1-[5'-O-(tert-butyldimethylsilyl)-β-D-arabinofuranosyl]cytosine | 82976-97-4

• 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: 1-[5'-O-(tert-butyldimethylsilyl)-β-D-arabinofuranosyl]cytosine
• 英文别名: 5'-O-(t-butyldimethylsilyl)arabinocytidine；4-amino-1-[(2R,3S,4S,5R)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-3,4-dihydroxyoxolan-2-yl]pyrimidin-2-one
• CAS: 82976-97-4
• 化学式: C₁₅H₂₇N₃O₅Si
• 分子量: 357.482
• InChiKey: FQURJFMVIDBLGD-FOUMNBMASA-N

物化性质

• 熔点：
  162-164 °C
• 沸点：
  480.8±55.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.47
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  119.83
• 氢给体数：
  3.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  1-[5'-O-(tert-butyldimethylsilyl)-β-D-arabinofuranosyl]cytosine 在 四氮唑 、 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 、 乙腈 为溶剂， 反应 37.0h， 生成
  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：

  叔丁基二甲基氯硅烷 、 阿糖胞苷 在 吡啶 作用下， 以85.4%的产率得到1-[5'-O-(tert-butyldimethylsilyl)-β-D-arabinofuranosyl]cytosine
  参考文献：
  名称：

  [EN] SUBSTITUTED NUCLEOSIDE AND NUCLEOTIDE ANALOGS
  [FR] NUCLEOSIDE SUBSTITUE ET ANALOGUES NUCLEOTIDIQUES

  摘要：

  本文披露了具有保护磷酸酯基团的核苷酸类似物，以及合成具有保护磷酸酯基团的核苷酸类似物的方法，以及利用具有保护磷酸酯基团的核苷酸类似物治疗病毒感染、癌症和/或寄生虫病等疾病和/或症状的方法。

  公开号：

  WO2010108140A1

文献信息

• Ogilvie, Kelvin K.; McGee, Danny P. C.; Boisvert, Suzanne M., Canadian Journal of Chemistry, 1983, vol. 61, p. 1204 - 1212
  作者：Ogilvie, Kelvin K.、McGee, Danny P. C.、Boisvert, Suzanne M.、Hakimelahi, Gholam H.、Proba, Zbigniew A.

  DOI：——

  日期：——
• Enhancing the Efficacy of Ara-C through Conjugation with PAMAM Dendrimer and Linear PEG: A Comparative Study
  作者：Ugir Hossain Sk、Siva P. Kambhampati、Manoj K. Mishra、Wojciech G. Lesniak、Fan Zhang、Rangaramanujam M. Kannan

  DOI：10.1021/bm3018615

  日期：2013.3.11

  1 beta-D-Arabinofuranosylcytosine (Cytarabine, Ara-C) is a key drug in the treatment of acute myeloid leukemia. Ara-C has a number of limitations such as a rapid deactivation by cytidine deaminase leading to the formation of a biologically inactive metabolite, Ara-U (1 beta-D-arabinofuranosyluracil), a low lipophilicity, and fast clearance from the body. To address these problems, we developed a conjugate in which hydroxyl-terminated PAMAM dendrimer, G4-OH ["D"] and PEG were used as carriers for the drug (Ara-C). The conjugates were synthesized using an efficient multistep protection/deprotection method resulting in the formation of a covalent bond between the primary hydroxyl group of Ara-C and dendrimer/PEG. The structure, physicochemical properties, and drug release kinetics were characterized extensively. H-1 NMR and MALDI-TOF mass spectrometry suggested covalent attachment of 10 Ara-C molecules to the dendrimer. The release profile of Ara-C in human plasma and in PBS buffer (pH 7.4) showed that the conjugates released the drug over 14 days in PBS, with the release sped up in plasma. In PBS, while most of the drug is released from PEG-Ara-C, the dendrimer continues to release the drug in a sustained fashion. The results also suggested that the formation of the inactive form of Ara-C (Ara-U) was delayed upon conjugation of Ara-C to the polymers. The inhibition of cancer growth by the dendrimer-Ara-C and PEG-Ara-C conjugates was evaluated in A549 human adenocarcinoma epithelial cells. Both dendrimer- and PEG-Ara-C conjugates were 4-fold more effective in inhibition of A549 cells compared to free Ara-C after 72 h of treatment.
• MACCOSS, M.
  作者：MACCOSS, M.

  DOI：——

  日期：——