7-{4-[3-tert-butyldimethylsilyloxy-17β-triethylsilyloxyestra-1,3,5(10)-triene-16α-yl]}-2E-but-2-enoic acid | 645404-75-7

• 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: 7-{4-[3-tert-butyldimethylsilyloxy-17β-triethylsilyloxyestra-1,3,5(10)-triene-16α-yl]}-2E-but-2-enoic acid
• CAS: 645404-75-7
• 化学式: C₃₄H₅₆O₄Si₂
• 分子量: 584.987
• InChiKey: KPUHUTVPTKWRRW-KLSUCNOESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.57
• 重原子数：
  40.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  55.76
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  紫杉醇 、 7-{4-[3-tert-butyldimethylsilyloxy-17β-triethylsilyloxyestra-1,3,5(10)-triene-16α-yl]}-2E-but-2-enoic acid 在 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 4-二甲氨基吡啶 作用下， 以 甲苯 为溶剂， 反应 24.25h， 以73%的产率得到2'-{4-[3-tert-butyldimethylsilyloxy-17β-triethylsilyloxyestra-1,3,5(10)-triene-16α-yl]-2E-but-2-enoyl}taxol
  参考文献：
  名称：

  Design, Synthesis, and Bioactivities of Steroid-Linked Taxol Analogues as Potential Targeted Drugs for Prostate and Breast Cancer

  摘要：

  The female steroid hormone 3,17beta-estradiol (2) was selected as an agent to target taxol (1) to estrogen receptor (ER) positive breast cancer cells. Estradiol-taxol conjugates (ETC) were synthesized through linkages from the 11- or 16-position of estradiol to the 2'-, 7-, or 10-position of taxol. All conjugates were cytotoxic to the A2870 ovarian cancer cell line, although less so than taxol. The MCF-7 breast cancer cell line (ER-alpha positive) and MDA-MB-231 breast cancer cell line (ER-a negative) were also used to evaluate the selectivity and cytotoxicity of these conjugates. One conjugate showed some selectivity for ER positive cells, but it was less potent than taxol. Two ETC hemisuccinates were also prepared to improve the solubility of the conjugates. The corresponding Na and triethanolammonium salts were slightly more cytotoxic than the acid form but were much less cytotoxic than the corresponding ETC.

  DOI：

  10.1021/np030296x
• 作为产物：
  描述：

  (E)-4-[(8R,9S,13S,14S,16R,17S)-3-(tert-Butyl-dimethyl-silanyloxy)-13-methyl-17-triethylsilanyloxy-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-16-yl]-but-2-enoic acid ethyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 36.0h， 以72%的产率得到7-{4-[3-tert-butyldimethylsilyloxy-17β-triethylsilyloxyestra-1,3,5(10)-triene-16α-yl]}-2E-but-2-enoic acid
  参考文献：
  名称：

  Design, Synthesis, and Bioactivities of Steroid-Linked Taxol Analogues as Potential Targeted Drugs for Prostate and Breast Cancer

  摘要：

  The female steroid hormone 3,17beta-estradiol (2) was selected as an agent to target taxol (1) to estrogen receptor (ER) positive breast cancer cells. Estradiol-taxol conjugates (ETC) were synthesized through linkages from the 11- or 16-position of estradiol to the 2'-, 7-, or 10-position of taxol. All conjugates were cytotoxic to the A2870 ovarian cancer cell line, although less so than taxol. The MCF-7 breast cancer cell line (ER-alpha positive) and MDA-MB-231 breast cancer cell line (ER-a negative) were also used to evaluate the selectivity and cytotoxicity of these conjugates. One conjugate showed some selectivity for ER positive cells, but it was less potent than taxol. Two ETC hemisuccinates were also prepared to improve the solubility of the conjugates. The corresponding Na and triethanolammonium salts were slightly more cytotoxic than the acid form but were much less cytotoxic than the corresponding ETC.

  DOI：

  10.1021/np030296x