1-((methylsulfonyl)methyl)-2-nitro-5,6,7,8-tetrahydroindolizine | 1581263-52-6

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 1-((methylsulfonyl)methyl)-2-nitro-5,6,7,8-tetrahydroindolizine
• 英文别名: 1-(Methylsulfonylmethyl)-2-nitro-5,6,7,8-tetrahydroindolizine
• CAS: 1581263-52-6
• 化学式: C₁₀H₁₄N₂O₄S
• 分子量: 258.298
• InChiKey: FHSCUKDXAFOYQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  93.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  哌啶 在 silver nitrate 、 间氯过氧苯甲酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.25h， 生成 1-((methylsulfonyl)methyl)-2-nitro-5,6,7,8-tetrahydroindolizine
  参考文献：
  名称：

  Nitro-substituted tetrahydroindolizines and homologs: Design, kinetics, and mechanism of α-glucosidase inhibition

  摘要：

  A series of 1-[(methylsulfonyl)methyl]-2-nitro-5,6,7,8-tetrahydroindolizines and homologs were designed, prepared, and evaluated as non-sugar-type a-glucosidase inhibitors. The inhibitory activity appeared to be related to cyclo homologation with the best congeners being tetrahydroindolizines. The introduction of a methoxycarbonyl group as an additional hydrogen bond acceptor into the exocyclic methylene group was beneficial affording the most potent congener 3e (half maximal inhibitory concentration, IC50 = 8.0 +/- 0.1 mu M) which displayed 25-fold higher inhibitory activity than 1-deoxynojirimycin (2, IC50 = 203 +/- 9 mu M)-the reference compound. Kinetic analysis indicated that compound 3e is a mixed inhibitor with preference for the free enzyme over the alpha-glucosidase-substrate complex (K-i,K-free = 3.6 mu M; K-i,K-bound = 7.6 mu M). Molecular docking experiments were in agreement with kinetic results indicating reliable interactions with both the catalytic cleft and other sites. Circular dichroism spectroscopy studies suggested that the inhibition exerted by 3e may involve changes in the secondary structure of the enzyme. Considering the relatively low molecular weight of 3e together with its high fraction of sp(3) hybridized carbon atoms, this nitro-substituted tetrahydroindolizine may be considered as a good starting point towards new leads in the area of alpha-glucosidase inhibitors. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.07.068

文献信息

• Ring-Opening/Ring-Closing Protocols from Nitrothiophenes: Easy Access to<i>N</i>-Fused Pyrroles through a Tandem 1,6-H Shift/6π-Electrocyclization
  作者：Lara Bianchi、Massimo Maccagno、Giovanni Petrillo、Carlo Scapolla、Cinzia Tavani、Alessandra Tirocco

  DOI：10.1002/ejoc.201301236

  日期：2014.1

  amines and proper modification of the resulting 1,3-diene enables a simple and versatile approach to N-fused pyrroles of both synthetic and biological interest through 1,6-H shift followed by 6π 1,5-electrocyclization. This protocol is effectively driven to the isolated pyrroles by an easy aromatization.

  3-硝基-4-（苯磺酰基）噻吩与胺的开环和所得 1,3-二烯的适当修饰使得通过 1,6-H 获得具有合成和生物学意义的 N-稠合吡咯的简单而通用的方法移位，然后是 6π 1,5-电环化。该协议通过简单的芳构化有效地驱动到分离的吡咯。