(3S)-17-(dicyanomethylidene)androst-5-en-3-yl acetate | 83035-78-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (3S)-17-(dicyanomethylidene)androst-5-en-3-yl acetate
• 英文别名: [(3S,8R,9S,10R,13S,14S)-17-(dicyanomethylidene)-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-yl] acetate
• CAS: 83035-78-3
• 化学式: C₂₄H₃₀N₂O₂
• 分子量: 378.514
• InChiKey: FKUNATBQKQGTSP-VJLLXTKPSA-N

物化性质

• 沸点：
  514.5±50.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  73.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3S)-17-(dicyanomethylidene)androst-5-en-3-yl acetate 在 氢氧化钾 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 、 乙二醇 为溶剂， 反应 12.0h， 生成 Methyl 3β-hydroxypregn-5-en-21-oate
  参考文献：
  名称：

  Use of malonic acid derivatives for the construction of substituted side chains in the position 17β of steroids

  摘要：

  使用Knoevenagel反应对3β-乙酰氧基雄烯-5-烯-17-酮与二乙基丙二酸酯、氰乙酸乙酯和丙二腈进行缩合反应，制备了3β-羟基孕酮-5-烯-21-酸衍生物。还研究了一些衍生物中5、6和17、20位置的双键的还原和氧化，以及C₍₁₇₎和C₍₂₀₎原子的立体化学。从23,24-二去甲胆甾-5,17(20)-二烯-21,22-二醇衍生物中制备了侧链中含有1,3-二氧杂环的化合物。

  DOI：

  10.1135/cccc19821240
• 作为产物：
  描述：

  去氢表雄酮 在 4-二甲氨基吡啶 、 ammonium acetate 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 (3S)-17-(dicyanomethylidene)androst-5-en-3-yl acetate
  参考文献：
  名称：

  D环修饰的甾体β-内酰胺类化合物、其制备方 法及其应用

  摘要：

  本发明属于药物化学及医药技术领域，公开了甾体β-内酰胺类化合物、其制备方法及其应用。该类化合物如式Ⅰ所示，体外抗肿瘤活性实验表明，该类化合物具有广谱的抗肿瘤活性，对多种人癌细胞如EC-109、MGC-803、GES-1及U-87等具有良好地抑制作用；适用于抗肿瘤先导化合物的研究或制备新型抗肿瘤药物。其合成方法简便，适合工业化生产。

  公开号：

  CN104311621B

文献信息

• High-Pressure-Mediated Extension of the Privileged Steroid Scaffold
  作者：Daniel Blanco-Ania、René W. M. Aben、Leon W. A. van Berkom、Hans W. Scheeren、Floris P. J. T. Rutjes

  DOI：10.1002/ejoc.201301511

  日期：2014.3

  The commercially available steroid dehydroepiandrosterone 3-acetate (DHEA) was converted into new, highly functionalized spiro derivatives by modification of the D-ring. The transformation proceeded through conversion of the C-17 carbonyl group into an electron-deficient alkene, followed by either [2+2] or [4+2] cycloaddition. The cycloaddition reactions were successful for alkylidene malononitriles

  市售的类固醇脱氢表雄酮 3-乙酸酯 (DHEA) 通过 D 环的修饰转化为新的、高度官能化的螺衍生物。转化过程是将 C-17 羰基转化为缺电子烯烃，然后进行 [2+2] 或 [4+2] 环加成。亚烷基丙二腈和 2-氰基丙烯酸酯的环加成反应是成功的。由于位置 C-17 的高位阻，高压 (15 kbar) 的应用对于良好的转化至关重要。由 2-氰基丙烯酸酯和丹麦谢夫斯基二烯反应形成的环加合物具有进一步功能化的潜力。
• Facile synthesis of novel D-ring modified steroidal dienamides via rearrangement of 2H-pyrans
  作者：Bin Yu、En Zhang、Xiao-Nan Sun、Jing-Li Ren、Yuan Fang、Bao-Le Zhang、De-Quan Yu、Hong-Min Liu

  DOI：10.1016/j.steroids.2013.02.004

  日期：2013.5

  and practical method for synthesis of the D-ring modified steroidal dienamides (4a-k) from the steroidal alpha,alpha-dicyanoalkene 3 and aldehydes via vinylogous aldol reaction was first reported. By using NaOAc as a base, the desired products were obtained in moderate to good yields in ethanol under mild conditions. All the synthesized steroidal dienamides are new and are currently being evaluated for

  首先报道了一种简单实用的方法，该方法通过乙烯基类醇醛醇醛酸酯反应从甾族α，α-二氰基烯烃3和醛类合成D环修饰的甾族二烯酰胺（4a-k）。通过使用NaOAc作为碱，在温和条件下在乙醇中以中等至良好的产率获得了所需的产物。所有合成的甾族二烯酰胺都是新的，目前正在评估其生物活性。
• Patel et al., Journal of the Chemical Society, 1952, p. 161,165
  作者：Patel et al.

  DOI：——

  日期：——
• Discovery of novel steroidal pyran–oxindole hybrids as cytotoxic agents
  作者：Bin Yu、Ping-Ping Qi、Xiao-Jing Shi、Li-Hong Shan、De-Quan Yu、Hong-Min Liu

  DOI：10.1016/j.steroids.2014.05.022

  日期：2014.10

  A series of novel steroidal pyran-oxindole hybrids were efficiently synthesized in a single operation through the vinylogous aldol reaction of vinyl malononitrile 3 with substituted isatins involving the construction of C-C and C-O bonds. Some compounds displayed moderate to good cytotoxicity against T24, SMMC-7721, MCF-7 and MGC-803 cells. Compounds 4f and 4i were more potent than 5-Fu against T24 and MGC-803 cells with the IC50 values of 4.43 and 8.45 μM, respectively. Further mechanism studies indicated that compound 4i induced G2/M arrest and early apoptosis in a concentration- and time-dependent manner.
• Efficient construction of novel D-ring modified steroidal dienamides and their cytotoxic activities
  作者：Bin Yu、Xiao-Jing Shi、Jing-li Ren、Xiao-Nan Sun、Ping-Ping Qi、Yuan Fang、Xian-Wei Ye、Meng-Meng Wang、Jun-Wei Wang、En Zhang、De-Quan Yu、Hong-Min Liu

  DOI：10.1016/j.ejmech.2013.05.035

  日期：2013.8

  Two series of steroidal dienamides 4a-q and 5a-f were designed, synthesized and evaluated for cytotoxic activities against five human cancer cell lines (MGC-803, EC109, PC-3, SMMC-7721 and MCF-7). The protocol developed efficiently achieved the construction of carbon carbon double bond and selective conversion of nitrile group into carboxamide in one-pot procedure. Besides, compounds 4a-q and 5a-f showed moderate to excellent cytotoxic activities with the IC50 values ranging from 0.1 to 40 mu M and most of them were more potent than 5-fluorouracil. Particularly, four compounds 4d, 4e, 4q and 5a showed excellent selectivity against MGC-803 with the IC50 values less than 1 mu M. Flow cytometry analysis demonstrated that compound 4c caused the cellular early apoptosis and cell cycle arrest in G2/M phase in a concentration-independent manner. (C) 2013 Elsevier Masson SAS. All rights reserved.