naphth-2-yl β-D-xylopyranoside

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: naphth-2-yl β-D-xylopyranoside
• 英文别名: 2-naphthyl β-D-xylopyranoside；2-naphthyl-β-D-xylopyranoside；XylNap；(2S,3R,4S,5R)-2-naphthalen-2-yloxyoxane-3,4,5-triol
• 化学式: C₁₅H₁₆O₅
• 分子量: 276.289
• InChiKey: FHHNMUNYRSLENZ-BARDWOONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  79.2
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  naphth-2-yl β-D-xylopyranoside 在 咪唑 、 三氟化硼乙醚 、 sodium hydride 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 38.0h， 生成 (1S,3S,4S,6R,9S,10R)-3,4-dimethoxy-3,4-dimethyl-10-(methylthio)thiocarbonyloxy-9-(2-naphthyl)oxy-2,5,8-trioxabicyclo[4.4.0]decane
  参考文献：
  名称：

  Synthesis, conformation and biology of naphthoxylosides

  摘要：

  Proteoglycans (PG) are polyanionic proteins consisting of a core protein substituted with carbohydrate chains, that is, glycosaminoglycans (GAG). The biosynthesis of GAG can be manipulated by simple xylosides carrying hydrophobic aglycons, which can enter the cell and initiate the biosynthesis. While the importance of the aglycon is well investigated, there is far less information on the effect of modifications in the xylose residue.We have developed a new synthetic protocol, based on acetal protection and selective benzylation, for modification of the three hydroxyl groups in xylose. Thus we have synthesized twelve analogs of 2-naphthyl beta-D-xylopyranoside (XylNap), where each hydroxyl group has been epimerized or replaced by methoxy, fluoro, or hydrogen.To gain more information about the properties of xylose, conformational studies were made on some of the analogs. It was found that the (4)C(1) conformation is highly predominant, accompanied by a nonnegligible population of the (2)S(0) conformation. However, deoxygenation at C3 results in a large portion of the (1)C(4) conformation.The GAG priming ability and proliferation activity of the twelve analogs, were investigated using a matched pair of human breast fibroblasts and human breast carcinoma cells. None of the analogs initiated the biosynthesis of GAG, but an inhibitory effect on endogenous PG production was observed for analogs fluorinated or deoxygenated at C4. From our data it seems reasonable that all three hydroxyl groups in XylNap are essential for the priming of GAG chains and for selective toxicity for tumor cells. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.05.007
• 作为产物：
  描述：

  β-naphthyl 2,3,4-tri-O-benzyl-β-D-xylopyranoside 在 盐酸 、 palladium 10% on activated carbon 、 氢气 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 以88%的产率得到naphth-2-yl β-D-xylopyranoside
  参考文献：
  名称：

  HCl / DMF可增强催化氢解反应的化学选择性

  摘要：

  已经开发了一种改进的化学选择性氢解方法。通过采用溶剂-酸组合（即DMF-HCl水溶液），我们能够促进脱苄基反应，而不是芳族氢化和酸介导的键断裂，这是这些反应的两个主要缺点。该方法的普遍性最初是作为解决碳水化合物问题的一种方法而开发的，它通过成功地氢解1,8-萘来解决，这是一个以前尚未解决的问题。

  DOI：

  10.1016/j.tetlet.2010.07.142

文献信息

• Disubstituted naphthyl β-D-xylopyranosides: Synthesis, GAG priming, and histone acetyltransferase (HAT) inhibition
  作者：Karin Thorsheim、Andrea Persson、Anna Siegbahn、Emil Tykesson、Gunilla Westergren-Thorsson、Katrin Mani、Ulf Ellervik

