N-(tert-butyloxycarbonyl)-5-O-methanesulfonyl-4-deoxy-2,3-O-isopropylidene-D-ribono-1,4-lactam | 1338787-21-5

• 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: N-(tert-butyloxycarbonyl)-5-O-methanesulfonyl-4-deoxy-2,3-O-isopropylidene-D-ribono-1,4-lactam
• 英文别名: N-(tert-butoxycarbonyl)-4-deoxy-2,3-O-isopropylidene-5-O-methanesulfonyl-D-ribono-1,4-lactam；(3R,4R,5R)-N-(tert-butoxycarbonyl)-3,4-dihydroxy-3,4-O-isopropylidene-5-[(methanesulfonyloxy)methyl]pyrrolidin-2-one
• CAS: 1338787-21-5
• 化学式: C₁₄H₂₃NO₈S
• 分子量: 365.405
• InChiKey: BJQGWRKAUQACCM-OPRDCNLKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.63
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  108.44
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  N-(tert-butyloxycarbonyl)-5-O-methanesulfonyl-4-deoxy-2,3-O-isopropylidene-D-ribono-1,4-lactam 在 sodium hydride 、 三氟乙酸 作用下， 以 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 3.17h， 生成 (3R,4R,5S)-3,4-dihydroxy-5-(hexylthiomethyl)pyrrolidin-2-one
  参考文献：
  名称：

  Substituted lactam and cyclic azahemiacetals modulate Pseudomonas aeruginosa quorum sensing

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2011.07.044
• 作为产物：
  描述：

  (3AR,4R,6AS)-5-苄基-4-(((叔丁基二甲基硅烷基)氧基)甲基)-2,2-二甲基四 在 sodium periodate 、 ruthenium(IV) oxide hydrate 、 5%-palladium/activated carbon 、 四丁基氟化铵 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 27.0h， 生成 N-(tert-butyloxycarbonyl)-5-O-methanesulfonyl-4-deoxy-2,3-O-isopropylidene-D-ribono-1,4-lactam
  参考文献：
  名称：

  Inhibition of LuxS by S-ribosylhomocysteine analogues containing a [4-aza]ribose ring

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2011.07.043

文献信息

• [EN] 2-METHYLTHIOPYRROLIDINES AND THEIR USE FOR MODULATING BACTERIAL QUORUM SENSING<br/>[FR] 2-MÉTHYLTHIOPYRROLIDINES ET LEUR UTILISATION POUR MODULER LA DÉTECTION DU QUORUM BACTÉRIEN
  申请人：FLORIDA INT UNIV BOARD TRUSTEES

  公开号：WO2012174511A1

  公开（公告）日：2012-12-20

  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中的群体感应中的应用。