tert-butyl (3aR,4R,6aS)-2,2-dimethyl-4-{[(methylsulfonyl)oxy]methyl}tetrahydro-5H-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate | 1338787-17-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: tert-butyl (3aR,4R,6aS)-2,2-dimethyl-4-{[(methylsulfonyl)oxy]methyl}tetrahydro-5H-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate
• 英文别名: 1-amino-1,4-anhydro-N-tert-butoxycarbonyl-1-deoxy-2,3-O-isopropylidene-5-O-methanesulfonyl-D-ribitol；N-tert-butoxycarbonyl-1,4-dideoxy-1,4-imino-2,3-O-isopropylidene-5-O-methanesulfonyl-D-ribitol；tert-butyl (3aR,4R,6aS)-2,2-dimethyl-4-(methylsulfonyloxymethyl)-3a,4,6,6a-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate
• CAS: 1338787-17-9
• 化学式: C₁₄H₂₅NO₇S
• 分子量: 351.421
• InChiKey: LBKOQRYGDMZVNW-OUAUKWLOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  99.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl (3aR,4R,6aS)-2,2-dimethyl-4-{[(methylsulfonyl)oxy]methyl}tetrahydro-5H-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate 在 ruthenium(IV) oxide hydrate sodium periodate 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 12.0h， 以95%的产率得到N-(tert-butyloxycarbonyl)-5-O-methanesulfonyl-4-deoxy-2,3-O-isopropylidene-D-ribono-1,4-lactam
  参考文献：
  名称：

  [EN] 2-METHYLTHIOPYRROLIDINES AND THEIR USE FOR MODULATING BACTERIAL QUORUM SENSING
  [FR] 2-MÉTHYLTHIOPYRROLIDINES ET LEUR UTILISATION POUR MODULER LA DÉTECTION DU QUORUM BACTÉRIEN

  摘要：

  本文披露了化学式（I）的化合物及其在抑制细菌中的群体感应中的应用。

  公开号：

  WO2012174511A1
• 作为产物：
  描述：

  tert-butyl {(2S)-1-[(tert-butyldiphenylsilyl)oxy]-4-(methylsulfinyl)butan-2-yl}carbamate 在 Grubbs catalyst first generation 、 四氧化锇 、 四丁基氟化铵 、 四丁基碘化铵 、 sodium hydride 、 对甲苯磺酸 、 N-甲基吗啉氧化物 、 三乙胺 、 calcium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 邻二氯苯 、 丙酮 、 mineral oil 为溶剂， 反应 7.5h， 生成 tert-butyl (3aR,4R,6aS)-2,2-dimethyl-4-{[(methylsulfonyl)oxy]methyl}tetrahydro-5H-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate
  参考文献：
  名称：

  手性吡咯烷支架修饰的异恶唑基CK1抑制剂的设计，合成和生物学评价。

  摘要：

  在这项研究中，我们报告了手性吡咯烷支架对3,4-二芳基-异恶唑基CK1抑制剂的修饰，以开发有效的和选择性的CK1抑制剂。铅结构的药效基团向由基于结构的药物设计驱动的三磷酸腺苷（ATP）结合位点的核糖口袋延伸。对于功能化的吡咯烷支架的高档兼容多谱图合成，我们使用了从蛋氨酸开始的手性库合成途径。在激酶和细胞分析中对关键化合物的生物学评估表明，支架对活性和选择性具有显着影响，但是，手性部分的绝对构型仅对抑制活性表现出有限的影响。配体-CK1δ配合物的X射线晶体学分析证实了3,4-二芳基-异恶唑抑制剂的预期结合方式。出乎意料的是，原始化合物在共结晶过程中经历了自发的Pictet-Spengler环化反应，并带有微量甲醛，以形成高效的新配体。我们的数据表明手性“核糖样”吡咯烷支架具有令人感兴趣的修饰药理活性化合物的潜力。

  DOI：

  10.3390/molecules24050873

文献信息

• 2-Methylthiopyrrolidines and Their Use for Modulating Bacterial Quorum Sensing
  申请人：Malladi Venkata L.

