(4S)-tert-butyl 4-((1R,2E,4E)-1-hydroxypentadeca-2,4-dienyl)-2,2-dimethyloxazolidine-3-carboxylate | 1561834-07-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (4S)-tert-butyl 4-((1R,2E,4E)-1-hydroxypentadeca-2,4-dienyl)-2,2-dimethyloxazolidine-3-carboxylate
• 英文别名: tert-butyl (4S)-4-[(1R,2E,4E)-1-hydroxypentadeca-2,4-dienyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
• CAS: 1561834-07-8
• 化学式: C₂₅H₄₅NO₄
• 分子量: 423.637
• InChiKey: OMPRCJUUKMLXGN-ZRYVUEQXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  30
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (E)-1-bromotridec-2-ene 在 二异丁基氢化铝 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 (4S)-tert-butyl 4-((1R,2E,4E)-1-hydroxypentadeca-2,4-dienyl)-2,2-dimethyloxazolidine-3-carboxylate
  参考文献：
  名称：

  3-Ketone-4,6-diene ceramide analogs exclusively induce apoptosis in chemo-resistant cancer cells

  摘要：

  Multidrug-resistance is a major cause of cancer chemotherapy failure in clinical treatment. Evidence shows that multidrug-resistant cancer cells are as sensitive as corresponding regular cancer cells under the exposure to anticancer ceramide analogs. In this work we designed five new ceramide analogs with different backbones, in order to test the hypothesis that extending the conjugated system in ceramide analogs would lead to an increase of their anticancer activity and selectivity towards resistant cancer cells. The analogs with the 3-ketone-4,6-diene backbone show the highest apoptosis-inducing efficacy. The most potent compound, analog 406, possesses higher pro-apoptotic activity in chemo-resistant cell lines MCF-7TN-R and NCI/ADR-RES than the corresponding chemo-sensitive cell lines MCF-7 and OVCAR-8, respectively. However, this compound shows the same potency in inhibiting the growth of another pair of chemo-sensitive and chemo-resistant cancer cells, MCF-7 and MCF-7/Dox. Mechanism investigations indicate that analog 406 can induce apoptosis in chemo-resistant cancer cells through the mitochondrial pathway. Cellular glucosylceramide synthase assay shows that analog 406 does not interrupt glucosylceramide synthase in chemo-resistant cancer cell NCI/ADR-RES. These findings suggest that due to certain intrinsic properties, ceramide analogs' pro-apoptotic activity is not disrupted by the normal drug-resistance mechanisms, leading to their potential use for overcoming cancer multidrug-resistance. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.12.065

文献信息

• 3-Ketone-4,6-diene ceramide analogs exclusively induce apoptosis in chemo-resistant cancer cells
  作者：Adharsh P. Ponnapakam、Jiawang Liu、Kaustubh N. Bhinge、Barbara A. Drew、Tony L. Wang、James W. Antoon、Thong T. Nguyen、Patrick S. Dupart、Yuji Wang、Ming Zhao、Yong-Yu Liu、Maryam Foroozesh、Barbara S. Beckman

  DOI：10.1016/j.bmc.2013.12.065

  日期：2014.2

  Multidrug-resistance is a major cause of cancer chemotherapy failure in clinical treatment. Evidence shows that multidrug-resistant cancer cells are as sensitive as corresponding regular cancer cells under the exposure to anticancer ceramide analogs. In this work we designed five new ceramide analogs with different backbones, in order to test the hypothesis that extending the conjugated system in ceramide analogs would lead to an increase of their anticancer activity and selectivity towards resistant cancer cells. The analogs with the 3-ketone-4,6-diene backbone show the highest apoptosis-inducing efficacy. The most potent compound, analog 406, possesses higher pro-apoptotic activity in chemo-resistant cell lines MCF-7TN-R and NCI/ADR-RES than the corresponding chemo-sensitive cell lines MCF-7 and OVCAR-8, respectively. However, this compound shows the same potency in inhibiting the growth of another pair of chemo-sensitive and chemo-resistant cancer cells, MCF-7 and MCF-7/Dox. Mechanism investigations indicate that analog 406 can induce apoptosis in chemo-resistant cancer cells through the mitochondrial pathway. Cellular glucosylceramide synthase assay shows that analog 406 does not interrupt glucosylceramide synthase in chemo-resistant cancer cell NCI/ADR-RES. These findings suggest that due to certain intrinsic properties, ceramide analogs' pro-apoptotic activity is not disrupted by the normal drug-resistance mechanisms, leading to their potential use for overcoming cancer multidrug-resistance. (C) 2014 Elsevier Ltd. All rights reserved.