(3S,4R,5R,6R)-benzyl 3,4,5-tris(benzyloxy)-6-hydroxyazepane-1-carboxylate | 924895-17-0

• 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: (3S,4R,5R,6R)-benzyl 3,4,5-tris(benzyloxy)-6-hydroxyazepane-1-carboxylate
• 英文别名: benzyl (3R,4R,5R,6S)-3-hydroxy-4,5,6-tris(phenylmethoxy)azepane-1-carboxylate
• CAS: 924895-17-0
• 化学式: C₃₅H₃₇NO₆
• 分子量: 567.682
• InChiKey: IDJMPAZUTQPHMS-KMKAFXEASA-N

物化性质

• 沸点：
  698.5±55.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  42
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  77.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3S,4R,5R,6R)-benzyl 3,4,5-tris(benzyloxy)-6-hydroxyazepane-1-carboxylate 在 甲醇 、 氢气 、 potassium carbonate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 反应 32.0h， 生成 (3S,4R,5R,6S)-4,5,6-tris(benzyloxy)-1-butylazepan-3-ol
  参考文献：
  名称：

  七元亚氨基糖的N和C烷基化产生有效的葡糖脑苷脂酶抑制剂和F508del-CFTR校正剂†

  摘要：

  已经广泛研究了合成的C-烷基和N-烷基六元亚氨基糖的糖苷酶抑制特性，从而产生了治疗候选物。尽管报道了有前途的结构，但相关的七元亚氨基环醇却很少被检查。使用室内环扩大/ C-烷基化以及交叉复分解方法学作为关键步骤，我们从易于获得的起始位置开始进行了14个2 C-和8个N-烷基四羟基化氮杂环丙烷的文库的合成和生物学评估。吡喃葡萄糖衍生的叠氮吲哚。已经引入了四个，六个，九个和十二个碳原子烷基链。两个不同的研究d -葡萄糖和大号- IDO为四醇图案以及立体化学ř和小号的C-2碳承载的配置Ç报道烷基链。我们观察到的该C-烷基化大号- IDO四羟基从α-氮杂环庚烷将其转换大号-fucosidase到β葡糖苷酶和β半乳糖苷酶抑制剂，而N-烷基化d -葡糖亚氨基糖显著提高了其抑制轮廓导致有力的无论烷基链的立体化学如何，β-葡萄糖苷酶，β-半乳糖苷酶，α- L-鼠李糖苷酶和β-葡萄糖醛酸苷酶抑制剂。有趣的是

  DOI：

  10.1039/c4ob00325j
• 作为产物：
  描述：

  (2R,3R,4S,5R,6S)-2-Azidomethyl-3,4,5-tris-benzyloxy-6-methoxy-tetrahydro-pyran 在 硫酸 、 sodium methylate 、 sodium cyanoborohydride 、 potassium hydrogencarbonate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 、 乙酸乙酯 为溶剂， 反应 10.0h， 生成 (3S,4R,5R,6R)-benzyl 3,4,5-tris(benzyloxy)-6-hydroxyazepane-1-carboxylate
  参考文献：
  名称：

  串联的Staudinger-azaWittig介导的环扩展：快速获得新的异黄花胺-四羟基氮杂环庚烷杂种。

  摘要：

  通过串联的Staudinger-azaWittig介导的扩环，已制备出对糖苷酶具有有效和选择性抑制作用的新的七元亚氨基糖，作为1-N-亚氨基糖同系物。

  DOI：

  10.1039/b610377d

文献信息

• Selective trihydroxyazepane NagZ inhibitors increase sensitivity of Pseudomonas aeruginosa to β-lactams
  作者：Martine Mondon、Soo Hur、Grishma Vadlamani、Prerana Rodrigues、Polina Tsybina、Antonio Oliver、Brian L. Mark、David J. Vocadlo、Yves Blériot

  DOI：10.1039/c3cc46646a

  日期：——

  AmpC beta-lactamase confers resistance to beta-lactam antibiotics in many Gram negative bacteria. Inducible expression of AmpC requires an N-acetylglucosaminidase termed NagZ. Here we describe the synthesis and characterization of hydroxyazepane inhibitors of NagZ. We find that these inhibitors enhance the susceptibility of clinically relevant Pseudomonas aeruginosa to beta-lactams.

  AmpCβ-内酰胺酶赋予许多革兰氏阴性细菌对β-内酰胺抗生素的抗性。AmpC的诱导表达需要一个称为NagZ的N-乙酰氨基葡糖苷酶。在这里，我们描述了NagZ的羟基氮杂环庚烷抑制剂的合成和表征。我们发现这些抑制剂增强了临床相关的铜绿假单胞菌对β-内酰胺的敏感性。
• Structural variation of the 3-acetamido-4,5,6-trihydroxyazepane iminosugar through epimerization and <i>C</i>-alkylation leads to low micromolar HexAB and NagZ inhibitors
  作者：J. Bouquet、N. Auberger、R. Ashmus、D. King、A. Bordes、N. Fontelle、S. Nakagawa、Z. Madden、C. Proceviat、A. Kato、J. Désiré、D. J. Vocadlo、Y. Blériot

  DOI：10.1039/d1ob02280f

  日期：——

  Escherichia coli NagZ. Capitalizing on the flexibility of azepanes and the active site tolerances of hexosaminidases, we explore the effects of epimerization of stereocenters at C-3, C-5 and C-6 and C-alkylation at the C-2 or C-7 positions. Accordingly, epimerization at C-6 (L-ido) and at C-5 (D-galacto) led to selective HexAB inhibitors whereas introduction of a propyl group at C-7 on the C-3 epimer furnished

  我们报告了衍生自 3 S -acetamido-4 R ,5 R ,6 S -trihydroxyazepane 支架的七元亚氨基糖的合成及其作为功能相关外-N -乙酰氨基己糖苷酶抑制剂的评估，包括人O -GlcNAcase (OGA)，人溶酶体 β-氨基己糖苷酶 (HexAB) 和大肠杆菌NagZ。利用氮杂环丁烷的灵活性和氨基己糖苷酶的活性位点耐受性，我们探讨了立体中心在 C-3、C-5 和 C-6 的差向异构化以及C-2 或 C-7 位置的C-烷基化的影响。因此，在 C-6 ( L -ido) 和 C-5 ( D-galacto) 导致选择性 HexAB 抑制剂，而在 C-3 差向异构体的 C-7 处引入丙基提供有效的 NagZ 抑制剂。
• Design and synthesis of acetamido tri- and tetra-hydroxyazepanes: Potent and selective β-N-acetylhexosaminidase inhibitors
  作者：Hongqing Li、Filipa Marcelo、Claudia Bello、Pierre Vogel、Terry D. Butters、Amélia P. Rauter、Yongmin Zhang、Matthieu Sollogoub、Yves Blériot

  DOI：10.1016/j.bmc.2009.06.022

  日期：2009.8

  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.
• 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.