10'-tert-butyloxycarbonyloxyanhydrovinblastine | 1341225-06-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: 10'-tert-butyloxycarbonyloxyanhydrovinblastine
• CAS: 1341225-06-6
• 化学式: C₅₁H₆₄N₄O₁₁
• 分子量: 909.089
• InChiKey: XKQMUETVAWOVGJ-IEPJDEMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.11
• 重原子数：
  66.0
• 可旋转键数：
  8.0
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  169.4
• 氢给体数：
  2.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  10'-tert-butyloxycarbonyloxyanhydrovinblastine 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以61%的产率得到10'-hydroxyanhydrovinblastine
  参考文献：
  名称：

  10′-Fluorovinblastine and 10′-Fluorovincristine: Synthesis of a Key Series of Modified Vinca Alkaloids

  摘要：

  A study on the impact of catharanthine C10 and C12 indole substituents on the biomimetic Fe(III)-mediated coupling with vindoline led to the discovery and characterization of two new and substantially more potent derivatives, 10'-fluorovinblastine and 10'-fluorovincristine. In addition to defining a pronounced and la unanticipated substituent effect on the biomimetic coupling, fluorine substitution at C10', which minimally alters the natural products, was found to uniquely enhance the activity 8-fold against both sensitive (IC50 = 800 pM, HCT116) and vinblastine-resistant tumor cell lines (IC50 = 80 nM, HCT166/VM46). As depicted in the X-ray structure of vinblastine bound to tubulin, this site resides at one end of the upper portion of the T-shaped conformation of the tubulin-bound molecule, suggesting that the 10'-fluorine substituent makes critical contacts with the protein at a hydrophobic site uniquely sensitive to steric interactions.

  DOI：

  10.1021/ml200236a
• 作为产物：
  描述：

  N-tert-butyloxycarbonyl-10-iodocatharanthine 在 盐酸 、 4-二甲氨基吡啶 、 2,2,2-三氟乙醇 、 iron(III) chloride hexahydrate 、 双氧水 、 potassium acetate 、 三乙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 33.67h， 生成 10'-tert-butyloxycarbonyloxyanhydrovinblastine
  参考文献：
  名称：

  10′-Fluorovinblastine and 10′-Fluorovincristine: Synthesis of a Key Series of Modified Vinca Alkaloids

  摘要：

  A study on the impact of catharanthine C10 and C12 indole substituents on the biomimetic Fe(III)-mediated coupling with vindoline led to the discovery and characterization of two new and substantially more potent derivatives, 10'-fluorovinblastine and 10'-fluorovincristine. In addition to defining a pronounced and la unanticipated substituent effect on the biomimetic coupling, fluorine substitution at C10', which minimally alters the natural products, was found to uniquely enhance the activity 8-fold against both sensitive (IC50 = 800 pM, HCT116) and vinblastine-resistant tumor cell lines (IC50 = 80 nM, HCT166/VM46). As depicted in the X-ray structure of vinblastine bound to tubulin, this site resides at one end of the upper portion of the T-shaped conformation of the tubulin-bound molecule, suggesting that the 10'-fluorine substituent makes critical contacts with the protein at a hydrophobic site uniquely sensitive to steric interactions.

  DOI：

  10.1021/ml200236a