3-acetyl-3-demethylthiocolchicine | 2730-86-1

• 分子结构分类: 有机化合物 - 碳氢化合物衍生物 - 环庚三烯酮
• 英文名称: 3-acetyl-3-demethylthiocolchicine
• 英文别名: Acetic acid 7-acetylamino-1,2-dimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[a]heptalen-3-yl ester；[(7S)-7-acetamido-1,2-dimethoxy-10-methylsulfanyl-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-3-yl] acetate
• CAS: 2730-86-1
• 化学式: C₂₃H₂₅NO₆S
• 分子量: 443.521
• InChiKey: OQNXQFMAEZAEKM-KRWDZBQOSA-N

物化性质

• 沸点：
  733.4±60.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-acetyl-3-demethylthiocolchicine 在 镍 氢气 作用下， 以 丙酮 为溶剂， 反应 0.5h， 以75%的产率得到Acetic acid (S)-7-acetylamino-1,2-dimethoxy-9-oxo-5,6,7,8,9,10,11,12-octahydro-benzo[a]heptalen-3-yl ester
  参考文献：
  名称：

  从硫代秋水仙碱及其同类物合成杀虫剂及其类似物的新方法：重新评估杀虫剂作为一种潜在的抗肿瘤剂。

  摘要：

  在氢气氛中用阮内镍对硫代秋水仙碱进行脱硫，得到四氢甲氧基秋水仙碱（2），该四氢甲氧基秋水仙碱易于通过色谱法与未反应的硫代秋水仙碱分离，并在回流的甲苯中通过Pd / C平滑氧化为10-脱甲氧基秋水仙碱（杀菌剂）。通过该方法从相应的硫代秋水仙碱中制备了几种杀菌剂的类似物。用浓硫酸处理杀菌剂，得到2-脱甲基杀菌剂。在微管蛋白结合试验中发现了杀菌剂及其类似物没有活性。有证据表明，较早之前在空中大气中用硫代秋水仙碱和阮内尼制备的助剂被1-2％的硫代秋水仙碱污染。

  DOI：

  10.1021/jm00387a028
• 作为产物：
  描述：

  (-)-3-去甲基秋水仙碱 以 吡啶 、 水 为溶剂， 反应 42.0h， 生成 3-acetyl-3-demethylthiocolchicine
  参考文献：
  名称：

  Muzaffar, Anjum; Chrzanowska, Maria; Brossi, Arnold, Heterocycles, 1989, vol. 28, # 1, p. 365 - 372

  摘要：

  DOI：

文献信息

• Esters of 1-O-Demethylthiocolchicines: Formation of Isomers in Chloroform Solution
  作者：Peter Kerekes、Arnold Brossi、Judith L. Flippen-Anderson、Colin F. Chignell

  DOI：10.1002/hlca.19850680306

  日期：1985.5.15

  standing in CHCl3 solution significant changes in optical rotation, a duplication of 1H-NMR signals, and the formation of new isomers on TLC. Solid-state X-ray diffraction of O-acetylated colchinoids and thio analogs, showed out of planar arrangements of the aromatic substituents, but the analysis could not help to explain the structures of the newly formed isomers in CHCl3 solution.

  1- ø -乙酰-1- ø -demethylcolchicine，和酰化1- ö，2- Ó -didemethylthiocolchicines，而相比之下，2- Õ乙酰基，2- ö，3- ö -diacetyl-和3- ö -乙酰基类似物显示，在CHCl 3溶液中放置后，旋光度发生明显变化，1 H-NMR信号重复，并且在TLC上形成新的异构体。O-乙酰化类蛇蝎类和硫代类似物的固态X射线衍射显示出芳族取代基的平面排列，但该分析无法解释CHCl 3中新形成的异构体的结构 解决方案。
• Antitubulin effects of derivatives of 3-demethylthiocolchicine, methylthio ethers of natural colchicinoids, and thioketones derived from thiocolchicine. Comparison with colchicinoids
  作者：Anjum Muzaffar、Arnold Brossi、Chii M. Lin、Ernest Hamel

  DOI：10.1021/jm00164a015

  日期：1990.2

  Esterification of the phenolic group in 3-demethylthiocolchicine and exchange of the N-acetyl group with other N-acyl groups or a N-carbalkoxy group afforded many compounds which showed superior activity over the parent drug as inhibitors of tubulin polymerization and of the growth of L1210 murine leukemia cells in culture. A comparison of naturally occurring Colchicum alkaloids with thio isosters, obtained by replacing the OMe group at C(10) with a SCH3 group, showed the thio ethers to be invariably more potent in these assays. The comparison included 3-demethylthiodemecolcine prepared from 3-demethylthiocolchicine by partial synthesis. Thiation of thiocolchicine with Lawesson's reagent afforded novel thiotropolones which exhibited high antitubulin activity. Their structures are fully secured by spectral data. Colchicine and several of its analogues show good antitumor effect in mice infected with P388 lymphocytic leukemia, and all of them show high affinity for tubulin and inhibit tubulin polymerization at low concentration. Consequently, antitubulin assays with this class of compounds can serve as valuable prescreens for the initial evaluation of potential antitumor drugs.
• Muzaffar, Anjum; Chrzanowska, Maria; Brossi, Arnold, Heterocycles, 1989, vol. 28, # 1, p. 365 - 372
  作者：Muzaffar, Anjum、Chrzanowska, Maria、Brossi, Arnold

  DOI：——

  日期：——
• A novel synthesis of colchicide and analogs from thiocolchicine and congeners: reevaluation of colchicide as a potential antitumor agent
  作者：Raymond Dumont、Arnold Brossi、Colin F. Chignell、Frank R. Quinn、Matthew Suffness

  DOI：10.1021/jm00387a028

  日期：1987.4

  Desulfurization of thiocolchicine with Raney nickel in a hydrogen atmosphere yielded tetrahydromethoxycolchicine (2), which was readily separated from unreacted thiocolchicine by chromatography and was smoothly oxidized to 10-demethoxycolchicine (colchicide) by Pd/C in refluxing toluene. Several analogues of colchicide were prepared from the corresponding thiocolchicines by this procedure. Treatment

  在氢气氛中用阮内镍对硫代秋水仙碱进行脱硫，得到四氢甲氧基秋水仙碱（2），该四氢甲氧基秋水仙碱易于通过色谱法与未反应的硫代秋水仙碱分离，并在回流的甲苯中通过Pd / C平滑氧化为10-脱甲氧基秋水仙碱（杀菌剂）。通过该方法从相应的硫代秋水仙碱中制备了几种杀菌剂的类似物。用浓硫酸处理杀菌剂，得到2-脱甲基杀菌剂。在微管蛋白结合试验中发现了杀菌剂及其类似物没有活性。有证据表明，较早之前在空中大气中用硫代秋水仙碱和阮内尼制备的助剂被1-2％的硫代秋水仙碱污染。