(1'R,4R,4'R,4aS,7S,7'R,7aR,12bS)-3-(cyclopropylmethyl)-9-methoxy-3',3',9',9'-tetramethylspiro[2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,6'-2,5,8-trioxa-10-azatricyclo[5.2.1.04,10]decane]-4a-ol | 1415643-03-6

• 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: (1'R,4R,4'R,4aS,7S,7'R,7aR,12bS)-3-(cyclopropylmethyl)-9-methoxy-3',3',9',9'-tetramethylspiro[2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,6'-2,5,8-trioxa-10-azatricyclo[5.2.1.04,10]decane]-4a-ol
• CAS: 1415643-03-6
• 化学式: C₃₀H₄₀N₂O₆
• 分子量: 524.657
• InChiKey: WFNQLASTILJLDZ-RDJAKBKHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  38
• 可旋转键数：
  3
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  72.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (1'R,4R,4'R,4aS,7S,7'R,7aR,12bS)-3-(cyclopropylmethyl)-9-methoxy-3',3',9',9'-tetramethylspiro[2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,6'-2,5,8-trioxa-10-azatricyclo[5.2.1.04,10]decane]-4a-ol 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以86%的产率得到(1'R,4R,4'R,4aS,7S,7'R,7aR,12bS)-3-(cyclopropylmethyl)-3',3',9',9'-tetramethylspiro[2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,6'-2,5,8-trioxa-10-azatricyclo[5.2.1.04,10]decane]-4a,9-diol
  参考文献：
  名称：

  Synthesis of novel triplet drugs with 1,3,5-trioxazatriquinane skeletons and their pharmacologies. 3: Synthesis of novel triplet drugs with the bis(epoxymethano) or bis(dimethylepoxymethano) structure (double-capped triplet)

  摘要：

  Novel double-capped triplet drugs, which have one pharmacophore unit and two epoxymethano or dimethylepoxymethano structures (termed cap or diMe-cap structures, respectively) were synthesized. Key intermediate oxazoline 16 derived from acetone enabled the effective synthesis of double-capped triplets. SYK-134 (7a) and SYK-135 (8a) with N-cyclopropylmethyl substituent and cap structures showed selectivities for the kappa opioid receptor. On the other hand, the N-Me series exhibited selectivities for the mu opioid receptor. The double-capped triplet drugs with diMe-cap structures preferred the mu receptor independently of their N-substituents. SYK-385 (19b), one of the mu-selective double-capped triplet drugs, showed the highest selectivity for the mu receptor among the reported mu-selective nonpeptide ligands. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.023
• 作为产物：
  描述：

  纳曲酮EP杂质J 在 camphor-10-sulfonic acid 、 potassium carbonate 作用下， 以 甲醇 、 氯仿 为溶剂， 生成 (1'R,4R,4'R,4aS,7S,7'R,7aR,12bS)-3-(cyclopropylmethyl)-9-methoxy-3',3',9',9'-tetramethylspiro[2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,6'-2,5,8-trioxa-10-azatricyclo[5.2.1.04,10]decane]-4a-ol
  参考文献：
  名称：

  Synthesis of novel triplet drugs with 1,3,5-trioxazatriquinane skeletons and their pharmacologies. 3: Synthesis of novel triplet drugs with the bis(epoxymethano) or bis(dimethylepoxymethano) structure (double-capped triplet)

  摘要：

  Novel double-capped triplet drugs, which have one pharmacophore unit and two epoxymethano or dimethylepoxymethano structures (termed cap or diMe-cap structures, respectively) were synthesized. Key intermediate oxazoline 16 derived from acetone enabled the effective synthesis of double-capped triplets. SYK-134 (7a) and SYK-135 (8a) with N-cyclopropylmethyl substituent and cap structures showed selectivities for the kappa opioid receptor. On the other hand, the N-Me series exhibited selectivities for the mu opioid receptor. The double-capped triplet drugs with diMe-cap structures preferred the mu receptor independently of their N-substituents. SYK-385 (19b), one of the mu-selective double-capped triplet drugs, showed the highest selectivity for the mu receptor among the reported mu-selective nonpeptide ligands. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.023