Illudin M 6-monoacetate | 28413-94-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: Illudin M 6-monoacetate
• 英文别名: 3-O-acetyl illudin M；3-O-Acetylilludin M；[(1S,5R)-5-hydroxy-2,2,5,7-tetramethyl-4-oxospiro[1H-indene-6,1'-cyclopropane]-1-yl] acetate
• CAS: 28413-94-7
• 化学式: C₁₇H₂₂O₄
• 分子量: 290.359
• InChiKey: CMQPZGFCPCQMER-ZBFHGGJFSA-N

物化性质

• 沸点：
  445.0±45.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (三苯基膦烯)乙烯酮 、 Illudin M 6-monoacetate 在 苯甲酸 作用下， 以 甲苯 为溶剂， 反应 3.0h， 以45%的产率得到[(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
• 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 、 乙酸酐 在 吡啶 作用下， 反应 16.0h， 以86%的产率得到Illudin M 6-monoacetate
  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

文献信息

• Secondary mould metabolites. Part 59. Sesquiterpene illudanes: semi-synthesis of new illudins, structures and biological activity
  作者：Alberto Arnone、Lucio Merlini、Gianluca Nasini、Orso Vajna de Pava、Franco Zunino

  DOI：10.1039/b007633n

  日期：——

  their unacceptable toxicity natural illudins are of limited interest as antitumor agents. In an attempt to exploit their cytotoxic potential several derivatives have been synthesized to obtain compounds with an improved therapeutic index. In this paper we describe some alkylation and oxidation reactions giving rise in some cases to less cytotoxic derivatives. Structures and relative stereochemistries have

  由于其天然毒性，天然伊兰度作为其抗肿瘤剂的兴趣有限。为了开发其细胞毒性潜力，已经合成了几种衍生物以获得具有改善的治疗指数的化合物。在本文中，我们描述了一些烷基化和氧化反应在某些情况下会产生较少的细胞毒性衍生物。结构和相对立体化学是根据1 H和13 C NMR证据。所有化合物的细胞毒性均不如illudin M和S，但仍具有很高的活性。