2-(4-Benzyloxy-butyl)-2-methyl-malonic acid diethyl ester | 364356-63-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(4-Benzyloxy-butyl)-2-methyl-malonic acid diethyl ester
• 英文别名: Diethyl 2-methyl-2-(4-phenylmethoxybutyl)propanedioate
• CAS: 364356-63-8
• 化学式: C₁₉H₂₈O₅
• 分子量: 336.428
• InChiKey: WNBXIFKPUIMVLL-UHFFFAOYSA-N

物化性质

• 沸点：
  406.8±40.0 °C(Predicted)
• 密度：
  1.060±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-Benzyloxy-butyl)-2-methyl-malonic acid diethyl ester 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 生成 2-(4-Benzyloxy-butyl)-2-methyl-propane-1,3-diol
  参考文献：
  名称：

  Acyl-CoA:Cholesterol O-Acyltransferase (ACAT) Inhibitors. 2. 2-(1,3-Dioxan-2-yl)-4,5-diphenyl-1H-imidazoles as Potent Inhibitors of ACAT

  摘要：

  The second in this series of papers concerns our further investigations into the search for a potent bioavailable acyl-CoA:cholesterol O-acyltransferase (ACAT) inhibitor suitable for the treatment of atherosclerosis. The design, synthesis, and structure-activity relationship for a series of ACAT inhibitors based on the 2-(1,3-dioxan-2-yl)-4,5-diphenyl-1H-imidazole pharmacophore are described. Compounds such as 13a bearing simple alkyl or hydroxymethyl substituents at the 5-position of the 1,3-dioxane ring are potent bioavailable inhibitors of the rat hepatic microsomal enzyme in vitro (IC50 < 100 nM) but are only weak inhibitors of the human hepatic enzyme. We have found however that 1,3-dioxanes substituted at the 5-cis position with pyrazolylalkyl or aminoalkyl groups are potent inhibitors in vitro of human macrophage ACAT, the potency depending on the nature of the terminal heterocycle and the length of the alkyl chain. An ex vivo bioassay described herein demonstrates that potent inhibitors such as 13t (IC50 = 10 nM) which contain lipophilic terminal heterocycles do not appear to be systemically available. Less potent but more water soluble compounds such as 13h (IC50 = 60 nM) and 13n (IC50 = 70 nM) are absorbed following oral dosing and achieve plasma levels significantly in excess of their IC50 for ACAT inhibition. These compounds are therefore possible candidates for further investigation as oral antiatherosclerotic agents.

  DOI：

  10.1021/jm9505876
• 作为产物：
  描述：

  4-苄氧基-1-丁醇 在 4-二甲氨基吡啶 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 27.0h， 生成 2-(4-Benzyloxy-butyl)-2-methyl-malonic acid diethyl ester
  参考文献：
  名称：

  Insoluble polystyrene-bound bis(oxazoline): batch and continuous-flow heterogeneous enantioselective glyoxylate–ene reaction

  摘要：

  The use of a new, insoluble polymer-bound bis(oxazoline) ligand (IPB-box) for the copper-catalyzed heterogeneous enantioselective glyoxylate-ene reaction is described. Good activity and ee values in the range 85-95% have been obtained during five to seven recycles, either in batch mode or under flow conditions, demonstrating also the recovery and reuse of the whole catalytically active copper complex. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2004.08.015

文献信息

• An Insoluble Polymer-Bound Bis-Oxazoline Copper(II) Complex: A Highly Efficient Heterogeneous Catalyst for the Enantioselective Mukaiyama Aldol Reaction
  作者：Simonetta Orlandi、Alessandro Mandoli、Dario Pini、Piero Salvadori

  DOI：10.1002/1521-3773(20010702)40:13<2519::aid-anie2519>3.0.co;2-d

  日期：2001.7.2

  polystyrene-supported bis-oxazoline 1 forms a complex with copper(II)triflate that is a highly effective catalyst for the heterogeneously catalyzed enantioselective Mukaiyama aldol reaction of silylthioketene acetals with methyl pyruvate (ca. 90 % yield, ca. 90 % ee). The catalyst can be recovered by simple filtration and reused several times without a decline in enantioselectivity.

  聚苯乙烯负载的双恶唑啉1与三氟甲磺酸铜（II）形成络合物，是一种高效的催化剂，用于甲硫基乙烯酮缩醛与丙酮酸甲酯的异质催化对映选择性Mukaiyama醛醇缩合反应（产率约90％，ee约90％） 。可以通过简单的过滤来回收催化剂，并且可以重复使用几次而不会降低对映选择性。
• Acyl-CoA:Cholesterol <i>O</i>-Acyltransferase (ACAT) Inhibitors. 2. 2-(1,3-Dioxan-2-yl)-4,5-diphenyl-1<i>H</i>-imidazoles as Potent Inhibitors of ACAT
  作者：Peter C. Astles、Michael J. Ashton、Andrew W. Bridge、Neil V. Harris、Terrance W. Hart、David P. Parrott、Barry Porter、David Riddell、Christopher Smith、Robert J. Williams

  DOI：10.1021/jm9505876

  日期：1996.1.1

  The second in this series of papers concerns our further investigations into the search for a potent bioavailable acyl-CoA:cholesterol O-acyltransferase (ACAT) inhibitor suitable for the treatment of atherosclerosis. The design, synthesis, and structure-activity relationship for a series of ACAT inhibitors based on the 2-(1,3-dioxan-2-yl)-4,5-diphenyl-1H-imidazole pharmacophore are described. Compounds such as 13a bearing simple alkyl or hydroxymethyl substituents at the 5-position of the 1,3-dioxane ring are potent bioavailable inhibitors of the rat hepatic microsomal enzyme in vitro (IC50 < 100 nM) but are only weak inhibitors of the human hepatic enzyme. We have found however that 1,3-dioxanes substituted at the 5-cis position with pyrazolylalkyl or aminoalkyl groups are potent inhibitors in vitro of human macrophage ACAT, the potency depending on the nature of the terminal heterocycle and the length of the alkyl chain. An ex vivo bioassay described herein demonstrates that potent inhibitors such as 13t (IC50 = 10 nM) which contain lipophilic terminal heterocycles do not appear to be systemically available. Less potent but more water soluble compounds such as 13h (IC50 = 60 nM) and 13n (IC50 = 70 nM) are absorbed following oral dosing and achieve plasma levels significantly in excess of their IC50 for ACAT inhibition. These compounds are therefore possible candidates for further investigation as oral antiatherosclerotic agents.
• Insoluble polystyrene-bound bis(oxazoline): batch and continuous-flow heterogeneous enantioselective glyoxylate–ene reaction
  作者：Alessandro Mandoli、Simonetta Orlandi、Dario Pini、Piero Salvadori

  DOI：10.1016/j.tetasy.2004.08.015

  日期：2004.10

  The use of a new, insoluble polymer-bound bis(oxazoline) ligand (IPB-box) for the copper-catalyzed heterogeneous enantioselective glyoxylate-ene reaction is described. Good activity and ee values in the range 85-95% have been obtained during five to seven recycles, either in batch mode or under flow conditions, demonstrating also the recovery and reuse of the whole catalytically active copper complex. (C) 2004 Elsevier Ltd. All rights reserved.