  DOI：10.1007/s10719-016-9662-6

  日期：2016.4

  Xylosides are a group of compounds that can induce glycosaminoglycan (GAG) chain synthesis independently of a proteoglycan core protein. We have previously shown that the xyloside 2-(6-hydroxynaphthyl)β-D-xylopyranoside has a tumor-selective growth inhibitory effect both in vitro and in vivo, and that the effect in vitro was correlated to a reduction in histone H3 acetylation. In addition, GAG chains have previously been reported to inhibit histone acetyltransferases (HAT). To investigate if xylosides, or the corresponding xyloside-primed GAG chains, can be used as HAT inhibitors, we have synthesized a series of naphthoxylosides carrying structural motifs similar to the aromatic moieties of the known HAT inhibitors garcinol and curcumin, and studied their biological activities. Here, we show that the disubstituted naphthoxylosides induced GAG chain synthesis, and that the ones with at least one free phenolic group exhibited moderate HAT inhibition in vitro, without affecting histone H3 acetylation in cell culture. The xyloside-primed GAG chains, on the other hand, had no effect on HAT activity, possibly explaining why the effect of the xylosides on histone H3 acetylation was absent in cell culture as the xylosides were recruited for GAG chain synthesis. Further investigations are required to find xylosides that are effective HAT inhibitors or xylosides producing GAG chains with HAT inhibitory effects.

  木糖苷是一类化合物，能独立于蛋白聚糖核心蛋白诱导糖胺聚糖（GAG）链的合成。我们之前已经证明，2-（6-羟基萘基）-β-D-吡喃木糖苷具有肿瘤特异性的生长抑制作用，无论是在体外还是在体内，而且体外效应与组蛋白H3乙酰化的减少有关。此外，已有报道称GAG链能够抑制组蛋白乙酰转移酶（HAT）。为了研究木糖苷或相应的以木糖苷为引物的GAG链是否能作为HAT抑制剂，我们合成了一系列含有与已知的HAT抑制剂——广藿香醇和姜黄素——的芳香基团相似的结构特征的萘基木糖苷，并研究了它们的生物活性。在这里，我们展示了二取代的萘基木糖苷能够诱导GAG链的合成，那些至少含有一个自由酚羟基的萘基木糖苷在体外表现出适度的HAT抑制作用，且不影响细胞培养中组蛋白H3的乙酰化。另一方面，以木糖苷为引物的GAG链对HAT活性没有影响，这可能解释了为什么木糖苷对组蛋白H3的乙酰化在细胞培养中没有影响，因为木糖苷被招募用于GAG链的合成。进一步的研究需要找到有效的HAT抑制性木糖苷或产生具有HAT抑制效应的GAG链的木糖苷。
• Exploration of the active site of β4GalT7: modifications of the aglycon of aromatic xylosides
  作者：Anna Siegbahn、Karin Thorsheim、Jonas Ståhle、Sophie Manner、Christoffer Hamark、Andrea Persson、Emil Tykesson、Katrin Mani、Gunilla Westergren-Thorsson、Göran Widmalm、Ulf Ellervik

  DOI：10.1039/c4ob02632b

  日期：——

  active site of the enzyme and that quite bulky aglycons are accepted. By separating the aromatic aglycon from the xylose moiety by linkers, a trend towards increased galactosylation with increased linker length is observed. The galactosylation is influenced by the identity and position of substituents in the aromatic framework, and generally, only xylosides with beta-glycosidic linkages function as good

  蛋白聚糖（PGs）是由长的线性多糖，糖胺聚糖（GAG）链组成的大分子，通过碳水化合物木糖共价附于核心蛋白。GAG链的生物合成通过核心蛋白的木糖基化，然后通过半乳糖基转移酶beta4GalT7进行半乳糖基化来启动。一些β-d-木糖苷，例如2-萘基β-d-木吡喃糖苷，可以通过充当beta4GalT7的受体底物来诱导GAG合成，并且还可以与核心蛋白上的GAG合成竞争。在这里，我们使用酶促测定，细胞研究和分子对接模拟，介绍了具有芳香族糖苷配基修饰的beta4GalT7和木糖苷的结构活性关系。结果表明，糖苷配基位于酶的活性位点的外部，并且接受了相当大的糖苷配基。通过通过接头将芳香族糖苷配基与木糖部分分离，观察到半乳糖基化随着接头长度增加而增加的趋势。半乳糖基化受芳香族骨架中取代基的身份和位置的影响，通常，只有具有β-糖苷键的木糖苷才能作为beta4GalT7的良好底物。我们还表明，木糖苷的半乳糖基化
• Synthesis of Double-Modified Xyloside Analogues for Probing the β4GalT7 Active Site
  作者：Daniel Willén、Dennis Bengtsson、Sebastian Clementson、Emil Tykesson、Sophie Manner、Ulf Ellervik

