Methyl 2-azido-3-O-benzyl-6-O-tert-butyldiphenylsilyl-2-deoxy-alpha-D-glucopyranoside | 1314746-18-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Methyl 2-azido-3-O-benzyl-6-O-tert-butyldiphenylsilyl-2-deoxy-alpha-D-glucopyranoside
• 英文别名: (2R,3S,4R,5R,6S)-5-azido-2-[[tert-butyl(diphenyl)silyl]oxymethyl]-6-methoxy-4-phenylmethoxyoxan-3-ol
• CAS: 1314746-18-3
• 化学式: C₃₀H₃₇N₃O₅Si
• 分子量: 547.726
• InChiKey: BVJTUAVUPWOUFK-JPHCZMGXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.56
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  71.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Methyl 2-azido-3-O-benzyl-6-O-tert-butyldiphenylsilyl-2-deoxy-alpha-D-glucopyranoside 在 四丁基氟化铵 、 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 24.0h， 生成 methyl 2-azido-3,4-di-O-benzyl-2-deoxy-α-D-glucopyranoside
  参考文献：
  名称：

  Glycans as Ligands in Bioinorganic Chemistry. Probing the Interaction of a Trinuclear Platinum Anticancer Complex with Defined Monosaccharide Fragments of Heparan Sulfate

  摘要：

  We report herein a detailed NMR study of the aquation and subsequent covalent binding of the trinuclear clinical agent [{trans-PtCl((NH3)-N-15)(2)}(2){mu-trans-Pt((NH3)-N-15)(2)((NH2)-N-15(CH2)(6)(NH2)-N-15)(2)}](4+) (1, 1,0,1/t,t,t or Triplatin) with three d-glucosamine residues containing varied O-sulfate and N-sulfate or N-acetyl substitutions, which represent monosaccharide fragments present within the repeating disaccharide sequences of cell surface heparan sulfate (HS). The monosaccharides GlcNS(6S), GlcNS, and GlcNAc(6S) were synthesized in good yield from a common 4,6-diol alpha-methyl glucopyranoside intermediate. The reactions of N-15-1 with sodium sulfate, GlcNS(6S), GlcNS, and GlcNAc(6S) were followed by 2D [H-1,N-15] heteronuclear single quantum coherence (HSQC) NMR spectroscopy using conditions (298 K, pH approximate to 5.4) similar to those previously used for other anionic systems, allowing for a direct comparison. The equilibrium constants (pK(1)) for the aquation of 1 in the presence of GlcNS(6S) and GlcNS were slightly higher compared to that of the aquation in a sulfate solution, while a comparable pK(1) value was observed in the presence of GlcNAc(6S). A comparison of the rate constants for sulfate displacement of the aqua ligand showed preferential binding to 2-N-sulfate compared to 6-O-sulfate but a more rapid liberation. For disulfated GlcNS(6S), equilibrium conditions were achieved rapidly (9 h) and strongly favored the dichloro form, with <2% sulfato species observed. The value of k(L1) was up to 15-fold lower than that for binding to sulfate, whereas the rate constant for the reverse ligation (k(-L1)) was comparable. Equilibrium conditions were achieved much more slowly (similar to 100 h) for the reactions of 1 with GlcNS and GlcNAc(6S), attributed to covalent binding also to the N-donor of the sulfamate (GlcNS) group and the O-donor of the N-acetyl [GlcNAc(6S)] group. The rate constants (k(L2)) were 20-40-fold lower than that for binding to the 2-N- or 6-O-sulfate, but the binding was less reversible, so that their equilibrium concentrations (5-8%) were comparable to the 2-N- or 6-O-sulfate-bound species. The results emphasize the relevance of glycans in bioinorganic chemistry and underpin a fundamental molecular description of the HS-Pt interactions that alter the profile of platinum agents from cytotoxic to metastatic in a systematic manner.

  DOI：

  10.1021/acs.inorgchem.8b03035
• 作为产物：
  描述：

  叔丁基二苯基氯硅烷 、 methyl 2-azido-3-O-benzyl-2-deoxy-α-D-glucopyranoside 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 以92%的产率得到Methyl 2-azido-3-O-benzyl-6-O-tert-butyldiphenylsilyl-2-deoxy-alpha-D-glucopyranoside
  参考文献：
  名称：

  抑制单纯疱疹病毒 1 型宿主细胞相互作用的 3-O-磺化硫酸乙酰肝素八糖的合成

  摘要：

  细胞表面碳水化合物在许多生物学上重要的过程中发挥着重要作用。例如，硫酸乙酰肝素是一种无处不在的多硫酸化多糖，除其他外，它参与了单纯疱疹病毒 1 型 (HSV-1) 感染的初始步骤。病毒与细胞表面硫酸乙酰肝素相互作用以促进宿主细胞附着和进入。已发现3- O-磺化硫酸乙酰肝素作为 HSV-1 进入受体发挥作用。实现对这些相互作用的完整理解需要对此类寡糖进行化学合成，但这仍然具有挑战性。在这里，我们提出了一种合成两种不规则 3- O的简便方法-磺化硫酸乙酰肝素八糖，利用关键的二糖中间体来获得寡糖链组装的不同结构单元。尽管存在显着的结构差异，但制备的 3- O-磺化糖以剂量依赖性方式阻断病毒感染，彼此之间具有显着的相似性。

