7-O-(2-chloroacetyl)paclitaxel | 162081-12-1

• 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: 7-O-(2-chloroacetyl)paclitaxel
• 英文别名: 7-O-chloroacetylpaclitaxel；[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-9-(2-chloroacetyl)oxy-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 162081-12-1
• 化学式: C₄₉H₅₂ClNO₁₅
• 分子量: 930.403
• InChiKey: KDGTZUTXQJBOEB-DDQCEMGUSA-N

物化性质

• 熔点：
  152-156 °C
• 沸点：
  982.1±65.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  66
• 可旋转键数：
  17
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  227
• 氢给体数：
  3
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  7-O-(2-chloroacetyl)paclitaxel 在 氨 作用下， 以 吡啶 为溶剂， 反应 12.0h， 以84%的产率得到紫杉醇
  参考文献：
  名称：

  Method of preparation of anticancer taxanes using 3-[(substituted-2-trialkylsilyl)ethoxycarbonyl]-5-oxazolidine carboxylic acids

  摘要：

  这项发明涉及一种制备紫杉醇的过程，包括将7,10-二保护中间体7-O-(2-卤代酰基)紫杉醇III 6c或7,10-O-二-(2-卤代酰基)-10-去乙酰紫杉醇III 6b置于存在缩合剂、活化剂和芳香烃的条件下，与(4S,5R)-3-[(2-烷基/芳基-2-三烷基硅基)乙氧羰基]-4-芳基-2-取代-1,3-噁唑烷-5-羧酸1进行偶联反应，以获得7-O-[2-(卤代酰基)]-13-[(4S,5R)-4-芳基-2-取代-3(2-未取代/取代-2-三烷基硅基)-乙氧羰基-1,3-噁唑烷-5-羧酰基]紫杉醇III 7a或7,10-二-O-[2-(卤代酰基)]-13-[(4S,5R)-4-芳基-2-取代-3-(2-未取代/取代-2-三烷基硅基)乙氧羰基-1,3-噁唑烷-5-羧酰基]-10-去乙酰紫杉醇III 7b； 将偶联产物7-O-[2-(卤代酰基)]-13-[(4S,5R)-4-芳基-2-取代-3-(2-取代-2-三烷基硅基)乙氧羰基-1,3-噁唑烷-5-羧酰基]紫杉醇III 7a或7,10-二-O-[2-(卤代酰基)]-13-[(4S,5R)-4-芳基-2-取代-3-(2-取代-2-三烷基硅基)乙氧羰基-1,3-噁唑烷-5-羧酰基]-10-去乙酰紫杉醇III 7b与卤代烷烃中的四烷基铵盐反应，以获得结构8的游离胺； 将游离胺8在异相中与酸氯或酸酐在碱存在下反应，以获得结构9的中间体； 将化合物9的中间体在温和碱性条件下在-20至+40°C的条件下与氨或脂肪胺或芳香胺或它们的组合物一起进行2-卤代酰基的去保护反应，以获得紫杉醇或多西他赛。

  公开号：

  US20030229135A1
• 作为产物：
  描述：

  紫杉醇 在 4-二甲氨基吡啶 、 氟化氢吡啶 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 吡啶 、 二氯甲烷 为溶剂， 反应 50.0h， 生成 7-O-(2-chloroacetyl)paclitaxel
  参考文献：
  名称：

  7-O-acylpaclitaxel analogues: potential probes to map the paclitaxel binding site

  摘要：

  The synthesis and biological evaluation of several 7-O-acylpaclitaxel analogues as potential photoaffinity, electrophilic, and fluorescent probes are described. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00329-6

文献信息

• Arginine-Based Molecular Transporters:  The Synthesis and Chemical Evaluation of Releasable Taxol-Transporter Conjugates
  作者：Thorsten A. Kirschberg、Chris L. VanDeusen、Jonathan B. Rothbard、Michael Yang、Paul A. Wender

  DOI：10.1021/ol035234c

  日期：2003.9.1

  [GRAPHICS]A flexible and efficient procedure has been developed for the conjugation of taxol to various arginine-based molecular transporters via the taxol C2' O-chloroacetyl derivative. The resultant taxol-transporter conjugates are highly water soluble and release free taxol with half-lives of minutes to hours depending on the pH and the linker structure.
• Mechanistic considerations pertaining to the solvolysis of paclitaxel analogs bearing ester groups at the C2′ position
  作者：Wieslaw A Klis、Jeffrey G Sarver、Paul W Erhardt

  DOI：10.1016/s0040-4039(01)01643-4

  日期：2001.10

  Dilute solutions of paclitaxel-related derivatives having chloroacetyl esters in the CT position undergo ready methanolysis according to pseudo first-order kinetics while more concentrated solutions appear to be stabilized, possibly by the formation of hydrophobic aggregates that tend to bury this reaction center. Methanolysis is also attenuated in the presence of weak acid, suggesting that paclitaxel's neighboring benzamide nitrogen may be participating in the reaction by serving as an assisting nucleophile. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Method of preparation of anticancer taxanes using 3-[(substituted-2-trialkylsilyl)ethoxycarbonyl]-5-oxazolidine carboxylic acids
  申请人：——

