(6R)-6'-羟基-2',2',4',6'-四甲基-螺[环丙烷-1,5'-[5H]茚]-3',7'(2'H,6'H)-二酮 | 28282-65-7

• 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
• 中文名称: (6R)-6'-羟基-2',2',4',6'-四甲基-螺[环丙烷-1,5'-[5H]茚]-3',7'(2'H,6'H)-二酮
• 英文名称: dehydroilludin M
• 英文别名: 3'-Oxoilludin M；(5'R)-5'-hydroxy-2',2',5',7'-tetramethylspiro[cyclopropane-1,6'-indene]-1',4'-dione
• CAS: 28282-65-7
• 化学式: C₁₅H₁₈O₃
• 分子量: 246.306
• InChiKey: PFURRCFDDZMGLA-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (6R)-6'-羟基-2',2',4',6'-四甲基-螺[环丙烷-1,5'-[5H]茚]-3',7'(2'H,6'H)-二酮 在 盐酸 作用下， 以 丙酮 为溶剂， 以56 mg的产率得到6-(2-chloroethyl)-3,4-dihydroxy-2,2,5,7-tetramethyl-3H-inden-1-one
  参考文献：
  名称：

  Structure-activity relationships of illudins: analogs with improved therapeutic index.

  摘要：

  Illudin S and M are extremely toxic sesquiterpenes produced by Omphalotus illudens. At low pH they behave as bifunctional alkylating agents, but at physiological pH they do not react with oxygen or nitrogen nucleophiles. Illudins react spontaneously with sulfur nucleophiles, glutathione or cysteine, at or slightly below pH 7, and toxicity to HL 60 cells can be modulated by altering glutathione levels in cells. Analogs of illudin M, e.g. the deoxy and, particularly, the dehydro derivatives, are less reactive to thiols and correspondingly less toxic to HL 60 cells than the parent compound. Dehydroilludin M has been found to be quite effective at inhibiting tumor growth in vivo at doses well tolerated by athymic nude mice.

  DOI：

  10.1021/jo00051a037
• 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 重铬酸吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 以140 mg的产率得到(6R)-6'-羟基-2',2',4',6'-四甲基-螺[环丙烷-1,5'-[5H]茚]-3',7'(2'H,6'H)-二酮
  参考文献：
  名称：

  Structure-activity relationships of illudins: analogs with improved therapeutic index.

  摘要：

  Illudin S and M are extremely toxic sesquiterpenes produced by Omphalotus illudens. At low pH they behave as bifunctional alkylating agents, but at physiological pH they do not react with oxygen or nitrogen nucleophiles. Illudins react spontaneously with sulfur nucleophiles, glutathione or cysteine, at or slightly below pH 7, and toxicity to HL 60 cells can be modulated by altering glutathione levels in cells. Analogs of illudin M, e.g. the deoxy and, particularly, the dehydro derivatives, are less reactive to thiols and correspondingly less toxic to HL 60 cells than the parent compound. Dehydroilludin M has been found to be quite effective at inhibiting tumor growth in vivo at doses well tolerated by athymic nude mice.

  DOI：

  10.1021/jo00051a037

文献信息

• Method of treating certain tumors using illudin analogs
  申请人：The Regents of the University of California

  公开号：US05439936A1

  公开（公告）日：1995-08-08

  A therapeutic method is provided to inhibit tumor cell growth in a subject in need of said therapy is provided, comprising parenterally administering a therapeutic amount of a compound in a pharmaceutically acceptable carrier, wherein said compound has the structure: ##STR1## wherein R is selected from the group consisting of: ##STR2## and wherein said tumor cell is sensitive to inhibition by said compound and is selected from the group consisting of a myeloid leukemia cell, a T-cell leukemia cell, a lung carcinoma cell, an ovarian carcinoma cell, and a breast carcinoma cell.

  提供了一种治疗方法，用于抑制需要该治疗的受体内的肿瘤细胞生长，包括经肠外途径给予一种化合物的治疗剂量，所述化合物以药学上可接受的载体为基础，并且该化合物具有以下结构：##STR1##其中R选择自以下组：##STR2##所述肿瘤细胞对该化合物敏感，并且被选择自以下组：骨髓性白血病细胞、T细胞白血病细胞、肺癌细胞、卵巢癌细胞和乳腺癌细胞。
• Illudin analogs
  申请人：The Regents of the University of California

  公开号：US05523490A1

  公开（公告）日：1996-06-04

  A compound to inhibit tumor cell growth in a subject in need of said therapy is provided, wherein said compound has the structure: ##STR1## wherein R is selected from the group consisting of: ##STR2## Tumor cells sensitive to inhibition by said compound are selected from the group consisting of a myeloid leukemia cell, a T-cell leukemia cell, a lung carcinoma cell, an ovarian carcinoma cell, and a breast carcinoma cell.

