N-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)succinamide | 205442-82-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: N-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)succinamide
• 英文别名: 4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosylamino)-4-oxobutanoic acid；4-oxo-4-[(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)amino]butanoic acid；N-4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosylamino)succinic acid；4-Oxo-4-(((2R,3R,4S,5R,6R)-3,4,5-triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-yl)amino)butanoic acid；4-oxo-4-[[(2R,3R,4S,5R,6R)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]amino]butanoic acid
• CAS: 205442-82-6
• 化学式: C₁₈H₂₅NO₁₂
• 分子量: 447.396
• InChiKey: JKKYZQZJZLUIGT-SOGIYBJLSA-N

物化性质

• 熔点：
  145-147 °C(Solv: hexane (110-54-3); ethyl acetate (141-78-6))
• 沸点：
  614.0±55.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  31
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  181
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  N-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)succinamide 在 sodium methylate 、 碳酸氢钠 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 26.0h， 生成 sodium 2-(N-(2-(N-(4-(β-D-glucopyranosylamino)succinyl))amino-D,L-dodecanoyl))-amino-D,L-dodecanoate
  参考文献：
  名称：

  用于增强口服药物递送的阴离子脂糖的开发和表征

  摘要：

  这项研究的目的是合成带电荷的两性分子，将其与生物利用度较差的药物复合后，有可能改善其口服吸收能力。通过溶液相肽合成法合成了含有d-葡萄糖和脂氨基酸的新型阴离子脂糖衍生物。使用高灵敏度等温滴定微量热法测定临界聚集浓度和热力学曲线。研究了脂糖的溶血和细胞毒性活性，结果表明，脂糖在口服给药的浓度下是无毒的。将模型药物妥布霉素与含有两种脂质的脂糖混合，在200 nm左右形成聚集体，从而增加妥布霉素在正辛醇/水之间的分配。

  DOI：

  10.1016/j.ijpharm.2012.04.018
• 作为产物：
  描述：

  1,2,3,4,6-alpha-D-葡萄糖五乙酸酯 在 钯 叠氮基三甲基硅烷 、 氢气 、 四氯化锡 作用下， 生成 N-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)succinamide
  参考文献：
  名称：

  Novel Lipoamino Acid- and Liposaccharide-Based System for Peptide Delivery:  Application for Oral Administration of Tumor-Selective Somatostatin Analogues

  摘要：

  Lipoamino acid and liposaccharide conjugates of somatostatin analogue TT-232 were synthesized to modify the physicochemical properties of the parent peptide. The relative position, the number, and the nature of the lipid and/or saccharide moieties were varied. Experiments in vitro clearly showed that many compounds modified at the N- and/or C-terminus with lipid or sugar moieties retained the biological activity of the parent compound. An interesting construct was synthesized containing lipid and sugar units at opposite ends of the somatostatin analogue, so that the entire molecule could be considered as an amphipathic surfactant.

  DOI：

  10.1021/jm9910167

文献信息

• Liposaccharide-based nanoparticulate drug delivery system
  作者：Adel S. Abdelrahim、Pavla Simerska、Istvan Toth

  DOI：10.1016/j.tet.2012.04.064

  日期：2012.6

  series of anionic liposaccharide derivatives were synthesized in order to develop a system, which would have the capacity to act as an absorption enhancer and to improve oral bioavailability of drugs. The addition of a liposaccharide to a drug enhances drug stability against enzymatic degradation, while the lipophilicity can be controlled by variation of the lipid side chain. All liposaccharide derivatives

  为了开发系统，合成了一系列阴离子脂糖衍生物，该系统具有充当吸收促进剂和改善药物的口服生物利用度的能力。向药物中添加脂糖可增强药物抵抗酶促降解的稳定性，而亲脂性可通过脂质侧链的变化来控制。所有脂糖衍生物均已纯化，并通过核磁共振和高分辨率质谱进行了全面表征。通过等温滴定微量热法，透射电子显微镜和动态光散射法测定了合成脂糖的热力学曲线，临界聚集浓度和大小。这些脂糖形成尺寸小于100nm的纳米颗粒。
• Synthesis, characterization and in vitro evaluation of amphiphilic ion pairs of erythromycin and kanamycin antibiotics with liposaccharides
  作者：Rosario Pignatello、Pavla Simerska、Antonio Leonardi、Adel S. Abdelrahim、Giulio Petronio Petronio、Virginia Fuochi、Pio Maria Furneri、Barbara Ruozi、Istvan Toth

  DOI：10.1016/j.ejmech.2016.04.074

  日期：2016.9

  describe the synthesis of some ion pairs of two model cationic antibiotics, erythromycin (ERY) and kanamycin A (KAN), with liposaccharides having different levels of lipophilicity and charge. The formation of drug-liposaccharide complexes was confirmed by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) analysis. The effect

