N-(2-furanoyl)-N-debenzoylpaclitaxel | 157187-76-3

• 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: N-(2-furanoyl)-N-debenzoylpaclitaxel
• 英文别名: N-debenzoyl-N-(2-furoyl)paclitaxel；[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-(furan-2-carbonylamino)-2-hydroxy-3-phenylpropanoyl]oxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 157187-76-3
• 化学式: C₄₅H₄₉NO₁₅
• 分子量: 843.882
• InChiKey: OZLOKBVNWFMQFL-MHHARFCSSA-N

物化性质

• 熔点：
  167-168 °C
• 沸点：
  947.2±65.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  61
• 可旋转键数：
  14
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  234
• 氢给体数：
  4
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  10-脱乙酰基巴卡丁 III 在 吡啶 、 咪唑 、 氢氟酸 、 sodium hexamethyldisilazane 、 碳酸氢钠 、 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 0.83h， 生成 N-(2-furanoyl)-N-debenzoylpaclitaxel
  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

• Synthesis, Conformational Analysis, and Biological Evaluation of Heteroaromatic Taxanes
  作者：Gunda I. Georg、Geraldine C. B. Harriman、Michael Hepperle、Jamie S. Clowers、David G. Vander Velde、Richard H. Himes

  DOI：10.1021/jo951961c

  日期：1996.1.1

  cytotoxicity against B16 melanoma cells. 3'-Dephenyl-3'-(2-pyridyl)paclitaxel (31), 3'-dephenyl-3'-(2-furyl)paclitaxel (34), N-BOC-3'-dephenyl-3'-(2-furyl)paclitaxel (43), 3'-dephenyl-3'-(2-furyl)-N-(hexanoyl)paclitaxel (44), and N-debenzoyl-N-(3-furoyl)paclitaxel (51) were found to be more cytotoxic than paclitaxel against this cell line. 3'-Dephenyl-3'-(4-pyridyl)paclitaxel (33) and N-debenzoyl-N-(2-furoyl)paclitaxel

  描述了通过手性酯烯酸酯-亚胺环缩合化学的不对称合成杂芳族3-[（叔丁基二甲基甲硅烷基）氧基] -2-氮杂环丁酮12-16。氮杂环丁酮含有杂芳族部分，在某些情况下，由于过渡态中可能的交替配位，导致对映选择性降低。随后将（3R，4S）-3-[（叔丁基二甲基甲硅烷基）氧基] -4-杂芳基-2-氮杂环丁烷酮转化为杂芳族紫杉烷31-36和43-45。3'-（2-吡啶基）类似物31和3'-（2-呋喃基）类似物43的构象分析表明，它们具有与紫杉醇和多西他赛几乎相同的溶液构象偏好。杂芳族N-酰基紫杉醇类似物47-51由N-去苯甲酰基紫杉醇经Schotten-Baumann酰化制备。与紫杉醇相比，14种类似物中的大多数在微管组装试验中显示出良好至优异的活性。还测试了类似物对B16黑素瘤细胞的细胞毒性。3'-脱苯基-3'-（2-吡啶基）紫杉醇（31），3'-脱苯基-3'-（2-呋喃基）紫杉醇（34），N-BO