perbenzyl fucosyl bromide | 76946-04-8

• 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: perbenzyl fucosyl bromide
• 英文别名: 2,3,4-tri-O-benzyl-fucopyranosyl bromide；(3S,4R,5R,6S)-2-bromo-6-methyl-3,4,5-tris(phenylmethoxy)oxane
• CAS: 76946-04-8
• 化学式: C₂₇H₂₉BrO₄
• 分子量: 497.429
• InChiKey: MJZXQAVNDOYDAP-OGPNLZSQSA-N

物化性质

• 沸点：
  564.8±50.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  36.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  perbenzyl fucosyl bromide 在 palladium on activated charcoal 四乙基溴化铵 、 氢气 、 sodium methylate 、 二正丁基氧化锡 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 113.0h， 生成 (3-O-[(S)-1-(oxycarbonyl)-2-cyclohexylethyloxy]-β-D-galactopyranosyl-O-(1->3)-[α-L-fucopyranosyl)-O-(1->4)]-1,2-dideoxy-D-glucopyranose
  参考文献：
  名称：

  Synthesis and Biological Evaluation of a Potent E-Selectin Antagonist

  摘要：

  An early step of the inflammatory response-the rolling of leukocytes on activated endothelial cells-is mediated by selectin/carbohydrate interactions. The tetrasaccharide sialyl Lewis(x) (sLe(x)) 1 is a ligand for E-, P-, and L-selectin and, therefore, serves as a lead structure to develop analogues which allow the control of acute and chronic inflammation. Here we describe the efficient synthesis (10 linear steps) of the potent sLe(x) mimetic 2. Compared to sLe(x), compound 2 showed a 30-fold improved affinity in a static, cell-free E-selectin-ligand binding assay (IC50 = 36 mu M). These data were confirmed by a marked inhibition in an in vitro cell-cell rolling assay which simulates in vivo conditions (IC50 approximate to 40 mu M). The assays are predictive for the in vivo efficacy of test compounds as indicated by a marked inhibitory effect of 2 in a thioglycollate induced peritonitis model of acute inflammation in mice (ED50 approximate to 15 mg/kg).

  DOI：

  10.1021/jm990422n
• 作为产物：
  描述：

  1-硫-乙基-2,3,4-三-氧-苄基-b-L-硫代呋喃岩藻糖苷 在 溴 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 perbenzyl fucosyl bromide
  参考文献：
  名称：

  血型 A 和 B（2 型）四糖的合成。最后阶段岩藻糖基化的策略

  摘要：

  传统上用于合成血型 A 和 B 四糖的策略包括乳糖胺的 2'-O-岩藻糖基化，然后插入 α1-3 连接的 N-乙酰半乳糖胺或半乳糖部分。在这里，我们报告了通过替代序列合成 A（2 型）和 B（2 型）四糖的 3-氨基丙基糖苷，即 α-半乳糖胺化（或 α-半乳糖基化），然后是 α-岩藻糖基化。该策略使我们能够合成不含岩藻糖的三糖 GalNAcα1-3Galβ1-4GlcNAc 和 Galα1-3Galβ1-4GlcNAc，它们是利用针对三糖的人类天然抗体进行免疫治疗的有前景的靶标。该方案的关键阶段是在具有第二个 (3-OH) 未保护基团的中间体三糖中对 βGal 的 2'-OH 基团进行选择性氯乙酰化。

  DOI：

  10.1016/j.carres.2020.108192

文献信息

• An easy access to halide ion-catalytic α-glycosylation using carbon tetrabromide and triphenylphosphine as multifunctional reagents
  作者：Yuko Shingu、Yoshihiro Nishida、Hirofumi Dohi、Kazukiyo Kobayashi

  DOI：10.1039/b303984f

  日期：——

  The reaction of a 2-O-benzyl-1-hydroxy sugar with CBr4 and Ph3P generates a glycosyl bromide in situ, which is coupled with an acceptor alcohol in the presence of N,N-tetramethylurea to afford an α-glycosyl product virtually quantitatively. In a proposed pathway, the reagent combination plays multiple roles such as the generation of a glycosyl donor, the activation of glycosylation, and the dehydration of the reaction system. These roles allow a simple α-glycosylation to be performed without special attention to dehydration. Various α-glycosyl (D-gluco-, D-galacto- and L-fuco-) products including glycosyl glycerols and cholesterols have been prepared with this method.

