5'-O-propionyl ara-C | 881848-60-8

• 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: 5'-O-propionyl ara-C
• 英文别名: [(2R,3S,4S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl propanoate
• CAS: 881848-60-8
• 化学式: C₁₂H₁₇N₃O₆
• 分子量: 299.283
• InChiKey: YJRHIFKPYBOFLT-ZAVXEINISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  135
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  丙酰氯 、 盐酸阿糖胞苷 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以39%的产率得到5'-O-propionyl ara-C
  参考文献：
  名称：

  Transdermal Penetration of Cytarabine and Its 5-O Alkyl Ester Derivatives

  摘要：

  本研究的目的是合成并确定胞嘧啶阿拉伯糖苷及其5-烷基酯的体外透皮渗透性，并建立与所选物理化学性质的相关性（如果有）。通过胞嘧啶阿拉伯糖苷（1）的药效团5-OH进行酰化反应合成了n-烷基酯。使用Franz扩散池方法测定了（1）及其酯的透皮通量值。测定了水溶性和log D（pH 7.4）值，并评估了其与透皮通量的相关性。观察到水溶性（Sw）与log D值之间存在反比关系。在所有酯中，（4）表现出最高的通量值22.2 nmol.cm-2.h-1，与母药胞嘧啶阿拉伯糖苷（3.70 nmol.cm-2.h-1）显著不同。在水溶性和通量值之间没有发现趋势。

  DOI：

  10.2174/157340610791321451

文献信息

• Regioselective synthesis of cytarabine monopropionate by using a fungal whole-cell biocatalyst in nonaqueous medium
  作者：Mei-yan Yang、Hui Wu、Zhi-hong Lu、Xiao-feng Li、Fu-rao Lai、Guang-lei Zhao

  DOI：10.1016/j.bmcl.2014.05.092

  日期：2014.8

  The utilization of a dehydrated fungal biocatalyst of Aspergillus oryzae cells was successfully performed to achieve efficient acylation modification of a polar nucleoside cytarabine (ara-C). Organic solvents showed evident influence on the reaction catalyzed by the A. oryzae whole-cells. Except for hexane-pyridine, the catalytic activity and regioselectivity of the whole-cells clearly increased with increasing the polarity of the hydrophobic organic solvents used. The effects of some crucial factors on the reaction were further examined. The best reaction medium, hydrophobic solvent concentration, vinyl propionate/ara-C ratio, reaction temperature and shaking speed were confirmed as isopropyl ether (IPE)-pyridine, 30% (v/v), 90, 30 degrees C and 140-180 rpm, respectively. The cell biocatalyst also showed good thermal stabilities in both IPE-pyridine and hexane-pyridine systems. In addition, the desired 3'-O-propional derivative of ara-C was synthesized with the yields of 88.3% and regioselectivity (>70%). The resulting biocatalytic system appears to be an effective alternative, and can thus be employed for application in highly regioselective modification of nucleoside analogues. (C) 2014 Published by Elsevier Ltd.
• Transdermal Penetration of Cytarabine and Its 5-O Alkyl Ester Derivatives
  作者：Lesetja J. Legoabe、Jaco C. Breytenbach、David D. N'Da、J. Wilma Breytenbach

  DOI：10.2174/157340610791321451

  日期：2010.3.1

  The purpose of this study was to synthesize and determine the in vitro transdermal penetration of cytarabine and its 5-alkyl esters and to establish a correlation, if any, with selected physicochemical properties. The n-alkyl esters were synthesized by acylation of cytarabine (1) at its pharmacophoric 5-OH. The transdermal flux values of (1) and its esters were determined in vitro using Franz diffusion cell methodology. Aqueous solubility and log D (pH 7.4) values were determined and assessed for correlation to transdermal flux. An inverse relation was observed between the water solubility (Sw) and log D values. Of all esters, (4) exhibited the highest flux value of 22.2 nmol.cm-2.h-1, which is significantly different to that of the parent drug cytarabine (3.70 nmol.cm-2.h-1). No trend was found between water solubility and flux values.

  本研究的目的是合成并确定胞嘧啶阿拉伯糖苷及其5-烷基酯的体外透皮渗透性，并建立与所选物理化学性质的相关性（如果有）。通过胞嘧啶阿拉伯糖苷（1）的药效团5-OH进行酰化反应合成了n-烷基酯。使用Franz扩散池方法测定了（1）及其酯的透皮通量值。测定了水溶性和log D（pH 7.4）值，并评估了其与透皮通量的相关性。观察到水溶性（Sw）与log D值之间存在反比关系。在所有酯中，（4）表现出最高的通量值22.2 nmol.cm-2.h-1，与母药胞嘧啶阿拉伯糖苷（3.70 nmol.cm-2.h-1）显著不同。在水溶性和通量值之间没有发现趋势。