(6aR)-1,2,9,10-四甲氧基-6-甲基-5,6,6A,7-四氢-4H-二苯并[De,G]喹啉 | 38325-02-9

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 阿朴菲
• 中文名称: (6aR)-1,2,9,10-四甲氧基-6-甲基-5,6,6A,7-四氢-4H-二苯并[De,G]喹啉
• 英文名称: (-)-(R)-glaucine
• 英文别名: (R)-5,6,6a,7-Tetrahydro-1,2,9,10-tetramethoxy-6-methyl-4H-dibenzo(de,g)quinoline；(6aR)-1,2,9,10-tetramethoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline
• CAS: 38325-02-9
• 化学式: C₂₁H₂₅NO₄
• mdl: MFCD00067283
• 分子量: 355.434
• InChiKey: RUZIUYOSRDWYQF-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  40.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (6aR)-1,2,9,10-四甲氧基-6-甲基-5,6,6A,7-四氢-4H-二苯并[De,G]喹啉 以 N,N-二甲基甲酰胺 为溶剂， 反应 168.0h， 以100%的产率得到去氢海罂粟碱
  参考文献：
  名称：

  Microbial transformations in organic synthesis. 4. Stereoselective fungal metabolism of 7-methylglaucine

  摘要：

  DOI：

  10.1021/jo00360a020
• 作为产物：
  描述：

  阿曲库铵杂质N 在 chromium(III) oxide 、 三氟化硼乙醚 、 三氟乙酸 、 三氟乙酸酐 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 以83%的产率得到(6aR)-1,2,9,10-四甲氧基-6-甲基-5,6,6A,7-四氢-4H-二苯并[De,G]喹啉
  参考文献：
  名称：

  Enantioselective synthesis of (R)-(−)-laudanosine and (R)-(−)-glaucine from L-ascorbic acid

  摘要：

  L-Ascorbic acid 1 was converted into L-gulonolactone 2 by catalytic hydrogenation. Treatment of 2 with 3,4-dimethoxyphenylethyl amine 3 afforded amide 4, which in several steps was transformed into the title alkaloids in good enantiomeric excesses. Also, chromium(III) oxide is proposed as an effective catalyst for the conversion of (R)-(-)-laudanosine into (R)-(-)-glaucine. Copyright (C) 1996 Published by Elsevier Science Ltd

  DOI：

  10.1016/0957-4166(96)00349-7

文献信息

• In vitro functional evaluation of isolaureline, dicentrine and glaucine enantiomers at 5-HT₂ and α₁ receptors
  作者：Hui Li Heng、Chin Fei Chee、Chun Keng Thy、Jia Ti Tee、Sek Peng Chin、Deron R. Herr、Michael J. C. Buckle、Ian C. Paterson、Stephen W. Doughty、Noorsaadah Abd. Rahman、Lip Yong Chung

  DOI：10.1111/cbdd.13390

  日期：2019.2

  Isolaureline, dicentrine and glaucine enantiomers were synthesized, and their in vitro functional activities at human 5‐HT2 and adrenergic α1 receptor subtypes were evaluated. The enantiomers of isolaureline and dicentrine acted as antagonists at 5‐HT2 and α1 receptors with (R)‐isolaureline showing the greatest potency (pKb = 8.14 at the 5‐HT2C receptor). Both (R)‐ and (S)‐glaucine also antagonized α1 receptors

  与血清素（5-羟色胺）活性的化合物5-HT 2和α 1个肾上腺素能受体有中枢神经系统障碍，药物成瘾或过量的治疗潜力。Isolaureline，荷包牡丹碱和对映体海罂粟碱合成，并且在人的它们的体外功能活性的5-HT 2和肾上腺素能α 1受体亚型进行了评价。isolaureline和荷包牡丹碱中的5-HT充当拮抗剂对映异构体2和α 1受体与（[R）-isolaureline显示最大效力（对ķ b  = 8.14在5-HT 2C受体）。（R）‐和（小号）-glaucine还拮抗α 1种受体，但它们表现得非常不同，以其它化合物在5-HT 2个受体：（小号）-glaucine充当部分激动剂在所有三个5-HT 2受体亚型，而（[R ）甘草酸似乎在5-HT 2A受体上起正变构调节剂的作用。
• Stereoselective Synthesis of Aporphine Alkaloids Using a Hypervalent Iodine­(III) Reagent-Promoted Oxidative Nonphenolic Biaryl Coupling Reaction­. Total Synthesis of (<i>S</i>)-(+)-Glaucine
  作者：Dolores Badía、Eneritz Anakabe、Luisa Carrillo、Jose L. Vicario、Maite Villegas

  DOI：10.1055/s-2004-816009

  日期：——

  hydrogenation led to the key intermediate, optically active, 1-benzyltetrahydroisoquinolines 7a-c. The final C-ring closure step was performed by C-C biaryl bond formation by an hypervalent iodine(III) reagent promoted oxidative coupling, affording the target heterocycles 8a-c in good yields and with no racemization at the formerly created stereogenic center.

