O-acetyl propranolol | 129459-75-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: O-acetyl propranolol
• 英文别名: (+/-)-propranolol acetate；Propranolol acetate；[1-naphthalen-1-yloxy-3-(propan-2-ylamino)propan-2-yl] acetate
• CAS: 129459-75-2
• 化学式: C₁₈H₂₃NO₃
• 分子量: 301.386
• InChiKey: KIQZYYYXMURMTK-UHFFFAOYSA-N

物化性质

• 沸点：
  439.7±35.0 °C(Predicted)
• 密度：
  1.091±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  O-acetyl propranolol 生成 普萘洛尔
  参考文献：
  名称：

  O-乙酰基普萘洛尔在大鼠组织匀浆中作为前药的立体选择性水解。

  摘要：

  使用磷酸盐缓冲液（pH 7.4），大鼠血浆和大鼠组织匀浆研究了O-乙酰基普萘洛尔水解的立体化学特征。在磷酸盐缓冲液中，在（R）-和（S）-普萘洛尔的酯之间的水解速率没有观察到差异。在大鼠血浆和组织匀浆中，酯的水解既加速又立体选择性。在大鼠血浆中，O-乙酰基（R）-普萘洛尔的水解速度比（S）-异构体的水解快五倍。但是，在肝脏和肠匀浆中，（S）-异构体的水解速度比（R）-异构体快。在实验条件下未观察到（R）-和（S）-异构体之间的相互转化。外消旋的O-乙酰基普萘洛尔也观察到相同的立体选择性水解。然而，观察到的水解速率常数低于纯异构体。这些结果表明，O-乙酰基普萘洛尔的酶促水解是立体选择性发生的，血浆酶的选择性不同于肝和肠酶。

  DOI：

  10.1002/jps.2600810307
• 作为产物：
  描述：

  乙酸酐 、 在 碳酸氢钠 作用下， 生成 O-acetyl propranolol
  参考文献：
  名称：

  β-肾上腺素能阻断剂。8.与普萘洛尔和普萘洛尔有关的β-卤代烷基胺的反应。

  摘要：

  DOI：

  10.1021/jm00297a015

文献信息

• Facile Synthesis of Propranolol and Novel Derivatives
  作者：Vy Anh Tran、Nguyen Hai Tai Tran、Long Giang Bach、Trinh Duy Nguyen、Thi Thuong Nguyen、Tan Tai Nguyen、Thi Anh Nga Nguyen、The Ky Vo、Thu-Thao Thi Vo、Van Thuan Le

  DOI：10.1155/2020/9597426

  日期：2020.8.24

  Propranolol is one of the first medications of the beta-blocker used for antihypertensive drugs. This study reports the facile route for the synthesis of propranolol and its novel derivatives. Herein, propranolol synthesis proceeded from 1-naphthol and isopropylamine under mild and less toxic conditions. Novel propranolol derivatives were designed by reactions of propranolol with benzoyl chloride,

  心得安是用于抗高血压药物的β受体阻滞剂的首批药物之一。本研究报告了合成普萘洛尔及其新型衍生物的简便途径。在此，普萘洛尔在温和且毒性较小的条件下由 1-萘酚和异丙胺合成。通过将普萘洛尔与苯甲酰氯、氯铬酸吡啶鎓和正丁基溴分别通过酯化、氧化还原和烷基化反应设计了新型普萘洛尔衍生物。使用柱色谱和薄层色谱进行化合物的分离和纯度。质谱和 1H-NMR 光谱用于鉴定新的化合物结构。来自 2-氯苯甲酰氯（化合物 3）、2-氟苯甲酰氯（化合物 5）的心得安衍生物，尤其是乙酸酐（化合物 6）表现出高产率和显着增加的水溶性。六种半合成的心得安衍生物有望提高抗氧化和生物活性。
• Biotransformations with Rhizopus arrhizus and Geotrichum candidum for the preparation of ( S )-Atenolol and ( S )-Propranolol
  作者：Subhash V Damle、Prashant N Patil、Manikrao M Salunkhe

  DOI：10.1016/s0968-0896(00)00131-0

  日期：2000.8

  (+/-)-Atenolol/(+/-)-propranolol and their acetates were incubated with the fungus Rhizopus arrhizus and Geotrichum candidum separately for different time intervals to afford (S)-atenolol/(S)-propranolol in good optical yield. The time and pH for this biotransformation was optimised. The present biodegradations using Rhizopus arrhizus and Geotrichum candidum provides a simple and useful method to obtain

