tert-butyl benzyl(3-(((3aR,4R,6S,7R,7aR)-7-(((benzyloxy)carbonyl)amino)-4-(1-(3-methoxyphenyl)-1H-1,2,3-triazol-4-yl)-2,2-dimethyltetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-6-yl)oxy)-2-hydroxypropyl)carbamate | 1355242-76-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl benzyl(3-(((3aR,4R,6S,7R,7aR)-7-(((benzyloxy)carbonyl)amino)-4-(1-(3-methoxyphenyl)-1H-1,2,3-triazol-4-yl)-2,2-dimethyltetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-6-yl)oxy)-2-hydroxypropyl)carbamate
• CAS: 1355242-76-0
• 化学式: C₄₀H₄₉N₅O₁₀
• 分子量: 759.857
• InChiKey: VBSPMZJIMPJZOA-ONRFPLLDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  55.0
• 可旋转键数：
  13.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  164.96
• 氢给体数：
  2.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  tert-butyl benzyl(3-(((3aR,4R,6S,7R,7aR)-7-(((benzyloxy)carbonyl)amino)-4-(1-(3-methoxyphenyl)-1H-1,2,3-triazol-4-yl)-2,2-dimethyltetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-6-yl)oxy)-2-hydroxypropyl)carbamate 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 25.0h， 生成 1-(benzyl(tert-butoxycarbonyl)amino)-3-(((3aR,4R,6S,7R,7aR)-4-(1-(3-methoxyphenyl)-1H-1,2,3-triazol-4-yl)-2,2-dimethyl-7-(2,2,2-trifluoroacetamido)tetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-6-yl)oxy)propan-2-yl 2,2,2-trifluoroacetate
  参考文献：
  名称：

  Glycomimetic Ligands for the Human Asialoglycoprotein Receptor

  摘要：

  The asialoglycoprotein receptor (ASGPR) is a high-capacity galactose-binding receptor expressed on hepatocytes that binds its native substrates with low affinity. More potent ligands are of interest for hepatic delivery of therapeutic agents. We report several classes of galactosyl analogues with varied substitution at the anomeric, C2-, C5-, and C6-positions. Significant increases in binding affinity were noted for several trifluoromethyl-acetamide derivatives without covalent attachment to the protein. A variety of new ligands were obtained with affinity for ASGPR as good as or better than that of the parent N-acetylgalactosamine, showing that modification on either side of the key C3,C4-diol moiety is well tolerated, consistent with previous models of a shallow binding pocket. The galactosyl pyranose motif therefore offers many opportunities for the attachment of other functional units or payloads while retaining low-micromolar or better affinity for the ASGPR.

  DOI：

  10.1021/ja2104679
• 作为产物：
  描述：

  在 lithium perchlorate 、 potassium carbonate 、 copper(II) sulfate 、 sodium ascorbate 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 62.17h， 生成 tert-butyl benzyl(3-(((3aR,4R,6S,7R,7aR)-7-(((benzyloxy)carbonyl)amino)-4-(1-(3-methoxyphenyl)-1H-1,2,3-triazol-4-yl)-2,2-dimethyltetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-6-yl)oxy)-2-hydroxypropyl)carbamate
  参考文献：
  名称：

  Glycomimetic Ligands for the Human Asialoglycoprotein Receptor

  摘要：

  The asialoglycoprotein receptor (ASGPR) is a high-capacity galactose-binding receptor expressed on hepatocytes that binds its native substrates with low affinity. More potent ligands are of interest for hepatic delivery of therapeutic agents. We report several classes of galactosyl analogues with varied substitution at the anomeric, C2-, C5-, and C6-positions. Significant increases in binding affinity were noted for several trifluoromethyl-acetamide derivatives without covalent attachment to the protein. A variety of new ligands were obtained with affinity for ASGPR as good as or better than that of the parent N-acetylgalactosamine, showing that modification on either side of the key C3,C4-diol moiety is well tolerated, consistent with previous models of a shallow binding pocket. The galactosyl pyranose motif therefore offers many opportunities for the attachment of other functional units or payloads while retaining low-micromolar or better affinity for the ASGPR.

  DOI：

  10.1021/ja2104679