2',7-disuccinyltaxol | 117527-52-3

• 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: 2',7-disuccinyltaxol
• 英文别名: 4-[[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-(3-carboxypropanoyloxy)-3-phenylpropanoyl]oxy-2-benzoyloxy-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-9-yl]oxy]-4-oxobutanoic acid
• CAS: 117527-52-3
• 化学式: C₅₅H₅₉NO₂₀
• 分子量: 1054.07
• InChiKey: NZQWSYQBMNULIX-CGFZLWGJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.57
• 重原子数：
  76.0
• 可旋转键数：
  18.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  308.03
• 氢给体数：
  4.0
• 氢受体数：
  18.0

反应信息

• 作为产物：
  描述：

  丁二酸酐 、 紫杉醇 在 4-二甲氨基吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 以68%的产率得到2',7-disuccinyltaxol
  参考文献：
  名称：

  Synthesis of congeners and prodrugs. 3. Water-soluble prodrugs of taxol with potent antitumor activity

  摘要：

  Taxol has shown good in vivo antitumor activity in a number of test systems. The formulation of taxol for antitumor testing has been difficult. Esterification at either C-2' or C-7 resulted in loss of in vitro tubulin assembly activity but not cytotoxicity. These observations suggested that esters at C-2' and/or C-7, which would tend to promote water solubility, might serve as useful prodrugs of taxol. The reaction of taxol with either succinic anhydride or glutaric anhydride in pyridine solution at room temperature gave the crystalline mono 2'-adducts 1b and 1f, respectively. Salts of these acids (1b, 1f, 1i) were formed by the addition of 1 equiv of the corresponding base, followed by evaporation and/or freeze-drying of the solvent(s). The salts had improved antitumor activity as compared to the free acids. The triethanolamine and N-methylglucamine salts showed greatly improved aqueous solubility and were more active than the sodium salts. The glutarate series was preferred because of the higher activity and the higher yields obtained. 2'-Glutaryltaxol (1f) was coupled with 3-(dimethylamino)-1-propylamine, using CDI, to form in excellent yield the amino amide 1o. The hydrochloride salt (1p) showed good solubility and was extremely potent and active. At 10 mg/kg, in the B16 screen, 1p gave a T/C of 352 with 5 out of 10 cures. In the MX-1 breast xenograft assay, this prodrug gave values of -100 at doses of 40 and 20 mg/kg, with all live animals being tumor free.

  DOI：

  10.1021/jm00124a011

文献信息

• Drug-Initiated, Controlled Ring-Opening Polymerization for the Synthesis of Polymer–Drug Conjugates
  作者：Rong Tong、Jianjun Cheng

  DOI：10.1021/ma202581d

  日期：2012.3.13

  Paclitaxel, a polyol chemotherapeutic agent, was covalently conjugated through its 2'-OH to polylactide with 100% regioselectivity via controlled polymerization of lactide mediated by paclitaxel/(BDI-II)ZnN(TMS)(2) (BDI-II = 2-((2,6-diisopropylphenyl)amino)-4-((2,6-diisopropylphenyl)imino)-2-pentene). The steric bulk of the substituents on the N-aryl groups of the BDI ligand drastically affected the regiochemistry of coordination of the metal catalysts to paclitaxel and the subsequent ring-opening polymerization of lactide. The drug-initiated, controlled polymerization of lactide was extended, again with 100% regioselectivity, to docetaxel, a chemotherapeutic agent that is even more structurally complex than paclitaxel. Regioselective incorporation of paclitaxel (or docetaxel) to other biopolymers (i.e., poly(delta-valerolactone), poly(trimethylene carbonate), and poly(epsilon-caprolactone)) was also achieved through drug/(BDI-II)ZnN(TMS)(2)-mediated controlled polymerization. These drug-polylactide conjugates with precisely controlled structures are expected to be excellent building blocks for drug delivery, coating, and controlled-release applications.