  2-O-苄基-1-羟基糖与CBr4和Ph3P反应生成一种即时的糖基溴化物，该溴化物在N,N-四甲基脲存在下与受体醇耦合，几乎定量地得到α-糖基产物。在提出的反应途径中，试剂组合扮演了多个角色，如糖基供体的生成、糖基化的活化以及反应体系的脱水作用。这些角色使得一个简单的α-糖基化反应得以进行，而无需特别关注脱水步骤。利用这种方法已经制备了多种α-糖基（D-葡萄糖、D-半乳糖和L-岩藻糖）产物，包括糖基甘油和胆固醇。
• Methods of use of glycomimetics with replacements for hexoses and n-acetyl hexosamines
  申请人：Magnani John L.

  公开号：US20080200406A1

  公开（公告）日：2008-08-21

  Methods are provided for using a compound to treat, for example, endothelial dysfunction including vascular abnormalities. More specifically, methods are described for using an oligosaccharide compound or glycomimetic compound wherein a cyclohexane derivative is incorporated in either.

  提供了一种使用化合物治疗内皮功能障碍，包括血管异常的方法。更具体地，描述了使用寡糖化合物或糖类模拟化合物的方法，其中环己烷衍生物被合并在其中。
• Synthesis and Biological Evaluation of E-Selectin Antagonists that Present Different Carbohydrate Ligands in a Multivalent Format
  作者：Gebhard Thoma、Franz Schwarzenbach

  DOI：10.1055/s-2005-865299

  日期：——

  The synthesis of the first polylysine conjugates that present different carbohydrate ligands in a multivalent format is reported. Glycopolymers 3c and 3d have been prepared with a highly predictable composition as indicated by 1 H NMR. They function as multivalent E-selectin inhibitors but their potencies are not superior compared to previously-described related compounds.

  报道了以多价形式呈现不同碳水化合物配体的第一种多聚赖氨酸缀合物的合成。如 1 H NMR 所示，已制备具有高度可预测的组成的糖聚合物 3c 和 3d。它们起到多价 E-选择素抑制剂的作用，但与先前描述的相关化合物相比，它们的效力并不优越。
• Synthesis and biological evaluation of a sialyl lewis X mimic with significantly improved E-selectin inhibition
  作者：Gebhard Thoma、John L Magnani、John T Patton

  DOI：10.1016/s0960-894x(01)00092-0

  日期：2001.4

  The synthesis of the highly potent E-selectin inhibitor 5 is described. Sialyl Lewis X mimic 5 was rationally designed by combining two previously disclosed beneficial sLe(x) modifications in a single molecule. The compound was found to be 30-fold more potent than sLe(x) in a static, cell-free equilibrium assay. Furthermore, compound 5 was highly active (IC50 = 10 microM) in a dynamic non-equilibrium

  描述了高效E-选择素抑制剂5的合成。通过在单个分子中结合两个先前公开的有益sLe（x）修饰，合理设计了Sialyl Lewis X mimic 5。在静态，无细胞的平衡分析中，该化合物的功效比sLe（x）强30倍。此外，化合物5在动态非平衡测定中具有很高的活性（IC50 = 10 microM），其中sLe（x）不会抑制高达1000 microM的嗜中性粒细胞滚动。
• [EN] PROCESS FOR PREPARING AN E-SELECTIN INHIBITOR INTERMEDIATE<br/>[FR] PROCÉDÉ DE PRÉPARATION D'UN INTERMÉDIAIRE INHIBITEUR DE LA E-SÉLECTINE
  申请人：GLYCOMIMETICS INC

  公开号：WO2021034796A1

  公开（公告）日：2021-02-25

  A process is provided for the synthesis of an intermediate of Formula 15 which is useful in the synthesis of E-selectin inhibitors. Also provided are useful intermediates obtained from the process.

  提供一种用于合成公式15的中间体的方法，该中间体在合成E-选择素抑制剂中很有用。还提供了从该方法获得的有用中间体。