  将（+/-）-阿替洛尔/（+/-）-普萘洛尔及其乙酸盐与真菌根霉和念珠菌分别孵育不同的时间间隔，从而以良好的光学收率得到（S）-atenolol /（S）-propranolol 。优化了该生物转化的时间和pH。本发明的使用阿扎根霉和白色假丝酵母的生物降解提供了一种简单而有用的方法来获得作为β-肾上腺素能阻滞剂的活性对映体的（S）-阿替洛尔和（S）-普萘洛尔。
• Chemoenzymatic Synthesis of (R) - and (S) - Atenolol and Propranolol employing Lipase Catalyzed Enantioselective Esterification and Hydrolysis
  作者：Subhash V. Darnle、Prashant N. Patil、Manikrao M. Salunkhe

  DOI：10.1080/00397919908085905

  日期：1999.11

  Abstract Chemoenzymatic synthesis of (R) - and (S) - atenolol and propranolol employing lipase catalyzed enantioselective esterification and hydrolysis is described

  摘要 描述了使用脂肪酶催化的对映选择性酯化和水解的 (R) - 和 (S) - 阿替洛尔和普萘洛尔的化学酶促合成
• Effects of the Ester Moiety on Stereoselective Hydrolysis of Several Propranolol Prodrugs in Rat Tissues.
  作者：Koichi TAKAHASHI、Satoko TAMAGAWA、Hitomi SAKANO、Toyoshi KATAGI、Nobuyasu MIZUNO

  DOI：10.1248/bpb.18.1401

  日期：——

  stereoselective hydrolysis of the succinate ester was observed only in intestine homogenate, but the S/R ratio was almost 1 in plasma, liver and intestine homogenates. No interconversion between (R)- and (S)-isomer was observed during the hydrolysis of any of the ester prodrugs. These results indicate that hydrolysis of ester-type prodrugs of propranolol occurs stereoselectively in rat tissues, and that

  在磷酸盐缓冲液（pH 7.4），大鼠血浆和大鼠组织匀浆中研究了普萘洛尔，O-乙酰基，O-丙酰基，O-丁酰基，O-新戊酰基和琥珀酰基酯的几种酯型前药水解的立体化学特征。在磷酸盐缓冲液中，在（R）-和（S）-普萘洛尔的酯之间的水解速率没有观察到差异。酯部分对在磷酸盐缓冲液中的水解速率的影响按以下顺序：乙酸盐>丙酸酯>丁酸酯>琥珀酸酯>新戊酸酯。在大鼠血浆和组织匀浆中，酯的水解被加速，并且观察到立体选择性水解。在血浆中，除了琥珀酸酯以外，（R）-异构体的水解比（S）-异构体的水解快。另一方面，在肝脏和肠的匀浆中，（S）-异构体的水解速度比（R）-异构体快，除了肝脏匀浆中的琥珀酸酯和新戊酸酯。而且，水解速率的比率（S / R）随前药的类型而变化。随着酯的烷基链长度的增加，肝脏中的S / R比值趋于统一，而肠的匀浆度却几乎保持恒定。对于新戊酸酯，在血浆和肠匀浆中观察到立体选择性水解，而在肝匀浆中未观
• Acetylation of (R,S)-propranolol catalyzed by Candida antarctica lipase B: An experimental and computational study
  作者：Andrés M. Escorcia、Daniel Molina、Martha C. Daza、Markus Doerr

  DOI：10.1016/j.molcatb.2013.09.019

  日期：2013.12

  The chemo- and enantioselectivity of the Candida antarctica lipase B (CalB)-catalyzed acetylation reaction of (R,S)-propranolol using vinyl acetate as acyl donor and toluene as organic solvent was studied. Because of the poor solubility of propranolol in toluene small quantities of methanol were added as cosolvent. The effects of the propranolol/vinyl acetate ratio, the enzyme purification procedure and the methanol concentration on the reaction were investigated. The reactions occurring in the system were quantitatively investigated using H-1 and C-13 NMR spectroscopy. The major reactions were the hydrolysis and alcoholysis of vinyl acetate, as a consequence of the presence of residual water and methanol in the reaction medium. Furthermore, the NMR analysis confirmed that O-acetyl-propranolol was formed exclusively. The reaction was also found to be enantioselective favoring the faster transformation of the R-propranolol. In addition to the experiments, molecular modeling was used to study the formation of the reactive Michaelis complexes between propranolol and acetylated CalB, using a combined molecular docking and molecular dynamics (MD) procedure. Only for the O-acetylation we found binding modes of the substrate leading to formation of the product, which explains the experimentally observed chemoselectivity of CalB. (C) 2013 Elsevier B.V. All rights reserved.