O-[4-N,N-2',3'-O-tetra-(tert-butyloxycarbonyl)-β-D-arabinofuranosylcytosine]-O'-[S-(2-(2,2-dimethyl-1,3-dioxan-5-yl)propionyl)-2-thioethyl]-O'-phenylphosphate | 1192047-91-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物
• 英文名称: O-[4-N,N-2',3'-O-tetra-(tert-butyloxycarbonyl)-β-D-arabinofuranosylcytosine]-O'-[S-(2-(2,2-dimethyl-1,3-dioxan-5-yl)propionyl)-2-thioethyl]-O'-phenylphosphate
• CAS: 1192047-91-8
• 化学式: C₄₅H₆₆N₃O₁₉PS
• 分子量: 1016.07
• InChiKey: YBHCDQMVJLSVTE-NATKDUCDSA-N

反应信息

• 作为反应物：
  描述：

  O-[4-N,N-2',3'-O-tetra-(tert-butyloxycarbonyl)-β-D-arabinofuranosylcytosine]-O'-[S-(2-(2,2-dimethyl-1,3-dioxan-5-yl)propionyl)-2-thioethyl]-O'-phenylphosphate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.25h， 以89%的产率得到O-[β-D-arabinofuranosylcytosine]-O'-[(S-(2,2-hydroxymethyl)propionyl)-2-thioethyl]-O''-phenylphosphate
  参考文献：
  名称：

  Special feature of mixed phosphotriester derivatives of cytarabine

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2009.07.038
• 作为产物：
  描述：

  在 叔丁基过氧化氢 作用下， 以 癸烷 、 乙腈 为溶剂， 以0.37 g的产率得到O-[4-N,N-2',3'-O-tetra-(tert-butyloxycarbonyl)-β-D-arabinofuranosylcytosine]-O'-[S-(2-(2,2-dimethyl-1,3-dioxan-5-yl)propionyl)-2-thioethyl]-O'-phenylphosphate
  参考文献：
  名称：

  Special feature of mixed phosphotriester derivatives of cytarabine

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2009.07.038