L-Tyrosine,N-[(phenylmethoxy)carbonyl]-3-[[(phenylmethoxy)carbonyl]oxy]-,phenylmethyl carbonate (ester) | 37178-32-8

• 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: L-Tyrosine,N-[(phenylmethoxy)carbonyl]-3-[[(phenylmethoxy)carbonyl]oxy]-,phenylmethyl carbonate (ester)
• 英文别名: N,O,O'-tricarbobenzoxy-L-Dopa
• CAS: 37178-32-8；37178-42-0
• 化学式: C₃₃H₂₉NO₁₀
• 分子量: 599.594
• InChiKey: MBDMXZYDIFYMAE-UHFFFAOYSA-N

物化性质

• 沸点：
  802.9±65.0 °C(Predicted)
• 密度：
  1.334±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.04
• 重原子数：
  44.0
• 可旋转键数：
  12.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  146.69
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  L-Tyrosine,N-[(phenylmethoxy)carbonyl]-3-[[(phenylmethoxy)carbonyl]oxy]-,phenylmethyl carbonate (ester) 在 palladium on activated charcoal 氢气 、 4-吡咯烷基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 20.0 ℃ 、250.01 kPa 条件下， 反应 44.0h， 生成 1,3-dihexadecanoyl-2-<(S)-2-amino-3-(3,4-dihydroxyphenyl)propanoyl>propane-1,2,3-triol
  参考文献：
  名称：

  A lymphotropic prodrug of L-dopa: synthesis, pharmacological properties and pharmacokinetic behavior of 1,3-dihexadecanoyl-2-[(S)-2-amino-3-(3,4-dihydroxyphenyl)propanoyl]propane-1,2,3-triol

  摘要：

  A glyceride derivative of L-Dopa, 1,3-dihexadecanoyl-2-[(S)-2-amino-3-(3,4-dihydroxyphenyl)propan oyl] propane-1,2,3-triol (1), was synthesized and tested as an orally administrable prodrug endowed with lymphotropic properties. In the oxotremorine and reserpine tests, 1 exhibited an anti-Parkinsonian activity of longer duration than L-Dopa. The time course of concentration of 1 in the intestinal lymph of rat was determined and compared to that of L-Dopa. The results clearly demonstrate that 1 is selectively absorbed from the intestinal tract by the lymphatic route without any chemical or enzymatic degradation. In the blood of rats and mice, 1 functions as a prodrug to release L-Dopa by hydrolysis. In comparison with L-Dopa itself, higher L-Dopa levels for a longer period of time were observed as well as much more favorable L-Dopa/dopamine ratios. Ultimately, studies using mice show that the administration of 1 brings about a prolonged increase of L-Dopa and dopamine levels in the brain, without initial transient peak in concentration observed after an equimolecular dose of L-Dopa.

  DOI：

  10.1021/jm00155a018

文献信息

• A lymphotropic prodrug of L-dopa: synthesis, pharmacological properties and pharmacokinetic behavior of 1,3-dihexadecanoyl-2-[(S)-2-amino-3-(3,4-dihydroxyphenyl)propanoyl]propane-1,2,3-triol
  作者：Aaron Garzon-Aburbeh、Jacques H. Poupaert、Michel Claesen、Pierre Dumont

  DOI：10.1021/jm00155a018

  日期：1986.5

  A glyceride derivative of L-Dopa, 1,3-dihexadecanoyl-2-[(S)-2-amino-3-(3,4-dihydroxyphenyl)propan oyl] propane-1,2,3-triol (1), was synthesized and tested as an orally administrable prodrug endowed with lymphotropic properties. In the oxotremorine and reserpine tests, 1 exhibited an anti-Parkinsonian activity of longer duration than L-Dopa. The time course of concentration of 1 in the intestinal lymph of rat was determined and compared to that of L-Dopa. The results clearly demonstrate that 1 is selectively absorbed from the intestinal tract by the lymphatic route without any chemical or enzymatic degradation. In the blood of rats and mice, 1 functions as a prodrug to release L-Dopa by hydrolysis. In comparison with L-Dopa itself, higher L-Dopa levels for a longer period of time were observed as well as much more favorable L-Dopa/dopamine ratios. Ultimately, studies using mice show that the administration of 1 brings about a prolonged increase of L-Dopa and dopamine levels in the brain, without initial transient peak in concentration observed after an equimolecular dose of L-Dopa.