methyl (2S,4R)-4-hydroxy-1-(3,4,5-trimethoxybenzoyl)pyrrolidine-2-carboxylate | 142962-31-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (2S,4R)-4-hydroxy-1-(3,4,5-trimethoxybenzoyl)pyrrolidine-2-carboxylate
• CAS: 142962-31-0
• 化学式: C₁₆H₂₁NO₇
• 分子量: 339.345
• InChiKey: OPHMORKKWGQJSD-MNOVXSKESA-N

物化性质

• 熔点：
  139.2-140.4 °C
• 沸点：
  524.6±50.0 °C(Predicted)
• 密度：
  1.288±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  94.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl (2S,4R)-4-hydroxy-1-(3,4,5-trimethoxybenzoyl)pyrrolidine-2-carboxylate 在 碳酸氢钠 、 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 以100%的产率得到methyl (2S)-4-oxo-1-(3,4,5-trimethoxybenzoyl)pyrrolidine-2-carboxylate
  参考文献：
  名称：

  Promysalin 类似物的转移全合成证明铁结合基序负责其窄谱抗菌活性

  摘要：

  Promysalin 是一种具有独特生物活性的物种特异性假单胞菌代谢物。为了更好地了解这种天然产物的作用方式，我们利用转向全合成 (DTS) 合成了 16 种类似物。我们的模拟研究表明，promysalin 的生物活性对其氢键网络内的变化很敏感，由此改变会产生剧烈的生物学后果。DTS 文库不仅产生了三种保留效力的类似物，而且还提供了洞察力，导致鉴定了以前未知的 promysalin 结合铁的能力。这些发现与先前的观察结果相结合，暗示了天然产物在根际内具有复杂的多方面作用。

  DOI：

  10.1021/jacs.6b03373
• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲酸 在 吡啶 、 磺酰氯 、 三乙胺 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 6.5h， 生成 methyl (2S,4R)-4-hydroxy-1-(3,4,5-trimethoxybenzoyl)pyrrolidine-2-carboxylate
  参考文献：
  名称：

  Design, synthesis, and evaluation of novel galloyl pyrrolidine derivatives as potential anti-tumor agents

  摘要：

  A series of novel galloyl pyrrolidine derivatives were synthesized as potential anti-tumor agents. Their inhibiting activities on gelatinase (NMP-2 and -9) were tested with succinylated gelatin as the substrate. Structure activity analyses demonstrate that introduction of longer and more flexible side chains at the C-4 position of the pyrrolidine ring brings higher activity against gelatinase. Free phenol hydroxyl group is more favorable than the methylated one, which confirms the important role of the phenol hydroxyl group when inhibitors interact with gelatinase. In particular, (2S,4S)-4-(3-(3,4-dimethoxyphenyl)acrylamido)-N-hydroxy-1-(3,4,5- trimethoxybenzoyl)pyrrolidine-2-carboxamide (18) stood out as the most attractive compound (IC50 = 0.9 nM). The anti-metastasis model of mice bearing H-22 tumor cells was used to evaluate their anti-tumor activities in vivo. The assay in vivo revealed that most of these inhibitors displayed favorable inhibitory activities (inhibitory rate > 35%) and no significant toxic effects were observed. The inhibition for 62.37% of 19 indicates the strategy used to design NIMP inhibitors (MMPIs) of galloyl pyrrolidine derivatives as potential anti-tumor agents is promising. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.09.031

文献信息

• [EN] NOVEL PROMYSALIN ANALOGUES AND METHODS OF USE THEREOF<br/>[FR] NOUVEAUX ANALOGUES DE PROMYSALINE ET PROCÉDÉS POUR LES UTILISER
  申请人：TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION

  公开号：WO2017184558A1

  公开（公告）日：2017-10-26

  The present invention includes novel analogs of promysalin useful in preventing or treating a microbial infection. The present invention also includes methods preventing or treating a microbial infection in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of the invention.