  公开号：US20140128446A1

  公开（公告）日：2014-05-08

  Compounds of Formula (I) are disclosed herein and their use in inhibiting quorum sensing in bacteria.

  本文披露了化学式（I）的化合物及其在抑制细菌群体感应中的应用。
• 2-METHYLTHIOPYRROLIDINES AND THEIR USE FOR MODULATING BACTERIAL QUORUM SENSING
  申请人：THE FLORIDA INTERNATIONAL UNIVERSITY BOARD OF TRUSTEES

  公开号：US20160137599A1

  公开（公告）日：2016-05-19

  Compounds of Formula (I) are disclosed herein and their use in inhibiting quorum sensing in bacteria.

  本文披露了式(I)的化合物及其在抑制细菌群体感应方面的应用。
• Substituted lactam and cyclic azahemiacetals modulate Pseudomonas aeruginosa quorum sensing
  作者：Venkata L.A. Malladi、Adam J. Sobczak、Natalie Maricic、Senthil Kumar Murugapiran、Lisa Schneper、John Makemson、Kalai Mathee、Stanislaw F. Wnuk

  DOI：10.1016/j.bmc.2011.07.044

  日期：2011.9

  Quorum sensing (QS) is a population-dependent signaling process bacteria use to control multiple processes including virulence that is critical for establishing infection. The most common QS signaling molecule used by Gram-negative bacteria are acylhomoserine lactones. The development of non-native acylhomoserine lactone (AHL) ligands has emerged as a promising new strategy to inhibit QS in Gram-negative bacteria. In this work, we have synthesized a set of optically pure gamma-lactams and their reduced cyclic azahemiacetal analogues, bearing the additional alkylthiomethyl substituent, and evaluated their effect on the AHL-dependent Pseudomonas aeruginosa las and rhl QS pathways. The concentration of these ligands and the simple structural modification such as the length of the alkylthio substituent has notable effect on activity. The c-lactam derivatives with nonylthio or dodecylthio chains acted as inhibitors of las signaling with moderate potency. The cyclic azahemiacetal with shorter propylthio or hexylthio substituent was found to strongly inhibit both las and rhl signaling at higher concentrations while the propylthio analogue strongly stimulated the las QS system at lower concentrations. (C) 2011 Elsevier Ltd. All rights reserved.
• Inhibition of LuxS by S-ribosylhomocysteine analogues containing a [4-aza]ribose ring
  作者：Venkata L.A. Malladi、Adam J. Sobczak、Tiffany M. Meyer、Dehua Pei、Stanislaw F. Wnuk

  DOI：10.1016/j.bmc.2011.07.043

  日期：2011.9

  LuxS (S-ribosylhomocysteinase) catalyzes the cleavage of the thioether linkage of S-ribosylhomocysteine (SRH) to produce homocysteine and 4,5-dihydroxy-2,3-pentanedione (DPD), the precursor to a small signaling molecule that mediates interspecies bacterial communication called autoinducer 2 (AI-2). Inhibitors of LuxS should interfere with bacterial interspecies communication and potentially provide a novel class of antibacterial agents. In this work, SRH analogues containing substitution of a nitrogen atom for the endocyclic oxygen as well as various deoxyriboses were synthesized and evaluated for LuxS inhibition. Two of the [4-aza] SRH analogues showed modest competitive inhibition (K-I similar to 40 mu M), while most of the others were inactive. One compound that contains a hemiaminal moiety exhibited time-dependent inhibition, consistent with enzyme-catalyzed ring opening and conversion into a more potent species (K-I* = 3.5 mu M). The structure-activity relationship of the designed inhibitors highlights the importance of both the homocysteine and ribose moieties for high-affinity binding to LuxS active site. (C) 2011 Elsevier Ltd. All rights reserved.
• US9249095B2
  申请人：——

  公开号：US9249095B2

  公开（公告）日：2016-02-02