3-deoxy-7,8-dihydromorphine | 55592-68-2

• 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: 3-deoxy-7,8-dihydromorphine
• 英文别名: 4,5-epoxy-17-methylmorphinan-6-ol；7,8-dihydro-3-desoxymorphine；3-Desoxydihydromorphin；4,5α-epoxy-17-methyl-morphinan-6α-ol；(4R,4aR,7S,7aR,12bS)-3-methyl-2,4,4a,5,6,7,7a,13-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-ol
• CAS: 55592-68-2
• 化学式: C₁₇H₂₁NO₂
• 分子量: 271.359
• InChiKey: OJHQLDQVBAFNJM-ZWRJDUBHSA-N

物化性质

• 沸点：
  431.9±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：
  0.65
• 拓扑面积：
  32.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-deoxy-7,8-dihydromorphine 在 盐酸 、 sodium periodate 、 lithium aluminium tetrahydride 、 二苯甲酮 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 乙酸乙酯 、 叔丁醇 、 苯 为溶剂， 反应 26.83h， 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：

  硫酸吗啡 在 palladium on activated charcoal 氢气 、 二乙胺 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 72.0h， 生成 3-deoxy-7,8-dihydromorphine
  参考文献：
  名称：

  钯在温和条件下对碳-二乙胺介导的苯酚衍生物的加氢脱氧作用

  摘要：

  我们发现，在二乙胺存在下，在Pd / C催化的氢化条件下，酚羟基很容易通过芳基磺酸盐脱氧，该方法也可用于吗啡的加氢脱氧，得到3-deoxy-7,8-dihydromorphine 。二乙胺不仅是在反应过程中产生的相应甲磺酸衍生物的清除剂，而且还是Pd / C催化的芳基磺酸盐还原的强促进剂。该催化剂体系由于其温和的反应条件，易于处理并且不需要特定的设备，因此可以为各种酚衍生物的脱氧提供通用的方法。

  DOI：

  10.1016/j.tet.2006.11.060

文献信息

• Early Process Development and Scale-Up of Orally Active Apomorphine Drug Candidates
  作者：Ekaterina Y. Melikhova、Nolwenn Derrien、Nadia Fleary-Roberts、Siân M. Forsyth、Sofia Papadouli、Antonio M. Ruda、Vargini G. Thangavadivale、Simon N. G. Tyler、Jonathan D. Moseley

  DOI：10.1021/acs.oprd.2c00297

  日期：2023.1.20

  steps were substantially redeveloped with alternative reagents. Now relying solely on crystallizations for isolation, the yield, purity, and color of each intermediate was greatly improved. All six process steps were easily transferred to the pilot plant with only minimal accommodation work required prior to manufacture on a 20–50 L scale per batch. Thus, the manufacturing campaign performed essentially

  新型阿扑吗啡帕金森氏症候选药物 (MCL-509) 的制造路线已从 mg 实验室规模发展到适用于 20-50 L 规模的规模。虽然无法改进合成顺序，但所有六个反应步骤都需要显着改进才能扩大规模。去除了有害和有毒的试剂以及有害的步骤；去除所有浓缩至干燥和层析纯化；隔离在操作上得到简化，工厂周期时间缩短。两对步骤（1 和 2；5 和 6）被成功地压缩，并且重新设想了步骤 3、4 和 5，以便所有三个步骤都用替代试剂进行了实质性的重新开发。现在完全依靠结晶分离，每个中间体的产率、纯度和颜色都有了很大的提高。所有六个工艺步骤都可以很容易地转移到中试工厂，在以每批次 20-50 L 的规模进行生产之前，只需要进行最少的调整工作。因此，制造活动基本上按预期进行，没有出现问题，同时材料产量增加了大约 10 倍，同时还实现了必要的质量改进。
• Opioids and Efflux Transporters. Part 2: P-Glycoprotein Substrate Activity of 3- and 6-Substituted Morphine Analogs
  作者：Christopher W. Cunningham、Susan L. Mercer、Hazem E. Hassan、John R. Traynor、Natalie D. Eddington、Andrew Coop

  DOI：10.1021/jm701457j

  日期：2008.4.1

  Continuing our studies investigating opioids with reduced P-glycoprotein (P-gp) substrate activity, a series of known 3- and 6-hydroxy, -methoxy, and -desoxymorphine analogs was synthesized and analyzed for Pgp substrate activity and opioid binding affinity. 6-Desoxymorphine (7) showed high affinity for opioid receptors and did not induce P-gp-mediated ATP hydrolysis. Additionally, 7 demonstrated morphine-like antinociceptive potency in mice, indicating this compound as an ideal lead to further evaluate the role of P-gp in opioid analgesic tolerance development.
• (-)-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：——