(3R,4S,5R,6R,7R)-N-(3,5,6-trihydroxy-7-(hydroxymethyl)azepan-4-yl)acetamide | 1147551-50-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (3R,4S,5R,6R,7R)-N-(3,5,6-trihydroxy-7-(hydroxymethyl)azepan-4-yl)acetamide
• 英文别名: N-[(3r,4s,5r,6r,7r)-3,5,6-Trihydroxy-7-(Hydroxymethyl)azepan-4-Yl]acetamide
• CAS: 1147551-50-5
• 化学式: C₉H₁₈N₂O₅
• 分子量: 234.252
• InChiKey: RJAFVDFBXXHCRJ-SYHAXYEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  122
• 氢给体数：
  6
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  在 盐酸 、 10% palladium on activated carbon 、 氢气 作用下， 以 甲醇 、 水 为溶剂， 反应 10.0h， 以100%的产率得到(3R,4S,5R,6R,7R)-N-(3,5,6-trihydroxy-7-(hydroxymethyl)azepan-4-yl)acetamide
  参考文献：
  名称：

  Design and synthesis of acetamido tri- and tetra-hydroxyazepanes: Potent and selective β-N-acetylhexosaminidase inhibitors

  摘要：

  A series of seven-membered iminosugars bearing an acetamido group beta- or gamma- to the endocyclic nitrogen have been synthesized via simple transformations of previously described polysubstituted azepanes. These tetra- and trihydroxylated acetamido azepanes are ring homologues of 2-acetamido-1,2-dideoxy-glyconojirimycins and 2-acetamido-1-N-iminosugars respectively. Screening of these azepanes towards a range of commercially available glycosidases demonstrated their potential as selective and potent hexosaminidase inhibitors with K-i's in the submicromolar range. A correlation between the relative configuration of the azepanes and their ability to inactivate hexosaminidases was also observed for the first time for this class of compounds with one notable exception for the most potent compound. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.06.022

文献信息

• Molecular Basis for Inhibition of GH84 Glycoside Hydrolases by Substituted Azepanes: Conformational Flexibility Enables Probing of Substrate Distortion
  作者：Filipa Marcelo、Yuan He、Scott A. Yuzwa、Lidia Nieto、Jesús Jiménez-Barbero、Matthieu Sollogoub、David J. Vocadlo、Gideon D. Davies、Yves Blériot

  DOI：10.1021/ja809776r

  日期：2009.4.22

  Here we report the synthesis of a series of polyhydroxylated 3- and 5-acetamido azepanes and detail the molecular basis of their inhibition of family 84 glycoside hydrolases. These family 84 enzymes include human O-GlcNAcase, an enzyme involved in post-translational processing of intracellular proteins modified by O-linked beta-N-acetylglucosamine residues. Detailed structural analysis of the binding of these azepanes to BtGH84, a bacterial homologue of O-GlcNAcase, highlights their conformational flexibility. Molecular mechanics and molecular dynamics calculations reveal that binding to the enzyme involves significant conformational distortion of these inhibitors from their preferred solution conformations. The binding of these azepanes provides structural insight into substrate distortion that likely occurs along the reaction coordinate followed by O-GlcNAcase during glycoside hydrolysis. This class of inhibitors may prove to be useful probes for evaluating the conformational itineraries of glycosidases and aid the development of more potent and specific glycosidase inhibitors.