splenocin B | 1148106-17-5

• 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: splenocin B
• 英文别名: [(2R,3S,6S,7R,8R)-8-benzyl-3-[(3-formamido-2-hydroxybenzoyl)amino]-2,6-dimethyl-4,9-dioxo-1,5-dioxonan-7-yl] 2-methylpropanoate
• CAS: 1148106-17-5
• 化学式: C₂₈H₃₂N₂O₉
• 分子量: 540.57
• InChiKey: POEKVQXERPXKAO-NIBHENIISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  157
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  splenocin B 、 苯甲酰氯 在 4-二甲氨基吡啶 作用下， 以 吡啶 为溶剂， 生成
  参考文献：
  名称：

  Potent Inhibitors of Pro-Inflammatory Cytokine Production Produced by a Marine-Derived Bacterium

  摘要：

  Cytokines produced through the antigen presenting cell (APC)-T-cell interaction play a key role in the activation of the allergic asthmatic response. Evaluating small molecules that inhibit the production of these pro-inflammatory proteins is therefore important for the discovery of novel chemical structures with potential antiasthma activity. We adapted a mouse splerrocyte cytokine assay to screen a library of 2,500 marine microbial extracts for their ability to inhibit T(H)2 cytokine release and identified potent activity in a marine-derived strain CNQ431, identified as a Streptomyces species. Bioactivity guided fractionation of the organic extract of this strain led to the isolation of ten new 9-membered bis-lactones, splenocins A-J (1-10). The new compounds display potent biological activities, comparable to that of the corticosteroid dexamethasone, with IC50 values from 2 to 50 nM in the splenocyte cytokine assay. This study provides the foundation for the optimization of these potent anti-inflammatory compounds for development in the treatment of asthma.

  DOI：

  10.1021/jm801110j
• 作为产物：
  描述：

  (2R,3R,4S)-2-benzyl-3-(tert-butyldimethylsilanyloxy)-4-hydroxypentanoic acid benzyl ester 在 N-甲基吗啉 、 吡啶 、 4-二甲氨基吡啶 、 [ruthenium(II)(η⁶-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]₂ 、 D(+)-10-樟脑磺酸 、 氢气 、 1-羟基苯并三唑 、 氟化氢吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 80.0 ℃ 、101.33 kPa 条件下， 反应 60.0h， 生成 splenocin B
  参考文献：
  名称：

  Splenocin B的全合成，一种海洋衍生的链霉菌sp。的促炎细胞因子的有效抑制剂。

  摘要：

  已经描述了脾脏B（1）的第一个全合成，一种新的有效的抗炎抗霉素类抗生素。1的合成已从市售N -Boc-L-苏氨酸苄酯4和3,4-二羟基戊酸衍生物2开始，以8个线性步骤完成。通过乙氧基乙烯基酯中间体进行的Kita-Trost内酯化被用于构建9元双内酯核。

  DOI：

  10.1016/j.tet.2015.10.075

文献信息

• Total synthesis of splenocin B, a potent inhibitor of the pro-inflammatory cytokine from marine-derived Streptomyces sp.
  作者：Ken-ichi Yoshida、Minako Ijiri、Hideo Iio、Yoshinosuke Usuki

  DOI：10.1016/j.tet.2015.10.075

  日期：2015.12

  The first total synthesis of splenocin B (1), a new potent anti-inflammatory antimycin-class antibiotic, has been described. The synthesis of 1 has been accomplished in 8 linear steps, starting from commercially available N-Boc-L-threonine benzyl ester 4 and 3,4-dihydroxypentanoic acid derivative 2. Kita–Trost lactonization via an ethoxyvinyl ester intermediate was utilized for the construction of

  已经描述了脾脏B（1）的第一个全合成，一种新的有效的抗炎抗霉素类抗生素。1的合成已从市售N -Boc-L-苏氨酸苄酯4和3,4-二羟基戊酸衍生物2开始，以8个线性步骤完成。通过乙氧基乙烯基酯中间体进行的Kita-Trost内酯化被用于构建9元双内酯核。
• Potent Inhibitors of Pro-Inflammatory Cytokine Production Produced by a Marine-Derived Bacterium
  作者：Wendy K. Strangman、Hak Cheol Kwon、David Broide、Paul R. Jensen、William Fenical

  DOI：10.1021/jm801110j

  日期：2009.4.23

  Cytokines produced through the antigen presenting cell (APC)-T-cell interaction play a key role in the activation of the allergic asthmatic response. Evaluating small molecules that inhibit the production of these pro-inflammatory proteins is therefore important for the discovery of novel chemical structures with potential antiasthma activity. We adapted a mouse splerrocyte cytokine assay to screen a library of 2,500 marine microbial extracts for their ability to inhibit T(H)2 cytokine release and identified potent activity in a marine-derived strain CNQ431, identified as a Streptomyces species. Bioactivity guided fractionation of the organic extract of this strain led to the isolation of ten new 9-membered bis-lactones, splenocins A-J (1-10). The new compounds display potent biological activities, comparable to that of the corticosteroid dexamethasone, with IC50 values from 2 to 50 nM in the splenocyte cytokine assay. This study provides the foundation for the optimization of these potent anti-inflammatory compounds for development in the treatment of asthma.