N-methyl 7,8-didehydro-4,5-epoxy-6-hydroxy-3-methoxy-(5α,6α)-morphinan carbamate | 210754-24-8

• 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: N-methyl 7,8-didehydro-4,5-epoxy-6-hydroxy-3-methoxy-(5α,6α)-morphinan carbamate
• 英文别名: N-Desmethyl-N-methoxycarbonyl Codeine >90%；methyl (4R,4aR,7S,7aR,12bS)-7-hydroxy-9-methoxy-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-3-carboxylate
• CAS: 210754-24-8
• 化学式: C₁₉H₂₁NO₅
• 分子量: 343.379
• InChiKey: ILZZMMLYELRJKX-IWKDVGJASA-N

物化性质

• 溶解度：
  可溶于氯仿（少许）、可溶于二氯甲烷、乙酸乙酯、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  68.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-methyl 7,8-didehydro-4,5-epoxy-6-hydroxy-3-methoxy-(5α,6α)-morphinan carbamate 在 L-Selectride 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以56%的产率得到去甲吗啡
  参考文献：
  名称：

  L-Selectride as a General Reagent for the O-Demethylation and N-Decarbomethoxylation of Opium Alkaloids and Derivatives¹

  摘要：

  L-Selectride was shown to be an efficient and general O-demethylating agent for the opium alkaloids and their derivatives and also an efficient reagent for the cleavage of methyl carbamates, thus offering a convenient method for the N-demethylation of opioids. Further, it was shown that by choice of reaction conditions it is possible to achieve both N-decarbomethoxylation and O-demethylation in one pot, or only render N-decarbomethoxylation in high yield without accompanying O-demethylation.

  DOI：

  10.1021/jo9801972
• 作为产物：
  描述：

  氯甲酸甲酯 、 可待因 在 碳酸氢钠 作用下， 以 氯仿 为溶剂， 反应 2.25h， 以99%的产率得到N-methyl 7,8-didehydro-4,5-epoxy-6-hydroxy-3-methoxy-(5α,6α)-morphinan carbamate
  参考文献：
  名称：

  对β-阿片和β-阿片受体具有拮抗活性的7β-羟基-8-酮阿片衍生物的合成

  摘要：

  尽管进行了多年的研究，到目前为止，阿片类药物的7,8-双键的直接氧化一直很少受到关注，并且关于这种修饰对不同阿片类药物受体活性的影响的知识很少。本文我们报告支撑在铁高锰酸钾（II）七水硫酸可以用作在一工序的方便氧化剂，异构Δ转换7,8--阿片类药物对应的7β-羟基-8-酮。给出了详细的反应机理，并讨论了几种阿片类药物第6位的取代基对反应结果的影响。所制备的阿片样物质羟基酮是μ阿片和δ阿片样物质受体的拮抗剂。对接模拟和详细的结构活性分析表明，所制备化合物中7β-羟基-8-酮官能团的存在可用于获得针对δ阿片受体的活性。用这种方法制备的7β-羟基-8-酮也可以被认为是合成其他目的阿片类药物的通用中间体。

  DOI：

  10.1016/j.ejmech.2018.02.074

文献信息

• Photochemistry of Structurally-Modified Morphine Alkaloids
  作者：Arthur G. Schultz、David M. Graves、Neal J. Green、Richard R. Jacobson、Deanne M. Nowak