  DOI：

  10.1038/nchem.1073

文献信息

• Synthesis of 3-O-sulfonated heparan sulfate octasaccharides that inhibit the herpes simplex virus type 1 host–cell interaction
  作者：Yu-Peng Hu、Shu-Yi Lin、Cheng-Yen Huang、Medel Manuel L. Zulueta、Jing-Yuan Liu、Wen Chang、Shang-Cheng Hung

  DOI：10.1038/nchem.1073

  日期：2011.7

  understanding of these interactions requires the chemical synthesis of such oligosaccharides, but this remains challenging. Here, we present a convenient approach for the synthesis of two irregular 3-O-sulfonated heparan sulfate octasaccharides, making use of a key disaccharide intermediate to acquire different building blocks for the oligosaccharide chain assembly. Despite substantial structural differences

  细胞表面碳水化合物在许多生物学上重要的过程中发挥着重要作用。例如，硫酸乙酰肝素是一种无处不在的多硫酸化多糖，除其他外，它参与了单纯疱疹病毒 1 型 (HSV-1) 感染的初始步骤。病毒与细胞表面硫酸乙酰肝素相互作用以促进宿主细胞附着和进入。已发现3- O-磺化硫酸乙酰肝素作为 HSV-1 进入受体发挥作用。实现对这些相互作用的完整理解需要对此类寡糖进行化学合成，但这仍然具有挑战性。在这里，我们提出了一种合成两种不规则 3- O的简便方法-磺化硫酸乙酰肝素八糖，利用关键的二糖中间体来获得寡糖链组装的不同结构单元。尽管存在显着的结构差异，但制备的 3- O-磺化糖以剂量依赖性方式阻断病毒感染，彼此之间具有显着的相似性。
• Glycans as Ligands in Bioinorganic Chemistry. Probing the Interaction of a Trinuclear Platinum Anticancer Complex with Defined Monosaccharide Fragments of Heparan Sulfate
  作者：Anil Kumar Gorle、Premraj Rajaratnam、Chih-Wei Chang、Mark von Itzstein、Susan J. Berners-Price、Nicholas P. Farrell

  DOI：10.1021/acs.inorgchem.8b03035

  日期：2019.6.3

  We report herein a detailed NMR study of the aquation and subsequent covalent binding of the trinuclear clinical agent [trans-PtCl((NH3)-N-15)(2)}(2)mu-trans-Pt((NH3)-N-15)(2)((NH2)-N-15(CH2)(6)(NH2)-N-15)(2)}](4+) (1, 1,0,1/t,t,t or Triplatin) with three d-glucosamine residues containing varied O-sulfate and N-sulfate or N-acetyl substitutions, which represent monosaccharide fragments present within the repeating disaccharide sequences of cell surface heparan sulfate (HS). The monosaccharides GlcNS(6S), GlcNS, and GlcNAc(6S) were synthesized in good yield from a common 4,6-diol alpha-methyl glucopyranoside intermediate. The reactions of N-15-1 with sodium sulfate, GlcNS(6S), GlcNS, and GlcNAc(6S) were followed by 2D [H-1,N-15] heteronuclear single quantum coherence (HSQC) NMR spectroscopy using conditions (298 K, pH approximate to 5.4) similar to those previously used for other anionic systems, allowing for a direct comparison. The equilibrium constants (pK(1)) for the aquation of 1 in the presence of GlcNS(6S) and GlcNS were slightly higher compared to that of the aquation in a sulfate solution, while a comparable pK(1) value was observed in the presence of GlcNAc(6S). A comparison of the rate constants for sulfate displacement of the aqua ligand showed preferential binding to 2-N-sulfate compared to 6-O-sulfate but a more rapid liberation. For disulfated GlcNS(6S), equilibrium conditions were achieved rapidly (9 h) and strongly favored the dichloro form, with <2% sulfato species observed. The value of k(L1) was up to 15-fold lower than that for binding to sulfate, whereas the rate constant for the reverse ligation (k(-L1)) was comparable. Equilibrium conditions were achieved much more slowly (similar to 100 h) for the reactions of 1 with GlcNS and GlcNAc(6S), attributed to covalent binding also to the N-donor of the sulfamate (GlcNS) group and the O-donor of the N-acetyl [GlcNAc(6S)] group. The rate constants (k(L2)) were 20-40-fold lower than that for binding to the 2-N- or 6-O-sulfate, but the binding was less reversible, so that their equilibrium concentrations (5-8%) were comparable to the 2-N- or 6-O-sulfate-bound species. The results emphasize the relevance of glycans in bioinorganic chemistry and underpin a fundamental molecular description of the HS-Pt interactions that alter the profile of platinum agents from cytotoxic to metastatic in a systematic manner.