3,3-Diaethoxy-2-phenyl-propanol-(1) | 96248-16-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 3,3-Diaethoxy-2-phenyl-propanol-(1)
• CAS: 96248-16-7
• 化学式: C₁₃H₂₀O₃
• 分子量: 224.3
• InChiKey: FHKBRBJBABRWME-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.16
• 重原子数：
  16.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  38.69
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3,3-Diaethoxy-2-phenyl-propanol-(1) 在 氨 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 Carbamic acid 3,3-diethoxy-2-phenyl-propyl ester
  参考文献：
  名称：

  Synthesis and in Vitro Reactivity of 3-Carbamoyl-2-phenylpropionaldehyde and 2-Phenylpropenal:  Putative Reactive Metabolites of Felbamate

  摘要：

  We propose that 3-carbamoyl-2-phenylpropionaldehyde is an intermediate in the metabolism of felbamate, an anti-epileptic drug with a unique profile of therapeutic activity, and undergoes a cascade of chemical reactions responsible for the toxic properties of the parent drug. To test this hypothesis, we have synthesized 3-carbamoyl-2-phenylpropionaldehyde and evaluated its in vitro reactivity. This molecule was found to be highly unstable at physiological pH (t(1/2) less than or equal to 30 s) and to undergo facile elimination to 2-phenylpropenal, an a,P-unsaturated aldehyde commonly termed atropaldehyde. However, the predominant reaction pathway for 3-carbamoyl-2-phenylpropionaldehyde was reversible cyclization to generate 4-hydroxy-5-phenyltetrahydro-1,3-oxazin-2-one, a urethane that has a considerably longer half-life at physiological pH (t(1/2) greater than or equal to 5 h) and may serve as a stable reservoir of the reactive aldehyde both in, vitro and in vivo. Atropaldehyde is a potent electrophile and was found to exhibit cytotoxicity to cultured fibroblasts (50% growth inhibition (GI(50)) = 4.1 +/- 1.1 mu M) comparable to the known unsaturated aldehyde toxins, 4-hydroxy-2-nonenal and acrolein. 3-Carbamoyl-2-phenylpropionaldehyde also exhibited significant cytotoxicity (GI(50) = 53 +/- 8 mu M), whereas 2-phenyl-1,3-propanediol monocarbamate (GI(50) > 500 mu M) and 3-carbamoyl-2-phenylpropionic acid (GI(50) > 500 mu M) were nontoxic. We have additionally demonstrated the formation of a glutathione-atropaldehyde conjugate from the in vitro incubation of 3-carbamoyl-2-phenylpropionaldehyde with glutathione. Thus, the potent cytotoxicity and potential allergenicity of atropaldehyde implicate this unsaturated aldehyde as a possible causative agent in the toxicities observed with felbamate treatment.

  DOI：

  10.1021/tx9601566
• 作为产物：
  描述：

  (3,3-二乙氧基-1-丙烯-2-基)苯 在 硼烷 、 sodium hydroperoxide 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以60%的产率得到3,3-Diaethoxy-2-phenyl-propanol-(1)
  参考文献：
  名称：

  Synthesis and in Vitro Reactivity of 3-Carbamoyl-2-phenylpropionaldehyde and 2-Phenylpropenal:  Putative Reactive Metabolites of Felbamate

  摘要：

  We propose that 3-carbamoyl-2-phenylpropionaldehyde is an intermediate in the metabolism of felbamate, an anti-epileptic drug with a unique profile of therapeutic activity, and undergoes a cascade of chemical reactions responsible for the toxic properties of the parent drug. To test this hypothesis, we have synthesized 3-carbamoyl-2-phenylpropionaldehyde and evaluated its in vitro reactivity. This molecule was found to be highly unstable at physiological pH (t(1/2) less than or equal to 30 s) and to undergo facile elimination to 2-phenylpropenal, an a,P-unsaturated aldehyde commonly termed atropaldehyde. However, the predominant reaction pathway for 3-carbamoyl-2-phenylpropionaldehyde was reversible cyclization to generate 4-hydroxy-5-phenyltetrahydro-1,3-oxazin-2-one, a urethane that has a considerably longer half-life at physiological pH (t(1/2) greater than or equal to 5 h) and may serve as a stable reservoir of the reactive aldehyde both in, vitro and in vivo. Atropaldehyde is a potent electrophile and was found to exhibit cytotoxicity to cultured fibroblasts (50% growth inhibition (GI(50)) = 4.1 +/- 1.1 mu M) comparable to the known unsaturated aldehyde toxins, 4-hydroxy-2-nonenal and acrolein. 3-Carbamoyl-2-phenylpropionaldehyde also exhibited significant cytotoxicity (GI(50) = 53 +/- 8 mu M), whereas 2-phenyl-1,3-propanediol monocarbamate (GI(50) > 500 mu M) and 3-carbamoyl-2-phenylpropionic acid (GI(50) > 500 mu M) were nontoxic. We have additionally demonstrated the formation of a glutathione-atropaldehyde conjugate from the in vitro incubation of 3-carbamoyl-2-phenylpropionaldehyde with glutathione. Thus, the potent cytotoxicity and potential allergenicity of atropaldehyde implicate this unsaturated aldehyde as a possible causative agent in the toxicities observed with felbamate treatment.

  DOI：

  10.1021/tx9601566