phenyl 2-azido-4-O-benzyl-6-O-{4,6-O-benzylidene-2-deoxy-2-[(R)-3-octacosanoyloxy-hexadecan]amido-β-D-glucopyranosyl}-2-deoxy-1-thio-α-D-glucopyranoside | 548486-15-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: phenyl 2-azido-4-O-benzyl-6-O-{4,6-O-benzylidene-2-deoxy-2-[(R)-3-octacosanoyloxy-hexadecan]amido-β-D-glucopyranosyl}-2-deoxy-1-thio-α-D-glucopyranoside
• CAS: 548486-15-3
• 化学式: C₇₆H₁₂₀N₄O₁₁S
• 分子量: 1297.88
• InChiKey: GLHCDFMQTUVFJI-FNMUFJAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  19.0
• 重原子数：
  92.0
• 可旋转键数：
  52.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  200.0
• 氢给体数：
  3.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  phenyl 2-azido-4-O-benzyl-6-O-{4,6-O-benzylidene-2-deoxy-2-[(R)-3-octacosanoyloxy-hexadecan]amido-β-D-glucopyranosyl}-2-deoxy-1-thio-α-D-glucopyranoside 在 吡啶 、 1,3-丙二硫醇 作用下， 以 水 为溶剂， 反应 16.0h， 以94%的产率得到phenyl 2-amino-4-O-benzyl-6-O-{4,6-O-benzylidene-2-deoxy-2-[(R)-3-octacosanoyloxy-hexadecan]amido-β-D-glucopyranosyl}-2-deoxy-1-thio-α-D-glucopyranoside
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Rhizobium sin-1 Lipid A Derivatives

  摘要：

  A highly convergent strategy for the synthesis of several derivatives of the lipid A of Rhizobium sin-1 has been developed. The approach employed the advanced intermediate 3-O-acetyl-6-O-(3-O-acetyl-4,6-O-benzylidene-2-deoxy-2-phthalimido-beta-D-glucopyrano-syl)-2-azido-4-O-benzyl-2-deoxy-1 -thio-alpha-D-glucopyranoside (5), which is protected in such a way that the anomeric center, the C-2 and C-2' amino groups, and the C-3 and C-3' hydroxyls can be selectively functionalized. The synthetic strategy was used for the preparation of 2-deoxy-6-O-12-deoxy-3-O-[(R)-3-hydroxy-hexadecanoyl]-2-[(R)-3-octacosanoyloxy-hexadecan]amido-beta-D-glucopyranosyl}-2-[(R)-3-hydroxy-hexadecan]amido-3-O-[(R)-3-hydroxy-hexadecanoyl]- alpha-D-glucopyranose (11) and 2-deoxy-6-O-{2-deoxy-3-O[(R)-3-hydroxy-hexadecanoyl]-2-[(R)-3-octacosanoyloxy-hexadecan]amido-D-glucopyranosyl}-2-[(R)-3-hydroxy-hexadecan]amido-3-O-[(R)-3-hydroxy-hexadecanoyl]-D-glucono-1,5-lactone (13), which contain an unusual octacosanoic acid moiety and differ in the oxidation state of the anomeric center. The results of biological studies indicate that 11 and 13 lack the proinflammatory effects of Escherichia coli lipopolysaccharicles (LPS). Furthermore, 13 emulated the ability of heterogeneous R. sin-1 LPS to antagonize enteric LPS, providing evidence for the critical role of the gluconolactone moiety of R. sin-1 LPS in mediating this antagonistic effect. Compound 13 is the first example of a lipid A derivative that is devoid of phosphate but possesses antagonistic properties, making it an attractive lead compound for development of a drug to use in the treatment of Gram-negative septicemia.

  DOI：

  10.1021/ja029316s
• 作为产物：
  描述：

  phenyl 3-O-acetyl-4,6-O-benzylidene-2-deoxy-2-phthalimido-1-seleno-β-D-glucopyranoside 在 MS 4 Angstroem 、 silver trifluoromethanesulfonate 、 potassium carbonate 、 乙二胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 正丁醇 为溶剂， 反应 38.0h， 生成 phenyl 2-azido-4-O-benzyl-6-O-{4,6-O-benzylidene-2-deoxy-2-[(R)-3-octacosanoyloxy-hexadecan]amido-β-D-glucopyranosyl}-2-deoxy-1-thio-α-D-glucopyranoside
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Rhizobium sin-1 Lipid A Derivatives

  摘要：

  A highly convergent strategy for the synthesis of several derivatives of the lipid A of Rhizobium sin-1 has been developed. The approach employed the advanced intermediate 3-O-acetyl-6-O-(3-O-acetyl-4,6-O-benzylidene-2-deoxy-2-phthalimido-beta-D-glucopyrano-syl)-2-azido-4-O-benzyl-2-deoxy-1 -thio-alpha-D-glucopyranoside (5), which is protected in such a way that the anomeric center, the C-2 and C-2' amino groups, and the C-3 and C-3' hydroxyls can be selectively functionalized. The synthetic strategy was used for the preparation of 2-deoxy-6-O-12-deoxy-3-O-[(R)-3-hydroxy-hexadecanoyl]-2-[(R)-3-octacosanoyloxy-hexadecan]amido-beta-D-glucopyranosyl}-2-[(R)-3-hydroxy-hexadecan]amido-3-O-[(R)-3-hydroxy-hexadecanoyl]- alpha-D-glucopyranose (11) and 2-deoxy-6-O-{2-deoxy-3-O[(R)-3-hydroxy-hexadecanoyl]-2-[(R)-3-octacosanoyloxy-hexadecan]amido-D-glucopyranosyl}-2-[(R)-3-hydroxy-hexadecan]amido-3-O-[(R)-3-hydroxy-hexadecanoyl]-D-glucono-1,5-lactone (13), which contain an unusual octacosanoic acid moiety and differ in the oxidation state of the anomeric center. The results of biological studies indicate that 11 and 13 lack the proinflammatory effects of Escherichia coli lipopolysaccharicles (LPS). Furthermore, 13 emulated the ability of heterogeneous R. sin-1 LPS to antagonize enteric LPS, providing evidence for the critical role of the gluconolactone moiety of R. sin-1 LPS in mediating this antagonistic effect. Compound 13 is the first example of a lipid A derivative that is devoid of phosphate but possesses antagonistic properties, making it an attractive lead compound for development of a drug to use in the treatment of Gram-negative septicemia.

  DOI：

  10.1021/ja029316s