2-去甲基硫代秋水仙碱 | 87424-26-8

• 分子结构分类: 有机化合物 - 碳氢化合物衍生物 - 环庚三烯酮
• 中文名称: 2-去甲基硫代秋水仙碱
• 英文名称: 2-demethylthiocolchicine
• 英文别名: N-((S)-2-hydroxy-1,3-dimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[a]heptalen-7-yl)-acetamide；(S)-7-Acetylamino-2-hydroxy-1,3-dimethoxy-10-methylmercapto-6,7-dihydro-5H-benzo[a]heptalen-9-on；N-((S)-2-Hydroxy-1,3-dimethoxy-10-methylmercapto-9-oxo-5,6,7,9-tetrahydro-benzo[a]heptalen-7-yl)-acetamid；N-[(7S)-2-hydroxy-1,3-dimethoxy-10-methylsulfanyl-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]acetamide
• CAS: 87424-26-8
• 化学式: C₂₁H₂₃NO₅S
• 分子量: 401.483
• InChiKey: OMQLBXIHBJAOIO-HNNXBMFYSA-N

物化性质

• 熔点：
  218-220°C
• 沸点：
  766.8±60.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)
• 溶解度：
  溶于氯仿

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-去甲基硫代秋水仙碱 在 硫酸 、 碳酸氢钠 、 potassium carbonate 作用下， 以 氯仿 、 丙酮 为溶剂， 反应 7.5h， 生成 2-trideuteromethyl-7-isothiocyanato-deacetamidothiocolchicine
  参考文献：
  名称：

  Muzaffar, Anjum; Hamel, Ernest; Bai, Rouli, Collection of Czechoslovak Chemical Communications, 1991, vol. 56, # 11.1, p. 2306 - 2312

  摘要：

  DOI：
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 在 streptomyces griseus 作用下， 生成 2-去甲基硫代秋水仙碱
  参考文献：
  名称：

  VELLUZ; BELLET, Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1959, vol. 248, # 24, p. 3453 - 3454

  摘要：

  DOI：

文献信息

• Oxidation Products of Phenolic Thiocolchicines: Ring a Quinones and Dienones
  作者：Jian Guan、Arnold Brossi、Xiao-Kang Zhu、Hui-Kang Wang、Kuo-Hsiung Lee

  DOI：10.1080/00397919808006862

  日期：1998.5

  Abstract An improved, highly selective demethylation of thiocolchicine (1) to the diphenol 5 is described. Oxidation of 2 to para-quinone 6 and of 4 and 5 to ortho-quinones 8 and 10 is first reported. Also, 2-demethylthiocolchicine (3) was oxidized to the quinone methide 7.

  摘要 描述了硫代秋水仙碱 (1) 到二酚 5 的改进的、高度选择性的去甲基化。2 氧化成对醌 6 以及 4 和 5 氧化成邻醌 8 和 10 是首次报道。此外，2-脱甲基硫代秋水仙碱 (3) 被氧化为醌甲基化物 7。
• 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。
• Synthesis and biological evaluation of colchicine and thiocolchicine derivatives bearing a Michael acceptor moiety in ring A
  作者：E. A. Mol’kova、E. S. Shchegravina、V. F. Otvagin、N. S. Kuzmina、Yu. B. Malysheva、E. V. Svirshchevskaya、E. A. Zaburdaeva、A. Yu. Fedorov

  DOI：10.1007/s11172-022-3449-7

  日期：2022.3

  A series of colchicine and thiocolchicine derivatives bearing a Michael acceptor moiety in ring A were synthesized. Some of these compounds exhibit cytotoxic activity in the nanomolar range, efficiently disrupt the mitotic spindle, and cause the accumulation of G2/M-phase cells resulting in the development of apoptosis. These derivatives can be covalently bound to the cysteine residues at the colchicine-binding site of tubulin.

  我们合成了一系列秋水仙碱和硫代秋水仙碱衍生物，其中环A部分带有迈克尔受体。其中一些化合物在纳摩尔范围内表现出细胞毒性活性，能够有效破坏有丝分裂纺锤体，并导致G2/M期细胞积累，从而引发细胞凋亡。这些衍生物可与微管蛋白秋水仙碱结合位点的半胱氨酸残基共价结合。
• Synthesis and biological effects of novel thiocolchicines. 3. evaluation of N-acyldeacetylthiocolchicines, N-(alkoxycarbonyl)deacetylthiocolchicines, and O-ethyldemethylthiocolchicines. New synthesis of thiodemecolcine and antileukemic effects of 2-demethyl- and 3-demethylthiocolchicine
  作者：Peter Kerkes、Padam N. Sharma、Arnold Brossi、Colin F. Chignell、Frank R. Quinn

  DOI：10.1021/jm00147a014

  日期：1985.9

  Novel and known analogues of thiocolchicine were evaluated in vitro in a tubulin binding assay and in vivo in mice for acute toxicity and in the P388 lymphocytic leukemia assay. This evaluation included N-acyldeacetylthiocolchicines, N-(alkoxycarbonyl)deacetylthiocolchicines, thiodemecolcine and its methyl carbamate, and O-ethyl ethers of demethylthiocolchicines. Selective ether cleavage of thiodemecolcine with concentrated sulfuric acid at 50 degree C afforded the 2-demethyl congener, characterized as its N,O-diacetyl derivative. Several of the compounds showed high potency in the tubulin binding assay, matching the potency of colchicine. Several N-(alkoxycarbonyl)deacetylcolchicines (carbamates) exhibited strong binding affinity to tubulin but had only weak activities against the P388 tumor system, suggesting that other factors besides tubulin binding may be important for the biological effects. The compounds potent in the tubulin binding assay and in the P388 leukemia assay in mice were generally also toxic to mice in the acute toxicity test, showing thus a similar behavior of thiocolchicines to that observed earlier with colchicines. A considerable amount of data collected for 2-demethyl- and 3-demethylthiocolchicine suggests that the latter represents a broad-spectrum antitumor agent of considerable promise and possibly a less toxic substitute for colchicine.
• Antitumor agents. 256. Conjugation of paclitaxel with other antitumor agents: Evaluation of novel conjugates as cytotoxic agents
  作者：Kyoko Nakagawa-Goto、Seikou Nakamura、Kenneth F. Bastow、Alexander Nyarko、Chieh-Yu Peng、Fang-Yu Lee、Fang-Chen Lee、Kuo-Hsiung Lee

  DOI：10.1016/j.bmcl.2007.02.051

  日期：2007.5

  Sixteen different taxoid conjugates were prepared by linking various anticancer compounds, including camptothecin (CPT), epipodophyllotoxin (EP), colchicine (COL), and glycyrrhetinic acid (GA), at the 2'- or 7-position on paclitaxel (TXL, 1) through an ester, imine, amine, or amide bond. Newly synthesized conjugates were evaluated for cytotoxic activity against replication of several human tumor cell lines. Among them, TXL-CPT conjugates, 8-10, were more potent than TXL itself against the human prostate carcinoma cell line PC-3 (ED50 = 14.8, 3.1, 19.4 nM compared with 55.5 nM), and conjugate 10 was also 8-fold more active than TXL against the LN-CAP prostate cancer cell line. These compounds also possessed anti-angiogenesis ability as well as lower inhibitory effects against a normal cell line (MRC-5). Thus, conjugates 8-10 are possible antitumor drug candidates, particularly for prostate cancer. (c) 2007 Elsevier Ltd. All rights reserved.