  亲水离子削皮策略（HIP）是一种探索方法，旨在改善吸附不良的药物在细胞/组织中的吸收并优化其理化特性。在这种情况下，我们在这里描述了两种模型阳离子抗生素，红霉素（ERY）和卡那霉素A（KAN）的一些离子对的合成，其中脂糖具有不同的亲脂性和电荷水平。通过傅里叶变换红外光谱（FT-IR），差示扫描量热法（DSC）和粉末X射线衍射（PXRD）分析确认了药物-脂糖复合物的形成。 通过测量化合物对一组对母体抗生素敏感或具有抗性的细菌菌株的最小抑制浓度（MIC），来评估两亲脂糖部分对ERY和KAN抗菌活性的影响。尽管未发现MIC值降低，但离子对并未降低体外抗生素活性。实验结果将激发该离子对策略在药物设计中的未来研究，例如，允许提高亲水性抗生素在脂质基纳米载体中的包封效率，或改变其体内生物分布和药代动力学特征。
• Synthesis of glycolipopeptidic building blocks for carbohydrate receptor discovery
  作者：Zyta M. Ziora、Norbert Wimmer、Roger New、Mariusz Skwarczynski、Istvan Toth

  DOI：10.1016/j.carres.2011.03.019

  日期：2011.9

  A class of glycolipopeptides for use as building blocks for a new type of dynamic combinatorial library is reported. The members of the library consist of a variable carbohydrate moiety, coded amino acids, and lipoamino acids in order to convert them into amphiphiles. Glycolipopeptidic amphiphiles interact through non-covalent bonding when mixed together in aqueous phase and form micelles in dynamic close-packed fluid mosaic arrays. The head groups of amphiphiles are exposed on the micelle surface, providing entities which could be screened in biological assays to find the most potent combination of building blocks in order to identify new bioactive carbohydrate ligands. (C) 2011 Elsevier Ltd. All rights reserved.
• Toward the Development of Prophylactic and Therapeutic Human Papillomavirus Type-16 Lipopeptide Vaccines
  作者：Peter M. Moyle、Colleen Olive、Mei-Fong Ho、Manisha Pandey、Joanne Dyer、Andreas Suhrbier、Yoshio Fujita、Istvan Toth

  DOI：10.1021/jm070287b

  日期：2007.9.1

  Four lipid-core peptide systems were synthesized using stepwise solid-phase peptide synthesis, incorporating a sequence from the human papillomavirus type-16 (HPV-16) E7 protein (E7(44-62)), for the purpose of developing vaccines against HPV-16 associated cervical cancer. D-Mannose was conjugated to the vaccine in order to investigate whether the targeting of dendritic cell mannose receptors would improve vaccine efficacy. The ability of the vaccines to clear or reduce the size of HPV-16 associated tumors was assessed in C57BL/6 (H-2(b)) mice using the TC-1 HPV-16 tumor model. Overall, significant reductions in the size of TC-1 tumors were observed in the mouse model, with the conjugation of mannose to these vaccines demonstrated to clear or reduce the size of TC-1 tumors to a greater extent than non-mannose-containing vaccines (37 out of 40 versus 21 out of 30 tumors cleared, respectively).
• Synthesis and in vitro evaluation of a library of modified endomorphin 1 peptides
  作者：Yasuko Koda、Mark Del Borgo、Susanne T. Wessling、Lawrence H. Lazarus、Yoshio Okada、Istvan Toth、Joanne T. Blanchfield

  DOI：10.1016/j.bmc.2008.04.020

  日期：2008.6

  Endomorphin 1 (Endo-1 = Tyr-Pro-Trp-Phe-NH(2)), an endogenous opioid with high affinity and selectivity for mu-opioid receptors, mediates acute and neuropathic pain in rodents. To overcome metabolic instability and poor membrane permeability, the N- and C-termini of Endo-1 were modified by lipoamino acids (Laa) and/or sugars, and 2',6'-dimethyltyrosine (Dmt) replacement of Tyr. Analogues were assessed for mu-opioid receptor affinity, inhibition of cAMP accumulation, enzymatic stability, and permeability across Caco-2 cell monolayers. C-Terminus modi. cation decreased receptor affinity, while N-terminus C8-Laa improved stability and permeability with slight change in receptor affinity. Dmt provided a promising lead compound: [C8Laa-Dmt[1]]-Endo-1 is nine times more stable (t(1/2) = 43.5 min), >8- fold more permeable in Caco-2 cell monolayers, and exhibits 140-fold greater mu-opioid receptor affinity (K(i mu) = 0.08 nM). (C) 2008 Elsevier Ltd. All rights reserved.