S-(4-amino-N-(tert-butoxycarbonyl)-4,5-dideoxy-2,3-O-isopropylidene-D-ribofuranos-5-yl)-N-(tert-butoxycarbonyl)-1-homocysteine tert-butyl ester | 1338787-25-9

• 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: S-(4-amino-N-(tert-butoxycarbonyl)-4,5-dideoxy-2,3-O-isopropylidene-D-ribofuranos-5-yl)-N-(tert-butoxycarbonyl)-1-homocysteine tert-butyl ester
• CAS: 1338787-25-9
• 化学式: C₂₆H₄₆N₂O₉S
• 分子量: 562.725
• InChiKey: LQQXHBKIGFPMBX-GGINLLQFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  38.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  132.86
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  S-(4-amino-N-(tert-butoxycarbonyl)-4,5-dideoxy-2,3-O-isopropylidene-D-ribofuranos-5-yl)-N-(tert-butoxycarbonyl)-1-homocysteine tert-butyl ester 在 三氟乙酸 、 水 作用下， 反应 11.0h， 以72%的产率得到S-(4-amino-4,5-dideoxy-D-ribofuranos-5-yl)-1-homocysteine
  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
• 作为产物：
  描述：

  S-(N-(tert-butoxycarbonyl)-4,5-dideoxy-2,3-O-isopropylidene-D-ribono-1,4-lactam-5-yl)-N-(tert-butoxycarbonyl)-1-homocysteine tert-butyl ester 在 lithium triethylborohydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以92%的产率得到S-(4-amino-N-(tert-butoxycarbonyl)-4,5-dideoxy-2,3-O-isopropylidene-D-ribofuranos-5-yl)-N-(tert-butoxycarbonyl)-1-homocysteine tert-butyl ester
  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