[(3aR,6S)-3a,5,7,7-tetramethyl-2-oxospiro[6H-cyclopenta[e][1]benzofuran-4,1'-cyclopropane]-6-yl] acetate | 1333403-10-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [(3aR,6S)-3a,5,7,7-tetramethyl-2-oxospiro[6H-cyclopenta[e][1]benzofuran-4,1'-cyclopropane]-6-yl] acetate
• CAS: 1333403-10-3
• 化学式: C₁₉H₂₂O₄
• 分子量: 314.381
• InChiKey: XZIWPSLTDIMOSW-AEFFLSMTSA-N

物化性质

• 沸点：
  500.7±50.0 °C(predicted)
• 密度：
  1.24±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [(3aR,6S)-3a,5,7,7-tetramethyl-2-oxospiro[6H-cyclopenta[e][1]benzofuran-4,1'-cyclopropane]-6-yl] acetate 在 甲醇 、 potassium carbonate 作用下， 反应 1.0h， 以90%的产率得到(3aR,6S)-6-hydroxy-3a,5,7,7-tetramethylspiro[6H-cyclopenta[e][1]benzofuran-4,1'-cyclopropane]-2-one
  参考文献：
  名称：

  Cancer Selective Metallocenedicarboxylates of the Fungal Cytotoxin Illudin M

  摘要：

  The diester 2a obtained from 1,1'-ferrocenedicarboxylic acid and the highly and indiscriminately cytotoxic fungal metabolite illudin M (1) displayed antiproliferative activity at submicromolar IC50 (72 h) values against a panel of eight cancer cell lines. Compound 2a was about 40 times less toxic than 1 to nonmalignant human foreskin fibroblasts (HF). The analogous bis(illudinyl M) 1,1'-ruthenocenedicarboxylate (2b) exhibited submicromolar IC50 (72 h) values only against MDA-MB-231 and MCF-7/Topo breast carcinoma and HL-60 leukemia cells. Cytotoxicity studies in the presence of inhibitors of c-Jun N-terminal kinase (INK) or extracellular signal-regulated kinase (ERK) revealed that the high efficacy of 2a, but not that of 2b, against HCT-116 colon cancer cells depends on active JNK/ERK signaling. A new illudin M lactone 5 was of low anticancer activity, but its ruthenocene diester 6b also reached single-digit micromolar IC50 (72 h) values in HCT-116, MCF-7, and HL-60 leukemia cells while not affecting HF. Compounds 2a and 6b were tolerated by mice symptom-free at single doses as high as 25 mg/kg body weight, which is evidence for them being chemically stable under physiological conditions. Compound 2a displayed a manageable in vivo toxicity profile when given repeatedly in high doses.

  DOI：

  10.1021/jm200359n
• 作为产物：
  描述：

  1,5-二羟基-2,2,5,7-四甲基螺[1H-茚-6,1'-环丙烷]-4-酮 在 吡啶 、 苯甲酸 作用下， 以 甲苯 为溶剂， 反应 19.0h， 生成 [(3aR,6S)-3a,5,7,7-tetramethyl-2-oxospiro[6H-cyclopenta[e][1]benzofuran-4,1'-cyclopropane]-6-yl] acetate
  参考文献：
  名称：

  Cancer Selective Metallocenedicarboxylates of the Fungal Cytotoxin Illudin M

  摘要：

  The diester 2a obtained from 1,1'-ferrocenedicarboxylic acid and the highly and indiscriminately cytotoxic fungal metabolite illudin M (1) displayed antiproliferative activity at submicromolar IC50 (72 h) values against a panel of eight cancer cell lines. Compound 2a was about 40 times less toxic than 1 to nonmalignant human foreskin fibroblasts (HF). The analogous bis(illudinyl M) 1,1'-ruthenocenedicarboxylate (2b) exhibited submicromolar IC50 (72 h) values only against MDA-MB-231 and MCF-7/Topo breast carcinoma and HL-60 leukemia cells. Cytotoxicity studies in the presence of inhibitors of c-Jun N-terminal kinase (INK) or extracellular signal-regulated kinase (ERK) revealed that the high efficacy of 2a, but not that of 2b, against HCT-116 colon cancer cells depends on active JNK/ERK signaling. A new illudin M lactone 5 was of low anticancer activity, but its ruthenocene diester 6b also reached single-digit micromolar IC50 (72 h) values in HCT-116, MCF-7, and HL-60 leukemia cells while not affecting HF. Compounds 2a and 6b were tolerated by mice symptom-free at single doses as high as 25 mg/kg body weight, which is evidence for them being chemically stable under physiological conditions. Compound 2a displayed a manageable in vivo toxicity profile when given repeatedly in high doses.

  DOI：

  10.1021/jm200359n