2-hexahydro-2',7-bis(triethylsilyl)paclitaxel | 155371-52-1

• 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: 2-hexahydro-2',7-bis(triethylsilyl)paclitaxel
• CAS: 155371-52-1
• 化学式: C₅₉H₈₅NO₁₄Si₂
• 分子量: 1088.49
• InChiKey: QOSPAJYYUBVRFB-SDXTULIHSA-N

物化性质

• 沸点：
  963.2±65.0 °C(predicted)
• 密度：
  1.19±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  10.06
• 重原子数：
  76.0
• 可旋转键数：
  20.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  199.29
• 氢给体数：
  2.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  2-hexahydro-2',7-bis(triethylsilyl)paclitaxel 在 吡啶 、 氢氟酸 作用下， 以 四氯化碳 、 乙腈 为溶剂， 反应 32.0h， 生成
  参考文献：
  名称：

  Studies on the photochemistry of taxol®

  摘要：

  Irradiation of taxol at 280 nm in a Rayonet reactor yielded a novel pentacyclic derivative containing a new bond between C-3 and C-II. The proposed mechanism involves a triplet intermediate and the first event of the oxa-di-pi-merhane rearrangement. Taxane derivatives that lack both the benzoate at C-2 and the benzamide function at C-3' do not undergo the rearrangement, suggesting the intervention of an intramolecular energy transfer. Irradiation at 300 nm also effects extrusion of the C-9 carbonyl, yielding a ring-contracted product.

  DOI：

  10.1016/s0040-4020(01)85337-0
• 作为产物：
  描述：

  巴卡丁 III 在 吡啶 、 咪唑 、 4-二甲氨基吡啶 、 氢氟酸 、 N,N'-二环己基碳二亚胺 、 红铝 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 1.5h， 生成 2-hexahydro-2',7-bis(triethylsilyl)paclitaxel
  参考文献：
  名称：

  Studies on the photochemistry of taxol®

  摘要：

  Irradiation of taxol at 280 nm in a Rayonet reactor yielded a novel pentacyclic derivative containing a new bond between C-3 and C-II. The proposed mechanism involves a triplet intermediate and the first event of the oxa-di-pi-merhane rearrangement. Taxane derivatives that lack both the benzoate at C-2 and the benzamide function at C-3' do not undergo the rearrangement, suggesting the intervention of an intramolecular energy transfer. Irradiation at 300 nm also effects extrusion of the C-9 carbonyl, yielding a ring-contracted product.

  DOI：

  10.1016/s0040-4020(01)85337-0

文献信息

• Synthesis and Structure-Activity Relationships of New Antitumor Taxoids. Effects of Cyclohexyl Substitution at the C-3' and/or C-2 of Taxotere (Docetaxel)
  作者：Iwao Ojima、Olivier Duclos、Martine Zucco、Marie-Christine Bissery、C. Combeau、P. Vrignaud、J. F. Riou、Francois Lavelle

  DOI：10.1021/jm00042a013

  日期：1994.8

  Synthesis and cytotoxicity of the new analogs (11-13) of docetaxel possessing cyclohexyl groups instead of phenyl groups at the C-3' and/or C-2 benzoate positions are described. The C-2 cyclohexanecarboxylate analog of paclitaxel(15) is also synthesized for comparison. The potency of these new taxoids were examined for their inhibitory activity for microtubule disassembly and also for their cytotoxicity against murine P388 leukemia cell line as well. as doxorubicin-resistant P388 leukemia cell line (P388/Dox). It is found that 3'-dephenyl-3'-cyclohexyldocetaxel (11) (0.72T) and 2-(hexahydro)docetaxel (12) (0.85T) possess strong inhibitory activity for microtubule disassembly equivalent to docetaxel (0.7T), which is more potent than paclitaxel (1.0T). The results clearly indicate that phenyl or an aromatic group at C-3' or C-2 is not a requisite for strong binding to the microtubules. This finding has opened an avenue for development of new nonaromatic analogs of docetaxel and paclitaxel. 3'-Dephenyl-3'-cyclohexyl-2-(hexahydro)docetaxel (13) (2T) turns out to be a substantially weaker inhibitor. The cytotoxicities of 11-13 against P388 are, however, in the same range that is 8-12 times weaker than docetaxel and 4-6 times weaker than paclitaxel, i.e., 13 shows equivalent cytotoxicity to that of 11 or 12 in spite of much lower microtubule disassembly inhibitory activity. The cytotoxicities of these new taxoids against the P388/Dox cell line are only 2-2.5 times lower than that of docetaxel. The potency of 2-(hexahydro)paclitaxel (15) for these assays is much lower than the docetaxel counterpart 12. The significant loss of activity in vivo against B16 melanoma is observed for 11-13, i.e., 11 is only marginal (T/C = 38% at 20 mg/kg/day), and 12 and 13 are inactive (T/C = 76% and 79%, respectively). This could be ascribed to faster metabolism, faster excretion or other bioavailability problems.