(1S,13S,15S,16S)-16-chloro-15-methoxy-5,7-dioxa-12-azapentacyclo[10.6.1.02,10.04,8.013,18]nonadeca-2,4(8),9,17-tetraene | 1138334-50-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: (1S,13S,15S,16S)-16-chloro-15-methoxy-5,7-dioxa-12-azapentacyclo[10.6.1.02,10.04,8.013,18]nonadeca-2,4(8),9,17-tetraene
• CAS: 1138334-50-5
• 化学式: C₁₇H₁₈ClNO₃
• 分子量: 319.788
• InChiKey: XUWWIIBGXFQMPN-AJNGGQMLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  30.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1S,13S,15S,16S)-16-chloro-15-methoxy-5,7-dioxa-12-azapentacyclo[10.6.1.02,10.04,8.013,18]nonadeca-2,4(8),9,17-tetraene 在 indium(III) triflate 、 N-碘代丁二酰亚胺 作用下， 以 乙腈 为溶剂， 反应 12.0h， 以55%的产率得到(1R,13S,15S,16S)-16-chloro-3,9-diiodo-15-methoxy-5,7-dioxa-12-azapentacyclo[10.6.1.02,10.04,8.013,18]nonadeca-2(10),3,8,17-tetraene
  参考文献：
  名称：

  Synthetic analogues of the montanine-type alkaloids with activity against apoptosis-resistant cancer cells

  摘要：

  In a search of small molecules active against apoptosis-resistant cancer cells, a skeletal rearrangement of alkaloid haemanthamine was utilized to generate a series of compounds possessing the alkaloid montanine ring system. The synthesized compounds were found to inhibit proliferation of cancer cells resistant to apoptosis at micromolar concentrations. Selected compounds were also active against patient-derived glioblastoma cells expressing stem-cell markers. This is the first report describing the preparation of synthetic analogues of the montanine-type alkaloids with antiproliferative activity. The compounds prepared in the current investigation appear to be a useful starting point for the development of agents to fight cancers with apoptosis resistance, and thus, associated with poor prognoses. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2018.01.041
• 作为产物：
  描述：

  haemanthamine 在 甲基磺酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 以55%的产率得到(1S,13S,15S,16S)-16-chloro-15-methoxy-5,7-dioxa-12-azapentacyclo[10.6.1.02,10.04,8.013,18]nonadeca-2,4(8),9,17-tetraene
  参考文献：
  名称：

  Synthetic analogues of the montanine-type alkaloids with activity against apoptosis-resistant cancer cells

  摘要：

  In a search of small molecules active against apoptosis-resistant cancer cells, a skeletal rearrangement of alkaloid haemanthamine was utilized to generate a series of compounds possessing the alkaloid montanine ring system. The synthesized compounds were found to inhibit proliferation of cancer cells resistant to apoptosis at micromolar concentrations. Selected compounds were also active against patient-derived glioblastoma cells expressing stem-cell markers. This is the first report describing the preparation of synthetic analogues of the montanine-type alkaloids with antiproliferative activity. The compounds prepared in the current investigation appear to be a useful starting point for the development of agents to fight cancers with apoptosis resistance, and thus, associated with poor prognoses. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2018.01.041

文献信息

• Antiproliferative and Structure Activity Relationships of Amaryllidaceae Alkaloids
  作者：Juan Cedrón、Ángel Ravelo、Leticia León、José Padrón、Ana Estévez-Braun

  DOI：10.3390/molecules200813854

  日期：——

  The antiproliferative activity of a set of seven natural Amaryllidaceae alkaloids and 32 derivatives against four cancer cell lines (A2780, SW1573, T47-D and WiDr) was determined. The best antiproliferative activities were achieved with alkaloids derived from pancracine (2), haemanthamine (6) and haemantidine (7). For each skeleton, some structure-activity relationships were outlined.

  确定了一组七种天然金莲花科生物碱和32种衍生物对四种癌细胞系（A2780，SW1573，T47-D和WiDr）的抗增殖活性。源自潘克拉辛（2），血红花胺（6）和雷曼替丁（7）的生物碱具有最佳的抗增殖活性。对于每个骨架，概述了一些构效关系。
• Bioactive Montanine Derivatives from Halide-induced Rearrangements of Haemanthamine-type Alkaloids. Absolute Configuration by VCD
  作者：Juan C. Cedrón、Ana Estévez-Braun、Ángel G. Ravelo、David Gutiérrez、Ninoska Flores、María A. Bucio、Nury Pérez-Hernández、Pedro Joseph-Nathan

  DOI：10.1021/ol900065x

  日期：2009.4.2

  An unexpected rearrangement of haemanthamine-type alkaloids in the presence of halogenating agents has been found. Rearranged compounds present the 5,11-methanomorphantridine framework characteristic of montanine-type alkaloids. These compounds are difficult to obtain because of their scarcity in natural sources and because the synthetic approaches developed so far require numerous steps. Vibrational circular dichroism (VCD) spectroscopy was used to determine the absolute configuration of one of the rearranged compounds. Several rearranged alkaloids showed antimalarial activity.
• Synthetic analogues of the montanine-type alkaloids with activity against apoptosis-resistant cancer cells
  作者：Karthik Govindaraju、Aude Ingels、Md Nabiul Hasan、Dandan Sun、Veronique Mathieu、Marco Masi、Antonio Evidente、Alexander Kornienko

  DOI：10.1016/j.bmcl.2018.01.041

  日期：2018.2

  In a search of small molecules active against apoptosis-resistant cancer cells, a skeletal rearrangement of alkaloid haemanthamine was utilized to generate a series of compounds possessing the alkaloid montanine ring system. The synthesized compounds were found to inhibit proliferation of cancer cells resistant to apoptosis at micromolar concentrations. Selected compounds were also active against patient-derived glioblastoma cells expressing stem-cell markers. This is the first report describing the preparation of synthetic analogues of the montanine-type alkaloids with antiproliferative activity. The compounds prepared in the current investigation appear to be a useful starting point for the development of agents to fight cancers with apoptosis resistance, and thus, associated with poor prognoses. (C) 2018 Elsevier Ltd. All rights reserved.