  本发明包括新型的类似物质，可用于预防或治疗微生物感染。本发明还包括一种预防或治疗需要的受试者微生物感染的方法，该方法包括向受试者施用本发明化合物的有效量。
• Promysalin analogues and methods of use thereof
  申请人：Temple University—Of The Commonwealth System of Higher Education

  公开号：US10647671B2

  公开（公告）日：2020-05-12

  The present invention includes novel analogs of promysalin useful in preventing or treating a microbial infection. The present invention also includes methods preventing or treating a microbial infection in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of the invention.

  本发明包括用于预防或治疗微生物感染的新型丙磺舒类似物。本发明还包括在有需要的受试者中预防或治疗微生物感染的方法，该方法包括向受试者施用有效量的本发明化合物。
• Novel Promysalin Analogues and Methods of Use Thereof
  申请人：Temple University-Of The Commonwealth System of Higher Education

  公开号：US20190161444A1

  公开（公告）日：2019-05-30

  The present invention includes novel analogs of promysalin useful in preventing or treating a microbial infection. The present invention also includes methods preventing or treating a microbial infection in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of the invention.
• Design, synthesis, and evaluation of novel galloyl pyrrolidine derivatives as potential anti-tumor agents
  作者：Xun Li、Yalin Li、Wenfang Xu

  DOI：10.1016/j.bmc.2005.09.031

  日期：2006.3

  A series of novel galloyl pyrrolidine derivatives were synthesized as potential anti-tumor agents. Their inhibiting activities on gelatinase (NMP-2 and -9) were tested with succinylated gelatin as the substrate. Structure activity analyses demonstrate that introduction of longer and more flexible side chains at the C-4 position of the pyrrolidine ring brings higher activity against gelatinase. Free phenol hydroxyl group is more favorable than the methylated one, which confirms the important role of the phenol hydroxyl group when inhibitors interact with gelatinase. In particular, (2S,4S)-4-(3-(3,4-dimethoxyphenyl)acrylamido)-N-hydroxy-1-(3,4,5- trimethoxybenzoyl)pyrrolidine-2-carboxamide (18) stood out as the most attractive compound (IC50 = 0.9 nM). The anti-metastasis model of mice bearing H-22 tumor cells was used to evaluate their anti-tumor activities in vivo. The assay in vivo revealed that most of these inhibitors displayed favorable inhibitory activities (inhibitory rate > 35%) and no significant toxic effects were observed. The inhibition for 62.37% of 19 indicates the strategy used to design NIMP inhibitors (MMPIs) of galloyl pyrrolidine derivatives as potential anti-tumor agents is promising. (c) 2005 Elsevier Ltd. All rights reserved.
• Diverted Total Synthesis of Promysalin Analogs Demonstrates That an Iron-Binding Motif Is Responsible for Its Narrow-Spectrum Antibacterial Activity
  作者：Andrew D. Steele、Colleen E. Keohane、Kyle W. Knouse、Sean E. Rossiter、Sierra J. Williams、William M. Wuest

  DOI：10.1021/jacs.6b03373

  日期：2016.5.11

  understand the mode of action of this natural product, we synthesized 16 analogs utilizing diverted total synthesis (DTS). Our analog studies revealed that the bioactivity of promysalin is sensitive to changes within its hydrogen bond network whereby alteration has drastic biological consequences. The DTS library not only yielded three analogs that retained potency but also provided insights that resulted in

  Promysalin 是一种具有独特生物活性的物种特异性假单胞菌代谢物。为了更好地了解这种天然产物的作用方式，我们利用转向全合成 (DTS) 合成了 16 种类似物。我们的模拟研究表明，promysalin 的生物活性对其氢键网络内的变化很敏感，由此改变会产生剧烈的生物学后果。DTS 文库不仅产生了三种保留效力的类似物，而且还提供了洞察力，导致鉴定了以前未知的 promysalin 结合铁的能力。这些发现与先前的观察结果相结合，暗示了天然产物在根际内具有复杂的多方面作用。