2-debenzoyl-2-(3-chlorobenzoyl)-7-triethylsilylbaccatin III | 189190-87-2

• 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: 2-debenzoyl-2-(3-chlorobenzoyl)-7-triethylsilylbaccatin III
• 英文别名: 2-(m-chlorobenzoyl)-2-debenzoyl-7-(triethylsilyl)baccatin III
• CAS: 189190-87-2
• 化学式: C₃₇H₅₁ClO₁₁Si
• 分子量: 735.344
• InChiKey: QRMOECYGGUVLFA-UZBMNOCMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.34
• 重原子数：
  50.0
• 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：
  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-chlorobenzoyl)-7-triethylsilylbaccatin III 在 4-二甲氨基吡啶 、 氟化氢吡啶 、 一水合肼 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 、 乙腈 为溶剂， 生成 [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-1,9-dihydroxy-15-[(2R,3S)-2-hydroxy-5-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]hex-4-enoyl]oxy-10,14,17,17-tetramethyl-12-[3-(methyldisulfanyl)propanoyloxy]-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] 3-chlorobenzoate
  参考文献：
  名称：

  Synthesis of potent taxoids for tumor-specific delivery using monoclonal antibodies

  摘要：

  The targeted delivery of taxoids, in the form of taxane-antibody immunoconjugates, requires the preparation of taxoids containing moieties suitable for their conjugation to monoclonal antibodies. A series of taxoids incorporating a disulfide-containing linker at various positions of the taxoid framework have been prepared to investigate the most suitable position for conjugation. A second series of taxoids modified at the C-2 position aimed at increasing the potency of these taxanes has also been prepared. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.05.027
• 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 2-debenzoyl-2-(3-chlorobenzoyl)-7-triethylsilylbaccatin III
  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

文献信息

• Synthesis and biological evaluation of amide-linked A-norpaclitaxels
  作者：Mahendra D. Chordia、David G.I. Kingston

  DOI：10.1016/s0040-4020(97)00281-0

  日期：1997.4

  A novel amide-linked A-norpaclitaxel 3a and two 2-aroyl analogs 3b and 3c were prepared from 10-deacetyl baccatin III. Key steps in the synthesis were the conversion of 7-(triethylsilyl)baccatin III to its 13β-chloro-A-nor derivative 6, reaction with sodium azide with inversion of stereochemistry to give the azide 8, and coupling of 8 with a protected β-phenylisoserine side chain 14 to give a protected

  由10-脱乙酰浆果赤霉素III制备了新的酰胺连接的A-或紫杉醇3a和两个2-芳酰基类似物3b和3c。合成的关键步骤是将7-（三乙基甲硅烷基）浆果赤霉素III转化为其13β-氯-A-nor衍生物6，与叠氮化钠反应，并通过立体化学转化得到叠氮化物8，以及将8与受保护的β偶联。-苯基异丝氨酸侧链14给出最终产物的保护形式15。在P-388细胞毒性试验中，三个类似物3a-3c的活性均低于紫杉醇，而3c 在微管蛋白组装测定中的活性也较低。
• Facile method for synthesizing baccatin III compounds
  申请人：Baloglu Erkan

  公开号：US20050256323A1

  公开（公告）日：2005-11-17

  A process for synthesizing a C-7 protected baccatin III compound represented by formula (A), which comprises reacting a 10-deacetylbaccatin III compound represented by formula (B) with a protecting agent and an acylating agent in the presence of a secondary amine and a nitrogen-containing compound. Also, a process for synthesizing a C-7 protected 10-deacetylbaccatin III compound represented by formula (C), which comprises reacting a 10-deacetylbaccatin III compound represented by formula (B) with a protecting agent in the presence of a secondary amine and a nitrogen-containing compound. In both processes the nitrogen-containing compound is selected from a nitrogen-containing heterocycle or a trialkylamine. When the nitrogen-containing heterocycle is selected, it may be an unsubstituted or a substituted pyridine or an unsubstituted or a substituted pyrazine. When a trialkylamine is selected, it may be, for example, triethylamine or diisopropylethylamine. wherein PG 1 represents the organic residue of the protecting agent, PG 2 represents the organic residue of the acylating agent, and R represents a simple or substituted aryl group or a heterocyclic group.

  一种合成C-7保护的巴卡汀III化合物的方法，其包括在辅助胺和含氮化合物的存在下，将式（B）所表示的10-去乙酰基巴卡汀III化合物与保护试剂和酰化试剂反应。同时，一种合成C-7保护的10-去乙酰基巴卡汀III化合物的方法，其包括在辅助胺和含氮化合物的存在下，将式（B）所表示的10-去乙酰基巴卡汀III化合物与保护试剂反应。在两种方法中，所述的含氮化合物是从含氮杂环或三烷基胺中选择的。当选择含氮杂环时，它可以是未取代或取代的吡啶或未取代或取代的吡嗪。当选择三烷基胺时，它可以是三乙胺或二异丙基乙胺等。其中，PG1表示保护试剂的有机残基，PG2表示酰化试剂的有机残基，R表示简单或取代的芳基或杂环基。
• Syntheses and structure–activity relationships of novel 3′-difluoromethyl and 3′-trifluoromethyl-taxoids
  作者：Larissa V. Kuznetsova、Antonella Pepe、Ioana M. Ungureanu、Paula Pera、Ralph J. Bernacki、Iwao Ojima

  DOI：10.1016/j.jfluchem.2008.05.013

  日期：2008.9

  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.