  公开号：US20030229135A1

  公开（公告）日：2003-12-11

  This invention relates to a process for preparation of taxanes comprising subjecting 7,10-diprotected intermediates 7-O-(2-haloacyl) baccatin III 6 c or 7,10-O-di-(2-haloacyl)-10-deacetylbaccatin III 6b to a step of coupling with (4S,5R)-3-[(2-alkyl/aryl-2-trialkylsilyl) ethoxy-carbonyl]-4-aryl-2-substituted-1,3-oxazolidine-5-carboxylic acid 1 in the presence of a condensation agent, an activating agent and an aromatic hydrocarbon to obtain 7-O-[2-(haloacyl)]-13-[(4S,5R)-4-aryl-2-substituted-3(2-unsubstituted/substituted-2-trialkylsilyl)-ethoxycarbonyl-1,3-oxazolidinyl-5-carbonyl]baccatin III 7a or 7,10-di-O[2-(haloacyl)]-13-[(4S,5R)-4-aryl-2-substituted-3-(2-unsubstituted/substituted-2-trialkylsilyl)ethoxy-carbonyl-1,3-oxazolidinyl-5-carbonyl]-10-deacetylbaccatin III 7b; treating the coupled products 7-O-[2-(haloacyl)]-13-[(4S,5R)-4-aryl-2-substituted-3-(2-substituted-2-trialkylsilyl)ethoxy-carbonyl-1,3-oxazolidinyl-S-carbonyl]baccatin III 7a or 7,10-di-0-[2[(haloacyl)]-13-[(4S,5R)-4-aryl-2-substituted-3-(2-substituted-2-trialkylsilyl)ethoxycarbonyl-1,3-oxazolidinyl-5-carbonyl]-10-deacetylbaccatin III 7b with tetraalkylammonium halide in a haloalkane to obtain free amine of structure 8; treating free amine 8 with acid chloride or acid anhydride in the presence of a base in a heterogeneous phase to obtain the intermediates of structure 9; subjecting the intermediates of compound 9 to the deprotection of 2-haloacyl group under mild alkaline condition at −20 to +40° C. for 6-24 h in the presence of ammonia or aliphatic amines or aromatic amines or their combination to obtain paclitaxel or docetaxel.

  这项发明涉及一种制备紫杉醇的过程，包括将7,10-二保护中间体7-O-(2-卤代酰基)紫杉醇III 6c或7,10-O-二-(2-卤代酰基)-10-去乙酰紫杉醇III 6b置于存在缩合剂、活化剂和芳香烃的条件下，与(4S,5R)-3-[(2-烷基/芳基-2-三烷基硅基)乙氧羰基]-4-芳基-2-取代-1,3-噁唑烷-5-羧酸1进行偶联反应，以获得7-O-[2-(卤代酰基)]-13-[(4S,5R)-4-芳基-2-取代-3(2-未取代/取代-2-三烷基硅基)-乙氧羰基-1,3-噁唑烷-5-羧酰基]紫杉醇III 7a或7,10-二-O-[2-(卤代酰基)]-13-[(4S,5R)-4-芳基-2-取代-3-(2-未取代/取代-2-三烷基硅基)乙氧羰基-1,3-噁唑烷-5-羧酰基]-10-去乙酰紫杉醇III 7b； 将偶联产物7-O-[2-(卤代酰基)]-13-[(4S,5R)-4-芳基-2-取代-3-(2-取代-2-三烷基硅基)乙氧羰基-1,3-噁唑烷-5-羧酰基]紫杉醇III 7a或7,10-二-O-[2-(卤代酰基)]-13-[(4S,5R)-4-芳基-2-取代-3-(2-取代-2-三烷基硅基)乙氧羰基-1,3-噁唑烷-5-羧酰基]-10-去乙酰紫杉醇III 7b与卤代烷烃中的四烷基铵盐反应，以获得结构8的游离胺； 将游离胺8在异相中与酸氯或酸酐在碱存在下反应，以获得结构9的中间体； 将化合物9的中间体在温和碱性条件下在-20至+40°C的条件下与氨或脂肪胺或芳香胺或它们的组合物一起进行2-卤代酰基的去保护反应，以获得紫杉醇或多西他赛。
• 7-O-acylpaclitaxel analogues: potential probes to map the paclitaxel binding site
  作者：Gunda I. Georg、Yanbin Liu、Thomas C. Boge、Richard H. Himes

  DOI：10.1016/s0960-894x(97)00329-6

  日期：1997.7

  The synthesis and biological evaluation of several 7-O-acylpaclitaxel analogues as potential photoaffinity, electrophilic, and fluorescent probes are described. (C) 1997 Elsevier Science Ltd.