(S)-9-Benzyloxy-11-hydroxy-5-oxo-2,3,11,11a-tetrahydro-1H,5H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carboxylic acid benzyl ester | 125299-57-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: (S)-9-Benzyloxy-11-hydroxy-5-oxo-2,3,11,11a-tetrahydro-1H,5H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carboxylic acid benzyl ester
• 英文别名: benzyl (6aS)-6-hydroxy-11-oxo-4-phenylmethoxy-6a,7,8,9-tetrahydro-6H-pyrrolo[2,1-c][1,4]benzodiazepine-5-carboxylate
• CAS: 125299-57-2
• 化学式: C₂₇H₂₆N₂O₅
• 分子量: 458.514
• InChiKey: KFXUQSSITIAAFA-CHQVSRGASA-N

物化性质

• 沸点：
  686.2±55.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.35
• 重原子数：
  34.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  79.31
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (S)-9-Benzyloxy-11-hydroxy-5-oxo-2,3,11,11a-tetrahydro-1H,5H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carboxylic acid benzyl ester 在 palladium on activated charcoal 氢气 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 150.0 ℃ 、202.65 kPa 条件下， 反应 5.0h， 生成 5-[6,8-二(苯基硫代)苯并[cd]吲哚-2(1H)-亚基]-1,3-二甲基-1H,3H,5H-嘧啶-2,4,6-三酮
  参考文献：
  名称：

  Stereoselective synthesis of tilivalline

  摘要：

  DOI：

  10.1016/s0040-4039(00)99602-3
• 作为产物：
  描述：

  3-羟基-2-氨基苯甲酸 在 sodium tetrahydroborate 、 叠氮磷酸二苯酯 、 potassium carbonate 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 5.06h， 生成 (S)-9-Benzyloxy-11-hydroxy-5-oxo-2,3,11,11a-tetrahydro-1H,5H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carboxylic acid benzyl ester
  参考文献：
  名称：

  A tricyclic pyrrolobenzodiazepine produced by Klebsiella oxytoca is associated with cytotoxicity in antibiotic-associated hemorrhagic colitis

  摘要：

  Cytotoxin-producing Klebsiella oxytoca is the causative agent of antibiotic-associated hemorrhagic colitis (AAHC). Recently, the cytotoxin associated with AAHC was identified as tilivalline, a known pentacyclic pyrrolobenzodiazepine (PBD) metabolite produced by K. oxytoca. Although this assertion of tilivalline's role in AAHC is supported by evidence from animal experiments, some key aspects of this finding appear to be incompatible with toxicity mechanisms of known PBD toxins. We therefore hypothesized that K. oxytoca may produce some other uncharacterized cytotoxins. To address this question, we investigated whether tilivalline alone is indeed necessary and sufficient to induce cytotoxicity or whether K. oxytoca also produces other cytotoxins. LC-MS- and NMR-based metabolomic analyses revealed the presence of an abundant tricyclic PBD, provisionally designated kleboxymycin, in the supernatant of toxigenic K. oxytoca strains. Moreover, by generating multiple mutants with gene deletions affecting tilivalline biosynthesis, we show that a tryptophanase-deficient, tilivalline-negative K. oxytoca mutant induced cytotoxicity in vitro similar to tilivalline-positive K. oxytoca strains. Furthermore, synthetic kleboxymycin exhibited greater than 9-fold higher cytotoxicity than tilivalline in TC50 cell culture assays. We also found that the biosynthetic pathways for kleboxymycin and tilivalline appear to overlap, as tilivalline is an indole derivative of kleboxymycin. In summary, our results indicate that tilivalline is not essential for inducing cytotoxicity observed in K. oxytoca-associated AAHC and that kleboxymycin is a tilivalline-related bacterial metabolite with even higher cytotoxicity.

  DOI：

  10.1074/jbc.m117.791558

文献信息

• NAGASAKA, TATSUO;KOSEKI, YUJI;HAMAGUCHI, FUMIKO, TETRAHEDRON LETT., 30,(1989) N4, C. 1871-1872
  作者：NAGASAKA, TATSUO、KOSEKI, YUJI、HAMAGUCHI, FUMIKO

  DOI：——

  日期：——