2'-O-(Methoxyacetyl)-7-O-(imidazolylcarbonyl)taxol | 161742-52-5

• 英文名称: 2'-O-(Methoxyacetyl)-7-O-(imidazolylcarbonyl)taxol
• 英文别名: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-(2-methoxyacetyl)oxy-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] imidazole-1-carboxylate
• CAS: 161742-52-5
• 化学式: C₅₄H₅₇N₃O₁₇
• 分子量: 1020.06
• InChiKey: BLKCSQFQCZJVRU-LNIXJACCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  74
• 可旋转键数：
  20
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  261
• 氢给体数：
  2
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  2'-O-(Methoxyacetyl)-7-O-(imidazolylcarbonyl)taxol 在 氨 作用下， 以 异丙醇 为溶剂， 反应 12.0h， 以70%的产率得到[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-9-carbamoyloxy-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
  参考文献：
  名称：

  Highly Water Soluble Taxol Derivatives: 7-Polyethylene Glycol Carbamates and Carbonates

  摘要：

  The first examples of highly water soluble taxol derivatives (0.1 mmol/mL) were prepared by the attachment of polyethylene glycol (molecular weight 2-5 kD) at the 7-position of taxol via a methane or carbonate linkage. When lower molecular weight polyethylene glycols (350 and 750) were used, the solubilities were considerably lower (1.87 x 10(-3) mmol/mL) but still substantially greater than taxol itself. Additional 7-substituted taxol derivatives were also prepared by utilizing small molecules consisting of sugars and ionic and multifunctional compounds. However, most of these derivatives had solubilities, calculated from HPLC retention times, that did not differ significantly from taxol itself. The use of methoxyacetate as a protecting group during these syntheses is discussed.

  DOI：

  10.1021/jo00107a010
• 作为产物：
  描述：

  紫杉醇 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 2'-O-(Methoxyacetyl)-7-O-(imidazolylcarbonyl)taxol
  参考文献：
  名称：

  Highly Water Soluble Taxol Derivatives: 7-Polyethylene Glycol Carbamates and Carbonates

  摘要：

  The first examples of highly water soluble taxol derivatives (0.1 mmol/mL) were prepared by the attachment of polyethylene glycol (molecular weight 2-5 kD) at the 7-position of taxol via a methane or carbonate linkage. When lower molecular weight polyethylene glycols (350 and 750) were used, the solubilities were considerably lower (1.87 x 10(-3) mmol/mL) but still substantially greater than taxol itself. Additional 7-substituted taxol derivatives were also prepared by utilizing small molecules consisting of sugars and ionic and multifunctional compounds. However, most of these derivatives had solubilities, calculated from HPLC retention times, that did not differ significantly from taxol itself. The use of methoxyacetate as a protecting group during these syntheses is discussed.

  DOI：

  10.1021/jo00107a010

文献信息

• Synthesis and Evaluation of Taxol–Folic Acid Conjugates as Targeted Antineoplastics † †See ref 1.
  作者：Jae Wook Lee、June Y Lu、P.S Low、P.L Fuchs

  DOI：10.1016/s0968-0896(02)00019-6

  日期：2002.7

  A series of Taxol derivatives tethered at C2' and C-7 to glutamate and folate have been synthesized for evaluation as prodrugs which release Taxol via hydrolytic lability of their alpha-alkoxy and alpha-amino esters. The half-time for hydrolysis of these materials was determined in pH 7 and pH 5 buffer. The in vitro cytotoxicity has been assessed in cell culture against A-549 lung cancer, MCF-7 breast cancer, and HT-29 colon cancer. Selected agents were further screened for folate binding and competitive binding with free folic acid, One agent (54), further evaluated in animal Studies as found to increase the lifespan in mice, but was less effective than Taxol itself. (C) 2002 Elsevier Science Ltd. All rights reserved.