tert-butyl (3aR,4R,6aS)-4-({[(1R)-2-methoxy-1-phenylethyl]amino}methyl)-2,2-dimethyltetrahydro-5H-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate | 860304-36-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: tert-butyl (3aR,4R,6aS)-4-({[(1R)-2-methoxy-1-phenylethyl]amino}methyl)-2,2-dimethyltetrahydro-5H-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate
• 英文别名: tert-butyl (3aR,4R,6aS)-4-[[[(1R)-2-methoxy-1-phenylethyl]amino]methyl]-2,2-dimethyl-3a,4,6,6a-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate
• CAS: 860304-36-5
• 化学式: C₂₂H₃₄N₂O₅
• 分子量: 406.522
• InChiKey: FPRYOGUYURRSER-ZSYWTGECSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  69.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl (3aR,4R,6aS)-4-({[(1R)-2-methoxy-1-phenylethyl]amino}methyl)-2,2-dimethyltetrahydro-5H-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate 在 三氟乙酸 作用下， 反应 1.0h， 以81 mg的产率得到(2R,3R,4S)-2-({[(1R)-2-methoxy-1-phenylethyl]amino}methyl)pyrrolidine-3,4-diol
  参考文献：
  名称：

  Functionalized Pyrrolidines Inhibit α-Mannosidase Activity and Growth of Human Glioblastoma and Melanoma Cells

  摘要：

  New substituted pyrrolidine-3,4-diol derivatives were prepared from D-(-)- and L-(+)-phenyl glycinol. The influence of the configuration and the substitution of the lateral side chain of these derivatives on the inhibition of 25 commercial glycosidases were determined. (2.R,3R,4S)-2-({[(1R)-2-Hydroxy-1-phenylethyl]amino}methyl)pyrrolidine-3,4-diol ((+)-7a) was a potent and selective inhibitor of jack bean a-mannosidase (K-i = 135 nM). However, when evaluated on human tumor cells, 7a, and the reference compound swainsonine, did not efficiently inhibit the growth of glioblastoma cells. Further derivatization of the hydroxyl group with lipophilic groups to increase bioavailability improved their growth inhibitory properties for human glioblastoma and melanoma cells. In particular, the 4-bromobenzoyl derivative 26 demonstrated high efficacy for human tumor cells whereas primary human fibroblasts were less sensitive to 26. Therefore, functionalized pyrrolidines have the potential to inhibit the growth of tumor cells and display selectivity for tumor cells when compared to normal cells.

  DOI：

  10.1021/jm0409019
• 作为产物：
  描述：

  D-苯甘氨醇 在 四丁基碘化铵 、 三乙酰氧基硼氢化钠 、 sodium hydride 、 碳酸氢钠 、 硫代水杨酸 、 1,4-双(二苯基膦)丁烷 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 作用下， 以 四氢呋喃 、 二甲基亚砜 、 1,2-二氯乙烷 为溶剂， 反应 15.17h， 生成 tert-butyl (3aR,4R,6aS)-4-({[(1R)-2-methoxy-1-phenylethyl]amino}methyl)-2,2-dimethyltetrahydro-5H-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate
  参考文献：
  名称：

  Functionalized Pyrrolidines Inhibit α-Mannosidase Activity and Growth of Human Glioblastoma and Melanoma Cells

  摘要：

  New substituted pyrrolidine-3,4-diol derivatives were prepared from D-(-)- and L-(+)-phenyl glycinol. The influence of the configuration and the substitution of the lateral side chain of these derivatives on the inhibition of 25 commercial glycosidases were determined. (2.R,3R,4S)-2-({[(1R)-2-Hydroxy-1-phenylethyl]amino}methyl)pyrrolidine-3,4-diol ((+)-7a) was a potent and selective inhibitor of jack bean a-mannosidase (K-i = 135 nM). However, when evaluated on human tumor cells, 7a, and the reference compound swainsonine, did not efficiently inhibit the growth of glioblastoma cells. Further derivatization of the hydroxyl group with lipophilic groups to increase bioavailability improved their growth inhibitory properties for human glioblastoma and melanoma cells. In particular, the 4-bromobenzoyl derivative 26 demonstrated high efficacy for human tumor cells whereas primary human fibroblasts were less sensitive to 26. Therefore, functionalized pyrrolidines have the potential to inhibit the growth of tumor cells and display selectivity for tumor cells when compared to normal cells.

  DOI：

  10.1021/jm0409019

文献信息

• Functionalized Pyrrolidines Inhibit α-Mannosidase Activity and Growth of Human Glioblastoma and Melanoma Cells
  作者：Hélène Fiaux、Florence Popowycz、Sylvain Favre、Catherine Schütz、Pierre Vogel、Sandrine Gerber-Lemaire、Lucienne Juillerat-Jeanneret

  DOI：10.1021/jm0409019

  日期：2005.6.1

  New substituted pyrrolidine-3,4-diol derivatives were prepared from D-(-)- and L-(+)-phenyl glycinol. The influence of the configuration and the substitution of the lateral side chain of these derivatives on the inhibition of 25 commercial glycosidases were determined. (2.R,3R,4S)-2-([(1R)-2-Hydroxy-1-phenylethyl]amino}methyl)pyrrolidine-3,4-diol ((+)-7a) was a potent and selective inhibitor of jack bean a-mannosidase (K-i = 135 nM). However, when evaluated on human tumor cells, 7a, and the reference compound swainsonine, did not efficiently inhibit the growth of glioblastoma cells. Further derivatization of the hydroxyl group with lipophilic groups to increase bioavailability improved their growth inhibitory properties for human glioblastoma and melanoma cells. In particular, the 4-bromobenzoyl derivative 26 demonstrated high efficacy for human tumor cells whereas primary human fibroblasts were less sensitive to 26. Therefore, functionalized pyrrolidines have the potential to inhibit the growth of tumor cells and display selectivity for tumor cells when compared to normal cells.