fredericamycin E | 1011723-58-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: fredericamycin E
• 英文别名: (8R)-5',8',9,9',10'-pentahydroxy-6'-methoxy-3-[(1E,3E)-penta-1,3-dienyl]spiro[6,7-dihydro-2H-cyclopenta[g]isoquinoline-8,3'-anthracene]-1,1',2',4'-tetrone
• CAS: 1011723-58-2
• 化学式: C₃₁H₂₃NO₁₀
• 分子量: 569.524
• InChiKey: CBYHZVAGTILQJR-GSIWLMKGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  42
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  191
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  fredericamycin E 反应 10.0h， 生成 fredericamycin A
  参考文献：
  名称：

  Identification of Fredericamycin E from Streptomyces griseus: Insights into Fredericamycin A Biosynthesis Highlighting Carbaspirocycle Formation

  摘要：

  Fredericamycin (FDM) A (1), a pentadecaketide featuring two sets of peri-hydroxy tricyclic aromatic moieties connected through a unique asymmetric carbaspiro center, exhibits potent cytotoxicity and represents a novel anticancer drug lead. We have localized previously the fdm gene cluster to a 33 kb DNA segment of Streptomyces griseus ATCC49344, the involvement of which in the biosynthesis of 1 was confirmed by gene inactivation, complementation, and heterologous expression experiments. We now report the isolation and characterization of FDM E (5), a heretofore undetected intermediate for I biosynthesis from S. griseus, shedding new insight into the mechanism of carbaspirocycle formation. The structure of 5 was elucidated through the combination of spectroscopic methods and isotope-labeling experiments. The core spiro[4.5]decane scaffold of 5 is characterized by a unique cyclohexa-1,2,4-triketone moiety. Transformation of the spiro[4.5]decane 5 into the spiro[4.4]nonane 1 can be rationalized by a biosynthetic benzilic acid-like rearrangement. This unusual rearrangement can be mimicked in vitro by proceeding under aerobic conditions in the absence of enzyme. FDM E displays cytotoxic activity on par with 1 against a selected set of cancer cells, a finding that further supports the unique molecular topology, resulting from the unprecedented carbaspirocycle as exemplified by 1 and 5, as a novel pharmacophore for this family of anticancer agents.

  DOI：

  10.1021/np070664n