(5α,6α)-17-(cyclopropylmethyl)-4,5-epoxy-3-methoxymorphinan-6,14-diol | 116388-85-3

• 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: (5α,6α)-17-(cyclopropylmethyl)-4,5-epoxy-3-methoxymorphinan-6,14-diol
• 英文别名: 3-O-methyl-6α-naltrexol；17-cyclopropylmethyl-4,5α-epoxy-3-methoxymorphinan-6α,14β-diol；Methyl-6-alpha-Naltrexol；(4R,4aS,7S,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: 116388-85-3
• 化学式: C₂₁H₂₇NO₄
• 分子量: 357.45
• InChiKey: UOUQRGSISDNGKD-LAKPAKELSA-N

物化性质

• 熔点：
  147-149 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  543.3±50.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  1.62
• 重原子数：
  26.0
• 可旋转键数：
  3.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  62.16
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (5α,6α)-17-(cyclopropylmethyl)-4,5-epoxy-3-methoxymorphinan-6,14-diol 在 三溴化硼 作用下， 以 氯仿 为溶剂， 反应 2.0h， 生成 3,6α,14-triacetoxy-17-cyclopropylmethyl-4,5α-epoxy-morphinane
  参考文献：
  名称：

  Morphine alkaloids, part 114. A stereohomogeneous synthesis of N-demethyl-N-substituted-14-hydroxydihydromorphines

  摘要：

  A new route for the stereohomogeneous synthesis of N-demethyl-N-substituted-14-hydroxydihydromorphines 2 a - f has been elaborated, involving O-demethylation of the novel dihydrocodeine derivatives 6 a - f, obtained upon alkylation of the hitherto unknown N-demethyl-14-hydroxydihydrocodeine (5).

  DOI：

  10.1007/bf00817599
• 作为产物：
  描述：

  纳曲酮 在 三乙酰氧基硼氢化钠 、 potassium carbonate 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 (5α,6α)-17-(cyclopropylmethyl)-4,5-epoxy-3-methoxymorphinan-6,14-diol
  参考文献：
  名称：

  Synthesis of (−)-Homogalanthamine from Naltrexone

  摘要：

  Acetylcholinesterase inhibitor (-)-homogalanthamine 3 was synthesized from mu opioid antagonist naltrexone (2) in 16% total yield. The synthesis features Grob fragmentation as a key reaction, which was especially accelerated in the presence of 15-crown-5.

  DOI：

  10.1021/jo1022487

文献信息

• Molecular structure of (-)3-acetyl-6.BETA.-(acetylthio)-N-(cyclopropylmethyl) normorphine and its 14-hydroxy congeners.
  作者：Ken KANEMATSU、Takashi YOSHIYASU、Mitsutaka YOSHIDA

  DOI：10.1248/cpb.38.1441

  日期：——

  The stereochemistry of the title compound 3 was confirmed by X-ray analysis. The 6-acetylthio derivatives with an OH group at C-14 were also designed and synthesized.

  标题化合物3的立体化学通过X射线分析得到确认。同时，设计并合成了带有C-14位OH基团的6-乙酰硫代衍生物。
• 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。
• Syntheses and receptor-binding studies of derivatives of the opioid antagonist naltrexone
  作者：Koji Uwai、Hiroko Uchiyama、Shinobu Sakurada、Chizuko Kabuto、Mitsuhiro Takeshita

  DOI：10.1016/j.bmc.2003.10.039

  日期：2004.1

  Naltrexone (1), which is a member of the group of competitive opioid antagonists, shows a strong affinity for mu-receptors and its derivatives have been notable as novel receptor antagonists. In this paper, the preparation of several naltrexone derivatives is described; these were used to investigate the role of the oxygenated functional groups in facilitating binding to a series of the opioid receptors

  纳曲酮（1）是竞争性阿片类药物拮抗剂的成员，对mu受体表现出很强的亲和力，其衍生物作为新型受体拮抗剂也很引人注目。本文描述了几种纳曲酮衍生物的制备方法。这些用于研究含氧官能团在促进与一系列阿片受体结合中的作用。衍生物显示出对阿片类mu受体的亲和力，类似于纳曲酮，但是这些具有掩蔽的羟基官能团的化合物显示出中等活性。这些结果表明，纳曲酮（1）中的每个含氧官能团在与阿片受体结合中都起着重要作用。
• Design, synthesis, and structure–activity relationship of novel opioid κ-agonists
  作者：Koji Kawai、Jun Hayakawa、Toru Miyamoto、Yoshifumi Imamura、Shinichi Yamane、Hisanori Wakita、Hideaki Fujii、Kuniaki Kawamura、Hirotoshi Matsuura、Naoki Izumimoto、Ryosuke Kobayashi、Takashi Endo、Hiroshi Nagase

  DOI：10.1016/j.bmc.2008.09.011

  日期：2008.10

  By focusing on 4,5-epoxymorphinan, a traditional opioid skeleton but a new structure in the opioid kappa-agonist research field, and by rationally applying the 'message-address concept' and 'accessory site hypothesis,' we discovered a new chemical class opioid kappa- gonist, TRK-820 (1). Its development as an antipruritus is now in the final stage. Here, the full scope of its design, synthesis, and structure-activity relationship are described. (C) 2008 Elsevier Ltd. All rights reserved.
• Stereoselective synthesis of β-naltrexol, β-naloxol β-naloxamine, β-naltrexamine and related compounds by the application of the mitsunobu reac
  作者：Csaba Simon、Sándor Hosztafi、Sándor Makleit

  DOI：10.1016/s0040-4020(01)85541-1

  日期：1994.1

  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.