Acetic acid (2R,3S,4S,5R,6R)-3,5-diacetoxy-2-acetoxymethyl-6-((2R,4aR,8R,8aS)-2-phenyl-hexahydro-pyrano[3,2-d][1,3]dioxin-8-yloxy)-tetrahydro-pyran-4-yl ester | 252896-22-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Acetic acid (2R,3S,4S,5R,6R)-3,5-diacetoxy-2-acetoxymethyl-6-((2R,4aR,8R,8aS)-2-phenyl-hexahydro-pyrano[3,2-d][1,3]dioxin-8-yloxy)-tetrahydro-pyran-4-yl ester
• 英文别名: [(2R,3S,4S,5R,6R)-6-[[(2R,4aR,8R,8aS)-2-phenyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-8-yl]oxy]-3,4,5-triacetyloxyoxan-2-yl]methyl acetate
• CAS: 252896-22-3
• 化学式: C₂₇H₃₄O₁₃
• 分子量: 566.559
• InChiKey: OTZJSUJWDMGQRM-LRTYLUHISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  40
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  151
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  Acetic acid (2R,3S,4S,5R,6R)-3,5-diacetoxy-2-acetoxymethyl-6-((2R,4aR,8R,8aS)-2-phenyl-hexahydro-pyrano[3,2-d][1,3]dioxin-8-yloxy)-tetrahydro-pyran-4-yl ester 在 盐酸 、 四乙基溴化铵 、 sodium methylate 、 二正丁基氧化锡 、 sodium cyanoborohydride 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 57.0h， 生成 benzyl (2S)-3-cyclohexyl-2-[(2R,3S,4S,5R,6R)-3,5-dihydroxy-2-(hydroxymethyl)-6-[(2R,3S,4R)-3-[(2S,3S,4R,5R,6S)-6-methyl-3,4,5-tris(phenylmethoxy)oxan-2-yl]oxy-2-(phenylmethoxymethyl)oxan-4-yl]oxyoxan-4-yl]oxypropanoate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of a Potent E-Selectin Antagonist

  摘要：

  An early step of the inflammatory response-the rolling of leukocytes on activated endothelial cells-is mediated by selectin/carbohydrate interactions. The tetrasaccharide sialyl Lewis(x) (sLe(x)) 1 is a ligand for E-, P-, and L-selectin and, therefore, serves as a lead structure to develop analogues which allow the control of acute and chronic inflammation. Here we describe the efficient synthesis (10 linear steps) of the potent sLe(x) mimetic 2. Compared to sLe(x), compound 2 showed a 30-fold improved affinity in a static, cell-free E-selectin-ligand binding assay (IC50 = 36 mu M). These data were confirmed by a marked inhibition in an in vitro cell-cell rolling assay which simulates in vivo conditions (IC50 approximate to 40 mu M). The assays are predictive for the in vivo efficacy of test compounds as indicated by a marked inhibitory effect of 2 in a thioglycollate induced peritonitis model of acute inflammation in mice (ED50 approximate to 15 mg/kg).

  DOI：

  10.1021/jm990422n
• 作为产物：
  描述：

  1,5-Anhydro-2-deoxy-4,6-O-(phenylmethylene)-D-arabino-hexopyranoside 、 2,3,4,6-O-四乙酰基-1-硫代-Β-D-乙基半乳糖苷 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， 以72%的产率得到Acetic acid (2R,3S,4S,5R,6R)-3,5-diacetoxy-2-acetoxymethyl-6-((2R,4aR,8R,8aS)-2-phenyl-hexahydro-pyrano[3,2-d][1,3]dioxin-8-yloxy)-tetrahydro-pyran-4-yl ester
  参考文献：
  名称：

  Synthesis and Biological Evaluation of a Potent E-Selectin Antagonist

  摘要：

  An early step of the inflammatory response-the rolling of leukocytes on activated endothelial cells-is mediated by selectin/carbohydrate interactions. The tetrasaccharide sialyl Lewis(x) (sLe(x)) 1 is a ligand for E-, P-, and L-selectin and, therefore, serves as a lead structure to develop analogues which allow the control of acute and chronic inflammation. Here we describe the efficient synthesis (10 linear steps) of the potent sLe(x) mimetic 2. Compared to sLe(x), compound 2 showed a 30-fold improved affinity in a static, cell-free E-selectin-ligand binding assay (IC50 = 36 mu M). These data were confirmed by a marked inhibition in an in vitro cell-cell rolling assay which simulates in vivo conditions (IC50 approximate to 40 mu M). The assays are predictive for the in vivo efficacy of test compounds as indicated by a marked inhibitory effect of 2 in a thioglycollate induced peritonitis model of acute inflammation in mice (ED50 approximate to 15 mg/kg).

  DOI：

  10.1021/jm990422n

文献信息

• WO2008/2449
  申请人：——

  公开号：——

  公开（公告）日：——