17-cyclopropylmethyl-4,5α-epoxy-3-methoxymorphinan-6β,14β-diol | 65150-66-5

• 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: 17-cyclopropylmethyl-4,5α-epoxy-3-methoxymorphinan-6β,14β-diol
• 英文别名: (4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-9-methoxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,7-diol
• CAS: 65150-66-5
• 化学式: C₂₁H₂₇NO₄
• 分子量: 357.45
• InChiKey: UOUQRGSISDNGKD-GQHLEUQBSA-N

物化性质

• 沸点：
  543.3±50.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  62.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  17-cyclopropylmethyl-4,5α-epoxy-3-methoxymorphinan-6β,14β-diol 在 三溴化硼 作用下， 以 氯仿 为溶剂， 反应 60.0h， 生成 6-beta-纳曲醇盐酸盐
  参考文献：
  名称：

  Hosztafi, Sandor; Simon, Csaba; Makleit, Sandor, Heterocycles, 1993, vol. 36, # 7, p. 1509 - 1520

  摘要：

  DOI：
• 作为产物：
  描述：

  在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 0.17h， 以53%的产率得到17-cyclopropylmethyl-4,5α-epoxy-3-methoxymorphinan-6β,14β-diol
  参考文献：
  名称：

  Stereoselective synthesis of β-naltrexol, β-naloxol β-naloxamine, β-naltrexamine and related compounds by the application of the mitsunobu reac

  摘要：

  As a continuation of our work, aimed at adopting the Mitsunobu reaction in the morphine series, a few representatives of dihydroisocodeines and dihydroisomorphines and their 14 beta-hydroxy analogues were prepared. p-Nitrobenzoic acid was used as carboxylic acid and the prepared esters were cleaved to obtain the title compounds. Using phthalimide as acidic component several new 6 beta-phthalimidodihydromorphine and dihydrocodeine derivatives and their 14 beta-hydroxy analogues have been synthesized. Cleavage of the phthalimido derivatives with hydrazine hydrate afforded the corresponding 6 beta-amino derivatives.

  DOI：

  10.1016/s0040-4020(01)85541-1

文献信息

• Hydrogenolysis of the cyclopropyl group into an isopropyl group in the presence of a platinum catalyst and hydrobromic acid
  作者：Hideaki Fujii、Kayoko Okada、Marina Ishihara、Shinichi Hanamura、Yumiko Osa、Toru Nemoto、Hiroshi Nagase

  DOI：10.1016/j.tet.2009.10.064

  日期：2009.12

  Reduction of cyclopropylmethylamines proceeded under mild reaction conditions in the presence of platinum (IV) oxide catalyst and hydrobromic acid at rt, providing isobutylamines and no linear butylamines. The ring cleavage reaction was widely applicable to cyclopropane rings in various compounds such as N-cyclopropylalkyl, O-cyclopropylalkyl, and C-cyclopropylalkyl derivatives. Although unactivated

  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。
• 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.