2,4,6-tri-O-acetyl-3-azido-α-D-galactopyranosyl bromide | 155301-09-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,4,6-tri-O-acetyl-3-azido-α-D-galactopyranosyl bromide
• 英文别名: 2,4,6-tri-O-acetyl-3-azido-3-deoxy-α-D-galactopyranosyl bromide；3-azidoglycosyl bromide；2,4,6-tri-O-acetyl-3-azido-3-deoxy-β-D-galactopyranosyl bromide；2,4,6-Tri-o-acetyl-3-azido-3-deoxy-alpha-d-galactopyranosyl bromide；[(2R,3R,4S,5R,6R)-3,5-diacetyloxy-4-azido-6-bromooxan-2-yl]methyl acetate
• CAS: 155301-09-0
• 化学式: C₁₂H₁₆BrN₃O₇
• 分子量: 394.179
• InChiKey: ZXOSPWZOEWHIFW-IIRVCBMXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  103
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2,4,6-tri-O-acetyl-3-azido-α-D-galactopyranosyl bromide 在 4 A molecular sieve 、 silver trifluoromethanesulfonate 、 乙二胺 、 正丁醇 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 N-[(2R,3R,4R,5S,6R)-5-((2S,3R,4S,5R,6R)-4-Azido-3,5-dihydroxy-6-hydroxymethyl-tetrahydro-pyran-2-yloxy)-4-benzyloxy-6-benzyloxymethyl-2-methoxy-tetrahydro-pyran-3-yl]-acetamide
  参考文献：
  名称：

  Methyl 3-amino-3-deoxy-β-d-galactopyranosyl-(1 → 4)-2-acetamido-2-deoxy-β-d-glucopyranoside: An inhibitor of UDP-d-galactose: β-d-galactopyranosyl-(1 → 4)-2-acetamido-2-deoxy-d-glucose(1 → 3)-α-d-galactopyranosyltransferase

  摘要：

  UDP-D-galactose: beta-D-galactopyranosyl-(1 --> 4)-2-acetamido-2-deoxy-D-glucose alpha(1 --> 3)-D-galactopyranosyltransferase [E.C. 2.4.1.151] transfers D-galactosyl-residues from the sugar nucleotide with retention of configuration. We report here that synthetic methyl 3'-amino-3'-deoxy-N-acetyllactosaminide (9), where the hydroxyl group normally undergoing galactosylation has been replaced by amino group, is an inhibitor for this enzyme with K-i = 104 mu M. The mode of inhibition is not competitive, but appears to be specific, since other glycosyltransferases were not affected by 9.

  DOI：

  10.1016/0008-6215(95)00165-p
• 作为产物：
  描述：

  phenyl 2-O-acetyl-4,6-O-benzylidene-1-thio-3-O-trifluoromethanesulfonyl-β-D-galactopyranoside 在 溴 、 叠氮化四丁基铵 、 四丁基亚硝酸铵 作用下， 以 吡啶 、 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 生成 2,4,6-tri-O-acetyl-3-azido-α-D-galactopyranosyl bromide
  参考文献：
  名称：

  [EN] METHODS, COMPOSITIONS AND KITS FOR TREATING, MODULATING, OR PREVENTING OCULAR ANGIOGENESIS OR FIBROSIS IN A SUBJECT USING A GALECTIN PROTEIN INHIBITOR
  [FR] MÉTHODES, COMPOSITIONS ET KITS DE TRAITEMENT, DE MODULATION OU DE PRÉVENTION DE L'ANGIOGENÈSE OU DE LA FIBROSE OCULAIRE CHEZ UN SUJET UTILISANT UN INHIBITEUR DE GALECTINE

  摘要：

  本文提供了用于抑制眼部血管生成或纤维化的制药组合物的方法和试剂盒，该组合物包括一种药用合适载体或稀释剂和足以抑制血管生成或纤维化的抑制剂组合物的数量，通过抑制表达和/或活性的低聚半乳糖蛋白或其部分来抑制血管生成或纤维化。

  公开号：

  WO2014078655A1

文献信息

• Efficient synthesis of a galectin inhibitor clinical candidate (TD139) using a Payne rearrangement/azidation reaction cascade
  作者：Jacob St-Gelais、Vincent Denavit、Denis Giguère

  DOI：10.1039/d0ob00910e

  日期：——

  Selective galectin inhibitors are valuable research tools and could also be used as drug candidates. In that context, TD139, a thiodigalactoside galectin-3 inhibitor, is currently being evaluated clinically for the treatment of idiopathic pulmonary fibrosis. Herein, we describe a new strategy for the preparation of TD139. Starting from inexpensive levoglucosan, we used a rarely employed reaction cascade:

  选择性半乳凝素抑制剂是有价值的研究工具，也可用作候选药物。在这种情况下，目前正在临床上评估TD139，一种硫代二糖半乳糖苷半乳糖凝集素3抑制剂，用于治疗特发性肺纤维化。在此，我们描述了TD139制备的新策略。从廉价的左旋葡聚糖开始，我们使用了很少使用的反应级联：Payne重排/叠氮化过程导致3-叠氮基-吡喃半乳糖。只需几个简单实用的步骤，即可将后者中间体有效转化为TD139。
• Recognition of synthetic O-methyl, epimeric, and amino analogues of the acceptor α-L-Fucp-(1 → 2)-β-D-Galp-OR glycosyltransferases
  作者：Todd L. Lowary、Ole Hindsgaul

