4,5-epoxy-17-methylmorphinan-6-one | 32295-31-1

• 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: 4,5-epoxy-17-methylmorphinan-6-one
• 英文别名: 4,5-epoxy-N-methylmorphinan-6-one；(4S,4aR,7aR,12bR)-3-methyl-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one；4,5α-epoxy-17-methylmorphinan-6-one；(4R,4aR,7aR,12bS)-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• CAS: 32295-31-1
• 化学式: C₁₇H₁₉NO₂
• 分子量: 269.343
• InChiKey: FLMGOWMGQLPFSR-LZDSYCOUSA-N

物化性质

• 沸点：
  431.4±45.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4,5-epoxy-17-methylmorphinan-6-one 在 盐酸 、 sodium periodate 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 乙酸乙酯 、 叔丁醇 、 苯 为溶剂， 反应 26.0h， 生成 3-deoxymorphine
  参考文献：
  名称：

  Deoxymorphines: role of the phenolic hydroxyl in antinociception and opiate receptor interactions

  摘要：

  Several 3-deoxy opioids and 3,6-dideoxydihydromorphine was synthesized to ascertain the effect of the phenolic hydroxyl group on antinociceptive potency and receptor binding affinity. Catalytic reduction of the 3-tetrazolyl ether derivatives of dihydromorphine provided the entry into the 3-deoxydihydro series. The prototype, 3-deoxymorphine, was prepared by lithium aluminum hydride reduction of 3-deoxy-N-carbethoxymorphinone, obtained via its 7-(phenylseleno) derivative. 3-Deoxydihydromorphinone and 3,6-dideoxydihydromorphine were found to be about as potent as, or more potent than, morphine in standard antiociceptive assays. Each of them, however, was less potent than the comparable 3-hydroxy analogue, and their binding affinity to the opiate receptor was substantially decreased. The epoxy ring in 3.6-dideoxydihydromorphine was found to increase the antinociceptive potency of the compound.

  DOI：

  10.1021/jm00189a007
• 作为产物：
  描述：

  氢吗啡酮 在 甲酸 、 palladium diacetate 、 三乙胺 、 三苯基膦 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4,5-epoxy-17-methylmorphinan-6-one
  参考文献：
  名称：

  A Stable Heroin Analogue That Can Serve as a Vaccine Hapten to Induce Antibodies That Block the Effects of Heroin and Its Metabolites in Rodents and That Cross-React Immunologically with Related Drugs of Abuse

  摘要：

  An improved synthesis of a haptenic heroin surrogate 1 (6-AmHap) is reported. The intermediate needed for the preparation of 1 was described in the route in the synthesis of 2 (DiAmHap). A scalable procedure was developed to install the C-3 amido group. Using the Boc protectng group in 18 allowed preparation of 1 in an overall yield of 53% from 4 and eliminated the necessity of preparing the diamide 13. Hapten 1 was conjugated to tetanus toxoid and mixed with liposomes containing monophosphoryl lipid A as an adjuvant. The 1 vaccine induced high anti-1 IgG levels that reduced heroin-induced antinociception and locomotive behavioral changes following repeated subcutaneous and intravenous heroin challenges in mice and rats. Vaccinated mice had reduced heroin-induced hyperlocomotion following a 50 mg/kg heroin challenge. The 1 vaccine induced antibodies bound to heroin and other abused opioids, including hydrocodone, oxycodone, hydromorphone, oxymorphone, and codeine.

  DOI：

  10.1021/acs.jmedchem.7b01427

文献信息

• (−)-4-Hydroxy-<i>N</i>-formylmorphinan-6-one, a versatile intermediate for the synthesis of 3-deoxyopioids
  作者：Maria D. Rozwadowska、Fu-Lian Hsu、Arthur E. Jacobson、Kenner C. Rice、Arnold Brossi

  DOI：10.1139/v80-292

  日期：1980.9.1

  (−)-4-Hydroxy-N-formylmorphinan-6-one (4) was prepared in 70% overall yield from ketone 1, via carbamate 2, and N-formylation of ketone 3. Bromination of 4 afforded either the 6-ketomorphinan 7 or the ketone 8, depending on the reaction conditions applied. Both bromo ketones 7 and 8 could be converted by standard reactions into 4,5-epoxy-N-methylmorphinan-6-one (1). The ketomorphinan 4 emerges from these investigations as a versatile intermediate, well suited for the synthesis of 4-hydroxymorphinans and 3-deoxyopioids.

