N-((4R,4aR,7R,7aR,12bS)-9-hydroxy-3-methyl-2,3,4,4a,7,7a-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)-2-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)acetamide | 851217-51-1

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: N-((4R,4aR,7R,7aR,12bS)-9-hydroxy-3-methyl-2,3,4,4a,7,7a-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)-2-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)acetamide
• CAS: 851217-51-1
• 化学式: C₅₃H₅₆N₂O₈
• 分子量: 849.036
• InChiKey: REXPQGWRZXZPGQ-BKFSSBETSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.45
• 重原子数：
  63.0
• 可旋转键数：
  16.0
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  107.95
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  N-((4R,4aR,7R,7aR,12bS)-9-hydroxy-3-methyl-2,3,4,4a,7,7a-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)-2-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)acetamide 在 palladium on activated charcoal 氢气 作用下， 以 盐酸 、 甲醇 为溶剂， 以52%的产率得到
  参考文献：
  名称：

  Synthesis and in vitro biological evaluation of a carbon glycoside analogue of morphine-6-glucuronide

  摘要：

  Attachment of a glucose moiety to 6-beta-aminomorphine afforded compound 3, where the glucose moiety was linked to the C-6 nitrogen atom by a two-carbon bridge. The synthesis of 3 was accomplished in eight steps from 3-triisopropylsilyl-6-P-aminomorphine and 2,3,4,6-tetra-O-benzyl-D-glucose. The C-glycoside 3 was prepared with the objective of examining a metabolically stable analogue of morphine-6-glucuronide and determining the potency and selectivity of opioid receptor binding. Competition binding assays showed that 3 bound to the mu opioid receptor with a K-i value of 3.5 nM. The C-glycoside 3 exhibited delta/mu and kappa/mu selectivity ratios of 76 and 165, respectively. The synthetic intermediate (i.e., benzyl precursor, compound 11) bound to the mu opioid receptor with a K-i value of 0.5 nM, was less selective for the mu opioid receptor. The [S-35]GTP gamma S assay was used to evaluate the functional properties of compounds 3 and 11. Compound 3 was determined to be a full agonist at the p opioid receptor, whereas compound 11 was found to be a partial agonist. Compound 3 was determined to be very stable in the presence of human liver S9, and rat and monkey liver microsomes: no detectable loss of 3 was observed up to 90 min. Compound 3 was also very stable at pH 2 and pH 7.4, suggesting that 3 possessed properties for sustained duration of action. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.072
• 作为产物：
  描述：

  2-deoxy-4,5,6,8-tetra-O-benzyl-α-D-gluco-3,7-pyranoso-3-octulosonate 在 三乙基硅烷 、 lithium hydroxide 、 氯化亚砜 、 三氟化硼乙醚 、 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 18.0h， 生成 N-((4R,4aR,7R,7aR,12bS)-9-hydroxy-3-methyl-2,3,4,4a,7,7a-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)-2-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)acetamide
  参考文献：
  名称：

  Synthesis and in vitro biological evaluation of a carbon glycoside analogue of morphine-6-glucuronide

  摘要：

  Attachment of a glucose moiety to 6-beta-aminomorphine afforded compound 3, where the glucose moiety was linked to the C-6 nitrogen atom by a two-carbon bridge. The synthesis of 3 was accomplished in eight steps from 3-triisopropylsilyl-6-P-aminomorphine and 2,3,4,6-tetra-O-benzyl-D-glucose. The C-glycoside 3 was prepared with the objective of examining a metabolically stable analogue of morphine-6-glucuronide and determining the potency and selectivity of opioid receptor binding. Competition binding assays showed that 3 bound to the mu opioid receptor with a K-i value of 3.5 nM. The C-glycoside 3 exhibited delta/mu and kappa/mu selectivity ratios of 76 and 165, respectively. The synthetic intermediate (i.e., benzyl precursor, compound 11) bound to the mu opioid receptor with a K-i value of 0.5 nM, was less selective for the mu opioid receptor. The [S-35]GTP gamma S assay was used to evaluate the functional properties of compounds 3 and 11. Compound 3 was determined to be a full agonist at the p opioid receptor, whereas compound 11 was found to be a partial agonist. Compound 3 was determined to be very stable in the presence of human liver S9, and rat and monkey liver microsomes: no detectable loss of 3 was observed up to 90 min. Compound 3 was also very stable at pH 2 and pH 7.4, suggesting that 3 possessed properties for sustained duration of action. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.072