[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-12-(3,3-dimethylbutanoyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-triethylsilyloxy-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate | 181705-96-4

• 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: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-12-(3,3-dimethylbutanoyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-triethylsilyloxy-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 181705-96-4
• 化学式: C₄₁H₆₀O₁₁Si
• 分子量: 757.006
• InChiKey: VINRTRSTBJTCJD-PUANDBHHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  53
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  155
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-12-(3,3-dimethylbutanoyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-triethylsilyloxy-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate 、 (3R,4R)-1-(tert-butoxycarbonyl)-3-triisopropylsilyloxy-4-difluoromethylazetidin-2-one 在 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  Syntheses and biological activity of C-3′-difluoromethyl-taxoids

  摘要：

  A series of new taxoids bearing difluoromethyl group at the C-3' position and modifications at the C-10 and C-14 positions has been synthesized and their biological activities studied. The in vitro cytotoxicity assay results indicate that these newly developed taxoids exhibit comparable to several times better activity against drug-sensitive cell line LCC6-WT, and 40-70 times better activity against the corresponding drug-resistant cancer cell line LCC6-MDR as compared to that of paclitaxel. Apoptosis analysis has revealed the exceptional activity of SB-T-12843 (le) in inducing apoptosis in both MDR-bearing and MDR-negative cancer cells. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00093-6
• 作为产物：
  描述：

  3,3-二甲基丁酰氯 、 7-O-(三乙基硅烷基)-10-去乙酰基浆果赤霉素III 在 lithium hexamethyldisilazane 作用下， 生成 [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-12-(3,3-dimethylbutanoyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-triethylsilyloxy-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
  参考文献：
  名称：

  Syntheses and Structure−Activity Relationships of the Second-Generation Antitumor Taxoids:  Exceptional Activity against Drug-Resistant Cancer Cells

  摘要：

  A series of new 3'-(2-methyl-1-propenyl) and 3'-(2-methylpropyl) taxoids with modifications at C-10 was synthesized by means of the beta-lactam synthon method using 10-modified 7-(triethylsilyl)-10-deacetylbaccatin III derivatives. The new taxoids thus synthesized show excellent cytotoxicity against human ovarian (A121), non-small-cell lung (A549), colon (HT-29), and breast (MCF-7) cancer cell lines. All but one of these new taxoids possess better activity than paclitaxel and docetaxel in the same assay, i.e., the IC50 values of almost all the taxoids are in the subnanomolar level. It is found that a variety of modifications at C-10 is tolerated for the activity against normal cancer cell lines, but the activity against a drug-resistant human breast cancer cell line expressing MDR phenotype (MCF7-R) is highly dependent on the structure of the C-10 modifier. A number of the new taxoids exhibit remarkable activity (IC50 = 2.1-9.1 nM) against MCF7-R. Among these, three new taxoids, SB-T-1213 (4a), SB-T-1214 (4b), and SB-T-1102 (5a), are found to be exceptionally potent, possessing 2 orders of magnitude better activity than paclitaxel and docetaxel. The observed exceptional activity of these taxoids may well be ascribed to an effective inhibition of P-glycoprotein binding by the modified C-10 moieties. The new taxoid SB-T-1213 (4a) shows an excellent activity (T/C = 0% at 12.4 and 7.7 mg/kg/dose, log(10) cell kill = 2.3 and 2.0, respectively) against B16 melanoma in B6D2F(1) mice via intravenous administration.

  DOI：

  10.1021/jm9604080

文献信息

• Synthesis and biological activity of novel 3′-trifluoromethyl taxoids
  作者：Iwao Ojima、John C. Slater、Paula Pera、Jean M. Veith、Ahmed Abouabdellah、Jean-Pierre Bégué、Ralph J. Bernacki

  DOI：10.1016/s0960-894x(96)00595-1

  日期：1997.1

  Second generation taxoids possessing a trifluoromethyl moiety in place of the 3'-phenyl group are synthesized by means of the beta-Lactam Synthon Method. The in vitro cytotoxicities of these new taxoids are evaluated against several different human cancer cell lines and found to exhibit greatly enhanced activities as compared to those of paclitaxel and docetaxel. The activity enhancement is most remarkable against a drug-resistant breast cancer cell line, MCF7-R, expressing MDR phenotype. (C) 1997, Elsevier Science Ltd.