2-debenzoyl-2-(3-methylbut-2-enoyl)-7-triethylsilylbaccatin III | 185850-76-4

• 英文名称: 2-debenzoyl-2-(3-methylbut-2-enoyl)-7-triethylsilylbaccatin III
• 英文别名: 2-debenzoyl-2-(3-methylbut-2-enoyl)-7-triethylsilyl-baccatin III
• CAS: 185850-76-4
• 化学式: C₃₅H₅₄O₁₁Si
• 分子量: 678.893
• InChiKey: MGRRDRLUNXVIAA-WNZPWSLDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.33
• 重原子数：
  47.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  154.89
• 氢给体数：
  2.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  2-debenzoyl-2-(3-methylbut-2-enoyl)-7-triethylsilylbaccatin III 在 palladium on activated charcoal 吡啶 、 氢氟酸 、 氢气 、 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 反应 24.0h， 生成 2-debenzoyl-2-(3-methylbutanoyl)paclitaxel
  参考文献：
  名称：

  Structure–activity relationship study of taxoids for their ability to activate murine macrophages as well as inhibit the growth of macrophage-like cells

  摘要：

  A series of new taxoids modified at the C-3', C-3'N, C-10, C-2 and C-7 positions has been designed, synthesized and evaluated for their potency to induce NO and TNF production by peritoneal murine macrophages (Mphi) from LPS-responsive C3H/HeN and LPS-hyporesponsive C3H/HeJ strains and human blood cells, and for their ability to inhibit the growth of Mphi-like cell lines J774.1 and J7.DEF3. The SAR-study has shown that the nature of the substituents at these positions have critical effect on the induction of TNF and NO production by Mphi. Positions G-3' and C-10 are the most flexible and an intriguing effect of the length of the substituents at the C-10 position is observed for taxoids bearing a straight chain alkanoyl moiety. An aromatic group at the C-3'N and C-2 positions is required for the activity, while only hydroxyl or acetyl substituents seem to be tolerated at the C-7 position. The natural stereochemistry in the C-13 isoserine side chain of the taxoids is an absolute requirement for macrophage activation. It has also been clearly shown that there is no correlation between the ability of the taxoids to induce TNF/NO production in C3H/HeN M and the cytotoxicity against Mphi-like cells. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00181-0
• 作为产物：
  描述：

  3,3-二甲基丙烯酸 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 5.0h， 生成 2-debenzoyl-2-(3-methylbut-2-enoyl)-7-triethylsilylbaccatin III
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Nonaromatic Taxoids:  Effects of Alkyl and Alkenyl Ester Groups on Cytotoxicity

  摘要：

  Several new nonaromatic taxoids are synthesized by means of the beta-lactam synthon method. These include taxoids modified with 3-methylbut-2-enoate, 3-methylbutanoate, and cyclohexanecarboxylate groups in place of the benzoate at the C-2 position. In addition, taxoids with 2-methylprop-1-enyl, 2-methylpropyl, (E)-prop-1-enyl, and cyclohexyl groups at the C-3' position are also prepared in combination with the modifications at C-2. The alkyl and alkenyl ester groups at C-2 displayed pronounced effects on the in vitro cytotoxicity. Two of the fully aliphatic taxoids possess similar or stronger activity than paclitaxel and docetaxel. It is clear that the 2-benzoate does not play a unique role, and replacement with the appropriate alkyl and alkenyl groups provides taxoids with equivalent or superior activity.

  DOI：

  10.1021/jm9606711