Boc-Glu(acyclothymidine ester)-OBn | 870287-52-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Boc-Glu(acyclothymidine ester)-OBn
• CAS: 870287-52-8
• 化学式: C₂₅H₃₃N₃O₉
• 分子量: 519.552
• InChiKey: ZVLPIYDRSSXCMW-IBGZPJMESA-N

物化性质

• 密度：
  1.236±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.78
• 重原子数：
  37.0
• 可旋转键数：
  12.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  155.02
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  Boc-Glu(acyclothymidine ester)-OBn 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 (S)-4-Amino-4-(carboxymethyl-methyl-carbamoyl)-butyric acid 2-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethoxy)-ethyl ester; compound with trifluoro-acetic acid
  参考文献：
  名称：

  Pyrimidine and nucleoside γ-esters of l-Glu-Sar: Synthesis, stability and interaction with hPEPT1

  摘要：

  The aim of the present study was to improve the synthetic pathway of bioreversible dipeptide derivatives as well as evaluate the potential of using L-Glu-Sar as a pro-moiety for delivering three newly synthesised nucleoside and pyrimidine L-Glu-Sar derivatives. L-Glu(trans-2-thymine-1-yl-tetrahydrofuran-3-yl ester)-Sar (I), L-Glu(thymine-1-yl-methyl ester)-Sar (II) and L-Glu(acyclothymidine)-Sar (III) were synthesised and in vitro stability was studied in various aqueous and biological media. Affinity to and translocation via hPEPT1 was investigated in mature Caco-2 cell monolayers, grown on permeable supports. Affinity was estimated in a competition assay, using [C-14] labelled Gly-Sar (glycylsarcosine). Translocation was measured as pHi-changes induced by the substrates using the fluorescent probe BCECF and an epifluorescence microscope setup. All dipeptide derivatives released the model drugs quantitatively by specific base-catalysed hydrolysis at pH > 6.0. II was labile in aqueous buffer solution, whereas 1 and III showed appropriate stability for oral administration. In 10% porcine intestinal homogenate, the half-lives of the dipeptide derivatives indicated limited enzyme catalyzed degradation. All compounds showed good affinity to hPEPT1, but the Compounds I and III showed not to be translocated by hPEPT1. The translocation of the L-Glu-Sar derivative of acyclovir, L-Glu(acyclovir)-Sar was also investigated and showed not to take place. Consequently, L-Glu-Sar seems to be a poor pro-moiety for hPEPT1-mediated transport. (c) 2005 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejps.2005.02.007
• 作为产物：
  描述：

  O,O-二(三甲基甲硅烷基)胸苷 在 4-二甲氨基吡啶 、 三甲基氯硅烷 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 potassium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 16.0h， 生成 Boc-Glu(acyclothymidine ester)-OBn
  参考文献：
  名称：

  Pyrimidine and nucleoside γ-esters of l-Glu-Sar: Synthesis, stability and interaction with hPEPT1

  摘要：

  The aim of the present study was to improve the synthetic pathway of bioreversible dipeptide derivatives as well as evaluate the potential of using L-Glu-Sar as a pro-moiety for delivering three newly synthesised nucleoside and pyrimidine L-Glu-Sar derivatives. L-Glu(trans-2-thymine-1-yl-tetrahydrofuran-3-yl ester)-Sar (I), L-Glu(thymine-1-yl-methyl ester)-Sar (II) and L-Glu(acyclothymidine)-Sar (III) were synthesised and in vitro stability was studied in various aqueous and biological media. Affinity to and translocation via hPEPT1 was investigated in mature Caco-2 cell monolayers, grown on permeable supports. Affinity was estimated in a competition assay, using [C-14] labelled Gly-Sar (glycylsarcosine). Translocation was measured as pHi-changes induced by the substrates using the fluorescent probe BCECF and an epifluorescence microscope setup. All dipeptide derivatives released the model drugs quantitatively by specific base-catalysed hydrolysis at pH > 6.0. II was labile in aqueous buffer solution, whereas 1 and III showed appropriate stability for oral administration. In 10% porcine intestinal homogenate, the half-lives of the dipeptide derivatives indicated limited enzyme catalyzed degradation. All compounds showed good affinity to hPEPT1, but the Compounds I and III showed not to be translocated by hPEPT1. The translocation of the L-Glu-Sar derivative of acyclovir, L-Glu(acyclovir)-Sar was also investigated and showed not to take place. Consequently, L-Glu-Sar seems to be a poor pro-moiety for hPEPT1-mediated transport. (c) 2005 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejps.2005.02.007