[2-azido-3-O-(4-bromobenzyl)-6-O-tert-butyldiphenylsilyl-2-deoxy-4-O-(2-naphthylmethyl)-α-D-glucopyranosyl]-(1->4)-(6-O-acetyl-2-O-benzoyl-3-O-benzyl-α-L-idopyranosyl)-(1->4)-[2-azido-3-O-(4-bromobenzyl)-6-O-tert-butyldiphenylsilyl-2-deoxy-α-D-glucopyranosyl]-(1->4)-1,6-anhydro-2-O-benzoyl-3-O-benzyl-β-L-idopyranose | 1374561-92-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [2-azido-3-O-(4-bromobenzyl)-6-O-tert-butyldiphenylsilyl-2-deoxy-4-O-(2-naphthylmethyl)-α-D-glucopyranosyl]-(1->4)-(6-O-acetyl-2-O-benzoyl-3-O-benzyl-α-L-idopyranosyl)-(1->4)-[2-azido-3-O-(4-bromobenzyl)-6-O-tert-butyldiphenylsilyl-2-deoxy-α-D-glucopyranosyl]-(1->4)-1,6-anhydro-2-O-benzoyl-3-O-benzyl-β-L-idopyranose
• 英文别名: [2-azido-3-O-(4-bromobenzyl)-6-O-tert-butyldiphenylsilyl-2-deoxy-4-O-(2-naphthylmethyl)-alpha-D-glucopyranosyl]-(1-->4)-(6-O-acetyl-2-O-benzoyl-3-O-benzyl-alpha-L-idopyranosyl)-(1-->4)-[2-azido-3-O-(4-bromobenzyl)-6-O-tert-butyldiphenylsilyl-2-deoxy-alpha-D-glucopyranosyl]-(1-->4)-1,6-anhydro-2-O-benzoyl-3-O-benzyl-beta-L-idopyranoside；[(1S,2R,3S,4R,5S)-2-[(2R,3R,4R,5S,6R)-5-[(2S,3R,4S,5R,6S)-6-(acetyloxymethyl)-5-[(2R,3R,4R,5S,6R)-3-azido-4-[(4-bromophenyl)methoxy]-6-[[tert-butyl(diphenyl)silyl]oxymethyl]-5-(naphthalen-2-ylmethoxy)oxan-2-yl]oxy-3-benzoyloxy-4-phenylmethoxyoxan-2-yl]oxy-3-azido-4-[(4-bromophenyl)methoxy]-6-[[tert-butyl(diphenyl)silyl]oxymethyl]oxan-2-yl]oxy-3-phenylmethoxy-6,8-dioxabicyclo[3.2.1]octan-4-yl] benzoate
• CAS: 1374561-92-8
• 化学式: C₁₁₁H₁₁₄Br₂N₆O₂₁Si₂
• 分子量: 2084.13
• InChiKey: TZVLNRLDJJXEAT-AUBNNBNFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  19.2
• 重原子数：
  142
• 可旋转键数：
  44
• 环数：
  17.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  246
• 氢给体数：
  0
• 氢受体数：
  25

反应信息

• 作为反应物：
  描述：

  [2-azido-3-O-(4-bromobenzyl)-6-O-tert-butyldiphenylsilyl-2-deoxy-4-O-(2-naphthylmethyl)-α-D-glucopyranosyl]-(1->4)-(6-O-acetyl-2-O-benzoyl-3-O-benzyl-α-L-idopyranosyl)-(1->4)-[2-azido-3-O-(4-bromobenzyl)-6-O-tert-butyldiphenylsilyl-2-deoxy-α-D-glucopyranosyl]-(1->4)-1,6-anhydro-2-O-benzoyl-3-O-benzyl-β-L-idopyranose 在 甲醇 、 sodium methylate 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以98%的产率得到[2-azido-3-O-(4-bromobenzyl)-6-O-tert-butyldiphenylsilyl-2-deoxy-4-O-(2-naphthylmethyl)-α-D-glucopyranosyl]-(1->4)-(3-O-benzyl-α-L-idopyranosyl)-(1->4)-[2-azido-3-O-(4-bromobenzyl)-6-O-tert-butyldiphenylsilyl-2-deoxy-α-D-glucopyranosyl]-(1->4)-1,6-anhydro-3-O-benzyl-β-L-idopyranose
  参考文献：
  名称：

