(-)-4-methoxy-6-keto-N-methylmorphinan | 79798-40-6

• 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-methoxy-6-keto-N-methylmorphinan
• 英文别名: (-)-4-methoxy-N-methylmorphinan-6-one；4-methoxy-17-methylmorphinan-6-one；4-methoxy-N-methylmorphinan-6-one；(+)-4-methoxy-6-keto-N-methylmorphinan；(+/-)-4-methoxy-N-methylmorphinan-6-one；(1S,9R,10R)-3-methoxy-17-methyl-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-13-one
• CAS: 79798-40-6
• 化学式: C₁₈H₂₃NO₂
• 分子量: 285.386
• InChiKey: IADSKKCDIYLTIM-DAYGRLMNSA-N

物化性质

• 沸点：
  445.2±45.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 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-methoxy-6-keto-N-methylmorphinan 在 三溴化硼 作用下， 以 氯仿 为溶剂， 反应 2.0h， 以68%的产率得到(+/-)-4-hydroxy-N-methylmorphinan-6-one
  参考文献：
  名称：

  A simplified synthesis of (.+-.)-4-hydroxy-N-methylmorphinan-6-one

  摘要：

  DOI：

  10.1021/jo00147a039
• 作为产物：
  描述：

  4,5-epoxy-17-methylmorphinan-6-one 在 氯化铵 、 锌 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 (-)-4-methoxy-6-keto-N-methylmorphinan
  参考文献：
  名称：

  (-)-4-Hydroxymorphinanones: their synthesis and analgesic activity

  摘要：

  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.

  DOI：

  10.1021/jm00144a013

文献信息

• Structure-Activity Relationships of Oxygenated Morphinans. I. 4-Mono- and 3,4-dimethoxy-N-methylmorphinans and -N-methyl-morphinan-6-ones with unusually high antinociceptive potency. Preliminary communication
  作者：Arthur E. Jacobson、Fu-Lian Hsu、Maria D. Rozwadowska、Helmut Schmidhammer、Louise Atwell、Arnold Brossi、Fedor Medzihradsky

  DOI：10.1002/hlca.19810640506

  日期：1981.7.22

  The antinociceptive potency and receptor affinity of several optically active aromatic mono- and di-oxygenated N-methylmorphinans and N-methylmorphinan-6-ones, prepared from natural morphine, were determined. Thus, in order of antinociceptive potency, 4-methoxy-N-methylmorphinan-6-one ≈ 3,4-dimethoxy-N-methylmorphinan-6-one ≈ 3,4-dimethoxy-N-methylmorphinan > 4-methoxy-N-methylmorphinan ≈ 4-acetox

  测定了由天然吗啡制得的几种光学活性芳族单加氧和双加氧的N-甲基吗啡喃和N-甲基吗啡喃-6-的抗伤害力和受体亲和力。因此，在镇痛效力的次序，4-甲氧基Ñ -methylmorphinan -6-酮≈3,4-二甲Ñ -methylmorphinan -6-酮≈3,4-二甲Ñ -methylmorphinan> 4-甲氧基- ñ -甲基吗啡喃≈4-乙酰氧基-N-甲基吗啡喃-6->> 4-乙酰氧基-N-甲基吗啡喃≈4-羟基-N-甲基吗啡喃-6-一个≈4-羟基-N-甲基吗啡喃。4-羟基化合物的效力比吗啡稍弱，发现4-甲氧基和3,4-二甲氧基化合物的效力是吗啡的三倍。4-甲氧基-N-甲基吗啡喃-6-的阿片受体亲和力为吗啡的三分之一；这对非酚类化合物具有极高的亲和力。
• 6-Keto-morphinan analgesics
  申请人：The United States of America as represented by Secretary of the

  公开号：US04388463A1

  公开（公告）日：1983-06-14

  This patent application describes the preparation and properties of novel and highly potent morphinan analgesics. The compounds include narcotic agnoists as well as narcotic antagonists and are represented by the following formula: ##STR1## R.sub.1 =OCH.sub.3, OCOCH.sub.3, H R.sub.2 =CH.sub.3, CH.sub.2 --CH.dbd.CH.sub.2, ##STR2## CH.sub.2 CH.sub.2 C.sub.6 H.sub.5

  这项专利申请描述了新型和高效的吗啡类镇痛剂的制备和性质。这些化合物包括麻醉药激动剂和麻醉药拮抗剂，并由以下公式代表：##STR1## R.sub.1 =OCH.sub.3, OCOCH.sub.3, H R.sub.2 =CH.sub.3, CH.sub.2 --CH.dbd.CH.sub.2, ##STR2## CH.sub.2 CH.sub.2 C.sub.6 H.sub.5
• Total Synthesis of (±)-3-Deoxy-7,8-dihydromorphine, (±)-4-Methoxy-N-methylmorphinan-6-one and 2,4-Dioxygenated (±)-Congeners
  作者：Fu-Lian Hsu、Kenner C. Rice、Arnold Brossi

  DOI：10.1002/hlca.19820650531

  日期：1982.7.28

  A total synthesis of racemic 3-deoxy-7,8-dihydromorphine ((±)-2) and 4-me-thoxy-ALmethylmorphinan-6-one ((±)-3) is described. The key intermediate was 2,4-dihydroxy-N-formylmorphinan-6-one (11), obtained from 3,5-dibenzyloxy-phenylacetic acid (4) in 41.8% overall yield. Bromination of 11, and treatment with aqueous NaOH-solution afforded, after N-deblocking and reductive N-methylation with concomitant

  描述了外消旋的3-脱氧-7,8-二氢吗啡（（±）-2）和4-甲氧基-AL甲基吗啡喃-6-一（（±）-3）的全合成。关键中间体是2,4-二羟基-N-甲酰基吗啡喃-6-一（11），由3,5-二苄氧基-苯乙酸（4）获得，总收率为41.8％。进行11的溴化和N的OH溶液处理，然后进行N脱嵌段和还原性N甲基化，并同时除去芳族结合的Br原子吗啡酮14。消除了HO–C（2）基团14是通过氢解其N-苯基四唑基醚15，得到3-脱氧-6,0-二脱氢-7,8-二氢吗啡（16）。在低温下用L-Selectride还原16可获得高产（±）-2。在更剧烈的还原条件下，醚15直接提供4-羟基-N-甲基吗啡喃6-1 （17）。在17的O-甲基化之后，获得甲基醚（±）-3。4-羟基-2-甲氧基-N-甲基mor-phinan-6-one （28）及其2-羟基-4-甲氧基异构体30的（1：1）混合物svere通过类似于这提供一
• Antitussive 6-keto morphinans of the (+)-series
  申请人：The United States of America as represented by the Department of Health

  公开号：US04552962A1

  公开（公告）日：1985-11-12

  The present invention is concerned with dextrorotatory morphinans, which are illustrated by (+)-4-methoxy-6-keto-N-methylmorphinan. Related compounds which also have been introduced as cough-suppressing agents include the (+)-3-methoxy-N-methylmorphinans (ROMILAR-Roche).

  本发明涉及右旋型吗啡类化合物，其中包括(+)-4-甲氧基-6-酮-N-甲基吗啡烷。相关的化合物也已被引入作为止咳剂，其中包括(+)-3-甲氧基-N-甲基吗啡烷（ROMILAR-Roche）。
• US4388463A
  申请人：——

  公开号：US4388463A

  公开（公告）日：1983-06-14