2-desbenzoyl-2-(3-chlorobenzoyl)-10-deacetyl-7,10-bis(triethylsilyl) baccatin III | 159211-96-8

• 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-desbenzoyl-2-(3-chlorobenzoyl)-10-deacetyl-7,10-bis(triethylsilyl) baccatin III
• 英文别名: 2-desbenzoyl-2-(3-chlorobenzoyl)-10-deacetyl-7,10-bis-O-(triethylsilyl)baccatin III
• CAS: 159211-96-8
• 化学式: C₄₁H₆₃ClO₁₀Si₂
• 分子量: 807.569
• InChiKey: ARTKHVANRUOBBH-RHJDUELYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.79
• 重原子数：
  54.0
• 可旋转键数：
  13.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  137.82
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  cis-1-(tert-butoxycarbonyl)-3-triethylsilyloxy-4-phenylazetidin-2-one 、 2-desbenzoyl-2-(3-chlorobenzoyl)-10-deacetyl-7,10-bis(triethylsilyl) baccatin III 在 lithium hexamethyldisilazane 、 溶剂黄146 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.5h， 以71 mg的产率得到(2'R,3'S)-2',7,10-tris(triethylsilyl)-2-desbenzoyl-2-(3-chlorobenzoyl)-10-deacetyl-N-desbenzoyl-N-(t-butoxycarbonyl) taxol
  参考文献：
  名称：

  C2 substituted phenyl taxane derivatives and pharmaceutical compositions containing them

  摘要：

  具有替代C2取代基的紫杉烷衍生物。

  公开号：

  US06339164B1
• 作为产物：
  描述：

  三乙基氯硅烷 、 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 生成 2-desbenzoyl-2-(3-chlorobenzoyl)-10-deacetyl-7,10-bis(triethylsilyl) baccatin III
  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

文献信息

• Process for the preparation of baccatin III analogs bearing new C2 and C4 functional groups
  申请人：Florida State University

  公开号：US06727369B1

  公开（公告）日：2004-04-27

  Process for the preparation of a derivative or analog of baccatin III or 10-desacetyl baccatin III having a C2 substituent other than benzoate and/or a C4 substituent other than acetate in which the C2 benzoate substituent and/or the C4 acetate substituent of a derivative of baccatin III or 10-desacetyl baccatin III is/are selectively reduced to the corresponding hydroxy group(s) and converted to R7COO— and/or R8COO—, respectively, wherein R7 and R8 are independently H, C1-C6 alkyl, C2-C6 alkenyl, C2-C8 alkynyl, moncyclic aryl, or monocyclic heteroaryl.

  这段文字是关于制备紫杉醇前体化合物——特别是baccatin III或10-desacetyl baccatin III的衍生物或类似物——的化学工艺描述。该工艺涉及对baccatin III或10-desacetyl baccatin III的C2位置上的苯甲酸酯基团和/或C4位置上的醋酸酯基团进行选择性还原，将它们转化为相应的羟基，并进一步转化为R7COO—和/或R8COO—，其中R7和R8独立地代表氢、C1-C6烷基、C2-C6烯基、C2-C8炔基、单环芳基或单环杂芳基。以下是中文翻译： 制备baccatin III或10-去乙酰基baccatin III的衍生物或类似物的工艺，该衍生物或类似物具有除苯甲酸酯以外的C2取代基和/或除醋酸酯以外的C4取代基，其中baccatin III或10-去乙酰基baccatin III衍生物的C2位苯甲酸酯取代基和/或C4位醋酸酯取代基被选择性地还原为相应的羟基，并且分别转化为R7COO—和/或R8COO—，其中R7和R8独立地为H，C1-C6烷基，C2-C6烯基，C2-C8炔基，单环芳基或单环杂芳基。