2,3,4,6-tetra-O-acetyl-1-O-7-(phenylcarbamoyl)hepthydroxamoyl-β-D-galactopyranose | 931415-43-9

• 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: 2,3,4,6-tetra-O-acetyl-1-O-7-(phenylcarbamoyl)hepthydroxamoyl-β-D-galactopyranose
• 英文别名: [(2R,3S,4S,5R,6S)-3,4,5-triacetyloxy-6-[(8-anilino-8-oxooctanoyl)amino]oxyoxan-2-yl]methyl acetate
• CAS: 931415-43-9
• 化学式: C₂₈H₃₈N₂O₁₂
• 分子量: 594.616
• InChiKey: VISVVKFZYLIOLL-ODRHMLNGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  42
• 可旋转键数：
  19
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  182
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  2,3,4,6-tetra-O-acetyl-1-O-7-(phenylcarbamoyl)hepthydroxamoyl-β-D-galactopyranose 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以100%的产率得到N-phenyl-N'-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoctanediamide
  参考文献：
  名称：

  Synthesis and biological evaluation of the suberoylanilide hydroxamic acid (SAHA) β-glucuronide and β-galactoside for application in selective prodrug chemotherapy

  摘要：

  The beta-O-glucuronide and beta-O-galactoside of SAHA have been prepared and evaluated as prodrugs for selective cancer chemotherapy (ADEPT, PMT). These new compounds are stable under physiological conditions and do not exhibit any antiproliferative activity compared to the parent drug after a 48-h treatment of H661 cells. The glucuronide derivative did not lead to the release of the drug in the presence of either Escherichia coli or bovine liver beta-glucuronidase. On the other hand, under enzymatic cleavage of galactoside prodrug by the corresponding enzyme, a rapid release of SARA was observed demonstrating that the beta-O-galactoside of SAHA is a promising candidate for in vivo investigations. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.11.042
• 作为产物：
  描述：

  2,3,4,6-四乙酰氧基-alpha-D-吡喃糖溴化物 在 四丁基硫酸氢铵 、 sodium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 肼 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 18.08h， 生成 2,3,4,6-tetra-O-acetyl-1-O-7-(phenylcarbamoyl)hepthydroxamoyl-β-D-galactopyranose
  参考文献：
  名称：

  Synthesis and biological evaluation of the suberoylanilide hydroxamic acid (SAHA) β-glucuronide and β-galactoside for application in selective prodrug chemotherapy

  摘要：

  The beta-O-glucuronide and beta-O-galactoside of SAHA have been prepared and evaluated as prodrugs for selective cancer chemotherapy (ADEPT, PMT). These new compounds are stable under physiological conditions and do not exhibit any antiproliferative activity compared to the parent drug after a 48-h treatment of H661 cells. The glucuronide derivative did not lead to the release of the drug in the presence of either Escherichia coli or bovine liver beta-glucuronidase. On the other hand, under enzymatic cleavage of galactoside prodrug by the corresponding enzyme, a rapid release of SARA was observed demonstrating that the beta-O-galactoside of SAHA is a promising candidate for in vivo investigations. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.11.042

文献信息

• First <i>O</i>-Glycosylation of Hydroxamic Acids
  作者：Mickaël Thomas、Jean-Pierre Gesson、Sébastien Papot

  DOI：10.1021/jo0701839

  日期：2007.5.1

  The first O-glycosylation of hydroxamic acids is reported. This process involves the use of glycosyl N-phenyl trifluoroacetimidates as glycosyl donors in the presence TMSOTf and 4 angstrom molecular sieves in dichloromethane. Under such conditions, a wide range of new glycosyl donors including glucosyl, galactosyl, mannosyl, glucuronyl, and ribosyl hydroxamates were prepared in good to high yields. This procedure appears to be an advantageous alternative for the synthesis of glycosyl hydroxamates of biological interest.