(4R,4aS,7S,7aR,12bS)-7-[(2'R,4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a-hydroxy-9-methoxyspiro[2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,5'-2H-1,3-oxazole]-2'-yl]-3-(cyclopropylmethyl)-9-methoxy-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,7-diol | 1339050-67-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: (4R,4aS,7S,7aR,12bS)-7-[(2'R,4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a-hydroxy-9-methoxyspiro[2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,5'-2H-1,3-oxazole]-2'-yl]-3-(cyclopropylmethyl)-9-methoxy-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,7-diol
• CAS: 1339050-67-7
• 化学式: C₄₄H₅₃N₃O₈
• 分子量: 751.92
• InChiKey: UEWPGTBXNJTLNJ-RLADBISYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  55
• 可旋转键数：
  7
• 环数：
  13.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  126
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (4R,4aS,7S,7aR,12bS)-7-[(2'R,4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a-hydroxy-9-methoxyspiro[2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,5'-2H-1,3-oxazole]-2'-yl]-3-(cyclopropylmethyl)-9-methoxy-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,7-diol 在 丙烷-1-硫醇 、 potassium tert-butylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 SYK-43
  参考文献：
  名称：

  Synthesis of novel triplet drugs with 1,3,5-trioxazatriquinane skeletons and their pharmacologies. Part 2: Synthesis of novel triplet drugs with the epoxymethano structure (capped homotriplet)

  摘要：

  An improved synthetic method for triplet drugs with the 1,3,5-trioxazatriquinane skeleton was developed that used p-toluenesulfonylmethyl isocyanide (TosMIC) instead of 1,3-dithiane. Using the improved method, we synthesized compounds with two identical pharmacophore units and an epoxymethano group, that is, capped homotriplets. Among the synthesized capped homotriplets, KNT-123 showed high selectivity for the p receptor over the kappa receptor, and the mu selectivity was the highest among the reported p selective nonpeptide ligands. KNT-123 administered subcutaneously induced a dose-dependent analgesic effect in the acetic acid writhing assay, and its potency was 11-fold more potent than that of morphine. KNT-123 may serve as a useful tool for the study of the pharmacological actions mediated specifically via the mu receptor. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.065
• 作为产物：
  描述：

  (4R,4aS,7S,7aR,12bS)-3-(cyclopropylmethyl)-4a,7-dihydroxy-9-methoxy-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7-carbaldehyde 在 sodium acetate 、 氯化铵 作用下， 以 甲醇 为溶剂， 生成 (4R,4aS,7S,7aR,12bS)-7-[(2'R,4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a-hydroxy-9-methoxyspiro[2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,5'-2H-1,3-oxazole]-2'-yl]-3-(cyclopropylmethyl)-9-methoxy-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,7-diol 、 (4R,4aS,7S,7aR,12bS)-7-[(2'S,4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a-hydroxy-9-methoxyspiro[2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,5'-2H-1,3-oxazole]-2'-yl]-3-(cyclopropylmethyl)-9-methoxy-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,7-diol
  参考文献：
  名称：

  使用新的重排反应合成具有氧杂双环[3.2.1]辛烷骨架的新型阿片样物质配体

  摘要：

  制备具有1,3,5-三氧杂氮杂三喹烷骨架的三聚体的尝试导致发现了新的重排反应，该反应提供了具有氧杂环[3.2.1]辛烷骨架的化合物，提出了其反应机理。基于这种机理，我们以优异的收率从二甲基乙缩醛中间体合成了重排产物。具有氧杂双环[3.2.1]辛烷骨架的化合物显示出对μ和κ的高亲和力，但对δ阿片受体类型没有亲和力。该化合物有望成为新型κ选择性配体的关键中间体。

  DOI：

  10.1016/j.bmcl.2009.03.068