B-homo-2-ethoxy-6-methoximino-3,17β-estradiol | 282531-63-9

• 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: B-homo-2-ethoxy-6-methoximino-3,17β-estradiol
• CAS: 282531-63-9
• 化学式: C₂₂H₃₁NO₄
• 分子量: 373.492
• InChiKey: XVGLAYGZARFXSO-ZTYQMOJCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.21
• 重原子数：
  27.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  71.28
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  乙酸酐 、 B-homo-2-ethoxy-6-methoximino-3,17β-estradiol 在 吡啶 作用下， 反应 20.0h， 以90%的产率得到B-homo-3,17β-di-O-acetyl-2-ethoxy-6-methoximinoestradiol
  参考文献：
  名称：

  Synthesis of B-Ring Homologated Estradiol Analogues that Modulate Tubulin Polymerization and Microtubule Stability

  摘要：

  2-Methoxyestradiol is a cytotoxic human metabolite of estradiol with the ability to bind to the colchicine site of tubulin and inhibit its polymerization, and its 2-ethoxy analogue is even more potent. On the basis of a hypothetical relationship between the structures of colchicine and 2-methoxyestradiol, a B-ring-expanded 2-ethoxyestradiol analogue was synthesized in which the B-ring of the steroid is replaced by the B-ring of colchicine. The synthesis relied on the B-ring expansion of available B-keto estradiol derivatives as opposed to a total synthesis of the homologated steroid framework. The relative configurations of the acetamido substituents in both epimers of the final product were determined by NQESY NMR and confirmed by X-ray crystallography. The epimer having the 6 alpha-acetamido substituent was more active as an inhibitor of tubulin polymerization, and it was also more cytotoxic than the 6 beta-epimer. These results are consistent with the proposed structural resemblance of 2-methoxyestradiol and colchicine. Several of the synthetic intermediates proved to be potent inhibitors of tubulin polymerization. On the other hand, a 3,17 beta-diacetylated, B-ring-expanded analogue of 2-ethoxyestradiol having a ketone at C-6 resembled paclitaxel (Taxol) in its ability to enhance tubulin polymerization and stabilize microtubules. The corresponding 3-acetate and the 17 beta-acetate were both synthesized, and it was determined that the 17 beta-acetate, but not the 3-acetate, conferred on the steroid derivative its paclitaxel-like activity.

  DOI：

  10.1021/jm0001119
• 作为产物：
  描述：

  2-Ethoxy-3,17β-Diacetoxy-6-Oxoestra-1,3,5(10)-triene 在 吡啶 、 三氟化硼乙醚 作用下， 以 正己烷 、 二氯甲烷 为溶剂， 反应 14.0h， 生成 B-homo-2-ethoxy-6-methoximino-3,17β-estradiol
  参考文献：
  名称：

  Synthesis of B-Ring Homologated Estradiol Analogues that Modulate Tubulin Polymerization and Microtubule Stability

  摘要：

  2-Methoxyestradiol is a cytotoxic human metabolite of estradiol with the ability to bind to the colchicine site of tubulin and inhibit its polymerization, and its 2-ethoxy analogue is even more potent. On the basis of a hypothetical relationship between the structures of colchicine and 2-methoxyestradiol, a B-ring-expanded 2-ethoxyestradiol analogue was synthesized in which the B-ring of the steroid is replaced by the B-ring of colchicine. The synthesis relied on the B-ring expansion of available B-keto estradiol derivatives as opposed to a total synthesis of the homologated steroid framework. The relative configurations of the acetamido substituents in both epimers of the final product were determined by NQESY NMR and confirmed by X-ray crystallography. The epimer having the 6 alpha-acetamido substituent was more active as an inhibitor of tubulin polymerization, and it was also more cytotoxic than the 6 beta-epimer. These results are consistent with the proposed structural resemblance of 2-methoxyestradiol and colchicine. Several of the synthetic intermediates proved to be potent inhibitors of tubulin polymerization. On the other hand, a 3,17 beta-diacetylated, B-ring-expanded analogue of 2-ethoxyestradiol having a ketone at C-6 resembled paclitaxel (Taxol) in its ability to enhance tubulin polymerization and stabilize microtubules. The corresponding 3-acetate and the 17 beta-acetate were both synthesized, and it was determined that the 17 beta-acetate, but not the 3-acetate, conferred on the steroid derivative its paclitaxel-like activity.

  DOI：

  10.1021/jm0001119