4-methoxyphenyl 2,4,6-tri-O-benzoyl-3-O-benzyl-α-L-idopyranoside | 445397-57-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-methoxyphenyl 2,4,6-tri-O-benzoyl-3-O-benzyl-α-L-idopyranoside
• CAS: 445397-57-9
• 化学式: C₄₁H₃₆O₁₀
• 分子量: 688.731
• InChiKey: QQIZBFQVARHHMT-KCMIUINGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.69
• 重原子数：
  51.0
• 可旋转键数：
  13.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  115.82
• 氢给体数：
  0.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  4-methoxyphenyl 2,4,6-tri-O-benzoyl-3-O-benzyl-α-L-idopyranoside 在 potassium bromide 吡啶 、 2,2,6,6-tetramethyl-piperidine-N-oxyl 、 calcium hypochlorite 、 ammonium cerium(IV) nitrate 、 三氟甲磺酸三甲基硅酯 、 sodium methylate 、 碳酸氢钠 、 溶剂黄146 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 9.08h， 生成 (methyl 2-O-benzoyl-3-O-benzyl-4-O-chloroacetyl-α-L-idopyranosyluronate)-(1->3)-4-O-acetyl-6-O-benzyl-2-deoxy-2-trichloroacetamido-1-O-trichloroacetamidoyl-α-D-galactopyranoside
  参考文献：
  名称：

  An access to various sulfation patterns in dermatan sulfate: chemical syntheses of sulfoforms of trisaccharide methyl glycosides

  摘要：

  The syntheses are reported for the first time of alpha-L-IdopA(2)SO(3)-(1-->3)-beta-D-GalpNAc4SO(3)-(1-->4)-alpha-L-IdopA2SO(3)-(1-->OMe), its disulfated analogue alpha-L-IdopA2SO(3)-(1-->3)-beta-D-GalpNAc4SO(3)-(1-->4)-alpha-L-IdopA2SO(3)-(1-->OMe), and of beta-D-GalpNAc4SO(3)-(1-->4)-alpha-L-IdopA2SO(3)-(1-->3)-beta-D-GalpNAc4SO(3)-(1-->OMe), which represent structural fragments of dermatan sulfate, unavailable directly by chemical or enzymatic degradation of the glycosaminoglycan polymer. These molecules were readily obtained from a pair of key disaccharide intermediates, in which the relative difference of stability of the D-GalNAc 4-hydroxy protecting groups (acetate or pivalate) toward saponification conditions allowed access to various sulfoforms from a common precursor. For the preparation of these blocks, the 4-O-pivaloyl-D-galacto moiety was readily obtained through a one-pot stereospecific intramolecular nucleophilic displacement on an easily available 3-O-pivaloyl-D-gluco precursor,and the L-IdoA moiety through selective radical oxidation at C-6 of a L-ido 4,6-diol derivative with oxoammonium salts. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0008-6215(02)00060-5
• 作为产物：
  描述：

  4-甲氧基苯酚 、 1,2,4,6-tetra-O-benzoyl-3-O-benzyl-β-L-idopyranose 在 三氟甲磺酸三甲基硅酯 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以98%的产率得到4-methoxyphenyl 2,4,6-tri-O-benzoyl-3-O-benzyl-α-L-idopyranoside
  参考文献：
  名称：

  An access to various sulfation patterns in dermatan sulfate: chemical syntheses of sulfoforms of trisaccharide methyl glycosides

  摘要：

  The syntheses are reported for the first time of alpha-L-IdopA(2)SO(3)-(1-->3)-beta-D-GalpNAc4SO(3)-(1-->4)-alpha-L-IdopA2SO(3)-(1-->OMe), its disulfated analogue alpha-L-IdopA2SO(3)-(1-->3)-beta-D-GalpNAc4SO(3)-(1-->4)-alpha-L-IdopA2SO(3)-(1-->OMe), and of beta-D-GalpNAc4SO(3)-(1-->4)-alpha-L-IdopA2SO(3)-(1-->3)-beta-D-GalpNAc4SO(3)-(1-->OMe), which represent structural fragments of dermatan sulfate, unavailable directly by chemical or enzymatic degradation of the glycosaminoglycan polymer. These molecules were readily obtained from a pair of key disaccharide intermediates, in which the relative difference of stability of the D-GalNAc 4-hydroxy protecting groups (acetate or pivalate) toward saponification conditions allowed access to various sulfoforms from a common precursor. For the preparation of these blocks, the 4-O-pivaloyl-D-galacto moiety was readily obtained through a one-pot stereospecific intramolecular nucleophilic displacement on an easily available 3-O-pivaloyl-D-gluco precursor,and the L-IdoA moiety through selective radical oxidation at C-6 of a L-ido 4,6-diol derivative with oxoammonium salts. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0008-6215(02)00060-5

文献信息

• Synthesis of a Targeted Library of Heparan Sulfate Hexa- to Dodecasaccharides as Inhibitors of β-Secretase: Potential Therapeutics for Alzheimer’s Disease
  作者：Ralf Schwörer、Olga V. Zubkova、Jeremy E. Turnbull、Peter C. Tyler

  DOI：10.1002/chem.201204519

  日期：2013.5.17

  HS has been shown to function as an inhibitor of the β‐site cleaving enzyme β‐secretase (BACE1), a protease responsible for generating the toxic Aβ peptides that accumulate in Alzheimer’s disease (AD), with 6‐O‐sulfation identified as a key requirement. Here, we demonstrate a novel generic synthetic approach to HS oligosaccharides applied to production of a library of 16 hexa‐ to dodecasaccharides targeted

  硫酸乙酰肝素 (HS) 是一类硫酸化多糖，可作为多种蛋白质功能的动态生物调节剂。然而，这些相互作用的结构基础仍然难以捉摸，定义结构的化学合成代表了一种具有挑战性但功能强大的方法，用于解开其复杂硫酸化模式的结构-活性关系。HS 已被证明可作为 β 位点裂解酶 β 分泌酶 (BACE1) 的抑制剂，BACE1 是一种负责产生在阿尔茨海默病 (AD) 中积累的有毒 Aβ 肽的蛋白酶，具有 6- O-硫酸盐化被确定为一项关键要求。在这里，我们展示了一种新的 HS 寡糖通用合成方法，该方法应用于生产针对 BACE1 抑制的 16 种六至十二糖库。对该文库的筛选为优化 BACE1 抑制的构效关系提供了新的见解，并产生了许多有效的非抗凝 BACE1 抑制剂，这些抑制剂具有开发潜力，可通过降低 Aβ 肽水平来治疗 AD。