(S)-Pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-[(2R,3S,5R)-5-(5-fluoro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3-hydroxy-tetrahydro-furan-2-ylmethyl] ester | 287731-64-0

• 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: (S)-Pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-[(2R,3S,5R)-5-(5-fluoro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3-hydroxy-tetrahydro-furan-2-ylmethyl] ester
• 英文别名: 1-O-tert-butyl 2-O-[[(2R,3S,5R)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methyl] (2S)-pyrrolidine-1,2-dicarboxylate
• CAS: 287731-64-0
• 化学式: C₁₉H₂₆FN₃O₈
• 分子量: 443.429
• InChiKey: CUPGEVKMFVGMTM-IGQOVBAYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  135
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (S)-Pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-[(2R,3S,5R)-5-(5-fluoro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3-hydroxy-tetrahydro-furan-2-ylmethyl] ester 在 TEA 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 [(2R,3S,5R)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methyl (2S)-1-[(2S)-2-formamido-4-methylsulfanylbutanoyl]pyrrolidine-2-carboxylate
  参考文献：
  名称：

  Activation of antibacterial prodrugs by peptide deformylase

  摘要：

  5'-Dipeptidyl derivatives of 5-fluorodeoxyuridine (FdU) (1a-d) were synthesized. These compounds are biologically inactive but can be activated by peptide deformylase, which removes the N-terminal formyl group of the dipeptide, to release the active drug FdU via an intramolecular cyclization reaction. Because the deformylase is ubiquitous among bacteria but absent in mammalian cells, 1a-d provide a novel class of potential antibacterial agents. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00167-0
• 作为产物：
  描述：

  BOC-L-脯氨酸 、 5-氟-2'-脱氧脲核苷 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 1,4-二氧六环 为溶剂， 生成 (S)-Pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-[(2R,3S,5R)-5-(5-fluoro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3-hydroxy-tetrahydro-furan-2-ylmethyl] ester
  参考文献：
  名称：

  Activation of antibacterial prodrugs by peptide deformylase

  摘要：

  5'-Dipeptidyl derivatives of 5-fluorodeoxyuridine (FdU) (1a-d) were synthesized. These compounds are biologically inactive but can be activated by peptide deformylase, which removes the N-terminal formyl group of the dipeptide, to release the active drug FdU via an intramolecular cyclization reaction. Because the deformylase is ubiquitous among bacteria but absent in mammalian cells, 1a-d provide a novel class of potential antibacterial agents. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00167-0

文献信息

• ——
  作者：Balvinder S. Vig、Philip J. Lorenzi、Sachin Mittal、Christopher P. Landowski、Ho‐Chul Shin、Henry I. Mosberg、John M. Hilfinger、Gordon L. Amidon

  DOI：10.1023/a:1025745824632

  日期：——

  homogenates, the L-amino acid ester prodrugs hydrolyzed 10 to 75 times faster than the corresponding D-amino acid ester prodrugs. Pro and Phe ester prodrugs hydrolyzed much faster (3- to 30-fold) than the corresponding Val ester prodrugs. Further, the 5'-monoester prodrugs hydrolyzed significantly faster (3-fold) than the 3',5'-diester prodrugs. CONCLUSIONS Novel amino acid ester prodrugs of FUdR were successfully

  目的合成氟尿苷（FUdR）的氨基酸酯前药，并研究结构，立体化学和蛋白质的酯化部位对这些前药在Caco-2细胞匀浆中水解速率的影响。方法采用既定程序合成FUdR的氨基酸酯前药。在人腺癌细胞系（Caco-2）匀浆和pH 7.4磷酸盐缓冲液中评估了前药水解的动力学。结果合成并表征了以脯氨酸，L-缬氨酸，D-缬氨酸，L-苯丙氨酸和D-苯丙氨酸为原基的FUdR的3'-单酯，5'-单酯和3'，5'-二酯前药。在Caco-2细胞匀浆中，L-氨基酸酯前药的水解速度是相应D-氨基酸酯前药的10到75倍。Pro和Phe酯前药的水解速度比相应的Val酯前药快得多（3至30倍）。此外，5'-单酯前药的水解明显快于3'，5'-二酯前药的水解（3倍）。结论成功合成了新型的FUdR氨基酸酯前药。此处显示的结果清楚地表明，Caco-2细胞匀浆中FUdR前药的活化速率受该结构的结构，立体化学和酯化部位的影响。最后，5'-V