4-oxo-4-[(2,3,6-tri-O-acetyl-4-O-2',3',4',6'-tetra-O-acetyl-β-D-galactopyranosyl-β-D-glucopyranosyl)amino]butanoic acid | 839722-28-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-oxo-4-[(2,3,6-tri-O-acetyl-4-O-2',3',4',6'-tetra-O-acetyl-β-D-galactopyranosyl-β-D-glucopyranosyl)amino]butanoic acid
• 英文别名: N¹-(2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-β-D-glucopyranosyl)succinamic acid；4-oxo-4-[(2,3,6-tri-O-acetyl-4-O-{2’,3’,4’,6’-tetra-O-acetyl-β-D-galactopyranosyl}-β-D-glucopyranoyl)amino]butanoic acid；N-[(2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl))-β-D-glucopyranosyl]succinamic acid；4-oxo-4-[(2,3,6-tetra-O-acetyl-4-O-{2',3',4',6'-tetra-O-acetyl-β-D-galactopyranosyl}-β-D-glucopyranosyl)amino]butanoic acid；4-[[(2R,3R,4S,5R,6R)-3,4-diacetyloxy-6-(acetyloxymethyl)-5-[(2S,3R,4S,5S,6R)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxyoxan-2-yl]amino]-4-oxobutanoic acid
• CAS: 839722-28-0
• 化学式: C₃₀H₄₁NO₂₀
• 分子量: 735.65
• InChiKey: APCABJICADZCJF-MUBGQVCJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  51
• 可旋转键数：
  22
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  278
• 氢给体数：
  2
• 氢受体数：
  20

反应信息

• 作为反应物：
  描述：

  4-oxo-4-[(2,3,6-tri-O-acetyl-4-O-2',3',4',6'-tetra-O-acetyl-β-D-galactopyranosyl-β-D-glucopyranosyl)amino]butanoic acid 在 copper(II) sulfate 、 sodium ascorbate 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 25.16h， 生成
  参考文献：
  名称：

  β-硫代和β-N-吡喃半乳糖苷和相关乳糖苷的二价配体的合成及其作为克鲁氏锥虫反唾液酸酶的底物和抑制剂的评估。

  摘要：

  在这项工作中，我们描述了在糖支架上构建的一价和二价β-N-和β-S-吡喃半乳糖苷和相关乳糖苷的合成及其作为锥虫锥虫唾液酸唾液酸酶（TcTS）的底物和抑制剂的评估。该酶催化唾液酸从宿主中的寡糖供体转移至寄生虫betaGalp末端单元，并且已证明其在感染中起重要作用。在本文中，还测试了该酶作为化学合成含唾液酸的糖簇的工具。在具有βGalp非还原端的受体的存在下，使用重组TcTS和3'-唾液乳糖作为唾液酸供体，进行唾液酸的转移反应。用高效阴离子交换色谱和脉冲安培检测法（HPAEC-PAD）对产物进行分析。还研究了不同的S-连接和N-连接的糖苷抑制唾液酸从3'-唾液乳糖向天然底物N-乙酰基乳糖胺转移的能力。大多数底物表现为良好的受体和中度竞争性抑制剂。在所测试的化合物中，二-N-乳糖苷显示出最强的竞争性抑制剂（在等摩尔浓度下抑制率为70％）。通过对二价底物进行制备性唾液酸化来评估酶促反唾液酸化用于

  DOI：

  10.3762/bjoc.10.324
• 作为产物：
  描述：

  1',2',3',6',2,3,4,6-octa-O-acetyl-β-D-lactose 在 吡啶 、 4-二甲氨基吡啶 、 sodium azide 、 palladium 10% on activated carbon 、 氢溴酸 、 氢气 、 溶剂黄146 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.5h， 生成 4-oxo-4-[(2,3,6-tri-O-acetyl-4-O-2',3',4',6'-tetra-O-acetyl-β-D-galactopyranosyl-β-D-glucopyranosyl)amino]butanoic acid
  参考文献：
  名称：

  Delivery of a lactose derivative of endomorphin 1 to the brain via the olfactory epithelial pathway

  摘要：

  The rapid and direct delivery of a neuroactive endomorphin 1 derivative to the brain via nasal delivery is reported. A synthetic derivative of the native opioid peptide, endomorphin 1 bearing a lactose unit on the N-terminus of the peptide has been previously reported to exhibit antinoceceptive activity similar to morphine after both intravenous and oral administration. This compound has been administered nasally to rats and appeared in the olfactory bulb within 10 min of administration with negligible levels appearing in the circulating blood or in the rest of the brain. These results indicate that the peptide is absorbed into the brain via the olfactory epithelial pathway suggesting nasal delivery may be a viable alternative route of delivery in clinical applications. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.041

文献信息

• α-1,4-Galactosyltransferase-catalyzed glycosylation of sugar and lipid modified Leu-enkephalins
  作者：Pavla Simerska、Michelle P. Christie、Daryn Goodwin、Freda E.-C. Jen、Michael P. Jennings、Istvan Toth

  DOI：10.1016/j.molcatb.2013.08.018

  日期：2013.12

  Glycosylation of therapeutic peptides has been reported to improve delivery and targeting of various vaccines and drugs to specific cells/tissues. However, chemical synthesis of complex oligosaccharide derivatives via conventional methods can be challenging due to the need for several orthogonal hydroxyl group protections. Liposaccharyl galactosyltransferase C, a naturally occurring glycosyltransferase enzyme from Neisseria meningitidis, was found to have the ability to transfer a galactosyl moiety to glyco(lipo)peptides. An enzymatic glycosylation of Leu-enkephalin glyco(lipo)peptides was developed and optimized in this study in order to prepare pain regulating peptides with potentially improved central nervous system delivery. (C) 2013 Elsevier B.V. All rights reserved.
• Synthesis and Biological Evaluation of an Orally Active Glycosylated Endomorphin-1
  作者：Pegah Varamini、Friederike M. Mansfeld、Joanne T. Blanchfield、Bruce D. Wyse、Maree T. Smith、Istvan Toth

  DOI：10.1021/jm300418d

  日期：2012.6.28

  The endogenous opioid peptide endomorphin-1 (1) was modified by attachment of lactose to the N-terminus via a succinamic acid spacer to produce compound 2. The carbohydrate modification significantly improved the metabolic stability and membrane permeability of 2 while retaining mu-opioid receptor binding affinity and agonist activity. Analogue 2 produced dose-dependent antinociceptive activity following intravenous administration in a chronic constriction injury (CCI) rat model of neuropathic pain with an ED50 of 8.3 (+/- 0.8) mu mol/kg. The corresponding ED50 for morphine was 2.6 (+/- 1.4) mu mol/kg. Importantly, compound 2 produced dose-dependent pain relief after oral administration in CCI rats (ED50 = 19.6 (+/- 1.2) mu mol/kg), which was comparable with that of morphine (ED50 = 20.7 (+/- 3.6) mu mol/kg). Antineuropathic effects of analogue 2 were significantly attenuated by pretreatment of animals with the opioid antagonist naloxone, confirming opioid receptor-mediated analgesia. In contrast to morphine, no significant constipation was produced by compound 2 after oral administration.