dimethyl 4,4'-(benzylazanediyl)dibutyrate | 35635-66-6

• 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: dimethyl 4,4'-(benzylazanediyl)dibutyrate
• 英文别名: Methyl 4-[benzyl-(4-methoxy-4-oxobutyl)amino]butanoate
• CAS: 35635-66-6
• 化学式: C₁₇H₂₅NO₄
• 分子量: 307.39
• InChiKey: QSQMJWZHWYKTAK-UHFFFAOYSA-N

物化性质

• 沸点：
  401.4±35.0 °C(Predicted)
• 密度：
  1.078±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  22
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  dimethyl 4,4'-(benzylazanediyl)dibutyrate 在 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 23.0h， 生成 4-((tert-butoxycarbonyl)(4-oxo-4-(pentadecan-8-yloxy)butyl)amino)butanoic acid (Z)-non-2-en-1-yl ester
  参考文献：
  名称：

  Property-Driven Design and Development of Lipids for Efficient Delivery of siRNA

  摘要：

  Ionizable cationic lipids are critical components involved in nanoparticle formulations, which are utilized in delivery platforms for RNA therapeutics. While general criteria regarding lipophilicity and measured pK(a) in formulation are understood to have impacts on utility in vivo, greater granularity with respect to the impacts of the structure on calculated and measured physicochemical parameters and the subsequent performance of those ionizable cationic lipids in in vivo studies would be beneficial. Herein, we describe structural alterations made within a lipid class exemplified by 4, which allow us to tune calculated and measured physicochemical parameters for improved performance, resulting in substantial improvements versus the state of the art at the outset of these studies, resulting in good in vivo activity within a range of measured basicity (pK(a) = 6.0-6.6) and lipophilicity (cLogD = 10-14).

  DOI：

  10.1021/acs.jmedchem.0c01407
• 作为产物：
  描述：

  4-溴丁酸甲酯 、 苄胺 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 16.0h， 以73%的产率得到dimethyl 4,4'-(benzylazanediyl)dibutyrate
  参考文献：
  名称：

  Property-Driven Design and Development of Lipids for Efficient Delivery of siRNA

  摘要：

  Ionizable cationic lipids are critical components involved in nanoparticle formulations, which are utilized in delivery platforms for RNA therapeutics. While general criteria regarding lipophilicity and measured pK(a) in formulation are understood to have impacts on utility in vivo, greater granularity with respect to the impacts of the structure on calculated and measured physicochemical parameters and the subsequent performance of those ionizable cationic lipids in in vivo studies would be beneficial. Herein, we describe structural alterations made within a lipid class exemplified by 4, which allow us to tune calculated and measured physicochemical parameters for improved performance, resulting in substantial improvements versus the state of the art at the outset of these studies, resulting in good in vivo activity within a range of measured basicity (pK(a) = 6.0-6.6) and lipophilicity (cLogD = 10-14).

  DOI：

  10.1021/acs.jmedchem.0c01407

文献信息

• [EN] IONIZABLE CATIONIC LIPIDS FOR RNA DELIVERY<br/>[FR] LIPIDES CATIONIQUES IONISABLES POUR L'ACHEMINEMENT D'ARN
  申请人：ARCTURUS THERAPEUTICS INC

  公开号：WO2023086514A1

  公开（公告）日：2023-05-19

  The present disclosure describes compounds of Formula (I) and pharmaceutically acceptable salts thereof.

  本公开说明书描述了公式（I）的化合物及其药学上可接受的盐。
• Ionic Hydrogen Bond‐Assisted Catalytic Construction of Nitrogen Stereogenic Center via Formal Desymmetrization of Remote Diols
  作者：Zhongfu Luo、Minghong Liao、Wei Li、Sha Zhao、Kun Tang、Pengcheng Zheng、Yonggui Robin Chi、Xinglong Zhang、Xingxing Wu

  DOI：10.1002/anie.202404979

  日期：2024.7.29

  The control of noncarbon stereogenic centers is of profound importance owing to their enormous interest in bioactive compounds and chiral catalyst or ligand design for enantioselective synthesis. Despite various elegant approaches have been achieved for construction of S‐, P‐, Si‐ and B‐stereocenters over the past decades, the catalyst‐controlled strategies to govern the formation of N‐stereogenic compounds have garnered less attention. Here, we disclose the first organocatalytic approach for efficient access to a wide range of nitrogen‐stereogenic compounds through a desymmetrization approach. Intriguingly, the pro‐chiral remote diols, which are previously not well addressed with enantiocontrol, are well differentiated by potent chiral carbene‐bound acyl azolium intermediates. Preliminary studies shed insights on the critical importance of the ionic hydrogen bond (IHB) formed between the dimer aggregate of diols to afford the chiral N‐oxide products that feature a tetrahedral nitrogen as the sole stereogenic element with good yields and excellent enantioselectivities. Notably, the chiral N‐oxide products could offer an attractive strategy for chiral ligand design and discovery of potential antibacterial agrochemicals.