  α-Glycosylation by d-Glucosamine-Derived Donors: Synthesis of Heparosan and Heparin Analogues That Interact with Mycobacterial Heparin-Binding Hemagglutinin

  摘要：

  Numerous biomolecules possess alpha-D-glucosamine as structural component. However, chemical glycosylations aimed at this backbone are usually not easily attained without generating the unwanted beta-isomer. We report herein a versatile approach in affording full alpha-stereoselectivity built upon a carefully selected set of orthogonal protecting groups on a D-glucosaminyl donor. The excellent stereoselectivity provided by the protecting group combination was found independent of leaving groups and activators. With the trichloroacetimidate as the optimum donor leaving group, core skeletons of glycosylphosphatidyl inositol anchors, heparosan, heparan sulfate, and heparin were efficiently assembled. The orthogonal protecting groups were successfully manipulated to further carry out the total syntheses of heparosan tri- and pentasaccharides and heparin di-, tetra-, hexa-, and octasaccharide analogues. Using the heparin analogues, heparin-binding hemagglutinin, a virulence factor of Mycobacterium tuberculosis, was found to bind at least six sugar units with the interaction notably being entropically driven.

  DOI：

  10.1021/ja302640p
• 作为产物：
  描述：

  1,6-anhydro-4-O-[2-azido-3-O-(4-bromobenzyl)-6-O-tert-butyldiphenylsilyl-2-deoxy-α-D-glucopyranosyl]-2-O-benzoyl-3-O-benzyl-β-L-idopyranose 、 4-Methylphenyl 6-O-acetyl-4-O-[2-azido-3-O-(4-bromobenzyl)-6-O-tert-butyldiphenylsilyl-2-deoxy-4-O-(2-naphthylmethyl)-alpha-D-glucopyranosyl]-2-O-benzoyl-3-O-benzyl-1-thio-alpha-L-idopyranoside 在 N-碘代丁二酰亚胺 、 三氟甲磺酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以80%的产率得到[2-azido-3-O-(4-bromobenzyl)-6-O-tert-butyldiphenylsilyl-2-deoxy-4-O-(2-naphthylmethyl)-α-D-glucopyranosyl]-(1->4)-(6-O-acetyl-2-O-benzoyl-3-O-benzyl-α-L-idopyranosyl)-(1->4)-[2-azido-3-O-(4-bromobenzyl)-6-O-tert-butyldiphenylsilyl-2-deoxy-α-D-glucopyranosyl]-(1->4)-1,6-anhydro-2-O-benzoyl-3-O-benzyl-β-L-idopyranose
  参考文献：
  名称：

  Trisaccharide Sulfate and Its Sulfonamide as an Effective Substrate and Inhibitor of Human Endo-O-sulfatase-1

  摘要：

  Human endo-O-sulfatases (Sulf-1 and Sulf-2) are extracellular heparan sulfate proteoglycan (HSPG)-specific 6-O-endosulfatases, which regulate a multitude of cell-signaling events through heparan sulfate (HS)-protein interactions and are associated with the onset of osteoarthritis. These endo-O-sulfatases are transported onto the cell surface to liberate the 6-sulfate groups from the internal D-glucosamine residues in the highly sulfated subdomains of HSPGs. In this study, a variety of HS oligosaccharides with different chain lengths and N-and O-sulfation patterns via chemical synthesis were systematically studied about the substrate specificity of human Sulf-1 employing the fluorogenic substrate 4-methylumbelliferyl sulfate (4-MUS) in a competition assay. The trisaccharide sulfate IdoA2S-GlcNS6S-IdoA2S was found to be the minimal-size substrate for Sulf-1, and substitution of the sulfate group at the 6-O position of the D-glucosamine unit with the sulfonamide motif effectively inhibited the Sulf-1 activity with IC50 = 0.53 mu M, K-i = 0.36 mu M, and K-D = 12 nM.

  DOI：

  10.1021/jacs.0c00005