7,8-didehydro-4,5-epoxy-17-methyl-(5α,6α)-morphinan-3,6-diol 3-benzoate | 105092-16-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: 7,8-didehydro-4,5-epoxy-17-methyl-(5α,6α)-morphinan-3,6-diol 3-benzoate
• 英文别名: 3-O-Benzoylmorphine；3-benzoyloxy-4,5α-epoxy-17-methyl-morphin-7-en-6α-ol；Benzoylmorphin；[(4R,4aR,7S,7aR,12bS)-7-hydroxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl] benzoate
• CAS: 105092-16-8
• 化学式: C₂₄H₂₃NO₄
• 分子量: 389.451
• InChiKey: KGZMFAAGEXEBLP-MEOVSQSXSA-N

物化性质

• 沸点：
  598.1±50.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.38
• 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：

  7,8-didehydro-4,5-epoxy-17-methyl-(5α,6α)-morphinan-3,6-diol 3-benzoate 在 palladium on activated charcoal 氢气 作用下， 生成 4,5-epoxy-17-methyl-(5α,6α)-morphinan-3,6-diol 3-benzoate
  参考文献：
  名称：

  Opiate receptor binding properties of morphine-, dihydromorphine-, and codeine 6-O-sulfate ester congeners

  摘要：

  A series of 3-O-acyl-6-O-sulfate esters of morphine, dihydromorphine, N-methylmorphinium iodide, codeine, and dihydrocodeine were prepared and evaluated for their ability to bind to mu-, delta-, kappa(1)-, kappa(2)-, and kappa(3)-opiate receptors. Several compounds exhibited good affinity for the p-opiate receptor. Morphine-3-O-propionyl-6-O-sulfate had four times greater affinity than morphine at the mu-opiate receptor and was the most selective compound at this receptor subtype. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.05.060
• 作为产物：
  描述：

  苯甲酰氯 、 吗啡 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以77%的产率得到7,8-didehydro-4,5-epoxy-17-methyl-(5α,6α)-morphinan-3,6-diol 3-benzoate
  参考文献：
  名称：

  吗啡苯甲酸酯及其衍生物的制备

  摘要：

  摘要持续镇痛对于遭受长效疼痛的患者至关重要。吗啡的酯衍生物可以增强吗啡的亲脂性。因此，其透皮递送及其作用持续时间也增加了。因此，二十一3- O-，6- O-和14- O合成了吗啡的苯甲酸酯及其衍生物，以阐明适用于这些广泛使用的化合物进行酯化的不同合成方法。Schotten-Baumann反应与碳酸氢钠，三乙胺或吡啶在二氯甲烷或1,2-二氯乙烷中的溶剂一起应用。主要在叔醇的情况下也成功地利用了4-二甲基氨基吡啶催化剂的存在。还提出了通过不含副产物的二乙酰基吗啡合成二氢吗啡的新方法。通过1 H核磁共振（NMR），13 C NMR，高分辨率质谱（HRMS）和电子电离质谱（EI-MS）阐明了所有合成化合物的结构。日志 D通过反相高效液相色谱（HPLC）–MS方法测定合成化合物的（pH 7.4）值，并提供计算出的水解速率常数。合成的苯甲酸酯是母体吗啡的潜在前药，具有增强的亲脂性，这些衍生物也可用于经皮给药，作为预期的长效麻醉镇痛药。

  DOI：

  10.1007/s00706-012-0803-8

文献信息

• 6-O-Glycosylation of Morphine Derivatives Using Thioglycosides as Glycosyl Donors
  作者：Igor Rukhman、Lev Yudovich、Gennadiy Nisnevich、Arie L. Gutman

  DOI：10.1055/s-2000-6413

  日期：——

  A novel approach was developed for the synthesis of the pharmaceutically important morphine and dihydromorphine 6-β-d-glucuronides. The key step involves a selective 6-O-glycosylation of 3-O-protected morphines and dihydromorphines with thioglycosides that serve as glycosyl donors in the presence of thiophilic promoters. This novel approach may be useful for the O-glycosylation of other alkaloid derivatives.

  针对合成在医药领域重要的吗啡和二氢吗啡-6-β-d-葡萄糖醛酸苷，开发了一种新颖的方法。关键步骤包括在硫亲和助推剂存在下，利用硫代糖苷作为糖基供体，对3-O-保护的吗啡和二氢吗啡进行选择性的6-O-糖基化反应。这一新颖方法可能对其他生物碱衍生物的O-糖基化具有应用价值。
• Morphine-6-sulfate analogues and their use for the treatment of pain
  申请人：The University of Kentucky Research Foundation

  公开号：US06403602B1

  公开（公告）日：2002-06-11

  3-O-Acetylmorphine-6-sulfate analogues are potent, centrally-acting morphine derivatives. The compounds are useful for the treatment of pain.

  3-O-乙酰基吗啡-6-硫酸盐类似物是有效的、中枢作用的吗啡衍生物。这些化合物可用于治疗疼痛。
• Medical contact adhesive comprising a two phase adhesive matrix of polyacrylates and polyamine salts
  申请人：——

  公开号：US20040010054A1

  公开（公告）日：2004-01-15

  A medical pressure sensitive adhesive based on polyacrylates and neutral polyamine salts is characterized in that it has a pressure-sensitive adhesive matrix of two polymer components A and B, with polymer component A being a polyacrylate pressure-sensitive adhesive containing carboxyl groups, the carboxyl groups of which are neutralised; the polymer component B being a neutral polyamine salt obtained by reacting a polyacrylate copolymer containing amino groups with an acid, with the polymer component B being dispersed in the polymer component A, and the two components forming a two-phase system.

  一种基于聚丙烯酸酯和中性聚胺盐的医用压敏胶，其特征在于它的压敏胶基体由两种聚合物组分 A 和 B 组成，其中聚合物组分 A 是含有羧基的聚丙烯酸酯压敏胶，其羧基被中和；聚合物组分 B 是由含有氨基的聚丙烯酸酯共聚物与酸反应得到的中性聚胺盐，聚合物组分 B 分散在聚合物组分 A 中，两种组分形成两相体系。
• Late-Stage Deoxyfluorination of Alcohols with PhenoFluor
  作者：Filippo Sladojevich、Sophie I. Arlow、Pingping Tang、Tobias Ritter

  DOI：10.1021/ja3125405

  日期：2013.2.20

  An operationally simple protocol for the selective deoxyfluorination of structurally complex alcohols is presented. Several fluorinated derivatives of natural products and pharmaceuticals have been prepared to showcase the potential of the method for late-stage diversification and its functional group compatibility. A series of simple guidelines for predicting the selectivity in substrates with multiple alcohols is given.
• Merck, E. Merck's Jahresberichte, 1898, p. 20
  作者：Merck

  DOI：——

  日期：——