  (-)-4-羟基-N-甲酰吗啡酮-6-酮（4）从酮1通过碳酸酯2和酮3的N-甲酰化反应，总产率为70%制备而成。4的溴化反应产物可以得到6-酮吗啡酮7或酮8，具体取决于所采用的反应条件。两种溴化酮7和8均可通过标准反应转化为4,5-环氧-N-甲基吗啡酮-6-酮（1）。这些研究表明，酮吗啡酮4是一种多功能中间体，非常适合用于合成4-羟基吗啡酮和3-去氧阿片类药物。
• Synthesis and immunological effects of heroin vaccines
  作者：Fuying Li、Kejun Cheng、Joshua F. G. Antoline、Malliga R. Iyer、Gary R. Matyas、Oscar B. Torres、Rashmi Jalah、Zoltan Beck、Carl R. Alving、Damon A. Parrish、Jeffrey R. Deschamps、Arthur E. Jacobson、Kenner C. Rice

  DOI：10.1039/c4ob01053a

  日期：——

  Multi-step syntheses provided three designed haptens for vaccines that were evaluated for their ability to block the effects of heroin and its metabolites.

  多步合成提供了三种设计的半抗原用于疫苗，评估它们是否能够阻断海洛因及其代谢物的作用。
• (-)-4-Hydroxymorphinanones: their synthesis and analgesic activity
  作者：Awinash Manmade、Haldean C. Dalzell、John F. Howes、Raj K. Razdan

  DOI：10.1021/jm00144a013

  日期：1981.12

  A facile procedure is described for the conversion of morphine, via the diphosphate ester derivative 1 followed by catalytic reduction and treatment with Li/NH3, to 3-deoxy-7,8-dihydromorphine (3). Oxidation with benzophenone tert-butoxide converted 3 to the ketone 4, which on treatment with Zn/NH4Cl formed (-)-4-hydroxymorphinan-6-one 5. Reaction of 5 with diazomethane formed the methyl ether 6. The N-cyclopropylmethyl analogues of 4 and 5 were also prepared, i.e., 8c and 9 from 4. The antinociceptive activity of these compounds was tested. Compounds 5, 6, 8c, and 9 showed potent antiwrithing activity and, based on these data, a structure-activity relationship in morphinans is discussed.
• Hsu,F.-L. et al., Heterocycles, 1979, vol. 13, p. 259 - 261
  作者：Hsu,F.-L. et al.

  DOI：——

  日期：——
• Synthesis of quinolinomorphinan-4-ol derivatives as δ opioid receptor agonists
  作者：Yoshihiro Ida、Toru Nemoto、Shigeto Hirayama、Hideaki Fujii、Yumiko Osa、Masayuki Imai、Takashi Nakamura、Toshiyuki Kanemasa、Akira Kato、Hiroshi Nagase

  DOI：10.1016/j.bmc.2011.11.047

  日期：2012.1

  The previously reported morphinan derivative SN-28 showed high selectivity and agonist activity for the delta opioid receptor. In the course of examining the structure-activity relationship of SN-28 derivatives, the derivatives with the 4-hydroxy group (SN-24, 26, 27) showed higher selectivities for the 8 receptor over the mu receptor than the corresponding SN-28 derivatives with the 3-hydroxy group (SN-11, 23, 28). Derivatives with the 4-hydroxy group showed potent agonist activities for the 5 receptor in the [S-35]GTPyS binding assay. Although the 17-cyclopropylmethyl derivative (SN-11) with a 3-hydroxy group showed the lowest selectivity for the delta receptor among the morphinan derivatives, the agonist activity toward the delta receptor was the most potent for candidates with the 3-hydroxy group. (C) 2011 Elsevier Ltd. All rights reserved.