(2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-acetoxy-9,11-dihydroxy-6-((methoxycarbonyl)oxy)-4a,8,13,13-tetramethyl-5-oxo-4-((triethylsilyl)oxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-yl 3-fluorobenzoate | 1007094-37-2

• 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: (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-acetoxy-9,11-dihydroxy-6-((methoxycarbonyl)oxy)-4a,8,13,13-tetramethyl-5-oxo-4-((triethylsilyl)oxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-yl 3-fluorobenzoate
• CAS: 1007094-37-2
• 化学式: C₃₇H₅₁FO₁₂Si
• 分子量: 734.889
• InChiKey: LVDBHLFVLVPZHW-FETXBOAXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.04
• 重原子数：
  51.0
• 可旋转键数：
  9.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  164.12
• 氢给体数：
  2.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-acetoxy-9,11-dihydroxy-6-((methoxycarbonyl)oxy)-4a,8,13,13-tetramethyl-5-oxo-4-((triethylsilyl)oxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-yl 3-fluorobenzoate 、 (3R,4R)-1-(tert-butoxycarbonyl)-3-triisopropylsiloxy-4-trifluoromethylazetidin-2-one 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 生成
  参考文献：
  名称：

  Syntheses and structure–activity relationships of novel 3′-difluoromethyl and 3′-trifluoromethyl-taxoids

  摘要：

  A series of novel 3'-difluoromethyl-taxoids and 3'-trifluoromethyl-taxoids with modifications at the C2 and C10 positions were synthesized and evaluated for their in vitro cytotoxicities against human breast carcinoma (MCF7-S, MCF7-R, LCC6-WT, LCC6-MDR), non-small cell lung carcinoma (H460) and colon adenocarcinoma (HT-29) cell lines. These second-generation fluoro-taxoids exhibited several times to more than 20 times better potency than paclitaxel against drug-sensitive cancer cell lines, MCF7-S, LCC6-WT. H460, and HT-29. These fluoro-taxoids also possess two orders of magnitude higher potency than paclitaxel against drug-resistant cancer cell lines, MCF7-R and LCC6-MDR. Structure-activity relationship study shows the importance of the C10 modification for increasing the activity against multidrug-resistant cancer cell lines. Effects of the C2-benzoate modifications on the potency in the 3'-difluoromethyl-taxoid series are very clear- (i.e., F < MeO < Cl < N-3), while those in the 3'-trifluoromethyl-taxoid series are less obvious. Also, different trends in the sensitivity to the C2-substitution are observed between drug-sensitive cell lines and drug-resistant cancer cell lines that overexpress efflux pumps. (c) 2008 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jfluchem.2008.05.013
• 作为产物：
  描述：

  10-脱乙酰基巴卡丁 III 在 吡啶 、 咪唑 、 4-二甲氨基吡啶 、 氢氟酸 、 红铝 、 lithium hexamethyldisilazane 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 2.0h， 生成 (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-acetoxy-9,11-dihydroxy-6-((methoxycarbonyl)oxy)-4a,8,13,13-tetramethyl-5-oxo-4-((triethylsilyl)oxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-yl 3-fluorobenzoate
  参考文献：
  名称：

  新型 3'-二氟乙烯基紫杉类化合物的合成与生物学评价

  摘要：

  一系列具有 C10 修饰以及具有 C2 和 C10 修饰的 3'-二氟乙烯基紫杉醇被战略性地设计为阻断细胞色素 P-450 3A4 酶的代谢并合成。评估了这些新型二氟乙烯基紫杉素对药物敏感的人乳腺 (MCF7)、多药耐药 (MDR) 人卵巢 (NCI/ADR)、人结肠 (HT-29) 和人胰腺 (PANC-1) 癌细胞的细胞毒性线。与紫杉醇相比，3'-二氟乙烯基紫杉醇对 MCF7、HT-29 和 PANC-1 细胞系的活性高出数倍至 16 倍，对 NCI/ADR 细胞系的效力高出三个数量级。构效关系研究表明 C2 修饰对 MDR 癌细胞系的活性至关重要，而 C10 修饰对效力的影响相当小，但有一些例外。C2 修饰对 MCF7 细胞系效力的影响按以下顺序增加：H < F < Cl < N3 . 在评估的 25 种 3'-二氟乙烯基紫杉类中，8 种紫杉类对 MCF7 细胞系的pM IC 50值小于

  DOI：

  10.1016/j.jfluchem.2012.07.007