  DOI：10.1021/ja00102a011

  日期：1994.11

  N-Carbomethoxynorcodeinone (1b) was found to be unreactive to photolysis in benzene solution, but irradiation (366 nm) in the presence of methanol, water, ethanol, or n-propyl alcohol gave the rearranged and solvent-incorporated phenols 13a-d. Under comparable photolysis conditions, N-carbomethoxynordihydrocodeinone (33) did not photorearrange at 366 or > 300 nm. Spirocyclopropane 15b is proposed to be an intermediate in this photorearrangement; addition of ROH to 15b occurs by nucleophilic attack with inversion of configuration at the cyclopropane carbon atom most able to stabilize a positive charge. In the absence of a suitable nucleophile (benzene or t-BuOH solutions) 15b reverts to 1b. Irradiation of the C(5)-methyl-substituted codeinone derivative 17a in methanol solution did not result in solvent incorporation, but rather gave the benzopyran 21a in quantitative yield by way of the intermediate dienone 20a. The carbamate 17b gave separable mixtures of 20b and 21b; dienone 20b was converted to benzopyran 21b in quantitative yield by treatment with diethylamine in CH2Cl2. Additional examples of this tandem photorearrangement-hydrogen atom transfer-intramolecular conjugate addition are described; e.g., 22 --> 24 and 25 --> 26. Photolysis of 1b in the presence of acetic acid gives a mixture of the solvent-incorporated phenol 27 and 8,9-dihydro-2-methoxy-7-carbomethoxydibenz[d,f]azonine-1,13-diol (28). The less nucleophilic oxalic acid provides a route to 28 free of solvent-incorporated products analogous to 27. The facial specific photoadditions of THF to enones 13b and 1b to give 30 and 31 occur by hydrogen atom transfer from C(2) of THF to the photosubstrate followed by radical coupling at the beta-position of the enone. The molecular structure and novel crystal packing arrangement of the monohydrate of 30 were determined by an X-ray diffraction study. Enones 1b and 17b also undergo SET-type photoreductions in the presence of triethylamine (TEA) to give alpha-thebainone derivatives 32a and 32b. A mechanism is proposed to account for photoproduct distributions when irradiations are carried out in the presence of varying amounts of both methanol and TEA. It was found that codeine is as effective as TEA in promoting the photoreduction of 1b to the alpha-thebainone derivative 32a. Opportunities for the utilization of the photochemistry of modified morphine alkaloids for approaches to opiate receptor photoaffinity labeling and the provision of new substrates for opiate receptor affinity studies are briefly discussed.
• L-Selectride as a General Reagent for the O-Demethylation and N-Decarbomethoxylation of Opium Alkaloids and Derivatives¹
  作者：Andrew Coop、James W. Janetka、John W. Lewis、Kenner C. Rice

  DOI：10.1021/jo9801972

  日期：1998.6.1

  L-Selectride was shown to be an efficient and general O-demethylating agent for the opium alkaloids and their derivatives and also an efficient reagent for the cleavage of methyl carbamates, thus offering a convenient method for the N-demethylation of opioids. Further, it was shown that by choice of reaction conditions it is possible to achieve both N-decarbomethoxylation and O-demethylation in one pot, or only render N-decarbomethoxylation in high yield without accompanying O-demethylation.
• Synthesis of 7β-hydroxy-8-ketone opioid derivatives with antagonist activity at mu- and delta-opioid receptors
  作者：Tiina J. Ahonen、Maiju Rinne、Peter Grutschreiber、Kert Mätlik、Mikko Airavaara、Dieter Schaarschmidt、Heinrich Lang、David Reiss、Henri Xhaard、Claire Gaveriaux-Ruff、Jari Yli-Kauhaluoma、Vânia M. Moreira

  DOI：10.1016/j.ejmech.2018.02.074

  日期：2018.5

  prepared are antagonists at the mu- and delta-opioid receptors. Docking simulations and detailed structure-activity analysis revealed that the presence of the 7β-hydroxy-8-ketone functionality in the prepared compounds can be used to gain activity towards the delta opioid receptor. The 7β-hydroxy-8-ketones prepared with this method can also be regarded as versatile intermediates for the synthesis of other

  尽管进行了多年的研究，到目前为止，阿片类药物的7,8-双键的直接氧化一直很少受到关注，并且关于这种修饰对不同阿片类药物受体活性的影响的知识很少。本文我们报告支撑在铁高锰酸钾（II）七水硫酸可以用作在一工序的方便氧化剂，异构Δ转换7,8--阿片类药物对应的7β-羟基-8-酮。给出了详细的反应机理，并讨论了几种阿片类药物第6位的取代基对反应结果的影响。所制备的阿片样物质羟基酮是μ阿片和δ阿片样物质受体的拮抗剂。对接模拟和详细的结构活性分析表明，所制备化合物中7β-羟基-8-酮官能团的存在可用于获得针对δ阿片受体的活性。用这种方法制备的7β-羟基-8-酮也可以被认为是合成其他目的阿片类药物的通用中间体。