4,5α-epoxy-14β-hydroxy-17-isobutyl-3-methoxymorphinan-6-one | 1073609-53-6

• 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: 4,5α-epoxy-14β-hydroxy-17-isobutyl-3-methoxymorphinan-6-one
• 英文别名: (4R,4aS,7aR,12bS)-4a-hydroxy-9-methoxy-3-(2-methylpropyl)-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• CAS: 1073609-53-6
• 化学式: C₂₁H₂₇NO₄
• 分子量: 357.45
• InChiKey: YNJAZIAKONRYPG-MBPVOVBZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4,5α-epoxy-14β-hydroxy-17-isobutyl-3-methoxymorphinan-6-one 在 丙烷-1-硫醇 、 camphor-10-sulfonic acid 、 potassium tert-butylate 、 sodium acetate 、 potassium carbonate 、 氯化铵 、 六甲基二硅氮烷 作用下， 以 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 生成 (1'S,4R,4'S,4aS,7S,7'S,7aR,12bS)-3-(2-methylpropyl)spiro[2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,3'-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 platinum(IV) oxide 、 氢溴酸 、 氢气 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 37.0h， 以61%的产率得到4,5α-epoxy-14β-hydroxy-17-isobutyl-3-methoxymorphinan-6-one
  参考文献：
  名称：

  在铂催化剂和氢溴酸存在下将环丙基氢解为异丙基

  摘要：

  在室温下，在氧化铂（IV）催化剂和氢溴酸存在下，在温和的反应条件下进行环丙基甲胺的还原，得到异丁胺，而没有线性丁胺。所述环裂解反应广泛适用于各种化合物如N-环丙基烷基，O-环丙基烷基和C-环丙基烷基衍生物中的环丙烷环。尽管未活化的环丙烷环也被裂解，但是环丁烷环在相同的反应条件下是可容忍的。

  DOI：

  10.1016/j.tet.2009.10.064

文献信息

• Synthesis of N-isobutylnoroxymorphone from naltrexone by a selective cyclopropane ring opening reaction
  作者：Hideaki Fujii、Yumiko Osa、Marina Ishihara、Shinichi Hanamura、Toru Nemoto、Mayumi Nakajima、Ko Hasebe、Hidenori Mochizuki、Hiroshi Nagase

  DOI：10.1016/j.bmcl.2008.08.019

  日期：2008.9

  Selective ring opening reaction of the N-cyclopropylmethyl group in naltrexone (1d) was effected in the presence of platinum (IV) oxide and hydrobromic acid under a hydrogen atmosphere at rt to selectively afford N-isobutyl derivative 10. The binding affinity of N-i-Bu derivative 10 for opioid receptors was 11 17 times less than that of the corresponding N-CPM compound, naltrexone (1d). However, compound 10 showed dose-dependent analgesic effects. Contrary to expectations based on previous structure-activity relationship studies for a series of N-substituted naltrexone derivatives that compound 10 would be an opioid antagonist, 10 showed dose-dependent analgesia in the mouse acetic acid writhing test (ED50: 5.05 mg/kg, sc), indicating it was an opioid agonist. This finding may have a great influence on the drug design of opioid agonists. (C) 2008 Elsevier Ltd. All rights reserved.