2',2"-methylenepaclitaxel | 214766-65-1

• 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',2"-methylenepaclitaxel
• 英文别名: 2',2''-Methylenepaclitaxel；[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-2-benzoyloxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-15-yl] (1S,2R)-1-benzamido-2-hydroxy-1,3-dihydroindene-2-carboxylate
• CAS: 214766-65-1
• 化学式: C₄₈H₅₁NO₁₄
• 分子量: 865.931
• InChiKey: ZDNNCMLZHKYRSN-YVUOUFJMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  63
• 可旋转键数：
  12
• 环数：
  8.0
• 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：

  ethyl 1H-indene-2-carboxylate 在 potassium dioxotetrahydroxoosmate(VI) 盐酸 、 4-二甲氨基吡啶 、 sodium hydroxide 、 Hydroquinone 1,4-phthalazinediyl diether 、 次氯酸叔丁酯 、 ammonium formate 、 4-甲基苯磺酸吡啶 、 碳酸氢钠 、 potassium carbonate 、 溶剂黄146 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 异丙醇 、 甲苯 为溶剂， 反应 24.0h， 生成 2',2"-methylenepaclitaxel
  参考文献：
  名称：

  Synthesis and NMR-Driven Conformational Analysis of Taxol Analogues Conformationally Constrained on the C13 Side Chain

  摘要：

  Analogues of Taxol (paclitaxel) with the side chain conformationally restricted by insertion of a carbon linker between the 2 ' -carbon and the ortho-position of the 3 ' -phenyl ring were synthesized. Biological evaluation of these new taxoids showed that activity was dependent on the length of the linker and the configuration at C2 ' and C3 '. Two analogues in the home series, 9a and 24a, showed tubulin binding and cytotoxicity comparable to that of Taxol. NAMFIS (NMR analysis of molecular flexibility in solution) deconvolution of the averaged 2-D NMR spectra for 9a yields seven conformations. Within the latter set, the hydrophobically collapsed "nonpolar" and "polar" classes are represented by one conformation each with predicted populations of 12-15%. The five remaining conformers, however, are extended, two of which correspond to the T-conformation (47% of the total population). The latter superimpose well with the recently proposed T-Taxol binding conformer in beta -tubulin. The results provide evidence for the existence of two previously unrecognized structural features that support Taxol-like activity: (1) a reduced torsion angle between C2 ' and C3 ' and (2) an orthogonal arrangement of the mean plane through C1 ', C2 ' and the 2 ' -hydroxyl and the 3 ' -phenyl plane, the latter ring bisected by the former plane. By contrast, epimerization at 2 ' ,3 ' and homologation of the tether to CH2-CH2 were both detrimental for activity. The decreased activity of these analogues is apparently due to configurational and steric factors, respectively.

  DOI：

  10.1021/jm001103v

文献信息

• Synthesis of a conformationally restricted analogue of paclitaxel
  作者：Luciano Barboni、Catia Lambertucci、Roberto Ballini、Giovanni Appendino、Ezio Bombardelli

  DOI：10.1016/s0040-4039(98)01537-8

  日期：1998.9

  A conformationally constrained analogue of the paclitaxel side-chain was synthesised in an enantioselective way from ethyl 1H-indene-2-carboxylate. Coupling with 7-triethylsilylbaccatin III and deprotection afforded 2',2 "-methylenepaclitaxel, a novel analogue of the natural product retaining anticancer activity. (C) 1998 Elsevier Science Ltd. All rights reserved.