  DOI：10.1021/acs.joc.7b02809

  日期：2018.2.2

  article, we explore the synthesis of 16 xyloside analogues, modified at two different positions, as well as their function as inhibitors of and/or substrates for the enzyme. Seemingly simple compounds turned out to require complex synthetic pathways. A meta-analysis of the synthetic work shows that, regardless of the abundance of methods available for carbohydrate synthesis, even simple modifications

  已经显示单取代的萘氧基氯化物作为酶β4GalT7的底物和抑制剂，β4GalT7是导致糖胺聚糖和蛋白聚糖的生物合成途径中的关键酶。在本文中，我们探索了在两个不同位置修饰的16种木糖苷类似物的合成，以及它们作为酶的抑制剂和/或底物的功能。看来简单的化合物需要复杂的合成途径。对合成工作的荟萃分析表明，不管碳水化合物合成方法的丰富性如何，即使简单的修饰也可能是有问题的，而双重修饰由于构象，空间和立体电子效应而带来了其他挑战。
• Rules for priming and inhibition of glycosaminoglycan biosynthesis; probing the β4GalT7 active site
  作者：Anna Siegbahn、Sophie Manner、Andrea Persson、Emil Tykesson、Karin Holmqvist、Agata Ochocinska、Jerk Rönnols、Anders Sundin、Katrin Mani、Gunilla Westergren-Thorsson、Göran Widmalm、Ulf Ellervik

  DOI：10.1039/c4sc01244e

  日期：——

  Xylose is the optimal substrate for β4GalT7, an essential enzyme in GAG biosynthesis, but analogs act as effective inhibitors.

  Xylose是GAG生物合成中必需的酶β4GalT7的最佳底物，但类似物作为有效的抑制剂。
• Synthesis and glycosaminoglycan priming activity of three disaccharides related to the linkage region tetrasaccharide of proteoglycans
  作者：Arun K. Sarkar、Jeffrey D. Esko

  DOI：10.1016/0008-6215(95)00304-5

  日期：1995.12

  To test if disaccharides might serve as primers of oligosaccharide synthesis in animal cells, we synthesized 2-naphthyl O-(beta-D-galactopyranosyl)-(1-->4)-beta-D-xylopyranoside, 2-naphthyl O-(beta-D-galactopyranosyl)-(1 -->3)-beta-D-galactopyranoside, and 2-naphthyl O-(beta-D-glucopyranosyluronic acid)-(1-->3)-beta-D-galactopyranoside. These three disaccharides are related to subunits of the linkage tetrasaccharide of heparan sulfate and chondroitin sulfate chains in animal cell proteoglycans. The disaccharides were synthesized with coupling efficiencies of 40-70% using thioglycosides or by activating the monosaccharides with trichloroacetimidate. The structures of these compounds were confirmed by H-1 NMR, C-13 NMR and elemental analysis. The ability of these disaccharides to prime glycosaminoglycan chains was examined in a Chinese hamster ovary cell mutant, pgsA 745, which lacks xylosyltransferase. The missing enzyme renders the cells dependent on exogenous primers for making glycosaminoglycan chains. 2-Naphthyl O-(beta-D-galactopyranosyl)-(1-->3)-beta-D-galactopyranoside and 2-naphthyl O-(beta-D-glucopyranosyluronic acid)-(1-->3)-beta-D-galactopyranoside did not stimulate glycosaminoglycan synthesis, but 2-naphthyl O-(beta-D-galactopyranosyl)-(1-->4)-beta-D-xylopyranoside at high concentration primed chains. The peracetylated derivative (2-naphthyl O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1-->4)2,3-di-O-acetyl-beta-D-xylopyranoside) primed chains at lower concentration (100 mu M), suggesting that cells took up the compound and removed the acetyl groups apparently in the compartment where glycosaminoglycan synthesis occurs.