  由适当的 1,2-二芳基乙胺衍生物（依次使用 (S)-(+) -苯基甘氨醇作为手性载体。接下来，一系列简单的转化：用溴乙醛二乙缩醛进行 N-烷基化、N-甲基化、Pommeranz-Fritsch 环化和离子加氢，得到关键的中间体、光学活性的 1-苄基四氢异喹啉 7a-c。最后的 C 环闭合步骤是通过高价碘 (III) 试剂形成的 CC 联芳键进行的，促进氧化偶联，以良好的收率提供目标杂环 8a-c，并且在以前创建的立体中心没有外消旋化。
• Thrombocyte aggregation inhibiting composition and methods
  申请人：Hermann Gottfried Schnabel Fa.

  公开号：US04279914A1

  公开（公告）日：1981-07-21

  Platelet aggregation inhibiting compositions containing as active agent at least one compound selected from the group consisting of tetrahydroxyaporphine, glaucine containing 50 to 100% l-glaucine, and the physiologically acceptable salts and N-alkyl ammonium salts thereof are disclosed, as is a method for inhibiting platelet aggregation by administration of effective dosages of such compounds admixed with suitable carriers.

  本发明公开了抑制血小板聚集的组合物，其中包含至少一种从由四羟基阿品啡、含有50至100％ L-格洛西汀的格洛西汀和其生理上可接受的盐和N-烷基铵盐组成的群体中选择的活性剂，以及通过将有效剂量的这种化合物与适当的载体混合物一起给药来抑制血小板聚集的方法。
• L-Glaucine containing composition for cough relief
  申请人：Karl O. Helm Aktiengesellschaft

  公开号：US04370331A1

  公开（公告）日：1983-01-25

  An antitussive composition comprising a pharmaceutically acceptable carrier and from about 4 to about 99 percent by weight of a glaucine compound selected from the group consisting of l-glaucine, d,l-glaucine, the physiologically acceptable salts thereof and mixtures thereof.

  一种抗咳嗽组合物，包括药用可接受载体和约4至99重量％的从以下组合中选择的蓝花碱化合物：l-蓝花碱，d，l-蓝花碱，其生理上可接受的盐和其混合物。
• Effects of L-dopa treatment on methylation in mouse brain: Implications for the side effects of L-dopa
  作者：X.X. Liu、K. Wilson、C.G. Charlton

  DOI：10.1016/s0024-3205(00)00557-9

  日期：2000.4

  The effects of L-dopa on methylation process in the mouse brain were investigated. The study is based on recent findings that methylation may play an important role in Parkinson's disease (PD) and in the actions of L-dopa. The methyl donor, S-adenosylmethionine (SAM) and a product of SAM, methyl beta-carboline, were shown to cause PD-like symptoms, when injected into the brain of animals. Furthermore, large amounts of 3-O-methyl dopa, the methyl product of L-dopa, are produced in PD patients receiving L-dopa treatment, and L-dopa induces methionine adenosyl transferase, the enzyme that produces SAM. The results show that, at 0.5 hr, L-dopa (100 mg/kg) decreased the methyl donor, S-adenosylmethionine (SAM) by 36%, increased its metabolite S-adenosylhomocysteine (SAH) by 89% and increased methylation (SAH/SAM) by about 200%. All parameters returned to control values within 4 hr. But 2, 3 and 4 consecutive injections of L-dopa, given at 45 min intervals, depleted SAM by 60, 64 and 76% and increased SAM/SAH to 818, 896, and 1524%. L-dopa (50, 100 and 200 mg/kg) dose-dependently depleted SAM from 24.9 +/- 1.7 nmol/g to 13.0 +/- 0.8, 14.7 +/- 0.8 and 7.7 +/- 0.7 nmol/g, and increased SAH from 1.88 +/- 0.14 to 3.43 +/- 0.26, 4.22 +/- 0.32 and 6.21 +/- 0.40 nmol/g. Brain L-dopa was increased to 326, 335 and 779%, dopamine to 138, 116 and 217% and SAH/SAM to 354, 392 and 1101%. The data show that L-dopa depletes SAM, and increases methylation 4-5 times more than dopamine, therefore, methylation may play a role in the actions of L-dopa. This and other studies suggest that the high level of utilization of methyl group by L-dopa leads to the induction of enzymes to replenish SAM and to increase the methylation of L-dopa as well as DA. These changes may be involved in the side effects of L-dopa.