[(2S,4R,5R,5aS,6S,9aS,10S,10aS)-5,6,10-triacetyloxy-2-[(2R,3S)-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]oxy-10a-(2-hydroxypropan-2-yl)-3,5a-dimethyl-9-methylidene-8-oxo-1,2,4,5,6,7,9a,10-octahydrobenzo[g]azulen-4-yl] benzoate | 1440522-41-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: [(2S,4R,5R,5aS,6S,9aS,10S,10aS)-5,6,10-triacetyloxy-2-[(2R,3S)-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]oxy-10a-(2-hydroxypropan-2-yl)-3,5a-dimethyl-9-methylidene-8-oxo-1,2,4,5,6,7,9a,10-octahydrobenzo[g]azulen-4-yl] benzoate
• CAS: 1440522-41-7
• 化学式: C₄₇H₅₇NO₁₅
• 分子量: 875.967
• InChiKey: HNEGFQLKJGWBNH-ORMWVESRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  63
• 可旋转键数：
  18
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  227
• 氢给体数：
  3
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  [(2S,4R,5R,5aS,6S,9aS,10S,10aS)-5,6,10-triacetyloxy-2-[tert-butyl(dimethyl)silyl]oxy-10a-(2-hydroxypropan-2-yl)-3,5a-dimethyl-9-methylidene-8-oxo-1,2,4,5,6,7,9a,10-octahydrobenzo[g]azulen-4-yl] benzoate 在 吡啶 、 盐酸 、 氢氟酸 、 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 6.5h， 生成 [(2S,4R,5R,5aR,9aS,10S,10aS)-5,10-diacetyloxy-2-[(2R,3S)-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]oxy-10a-(2-hydroxypropan-2-yl)-3,5a-dimethyl-9-methylidene-8-oxo-1,2,4,5,9a,10-hexahydrobenzo[g]azulen-4-yl] benzoate 、 [(2S,4R,5R,5aS,6S,9aS,10S,10aS)-5,6,10-triacetyloxy-2-[(2R,3S)-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]oxy-10a-(2-hydroxypropan-2-yl)-3,5a-dimethyl-9-methylidene-8-oxo-1,2,4,5,6,7,9a,10-octahydrobenzo[g]azulen-4-yl] benzoate
  参考文献：
  名称：

  Dual-Functional abeo-Taxane Derivatives Destabilizing Microtubule Equilibrium and Inhibiting NF-κB Activation

  摘要：

  Taxchinin A, with a 11(15 -> 1)-abeo-taxane skeleton, is a major, but inactive taxoid contained in leaves of Taxus chinensis. In our design of dual-functional antitumor abeo-taxane derivatives, two fragments from antitumor agents with different molecular targets (the N-acyl-3'-phenylisoserine side chain from the antimitotic agent paclitaxel and an alpha,beta-unsaturated carbonyl system from NF-kappa B inhibitors) were incorporated into the scaffold of taxchinin A. The resulting compounds displayed broad inhibitory effects against proliferation of tumor cell lines, with notable selectivity toward colon cancer, melanoma, and renal cancer, when evaluated in the NCI-60 human tumor cell line screening panel. On the basis of the NCI-60 assay data, structure-activity relationship (SAR) correlations were elucidated. Mechanistic studies indicated that this new compound type can both destabilize microtubules and inhibit NF-kappa B activation, thereby inducing tumor cell apoptosis. This first report of the dual-functional taxoid-core compounds thus provides new opportunities for future drug development based on natural axoid scaffolds.

  DOI：

  10.1021/jm400479p

文献信息

• Dual-Functional <i>abeo</i>-Taxane Derivatives Destabilizing Microtubule Equilibrium and Inhibiting NF-κB Activation
  作者：Yu Zhao、Jia Su、Masuo Goto、Susan L. Morris-Natschke、Yan Li、Qin-Shi Zhao、Zhu-Jun Yao、Kuo-Hsiung Lee

  DOI：10.1021/jm400479p

  日期：2013.6.13

  Taxchinin A, with a 11(15 -> 1)-abeo-taxane skeleton, is a major, but inactive taxoid contained in leaves of Taxus chinensis. In our design of dual-functional antitumor abeo-taxane derivatives, two fragments from antitumor agents with different molecular targets (the N-acyl-3'-phenylisoserine side chain from the antimitotic agent paclitaxel and an alpha,beta-unsaturated carbonyl system from NF-kappa B inhibitors) were incorporated into the scaffold of taxchinin A. The resulting compounds displayed broad inhibitory effects against proliferation of tumor cell lines, with notable selectivity toward colon cancer, melanoma, and renal cancer, when evaluated in the NCI-60 human tumor cell line screening panel. On the basis of the NCI-60 assay data, structure-activity relationship (SAR) correlations were elucidated. Mechanistic studies indicated that this new compound type can both destabilize microtubules and inhibit NF-kappa B activation, thereby inducing tumor cell apoptosis. This first report of the dual-functional taxoid-core compounds thus provides new opportunities for future drug development based on natural axoid scaffolds.