(-)-(S)-chlorizidine A | 1422269-50-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: (-)-(S)-chlorizidine A
• 英文别名: (-)-chlorizidine A；Chlorizidine A；2,3-dichloro-7-[(3S)-5,6-dichloro-2,3-dihydro-1H-pyrrolizin-3-yl]-6,8-dihydroxypyrrolo[1,2-b]isoindol-5-one
• CAS: 1422269-50-8
• 化学式: C₁₈H₁₀Cl₄N₂O₃
• 分子量: 444.101
• InChiKey: PNWJMZXCEYWQFJ-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  27
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (-)-(S)-chlorizidine A 在 三乙胺 、 sodium hydroxide 作用下， 以 水 、 乙腈 为溶剂， 反应 3.0h， 生成 methyl 6-(1-acetyl-4,5-dichloropyrrol-2-yl)-2,4-diacetyloxy-3-[(3S)-5,6-dichloro-2,3-dihydro-1H-pyrrolizin-3-yl]benzoate
  参考文献：
  名称：

  Chlorizidine, a Cytotoxic 5H-Pyrrolo[2,1-a]isoindol-5-one-Containing Alkaloid from a Marine Streptomyces sp.

  摘要：

  Cultivation of an obligate marine Streptomyces strain has provided the cytotoxic natural product chlorizidine A. X-ray crystallographic analysis revealed that the metabolite is composed of a chlorinated 2,3-dihydropyrrolizine ring attached to a chlorinated 5H-pyrrolo[2,1-a]isoindol-5-one. The carbon stereocenter in the dihydropyrrolizine is S-configured. Remarkably, the 5H-pyrrolo[2,1-a]isoindol-5-one moiety has no precedence in the field of natural products. The presence of this ring system, which was demonstrated to undergo facile nucleophilic substitution reactions at the activated carbonyl group, is essential to the molecule's cytotoxicity against HCT-116 human colon cancer cells.

  DOI：

  10.1021/ol303374e

文献信息

• The Hybrid Pyrroloisoindolone-Dehydropyrrolizine Alkaloid (−)-Chlorizidine A Targets Proteins within the Glycolytic Pathway
  作者：Xavier Álvarez-Micó、Danilo D. Rocha、Larissa A. Guimarães、Andrew Ambrose、Eli Chapman、Leticia V. Costa-Lotufo、James J. La Clair、William Fenical

  DOI：10.1002/cbic.201500229

  日期：2015.9

  Cellular and molecular biological studies have identified that the chlorinated marine alkaloid (−)‐chlorizidine A targets the cytosolic proteins GAPDH and ENO1, two multifunctional proteins associated with the glycolytic pathway and implicated in multiple diseases, including metastatic cancer, autoimmune disorders, neurological disorders, and bacterial infections.

  细胞和分子生物学研究已经确定，氯化海洋生物碱（-）-氯唑烷A靶向胞质蛋白GAPDH和ENO1，这两种与糖酵解途径有关的多功能蛋白，涉及多种疾病，包括转移性癌症，自身免疫性疾病，神经系统疾病，和细菌感染。
• Chlorizidine, a Cytotoxic 5<i>H</i>-Pyrrolo[2,1-<i>a</i>]isoindol-5-one-Containing Alkaloid from a Marine <i>Streptomyces</i> sp.
  作者：Xavier Alvarez-Mico、Paul R. Jensen、William Fenical、Chambers C. Hughes

  DOI：10.1021/ol303374e

  日期：2013.3.1

  Cultivation of an obligate marine Streptomyces strain has provided the cytotoxic natural product chlorizidine A. X-ray crystallographic analysis revealed that the metabolite is composed of a chlorinated 2,3-dihydropyrrolizine ring attached to a chlorinated 5H-pyrrolo[2,1-a]isoindol-5-one. The carbon stereocenter in the dihydropyrrolizine is S-configured. Remarkably, the 5H-pyrrolo[2,1-a]isoindol-5-one moiety has no precedence in the field of natural products. The presence of this ring system, which was demonstrated to undergo facile nucleophilic substitution reactions at the activated carbonyl group, is essential to the molecule's cytotoxicity against HCT-116 human colon cancer cells.