
  描述：

  阿糖胞苷 在 吡啶 、 咪唑 、 4-二甲氨基吡啶 、 triethylamine trihydrofluoride 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 38.0h， 生成 tetra(Boc)-araC
  参考文献：
  名称：

  Synthetic Approaches to a Mononucleotide Prodrug of Cytarabine

  摘要：

  Synthetic pathways to a mononucleotide prodrug of cytarabine (Ara-C) bearing S-pivaloyl-2-thioethyl (tBuSATE) groups, as biolabile phosphate protections, are reported. Using a common phosphoramidite approach, two different kinds of nucleoside protecting groups have been investigated. During this study, we observed an intermolecular migration of the Boc protecting group in the course of the tert-butyldimethylsilyl ether cleavage using tetrabutyl ammonium fluoride.

  DOI：

  10.1080/15257770500267006

文献信息

• Special feature of mixed phosphotriester derivatives of cytarabine
  作者：Marie-Hélène Gouy、Lars P. Jordheim、Isabelle Lefebvre、Emeline Cros、Charles Dumontet、Suzanne Peyrottes、Christian Périgaud

  DOI：10.1016/j.bmc.2009.07.038

  日期：2009.9.1

  Despite the unquestionable therapeutic interest of bis(SATE) pronucleotides, a presystemic metabolism preventing the delivery of the prodrugs in target cancer cells or tumours may constitute a limitation to the in vivo development of such derivatives. In order to overcome these drawbacks several strategies have been envisaged and we report herein the application of the S-acyl-2-thioethyl (SATE) phenyl pronucleotide approach to the well-known cytotoxic nucleoside cytosine-1-beta-D-arabinofuranoside (cytarabine, araC). We describe modifications of the SATE moieties with the introduction of polar groups on the acyl residue, in order to study how these changes affect antitumoral activity and metabolic stability. Two different synthetic pathways were explored and lead to obtain the corresponding mixed derivatives in satisfactory yields. Cytotoxicity was studied in murine leukaemia cells L1210 as well as in cells derived from solid human tumours (Messa and MCF7). Biological evaluation of these compounds in cell culture experiments with nucleoside analogue-sensitive and resistant cell lines showed that the modified compounds were active at higher concentrations than unmodified cytarabine, yet were much able to partially reverse resistance due to deficient nucleoside transport or activation. These results can be correlated with an incomplete decomposition mechanism into the corresponding 5'-mononucleotide. (C) 2009 Elsevier Ltd. All rights reserved.