  提供一种化合物，用于抑制需要该疗法的主体中的肿瘤细胞生长，其中该化合物具有以下结构：##STR1##其中R从以下组中选择：##STR2##对该化合物敏感的肿瘤细胞从以下组中选择：骨髓性白血病细胞、T细胞白血病细胞、肺癌细胞、卵巢癌细胞和乳腺癌细胞。
• Illudin analogs useful as antitumor agents
  申请人：The Regents of the University of California

  公开号：US05563176A1

  公开（公告）日：1996-10-08

  Antineoplastic illudin analogs are provided of the formula: wherein R.sub.4, R.sub.5 and R.sub.6 are (C.sub.1 -C.sub.4)alkyl, Y is H, (C.sub.1 -C.sub.3)alkyl, (R.sub.4)R.sub.5)(R.sub.6)Si or alkanoyl ((C.sub.1 -C.sub.4)alkylC(O)) and R is CH.sub.2 OH, halo, benzyl optionally substituted with OY, or alkanoylmethyl (CH.sub.2 OC(O)R.sub.7), wherein R.sub.7 is (C.sub.1 -C.sub.4)alkyl, (C.sub.6 -C.sub.2)aryl or N(X).sub.2, wherein each X is H or (C.sub.1 -C.sub.4)alkyl, and the pharmaceutically-acceptable salts thereof.

  提供公式为Antineoplastic illudin类似物：其中R.sub.4、R.sub.5和R.sub.6是（C.sub.1-C.sub.4）烷基，Y是H，（C.sub.1-C.sub.3）烷基，（R.sub.4）R.sub.5）（R.sub.6）Si或烷酰（（C.sub.1-C.sub.4）烷基C（O））和R是CH.sub.2 OH，卤素，苄基（可以用OY取代）或烷酰甲基（CH.sub.2 OC（O）R.sub.7），其中R.sub.7是（C.sub.1-C.sub.4）烷基，（C.sub.6-C.sub.2）芳基或N（X）.sub.2，其中每个X是H或（C.sub.1-C.sub.4）烷基，以及其药学上可接受的盐。
• Synthesis of [3H]-illudin S, [3H]-acylfulvene, [3H] & [14C]-hydroxymethylacylfulvene (MGI 114)
  作者：Trevor C. McMorris、Jian Yu、David M. Herman、Michael J. Kelner、Robin Dawe、Akira Minamida

  DOI：10.1002/(sici)1099-1344(199804)41:4<279::aid-jlcr86>3.0.co;2-j

  日期：1998.4

  Tritiated derivatives of the toxic sesquiterpene illudin S (1) have been prepared by fermentation of Omphalotus illudens in the presence of [H-3]-sodium acetate. [H-3]-illudin S was converted to antitumor [H-3]-acylfulvene (4) by treatment with dilute sulfuric acid. Antitumor [C-14]-hydroxymethylacylfulvene (5) was best prepared by reacting acylfulvene with [C-14]-paraformaldehyde in dilute sulfuric acid.
• Structure-activity relationships of illudins: analogs with improved therapeutic index.
  作者：Trevor C. McMorris、Michael J. Kelner、Wen Wang、Leita A. Estes、Mark A. Montoya、Raymond Taetle

  DOI：10.1021/jo00051a037

  日期：1992.12

  Illudin S and M are extremely toxic sesquiterpenes produced by Omphalotus illudens. At low pH they behave as bifunctional alkylating agents, but at physiological pH they do not react with oxygen or nitrogen nucleophiles. Illudins react spontaneously with sulfur nucleophiles, glutathione or cysteine, at or slightly below pH 7, and toxicity to HL 60 cells can be modulated by altering glutathione levels in cells. Analogs of illudin M, e.g. the deoxy and, particularly, the dehydro derivatives, are less reactive to thiols and correspondingly less toxic to HL 60 cells than the parent compound. Dehydroilludin M has been found to be quite effective at inhibiting tumor growth in vivo at doses well tolerated by athymic nude mice.