阿托伐他汀酸异丙酯 | 1035205-25-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 中文名称: 阿托伐他汀酸异丙酯
• 英文名称: (3R,5R)-isopropyl 7-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoate
• 英文别名: (3R,5R)-isopropyl 7-(2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl)-3,5-dihydroxyheptanoate；isopropyl (3R,5R)-7-(2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl)-3,5-dihydroxyheptanoate；Atorvastatin Isopropyl Ester；propan-2-yl (3R,5R)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoate
• CAS: 1035205-25-4
• 化学式: C₃₆H₄₁FN₂O₅
• 分子量: 600.73
• InChiKey: OAXYMQWHRMFLAR-LOYHVIPDSA-N

物化性质

• 沸点：
  716.4±60.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  44
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  阿托伐他汀酸异丙酯 在 sodium hydroxide 、 calcium chloride 作用下， 以 甲醇 、 水 为溶剂， 反应 2.0h， 以90%的产率得到lipitor
  参考文献：
  名称：

  用于钛介导的α，β-不饱和醛与双烯酮的不对称羟醛羟醛反应的新型氯霉素席夫碱配体：阿托伐他汀钙的短合成†

  摘要：

  从可商购的氯霉素碱制备了几种新颖的手性席夫碱配体，并将其应用于双烯酮与各种α，β-不饱和醛的钛介导的不对称醛醇缩合反应。该反应以高收率和高对映选择性进行。这种方法的合成效用在阿托伐他汀钙的短时合成中得到了证明。

  DOI：

  10.1039/c6ra15304f
• 作为产物：
  描述：

  (R)-isopropyl 7-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-pheny1-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-5-hydroxy-3-oxoheptanoate 在 二乙基甲氧基硼烷 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.0h， 以83%的产率得到阿托伐他汀酸异丙酯
  参考文献：
  名称：

  用于钛介导的α，β-不饱和醛与双烯酮的不对称羟醛羟醛反应的新型氯霉素席夫碱配体：阿托伐他汀钙的短合成†

  摘要：

  从可商购的氯霉素碱制备了几种新颖的手性席夫碱配体，并将其应用于双烯酮与各种α，β-不饱和醛的钛介导的不对称醛醇缩合反应。该反应以高收率和高对映选择性进行。这种方法的合成效用在阿托伐他汀钙的短时合成中得到了证明。

  DOI：

  10.1039/c6ra15304f

文献信息

• Synthetic studies on statins. Part 1: a short and cyanide-free synthesis of atorvastatin calcium via an enantioselective aldol strategy
  作者：Lemeng Hu、Fangjun Xiong、Xiaofei Chen、Wenxue Chen、Qiuqin He、Fener Chen

  DOI：10.1016/j.tetasy.2012.12.009

  日期：2013.2

  A short and cyanide-free enantioselective synthesis of atorvastatin calcium has been achieved starting from a commercially available highly substituted 1,4-diketone in an overall yield of 40%. The key step in this approach is the asymmetric aldol reaction of an aldehyde with diketene in the presence of Ti(O-i-Pr)(4)-Schiff base complex to create the (5R)-stereochemistry of atorvastatin calcium. (C) 2013 Elsevier Ltd. All rights reserved.
• Structure-activity relationship of atorvastatin derivatives for metabolic activation by hydrolases
  作者：Kenta Mizoi、Masato Takahashi、Sachiko Sakai、Takuo Ogihara、Masami Haba、Masakiyo Hosokawa

  DOI：10.1080/00498254.2019.1625083

  日期：2020.3.3

  1. We investigated the structure-activity relationship of 31 kinds of synthesized atorvastatin esters, thioesters, amides and lactone, selected as prodrug models, for metabolic activation by microsomes and hydrolases. 2. The susceptibility to human carboxylesterase 1 (hCES1) was influenced not only by the size of the acyl group and alkoxy group but also by the degree of steric crowding around the alkoxy group. 3. The susceptibility to human carboxylesterase 2 (hCES2) increased with a decrease in electron density around the alkoxy group of the substrate. 4. Lactone was specifically hydrolyzed by paraoxonase 3 (PON3). 5. These findings should be useful in prodrug design for controlling metabolic activation.
• New chloramphenicol Schiff base ligands for the titanium-mediated asymmetric aldol reaction of α,β-unsaturated aldehydes with diketene: a short synthesis of atorvastatin calcium
  作者：Haifeng Wang、Linjie Yan、Fangjun Xiong、Yan Wu、Fener Chen

  DOI：10.1039/c6ra15304f

  日期：——

  Several novel chiral Schiff base ligands were prepared from a commercially available chloramphenicol base and applied to the titanium-mediated asymmetric aldol reaction of diketene with various α,β-unsaturated aldehydes. This reaction proceeded in good yield with high enantioselectivity. The synthetic utility of this methodology was demonstrated in the short synthesis of atorvastatin calcium.

  从可商购的氯霉素碱制备了几种新颖的手性席夫碱配体，并将其应用于双烯酮与各种α，β-不饱和醛的钛介导的不对称醛醇缩合反应。该反应以高收率和高对映选择性进行。这种方法的合成效用在阿托伐他汀钙的短时合成中得到了证明。