paclitaxel | 300833-68-5

• 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: paclitaxel
• 英文别名: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-12-propanoyloxy-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 300833-68-5
• 化学式: C₄₈H₅₃NO₁₄
• 分子量: 867.947
• InChiKey: NCTHUZDWFREONY-WUBXVAPUSA-N

物化性质

• 熔点：
  156-158 °C
• 沸点：
  962.6±65.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  63
• 可旋转键数：
  15
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  221
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  10-脱乙酰基巴卡丁 III 在 咪唑 、 sodium hexamethyldisilazane 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 paclitaxel
  参考文献：
  名称：

  Structure–activity relationship study of taxoids for their ability to activate murine macrophages as well as inhibit the growth of macrophage-like cells

  摘要：

  A series of new taxoids modified at the C-3', C-3'N, C-10, C-2 and C-7 positions has been designed, synthesized and evaluated for their potency to induce NO and TNF production by peritoneal murine macrophages (Mphi) from LPS-responsive C3H/HeN and LPS-hyporesponsive C3H/HeJ strains and human blood cells, and for their ability to inhibit the growth of Mphi-like cell lines J774.1 and J7.DEF3. The SAR-study has shown that the nature of the substituents at these positions have critical effect on the induction of TNF and NO production by Mphi. Positions G-3' and C-10 are the most flexible and an intriguing effect of the length of the substituents at the C-10 position is observed for taxoids bearing a straight chain alkanoyl moiety. An aromatic group at the C-3'N and C-2 positions is required for the activity, while only hydroxyl or acetyl substituents seem to be tolerated at the C-7 position. The natural stereochemistry in the C-13 isoserine side chain of the taxoids is an absolute requirement for macrophage activation. It has also been clearly shown that there is no correlation between the ability of the taxoids to induce TNF/NO production in C3H/HeN M and the cytotoxicity against Mphi-like cells. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00181-0

文献信息

• Design and Synthesis of a Combinatorial Chemistry Library of 7-Acyl, 10-Acyl, and 7,10-Diacyl Analogues of Paclitaxel (Taxol) Using Solid Phase Synthesis
  作者：Prakash G. Jagtap、Erkan Baloglu、Donna M. Barron、Susan Bane、David G. I. Kingston

  DOI：10.1021/np010552a

  日期：2002.8.1

  A series of 10-acyl and 7,10-diacyl paclitaxel analogues (7a-7e and 9a-9u) have been synthesized using a solid phase combinatorial chemistry approach, and a second series of 7-acyl-10-deacetylpaclitaxel analogues have been prepared by conventional chemistry. In the first series, 10-deacetylpaclitaxel (4) was linked through its 2'-hydroxyl group using 1% polystyrene-divinyl benzene resin functionalized

  使用固相组合化学方法合成了一系列10酰基和7,10二酰基紫杉醇类似物（7a-7e和9a-9u），并制备了第二系列的7酰基-10-去乙酰基紫杉醇类似物。通过常规化学。在第一个系列中，使用1％的丁基二乙基硅烷连接基（PS-DES）官能化的1％聚苯乙烯-二乙烯基苯树脂通过其2'-羟基连接10-去乙酰基紫杉醇（4），然后在C-10羟基上用各种酸酐酰化和在CeCl（3）存在下的二碳酸二烷基酯。然后在甲苯中有1,3-二异丙基碳二亚胺存在下，用各种羧酸处理与树脂结合的C-10酰化的紫杉醇衍生物（6a-6e），以提供聚合物负载的7,10-二酰基紫杉醇（8a-8u）。这些7酰基和7 从树脂上裂解10-二酰基紫杉醇（6a-6e和8a-8u），得到24个紫杉醇类似物7a-7e和9a-9u。还通过常规化学方法制备了9个7-酰基-10-去乙酰基紫杉醇类似物。已经开发了确定通过组合方法少量制备的化合物的微管蛋白组装活
• Structure–activity relationship study of taxoids for their ability to activate murine macrophages as well as inhibit the growth of macrophage-like cells
  作者：Iwao Ojima、Cecilia L Fumero-Oderda、Scott D Kuduk、Zhuping Ma、Fumiko Kirikae、Teruo Kirikae

  DOI：10.1016/s0968-0896(03)00181-0

  日期：2003.7

  A series of new taxoids modified at the C-3', C-3'N, C-10, C-2 and C-7 positions has been designed, synthesized and evaluated for their potency to induce NO and TNF production by peritoneal murine macrophages (Mphi) from LPS-responsive C3H/HeN and LPS-hyporesponsive C3H/HeJ strains and human blood cells, and for their ability to inhibit the growth of Mphi-like cell lines J774.1 and J7.DEF3. The SAR-study has shown that the nature of the substituents at these positions have critical effect on the induction of TNF and NO production by Mphi. Positions G-3' and C-10 are the most flexible and an intriguing effect of the length of the substituents at the C-10 position is observed for taxoids bearing a straight chain alkanoyl moiety. An aromatic group at the C-3'N and C-2 positions is required for the activity, while only hydroxyl or acetyl substituents seem to be tolerated at the C-7 position. The natural stereochemistry in the C-13 isoserine side chain of the taxoids is an absolute requirement for macrophage activation. It has also been clearly shown that there is no correlation between the ability of the taxoids to induce TNF/NO production in C3H/HeN M and the cytotoxicity against Mphi-like cells. (C) 2003 Elsevier Science Ltd. All rights reserved.