  DOI：10.1016/0008-6215(94)84275-2

  日期：1994.1

  The disaccharide alpha-L-Fuc p-(1-->2)-beta-D-Gal p-O-(CH2)7CH3 (6) is an acceptor for the glycosyltransferases responsible for the biosynthesis of the A and B blood-group antigens. These enzymes respectively transfer GalNAc and Gal in an alpha linkage to OH-3 of the Gal residue in 6. All eight possible O-methyl, epimeric, and amino analogues of 6 having modifications on the target Gal residue were

  二糖α-L-Fucp-（1→2）-β-D-GalpO-（CH2）7CH3（6）是负责A和B血型抗原生物合成的糖基转移酶的受体。这些酶分别将GalNAc和Gal转移到6中Gal残基的OH-3的alpha键上。化学合成了8种可能的在目标Gal残基上有修饰的O-甲基，差向异构体和氨基类似物，并进行了动力学评估作为A和B糖基转移酶的底物和抑制剂。该结果支持了较早的发现，即两种酶均能耐受Gal残基的3位和6位羟基取代。但是，取代或取代了Gal残基的OH-4可以消除识别。6-O-甲基和6-氨基化合物是两种酶的底物，而3-表异构体（10）和3-氨基（12）化合物是抑制剂。对于B转移酶，Ki是7.8 microM的竞争性抑制剂。由于抑制作用的模式复杂，尝试用B转移酶确定12 Ki的尝试失败。同样，10和12都是A转移酶的有效抑制剂，但是由于其抑制方式很复杂，类似于B转移酶，因此无法计算出抑制常数。使用A转移酶，估计12的Ki在200
• Arynes in the Monoarylation of Unprotected Carbohydrate Amines
  作者：Kumar Bhaskar Pal、Mukul Mahanti、Ulf J. Nilsson

  DOI：10.1021/acs.orglett.7b03741

  日期：2018.2.2

  A CsF-mediated method has been developed for the N-arylation of amino sugars that affords good to excellent yields of arylated products under mild conditions involving the in situ generation of arynes. The reaction conditions tolerate a variety of common carbohydrate protecting groups and also performs exceptionally well on unprotected amino sugar derivatives. The reactions are scalable in moderate

  已经开发出用于氨基糖的N-芳基化的CsF介导的方法，其在涉及原位生成芳烃的温和条件下提供良好至优异的芳基化产物收率。反应条件可耐受多种常见的碳水化合物保护基，并且在未保护的氨基糖衍生物上也表现出色。反应范围宽广，可以中等至良好的收率进行扩展。
• Tri-isopropylsilyl thioglycosides as masked glycosyl thiol nucleophiles for the synthesis of S-linked glycosides and glyco-conjugates
  作者：S. Mandal、U. J. Nilsson

  DOI：10.1039/c4ob00741g

  日期：——

  Tri-isopropylsilyl thio-glycosides (TIPS S-glycosides), readily synthesized from glycosyl halides, glycosyl acetates, orp-methoxyphenyl glycosides, were in one-pot de-silylated and S-alkylated, -acylated, or -glycosylated in high yields and short time.

  三异丙基硅硫代糖苷（TIPS S-糖苷）可以从糖基卤化物、糖基醋酸酯或对甲氧苯基糖苷中轻松合成，一锅法中可以高产率、短时间内去硅基并进行S-烷基化、酰化或糖基化。
• Double Affinity Amplification of Galectin–Ligand Interactions through Arginine–Arene Interactions: Synthetic, Thermodynamic, and Computational Studies with Aromatic Diamido Thiodigalactosides
  作者：Ian Cumpstey、Emma Salomonsson、Anders Sundin、Hakon Leffler、Ulf J. Nilsson

  DOI：10.1002/chem.200701932

  日期：2008.5.9

  interactions in galectin-ligand binding. Computational studies were employed to explain binding preferences for the different galectins. Galectin-3 formed two almost ideal arene-arginine stacking interactions according to computer modeling and also had the highest affinity for the diamido-thiodigalactosides (K(d) below 50 nM). Site-directed mutagenesis of galectin-3 arginines involved in binding corroborated

  合成了一系列芳族单-或二酰胺基-硫代双嘧糖苷衍生物，并研究了它们作为半乳凝素-1，-3，-7，-8N末端结构域和-9N末端结构域的配体。用竞争性荧光偏振实验进行体外亲和力测定，并通过等温微量热法进行热力学分析，从而给出了半乳糖凝集素与配体结合中精氨酸与芳烃相互作用的结构要求的连贯图片。计算研究被用来解释不同半乳糖凝集素的结合偏好。Galectin-3根据计算机建模形成了两个几乎理想的芳烃-精氨酸堆积相互作用，并且对二酰胺基-硫代二糖半乳糖苷（K（d）低于50 nM）具有最高的亲和力。参与结合的galectin-3精氨酸的定点诱变证实了它们与芳香族二酰胺基-硫代二糖半乳糖苷相互作用的重要性。此外，精氨酸突变体显示出与芳香族系统相互作用的游离，柔性和溶剂暴露的精氨酸侧链与紧密的离子对精氨酸侧链之间存在明显差异。